1 6290 145 THE POTENTIAL ROLE OF NUTRITIONAL GENOMICS TOOLS IN VALIDATING HIGH HEALTH FOODS FOR CANCER CONTROL: BROCCOLI AS EXAMPLE. NUTRITIONAL GENOMICS REFLECTS GENE/NUTRIENT INTERACTIONS, UTILISING HIGH-THROUGHPUT GENOMIC TOOLS IN NUTRITION RESEARCH. THE FIELD ALSO CONSIDERS THE CONTRIBUTION OF INDIVIDUAL GENOTYPES TO WELLNESS AND THE RISK OF CHRONIC DISEASE (NUTRIGENETICS), AND HOW SUCH GENETIC PREDISPOSITION MAY BE MODIFIED BY APPROPRIATE DIETS. FOR EXAMPLE, HIGH CONSUMPTION OF BRASSICACEOUS VEGETABLES, INCLUDING BROCCOLI, HAS REGULARLY ASSOCIATED WITH LOW CANCER RISK. BIOACTIVE CHEMICALS IN BROCCOLI INCLUDE GLUCOSINOLATES, PLANT PIGMENTS INCLUDING KAEMPFEROL, QUERCETIN, LUTEIN AND CAROTENOIDS, VARIOUS VITAMINS, MINERALS AND AMINO ACIDS. CANCER PREVENTION IS HYPOTHESISED TO ACT THROUGH VARIOUS MECHANISMS INCLUDING MODULATION OF XENOBIOTIC METABOLISING ENZYMES, NF-E2 P45-RELATED FACTOR-2 (NRF2)-MEDIATED STRESS-RESPONSE MECHANISMS, AND PROTECTION AGAINST GENOMIC INSTABILITY. BROCCOLI AND BROCCOLI EXTRACTS ALSO REGULATE THE PROGRESSION OF CANCER THROUGH ANTI-INFLAMMATORY EFFECTS, EFFECTS ON SIGNAL TRANSDUCTION, EPIGENETIC EFFECTS AND MODULATION OF THE COLONIC MICROFLORA. HUMAN INTERVENTION STUDIES WITH BROCCOLI AND RELATED FOODS, USING STANDARD BIOMARKER METHODOLOGIES, REVEAL PART OF A COMPLEX PICTURE. NUTRIGENOMIC APPROACHES, ESPECIALLY TRANSCRIPTOMICS, ENABLE SIMULTANEOUS STUDY OF VARIOUS SIGNALLING PATHWAYS AND NETWORKS. PHENOTYPIC, GENETIC AND/OR METABOLIC STRATIFICATION MAY IDENTIFY INDIVIDUALS MOST LIKELY TO RESPOND POSITIVELY TO FOODS OR DIETS. JOINTLY, THESE TECHNOLOGIES CAN PROVIDE PROOF OF HUMAN EFFICACY, AND MAY BE ESSENTIAL TO ENSURE EFFECTIVE MARKET TRANSFER AND UPTAKE OF BROCCOLI AND RELATED FOODS. 2012 2 2986 41 GENETIC ENGINEERING TO ENHANCE CROP-BASED PHYTONUTRIENTS (NUTRACEUTICALS) TO ALLEVIATE DIET-RELATED DISEASES. NUTRITION STUDIES HAVE PROVIDED UNAMBIGUOUS EVIDENCE THAT A NUMBER OF HUMAN HEALTH MALADIES INCLUDING CHRONIC CORONARY ARTERY, HYPERTENSION, DIABETES, OSTEOPOROSIS, CANCER AND AGE- AND LIFESTYLE-RELATED DISEASES ARE ASSOCIATED WITH THE DIET. SEVERAL FAVORABLE AND A FEW DELETERIOUS NATURAL DIETARY INGREDIENTS HAVE BEEN IDENTIFIED THAT PREDISPOSE HUMAN POPULATIONS TO VARIOUS GENETIC AND EPIGENETIC BASED DISORDERS. MEDIA DISSEMINATION OF THIS INFORMATION HAS GREATLY RAISED PUBLIC AWARENESS OF THE BENEFICIAL EFFECTS DUE TO INCREASED CONSUMPTION OF FRUIT, VEGETABLES AND WHOLE GRAIN CEREALS-FOODS RICH IN PHYTONUTRIENTS, PROTEIN AND FIBER. HOWEVER, THE PRESENCE OF INTRINSICALLY LOW LEVELS OF THE BENEFICIAL PHYTONUTRIENTS IN THE AVAILABLE GENOTYPES OF CROP PLANTS IS NOT ALWAYS AT PAR WITH THE RECOMMENDED DAILY ALLOWANCE (RDA) FOR DIFFERENT PHYTONUTRIENTS (NUTRACEUTICALS). MOLECULAR ENGINEERING OF CROP PLANTS HAS OFFERED A NUMBER OF TOOLS TO MARKEDLY ENHANCE INTRACELLULAR CONCENTRATIONS OF SOME OF THE BENEFICIAL NUTRIENTS, LEVELS THAT, IN SOME CASES, ARE CLOSER TO THE RDA THRESHOLD. THIS REVIEW BRINGS TOGETHER LITERATURE ON VARIOUS STRATEGIES UTILIZED FOR BIOENGINEERING BOTH MAJOR AND MINOR CROPS TO INCREASE THE LEVELS OF DESIRABLE PHYTONUTRIENTS WHILE ALSO DECREASING THE CONCENTRATIONS OF DELETERIOUS METABOLITES. SOME OF THESE INCLUDE INCREASES IN: PROTEIN LEVEL IN POTATO; LYSINE IN CORN AND RICE; METHIONINE IN ALFALFA; CAROTENOIDS (BETA-CAROTENE, PHYTOENE, LYCOPENE, ZEAXANTHIN AND LUTEIN) IN RICE, POTATO, CANOLA, TOMATO; CHOLINE IN TOMATO; FOLATES IN RICE, CORN, TOMATO AND LETTUCE; VITAMIN C IN CORN AND LETTUCE; POLYPHENOLICS SUCH AS FLAVONOL, ISOFLAVONE, RESVERATROL, CHLOROGENIC ACID AND OTHER FLAVONOIDS IN TOMATO; ANTHOCYANIN LEVELS IN TOMATO AND POTATO; ALPHA-TOCOPHEROL IN SOYBEAN, OIL SEED, LETTUCE AND POTATO; IRON AND ZINC IN TRANSGENIC RICE. ALSO, MOLECULAR ENGINEERING HAS SUCCEEDED IN CONSIDERABLY REDUCING THE LEVELS OF THE OFFENDING PROTEIN GLUTELIN IN RICE, OFFERING PROOF OF CONCEPT AND A NEW BEGINNING FOR THE DEVELOPMENT OF SUPER-LOW GLUTELIN CEREALS FOR CELIAC DISEASE PATIENTS. 2010 3 6872 32 [POLYPHENOLS AS PROMISING BIOACTIVE COMPOUNDS]. POLYPHENOLS ARE DIVERSE AND WIDESPREAD BIOACTIVE PLANT-BASED COMPOUNDS. THESE COMPOUNDS ARE FOUND IN VARIOUS FOODS SUCH AS BERRIES, FRUITS, VEGETABLES, CEREALS, NUTS, COFFEE, CACAO, SPICES, SEEDS. THEY ARE DIVIDED INTO PHENOLIC ACIDS, STILBENES, FLAVONOIDS, LIGNANS DEPENDING ON THEIR MOLECULAR STRUCTURE. THEY ATTRACT THE ATTENTION OF RESEARCHERS DUE TO WIDE RANGE OF BIOLOGICAL EFFECTS ON HUMAN BODY. THE PURPOSE OF THIS WORK WAS TO ANALYZE MODERN SCIENTIFIC PUBLICATIONS ON THE BIOLOGICAL EFFECTS OF POLYPHENOLS. MATERIAL AND METHODS. THE REVIEW IS BASED ON PUBLICATIONS PRESENTED IN THE PUBMED, GOOGLE SCHOLAR, RESEARCHGATE, ELSEVIER, ELIBRARY, CYBERLENINKA DATABASES USING "POLYPHENOLS", "FLAVONOIDS", "RESVERATROL", "QUERCETIN", "CATECHINS" AS KEY WORDS. PREFERENCE WAS GIVEN TO ORIGINAL RESEARCHES OVER THE PAST 10 YEARS PUBLISHED IN REFEREED JOURNALS. RESULTS. OXIDATIVE STRESS, CHRONIC INFLAMMATION, MICROBIOME DISORDERS, INSULIN RESISTANCE, EXCESSIVE PROTEIN GLYCATION, AND GENOTOXIC EFFECTS ARE AT THE HEART OF THE PATHOGENESIS OF MANY DISEASES, INCLUDING THOSE ASSOCIATED WITH AGE. A LARGE AMOUNT OF MATERIAL HAS BEEN ACCUMULATED ON THE ANTIOXIDANT, ANTICARCINOGENIC, EPIGENETIC, METABOLIC, GEROPROTECTIVE, ANTI-INFLAMMATORY AND ANTIVIRAL EFFECTS OF POLYPHENOLS. THIS GIVES REASONS TO CONSIDER POLYPHENOLS AS VERY PROMISING MICRONUTRIENTS, WHICH INCLUSION IN THE DIET CAN REDUCE THE RISK OF DEVELOPING CARDIOVASCULAR, ONCOLOGICAL, NEURODEGENERATIVE DISEASES, DIABETES MELLITUS, OBESITY, METABOLIC SYNDROME, PREMATURE AGING, THAT IS, THE MAIN CAUSES OF DEATH, A DECREASE IN THE DURATION AND QUALITY OF LIFE OF A MODERN PERSON. CONCLUSION. EXPANDING THE RANGE OF PRODUCTS ENRICHED WITH POLYPHENOLS WITH THEIR HIGH BIOAVAILABILITY IS A PROMISING AREA OF SCIENTIFIC RESEARCH AND DEVELOPMENT OF PRODUCTION IN ORDER TO PREVENT SOCIALLY SIGNIFICANT AGE-ASSOCIATED DISEASES. 2023 4 424 33 ANTHOCYANINS: FROM MECHANISMS OF REGULATION IN PLANTS TO HEALTH BENEFITS IN FOODS. ANTHOCYANINS REPRESENT THE MAJOR RED, PURPLE, AND BLUE PIGMENTS IN MANY FLOWERS, FRUITS, VEGETABLES, AND CEREALS. THEY ARE ALSO RECOGNIZED AS IMPORTANT HEALTH-PROMOTING COMPONENTS IN THE HUMAN DIET WITH PROTECTIVE EFFECTS AGAINST MANY CHRONIC DISEASES, INCLUDING CARDIOVASCULAR DISEASES, OBESITY, AND CANCER. ANTHOCYANIN BIOSYNTHESIS HAS BEEN STUDIED EXTENSIVELY, AND BOTH BIOSYNTHETIC AND KEY REGULATORY GENES HAVE BEEN ISOLATED IN MANY PLANT SPECIES. HERE, WE WILL PROVIDE AN OVERVIEW OF RECENT PROGRESS IN UNDERSTANDING THE ANTHOCYANIN BIOSYNTHETIC PATHWAY IN PLANTS, FOCUSING ON THE TRANSCRIPTION FACTORS CONTROLLING ACTIVATION OR REPRESSION OF ANTHOCYANIN ACCUMULATION IN CEREALS AND FRUITS OF DIFFERENT PLANT SPECIES, WITH SPECIAL EMPHASIS ON THE DIFFERENCES IN MOLECULAR MECHANISMS BETWEEN MONOCOT AND DICOT PLANTS. RECENTLY, NEW INSIGHT INTO THE TRANSCRIPTIONAL REGULATION OF THE ANTHOCYANIN BIOSYNTHESIS, INCLUDING POSITIVE AND NEGATIVE FEEDBACK CONTROL AS WELL AS EPIGENETIC AND POST-TRANSLATIONAL REGULATION OF MYB-BHLH-WD40 COMPLEXES, HAS BEEN GAINED. WE WILL CONSIDER HOW KNOWLEDGE OF REGULATORY MECHANISMS HAS HELPED TO PRODUCE ANTHOCYANIN-ENRICHED FOODS THROUGH CONVENTIONAL BREEDING AND METABOLIC ENGINEERING. ADDITIONALLY, WE WILL BRIEFLY DISCUSS THE BIOLOGICAL ACTIVITIES OF ANTHOCYANINS AS COMPONENTS OF THE HUMAN DIET AND RECENT FINDINGS DEMONSTRATING THE IMPORTANT HEALTH BENEFITS OF ANTHOCYANIN-RICH FOODS AGAINST CHRONIC DISEASES. 2021 5 4652 25 NEUROPROTECTION WITH NATURAL ANTIOXIDANTS AND NUTRACEUTICALS IN THE CONTEXT OF BRAIN CELL DEGENERATION: THE EPIGENETIC CONNECTION. BIOACTIVE ANTIOXIDANT AGENTS PRESENT IN SELECTED PLANTS ARE KNOWN TO PROVIDE THE FIRST LINE OF BIOLOGICAL DEFENSE AGAINST OXIDATIVE STRESS. IN PARTICULAR, SOLUBLE VITAMIN C, E, CAROTENOIDS AND PHENOLIC COMPOUNDS HAVE DEMONSTRATED CRUCIAL BIOLOGICAL EFFECTS IN CELLS AGAINST OXIDATIVE DAMAGE, PREVENTING PREVALENT CHRONIC DISEASES, SUCH AS DIABETES, CANCER AND CARDIOVASCULAR DISEASE. THE REPORTED WIDE RANGE OF EFFECTS THAT INCLUDED ANTI-AGING, ANTI-ATHEROSCLEROSIS, ANTI-INFLAMMATORY AND ANTICANCER ACTIVITY WERE STUDIED AGAINST DEGENERATIVE PATHOLOGIES OF THE BRAIN. VITAMINS AND DIFFERENT PHYTOCHEMICALS ARE IMPORTANT EPIGENETIC MODIFIERS THAT PREVENT NEURODEGENERATION. IN ORDER TO EXPLORE THE POTENTIAL ANTIOXIDANT SOURCES IN FUNCTIONAL FOODS AND NUTRACEUTICALS AGAINST NEURODEGENERATION, THE PRESENT PAPER AIMS TO SHOW A COMPREHENSIVE ASSESSMENT OF ANTIOXIDANT ACTIVITY AT CHEMICAL AND CELLULAR LEVELS. THE EFFECTS OF THE DIFFERENT BIOACTIVE COMPOUNDS AVAILABLE AND THEIR ANTIOXIDANT ACTIVITY THROUGH AN EPIGENETIC POINT OF VIEW ARE ALSO DISCUSSED. 2019 6 1402 31 DIETARY ANTIOXIDANTS REMODEL DNA METHYLATION PATTERNS IN CHRONIC DISEASE. CHRONIC DISEASES ACCOUNT FOR OVER 60% OF ALL DEATHS WORLDWIDE ACCORDING TO THE WORLD HEALTH ORGANIZATION REPORTS. MAJORITY OF CASES ARE TRIGGERED BY ENVIRONMENTAL EXPOSURES THAT LEAD TO ABERRANT CHANGES IN THE EPIGENOME, SPECIFICALLY, THE DNA METHYLATION PATTERNS. THESE CHANGES RESULT IN ALTERED EXPRESSION OF GENE NETWORKS AND ACTIVITY OF SIGNALLING PATHWAYS. DIETARY ANTIOXIDANTS, INCLUDING CATECHINS, FLAVONOIDS, ANTHOCYANINS, STILBENES AND CAROTENOIDS, DEMONSTRATE BENEFITS IN THE PREVENTION AND/OR SUPPORT OF THERAPY IN CHRONIC DISEASES. THIS REVIEW PROVIDES A COMPREHENSIVE DISCUSSION OF POTENTIAL EPIGENETIC MECHANISMS OF ANTIOXIDANT COMPOUNDS IN REVERSING ALTERED PATTERNS OF DNA METHYLATION IN CHRONIC DISEASE. ANTIOXIDANTS REMODEL THE DNA METHYLATION PATTERNS THROUGH MULTIPLE MECHANISMS, INCLUDING REGULATION OF EPIGENETIC ENZYMES AND CHROMATIN REMODELLING COMPLEXES. THESE EFFECTS CAN FURTHER CONTRIBUTE TO ANTIOXIDANT PROPERTIES OF THE COMPOUNDS. ON THE OTHER HAND, DECREASE IN OXIDATIVE STRESS ITSELF CAN IMPACT DNA METHYLATION DELIVERING ADDITIONAL LINK BETWEEN ANTIOXIDANT MECHANISMS AND EPIGENETIC EFFECTS OF THE COMPOUNDS. LINKED ARTICLES: THIS ARTICLE IS PART OF A THEMED SECTION ON THE PHARMACOLOGY OF NUTRACEUTICALS. TO VIEW THE OTHER ARTICLES IN THIS SECTION VISIT HTTP://ONLINELIBRARY.WILEY.COM/DOI/10.1111/BPH.V177.6/ISSUETOC. 2020 7 2424 31 EPIGENETIC SIGNATURES UNDERLYING INFLAMMATION: AN INTERPLAY OF NUTRITION, PHYSICAL ACTIVITY, METABOLIC DISEASES, AND ENVIRONMENTAL FACTORS FOR PERSONALIZED NUTRITION. AIM AND OBJECTIVE: EMERGING TRANSLATIONAL EVIDENCE SUGGESTS THAT EPIGENETIC ALTERATIONS (DNA METHYLATION, MIRNA EXPRESSION, AND HISTONE MODIFICATIONS) OCCUR AFTER EXTERNAL STIMULI AND MAY CONTRIBUTE TO EXACERBATED INFLAMMATION AND THE RISK OF SUFFERING SEVERAL DISEASES INCLUDING DIABETES, CARDIOVASCULAR DISEASES, CANCER, AND NEUROLOGICAL DISORDERS. THIS REVIEW SUMMARIZES THE CURRENT KNOWLEDGE ABOUT THE HARMFUL EFFECTS OF HIGH-FAT/HIGH-SUGAR DIETS, MICRONUTRIENT DEFICIENCIES (FOLATE, MANGANESE, AND CAROTENOIDS), OBESITY AND ASSOCIATED COMPLICATIONS, BACTERIAL/VIRAL INFECTIONS, SMOKING, EXCESSIVE ALCOHOL CONSUMPTION, SLEEP DEPRIVATION, CHRONIC STRESS, AIR POLLUTION, AND CHEMICAL EXPOSURE ON INFLAMMATION THROUGH EPIGENETIC MECHANISMS. ADDITIONALLY, THE EPIGENETIC PHENOMENA UNDERLYING THE ANTI-INFLAMMATORY POTENTIAL OF CALORIC RESTRICTION, N-3 PUFA, MEDITERRANEAN DIET, VITAMIN D, ZINC, POLYPHENOLS (I.E., RESVERATROL, GALLIC ACID, EPICATECHIN, LUTEOLIN, CURCUMIN), AND THE ROLE OF SYSTEMATIC EXERCISE ARE DISCUSSED. METHODS: ORIGINAL AND REVIEW ARTICLES ENCOMPASSING EPIGENETICS AND INFLAMMATION WERE SCREENED FROM MAJOR DATABASES (INCLUDING PUBMED, MEDLINE, SCIENCE DIRECT, SCOPUS, ETC.) AND ANALYZED FOR THE WRITING OF THE REVIEW PAPER. CONCLUSION: ALTHOUGH CAUTION SHOULD BE EXERCISED, RESEARCH ON EPIGENETIC MECHANISMS IS CONTRIBUTING TO UNDERSTAND PATHOLOGICAL PROCESSES INVOLVING INFLAMMATORY RESPONSES, THE PREDICTION OF DISEASE RISK BASED ON THE EPIGENOTYPE, AS WELL AS THE PUTATIVE DESIGN OF THERAPEUTIC INTERVENTIONS TARGETING THE EPIGENOME. 2021 8 4396 27 MODULATION OF CHRONIC INFLAMMATION BY QUERCETIN: THE BENEFICIAL EFFECTS ON OBESITY. OBESITY HAS BECOME A MAJOR RISK FACTOR FOR THE DEVELOPMENT OF CHRONIC DISEASES SUCH AS INSULIN RESISTANCE, TYPE 2 DIABETES MELLITUS, AND CARDIOVASCULAR DISEASE. MOREOVER, OBESITY INDUCES CHRONIC INFLAMMATION IN ADIPOSE TISSUE, LIVER, SKELETAL MUSCLE, AND THE VASCULAR SYSTEM. QUERCETIN IS THE MAJOR REPRESENTATIVE OF THE FLAVONOID SUBCLASS OF FLAVONOLS, WHICH IS UBIQUITOUSLY CONTAINED WITHIN NATURAL PLANTS SUCH AS GREEN TEA, AND VEGETABLES, INCLUDING ONIONS AND APPLES. RESEARCHERS HAVE FOCUSED GREATER ATTENTION TO THE BENEFICIAL PHYSIOLOGICAL ROLES OF QUERCETIN, WHICH HAS ANTI-OXIDATIVE, ANTI-INFLAMMATORY, AND ANTI-FIBROTIC EFFECTS ON INSULIN RESISTANCE AND ATHEROSCLEROSIS IN OBESITY-RELATED DISEASES. ALSO, THE ANTI-INFLAMMATORY EFFECTS OF QUERCETIN ON INTESTINAL MICROBIOTA HAVE BEEN DEMONSTRATED IN OBESITY. IN ADDITION, THERE IS INCREASING EVIDENCE THAT QUERCETIN IS ASSOCIATED WITH EPIGENETIC ACTIVITIES IN CANCER, AND IN MATERNAL UNDERNUTRITION DURING GESTATION AND LACTATION. IN THIS REVIEW, WE FOCUS ON THE CHEMICAL PROPERTIES OF QUERCETIN, ITS DIETARY SOURCES IN OBESITY, AND ITS ANTI-INFLAMMATORY EFFECTS ON INSULIN RESISTANCE, ATHEROSCLEROSIS, INTESTINAL MICROBIOTA, AND MATERNAL UNDER-NUTRITION WITH EPIGENETIC ACTIVITY. 2020 9 5409 32 REGULATION OF ACETYLATION STATES BY NUTRIENTS IN THE INHIBITION OF VASCULAR INFLAMMATION AND ATHEROSCLEROSIS. ATHEROSCLEROSIS (AS) IS A CHRONIC METABOLIC DISORDER AND PRIMARY CAUSE OF CARDIOVASCULAR DISEASES, RESULTING IN SUBSTANTIAL MORBIDITY AND MORTALITY WORLDWIDE. INITIATED BY ENDOTHELIAL CELL STIMULATION, AS IS CHARACTERIZED BY ARTERIAL INFLAMMATION, LIPID DEPOSITION, FOAM CELL FORMATION, AND PLAQUE DEVELOPMENT. NUTRIENTS SUCH AS CAROTENOIDS, POLYPHENOLS, AND VITAMINS CAN PREVENT THE ATHEROSCLEROTIC PROCESS BY MODULATING INFLAMMATION AND METABOLIC DISORDERS THROUGH THE REGULATION OF GENE ACETYLATION STATES MEDIATED WITH HISTONE DEACETYLASES (HDACS). NUTRIENTS CAN REGULATE AS-RELATED EPIGENETIC STATES VIA SIRTUINS (SIRTS) ACTIVATION, SPECIFICALLY SIRT1 AND SIRT3. NUTRIENT-DRIVEN ALTERATIONS IN THE REDOX STATE AND GENE MODULATION IN AS PROGRESSION ARE LINKED TO THEIR PROTEIN DEACETYLATING, ANTI-INFLAMMATORY, AND ANTIOXIDANT PROPERTIES. NUTRIENTS CAN ALSO INHIBIT ADVANCED OXIDATION PROTEIN PRODUCT FORMATION, REDUCING ARTERIAL INTIMA-MEDIA THICKNESS EPIGENETICALLY. NONETHELESS, KNOWLEDGE GAPS REMAIN WHEN IT COMES TO UNDERSTANDING EFFECTIVE AS PREVENTION THROUGH EPIGENETIC REGULATION BY NUTRIENTS. THIS WORK REVIEWS AND CONFIRMS THE UNDERLYING MECHANISMS BY WHICH NUTRIENTS PREVENT ARTERIAL INFLAMMATION AND AS, FOCUSING ON THE EPIGENETIC PATHWAYS THAT MODIFY HISTONES AND NON-HISTONE PROTEINS BY REGULATING REDOX AND ACETYLATION STATES THROUGH HDACS SUCH AS SIRTS. THESE FINDINGS MAY SERVE AS A FOUNDATION FOR DEVELOPING POTENTIAL THERAPEUTIC AGENTS TO PREVENT AS AND CARDIOVASCULAR DISEASES BY EMPLOYING NUTRIENTS BASED ON EPIGENETIC REGULATION. 2023 10 617 39 BIOACTIVE FOOD COMPOUNDS, EPIGENETICS AND CHRONIC DISEASE PREVENTION: FOCUS ON EARLY-LIFE INTERVENTIONS WITH POLYPHENOLS. CONSUMPTION OF BIOACTIVE COMPOUNDS SUCH AS POLYPHENOLS, ISOTHIOCYANATES, SULFUR-CONTAINING COMPOUNDS AND TERPENOIDS, FOUND IN FRUITS AND VEGETABLES, IS ASSOCIATED WITH PREVENTION OF CHRONIC DISEASE. THESE BIOACTIVE FOOD COMPOUNDS ELICIT THEIR PROTECTIVE EFFECTS THROUGH COMPLEX MECHANISMS AT THE CELLULAR AND MOLECULAR, INCLUDING EPIGENETIC LEVELS. ACCORDING TO THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) PARADIGM, IN UTERO EXPOSURE TO STRESSORS SUCH AS MALNUTRITION THROUGH MATERNAL DIET WOULD IMPAIR FETAL DEVELOPMENT AND EPIGENETICALLY PROGRAM INCREASED RISK OF METABOLIC DISEASES AND SOME CANCERS IN ADULT LIFE. IN ADDITION, A ROLE FOR FATHERS DIET DURING PRECONCEPTION ON THEIR OFFSPRING HEALTH AND CHRONIC DISEASE SUSCEPTIBILITY HAS ALSO EMERGED. THIS HIGHLIGHTS EARLY LIFE AS A PROMISING WINDOW OF OPPORTUNITY FOR STARTING DIETARY INTERVENTIONS FOCUSING ON PREVENTING CHRONIC DISEASES. HOWEVER, KNOWLEDGE ON THE POTENTIAL BENEFICIAL IMPACT OF EARLY LIFE EXPOSURE TO BIOACTIVE FOOD COMPOUNDS IS LIMITED. AMONG THE STUDIES THAT HAVE INVESTIGATED BIOACTIVE FOOD COMPOUNDS IN THE CONTEXT OF DOHAD, MOST HAVE FOCUSED ON THE IMPACT OF DIETARY POLYPHENOLS. THUS, IN THIS REVIEW WE DISCUSS EXPERIMENTAL EVIDENCE SUPPORTING A ROLE FOR THE DIETARY POLYPHENOLS RESVERATROL, GENISTEIN, EPIGALLOCATECHIN-3-GALLATE AND ANTHOCYANINS IN CHRONIC DISEASE PREVENTION CONSIDERING A PERSPECTIVE FROM EARLY-LIFE INTERVENTIONS THROUGH MATERNAL AND PATERNAL DIETS AND FOCUSING ON EPIGENETICS AS A POTENTIAL UNDERLYING MECHANISM. 2019 11 1836 21 EFFECTS OF NUTRIENT AND BIOACTIVE FOOD COMPONENTS ON ALZHEIMER'S DISEASE AND EPIGENETIC. ALZHEIMER'S DISEASE (AD) IS THE MOST COMMON FORM OF DEMENTIA IN THE ELDERLY AND IS A CHRONIC NEURODEGENERATIVE DISEASE THAT IS BECOMING WIDESPREAD. FOR THIS REASON, IN RECENT YEARS FACTORS AFFECTING THE DEVELOPMENT, PROGRESSION AND COGNITIVE FUNCTION OF THE AD HAVE BEEN EMPHASIZED. NUTRIENTS AND OTHER BIOACTIVE NUTRIENTS ARE AMONG THE FACTORS THAT ARE EFFECTIVE IN AD. IN PARTICULAR, VITAMINS A, C AND E, VITAMINS B(1), B(6) AND B(12), FOLATE, MAGNESIUM, CHOLINE, INOSITOL, ANTHOCYANINS, ISOFLAVONES ETC. NUTRIENTS AND BIOACTIVE NUTRIENTS ARE KNOWN TO BE EFFECTIVE IN THE DEVELOPMENT OF AD. NUTRIENTS AND NUTRIENT COMPONENTS MAY ALSO HAVE AN EPIGENETIC EFFECT ON AD. AT THE SAME TIME, NUTRIENTS AND BIOACTIVE FOOD COMPONENTS SLOW DOWN THE PROGRESSION OF THE DISEASE. FOR THIS REASON, THE EFFECT OF NUTRIENTS AND FOOD COMPONENTS ON AD WAS EXAMINED IN THIS REVIEW. 2019 12 4786 39 NUTRITION AND HEALTH DURING MID-LIFE: SEARCHING FOR SOLUTIONS AND MEETING CHALLENGES FOR THE AGING POPULATION. INTERACTIONS BETWEEN GENETIC (GENOME) AND ENVIRONMENTAL FACTORS (EPIGENOME) OPERATE DURING A PERSON'S ENTIRE LIFESPAN. THE AGING PROCESS IS ASSOCIATED WITH SEVERAL CELLULAR AND ORGANIC FUNCTIONAL ALTERATIONS THAT, AT THE END, CAUSE MULTI-ORGANIC CELL FAILURE. EPIGENETIC MECHANISMS OF AGING ARE MODIFIABLE BY APPROPRIATE PREVENTIVE ACTIONS MEDIATED BY SIRTUINS, CALORIC INPUT, DIET COMPONENTS, ADIPOSE TISSUE-RELATED INFLAMMATORY REACTIONS, AND PHYSICAL ACTIVITY. THE MEDITERRANEAN LIFESTYLE HAS BEEN FOR MANY MILLENNIA A DAILY HABIT FOR PEOPLE IN WESTERN CIVILIZATIONS LIVING AROUND THE MEDITERRANEAN SEA WHO WORKED INTENSIVELY AND SURVIVED WITH VERY FEW SEASONAL FOODS. A HIGH ADHERENCE TO THE TRADITIONAL MEDITERRANEAN DIET IS ASSOCIATED WITH LOW MORTALITY (HIGHER LONGEVITY) AND REDUCED RISK OF DEVELOPING CHRONIC DISEASES, INCLUDING CANCER, THE METABOLIC SYNDROME, DEPRESSION AND CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES. REPORTS INDICATE THAT SOME DIETARY COMPONENTS, SUCH AS OLIVE OIL, ANTIOXIDANTS, OMEGA-3 AND -6 POLYUNSATURATED ACIDS, POLYPHENOLS AND FLAVONOIDS, MEDIATE BENEFICIAL ANTI-AGING EFFECTS (ANTI-CHRONIC DISEASES AND INCREASED LONGEVITY). EQUALLY, PHYSICAL ACTIVITY DISPLAYS A POSITIVE EFFECT, PRODUCING CALORIC CONSUMPTION AND REGULATION OF ADIPOSE AND PANCREATIC FUNCTION. THE PREDICTIVE STRENGTH OF SOME FOOD PATTERNS MAY BE A WAY OF DEVELOPING RECOMMENDATIONS FOR FOOD AND HEALTH POLICIES. THIS PAPER WILL DISCUSS SEVERAL WAYS OF IMPROVING HEALTH DURING MID-LIFE, FOCUSING ON CERTAIN GROUPS OF FUNCTIONAL FOODS AND HEALTHY HABITS WHICH MAY REDUCE OR PREVENT AGE-RELATED CHRONIC DISEASES. 2013 13 2100 27 EPIGENETIC EFFECTS OF NATURAL POLYPHENOLS: A FOCUS ON SIRT1-MEDIATED MECHANISMS. POLYPHENOLS ARE A CLASS OF NATURAL COMPOUNDS WIDELY DISTRIBUTED IN FRUITS, VEGETABLES, AND PLANTS. THEY HAVE BEEN REPORTED TO POSSESS A WIDE RANGE OF ACTIVITIES IN PREVENTION AND ALLEVIATION OF VARIOUS DISEASES LIKE CANCER, NEUROINFLAMMATION, DIABETES, AND AGING. POLYPHENOLS ARE EFFECTIVE AGAINST CHRONIC DISEASES AND RECENT REPORTS INDICATED STRONG EPIGENETIC EFFECTS OF POLYPHENOLS. MOST OF THE STUDIES INVESTIGATING EPIGENETIC EFFECTS OF NATURAL POLYPHENOLS HAVE FOCUSED ON THEIR BENEFICIAL EFFECTS IN CANCER TREATMENT. HOWEVER, EPIGENETIC DEFECTS HAVE BEEN DEMONSTRATED IN MANY OTHER DISEASES AS WELL, AND APPLICATION OF POLYPHENOLS TO MODULATE THE EPIGENOME IS BECOMING AN INTERESTING FIELD OF RESEARCH. THIS REVIEW SUMMARIZES THE EFFECTS OF NATURAL POLYPHENOLS IN MODULATING EPIGENETIC-RELATED ENZYMES AS WELL AS THEIR EFFECT IN PREVENTION AND TREATMENT OF CHRONIC DISEASES WITH A FOCUS ON SIRT1 MODULATION. WE HAVE ALSO DISCUSSED THE RELATION BETWEEN THE STRUCTURE AND FUNCTION OF EPIGENETIC-MODIFYING POLYPHENOLS. 2014 14 4792 41 NUTRITIONAL EPIGENETICS AND PHYTOCHEMICALS IN CANCER FORMATION. NUTRIGENETICS AND NUTRIGENOMICS ARE TWO CONCEPTS IN THE AREA OF NUTRITIONAL GENOMICS. EPIGENETICS IS A NEW DISCIPLINE WITH SIGNIFICANT POTENTIAL IN THE PREVENTION AND MANAGEMENT OF CERTAIN CARCINOMAS AND DISEASES. EPIGENETICS CONSISTS OF DNA METHYLATION, HISTONE MODIFICATION, NON-CODING RNAS, AND TELOMERASE ACTIVITY. EPIGENETIC-BASED MECHANISMS ACT ON THE INHIBITION OF CANCER CELLS BY MODULATING ENZYMES SUCH AS DNA METHYLTRANSFERASE AND HISTONE DEACETYLASE, AS WELL AS NON-CODING RNAS. PHYTOCHEMICALS ARE NATURAL BIOACTIVE COMPONENTS OF PLANT ORIGIN THAT HAVE ANTIOXIDANT, ANTI-INFLAMMATORY, AND ANTI-ANGIOGENIC EFFECTS ON VARIOUS DISEASES, ESPECIALLY CANCER. THE EPIGENETIC DIET IS A NUTRITIONAL MODEL BASED ON THE CONSUMPTION OF VARIOUS PHYTOCHEMICALS SUCH AS EPIGALLOCATECHIN-3-GALLATE, MORIN, CAFFEIC ACID PHENYL ESTER, APIGENIN, GENISTEIN, CURCUMIN, RESVERATROL, AND SULFORAPHANE. PHYTOCHEMICALS EXERT THEIR EFFECTS ON CANCER-BASED BY REDUCING CELL PROLIFERATION, INVASION, AND METASTASIS AND INCREASING CELL APOPTOSIS. SIMULTANEOUSLY, IT HAS FUNCTIONS SUCH AS REDUCING ONCOGENES THAT HAVE EFFECTS ON CANCER ETIOLOGY AND INCREASING TUMOR SUPPRESSOR GENES.KEY TEACHING POINTSCANCER IS A CHRONIC DISEASE WITH A HIGH MORTALITY RATE, IN WHICH VARIOUS GENETIC AND ENVIRONMENTAL FACTORS ARE INVOLVED IN ITS ETIOLOGY.PROTOONCOGENES, TUMOR SUPPRESSOR GENES, AND DNA REPAIR GENES ARE AMONG THE GENE GROUPS THAT FORM THE BASIS OF CANCER AND GENETIC STRUCTURE.THE BIDIRECTIONAL INTERACTION BETWEEN NUTRITION AND THE HUMAN GENOME HAS BEEN EFFECTIVE IN THE EMERGENCE OF THE CONCEPTS OF NUTRIGENETICS AND NUTRIGENOMICS.EPIGENETIC DIET IS A DIET BASED ON THE CONSUMPTION OF FOODS SUCH AS SOY, GRAPES, BLUEBERRIES, TURMERIC, CRUCIFEROUS VEGETABLES, AND GREEN TEA, WHICH INDUCE EPIGENETIC MECHANISMS THAT PROTECT AGAINST CANCER AND AGING. 2023 15 4534 31 MULTIPLE REGULATIONS OF KEAP1/NRF2 SYSTEM BY DIETARY PHYTOCHEMICALS. KEAP1/NRF2 SYSTEM PLAYS A CRITICAL ROLE ON CELLULAR PROTECTION BY REGULATING MANY ANTIOXIDANT AND DETOXIFICATION ENZYME GENES THROUGH THE ANTIOXIDANT RESPONSE ELEMENT (ARE). THUS, IT MUST WORK CONSTANTLY TO PREVENT THE ACCUMULATION OF REACTIVE OXYGEN SPECIES (ROS) BECAUSE EXCESS ROS ARE ASSOCIATED WITH MANY DISEASES SUCH AS CANCER, CARDIOVASCULAR COMPLICATIONS, INFLAMMATION, AND NEURODEGENERATION. DIETARY PHYTOCHEMICALS WIDELY DISTRIBUTING IN FRUITS AND VEGETABLES HAVE BEEN CONSIDERED TO POSSESS CANCER CHEMOPREVENTIVE POTENTIAL THROUGH THE INDUCTION OF KEAP1/NRF2 SYSTEM-MEDIATED ANTIOXIDANT AND DETOXIFICATION ENZYMES IN A VARIETY OF MANNERS. THE DATA ARE EXTENSIVE AND ARE NOT WELL CLASSIFIED ON THE MOLECULAR MECHANISMS. IN THIS REVIEW, WE FIRST BRIEFLY INTRODUCE THE CURRENT KNOWLEDGE ON KEAP1/NRF2 SYSTEM REGULATION INCLUDING KEAP1-DEPENDENT AND KEAP1-INDEPENDENT CASCADES, AND EPIGENETIC PATHWAY. THEN, WE SUMMARIZE THE MOLECULAR TARGETS OF KEAP1/NRF2 SYSTEM BY DIETARY PHYTOCHEMICALS, AND FINALLY REVIEW THE CROSSTALK BETWEEN KEAP1/NRF2 SYSTEM AND OTHER CELLULAR SIGNALING PATHWAYS TO REGULATE DIVERSE CHRONIC DISEASES BY DIETARY PHYTOCHEMICALS. THESE COMPREHENSIVE DATA WILL HELP US TO UNDERSTAND THE POTENTIAL EFFECTS OF DIETARY PHYTOCHEMICALS ON THE PREVENTION OF CHRONIC DISEASES AND MAINTENANCE OF HUMAN HEALTH. 2016 16 1398 37 DIET, GUT MICROBIOME AND EPIGENETICS: EMERGING LINKS WITH INFLAMMATORY BOWEL DISEASES AND PROSPECTS FOR MANAGEMENT AND PREVENTION. INFLAMMATORY BOWEL DISEASES (IBD) REPRESENT A GROWING PUBLIC HEALTH CONCERN DUE TO INCREASING INCIDENCE WORLDWIDE. THE CURRENT NOTION ON THE PATHOGENESIS OF IBD IS THAT GENETICALLY SUSCEPTIBLE INDIVIDUALS DEVELOP INTOLERANCE TO DYSREGULATED GUT MICROFLORA (DYSBIOSIS) AND CHRONIC INFLAMMATION DEVELOPS AS A RESULT OF ENVIRONMENTAL TRIGGERS. AMONG THE ENVIRONMENTAL FACTORS ASSOCIATED WITH IBD, DIET PLAYS AN IMPORTANT ROLE IN MODULATING THE GUT MICROBIOME, INFLUENCING EPIGENETIC CHANGES, AND, THEREFORE, COULD BE APPLIED AS A THERAPEUTIC TOOL TO IMPROVE THE DISEASE COURSE. NEVERTHELESS, THE CURRENT DIETARY RECOMMENDATIONS FOR DISEASE PREVENTION AND MANAGEMENT ARE SCARCE AND HAVE WEAK EVIDENCE. THIS REVIEW SUMMARISES THE CURRENT KNOWLEDGE ON THE COMPLEX INTERACTIONS BETWEEN DIET, MICROBIOME AND EPIGENETICS IN IBD. WHEREAS AN OVERABUNDANCE OF CALORIES AND SOME MACRONUTRIENTS INCREASE GUT INFLAMMATION, SEVERAL MICRONUTRIENTS HAVE THE POTENTIAL TO MODULATE IT. IMMUNONUTRITION HAS EMERGED AS A NEW CONCEPT PUTTING FORWARD THE IMPORTANCE OF VITAMINS SUCH AS VITAMINS A, C, E, AND D, FOLIC ACID, BETA CAROTENE AND TRACE ELEMENTS SUCH AS ZINC, SELENIUM, MANGANESE AND IRON. HOWEVER, WHEN ASSESSED IN CLINICAL TRIALS, SPECIFIC MICRONUTRIENTS EXERTED A LIMITED BENEFIT. BEYOND NUTRIENTS, AN ANTI-INFLAMMATORY DIETARY PATTERN AS A COMPLEX INTERVENTION APPROACH HAS BECOME POPULAR IN RECENT YEARS. HENCE, EXCLUSIVE ENTERAL NUTRITION IN PAEDIATRIC CROHN'S DISEASE IS THE ONLY NUTRITIONAL INTERVENTION CURRENTLY RECOMMENDED AS A FIRST-LINE THERAPY. OTHER NUTRITIONAL INTERVENTIONS OR SPECIFIC DIETS INCLUDING THE SPECIFIC CARBOHYDRATE DIET (SCD), THE LOW FERMENTABLE OLIGOSACCHARIDES, DISACCHARIDES, MONOSACCHARIDES, AND POLYOL (FODMAP) DIET AND, MOST RECENTLY, THE MEDITERRANEAN DIET HAVE SHOWN STRONG ANTI-INFLAMMATORY PROPERTIES AND SHOW PROMISE FOR IMPROVING DISEASE SYMPTOMS. MORE WORK IS REQUIRED TO EVALUATE THE ROLE OF INDIVIDUAL FOOD COMPOUNDS AND COMPLEX NUTRITIONAL INTERVENTIONS WITH THE POTENTIAL TO DECREASE INFLAMMATION AS A MEANS OF PREVENTION AND MANAGEMENT OF IBD. 2017 17 6436 28 THERAPEUTIC ACTIONS OF TEA PHENOLIC COMPOUNDS AGAINST OXIDATIVE STRESS AND INFLAMMATION AS CENTRAL MEDIATORS IN THE DEVELOPMENT AND PROGRESSION OF HEALTH PROBLEMS: A REVIEW FOCUSING ON MICRORNA REGULATION. MANY HEALTH PROBLEMS INCLUDING CHRONIC DISEASES ARE CLOSELY ASSOCIATED WITH OXIDATIVE STRESS AND INFLAMMATION. TEA HAS ABUNDANT PHENOLIC COMPOUNDS WITH VARIOUS HEALTH BENEFITS INCLUDING ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES. THIS REVIEW FOCUSES ON THE PRESENT UNDERSTANDING OF THE IMPACT OF TEA PHENOLIC COMPOUNDS ON THE EXPRESSION OF MIRNAS, AND ELUCIDATES THE BIOCHEMICAL AND MOLECULAR MECHANISMS UNDERLYING THE TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL PROTECTIVE ACTIONS OF TEA PHENOLIC COMPOUNDS AGAINST OXIDATIVE STRESS- AND/OR INFLAMMATION-MEDIATED DISEASES. CLINICAL STUDIES SHOWED THAT DRINKING TEA OR TAKING CATECHIN SUPPLEMENT ON A DAILY BASIS PROMOTED THE ENDOGENOUS ANTIOXIDANT DEFENSE SYSTEM OF THE BODY WHILE INHIBITING INFLAMMATORY FACTORS. THE REGULATION OF CHRONIC DISEASES BASED ON EPIGENETIC MECHANISMS, AND THE EPIGENETIC-BASED THERAPIES INVOLVING DIFFERENT TEA PHENOLIC COMPOUNDS, HAVE BEEN INSUFFICIENTLY STUDIED. THE MOLECULAR MECHANISMS AND APPLICATION STRATEGIES OF MIR-27 AND MIR-34 INVOLVED IN OXIDATIVE STRESS RESPONSE AND MIR-126 AND MIR-146 INVOLVED IN INFLAMMATION PROCESS WERE PRELIMINARILY INVESTIGATED. SOME EMERGING EVIDENCE SUGGESTS THAT TEA PHENOLIC COMPOUNDS MAY PROMOTE EPIGENETIC CHANGES, INVOLVING NON-CODING RNA REGULATION, DNA METHYLATION, HISTONE MODIFICATION, UBIQUITIN AND SUMO MODIFICATIONS. HOWEVER, EPIGENETIC MECHANISMS AND EPIGENETIC-BASED DISEASE THERAPIES INVOLVING PHENOLIC COMPOUNDS FROM DIFFERENT TEAS, AND THE POTENTIAL CROSS-TALKS AMONG THE EPIGENETIC EVENTS, REMAIN UNDERSTUDIED. 2023 18 4598 29 NATURAL PRODUCTS: THE ROLE AND MECHANISM IN LOW-DENSITY LIPOPROTEIN OXIDATION AND ATHEROSCLEROSIS. ATHEROSCLEROSIS IS A CHRONIC INFLAMMATORY, METABOLIC, AND EPIGENETIC DISEASE, WHICH LEADS TO THE LIFE-THREATENING CORONARY ARTERY DISEASE. EMERGING STUDIES FROM BENCH TO BEDSIDE HAVE DEMONSTRATED THE PIVOTAL ROLE OF LOW-DENSITY LIPOPROTEIN (LDL) OXIDATION IN THE INITIATION AND PROGRESSION OF ATHEROSCLEROSIS. THIS ARTICLE HEREBY REVIEWS OXIDATION MECHANISM OF LDL, AND THE PRO-ATHEROGENIC AND BIOMARKER ROLE OF OXIDIZED LDL IN ATHEROSCLEROSIS. WE ALSO REVIEW THE PHARMACOLOGICAL EFFECTS OF SEVERAL REPRESENTATIVE NATURAL PRODUCTS (VITAMIN E, RESVERATROL, QUERCETIN, PROBUCOL, TANSHINONE IIA, EPIGALLOCATECHIN GALLATE, AND LYCOPENE) IN PROTECTING AGAINST LDL OXIDATION AND ATHEROSCLEROSIS. CLINICAL AND BASIC RESEARCH SUPPORTS THE BENEFICIAL EFFECTS OF THESE NATURAL PRODUCTS IN INHIBITING LDL OXIDATION AND PREVENTING ATHEROSCLEROSIS, BUT THE DATA ARE STILL CONTROVERSIAL. THIS MAY BE RELATED TO FACTORS SUCH AS THE POPULATION AND THE DOSAGE AND TIME OF TAKING NATURAL PRODUCTS INVOLVED IN DIFFERENT STUDIES. UNDERSTANDING THE MECHANISM OF LDL OXIDATION AND EFFECT OF OXIDIZED LDL HELP RESEARCHERS TO FIND NOVEL THERAPIES AGAINST ATHEROSCLEROSIS. 2021 19 4147 40 MECHANISMS UNDERLYING BIOLOGICAL EFFECTS OF CRUCIFEROUS GLUCOSINOLATE-DERIVED ISOTHIOCYANATES/INDOLES: A FOCUS ON METABOLIC SYNDROME. AN INVERSE CORRELATION BETWEEN VEGETABLE CONSUMPTION AND THE INCIDENCE OF CANCER HAS LONG BEEN DESCRIBED. THIS PROTECTIVE EFFECT IS STRONGER WHEN CRUCIFEROUS VEGETABLES ARE SPECIFICALLY CONSUMED. THE BENEFICIAL PROPERTIES OF VEGETABLES ARE ATTRIBUTED TO THEIR BIOACTIVE COMPONENTS LIKE FIBER, ANTIOXIDANTS VITAMINS, ANTIOXIDANTS, MINERALS, AND PHENOLIC COMPOUNDS. CRUCIFEROUS VEGETABLES CONTAIN ALL THESE MOLECULES; HOWEVER, WHAT MAKES THEM DIFFERENT ARE THEIR SULFUROUS COMPONENTS, CALLED GLUCOSINOLATES, RESPONSIBLE FOR THEIR SPECIAL SMELL AND TASTE. GLUCOSINOLATES ARE INACTIVE BIOLOGICALLY IN THE ORGANISM BUT ARE HYDROLYZED BY THE ENZYME MYROSINASE RELEASED AS A RESULT OF CHEWING, LEADING TO THE FORMATION OF ACTIVE DERIVATIVES SUCH AS ISOTHIOCYANATES AND INDOLES. A CONSIDERABLE NUMBER OF IN VITRO AND IN VIVO STUDIES HAVE REPORTED THAT ISOTHIOCYANATES AND INDOLES ELICIT CHEMOPREVENTIVE POTENCY THROUGH MULTIPLE MECHANISMS THAT INCLUDE MODULATION OF PHASES I AND II DETOXIFICATION PATHWAY ENZYMES, REGULATION OF CELL CYCLE ARREST, AND CONTROL OF CELL GROWTH, INDUCTION OF APOPTOSIS, ANTIOXIDANT ACTIVITY, ANTI-ANGIOGENIC EFFECTS, AND EPIGENETIC REGULATION. NUCLEAR ERYTHROID 2-RELATED FACTOR 2 (NRF2) AND NUCLEAR FACTOR-KAPPAB (NF-KAPPAB) ARE KEY AND CENTRAL REGULATORS IN ALL THESE PROCESSES WITH A MAIN ROLE IN OXIDATIVE STRESS AND INFLAMMATION CONTROL. IT HAS BEEN DESCRIBED THAT ISOTHIOCYANATES AND INDOLES REGULATE THEIR ACTIVITY DIRECTLY AND INDIRECTLY. TODAY, THE METABOLIC SYNDROME (CENTRAL OBESITY, INSULIN RESISTANCE, HYPERLIPIDEMIA, AND HYPERTENSION) IS RESPONSIBLE FOR A MAJORITY OF DEATHS WORLDWIDE. ALL COMPONENTS OF METABOLIC SYNDROME ARE CHARACTERIZED BY CHRONIC INFLAMMATION WITH DEREGULATION OF THE PI3K/AKT/MTOR, MAPK/EKR/JNK, NRF2, AND NF-KAPPAB SIGNALING PATHWAYS. THE EFFECTS OF GLSS DERIVATIVES CONTROLLING THESE PATHWAYS HAVE BEEN WIDELY DESCRIBED IN RELATION TO CANCER. CHANGES IN FOOD CONSUMPTION PATTERNS OBSERVED IN THE LAST DECADES TO HIGHER CONSUMPTION OF ULTRA-PROCESSED FOODS, WITH ELEVATION IN SIMPLE SUGAR AND SATURATED FAT CONTENTS AND LOWER CONSUMPTION OF VEGETABLES AND FRUITS HAVE BEEN DIRECTLY CORRELATED WITH METABOLIC SYNDROME PREVALENCE. IN THIS REVIEW, IT IS SUMMARIZED THE KNOWLEDGE REGARDING THE MECHANISMS BY WHICH CRUCIFEROUS GLUCOSINOLATE DERIVATIVES (ISOTHIOCYANATES AND INDOLES) DIRECTLY AND INDIRECTLY REGULATE THESE PATHWAYS. HOWEVER, THE REVIEW PLACES A SPECIAL FOCUS ON THE KNOWLEDGE OF THE EFFECTS OF GLUCOSINOLATES DERIVATIVES IN METABOLIC SYNDROME, SINCE THIS HAS NOT BEEN REVIEWED BEFORE. 2020 20 2045 24 EPIGENETIC CLOCK ANALYSIS OF DIET, EXERCISE, EDUCATION, AND LIFESTYLE FACTORS. BEHAVIORAL AND LIFESTYLE FACTORS HAVE BEEN SHOWN TO RELATE TO A NUMBER OF HEALTH-RELATED OUTCOMES, YET THERE IS A NEED FOR STUDIES THAT EXAMINE THEIR RELATIONSHIP TO MOLECULAR AGING RATES. TOWARD THIS END, WE USE RECENT EPIGENETIC BIOMARKERS OF AGE THAT HAVE PREVIOUSLY BEEN SHOWN TO PREDICT ALL-CAUSE MORTALITY, CHRONIC CONDITIONS, AND AGE-RELATED FUNCTIONAL DECLINE. WE ANALYZE CROSS-SECTIONAL DATA FROM 4,173 POSTMENOPAUSAL FEMALE PARTICIPANTS FROM THE WOMEN'S HEALTH INITIATIVE, AS WELL AS 402 MALE AND FEMALE PARTICIPANTS FROM THE ITALIAN COHORT STUDY, INVECCHIARE NEL CHIANTI.EXTRINSIC EPIGENETIC AGE ACCELERATION (EEAA) EXHIBITS SIGNIFICANT ASSOCIATIONS WITH FISH INTAKE (P=0.02), MODERATE ALCOHOL CONSUMPTION (P=0.01), EDUCATION (P=3X10(-5)), BMI (P=0.01), AND BLOOD CAROTENOID LEVELS (P=1X10(-5))-AN INDICATOR OF FRUIT AND VEGETABLE CONSUMPTION, WHEREAS INTRINSIC EPIGENETIC AGE ACCELERATION (IEAA) IS ASSOCIATED WITH POULTRY INTAKE (P=0.03) AND BMI (P=0.05). BOTH EEAA AND IEAA WERE ALSO FOUND TO RELATE TO INDICATORS OF METABOLIC SYNDROME, WHICH APPEAR TO MEDIATE THEIR ASSOCIATIONS WITH BMI. METFORMIN-THE FIRST-LINE MEDICATION FOR THE TREATMENT OF TYPE 2 DIABETES-DOES NOT DELAY EPIGENETIC AGING IN THIS OBSERVATIONAL STUDY. FINALLY, LONGITUDINAL DATA SUGGESTS THAT AN INCREASE IN BMI IS ASSOCIATED WITH INCREASE IN BOTH EEAA AND IEAA.OVERALL, THE EPIGENETIC AGE ANALYSIS OF BLOOD CONFIRMS THE CONVENTIONAL WISDOM REGARDING THE BENEFITS OF EATING A HIGH PLANT DIET WITH LEAN MEATS, MODERATE ALCOHOL CONSUMPTION, PHYSICAL ACTIVITY, AND EDUCATION, AS WELL AS THE HEALTH RISKS OF OBESITY AND METABOLIC SYNDROME. 2017