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  • Dr. Angelos Sikalidis, is currently serving as a Professor of Nutrition at CalPoly Food Science and Nutrition Departm... moreedit
Dietary protein is required to support recovery and adaptation following exercise training. While prior research demonstrates that many athletes meet total daily protein needs, intake seems to be predominantly skewed toward the evening... more
Dietary protein is required to support recovery and adaptation following exercise training. While prior research demonstrates that many athletes meet total daily protein needs, intake seems to be predominantly skewed toward the evening meal. An even distribution of protein doses of ≥0.24 g/kg BW consumed throughout the course of a day is theorized to confer greater skeletal muscle anabolism outcomes compared to a skewed pattern of intake. Protein quality is also an important dietary consideration for athletes, with the amino acid leucine seemingly serving as the primary driver of the postprandial anabolic response. The present study investigates protein consumption characteristics among a cohort of NCAA D1 soccer players and evaluates differences between male and female athletes. Athletes were instructed to complete 3-day food diaries, which were subsequently analyzed and compared to UEFA expert group-issued nutrition guidelines for soccer players. Breakfast, lunch, and dinner accou...
In our project herein, we use the case of farmworkers, an underserved and understudied population at high risk for Type-2 Diabetes Mellitus (T2DM), as a paradigm of an integrated action-oriented research, education and extension approach... more
In our project herein, we use the case of farmworkers, an underserved and understudied population at high risk for Type-2 Diabetes Mellitus (T2DM), as a paradigm of an integrated action-oriented research, education and extension approach involving the development of long-term equitable strategies providing empowerment and tailored-made solutions that support practical decision-making aiming to reduce risk of T2DM and ensuing cardiovascular disease (CVD). A Technology-based Empowerment Didactic module (TEDm) and an Informed Decision-Making enhancer (IDMe) coupled in a smart application (app) for farmworkers aiming to teach, set goals, monitor, and support in terms of nutrition, hydration, physical activity, sleep, and circadian rhythm towards lowering T2DM risk, is to be developed and implemented considering the particular characteristics of the population and setting. In parallel, anthropometric, biochemical, and clinical assessments will be utilized to monitor risk parameters for T...
Aim: This study aimed to investigate the relationships between dietary habits, income levels and type 2 diabetes mellitus (T2DM) risk in Turkish female university students who are living with their family or in the dormitory. Materials... more
Aim: This study aimed to investigate the relationships between dietary habits, income levels and type 2 diabetes mellitus (T2DM) risk in Turkish female university students who are living with their family or in the dormitory. Materials and Methods: This work was a cross-sectional pilot study conducted during December 2016–January 2017 in Istanbul Yeni Yuzyıl University. A survey was administered to 100 female students, 60 living with their family and 40 in dormitories. Income level was determined based on TURKSTAT 2015 percentiles. T2DM risk was determined using the Finnish Diabetes Association Type 2 Diabetes Risk Assessment Form (FINDRISC). Food frequency questionnaire and 24 h dietary recall results were analyzed by the diet analysis software Beslenme Bilgi Sistemi (BeBiS), specially developed for Turkey. Results: Results indicated inadequacies and imbalanced nutrition among female college students overall. Notably, there was a statistically significant higher diet quality for th...
The success of performance in basketball relies on both optimal body composition and nutrient intake. The purpose of this study was to examine seasonal changes in body composition (BC), resting metabolic rate (RMR) and respiratory... more
The success of performance in basketball relies on both optimal body composition and nutrient intake. The purpose of this study was to examine seasonal changes in body composition (BC), resting metabolic rate (RMR) and respiratory quotient (RQ), as well as dietary intake of National Collegiate Athletic Association (NCAA) Division I (DI) male basketball players. BC, RMR and RQ were assessed during pre-season, in-season, and post-season (September, December, and March) while dietary assessment data were collected in September and February. Results of this study indicated that players received inadequate energy (p < 0.0001), protein (p < 0.001) and carbohydrate (p < 0.0001) relative to the recommendations for exercising individuals during the September baseline period. However, following diet analysis and consultations and relative to recommendations, athletes received adequate amounts of energy and protein during follow-up, yet intakes of carbohydrate (p = 0.0025) were still ...
The beverage industry is a significant market that is seeing a growth albeit certain types of beverages such as wine and soda-type drinks are seemingly declining. There is certainly seen a growing interest for novel beverages, especially... more
The beverage industry is a significant market that is seeing a growth albeit certain types of beverages such as wine and soda-type drinks are seemingly declining. There is certainly seen a growing interest for novel beverages, especially when creating healthy options aiming to support health via enhanced functional food/beverage properties. Furthermore, understanding how the public perceives and makes purchasing decisions towards novel and unconventional options is of key importance. The Soft Seltzer category is an emerging category defined as a sparkling water-based low calorie, no added sugar, no artificial sweetener, non-alcoholic, carbonated beverage. In our pilot study herein, we aimed to assess interest and willingness to pay for such a product produced in Sonoma, California, specifically H2O/H2♡, a dealcoholized wine-type beverage enriched with vitamins, potassium, and calcium, using a perception and acceptability study to health-conscious college students in California. Resp...
ABSTRACTThe efficiency of two low-cost, abundant and natural clay minerals, palygorskite and vermiculite, in terms of reducing the concentation of Cu2+ and Ni2+ ions was evaluated here. Natural clay minerals were characterized by X-ray... more
ABSTRACTThe efficiency of two low-cost, abundant and natural clay minerals, palygorskite and vermiculite, in terms of reducing the concentation of Cu2+ and Ni2+ ions was evaluated here. Natural clay minerals were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), BET specific surface area and pore-diameter analysis. Batch-type experiments were performed and various parameters, i.e. pH, clay amount, contact time and initial metal concentration, that affect adsorption processes were investigated. The adsorption of Cu2+ and Ni2+ ions is pH-dependent, while minor clay quantities were sufficient to achieve high removal efficiencies. Adsorption equilibrium occurred in 60 min and the adsorption kinetics were better described by pseudo-second-order kinetics. Experimental results were analysed by the Langmuir, Freundlich, Dubinin–Radushkevich (D–R), Temkin and Halsey isotherm equations. The release of exchangea...
Abstract Human nutrition has progressed impressively from the hunter-gatherer mode to that of promising personalized nutrition for health optimization through advanced and sophisticated omics technologies. The contemporary major diseases,... more
Abstract Human nutrition has progressed impressively from the hunter-gatherer mode to that of promising personalized nutrition for health optimization through advanced and sophisticated omics technologies. The contemporary major diseases, while having strong genetic components, do not conform to Mendelian genetics; hence, their expression/manifestation is not controlled by a single gene. Noncommunicable diseases such as obesity, cancer, type 2 diabetes mellitus, and cardiovascular disease are attributed to a series of chronic anomalies closely related to dietary, among other, environmental factors, and consistent deregulation of one or more groups of genes (polygenic). Collectively, these diseases constitute the main cause of death globally and pose tremendous financial burden on healthcare systems. Dietary interventions offer significant possibilities for cost-effective strategies to reduce risk of a series of metabolic diseases and/or improve the outcome of prognosis. In recent decades, the ability of particular nutrients to influence certain cellular functions as well as the regulation of several metabolic pathways via genomic interplay has been demonstrated. Nutrients can influence cellular responses and hence exert an effect on health parameters and outcomes. Several nutrients have been documented to extend their regulatory capacity at various levels including gene expression profile signatures’ modulation. In addition, specific nutrients can modulate expression/activation of genes that encode regulatory hormones, which in turn are signaling agents strongly affecting metabolism and subsequently risk levels for certain metabolic diseases. The field of nutrigenomics attempts to revolutionize modern thinking on diet, food, and health; whether it will deliver is still an open matter of debate Key teaching points: A brief, yet comprehensive account on how food and nutrition evolved to give rise to nutrigenomics. Discusses potential of nutrigenomics for public health contribution in noncommunicable diseases. Debates credibility of nutrigenomics’ commercial products versus the bio-hype in the field. Presents experts’ and stakeholders’ opinions for future directions of nutrigenomics.
Bile was sequestered with clinoptilolite under simulated digestion of a high-fat meal. Molecular docking modeling indicates the most electronegative parts of the bile acids (here: cholic acid) docking at an electropositive region of the... more
Bile was sequestered with clinoptilolite under simulated digestion of a high-fat meal. Molecular docking modeling indicates the most electronegative parts of the bile acids (here: cholic acid) docking at an electropositive region of the clinoptilolite matrix.
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Translation initiation is known to be regulated by the binding of eukaryotic initiation factor 4E (eIF4E)... more
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Translation initiation is known to be regulated by the binding of eukaryotic initiation factor 4E (eIF4E) by binding proteins (4EBPs), and there is evidence that amino acid deprivation and other cellular stresses upregulate 4EBP1 expression. To pursue the question of whether diets limited in an essential amino acid lead to induction of 4EBP1 expression in vivo, diets that varied in methionine and cystine content were fed to rats for 7 days, and 4EBP1 mRNA and protein levels and 4EBP1 phosphorylation state were determined. Total 4EBP1 mRNA and protein abundance increased in liver of rats with severely deficient intakes of sulfur amino acids (0.23 % or 0.11%methioninewithout cystine) but not in animalswith a less restricted intake of sulfur amino acids (0.11%methionine plus 0.35% cystine) but a similarly restricted intake of total diet (53 to 62 % of con...
The Mediterranean diet (MD) is considered one of the healthiest dietary patterns due to its rich provision of phytochemicals, antioxidants, vitamins, fiber, polyunsaturated, omega-3, and short-chain fatty acids through a variety of foods.... more
The Mediterranean diet (MD) is considered one of the healthiest dietary patterns due to its rich provision of phytochemicals, antioxidants, vitamins, fiber, polyunsaturated, omega-3, and short-chain fatty acids through a variety of foods. The supply of such nutrients and bioactive components can support gut health and reduce systemic inflammation, with accumulating evidence from several human studies demonstrating the utility of the Mediterranean diet in the prevention of chronic and metabolic diseases. Further studies are needed to explore the role of the Mediterranean diet protecting against such diseases and the related mechanisms, including the interplay between components of the MD and gut microbiota. This brief systematic review specifically explores the recent evidence in humans investigating the link between MD and the human microbiota. Herein, over 50 articles were revised and referenced, after a careful vetting process, to produce this manuscript. Articles were ultimately ...
The beverage industry is a significant market that is seeing a growth albeit certain types of beverages such as wine and soda-type drinks are seemingly declining. There is certainly seen a growing interest for novel beverages, especially... more
The beverage industry is a significant market that is seeing a growth albeit certain types of beverages such as wine and soda-type drinks are seemingly declining. There is certainly seen a growing interest for novel beverages, especially when creating healthy options aiming to support health via enhanced functional food/beverage properties. Furthermore, understanding how the public perceives and makes purchasing decisions towards novel and unconventional options is of key importance. The Soft Seltzer category is an emerging category defined as a sparkling waterbased low calorie, no added sugar, no artificial sweetener, non-alcoholic, carbonated beverage. In our pilot study herein, we aimed to assess interest and willingness to pay for such a product produced in Sonoma, California, specifically H2O/H2♡, a dealcoholized wine-type beverage enriched with vitamins, potassium, and calcium, using a perception and acceptability study to health-conscious college students in California. Respe...
Non-alcoholic fatty liver disease (NAFLD) is a serious metabolic condition affecting millions of people worldwide. A “Western-style diet” has been shown to induce pediatric NAFLD with the potential disruption of skeletal muscle... more
Non-alcoholic fatty liver disease (NAFLD) is a serious metabolic condition affecting millions of people worldwide. A “Western-style diet” has been shown to induce pediatric NAFLD with the potential disruption of skeletal muscle composition and metabolism. To determine the in vivo effect of a “Western-style diet” on pediatric skeletal muscle fiber type and fuel utilization, 28 juvenile Iberian pigs were fed either a control diet (CON) or a high-fructose, high-fat diet (HFF), with or without probiotic supplementation, for 10 weeks. The HFF diets increased the total triacylglycerol content of muscle tissue but decreased intramyocellular lipid (IMCL) content and the number of type I (slow oxidative) muscle fibers. HFF diets induced autophagy as assessed by LC3I and LC3II, and inflammation, as assessed by IL-1α. No differences in body composition were observed, and there was no change in insulin sensitivity, but HFF diets increased several plasma acylcarnitines and decreased expression o...
Plant-based diets have become increasingly popular in the past decade, with approximately 11% of Americans self-identifying as vegan or vegetarian and many others trying to reduce meat consumption. Due to increasing interest, the... more
Plant-based diets have become increasingly popular in the past decade, with approximately 11% of Americans self-identifying as vegan or vegetarian and many others trying to reduce meat consumption. Due to increasing interest, the plant-based food market has significantly expanded, with several innovative products serving as alternatives to animal-based products. One such example is almond protein powder, a new protein supplement created as an alternative to whey protein. Due to the novelty of almond protein products, little is known regarding how well the protein supplement supports nitrogen metabolism. The effects of both an almond-based protein beverage and a whey-based protein beverage on nitrogen balance are investigated in the work presented herein. Twenty female college students aged 20–25 years were randomly assigned to consume either an almond- or whey-based protein drink twice daily for one week; 24-h urine collection was performed at the baseline and endpoint of the 7-day ...
The use of technological devices is increasing in all age groups, especially in preschool-aged children. However, there is a limiting number of studies investigating the relationship between the use of technological devices, eating... more
The use of technological devices is increasing in all age groups, especially in preschool-aged children. However, there is a limiting number of studies investigating the relationship between the use of technological devices, eating behavior, and weight status in preschool children. The aim of this study was (1) to describe total usage of technological devices, (2) to evaluate level of exclusive use of such devices by children, (3) to investigate children’s eating behaviors and diet in relation to screen time and type. A cross-sectional study was conducted with 104 children aged 2–5 years in Küçükçekmece and Bakırköy, Istanbul. Data collection consisted of a validated parental questionnaire on demographics and the child’s use of technology and eating behavior, while associations in children were examined using logistic regression analysis. The analysis of the obtained data uncovered a strong association between children’s TV and tablet/smart phone use and the foods consumed by childr...
Objectives This study aimed to investigate relationships between dietary habits, income levels and type 2 diabetes mellitus (T2DM) risk in Turkish female university students who are living with their family or in the dormitory. Methods... more
Objectives This study aimed to investigate relationships between dietary habits, income levels and type 2 diabetes mellitus (T2DM) risk in Turkish female university students who are living with their family or in the dormitory. Methods This work was a cross-sectional study conducted during December 2017 – February 2018 in Istanbul Yeni Yuzyil University. A survey was applied on 127 female students of which 60 were living with their family and 40 in dormitory. Income level was determined based on TURKSTAT 2015 percentiles. T2DM risk was determined using the Finnish Diabetes Association Type 2 Diabetes Risk Assessment Form. Food frequency questionnaire and 24-hour dietary recall results were analysed by specially developed for Turkey diet analysis software Beslenme Bilgi Sistemi (BeBiS). Data were statistically analysed with SPSS for Windows 20.0. Results Our results show university students do not have adequate and balanced nutrition in general. On the other hand, students who are li...
Healthy nutritional habits are of vital importance for good health and quality of life for all individuals in all life stages. Nutritional habits shaped in early childhood set the foundation for future dietary practices applied through... more
Healthy nutritional habits are of vital importance for good health and quality of life for all individuals in all life stages. Nutritional habits shaped in early childhood set the foundation for future dietary practices applied through lifespan, hence informing risk towards chronic diseases. A key contributor to child health is maternal impact. A healthy childhood status translates into increased lifespan, health, and life-quality, as well as better family and social interactions and improved academic performance. These conditions can contribute to a healthier and more vibrant workforce, and thus extend positive impact on the economic and overall development of a country. Evidence related to maternal impact on childhood dietary habits is limited in Turkey, an emerging economy with notable disparities and a significant segment (approximately one third) of its 83 million population under the age of 30. Hence, the aim of this study was to investigate the relationship between the socioe...
The Mediterranean diet is a food pattern incorporated into a set of lifestyle practices typical of Greece and Southern Italy in the early 1960s, where adult life expectancy was notably high, while rates of diet-related chronic diseases... more
The Mediterranean diet is a food pattern incorporated into a set of lifestyle practices typical of Greece and Southern Italy in the early 1960s, where adult life expectancy was notably high, while rates of diet-related chronic diseases were low. The Mediterranean diet was described initially by the work of LG Allbaugh, commissioned by the Rockefeller foundation and the Greek government post-WW2 on the Greek island of Crete in 1948. The Mediterranean diet was accepted as Intangible Cultural Heritage of Humanity by UNESCO in 2013. The primary advantages of the Mediterranean diet include health benefits pertinent to cardiovascular, metabolic syndrome, and cognition.
From the ancient times, when wine/oenos was described as “Wine, the benevolent demon” by ancient Greek gastronomist and philosopher Athinaios in “Dipnosofistes”, to modern days, the craft has seen significant fruition. The wine industry... more
From the ancient times, when wine/oenos was described as “Wine, the benevolent demon” by ancient Greek gastronomist and philosopher Athinaios in “Dipnosofistes”, to modern days, the craft has seen significant fruition. The wine industry has evolved over time, and more so recently, to encompass many different subsets, one of which is the organic wine market. The organic wine industry has grown in recent years, especially in California. This rapid gain in interest has resulted in the evolution of several subsets, including biodynamic, natural, and clean wine. While biodynamic and natural wine, function more as a fulfillment of niche markets, clean wine may provide benefits for consumers that otherwise suffer from side effects of wine consumption. Low sulfite levels and lack of histamines in clean wine plausibly decrease headaches and adverse effects some consumers experience when drinking wine. An overview of the organic wine industry and its evolution with potential contributions to ...
Type 2 diabetes mellitus (T2DM) is a chronic metabolic condition characterized by glucose clearance abnormalities and insufficient insulin response. Left uncontrolled, T2DM can result in serious complications and death. With no cure... more
Type 2 diabetes mellitus (T2DM) is a chronic metabolic condition characterized by glucose clearance abnormalities and insufficient insulin response. Left uncontrolled, T2DM can result in serious complications and death. With no cure available currently and the prevalence of major risk factors such as pre-diabetes and the metabolic syndrome continuously increasing, there is an urgent need for effective treatments with limited or no side effects. Red raspberries (RR) contain various phytonutrients with potential for modulating insulin function, glucose, and lipid metabolism. The objective of this literature review was to investigate the potential metabolic benefits of dietary RR in individuals with T2DM and pre-diabetes. A search of major scientific databases was employed to identify peer-reviewed, in vivo, or human studies that utilized whole RR or its functional constituents as treatment. The studies examined provide evidence that RR may offer clinically beneficial effects for the p...
While onset characteristics may vary, sarcopenia gradually develops over time as a result of the aging process, leading to muscle loss, disturbance of the muscle to fat ratio, and a variety of negative symptoms undermining the wellbeing,... more
While onset characteristics may vary, sarcopenia gradually develops over time as a result of the aging process, leading to muscle loss, disturbance of the muscle to fat ratio, and a variety of negative symptoms undermining the wellbeing, quality of life, and lifespan in the aging population globally. There is evidence that sarcopenia may be a cause and consequence of type 2 diabetes mellitus (T2DM) in the aging population. The importance of nutritional management in the prevention and/or deceleration of sarcopenia is critical, with the main focus placed on the amount and quality of protein intake. Significant efforts are being made towards the development of medical nutrition therapies involving certain amino acids and amino compounds, as well as their combinations, for the improvement in muscle strength, muscle function and protein synthesis. This may reduce hospitalization times and hasten the recovery of patients with sarcopenia. The administration of protocols with varying dose ...
The Beverage Guidance System has established dietary recommendations for daily intake of commonly consumed beverages including water, tea, coffee, milk, non-calorically sweetened beverages, and calorically sweetened beverages. As obesity... more
The Beverage Guidance System has established dietary recommendations for daily intake of commonly consumed beverages including water, tea, coffee, milk, non-calorically sweetened beverages, and calorically sweetened beverages. As obesity in America continues to be a growing problem, this guidance becomes of increasing importance due to many beverages’ potential links to Type 2 Diabetes Mellitus (T2DM), Cardiovascular disease (CVD), and numerous other harmful health effects. However, the growing popularity of “better for you” beverages is causing a shift in the market, with consumers pushing for healthier beverage alternatives. Beverages simultaneously present advantages while posing concerns that need to be evaluated and considered. In this review, health effects of nonalcoholic beverages are discussed including various aspects of consumption and current trends of the beverage market such as the novel Soft Seltzer category as an alternative to Hard Seltzer and various mashups. A var...
Type 2 diabetes mellitus (T2DM) is a disease that affects over 9% of the United States population and is closely linked to obesity. While obesity was once thought to stem from a sedentary lifestyle and diets high in fat, recent evidence... more
Type 2 diabetes mellitus (T2DM) is a disease that affects over 9% of the United States population and is closely linked to obesity. While obesity was once thought to stem from a sedentary lifestyle and diets high in fat, recent evidence supports the idea that there is more complexity pertinent to the issue. The human gut microbiome has recently been the focus in terms of influencing disease onset. Evidence has shown that the microbiome may be more closely related to T2DM than what was originally thought. High fat diets typically result in poor microbiome heath, which then shifts the gut into a state of dysbiosis. Dysbiosis can then lead to metabolic deregulation, including increased insulin resistance and inflammation, two key factors in the development of T2DM. The purpose of this review is to discuss how microbiome relates to T2DM onset, especially considering obesity, insulin resistance, and inflammation.
Evidence associates scholastic performance to quality of eating habits. However, there is limited information on this topic in Turkey, an emerging economy with notable disparities. Our work aimed to evaluate the effect of eating habits... more
Evidence associates scholastic performance to quality of eating habits. However, there is limited information on this topic in Turkey, an emerging economy with notable disparities. Our work aimed to evaluate the effect of eating habits quality of high-school students in Turkey, on the Scholastic Aptitude Standardized Examination (TEOG) scores. The study was conducted in 29 different cities in Turkey during the academic year 2016–2017, involving students of ages 14–17 years (up to senior-high school). A dietary habits survey developed and validated for this population was distributed over the internet in February 2017. Apart from students’ TEOG scores, Family Affluence Score (FAS) was used to categorize the students into low, medium, and high financial standing. Eating Habits Score (EHS) was calculated by using a validated scoring system. A working sample of 298 participants was used. Based on our results, we observed that there is a significant positive correlation between EHS, FAS ...
While proteins are critical for immunity, T-cells constitute a critical component of adaptive immunity by clearing cancerous cells among other abnormal cells. However, cancer cells exhibit a potential to escape T-cell control by employing... more
While proteins are critical for immunity, T-cells constitute a critical component of adaptive immunity by clearing cancerous cells among other abnormal cells. However, cancer cells exhibit a potential to escape T-cell control by employing mechanisms not completely delineated. Interesting work has investigated how certain amino acids affect the proliferation rate of T-cells as well as their effectiveness in clearing tumors. The role of amino acids cysteine, glutamine, phenylalanine, tryptophan and arginine in immunomodulation and particularly regarding T-cell proliferation and activation is discussed. The redox balance is reported to affect T-cell proliferation via modulation of cysteine availability. In addition antigen presenting cells (APCs), similar to myeloid cells determine the availability of amino acids in the extracellular microenvironment affecting T-cell proliferation and activation. A better mechanistic understanding of T-cell function modulation via amino acid signaling ...
Bile, important for cholesterol homeostasis, is a potential target of hypercholesterolemia management. Bile sequestration by orally administered resins, while mostly effective in reducing blood cholesterol, presents several side effects... more
Bile, important for cholesterol homeostasis, is a potential target of hypercholesterolemia management. Bile sequestration by orally administered resins, while mostly effective in reducing blood cholesterol, presents several side effects and disadvantages. Thus, widely available natural edible minerals such as clinoptilolite with adsorptive properties offer an alternative for bile sequestration. In an experimental setting mimicking the physiological conditions of digestion/absorption (pH, temperature, and retention times) with a series of assessment methods, scanning electron microscopy-energy dispersion X-ray analysis (SEM-EDX), X-ray diffraction (XRD), Fourier transform infrared analysis (FT-IR), thermogravimetric differential thermal analysis (TG-DTA), and molecular docking modeling, the ability of natural unmodified clinoptilolite to retain bile, while mixed with a simulated high-fat meal, was investigated. Our results demonstrate that clinoptilolite sequesters bile via adsorption of macromicelles at 75.4% efficiency, when the former is administered at a reasonable dose of 4% (w/w) of a meal's weight. This work provides the possibility of clinoptilolite utilization as a bile-sequestering/cholesterol-reducing agent.
While proteins are critical for immunity, T-cells constitute a critical component of adaptive immunity by clearing cancerous cells among other abnormal cells. However, cancer cells exhibit a potential to escape T-cell control by employing... more
While proteins are critical for immunity, T-cells constitute a critical component of adaptive immunity by clearing cancerous cells among other abnormal cells. However, cancer cells exhibit a potential to escape T-cell control by employing mechanisms not completely delineated. Interesting work has investigated how certain amino acids affect the proliferation rate of T-cells as well as their effectiveness in clearing tumors. The role of amino acids cysteine, glutamine, phenylalanine, tryptophan and arginine in immunomodulation and particularly regarding T-cell proliferation and activation is discussed. The redox balance is reported to affect T-cell proliferation via modulation of cysteine availability. In addition antigen presenting cells (APCs), similar to myeloid cells determine the availability of amino acids in the extracellular microenvironment affecting T-cell proliferation and activation. A better mechanistic understanding of T-cell function modulation via amino acid signaling or metabolic properties may be helpful towards optimization of adaptive immunity with implications for cancer prognosis and treatment.
Using HepG2/C3A cells and MEFs, we investigated whether induction of GSH synthesis in response to sulfur amino acid deficiency is mediated by the decrease in cysteine levels or whether it requires a decrease in GSH levels per se. Both the... more
Using HepG2/C3A cells and MEFs, we investigated whether induction of GSH synthesis in response to sulfur amino acid deficiency is mediated by the decrease in cysteine levels or whether it requires a decrease in GSH levels per se. Both the glutamate–cysteine ligase catalytic (GCLC) and modifier (GCLM) subunit mRNA levels were upregulated in response to a lack of cysteine or other essential amino acids, independent of GSH levels. This upregulation did not occur in MEFs lacking GCN2 (general control non-derepressible 2, also known as eIF2α kinase 4) or in cells expressing mutant eIF2α lacking the eIF2α kinase Ser51 phosphorylation site, indicating that expression of both GCLC and GCLM was mediated by the GCN2/ATF4 stress response pathway. Only the increase in GCLM mRNA level, however, was accompanied by a parallel increase in protein expression, suggesting that the enhanced capacity for GSH synthesis depended largely on increased association of GCLC with its regulatory subunit. Upregulation of both GCLC and GLCM mRNA levels in response to cysteine deprivation was dependent on new protein synthesis, which is consistent with expression of GCLC and GCLM being mediated by proteins whose synthesis depends on activation of the GCN2/ATF4 pathway. Our data suggest that the regulation of GCLC expression may be mediated by changes in the abundance of transcriptional regulators, whereas the regulation of GCLM expression may be mediated by changes in the abundance of mRNA stabilizing or destabilizing proteins. Upregulation of GCLM levels in response to low cysteine levels may serve to protect the cell in the face of a future stress requiring GSH as an antioxidant or conjugating/detoxifying agent.
Alzheimer's disease (AD) is characterized by intraneuronal β-amyloid plaques and hyperphosphorylated tau, leading to neuronal cell death and progressive memory losses. This exploratory work investigates if dietary resveratrol, previously... more
Alzheimer's disease (AD) is characterized by intraneuronal β-amyloid plaques and hyperphosphorylated tau, leading to neuronal cell death and progressive memory losses. This exploratory work investigates if dietary resveratrol, previously shown to have broad anti-aging effects and improve AD pathology in vivo, leads to neuroprotective changes in specific protein targets in the mouse brain. Both wild-type and APP/PS1 mice, a transgenic AD mouse model, received control AIN-93G diet or AIN-93G supplemented with resveratrol. Pathology parameters and AD risk were assessed via measurements on plaque burden, levels of phosphorylated glycogen synthase kinase 3-β (GSK3-β), tau, transthyretin and drebrin. Dietary resveratrol treatment did not decrease plaque burden in APP/PS1 mice. However, resveratrol-fed mice demonstrated increases in GSK3-β phosphorylation, a 3.8-fold increase in protein levels of transthyretin, and a 2.2-fold increase in drebrin. This study broadens our understanding of specific mechanisms and targets whereby resveratrol provides neuroprotection.
Cellular growth repression can mediate positive health outcomes by improving resistance while delaying the manifestation and decelerating the progression, of chronic diseases. Sensing systems that respond to amino acid limitation are, the... more
Cellular growth repression can mediate positive health outcomes by improving resistance while delaying the manifestation and decelerating the progression, of chronic diseases. Sensing systems that respond to amino acid limitation are, the general control non-derepressible kinase 2 (GCN2), the mammalian target of rapamycin (mTOR; namely mammalian target of rapamycin complex 1), the extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase pathway, the adenosine 5-mono-phosphate-activated protein kinase system. GCN2 particularly, under limiting essential amino acid conditions, activates the integrated stress response (ISR) causing selective up- /down-regulation of pro-survival/pro-apoptotic genes, respectively, rendering beneficial adaptation responses to amino acid limitation. This review attempts to bridge the link between molecular events and mechanisms observed at the cellular level with the potential health benefits possibly achieved at the whole organism level. The article describes mechanisms of essential amino acid sensing and provides a discussion on relevant research that suggests a potential role of essential amino acid sensing for promoting health.
A large body of epidemiological data indicates that obesity increases the risk of colon cancer in humans. There are limited studies using rodent models where the relationship between obesity and colon cancer has been studied. In this... more
A large body of epidemiological data indicates that obesity increases the risk of colon cancer in humans. There are limited studies using rodent models where the relationship between obesity and colon cancer has been studied. In this study, wild-type diet-induced obese (DIO) mice and lean wild-type controls were used to investigate the influence of obesity on the risk of colon cancer. We hypothesized that the obese phenotype would exhibit increased colonic tumorigenesis. Colon cancer was chemically induced by injecting the mice with azoxymethane (AOM) at levels that we experimentally determined to result in equivalent AOM concentrations in circulating blood. Risk of colon cancer was assessed via microscopic examination of entire colons for aberrant crypts, aberrant crypt foci and proliferation levels. The DIO mice were found to have significantly more aberrant crypts and aberrant crypt foci as well as increased proliferation of colonocytes per mouse compared to wild-type control mice, supporting the epidemiological data that obesity increases the risk of colonic tumorigenesis.

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