Browsing by Author "Ju, Young Hwa"

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    Analysis of the Stakeholder Derived Conceptual Models and Exploration of Lung Cancer Screening Barriers in a Medically Underserved Area
    Zarghami, Fatemeh (Virginia Tech, 2018-06-13)
    The number of new cases of lung and bronchus cancer was 55.8 per 100,000 men and women per year. The number of deaths was 44.7 per 100,000 men and women per year. These rates are age-adjusted and based on 2010-2014 cases and deaths. Each year, more people die of lung cancer than of colon, breast, and prostate cancers combined. The knowledge that lung cancer can be successfully treated if caught early has driven a decades-long search to find an accurate and reliable screening test. National Cancer Institute's National Lung Screening Trial (NLST) found that annual screening with Low-Dose CT (LDCT) for asymptomatic patients aged 55 to 74, with a smoking history of at least 30 pack-years, and smokers who quit less than 15 years ago, had a 20% reduction in risk of death from lung cancer. Findings of this trial resulted in that LDCT becoming the gold standard of screening for lung cancer. The SEED method is a community-engaged research approach to develop conceptual models and generate patient-centered research questions. This method has been used to engage community stakeholders of Martinsville, Virginia to develop conceptual models of the factors contributing to lung cancer outcomes. In the first manuscript of this dissertation, these models which were produced by 3 different groups of stakeholders have been examined closely to explore the complexity, similarities, and differences. The models were used to produce a research agenda on the topic of factors impacting lung cancer outcomes for future researchers. A literature review was conducted by the study team on the final research agenda. The goal of this literature review was to avoid duplication of research and to focus future research on the identified gaps. The knowledge and attitudes of the health care providers and patients about lung cancer screening and the barriers in the uptake of LDCT were identified as a research gap. The design of the Martinsville lung cancer study described in the second manuscript of this dissertation responds to this identified research gap. These studies and their results shed light on the factors that impact lung cancer outcomes using a community based participatory approach.
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    The Effect of Health Information on the Acceptability of a Functional Beverage with Fresh Turmeric
    Grasso, Stephanie Marie (Virginia Tech, 2018-06-29)
    BACKGROUND: Turmeric is a root with curcumin and non-curcumin derivatives that serve as antioxidants, which reduce the risk of oxidative stress-induced chronic disease. The provision of health information has shown to increase the acceptability of functional foods that impart unfamiliar flavors. PURPOSE: The purpose of this study was to evaluate the acceptability and sensory qualities of a functional beverage with fresh turmeric, and the impact of information related to the beverage's health benefits on acceptability. This study also investigated personal and psychological factors associated with food acceptance. METHODS: Antioxidant capacity (ferrous equivalents) and polyphenolic content were evaluated in a fruit-based beverage containing 0g, 7g, 14g, and 22g of fresh turmeric. Sixty-one individuals were recruited to participate in a sensory evaluation of two fruit-based beverages with and without fresh turmeric. Thirty-one participants were given health information related to the beverage and 30 participants received no health information. The degree of liking was measured on a hedonic scale and sensory attributes were measured using a Just About Right (JAR) scale. Food choice motives and demographic characteristics were measured using a Food Choice Questionnaire and demographics questionnaire. RESULTS: The development of a functional beverage with 14 grams of turmeric was considered significantly more acceptable with the provision of health information and resulted in a significant increase in antioxidant capacity and polyphenolic content. There was a significant difference in acceptability scores of the functional beverage across antioxidant interest groups and health motivation groups.
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    Estrogen signaling interacts with Sirt1 in adipocyte autophagy
    Tao, Zhipeng (Virginia Tech, 2019-06-18)
    Obesity is a rapidly growing epidemic. It is associated with preventable chronic disease and vast healthcare cost in the United States (about 200 billion per year). Therefore, dissecting pathogenic mechanisms of obesity would provide effective strategies to prevent its development and reduce related cost. Obesity is characterized by excessive expansion of white adipose tissue (WAT). Autophagy, a cellular self-digestive process, is associated with WAT expansion and may be a promising target for combating obesity. Both hormone signaling (e.g., ERα) and energy sensing factors (e.g., Sirt1) control metabolism and prevent adiposity, and in which they have been shown to play collaborate roles. However, how autophagy is involved in ERα and Sirt1's inhibitory roles on adiposity is unknown. These questions have been addressed in my dissertation studies. To address this fundamental questions, I have established a method to monitor autophagy flux during adipocyte differentiation, which better reflected the dynamic process of autophagy. Compared with preadipocytes, autophagy flux activity was increased in mature adipocytes after differentiation. And then, my thesis project has addressed three main questions. Firstly, the gender difference in visceral fat distribution (Males have higher deposit of visceral fat than females) is controlled by an estradiol (E2)-autophagy axis. In C57BL/6J and wild type control mice, a higher visceral fat mass was detected in the males than in the females, which was associated with lower expression of estrogen receptor  (ER) and more active autophagy in males vs. females. ER knockout normalized this difference. Mechanistically, E2-ER- mTOR-ULK1-autophagy signaling contributed to the gender difference in visceral fat distribution. Secondly, in vitro and in vivo studies demonstrated that Sirt1 suppressed autophagy and reduced adipogenesis and adiposity via inducing mTOR-ULK1 signaling. Specific activation and overexpression of Sirt1 induced mTOR-ULK1 signaling to suppress autophagy and adipogenesis. And knockdown of Sirt1 exhibited opposite effects. The first and second studies revealed that ER and Sirt1 acted on mTOR-ULK1 signaling pathway, underlying the importance of their interaction in inhibiting autophagy and adipogenesis. As such, the third study was conducted and it unraveled that ER acted as upstream of Sirt1, possibly through its direct binding to Sirt1 promoter. Specifically, E2 signaling suppressed autophagy and adipogenesis. But when Sirt1 was knockdown, the effects of E2 on autophagy and adipogenesis were abolished. Taken together, my dissertation project underscores the importance for future research to consider gender difference and how E2-ER-autophagy axis contributes to this difference in other metabolic diseases. Also, the unraveled interaction between ERα and Sirt1 might lead to new therapeutic approach to adiposity and metabolic dysfunction in post-menopausal women or individuals with abnormal estrogen secretion. For example, dietary intervention or exercise challenge to activate Sirt1 may partially compensate estrogen deficiency.
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    Evaluation of Teen Cuisine: An Extension-Based Cooking Program to Increase Self-efficacy in Teens
    Petty, Heather Keyronica (Virginia Tech, 2016-12-15)
    Background: Childhood, adolescent, and adult obesity is a major health and economic concern affecting the United States and various countries across the globe. Obese children and adolescents are at a potential risk for developing certain chronic diseases as they transition into adulthood. There are community-based cooking intervention programs designed to increase children and adolescents' intake of fruits, vegetables, and whole grains, whether these programs improve self-efficacy and perceptions related to food and eating behaviors is not currently known. Objective: The aim of the study was to evaluate the effectiveness of Teen Cuisine, an Extension-based cooking program on self-efficacy with cooking and perceptions of their eating behaviors in a diverse group of adolescents across the Commonwealth of Virginia. Subjects: Students involved in the 4-H Teen Cuisine Program during the 2013-2015 academic years. Cooking Program: Teen Cuisine is a six-week 90-minute extension-based cooking program created by the Virginia Family Nutrition Program targeting adolescents and teens throughout the Commonwealth of Virginia. The program focused on kitchen safety and sanitation, knife skills, food preparation, and nutrition education. Measures: A survey was used to assess n=531 student's self-efficacy for general nutrition knowledge, food choices, and cooking skills as a result of the 4-H Teen Cuisine Program during the academic year of fall 2013 to spring 2015. Methods: Surveys were administered upon completion of the Teen Cuisine program to assess students' self-efficacy and perceived gains in kitchen skills, dietary patterns and preferences, and nutrition knowledge. Results: Teens that self-reported living in rural areas throughout the Commonwealth of Virginia perceived gains (p < 0.05) in an increased consumption of fruits and vegetables. Teens also indicated an increased frequency in cooking and a decrease in their consumption of soda/soft drinks. Conclusion: Overall Teen Cuisine was found to be effective in improving perceptions of curriculum specific health behaviors, cooking skills, food safety and sanitation, and perceived gains in self-efficacy in the kitchen.
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    The Examination of Mindfulness, Stress, and Eating Behaviors in Mothers of Young Children
    Kennedy, Lauren E. (Virginia Tech, 2016-05-03)
    With the alarming prevalence of overweight and obesity, it is important to explore new approaches and strategies to improve dietary quality and weight status. Recently, a neuropsychological model of obesity was proposed. This new model illustrates an evidencebased relationship between a chronically activated hypothalamic-pituitary-adrenal (HPA) axis, due to chronic psychological stress and mood disturbance, and the food reward-related mechanisms within the brain. Intensive mindfulness-based training programs, such as Jon Kabat-Zinn's Mindfulness-Based Stress Reduction have demonstrated impressive results with a variety of populations. Given the relationship of stress to eating behavior and the capacity of mindfulness in managing stress, a relationship between mindfulness and eating is expected. The goal of this dissertation research was to help understand the concept of mindful eating and the relationship between stress and eating behavior for mothers of young children in order to inform the development of a mindfulness-based stress management and dietary intervention. The research consisted of three components: 1) an informative photo-elicitation study with working mothers of young children aiming to understand how mothers define, perceive, and experience mindful eating; 2) a crosssectional study investigating the relationship between mindful eating, dietary quality, and stress; and 3) the development and mixed-methods pilot intervention of the Slow Down Program, a mindfulness-based stress management and nutrition program for mothers of young children. Results from these studies give further evidence on how mindfulness can be utilized in nutrition research and they further confirm the success of mindfulness-based training on health and dietary outcomes. This research can inform public health programs and practice to encourage mindfulness, as it relates to dietary behavior, for families and other audiences, as well as future research studies that explore the interaction between mindfulness and eating behaviors.
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    Exploring the metabolic role of GPR30 in mice
    Luo, Jing (Virginia Tech, 2019-06-21)
    Recent studies showed that GPR30, a seven-transmembrane G protein-coupled receptor, is a novel estrogen receptor (ER) that mediates some biological events elicited by estrogen in several types of cancer cells. However, its physiological or pathological role in vivo is unclear. For the first project of my dissertation, I investigated the physiological role(s) of GPR30 in energy metabolism by using transgenic mouse model as well as immortalized cell lines and primary stromal cells. We discovered for the first time that GPR30 knockout (GPRKO) female mice were protected from high-fat diet (HFD)-induced obesity, glucose intolerance, and insulin resistance. The decreased body weight gain in GPRKO female mice is due to the reduction in body fat mass. These effects occurred in the absence of significant changes in food intake, intestinal fat absorption, or triglyceride metabolism. However, GPR30 had no significant metabolic effects in male mice fed the HFD and both sexes of mice fed a chow diet. Further, GPR30 expression levels in fat tissues of WT obese female mice greatly increased, whereas ERα/β expression was not altered. Deletion of GPR30 reduced adipogenic differentiation of adipose tissue-derived stromal cells. Conversely, activation of GPR30 enhanced adipogenic differentiation of 3T3-L1 preadipocytes. For the second project, I explored whether estrogen acts through GPR30 to affect adiposity in female mice. For this study, I generated and examined three independent transgenic mouse models, aromatase (Ar) knockout (ArKO) mice, GPRKO, and GPR30 and Ar double knockout (DKO) mice. We discovered that GPR30 deficiency had limited effects on energy metabolism in mice fed a standard chow diet (STD). However, deletion of GPR30 promoted metabolic flexibility in both genders fed a HFD regardless of the presence of estrogen, suggesting that GPR30 may not solely act as an ER. Consistent with our previous findings, GPRKO mice had higher body temperature, indicating that GPR30 deficiency may promote thermogenesis and energy metabolism, resulting in the reduced fat depots and enhanced metabolic flexibility. For the third project, I further explored whether GPR30 is involved in regulating browning of adipose tissue and thermogenesis in mice. The results show that the expression of UCP-1, the key regulator of thermogenic browning, was higher in the adipose tissue of HFD-fed GPRKO female mice as compared with that of WT mice. Consistently, deletion of GPR30 enhanced mitochondrial respiration in brown adipose tissue (BAT), suggesting that GPR30 deficiency at least partially suppressed the fat accumulation by promoting thermogenesis and dissipating energy. Ex vivo, the expression of thermogenic genes and UCP-1 protein level were upregulated in beige adipocytes differentiated from GPR30-deficient stromal vascular fraction (SVF) cells. These findings provide evidence for the first time that deletion of GPR30 reduces adiposity, promotes white adipose beigeing and thermogenesis, therefore preventing the development of obesity in female mice exposed to excess energy. Further investigations elucidating the underlying mechanism by which GPR30 promotes obesity in females could provide a novel therapeutic target to fight obesity in females.
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    Investigating the potential anti-diabetic effect of sulforaphane
    Luo, Jing (Virginia Tech, 2014-07-01)
    Type 2 diabetes (T2D) is a major public health issue worldwide and it currently affects nearly 26 million people in the United States. It is estimated that one third of Americans will have diabetes by 2050. T2D is a result of chronic insulin resistance and loss of beta-cell mass and function. Both in experimental animals and people, obesity is a leading pathogenic factor for developing insulin resistance, which is always associated with the impairment in energy metabolism, causing increased intracellular fat content in skeletal muscle, liver, fat, as well as pancreatic islets. Constant insulin resistance will progress to T2D when beta-cells are unable to secret adequate amount of insulin to compensate for decreased insulin sensitivity. In the present study, I investigated whether sulforaphane, a natural compound derived from cruciferous vegetables, can prevent high-fat (HF) diet-induced obesity and diabetes in C57BL/6 mice. Dietary intake of sulforaphane (250 mg/kg diet) prevented hyperglycemia and increased insulin sensitivity in HF diet-induced obese mice. Mice treated with sulforaphane had significant lower serum insulin levels (1.93±0.11 μg/dl) as compared to those without treatment (3.09±0.27 μg/dl, P<0.05). In second study, administration of sulforaphane (40 mg/kg body weight daily via gavage) in obese mice enhanced body weight loss and improved insulin sensitivity. Moreover, sulforaphane increased pyruvate oxidation by 28.85% (P<0.05) and enhanced fatty acid oxidation efficiency by 2.2 fold (P<0.05) in primary human muscle cells. These results suggest that sulforaphane may be a naturally occurring insulin-sensitizing agent that is capable of preventing T2D.
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    Relationship of dietary antioxidant intake, antioxidant serum capacity, physical activity and inflammation in breast cancer survivors and individuals without a history of cancer
    Mozhi, Dimple Aneka (Virginia Tech, 2018-07-02)
    Background: Dietary and serum antioxidants and physical activity can effect inflammation, which is associated with breast cancer risk and recurrence. This study investigated the relationship between diet, serum antioxidant capacity, physical activity, and inflammation in breast cancer survivors and individuals without cancer. Methods: Existing demographic, dietary intake, and physical activity data of 78 breast cancer survivors and 30 individuals without cancer from the Day and Night Study conducted at Virginia Commonwealth University were used. Participants were recruited from southern Virginia. Metabolic equivalents were calculated through type, intensity, and duration of physical activity. Dietary antioxidant intake (FRAP) was calculated from Harvard Food Frequency Questionnaire data. Serum samples were analyzed for inflammation (hsCRP,IL-6,IL-1,and TNF alpha) and serum antioxidant capacity (ORAC) at Virginia Tech. Results: Anthropometrics and inflammation were higher, and FRAP and ORAC lower in breast cancer survivors compared to individuals without cancer, although not significant. There was a significant direct relationship between FRAP and ORAC and inverse relationship between FRAP and hsCRP. Breast cancer survivors 6+ years since diagnosis showed significant direct FRAP and IL-1 association, and inverse ORAC and TNF-alpha association. BMI was directly associated with IL-6 and CRP. Inflammation was not associated with METs or weekly activity, although there was an increasing inverse relation between METs, IL-1 and TNF- α with increasing ORAC. Conclusion: There is a significant relationship between dietary antioxidant intake and serum antioxidant capacity and inflammation. Increased body mass index increases inflammation. Diets high in antioxidants and maintaining a healthy weight may help reduce inflammation in breast cancer survivors.
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    Small molecule kaempferol, a novel regulator of glucose homeostasis in diabetes
    Moore, William Thomas (Virginia Tech, 2017-12-01)
    Diabetes mellitus is a growing public health concern, presently affecting 25.8 million or 8.3% of the American population. While the availability of novel drugs, techniques, and surgical intervention has improved the survival rate of individuals with diabetes, the prevalence of diabetes is still rising. Type 2 diabetes (T2D) is a result of chronic insulin resistance and loss of -cell mass and function, and it is is always associated with the impairment in energy metabolism, causing increased intracellular fat content in skeletal muscle (SkM), liver, fat, as well as pancreatic islets. As such, the search for novel agents that simultaneously promotes insulin sensitivity and 𝜷-cell survival may provide a more effective strategy to prevent the onset and progression of this disease. Kaempferol is a flavonol that has been identified in many plants and used in traditional medicine. It has been shown to elicit various pharmacological activities in epidemiological and preclinical studies. However, to date, the studies regarding its effect on the pathogenesis of diabetes are very limited. In this dissertation, I explored the anti-diabetic potential of the dietary intake of kaempferol in diet-induced obese mice and insulin-deficient diabetic mice. For the first animal study, kaempferol was supplemented in the diet to determine whether it can prevent insulin resistance and hyperglycemia in high fat (HF) diet-induced obese mice or STZ-induced obese diabetic mice. For the second animal study, kaempferol was administrated once daily via oral gavage to diet-induced obese and insulin-resistant mice or lean STZ-induced diabetic mice to evaluate its efficacy for treating diabetes and further determining the underlying mechanism. The results demonstrated that dietary intake of kaempferol for 5 months (mo) improved insulin sensitivity and glucose tolerances, which were associated with increased Glut4 and AMPKα expression in muscle and adipose tissues in middle-aged mice fed a high-fat (HF) diet. In vitro, kaempferol increased lipolysis and restored chronic high fatty acid-impaired glucose uptake and glycogen synthesis in SkM cells, which were associated with improved AMPKα activity and Glut4 expression. In addition, dietary kaempferol treatment preserved functional pancreatic 𝜷-cell mass and prevented hyperglycemia and glucose intolerance in STZ-induced diabetic mice. Data from the second study show that oral administration of kaempferol significantly improved blood glucose control in obese mice, which was associated with reduced hepatic glucose production and improved whole body insulin sensitivity without altering body weight gain, food consumption, or the adiposity. In addition, kaempferol treatment increased Akt and hexokinase activity, but decreased pyruvate carboxylase and glucose-6 phosphatase activity in the liver homogenate without altering their protein expression. Consistently, kaempferol decreased pyruvate carboxylase activity and suppressed gluconeogenesis in HepG2 cells as well as primary hepatocytes isolated from the livers of obese mice. Kaempferol directly blunted the activity of purified pyruvate carboxylase. In the last study, we found that kaempferol stimulates basal glucose uptake in primary human SkM. In C2C12 mouse myotubes, kaempferol also increased insulin stimulated glycogen synthesis and preserved insulin dependent glycogen synthesis and glucose uptake in the presence of fatty acids. Kaempferol stimulated Akt phosphorylation in a similar time-dependent manner as insulin in human SkM cells. Consistent with this, kaempferol increased Akt and AMPK phosphorylation in isolated murine red SkM tissue. The effect of kaempferol on glucose uptake was blunted in the presence of chemical inhibitors of glucose transporter 4 (Glut4), phosphoinositide 3-kinase (PI3K), glucose transporter 1 (Glut1), and AMPK. The AMPK inhibitor also prevented kaempferol-stimulated Akt phosphorylation. Further, kaempferol improved the stability of insulin receptor substrate-1. Taken together, these studies suggest that the kaempferol is a naturally occurring compound that may be of use in the regulation of glucose homeostasis and diabetes by improving insulin sensitivity and glucose metabolism, as well as by preserving functional 𝜷-cell mass.