Molecular, Genetic, and Biochemical Nutrition Commons^™

Analysis Of The Effects Of Astaxanthin On Human Colorectal Cancer Cells, Kara A. Walters

Theses/Capstones/Creative Projects

Astaxanthin (AXT) is an antioxidant carotenoid that is produced by the microalgae Haemococcus pluvialis. This supplement is best known for its potential health benefits including anti-inflammatory, antitumor, immunomodulatory, anticancer and antidiabetic activities. Astaxanthin is marketed as an oral dietary supplement and is widely used in the nutraceutical industry as well as a coloring agent in the food industry. Since Astaxanthin has been increasingly popular as a dietary supplement, cytotoxicity is relevant to consumer exposure. Obtaining the IC50, the concentration that inhibits 50% of cell growth, is important to find how Astaxanthin may interact with cancer, and this can be found …

Mechanistic Insights Into Enterolactone-Mediated Glut4-Dependent Glucose Uptake, Merritt Smith

Senior Honors Theses

Type 2 diabetes mellitus (T2D) is one of the leading causes of morbidity and mortality in the United States, with approximately 25% of healthcare expenditures directed toward its management and associated metabolic complications. In response to the urgent need for novel therapeutic strategies, recent research has focused on bioactive compounds derived from dietary sources. In light of that, we identified the plant lignan matairesinol (MA) and its gut-derived metabolite, enterolactone (ENL), as agents capable of enhancing glucose uptake in 3T3-L1 differentiated adipocytes. These results suggest that enterolactone may represent a promising dietary supplement for improving glycemic control in patients with …

Dietary Flavonoid Intake And Psychological Well-Being – A Bidirectional Relationship, Alysha S. Thompson, Nicola P. Bondonno, Yan Lydia Liu, Farah Qureshi, Laura D. Kubzansky, Claudia Trudel-Fitzgerald, Julia K. Boehm, Eric B. Rimm, Aedín Cassidy

Psychology Faculty Articles and Research

Background and aim

Methods

Nutrient-Driven Transcription Factor-Dna Interactions And Their Signaling Mechanisms In Metabolic Disease, Evelyn A. Bates

Theses and Dissertations--Nutritional Sciences

Metabolic homeostasis is maintained through tightly coordinated signaling networks that integrate diverse physiological inputs. Central to this regulation are transcription factors, which sense nutrient, hormonal, and vitamin-derived signals and translate them into coordinated gene expression programs. Transcription factor activity is governed by DNA binding, recruitment of coregulatory proteins, and interactions with specific response elements in gene promoters, which allows them to selectively modulate diverse metabolic pathways. Owing to their multifactorial and tunable nature, transcription factors have emerged as promising targets for the treatment and diagnosis of metabolic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). This dissertation explores the molecular …

The Triangular Interaction Between Dietary Polyphenols, Gut Microbiota, And Metabolic Syndrome, Emily Bayliss

Senior Honors Theses

Type 2 diabetes mellitus (T2DM) is a growing global health concern characterized by peripheral insulin resistance as well as impaired insulin secretion from pancreatic β-cells. Emerging evidence suggests that the gut microbiome, specifically gut dysbiosis, an imbalance in the gut microbiome, is a critical modulator of the pathophysiology of T2DM. Dietary polyphenols, a diverse group of bioactive compounds that are abundant in plant-based foods, have recently gained attention for their potential to attenuate metabolic disorders through their antioxidant and anti-inflammatory properties as well as through modulating the composition and activity of gut microbes, thereby attenuating dysbiosis. However, the diabetic state …

Optimizing Endothelial Cell Specific Polymersome-Based Atheroprotective Therapies, Ally C. Brawner

All Theses

Atherosclerotic cardiovascular disease is the number one cause of death in the United States and the world. Every year, billions of dollars are spent in the US alone for direct treatments of this disease, especially on prescription medicines like statins. However, these medications have been unable to curtail global mortality rates, partially because they do not target the entirety of atherosclerotic pathophysiology. A key area of this pathophysiology is that atheroprone arteries typically include pro-inflammatory endothelial cells that exhibit decreased levels of apoAI-mediated cholesterol efflux and an increased release of adhesion molecules, such as VCAM-1. The objective of my project …

Development Of Databases For Glycan Utilization And Anti-Prokaryotic Defense In Microbiomes, Yuchen Yan

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Microbiomes in humans, animals, plants, and other environments are necessary components of the biosphere for global nutrient cycling and maintaining ecosystem balance. In particular, the gut microbiome plays an essential role in modulating human health through glycan utilization. Carbohydrate-active enzymes (CAZymes), CAZyme gene clusters (CGCs), and polysaccharide utilization loci (PULs) are key genomic features that determine microbial capacities for carbohydrate metabolism. Meanwhile, the arms race between phages and prokaryotes has led to the evolution of various anti-prokaryotic immune systems (APIS) in phages to counteract prokaryotic immune systems (PIS).

As bioinformatics methods used to analyze microbiome information advance rapidly, there is …

The Role Of Peroxisomal Acot4 And Acot8 In Modulating Lipid Metabolism And Stress Pathways In Steatotic Hepatocytes, Sylwia Miekus

Department of Nutrition and Health Sciences: Dissertations, Theses, and Student Research

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by excessive lipid accumulation in hepatocytes and the development of lipotoxic stress that disrupts cellular homeostasis. Peroxisomal lipid metabolism plays an important role in maintaining acyl-CoA balance during fatty acid overload, yet the contribution of peroxisomal acyl-CoA thioesterases to early lipotoxic responses remains insufficiently understood. The aim of this study was to investigate the functional involvement of the peroxisomal enzymes acyl-CoA thioesterase 4 (ACOT4) and acyl-CoA thioesterase 8 (ACOT8) in hepatocyte lipid handling under acute lipotoxic conditions. An in vitro model of steatosis was established in AML12 cells through exposure to a …

Metagenomic Characterization Of Gut Microbiota In Children With Autism Spectrum Disorder: Microbial Signatures And Modulation By Anti-Inflammatory Diet And Probiotics, Marysol Valencia-Buitrago, Rodrigo Dias Oliveira-Carvalho, Valbert Cardoso, Jessica Triviño-Valencia, Luisa Matilde Salamanca-Duque, Vanessa Martínez-Díaz, Jovanny Zabaleta, Narmer Fernando Galeano-Vanegas, Carlos Andrés Naranjo-Galvis

School of Medicine Faculty Publications

Background: Autism Spectrum Disorder (ASD) is increasingly associated with alterations in gut microbiota, intestinal permeability, and immune dysregulation. However, integrative studies exploring these mechanisms in Latin American populations are lacking. Objective: To characterize gut microbiota profiles in Colombian children with ASD and evaluate the effects of two microbiota-targeted interventions, an anti-inflammatory diet and a probiotic formulation, on microbial diversity and taxonomic composition. Methods: In a two-phase study, shotgun metagenomic sequencing was performed on fecal samples from 23 children with ASD and 7 typically developing (TD) controls. In the second phase, 17 children with ASD were randomized to receive a 12-week …

Improved Rumen Microbiome Interpretation Via Empirical Filtration Derived From Known Mock Microbiomes, Wesley A. Tom

School of Biological Sciences: Dissertations, Theses, and Student Research

The rumen microbiome plays a critical role in ruminant health and performance. As a consequence, many studies investigate microbial community composition using 16S rDNA based sequencing. As such, data quality and data filtering are critical to accurately identify microbial community composition. In this study we use mock communities to empirically select data filtering parameters to reduce artifact populations and compared the effect of filtering using different bioinformatic pipelines using rumen bacterial community data. The filtering parameters identified provides consistent estimates of rumen microbial diversity, regardless of bioinformatic pipeline utilized and provides a more accurate view of microbiome structure and composition. …

Alternative Therapeutics For Human Breast Cancer: Nutraceutical Underpinnings, In Vitro Metabolomic Profiling, Treatment Efficacy, And Contextual Ethical Implications, Aubrey A. Mattingly

All Dissertations

Breast cancer remains one of the most prevalent diseases worldwide, yet therapeutic equity is still lacking. Standard treatments including surgery, radiotherapy, chemotherapy, and long-term hormone therapy. These approaches are often accompanied by significant side effects. While newer methods such as immunotherapy and targeted therapies have emerged, chemotherapy protocols and incorporation have remained largely unchanged in the past decades. In this context, nutraceuticals represent an alternative or adjuvant to therapy worthy of exploration. The reviewed literature highlights the anti-carcinogenic activity in selected nutraceuticals, marjoram, thyme and persimmon, considering their phytochemical constituents and secondary metabolites. Metabolomic profiling using the Biolog Phenotype Mammalian …

The Effect Of Diet Formulations Containing Different Protein Sources On Energy And Nitrogen Utilization In Lactating Jersey Cows, Kortney Ann Harpestad

Department of Animal Science: Dissertations, Theses, and Student Research

It is well understood that lactating dairy cows require metabolizable protein (MP) for milk yield and milk protein synthesis. Diets with conventional feed sources like corn and soybean meal (SBM) may not sufficiently meet all MP and amino acid (AA) requirements so supplementation with more rumen undegradable protein (RUP) rich feeds or rumen-protected AA can be fed to support animal performance. The growth trajectory of biofuels has resulted in dramatic increases in the production of feeds like heat treated soybean meal (HTSBM). While the chemical composition of this product is understood, there is a need to better understand how HTSBM …

Antimicrobial Eats: How Food Additives Are Contributing To Obesity Via The Gut Microbiome, Olivia Mankos

Senior Honors Theses

The typical modern diet is brimming with food additives used in food processing. Additives such as antibiotic residues, GMOs, pesticide residues, anti-caking agents, emulsifiers, artificial sweeteners, colorants, flavor enhancers, and preservatives. Most of these additives seem to shift the gut microbiome towards more pro-inflammatory signals. When all these additives are considered as an amalgam, such as with the modern processed diet, the ramifications on the gut microbiome are concerning. Obesity, which is characterized by low-level chronic inflammation, is likely exacerbated by these food additives. Consequently, most of these additives should be avoided or banned for optimal health.

The Impact Of Paternal Obesity On Placental Development And Function During Pregnancy, Delaney G. Wolfe, Delaney G. Wiolfe

Department of Nutrition Student Projects

Paternal obesity is a rising concern in conception and reproductive health, with increasing evidence suggesting its impact on pregnancy outcomes. While maternal obesity's effects on fetal development and placental function are well-documented, the role of paternal obesity remains less understood. The placenta, crucial for nutrient exchange and fetal development, can be disrupted by inflammation, oxidative stress, and epigenetic modifications, potentially leading to long-term health implications for both maternal and fetal health. Understanding the paternal influence on placental development is essential for improving pregnancy outcomes and offspring
health. This study aims to investigate the relationship between paternal obesity on placental function …

Could Psilocin Rescue Chronic, Stress-Accelerated, Transcriptional Aging In Brain?, Danny R. Craig, Eric M. Blalock

Journal of Pharmacology & Nutritional Sciences

Brain aging (BA) processes are complex, often affect multiple systems, and frequently lead to cognitive decline and increased susceptibility to insults. BA appears to be a primary risk for the development of many prominent neurodegenerative pathologies. The US Census Bureau predicts that the aging population (65+) will represent a greater proportion of the US population than children (under 18) by 2034, dramatically increasing the burden on health-care infrastructure.¹⁷ Several mechanisms of stress driven, aging-related neurologic dysfunction have been advanced in the past 50 years and include: Stress hormone exposure and glucocorticoid cascade;^{7, 16} calcium ion dyshomeostasis;⁸ allostatic …

Impact Of Minimally Processed Red Meat On Biomarkers Of Cognitive Decline, Saba Vaezi

Electronic Theses and Dissertations

No abstract provided.

Raman Spectroscopy For Rapid Quantification Of Macronutrients In Heirloom Beans, K. Chandler Williams

Graduate Theses, Dissertations, and Problem Reports (ETD)

Quantification of macronutrients in food requires a large investment in facilities and instrumentation as well as ongoing expenses of labor, reagents, and hazardous waste disposal. These costs pose a significant barrier to determining macronutrient quantities in the thousands of uncharacterized landrace and heirloom crops and discourage traditional crop breeding projects from ensuring that their selected crops maintain desirable macronutrient profiles in addition to target agronomic traits. Our objective was to test whether a hand-held Raman spectrometer—a technology which has found use in plant disease diagnostics but remains largely overlooked in nutrient quantification-- could provide a feasible means for quantifying the …

Increasing The Impact Of Dietary Fiber From Grains On Human Health Through Gut Microbiome, Sujun Liu

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

The relationship between dietary fiber intake and human health has gained significant attention due to its potential in preventing chronic diseases and promoting gut health. Grains are a primary source of dietary fiber; however, the health impact of grain fibers is often limited because they are incompletely metabolized by gut bacteria. This dissertation explores innovative strategies to enhance the concentration and of dietary fiber from grains and its utilization by gut bacteria. By investigating various treatments, this research aims to maximize the health benefits of grain-derived dietary fibers, thereby contributing to a healthier society.

This dissertation is organized into four …

The Role Of Lymph-Adipose Crosstalk In Alcohol-Induced Perilymphatic Adipose Tissue Dysfunction, Kourtney D. Weaver, Liz Simon, Patricia E. Molina, Flavia Souza-Smith

School of Graduate Studies Faculty Publications

Chronic alcohol use leads to metabolic dysfunction in adipose tissue. The underlying mechanisms and the contribution of alcohol-induced adipose tissue dysfunction to systemic metabolic dysregulation are not well understood. In our previous studies, we found that chronic alcohol feeding induces mesenteric lymphatic leakage, perilymphatic adipose tissue (PLAT) inflammation, and local insulin resistance in rats. The goal of this study was to further explore the link between alcohol-induced lymphatic leakage and PLAT immunometabolic dysregulation, locally and systemically, using in vivo and ex vivo approaches. Male rats received a Lieber–DeCarli liquid diet, of which 36% of the calories were from alcohol, for …

The Epigenetic Impact Of Dietary Choline On Growth Outcomes Of Children Exposed To Gestational Diabetes Mellitus, Ismail Kadam

Dissertations, Theses, and Capstone Projects

Maternal insulin resistance and hyperglycemia lead to gestational diabetes mellitus (GDM) which can cause fetal hyperinsulinemia, ultimately leading to excessive fetal growth associated with macrosomia and increased adiposity at birth. Increased placental macronutrient transport and epigenetic changes in growth and metabolic genes affected by GDM contribute to fetal overgrowth and can result in complications such as overweight/obesity, insulin resistance/type 2 diabetes, cardiovascular disease risk factors, as well as cognitive impairment later in life. Choline, an essential nutrient, participates in lipid and energy metabolism by providing methyl groups for DNA methylation and thus may overcome the hypomethylation of growth and metabolic …

Characterizing Gait In Young Male 5xfad Mice, Sophiya L. Sims, Kate E. Pauss, Sami L. Case, Ruei-Lung Lin, Leopoldine B. Galopin, Nicholas A. Wright, Olivier Thibault

Journal of Pharmacology & Nutritional Sciences

Gait control represents a non-cognitive domain that is affected negatively during late stages of Alzheimer’s Disease (AD) and AD Related Dementias (ADRDs). In some cases, early identification can be predictive of worsened cognitive function. Prompt detection could help define intervention windows, perhaps even years prior to formal diagnosis of dementia. In this study, the locomotor function of 3-month-old male 5xFAD mice was evaluated using several variables (speed, deviance from center, paw precision index, stride length, stride length deviation, and stride time) to characterize the change in ambulatory behavior prior to the onset of cognitive decline. The data presented here show …

Molecular Mechanisms Of Exercise-Stimulated Resolution Of Inflammation And Its Dietary Dependence., Ernesto H. Pena Calderin

Electronic Theses and Dissertations

Diet-induced obesity and adipose tissue (AT) inflammation that ensues sets the stage for systemic metabolic inflammation, disrupted insulin signaling, and eventual type 2 diabetes (T2D) development. At the center of this pathology lies a disruption in endogenous inflammation resolution pathways characterized by an imbalance in lipid mediator production (greater abundance of pro-inflammatory to pro-resolving lipids). Additionally, obese states are characterized by adrenergic deficiency, especially in response to physical activity. Inflammatory processes have been experimentally mitigated by either the pharmacological inhibition of pro-inflammatory signals (i.e., Leukotriene B₄ (LTB₄) and its receptor BLT1, which establishes a potent chemotactic stimulus …

The Lipid-Heart Hypothesis And The Keys Equation Defined The Dietary Guidelines But Ignored The Impact Of Trans-Fat And High Linoleic Acid Consumption, Mary T. Newport, Fabian M. Dayrit

Chemistry Faculty Publications

In response to a perceived epidemic of coronary heart disease, Ancel Keys introduced the lipid-heart hypothesis in 1953 which asserted that high intakes of total fat, saturated fat, and cholesterol lead to atherosclerosis and that consuming less fat and cholesterol, and replacing saturated fat with polyunsaturated fat, would reduce serum cholesterol and consequently the risk of heart disease. Keys proposed an equation that would predict the concentration of serum cholesterol (ΔChol.) from the consumption of saturated fat (ΔS), polyunsaturated fat (ΔP), and cholesterol (ΔZ): ΔChol. = 1.2(2ΔS - ΔP) + 1.5ΔZ. However, the Keys equation conflated natural saturated fat and …

Overall And Sex-Specific Associations Of Serum Lipid-Soluble Micronutrients With Metabolic Dysfunction-Associated Steatotic Liver Disease Among Adults In The United States, Weiwen Chai, Meng-Hua Tao

Department of Nutrition and Health Sciences: Faculty Publications

This study examined overall and sex-specific associations of serum lipid-soluble micronutrients including α- and γ-tocopherols, 25-hydroxy-vitamin D (25(OH)D), retinol, and six major carotenoids with metabolic dysfunction-associated steatotic lever disease (MASLD) using the 2017–2018 National Health and Nutrition Examination Survey. This analysis included 3956 adults (1991 men, 1965 women) aged ≥ 20 years. Steatotic liver disease was determined through transient elastography examination. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for MASLD associated with micronutrients were estimated using logistic regressions. Higher serum α-tocopherol (highest vs. lowest quartile: OR = 1.53, 95% CI = 1.05–2.22, p = 0.03) and γ-tocopherol (highest …

Association Of Habitual Intake Of Probiotic Supplements And Yogurt With Characteristics Of The Gut Microbiome In The Multiethnic Cohort Adiposity Phenotype Study, Weiwen Chai, Gertraud Maskarinec, Unhee Lim, Carol J. Boushey, Lynne R. Wilkens, V. Wendy Setiawan, Loïc Le Marchand, Timothy W. Randolph, Isaac C. Jenkins, Johanna W. Lampe, Meredith A.J. Hullar

Department of Nutrition and Health Sciences: Faculty Publications

Consumption of probiotics and/or yogurt could be a solution for restoring the balance of the gut microbiota. This study examined associations of regular intake of probiotic supplements or yogurt with the gut microbiota among a diverse population of older adults (N=1,861; 60–72 years). Fecal microbial composition was obtained from 16S rRNA gene sequencing (V1-V3 region). General Linear Models were used to estimate the associations of probiotic supplement or yogurt intake with microbiome measures adjusting for covariates. Compared to non-yogurt consumers (N=1,023), regular yogurt consumers (≥once/week, N=818) had greater Streptococcus (β=0.29, P=0.0003) and lower Odoribacter (β=−0.33, P<0.0001) abundance. The directions of the above associations were consistent across the five ethnic groups but stronger among Japanese Americans (Streptococcus: β=0.56, P=0.0009; Odoribacter: …

The Impact Of Iron Supplementation On The Preterm Neonatal Gut Microbiome: A Pilot Study, Matthew Van Ormer, Maranda Thompson, Melissa K. Thoene, Jean-Jack Riethoven, Sathish Kumar Natarajan, Ann Anderson-Berry

Department of Nutrition and Health Sciences: Faculty Publications

Objective The gastrointestinal microbiome in preterm infants exhibits significant influence on optimal outcomes–with dysbiosis shown to substantially increase the risk of the life-threatening necrotizing enterocolitis. Iron is a vital nutrient especially during the perinatal window of rapid hemoglobin production, tissue growth, and foundational neurodevelopment. However, excess colonic iron exhibits potent oxidation capacity and alters the gut microbiome–potentially facilitating the proliferation of pathological bacterial strains. Breastfed preterm infants routinely receive iron supplementation starting 14 days after delivery and are highly vulnerable to morbidities associated with gastrointestinal dysbiosis. Therefore, we set out to determine if routine iron supplementation alters the preterm gut …

The Role Of Ferroptosis In Cholangiocarcinoma, Apiwit Sae-Fung

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cholangiocarcinoma (CCA) is a highly heterogeneous and aggressive malignancy of the bile ducts, characterized by a poor prognosis and high mortality rate. Despite advancements in treatment, effective targeted therapies and reliable prognostic biomarkers remain limited. Ferroptosis, a regulated form of cell death, has emerged as a potential therapeutic target in various cancers. However, its role in CCA remains poorly understood. In this study, we conducted a comprehensive analysis of ferroptosis-related genes (FRGs) to predict the prognosis of CCA and identify potential therapeutic targets. Using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis on a training dataset, followed …

Sphingosine Kinase 2 Depletion Dysregulates Hepatic Redox Metabolism And Enhances Inflammation In Early Metabolic Dysfunction-Associated Steatohepatitis (Mash), Kaitlyn Georgene Jackson

Theses and Dissertations

Metabolic dysfunction-associated steatotic liver disease (MASLD) currently affects one in three people worldwide; its prevalence is growing alongside other cardiometabolic disorders. Aberrations to redox and sphingolipid metabolism contribute to MASLD pathologic progression. Sphingosine-1-phosphate (S1P) is an active lipid, meaning that S1P participates in biochemical processes within the cell. S1P is generated by two distinct isoenzymes, sphingosine kinase (SphK)1 and SphK2. The localization of the SphK enzyme dictates S1P function. While cytosolic SphK1-generated S1P is well-characterized, nuclear and mitochondrial SphK2-generated S1P is less known. Moreover, SphK2 depletion effects on cellular redox processes and inflammation are not well-defined.

This study defines the …

Development Of Nanomaterial-Based Electrochemical Detection Devices For Point-Of-Care Testing, Khageephun Permpoka

Chulalongkorn University Theses and Dissertations (Chula ETD)

Electrochemical detection aligns with the REASSURED criteria established by the World Health Organization. Nanomaterials also play a crucial role in enhancing detection performance. Therefore, this research integrates nanomaterials into the development of pointof-care testing (POCT) devices for detecting prostate cancer biomarkers and monitoring wound infection status. Timely diagnosis can significantly reduce the physical burden of illness, ease pressure on healthcare systems, and lessen the broader socioeconomic impact. The first part of the research involves the development of a paper-based analytical device for detecting the enzyme myeloperoxidase (MPO). Glucose oxidase (GOx) was immobilized on paper to produce hydrogen peroxide (H2O2 ), …

Mitigating Risks For Dementia In Apoe4 Mice: Efficacy Of Prebiotic Inulin, Probiotics, And Fecal Microbiota Transplants, Ya-Hsuan Chang

Theses and Dissertations--Pharmacology and Nutritional Sciences

Apolipoprotein E4 allele (APOE4) carriers show early metabolic changes, heightening the genetic risk of late-onset Alzheimer's Disease (AD), characterized by amyloid-β and tau tangle plaques and neurodegeneration. Its development is influenced by age, environment, and genetics, with Mild Cognitive Impairment (MCI) often preceding AD, providing a crucial window for early intervention. Factors in AD progression include sex differences and gut microbiome imbalances, with women disproportionately affected and APOE4 carriers showing early metabolic and cognitive changes. This study explores the potential of prebiotic inulin, probiotic Bifidobacterium animalis, and fecal microbiota transplants (FMT) from healthy donors to mitigate AD …