1  2986 182 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
2  3889  26 KLOTHO RECOVERY BY GENISTEIN VIA PROMOTER HISTONE ACETYLATION AND DNA DEMETHYLATION MITIGATES RENAL FIBROSIS IN MICE. RENAL FIBROSIS IS A COMMON HISTOMORPHOLOGICAL FEATURE OF RENAL AGING AND CHRONIC KIDNEY DISEASES OF ALL ETIOLOGIES, AND ITS INITIATION AND PROGRESSION ARE SUBSTANTIALLY INFLUENCED BY ABERRANT EPIGENETIC MODIFICATIONS OF FIBROSIS-SUSCEPTIBLE GENES, YET WITHOUT EFFECTIVE THERAPY. "EPIGENETIC DIETS" EXHIBIT TISSUE-PROTECTIVE AND EPIGENETIC-MODULATING PROPERTIES; HOWEVER, THEIR ANTI-RENAL FIBROSIS FUNCTIONS AND THE UNDERLYING MECHANISMS ARE LESS UNDERSTOOD. IN THIS STUDY, WE SHOW THAT GENISTEIN, A PHYTOESTROGENIC ISOFLAVONE ENRICHED IN DIETARY SOY PRODUCTS, EXHIBITS IMPRESSIVE ANTI-RENAL FIBROSIS ACTIVITIES BY RECOVERING EPIGENETIC LOSS OF KLOTHO, A KIDNEY-ENRICHED ANTI-AGING AND FIBROSIS-SUPPRESSING PROTEIN. MOUSE FIBROTIC KIDNEYS INDUCED BY UUO (UNILATERAL URETERAL OCCLUSION) DISPLAYED SEVERER KLOTHO SUPPRESSION AND ADVERSE EXPRESSION OF RENAL FIBROSIS-ASSOCIATED PROTEINS, BUT GENISTEIN ADMINISTRATION MARKEDLY RECOVERED THE KLOTHO LOSS AND ATTENUATED RENAL FIBROSIS AND THE PROTEIN EXPRESSION ABNORMALITIES. THE EXAMINATION OF POSSIBLE CAUSES OF THE KLOTHO RECOVERY REVEALED THAT GENISTEIN SIMULTANEOUSLY INHIBITED HISTONE 3 DEACETYLATION OF KLOTHO PROMOTER AND NORMALIZED THE PROMOTER DNA HYPERMETHYLATION BY SUPPRESSING ELEVATED DNA METHYLTRANSFERASE DNMT1 AND DNMT3A. MORE IMPORTANTLY, GENISTEIN'S ANTI-RENAL FIBROSIS EFFECTS ON THE RENAL FIBROTIC LESIONS AND THE ABNORMAL EXPRESSIONS OF FIBROSIS-ASSOCIATED PROTEINS WERE ABROGATED WHEN KLOTHO IS KNOCKDOWN BY RNA INTERFERENCES IN UUO MICE. THUS, OUR RESULTS IDENTIFY KLOTHO RESTORATION VIA EPIGENETIC HISTONE ACETYLATION AND DNA DEMETHYLATION AS A CRITICAL MECHANISM OF GENISTEIN'S ANTI-FIBROSIS FUNCTION AND SHED NEW LIGHTS ON THE POTENTIALS OF EPIGENETIC DIETS IN PREVENTING OR TREATING AGING OR RENAL FIBROSIS-ASSOCIATED KIDNEY DISEASES. KEY MESSAGES: GENISTEIN PREVENTS RENAL FIBROSIS AND THE ASSOCIATED KLOTHO SUPPRESSION IN UUO MICE. GENISTEIN UPREGULATES KLOTHO IN PART BY REVERSING THE PROMOTER HISTONE 3 HYPOACETYLATION. GENISTEIN ALSO PRESERVES KLOTHO VIA RELIEVING KLOTHO PROMOTER HYPERMETHYLATION. GENISTEIN DEMETHYLATES KLOTHO PROMOTER BY INHIBITING ABERRANT DNMT1/3A EXPRESSION. GENISTEIN RESTORATION OF KLOTHO IS ESSENTIAL FOR ITS ANTI-RENAL FIBROSIS FUNCTION.	2019	
                                                                                                                                                                                                                                                                                                                                          
3  3741  29 INSIGHT INTO THE POTENTIAL MECHANISMS OF ENDOCRINE DISRUPTION BY DIETARY PHYTOESTROGENS IN THE CONTEXT OF THE ETIOPATHOGENESIS OF ENDOMETRIOSIS. PHYTOESTROGENS (PES) ARE ESTROGEN-LIKE NONSTEROIDAL COMPOUNDS DERIVED FROM PLANTS (E.G., NUTS, SEEDS, FRUITS, AND VEGETABLES) AND FUNGI THAT ARE STRUCTURALLY SIMILAR TO 17BETA-ESTRADIOL. PES BIND TO ALL TYPES OF ESTROGEN RECEPTORS, INCLUDING ERALPHA AND ERBETA RECEPTORS, NUCLEAR RECEPTORS, AND A MEMBRANE-BOUND ESTROGEN RECEPTOR KNOWN AS THE G PROTEIN-COUPLED ESTROGEN RECEPTOR (GPER). AS ENDOCRINE-DISRUPTING CHEMICALS (EDCS) WITH PRO- OR ANTIESTROGENIC PROPERTIES, PES CAN POTENTIALLY DISRUPT THE HORMONAL REGULATION OF HOMEOSTASIS, RESULTING IN DEVELOPMENTAL AND REPRODUCTIVE ABNORMALITIES. HOWEVER, A LACK OF PES IN THE DIET DOES NOT RESULT IN THE DEVELOPMENT OF DEFICIENCY SYMPTOMS. TO PROPERLY ASSESS THE BENEFITS AND RISKS ASSOCIATED WITH THE USE OF A PE-RICH DIET, IT IS NECESSARY TO DISTINGUISH BETWEEN ENDOCRINE DISRUPTION (ENDOCRINE-MEDIATED ADVERSE EFFECTS) AND NONSPECIFIC EFFECTS ON THE ENDOCRINE SYSTEM. ENDOMETRIOSIS IS AN ESTROGEN-DEPENDENT DISEASE OF UNKNOWN ETIOPATHOGENESIS, IN WHICH TISSUE SIMILAR TO THE LINING OF THE UTERUS (THE ENDOMETRIUM) GROWS OUTSIDE OF THE UTERUS WITH SUBSEQUENT COMPLICATIONS BEING MANIFESTED AS A RESULT OF LOCAL INFLAMMATORY REACTIONS. ENDOMETRIOSIS AFFECTS 10-15% OF WOMEN OF REPRODUCTIVE AGE AND IS ASSOCIATED WITH CHRONIC PELVIC PAIN, DYSMENORRHEA, DYSPAREUNIA, AND INFERTILITY. IN THIS REVIEW, THE ENDOCRINE-DISRUPTIVE ACTIONS OF PES ARE REVIEWED IN THE CONTEXT OF ENDOMETRIOSIS TO DETERMINE WHETHER A PE-RICH DIET HAS A POSITIVE OR NEGATIVE EFFECT ON THE RISK AND COURSE OF ENDOMETRIOSIS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
4  4805  30 OBESITY AND METABOLIC COMORBIDITIES: ENVIRONMENTAL DISEASES? OBESITY AND METABOLIC COMORBIDITIES REPRESENT INCREASING HEALTH PROBLEMS. ENDOCRINE DISRUPTING COMPOUNDS (EDCS) ARE EXOGENOUS AGENTS THAT CHANGE ENDOCRINE FUNCTION AND CAUSE ADVERSE HEALTH EFFECTS. MOST EDCS ARE SYNTHETIC CHEMICALS; SOME ARE NATURAL FOOD COMPONENTS AS PHYTOESTROGENS. PEOPLE ARE EXPOSED TO COMPLEX MIXTURES OF CHEMICALS THROUGHOUT THEIR LIVES. EDCS IMPACT HORMONE-DEPENDENT METABOLIC SYSTEMS AND BRAIN FUNCTION. LABORATORY AND HUMAN STUDIES PROVIDE COMPELLING EVIDENCE THAT HUMAN CHEMICAL CONTAMINATION CAN PLAY A ROLE IN OBESITY EPIDEMIC. CHEMICAL EXPOSURES MAY INCREASE THE RISK OF OBESITY BY ALTERING THE DIFFERENTIATION OF ADIPOCYTES. EDCS CAN ALTER METHYLATION PATTERNS AND NORMAL EPIGENETIC PROGRAMMING IN CELLS. OXIDATIVE STRESS MAY BE INDUCED BY MANY OF THESE CHEMICALS, AND ACCUMULATING EVIDENCE INDICATES THAT IT PLAYS IMPORTANT ROLES IN THE ETIOLOGY OF CHRONIC DISEASES. THE INDIVIDUAL SENSITIVITY TO CHEMICALS IS VARIABLE, DEPENDING ON ENVIRONMENT AND ABILITY TO METABOLIZE HAZARDOUS CHEMICALS. A NUMBER OF GENES, ESPECIALLY THOSE REPRESENTING ANTIOXIDANT AND DETOXIFICATION PATHWAYS, HAVE POTENTIAL APPLICATION AS BIOMARKERS OF RISK ASSESSMENT. THE POTENTIAL HEALTH EFFECTS OF COMBINED EXPOSURES MAKE THE RISK ASSESSMENT PROCESS MORE COMPLEX COMPARED TO THE ASSESSMENT OF SINGLE CHEMICALS. TECHNIQUES AND METHODS NEED TO BE FURTHER DEVELOPED TO FILL DATA GAPS AND INCREASE THE KNOWLEDGE ON HARMFUL EXPOSURE COMBINATIONS.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
5  6872  43 [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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
6   617  46 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
7   426  33 ANTI-DIABETIC FUNCTIONS OF SOY ISOFLAVONE GENISTEIN: MECHANISMS UNDERLYING ITS EFFECTS ON PANCREATIC BETA-CELL FUNCTION. TYPE 2 DIABETES IS A RESULT OF CHRONIC INSULIN RESISTANCE AND LOSS OF FUNCTIONAL PANCREATIC BETA-CELL MASS. STRATEGIES TO PRESERVE BETA-CELL MASS AND A GREATER UNDERSTANDING OF THE MECHANISMS UNDERLYING BETA-CELL TURNOVER ARE NEEDED TO PREVENT AND TREAT THIS DEVASTATING DISEASE. GENISTEIN, A NATURALLY OCCURRING SOY ISOFLAVONE, IS REPORTED TO HAVE NUMEROUS HEALTH BENEFITS ATTRIBUTED TO MULTIPLE BIOLOGICAL FUNCTIONS. OVER THE PAST 10 YEARS, NUMEROUS STUDIES HAVE DEMONSTRATED THAT GENISTEIN HAS ANTI-DIABETIC EFFECTS, IN PARTICULAR, DIRECT EFFECTS ON BETA-CELL PROLIFERATION, GLUCOSE-STIMULATED INSULIN SECRETION AND PROTECTION AGAINST APOPTOSIS, INDEPENDENT OF ITS FUNCTIONS AS AN ESTROGEN RECEPTOR AGONIST, ANTIOXIDANT, OR TYROSINE KINASE INHIBITOR. EFFECTS ARE STRUCTURE-SPECIFIC AND NOT COMMON TO ALL FLAVONOIDS. WHILE THERE ARE LIMITED DATA ON THE EFFECTS OF GENISTEIN CONSUMPTION IN HUMANS WITH DIABETES, THERE ARE A PLETHORA OF ANIMAL AND CELL-CULTURE STUDIES THAT DEMONSTRATE A DIRECT EFFECT OF GENISTEIN ON BETA-CELLS AT PHYSIOLOGICALLY RELEVANT CONCENTRATIONS (<10 MUM). THE EFFECTS APPEAR TO INVOLVE CAMP/PKA SIGNALING AND THERE ARE SOME STUDIES THAT SUGGEST AN EFFECT ON EPIGENETIC REGULATION OF GENE EXPRESSION. THIS REVIEW FOCUSES ON THE ANTI-DIABETIC EFFECTS OF GENISTEIN IN BOTH IN VITRO AND IN VIVO MODELS AND POTENTIAL MECHANISMS UNDERLYING ITS DIRECT EFFECTS ON BETA-CELLS.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
8   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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
9  5450  37 REPRODUCTIVE TOXICITY OF COMBINED EFFECTS OF ENDOCRINE DISRUPTORS ON HUMAN REPRODUCTION. CONFLUENCE OF ENVIRONMENTAL, GENETIC, AND LIFESTYLE VARIABLES IS RESPONSIBLE FOR DETERIORATION OF HUMAN FECUNDITY. ENDOCRINE DISRUPTORS OR ENDOCRINE DISRUPTING CHEMICALS (EDCS) MAY BE FOUND IN A VARIETY OF FOODS, WATER, AIR, BEVERAGES, AND TOBACCO SMOKE. IT HAS BEEN DEMONSTRATED IN EXPERIMENTAL INVESTIGATIONS THAT A WIDE RANGE OF ENDOCRINE DISRUPTING CHEMICALS HAVE NEGATIVE EFFECTS ON HUMAN REPRODUCTIVE FUNCTION. HOWEVER, EVIDENCE ON THE REPRODUCTIVE CONSEQUENCES OF HUMAN EXPOSURE TO ENDOCRINE DISRUPTING CHEMICALS IS SPARSE AND/OR CONFLICTING IN THE SCIENTIFIC LITERATURE. THE COMBINED TOXICOLOGICAL ASSESSMENT IS A PRACTICAL METHOD FOR ASSESSING THE HAZARDS OF COCKTAILS OF CHEMICALS, CO-EXISTING IN THE ENVIRONMENT. THE CURRENT REVIEW PROVIDES A COMPREHENSIVE OVERVIEW OF STUDIES EMPHASIZING THE COMBINED TOXICITY OF ENDOCRINE DISRUPTING CHEMICALS ON HUMAN REPRODUCTION. ENDOCRINE DISRUPTING CHEMICALS INTERACT WITH EACH OTHER TO DISRUPT THE DIFFERENT ENDOCRINE AXES, RESULTING IN SEVERE GONADAL DYSFUNCTIONS. TRANSGENERATIONAL EPIGENETIC EFFECTS HAVE ALSO BEEN INDUCED IN GERM CELLS, MOSTLY THROUGH DNA METHYLATION AND EPIMUTATIONS. SIMILARLY, AFTER ACUTE OR CHRONIC EXPOSURE TO ENDOCRINE DISRUPTING CHEMICALS COMBINATIONS, INCREASED OXIDATIVE STRESS (OS), ELEVATED ANTIOXIDANT ENZYMATIC ACTIVITY, DISRUPTED REPRODUCTIVE CYCLE, AND REDUCED STEROIDOGENESIS ARE OFTEN REPORTED CONSEQUENCES. THE ARTICLE ALSO DISCUSSES THE CONCENTRATION ADDITION (CA) AND INDEPENDENT ACTION (IA) PREDICTION MODELS, WHICH REVEAL THE IMPORTANCE OF VARIOUS SYNERGISTIC ACTIONS OF ENDOCRINE DISRUPTING CHEMICALS MIXTURES. MORE CRUCIALLY, THIS EVIDENCE-BASED STUDY ADDRESSES THE RESEARCH LIMITATIONS AND INFORMATION GAPS, AS WELL AS PARTICULARLY PRESENTS THE FUTURE RESEARCH VIEWS ON COMBINED ENDOCRINE DISRUPTING CHEMICALS TOXICITY ON HUMAN REPRODUCTION.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
10  6290  41 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
11  4652  30 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
12  6338  29 THE ROLE OF ENDOCRINE-DISRUPTING CHEMICALS IN UTERINE FIBROID PATHOGENESIS. PURPOSE OF REVIEW: UTERINE LEIOMYOMA (FIBROIDS) IS A GYNECOLOGIC DISORDER IMPACTING THE MAJORITY OF WOMEN IN THE UNITED STATES. WHEN SYMPTOMATIC, THESE NONCANCEROUS TUMORS CAN CAUSE SEVERE MORBIDITY INCLUDING PELVIC PAIN, MENORRHAGIA, AND INFERTILITY. ENDOCRINE-DISRUPTING CHEMICALS (EDCS) MAY REPRESENT A MODIFIABLE RISK FACTOR. THE AIM OF THIS REVIEW IS TO SUMMARIZE RECENT HUMAN AND EXPERIMENTAL EVIDENCE ON EDCS EXPOSURES AND FIBROIDS. RECENT FINDINGS: MULTIPLE EDCS ARE ASSOCIATED WITH FIBROID OUTCOMES AND/OR PROCESSES INCLUDING PHTHALATES, PARABENS, ENVIRONMENTAL PHENOLS, ALTERNATE PLASTICIZERS, DIETHYLSTILBESTROL, ORGANOPHOSPHATE ESTERS, AND TRIBUTYLTIN. EPIDEMIOLOGIC STUDIES SUGGEST EXPOSURE TO CERTAIN EDCS, SUCH AS DI-(2-ETHYLHXYL)-PHTHALATE (DEHP), ARE ASSOCIATED WITH INCREASED FIBROID RISK AND SEVERITY. BOTH HUMAN AND EXPERIMENTAL STUDIES INDICATE THAT EPIGENETIC PROCESSES MAY PLAY AN IMPORTANT ROLE IN LINKING EDCS TO FIBROID PATHOGENESIS. IN-VITRO AND IN-VIVO STUDIES SHOW THAT DEHP, BISPHENOL A, AND DIETHYLSTILBESTROL CAN IMPACT BIOLOGICAL PATHWAYS CRITICAL TO FIBROID PATHOGENESIS. SUMMARY: WHILE RESEARCH ON EDCS AND FIBROIDS IS STILL EVOLVING, RECENT EVIDENCE SUGGESTS EDC EXPOSURES MAY CONTRIBUTE TO FIBROID RISK AND PROGRESSION. FURTHER RESEARCH IS NEEDED TO EXAMINE THE IMPACTS OF EDC MIXTURES AND TO IDENTIFY CRITICAL BIOLOGICAL PATHWAYS AND WINDOWS OF EXPOSURE. THESE RESULTS COULD OPEN THE DOOR TO NEW PREVENTION STRATEGIES FOR FIBROIDS.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
13  1417  40 DIETARY TRENDS AND THE DECLINE IN MALE REPRODUCTIVE HEALTH. OVER THE TWENTIETH CENTURY, MALE REPRODUCTIVE HEALTH HAS SUFFERED A SUBSTANTIAL DECLINE, AS EVIDENCED BY DECREASES IN SPERM COUNTS AND TESTOSTERONE LEVELS AND INCREASES IN REPRODUCTIVE PATHOLOGIES. AT THE SAME TIME, THE PREVALENCE OF CHRONIC DISEASES SUCH AS OBESITY, DIABETES, AND METABOLIC SYNDROME HAS RISEN DRAMATICALLY. METABOLIC AND REPRODUCTIVE HEALTH ARE HIGHLY INTERCONNECTED, SUGGESTING THAT THEIR RESPECTIVE TRENDS ARE INTERTWINED AND, GIVEN THE TIMEFRAME OF SUCH TRENDS, ENVIRONMENTAL AND NOT GENETIC FACTORS ARE MOST LIKELY TO BE THE PRIMARY CAUSES. INDUSTRIALIZATION, WHICH BEGAN IN EUROPE IN THE MID-EIGHTEENTH CENTURY, HAS RESULTED IN PROFOUND CHANGES TO OUR DIET, LIFESTYLE, AND ENVIRONMENT, MANY OF WHICH ARE CAUSAL FACTORS IN THE RISE IN CHRONIC DISEASES. INDUSTRIALIZATION RESULTS IN A NUTRITION TRANSITION FROM AN AGRICULTURAL UNPROCESSED TO A MODERN PROCESSED DIET, INCORPORATING INCREASES IN SUGAR, VEGETABLE OILS, ULTRA-PROCESSED FOODS, LINOLEIC ACID, TRANS-FATS, AND TOTAL ENERGY. THIS DIETARY SHIFT HAS INCURRED NUMEROUS ADVERSE EFFECTS ON METABOLIC AND REPRODUCTIVE HEALTH, CHARACTERIZED BY CHRONIC INFLAMMATION, OXIDATIVE STRESS, AND INSULIN RESISTANCE. MOREOVER, THESE EFFECTS APPEAR TO MULTIPLY ACROSS SUBSEQUENT GENERATIONS VIA EPIGENETIC INHERITANCE. MEN'S FERTILITY IS MARKEDLY AFFECTED BY OBESITY AND DIABETES, WITH AN INCREASE IN TOTAL ENERGY VIA PROCESSED FOOD INTAKE ARGUABLY BEING THE KEY FACTOR DRIVING THE DIABESITY PANDEMIC. IN CONTRAST, WHOLEFOODS RICH IN MICRONUTRIENTS AND PHYTONUTRIENTS SUPPORT MALE FERTILITY AND A HEALTHY BODY WEIGHT. THEREFORE, MEN WANTING TO MAXIMIZE THEIR FERTILITY SHOULD CONSIDER MAKING POSITIVE DIETARY CHANGES, SUCH AS REPLACING PROCESSED FOODS WITH UNPROCESSED FOODS THAT SUPPORT METABOLIC AND REPRODUCTIVE HEALTH.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
14  4786  46 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
15  1767  26 EARLY-LIFE EXPOSURE TO ENDOCRINE DISRUPTING CHEMICALS AND LATER-LIFE HEALTH OUTCOMES: AN EPIGENETIC BRIDGE? A GROWING BODY OF EVIDENCE DEMONSTRATES THAT ADVERSE EVENTS EARLY IN DEVELOPMENT, AND PARTICULARLY DURING INTRAUTERINE LIFE, MAY PROGRAM RISKS FOR DISEASES IN ADULT LIFE. INCREASING EVIDENCE HAS BEEN ACCUMULATED INDICATING THE IMPORTANT ROLE OF EPIGENETIC REGULATION INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS AND MIRNAS IN DEVELOPMENTAL PROGRAMMING. AMONG THE ENVIRONMENTAL FACTORS WHICH PLAY AN IMPORTANT ROLE IN PROGRAMMING OF CHRONIC PATHOLOGIES, THE ENDOCRINE-DISRUPTING CHEMICALS (EDCS) THAT HAVE ESTROGENIC, ANTI-ESTROGENIC, AND ANTI-ANDROGENIC ACTIVITY ARE OF SPECIFIC CONCERN BECAUSE THE DEVELOPING ORGANISM IS EXTREMELY SENSITIVE TO PERTURBATION BY SUBSTANCES WITH HORMONE-LIKE ACTIVITY. AMONG EDCS, THERE ARE MANY SUBSTANCES THAT ARE CONSTANTLY PRESENT IN THE MODERN HUMAN ENVIRONMENT OR ARE IN WIDESPREAD USE, INCLUDING DIOXIN AND DIOXIN-LIKE COMPOUNDS, PHTHALATES, AGRICULTURAL PESTICIDES, POLYCHLORINATED BIPHENYLS, INDUSTRIAL SOLVENTS, PHARMACEUTICALS, AND HEAVY METALS. APART FROM THEIR COMMON ENDOCRINE ACTIVE PROPERTIES, SEVERAL EDCS HAVE BEEN SHOWN TO DISRUPT DEVELOPMENTAL EPIGENOMIC PROGRAMMING. THE PURPOSE OF THIS REVIEW IS TO PROVIDE A SUMMARY OF RECENT RESEARCH FINDINGS WHICH INDICATE THAT EXPOSURE TO EDCS DURING IN-UTERO AND/OR NEONATAL DEVELOPMENT CAN CAUSE LONG-TERM HEALTH OUTCOMES VIA MECHANISMS OF EPIGENETIC MEMORY.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
16  4396  38 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
17   111  29 A ROLE FOR G-PROTEIN COUPLED ESTROGEN RECEPTOR (GPER) IN ESTROGEN-INDUCED CARCINOGENESIS: DYSREGULATED GLANDULAR HOMEOSTASIS, SURVIVAL AND METASTASIS. MECHANISMS OF CARCINOGENESIS BY ESTROGEN CENTER ON ITS MITOGENIC AND GENOTOXIC POTENTIAL ON TUMOR TARGET CELLS. THESE MODELS SUGGEST THAT ESTROGEN RECEPTOR (ER) SIGNALING PROMOTES EXPANSION OF THE TRANSFORMED POPULATION AND THAT SUBSEQUENT ACCUMULATION OF SOMATIC MUTATIONS THAT DRIVE CANCER PROGRESSION OCCUR VIA METABOLIC ACTIVATION OF CATHECOL ESTROGENS OR BY EPIGENETIC MECHANISMS. RECENT FINDINGS THAT GPER IS LINKED TO OBESITY, VASCULAR PATHOLOGY AND IMMUNOSUPPRESSION, KEY EVENTS IN THE DEVELOPMENT OF METABOLIC SYNDROME AND INTRA-TISSULAR ESTROGEN SYNTHESIS, PROVIDES AN ALTERNATE VIEW OF ESTROGEN-INDUCED CARCINOGENESIS. CONSISTENT WITH THIS CONCEPT, GPER IS DIRECTLY ASSOCIATED WITH CLINICOPATHOLOGICAL INDICES THAT PREDICT CANCER PROGRESSION AND POOR SURVIVAL IN BREAST AND GYNECOLOGICAL CANCERS. MOREOVER, GPER MANIFESTS CELL BIOLOGICAL RESPONSES AND A MICROENVIRONMENT CONDUCIVE FOR TUMOR DEVELOPMENT AND CANCER PROGRESSION, REGULATING CELLULAR RESPONSES ASSOCIATED WITH GLANDULAR HOMEOSTASIS AND SURVIVAL, INVADING SURROUNDING TISSUE AND ATTRACTING A VASCULAR SUPPLY. THUS, THE CELLULAR ACTIONS ATTRIBUTED TO GPER FIT WELL WITH THE KNOWN MOLECULAR MECHANISMS OF G-PROTEIN COUPLED RECEPTORS, GPCRS, NAMELY, THEIR ABILITY TO TRANSACTIVATE INTEGRINS AND EGF RECEPTORS AND ALTER THE INTERACTION BETWEEN GLANDULAR EPITHELIA AND THEIR EXTRACELLULAR ENVIRONMENT, AFFECTING EPITHELIAL-TO-MESENCHYMAL TRANSITION (EMT) AND ALLOWING FOR TUMOR CELL SURVIVAL AND DISSEMINATION. THIS PERSPECTIVE REVIEWS THE MOLECULAR AND CELLULAR RESPONSES MANIFESTED BY GPER AND EVALUATES ITS CONTRIBUTION TO FEMALE REPRODUCTIVE CANCERS AS DISEASES THAT PROGRESS AS A RESULT OF DYSREGULATED GLANDULAR HOMEOSTASIS RESULTING IN CHRONIC INFLAMMATION AND METASTASIS. THIS REVIEW IS ORGANIZED IN SECTIONS AS FOLLOWS: I) A BRIEF SYNOPSIS OF THE CURRENT STATE OF KNOWLEDGE REGARDING ESTROGEN-INDUCED CARCINOGENESIS, II) A REVIEW OF EVIDENCE FROM CLINICAL AND ANIMAL-BASED STUDIES THAT SUPPORT A ROLE FOR GPER IN CANCER PROGRESSION, AND III) A MECHANISTIC FRAMEWORK DESCRIBING HOW GPER-MEDIATED ESTROGEN ACTION MAY INFLUENCE THE TUMOR AND ITS MICROENVIRONMENT.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                
18  1398  48 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
19  1836  28 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
20  4147  38 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