Biochemical Phenomena, Metabolism, and Nutrition Commons^™

Characterizing The Roles Of Cannabinoid Receptor 1 & 2 In Zebrafish Behavior, Metabolism, And Seizure-Induced Activity, Kayci Kimmons

Honors Theses

Epileptic disorders like Dravet Syndrome require novel studies to determine the most ideal treatment. New research linking the endocannabinoid system (ECS) to epileptic disorders is arising, but there is still much to be discovered about the function and regulatory impact of the endocannabinoid system and its receptors in epilepsies like Dravet. In this study, knockout models of larval and adult zebrafish (Danio rerio) were used to investigate the roles of cannabinoid receptors 1 & 2 in behavior, brain mitochondrial metabolism, and seizure-induced activity following exposure to THC and CBD. Larval zebrafish which lacked cannabinoid receptor 1 exhibited increased …

The Tca Cycle As A Nexus Of Metabolic Vulnerabilities In Cancer, Sunada Khadka

Dissertations and Theses (Open Access)

Uncontrolled proliferation of cancer cells necessitates rewiring of metabolic pathways to meet biosynthetic and bioenergetic demands of proliferation and fortify redox homeostasis. An increasing body of literature suggests that mitochondrial metabolism (tricarboxylic acid cycle (TCA) and oxidative phosphorylation) is imperative for cancer cell growth and proliferation. The scope of the works presented in this dissertation is to explore the importance of mitochondrial metabolism, and primarily the TCA cycle—the anabolic factory of cancer cells and leverage it as a targetable vulnerability in cancer. Cancer cells consume anabolic nutrients that are used to generate biosynthetic precursors in the TCA cycle. Continuous efflux …

Development And Characterization Of Anti-Galectin-9 Antibodies That Protect T Cells From Galectin-9-Induced Cell Death, Riyao Yang, Linlin Sun, Ching-Fei Li, Yu-Han Wang, Weiya Xia, Boning Liu, Yu-Yi Chu, Laura Bover, Long Vien, Mien-Chie Hung

Faculty, Staff and Student Publications

Antibodies that target immune checkpoint proteins such as programmed cell death protein 1, programmed death ligand 1, and cytotoxic T-lymphocyte-associated antigen 4 in human cancers have achieved impressive clinical success; however, a significant proportion of patients fail to respond to these treatments. Galectin-9 (Gal-9), a β-galactoside-binding protein, has been shown to induce T-cell death and facilitate immunosuppression in the tumor microenvironment by binding to immunomodulatory receptors such as T-cell immunoglobulin and mucin domain-containing molecule 3 and the innate immune receptor dectin-1, suggesting that it may have potential as a target for cancer immunotherapy. Here, we report the development of two …

An Asian Case Of Combined 17Α-Hydroxylase/17,20-Lyase Deficiency Due To Homozygous Pr96q Mutation: A Case Report And Review Of The Literature, Qian Liao, Rufei Shen, Mingyu Liao, Chenxi Ran, Ling Zhou, Yuling Zhang, Guiliang Peng, Zheng Sun, Hongting Zheng, Min Long

Center on Aging Staff Publications

Background: Combined 17α-hydroxylase/17,20-lyase deficiency (17-OHD) is a very rare form of congenital adrenal hyperplasia (CAH) caused by mutations in the CYP17A1 gene. Almost 100 different mutations of the CYP17A1 gene have been reported, including p.R96Q mutation, but no case of p.R96Q mutation has been described in Asian populations.

Case presentation: We describe a 22-year-old female patient of 46,XY karyotype, who presented with pseudohermaphrodism, primary amenorrhea, underdeveloped secondary sexual characteristics, delayed epiphyseal healing, hypertension, and hypokalemia. The diagnosis of 17-OHD was reached by measurement of steroid hormones and abdominal CT scan and confirmed by genetic sequencing, which revealed a homozygous p.R96Q …

The Sulfur Microbial Diet Is Associated With Increased Risk Of Early-Onset Colorectal Cancer Precursors, Long H. Nguyen, Yin Cao, Jinhee Hur, Raaj S. Mehta, Daniel R. Sikavi, Yiqing Wang, Wenjie Ma, Kana Wu, Mingyang Song, Edward L. Giovannucci, Eric B. Rimm, Walter C. Willett, Wendy S. Garrett, Jacques Izard, Curtis Huttenhower, Andrew T. Chan

Food for Health: Publications

Background and aims: Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H₂S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking.

Methods: We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses’ Health Study II …

Analysis Of Potentially Toxic Contaminants In Milk Powder, Magdalena Mititelu, Lucian Hîncu, Emma Adriana Ozon, Daniela Luiza Baconi, Ioana Paunica, Oana Denisa Bălălău

Journal of Mind and Medical Sciences

The aim of this study was to identify potentially toxic contaminants in milk powder. Powdered milk contains a range of toxic and non-toxic substances that are present in a wide variety, also having very different origins. A number of seven milk powder samples from different producers sold on the Romanian market were analyzed, the samples that were collected from the original packaging: P1, P 2, P3, P4, P5, P6 and P7. The concentration of the following elements was analyzed using the X-ray (XRF) fluorescence method: potassium (K), chlorine (Cl), calcium (Ca), phosphorus (P) and aluminum (Al). The vast majority of …

A Cancer Ubiquitome Landscape Identifies Metabolic Reprogramming As Target Of Parkin Tumor Suppression, Ekta Agarwal, Aaron R Goldman, Hsin-Yao Tang, Andrew V Kossenkov, Jagadish C Ghosh, Lucia Languino, Valentina Vaira, David W Speicher, Dario C Altieri

Department of Cancer Biology Faculty Papers

Changes in metabolism that affect mitochondrial and glycolytic networks are hallmarks of cancer, but their impact in disease is still elusive. Using global proteomics and ubiquitome screens, we now show that Parkin, an E3 ubiquitin ligase and key effector of mitophagy altered in Parkinson's disease, shuts off mitochondrial dynamics and inhibits the non-oxidative phase of the pentose phosphate pathway. This blocks tumor cell movements, creates metabolic and oxidative stress, and inhibits primary and metastatic tumor growth. Uniformly down-regulated in cancer patients, Parkin tumor suppression requires its E3 ligase function, is reversed by antioxidants, and is independent of mitophagy. These data …

Modulation Of Glucose Homeostasis By Nucleotide P2y2 Receptor And Biological Sex, Hailee Anne Marino

Graduate Theses/Dissertations

Recent insights into the pathological role of Nucleotide P2Y₂ receptor suggest P2Y₂R involvement in high fat diet-induced obesity and potentiates insulin resistance. However, these recent insights do not demonstrate how P2Y₂R modulates glucose homeostasis under physiological conditions. Further, it remains unknown how sex biological factors influence P2Y₂R receptor signaling in the regulation of glucose homeostasis. The research objective for the present study is to elucidate the novel roles of P2Y₂ in fasting blood glucose and glucose tolerance (basal insulin sensitivity) under resting conditions in males and females. We expected that under physiological …

The Associations Of Chronic Stress, Social Support, Health Behaviors And Metabolic Syndrome Among Hispanic Women, Edna Esquer

Dissertations

The Associations of Chronic Stress, Social Support, Health Behaviors and Metabolic Syndrome Among Hispanic Women

Background: Metabolic syndrome (MetS) prevalence is 25% among Mexican American women 30 – 49 years of age, compared to 22% among non-Hispanic Whites in the United States. Little is known about the additional contributions of chronic stress, social support and health behaviors to the development of MetS among this population.

Purpose: Describe the associations between chronic stress, social support, and health behaviors and the presence of MetS in Hispanic women living in an underserved community.

Methods: A retrospective cohort study design. The Adult Treatment Panel …

A Neural Basis For Brain Leptin Action On Reducing Type 1 Diabetic Hyperglycemia, Shengjie Fan, Yuanzhong Xu, Yungang Lu, Zhiying Jiang, Hongli Li, Jessie C Morrill, Jing Cai, Qi Wu, Yong Xu, Mingshan Xue, Benjamin R Arenkiel, Cheng Huang, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

Central leptin action rescues type 1 diabetic (T1D) hyperglycemia; however, the underlying mechanism and the identity of mediating neurons remain elusive. Here, we show that leptin receptor (LepR)-expressing neurons in arcuate (LepRArc) are selectively activated in T1D. Activation of LepRArc neurons, Arc GABAergic (GABAArc) neurons, or arcuate AgRP neurons, is able to reverse the leptin’s rescuing effect. Conversely, inhibition of GABAArc neurons, but not AgRP neurons, produces leptin-mimicking rescuing effects. Further, AgRP neuron function is not required for T1D hyperglycemia or leptin’s rescuing effects. Finally, T1D LepRArc neurons show defective nutrient sensing and signs of cellular energy deprivation, which are …

Fucoxanthin: A Review Of Potential Benefits Relative To Human Health, Michael R. White

Masters Theses, 2020-current

Fucoxanthin is a carotenoid sourced and extracted mainly from dark orange and brown seaweeds found in the pacific ocean, such as the wakame algae. The allenic bonds and unique oxygen groups give fucoxanthin its unique structure and are thought to be part of the reason fucoxanthin has unique physiological functions. Fucoxanthin has potentially numerous effects on the physiology of human health, ranging from skin health to metabolic health, which have been demonstrated in animal model research. The goal of this review is to examine current literature to discuss fucoxanthin’s potential application as a nutraceutical, treatment for obesity, type 2 diabetes, …

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

Graduate Theses/Dissertations

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 …

Perivascular Adipose Tissue In Relation To Diet, Thermogenesis And Cardiovascular Health, Ginger Paquette, Caitlin Stieber, Ashely Soucy, Benjamin Tero, Lucy Liaw

Thinking Matters Symposium

Adipose tissue is a diverse and crucial component to vascular health due to its role in energy storage and heat production. The primary function of white adipose tissue (WAT) is energy storage while the function of mitochondria-rich brown adipose tissue (BAT) is heat production. Perivascular adipose tissue (PVAT), which surrounds blood vessels, contains both WAT and BAT adipocytes. Dietary calorie restriction is associated with increased lifespan with decreased adiposity. Increased prevalence of WAT-like PVAT, due to high-fat diets and obesity, leads to increased metabolic disfunction and cardiovascular-disease. We used a calorie-restriction model in C57BL6/J mice to test the hypothesis that …

Purification And Functional Characterization Of The Iron-Responsive Transcription Factor Aft1 From C. Glabrata, Jade Ikahihifo-Bender

Senior Theses

Due to its unique ability to serve as both an electron donor and acceptor, iron is utilized as a co-factor for many biological processes, including electron transfer, oxygen binding, and vitamin synthesis. Iron is also a key factor during fungal infections as the human host and invading pathogens battle over limited iron pools. The primary iron-responsive transcription factor Aft1 in the opportunistic pathogenic yeast Candida glabrata responds to iron deficiency by activating expression of iron acquisition genes. However, the mechanisms for sensing intracellular iron levels and regulating Aft1 activity in response to iron are unknown. The C. glabrata iron regulation …

Metabolism And Oncology: The Role Of Nutrition In Improving Cancer Outcomes, Michael A. Chapek

University Honors Theses

Despite significant advances in oncologic treatment, underlying cancer-associated metabolic derangements and nutritional needs remain largely neglected in cancer care. Cancer cachexia and protective metabolic changes exhibited by cancerous cells continue to pose formidable barriers to improving therapeutic outcomes and quality of life for patients. Cancer has traditionally been viewed as a proliferative disease caused by genetic mutations, but newer perspectives suggest that it is primarily a metabolic disease. The present paper discusses the etiology of cachexia and sarcopenia, and nutritional interventions that can be offered to patients suffering from these wasting disorders. The role of inflammation in cancer and the …

Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish

Graduate Theses, Dissertations, and Problem Reports (ETD)

Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and consistent …

Pre-Clinical Advancements In Biomarkers, Tools, And Therapeutics For A Metabolic Neurodegenerative Disease, Zoë Simmons

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is the storage form of glucose and a highly important substrate for cellular metabolism. Characterization of the enzymes and mechanisms of glycogen metabolism began over 70 years ago and over the last 20 years, a previously unknown protein called laforin has emerged as an important contributor to glycogen metabolism homeostasis. Multiple labs demonstrated that laforin is a glycogen phosphatase and mutations in the gene encoding laforin cause the formation of aberrant glycogen-like aggregates called Lafora bodies (LBs). LBs are cytoplasmic, water-insoluble aggregates that drive neurodegeneration and early death in Lafora disease (LD) patients. The direct relationship between mutated laforin, …

Hyperpolarized Carbon-13 Magnetic Resonance Measurements Of Tissue Perfusion And Metabolism, Keith Michel

Dissertations and Theses (Open Access)

Hyperpolarized Magnetic Resonance Imaging (HP MRI) is an emerging modality that enables non-invasive interrogation of cells and tissues with unprecedented biochemical detail. This technology provides rapid imaging measurements of the activity of a small quantity of molecules with a strongly polarized nuclear magnetic moment. This polarization is created in a polarizer separate from the imaging magnet, and decays continuously towards a non-detectable thermal equilibrium once the imaging agent is removed from the polarizer and administered by intravenous injection. Specialized imaging strategies are therefore needed to extract as much information as possible from the HP signal during its limited lifetime.

In …

Great Expectations: Phosph(On)Ate Prodrugs In Drug Design—Opportunities And Limitations, Victoria Yan

Dissertations and Theses (Open Access)

Phosphate and phosphonates are chemical moieties with historical precedence in anticancer and antiviral nucleotide analogues. Synchronous to modern efforts identifying novel therapeutic targets in cancer, such chemical moieties are being investigated in the design of novel inhibitors with antineoplastic potential. A central challenge to the delivery of phosph(on)ate-containing drugs is their anionic character at physiological pH, which portends poor membrane permeability. This limitation has been successfully overcome through the use of prodrugs. When attached to the phosph(on)ate moiety, prodrugs mask the negative charge and easily enable cell permeability. Upon cellular entry, the promoieties are enzymatically or environmentally cleaved to unveil …

Attenuation Of Interferon Responses In The Obese Host And Ramifications For Influenza Virus Evolution, Rebekah Reed Honce

Theses and Dissertations (ETD)

The most insidious pandemic of modern life does not arise from an infectious agent but rather from malnutrition. With its global incidence tripling over the past three decades, obesity is a major public health concern. Obesity’s rising prevalence has also illuminated its impact on communicable diseases. Following the 2009 H1N1 influenza A virus pandemic, obesity was identified as a risk factor for increased disease severity and mortality in infected individuals. Obesity causes a chronic state of meta-inflammation with systemic implications for immunity, including delayed antiviral responses to influenza virus infection, poor recovery, and impaired immunological memory. However, the majority of …

A Body Shape Index Significantly Predicts Mri-Defined Abdominal Adipose Tissue Depots In Non-Obese Asian Indians With Type 2 Diabetes Mellitus, Shajith Anoop, Jesse Krakauer, Nir Krakauer, Anoop Misra

Publications and Research

Introduction: We aimed to determine the correlations of volumes of subcutaneous abdominal adipose tissue (SCAT) (anterior, posterior, superficial and deep), total SCAT, intraperitoneal adipose tissue, retroperitoneal abdominal adipose tissue (RPAT), total intra-abdominal adipose tissue (IAAT), pancreatic volume, liver span, total body fat (TBF) and truncal fat mass (TFM) with anthropometric indices, viz., A Body Shape Index (ABSI), Hip Index, their Z scores and Anthropometric Risk Index in non-obese (body mass index (BMI) /m²) Asian Indians with type 2 diabetes mellitus (T2DM).

Research design and methods: Non-obese patients with T2DM (cases; n, 85) and BMI-matched, healthy subjects …

Investigating The Metabolic Progression Of Glioblastoma With Hyperpolarized Magnetic Resonance, Travis Salzillo

Dissertations and Theses (Open Access)

Rapid diagnosis and therapeutic monitoring of aggressive diseases such as glioblastoma (GBM) can improve patient survival by providing physicians the time to optimally deliver treatment. This includes early in development, while the tumor is still manageable, or following initial therapy, when alternative treatments should be considered. The main goal of this project was to determine whether metabolic imaging with hyperpolarized magnetic resonance spectroscopy (MRS) could detect changes in tumor progression more rapidly than conventional anatomic magnetic resonance imaging (MRI) in patient-derived GBM murine models. To comprehensively capture the dynamic nature of cancer metabolism, in vivo pyruvate-to-lactate conversion with hyperpolarized MRI, …

The Role Of Nutrition In Promoting Gut Health And Treating Chronic Illness Through The Attenuation Of Inflammation, Allison Dalton

HCA Healthcare Journal of Medicine

Over the millennia, the human body and microorganisms such as bacteria, viruses, archaea, protozoa and parasites have coevolved together forming an intimate relationship. These microorganisms are found on the skin, in the mouth, genitourinary tract and most abundantly in the large intestine of the digestive tract. States of microbial dysbiosis contribute to chronic inflammation, which can lead to the pathogenesis and progression of numerous diseases. Micro- and macro-nutrients as well as dietary patterns like the Mediterranean diet can help improve health outcomes.

How Immune T-Cell Augmentation Can Help Prevent Covid-19: A Possible Nutritional Solution Using Ketogenic Lifestyle, Ravi K. Kamepalli Md,Fidsa,Cwsp

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer

Capstone Showcase

ABSTRACT

Introduction: Anterior Cruciate Ligament (ACL) injuries are an upsetting setback for many athletes that require a long and costly recovery process. The injury rates are four times greater in women than men. Preventative measures that help to prevent ACL injuries are limited to stretching and strengthening. Therefore, this review aims to investigate if oral contraceptive [I] usage provides a possible new avenue for prevention of ACL injury [O] in young female athletes (ages 18-30) [P] compared to those that do not take oral contraceptives [C].

Methods: A literature review was performed though PubMed, Google Scholar, SCOPUS Database, and ClinicalKey …

An In-Depth Review Of Retinitis Pigmentosa Development And Pathologies Overtime In Patients, Abdul Harris

Honors College Theses

Retinitis Pigmentosa is a disease which can cause blindness and affects around 2.5 million people worldwide. It is a disorder that has a multitude of ways of being inherited, such as autosomal dominant, autosomal recessive as well as X-linked and mitochondrial linked disorder. While some versions of RP may be syndromic (20%-30%), a majority of cases are in fact non-syndromic. The majority of non-syndromic cases inherited via autosomal dominant RP having RHO gene mutations, and X-linked means of inheritance having majority of patients with RPGR gene mutations. Ushers Syndrome, a syndromic version of retinitis pigmentosa and autosomal recessive RP having …

Role Of Non-Nutritive Sweeteners In Obesity And Diabetes, Erica Schoenberger, Ellen Hazelet, Kaitlin Sanders, Lindsey Hallman, David Bright, Amy Stockert

Pharmacy and Wellness Review

Artificial sweeteners have become a central component of the Western diet in order to facilitate weight loss and enhance glucose control. Despite their popularity, evidence supporting the benefits of artificial sweeteners remains contradictory; different trials have shown weight loss, weight gain or no change with artificial sweetener consumption. Multiple trials have correlated artificial sweetener usage, in the form of diet soda, with an increased risk of obesity, diabetes and/or metabolic syndrome. Hypotheses speculate that individuals who consume larger loads of artificial sweeteners may be more likely to make unhealthy lifestyle choices, putting them at an increased risk for the development …

Effectiveness Of Individual Nutrition Education Compared To Group Education, In Improving Anthropometric And Biochemical Indices Among Hypertensive Adults With Excessive Body Weight: A Randomized Controlled Trial, Danuta Gajewska, Alicja Kucharska, Marcin Kozak, Shahla M. Wunderlich, Joanna Niegowska

Department of Nutrition and Food Studies Scholarship and Creative Works

Objective: The study aims to compare the effectiveness of individual and group nutrition education methods in improving key anthropometric and biochemical markers in drug-treated, overweight-obese hypertensive adults. Methods: The randomized trial included 170 patients with pharmacologically well-controlled primary hypertension and body mass index (BMI) ≥ 25 kg/m². For six months, the patients received six sessions, either one-to-one individual nutrition education (IE, n = 89) or group education (GE, n= 81), developed by dietitians. Anthropometric measurements, body composition, and fasting measures of biochemical parameters were obtained at baseline and after six months of intervention. Results: 150 patients completed the …

The Acute Effect Of Water Intake On Glucose Regulation In Low Drinkers, Adam David Seal

Graduate Theses and Dissertations

Previous evidence suggests the hormone arginine vasopressin (AVP) may be a modifiable factor contributing to hyperglycemia. Significant differences in urine concentration and copeptin, a marker for AVP, have been observed between low and high water drinkers. Purpose: The purpose was to investigate the acute effect of adequate water intake on glucose regulation in low drinkers. Methods: 7 healthy (5 males, 2 female) low drinkers were recruited using a water frequency questionnaire (WFQ), spot and 24-h urine sample (age 43±6 y, BMI 30.9±3, WFQ volume 823±403 mL∙d-1, 24 h Uosm 961±105 mmol∙kg-1, copeptin 8.17±3.05 pmol∙L-1). During two experimental protocols, participants remained …

Oxidative Phosphorylation: A Critical Feature And Novel Therapeutic Target In Melanoma Brain Metastases, Grant Fischer

Dissertations and Theses (Open Access)

We recently showed via RNA-sequencing (RNA-seq) analysis of clinical samples that melanoma brain metastases (MBMs) have higher expression of oxidative phosphorylation (OXPHOS) genes (including PPARGC1A or PGC1α) than patient-matched extracranial metastases (ECMs). Thus, the central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis of MBMs.

RNA-seq analysis identified increased expression of OXPHOS genes in intracranial (ICr) vs. subcutaneous (SQ) xenografts of 4 different human melanoma cell lines. Increased OXPHOS in the ICr xenografts was confirmed by direct metabolite analysis and [U-¹³C]-glucose tracing analysis. Together, these studies indicate that the brain TME …