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 …

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 …

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 …

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 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 …

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 …

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 …

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 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 …

Intestinal Microbiome, Fecal Fermentation Profile, And Health Indices In Hiv Infected Men Versus Non-Infected Controls, Mary Andreae, Mary C. Andreae Mrs

Electronic Theses and Dissertations

Many HIV-positive (HIV+) males on Highly Active Anti-Retroviral Therapy (HAART) experience metabolic abnormalities, including Non-Alcoholic Fatty Liver Disease (NAFLD) and lipodystrophy. The intestinal microbiota and short chain fatty acids (SCFA), participate in bidirectional communication with their host. Dysbiosis in HIV+ males on HAART demonstrate a Prevotella-rich enterotype shaped by multiple factors including, medications, adiposity, diet, intestinal permeability, and lifestyle; our objective was to investigate these factors. 19 HIV+ and 21 HIV- males were enrolled. BMI and hip-to-waist ratio (H:W) were obtained, and FibroScan for liver health. Intestinal permeability markers Claudin-21, flagellin, and intestinal fatty acid binding protein (IFABP) in …

Characteristics Of Yogurt And Culture Bacteria As Affected By Ingredients That Help Treat Leaky Gut, Ricardo Jose Santos Aleman

LSU Doctoral Dissertations

At least 100 million people have leaky gut syndrome. This syndrome is associated with multiple health problems such as diabetes, celiac disease, asthma, multiple sclerosis, and inflammatory bowel disease, costing more than $3 billion per year to treat. L-Glutamine, quercetin, slippery elm bark, marshmallow root, N-acetyl-d-glucosamine (NAG), licorice root, maitake mushrooms, and zinc orotate have been reported to help treat leaky gut.

The objectives were to explore the characteristics of yogurt and culture bacteria as affected by ingredients that help treat leaky gut. In yogurt, the pH, titratable acidity, syneresis, viscosity, color, Streptococcus thermophilus, Lactobacillus bulgaricus, yeast and mold and …

Determining The Effects Of Maternal Adiposity On Preterm Neonatal Microbiome And Short Chain Fatty Acid Profiles, Dalton James, William A. Clark Phd, Kristy L. Thomas

Undergraduate Honors Theses

The gut microbiota and its metabolites have vast impacts on the human digestive system, immune system, and health outcomes. Short chain volatile fatty acids (SCVFAs) present in feces can be representative of the interactions of the microbiota present in the gut. Low microbiota diversity in the human gut is highly associated with obesity and adverse health outcomes. Furthermore, the maternal microbiome has a direct impact on neonatal microbiota through various pathways such as environment, skin flora, breast milk composition, and vaginal secretions. This study is aimed to further understand the associations between various factors (maternal adiposity, gestational time, length of …

Gut Microbial Metabolite Indole: A Stimulator Of Enteroendocrine Cell Differentiation Via Activation Of Aryl Hydrocarbon Receptor, James Hart

Theses, Dissertations and Capstones

Enteroendocrine cells (EECs) regulate energy balance and glucose homeostasis by releasing hormones in response to food intake. Dysregulated EEC differentiation is observed in obesity, while gut microbiota metabolites influence this process. Here, we investigated the role of indole, a biologically active gut microbial metabolite, in EEC differentiation through aryl hydrocarbon receptor (AhR) activation. Human intestinal organoids derived from jejunal mucosal biopsies were exposed to indole. Indole treatment significantly increased mRNA levels of chromogranin A, an EEC marker. The effect was reversed by an AhR antagonist, indicating AhR involvement. Indole also upregulated AhR target gene mRNA levels. These findings highlight the …

การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีนในวิถีวิตามินดีและความเสี่ยงต่อภาวะออทิซึมสเปกตรัมในประชากรไทย, ชาญณรงค์ แซ่ฉั่ว

Chulalongkorn University Theses and Dissertations (Chula ETD)

กลุ่มอาการออทิซึมสเปกตรัม (Autism spectrum disorder; ASD) เป็นปัญหาสุขภาพระดับโลกที่สำคัญ โดยพบว่ามีความชุกของโรคที่เพิ่มสูงขึ้น อย่างไรก็ตามสาเหตุและกลไกในการเกิดภาวะออทิซึมสเปกตรัมยังไม่ทราบแน่ชัดอาจเกี่ยวข้องกับปัจจัยด้านพันธุกรรมและสิ่งแวดล้อม โดยปัจจุบันมีรายงานถึงบทบาทของวิตามินกับภาวะออทิซึมสเปกตรัม วัตถุประสงค์ของการศึกษานี้คือศึกษาการเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีนในวิถีเมทาบอลิกของวิตามินดีและความเสี่ยงต่อการเกิดภาวะออทิซึมสเปกตรัมและระดับความรุนแรงของโรคในเด็กไทย การศึกษานี้มีจำนวนอาสาสมัคร 276 ราย โดยเป็นกลุ่มเด็กที่มีภาวะออทิซึมสเปกตรัม 169 ราย และกลุ่มควบคุมเป็นเด็กที่ไม่มีโรคทางระบบประสาท 107 ราย ซึ่งได้ทำการตรวจวิเคราะห์ภาวะพหุสัณฐานทางพันธุกรรมของยีน CYP2R1, CYP27B1, GC และ VDR โดยเทคนิค TaqMan-based real-time Polymerase Chain Reaction (PCR) และตรวจวิเคราะห์ระดับวิตามินดีในกระแสเลือดโดยใช้เทคนิค Chemiluminescence Immunoassay (CLIA) โดยเด็กที่พบภาวะออทิซึมสเปกตรัมจะได้รับการตรวจระดับความรุนแรงของภาวะออทิซึมสเปกตรัมด้วย Childhood Autism Rating Scale, 2nd Edition (CARS2) โดยผลที่ได้จากการศึกษาพบว่า การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีน CYP2R1, CYP27B1, VDR และ GC (rs4588) ไม่มีความสัมพันธ์กับการเกิดภาวะออทิซึมสเปกตรัมและความรุนแรงของอาการออทิซึมสเปกตรัม อย่างไรก็ตามการศึกษาชี้ให้เห็นว่า การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีน GC (rs7041 (A>C)) มีความสัมพันธ์อย่างมีนัยสำคัญกับความเสี่ยงที่เพิ่มขึ้นต่อการเกิดภาวะออทิซึมสเปกตรัมและความรุนแรงของอาการออทิซึมสเปกตรัมด้วย โดยเฉพาะอย่างยิ่งบุคคลที่มีการขาดระดับวิตามินดีร่วมด้วย นอกจากนี้ผลศึกษาพบว่าไอโซฟอร์มของ GC1s และ GC1s-GC1s ฟีโนไทป์มีความสัมพันธ์อย่างมีนัยสำคัญกับความเสี่ยงต่อการเกิดภาวะออทิซึมสเปกตรัมตลอดจนความรุนแรงของอาการออทิซึมสเปกตรัม โดยสรุปการศึกษาวิจัยในครั้งนี้ชี้ให้เห็นว่า การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีน GC (rs7041 (A>C)) และไอโซฟอร์ม GC1s อาจเป็นตัวบ่งชี้ทางพันธุกรรมที่สามารถช่วยในการประเมินความเสี่ยงต่อการเกิดภาวะออทิซึมสเปกตรัมและความรุนแรงของอาการออทิซึมสเปกตรัมในเด็กไทยได้ในอนาคต อย่างไรก็ตามการศึกษาในอนาคตควรศึกษาในกลุ่มประชากรที่ใหญ่ขึ้นเพื่อยืนยันผลการศึกษาวิจัยครั้งนี้

Role Of Grb2 Intracellular Localization In Progesterone Receptor Positive Breast Cancer, Nattamolphan Wittayavimol

Chulalongkorn University Theses and Dissertations (Chula ETD)

Progesterone receptor (PR) extranuclear signaling mediates mainly through PR polyproline domain (PPD) interaction with SH3 domain of cytoplasmic signaling molecules. PR-PPD interfered with Grb2-SOS binding through SH3 interaction resulting in decreased cell proliferation and correlates with a good prognosis in PR positive breast cancer. Grb2 is a key adaptor molecule and expressed in both nucleus and cytoplasm. We hypothesized that change in Grb2 localization alters PR transcription resulting in better clinical outcomes in PR positive breast cancer. BT-474 breast cancer cells expressing inducible Grb2-SV402x (nuclear Grb2, nuGrb2) or Grb2-MYR (membrane Grb2, memGrb2) were constructed. MemGrb2-BT-474 showed higher levels of PR …

Roles Of Progesterone Signaling On Dna Repair And Cell Survival In Ovarian Cancer Cells, Pattarasiri Rangsrikitphoti

Chulalongkorn University Theses and Dissertations (Chula ETD)

Every year over 300,000 women worldwide are diagnosed with ovarian cancer and half of these patients die from this disease. The symptoms of ovarian cancer are very general and often confused with other common female diseases making ovarian cancer a challenging disease to diagnose and treat. Platinum-based chemotherapy, including cisplatin, stands as the first-line treatment for ovarian cancer. However, chemotherapy resistance remains a continuing problem, contributing to a high mortality rate. Progesterone receptor (PR) signaling has been implicated in various aspects of ovarian cancer biology. Clinical studies show a positive correlation between PR expression, improved patient survival and cisplatin response, …

Alzheimer’S Disease Genetics And Short-Chain Fatty Acid Treatment In Studies Of The Murine Gut Microbiome, Diana Zajac

Theses and Dissertations--Physiology

Elucidating the relationship of the gut microbiome in Alzheimer's Disease (AD) risk and pathogenesis is an area of intense interest. Since 60 to 80% of AD risk is related to genetics and APOE alleles represent the most impactful genetic risk factors for AD, their mechanism(s) of action are under intense scrutiny.

First, I conducted a study on APOE targeted replacement mice to investigate the impact of APOE alleles on the murine gut microbiome. The relative abundance of bacteria from the family Ruminococacceae and related genera increased with APOE2 status. The relative abundance of the class Erysipelotrichia increased with APOE4 status, …

Prenatal Choline Supplementation During Maternal Obesity Alters Offspring Response To Western Diets, Hunter W. Korsmo

Dissertations, Theses, and Capstone Projects

Maternal obesity has led to an increase in adverse offspring developmental outcomes and a greater risk for long-term metabolic diseases. Choline, a semi-essential nutrient, can be incorporated into phosphatidylcholine (PC) as well as sphingomyelin (SM) and donate its labile methyl group for the remethylation of homocysteine after choline is oxidized to betaine. Prenatal choline insufficiency has been related to maternal obesity and metabolic diseases, such as metabolic associated fatty liver disease (MAFLD). Choline may interact with maternal obesity to influence the programming offspring.

Chapter 1 presents an introduction of choline and the various clinical outcomes associated with choline supplementation during …

Optimized Selenium Status, Gut Microbiota, And Type 2 Diabetes, Ying-Chen Huang

Theses and Dissertations

We have previously demonstrated that long-term dietary Se deficiency in old Terc^-/- mice with humanized telomeres induces type-2 diabetes and exacerbates age-dependent increases in the abundance of A. muciniphila and Lachnospiraceae, which are related to obesity and metabolic syndromes. The objectives of this dissertation are: 1) to determine the minimum intake of Se required for type 2 diabetes prevention in middle-aged mice; 2) to evaluate the efficacy of A. muciniphila and R. torques (a Lachnospiraceae family member) to intervene dietary Se deficiency-induced type 2 diabetes and the underlying mechanisms; 3) to assess sex differences in the responses to …

The Relationship Between Single Nucleotide Polymorphism In Taste Receptor Genes And Body Composition, Energy Intake, And Macronutrient Consumption In Young Adults​, Manal Abbas Sunbul

Theses and Dissertations

Genetic variations in taste receptor genes play a notable role in human taste perception and food preferences and intake, which may affect nutritional and health status. Understanding how genetic variations in taste receptor genes influence food perception, preferences, and intake can play an important role in designing effective interventions to improve the quality of peoples' nutrition and minimize the risk of diet-related diseases such as obesity. The objective of this study was to investigate single nucleotide polymorphisms (SNPs) of umami taste receptor gene TAS1R1 and GRM4 and sweet taste receptor gene TAS1R3 and percentage of body fat mass (BF%) among …

The Effect Of Different Feeding Regimes On Recent Nutritional And Growth Measurements In Juvenile California Killifish (Fundulus Parvipinnis), Emily Parks

Theses

Gaining a deeper understanding of in-situ growth approximations for juvenile fishes is one way to understand how food consumption may affect fish growth. If variations in growth rate are strongly mirrored by past food status, then the condition (degree of well-being) of fish can be potentially used as a reference for relative prey availability. Furthermore, confirming that there is a positive relationship between food availability and fish growth rate is a critical first step to deepen our understanding of growth rate variation as well as examining if growth can be a proxy for habitat quality.

The California killifish (Fundulus …

Essential Amino Acid (Eaa) Regulation Of Skeletal Muscle Protein Turnover With Age, Mary Komp

Graduate Theses and Dissertations

Skeletal muscle (SM) is vital for both long term health and quality of life. Recent research suggests an increase in catabolic signals with age triggers pathologic conditions, such as sarcopenia. Although results from in vitro studies model how EAA can regulate muscle protein synthesis (MPS), the relevance of these models to muscle protein breakdown (MPB) and the presence of physiological EAA concentrations remains to be established. Therefore, the objective of this study was to determine the effects of a low, normal, and supra physiological dose of EAA (0.2, 1.0, and 3.0 x EAA) in a young (passages 2-10) and aging …

Efficacy Of Multivitamin-Mineral Supplementation On Measures Of Anxiety, Depression, Self-Esteem, Dysregulation, And Perceived Stress In Young Adults, Courtney Gorden

Graduate Theses and Dissertations

Mental health in the United States is at an all-time low with 21% of adults 18+ suffering from depression or anxiety. When compared with other categories, emerging adults (18-25 years old) have the highest prevalence of mental health disorders at 30%. Young adults face an inordinate amount of stress given the COVID-19 pandemic, being in a unique developmental stage, experiencing new relationships, and transitioning from high school to their professional lives. Vitamins and minerals have roles in neurobiochemistry and have been investigated for effects on mental health with mixed results. Few studies factor in the unique emerging adult developmental stage …

Anti-Neuroinflammatory Effects And Underlying Mechanismsof Cleistocalyx Nervosum Var. Paniala Extracts In Microglia Cells, Sakawrat Janpaijit

Chulalongkorn University Theses and Dissertations (Chula ETD)

Sustained inflammatory responses have been implicated in various neurodegenerative disorders. Cleistocalyx nervosum var. paniala (CN), an edible berry, has been reported to exhibit several beneficial properties. However, only limited research is available on this fruit seed, which is classified as agricultural food waste. We therefore focused on the anti-neuroinflammatory effects and underlying mechanism of C. nervosum var. paniala seed extract (CNSE) on BV-2 mouse microglial cells induced by lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-α). CN seeds were extracted in 95% ethanol by Soxhlet extraction. HPLC was carried out to identified resveratrol (RESV) in CNSE. For cell-based studies, the expression …

ฮอร์โมนเอสโตรเจนเหนี่ยวนำให้เกิดการแทรกของ Line-1 ดีเอ็นเอเข้าไปในจีโนมของเซลล์มะเร็งเต้านม, กุลจิรา โรจน์ไพศาลกิจ

Chulalongkorn University Theses and Dissertations (Chula ETD)

ในปัจจุบันโรคมะเร็งเต้านมเป็นมะเร็งที่มีอุบัติการณ์และอัตราการตายสูงที่สุดในเพศหญิงทั่วโลกรวมถึงในประเทศไทยด้วย โดยพบว่า LINE-1 ถือว่าเป็น Retrotransposon element ที่พบมากที่สุดถึง 17 % ของจีโนมและมีความสามารถในการคัดลอกแล้วแทรกตัวเองในบริเวณอื่นของจีโนมซึ่งเป็นสาเหตุของทำให้เกิดความไม่สเถียรของจีโนมอันเป็นสาเหตุของการเกิดโรคมะเร็ง และยังพบว่าการแสดงออกของLINE-1 มีผลต่อการลุกลาม, ขนาด, และระยะของโรคมะเร็งเต้านมด้วย นอกจากนี้ยังพบว่าผู้หญิงที่การได้รับฮอร์โมนเอสโตรเจนต่อเนื่องเป็นระยะเวลานานทำให้ความเสี่ยงของโรคมะเร็งเต้านมเพิ่มมากขึ้น ถึงกระนั้นยังคงไม่ทราบถึงกลไกการทำงานของเอสโตรเจน ดังนั้นผู้วิจัยจึงตั้งสมมุติฐานว่า เอสโตรเจนสามารถเหนี่ยวนำให้เกิดการแทรกของ LINE-1 ดีเอ็นเอเข้าไปในจีโนมของเซลล์มะเร็งเต้านม โดยทำการศึกษาบผลของเอสโตรเจนที่ได้รับต่อการแสดงออกของ LINE-1 mRNA และ LINE-1 โปรตีน รวมถึงผลของเอสโตรเจนที่ได้รับต่อการแทรกของ LINE-1 ดีเอ็นเอโดยวิเคราะห์จากปริมาณดีเอ็นเอในเซลล์มะเร็งเต้านม T47D ผลการทดลองพบว่าที่เอสโตรเจนมีผลทำให้การแสดงออกของ LINE-1 mRNA เพิ่มขึ้นสูงที่สุดอย่างมีนัยสำคัญที่ความเข้มข้นของเอสโตรเจน 5 nM ด้วยวิธี Realtime RT-PCR ในเซลล์มะเร็งเต้านม T47D และผลทำให้การแสดงออกของ LINE-1 mRNA เพิ่มขึ้นสูงที่สุดอย่างมีนัยสำคัญที่ 12 ชม. ด้วยวิธี Realtime RT-PCR ในเซลล์มะเร็งเต้านม T47D และเอสโตรเจนมีผลทำให้การแสดงออกของโปรตีน LINE-1 ORF1p เพิ่มขึ้นสูงที่สุดอย่างมีนัยสำคัญที่ 48 และ 72 ชม. ในเซลล์มะเร็งเต้านม T47D ด้วยวิธี Western blot โดยพบว่าการแสดงออกของโปรตีน LINE-1 ORF1p เพิ่มขึ้นสูงที่สุดอย่างมีนัยสำคัญ 72 ชม. นอกจากนี้เอสโตรเจนมีผลทำให้ปริมาณของ LINE-1 ดีเอ็นเอบริเวณ ORF2 เพิ่มขึ้นสูงที่สุดอย่างมีนัยสำคัญที่ 72 ชม.ในเซลล์มะเร็งเต้านม T47D มากที่สุดอย่างมีนัยสำคัญด้วยวิธี Real-time PCR แสดงให้เห็นว่าเอสโตรเจนมีผลทำให้เกิดการแทรกของ LINE-1 ดีเอ็นเอเข้าไปในจีโนมได้ จากผลการทดลองทั้งหมดจึงสรุปได้ว่า เอสโตรเจนมีผลต่อการเพิ่มแสดงออกของ LINE-1 mRNA และ LINE-1 โปรตีน รวมถึงเพิ่มปริมาณ LINE-1 ดีเอ็นเอ อย่างมีนัยสำคัญในเซลล์มะเร็งเต้านม T47D แสดงว่าเอสโตรเจนสามารถเหนี่ยวนำให้เกิดการแทรกของ LINE-1 ดีเอ็นเอเข้าไปในจีโนมนำไปสู่การกลายพันธุ์ของยีนและความไม่เสถียรของจีโนม

Protumorigenic Effects Of Mixed Lineage Kinase Domain-Like Protein In Cholangiocarcinoma Cells, Nattaya Duangthim

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cholangiocarcinoma (CCA), a heterogeneous malignancy of bile duct system, has the highest incidence in Thailand. CCA is one of the leading causes of death which has low 5-year survival rate from 5% to 10% in advanced stages due to the difficulty of diagnosis in early stage and lack of effective therapies. Therefore, understanding the molecular mechanisms and pathogenesis of CCA development and progression is urgently needs and will lead to the development of novel therapeutic targets and strategies. Mixed lineage kinase domain-like (MLKL) was identified as a key effector in a novel regulated necrosis or necroptosis pathway. Recently studies have …