1 6872 167 [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 2 4587 30 NANO-ENGINEERED VITAMINS AS A POTENTIAL EPIGENETIC MODIFIER AGAINST ENVIRONMENTAL AIR POLLUTANTS. AIR POLLUTION HAS EMERGED AS A SERIOUS THREAT TO HUMAN HEALTH DUE TO CLOSE ASSOCIATION WITH SPECTRUM OF CHRONIC AILMENTS INCLUDING CARDIOVASCULAR DISORDERS, RESPIRATORY DISEASES, NERVOUS SYSTEM DYSFUNCTIONS, DIABETES AND CANCER. EXPOSURE TO AIR-BORNE POLLUTANTS ALONG WITH POOR EATING BEHAVIOURS AND INFERIOR DIETARY QUALITY IRREVERSIBLY IMPACTS EPIGENOMIC LANDSCAPE, LEADING TO ABERRANT TRANSCRIPTIONAL CONTROL OF GENE EXPRESSION WHICH IS CENTRAL TO PATHO-PHYSIOLOGY OF NON-COMMUNICABLE DISEASES. IT IS ASSUMED THAT NUTRIEPIGENOMIC INTERVENTIONS SUCH AS VITAMINS CAN CONTROL SUCH ADVERSE EFFECTS THROUGH THEIR IMMEDIATE ACTION ON MITOCHONDRIAL EPIGENOMIC-AXIS. IMPORTANTLY, THE EXHAUSTIVE CLINICAL UTILITY OF VITAMINS-INTERCEDED EPIGENETIC SYNCHRONIZATION IS NOT WELL CHARACTERIZED. THEREFORE, IMPROVING THE CURRENT LIMITATIONS LINKED TO STABILITY AND BIOAVAILABILITY ISSUES IN VITAMIN FORMULATIONS IS HIGHLY WARRANTED. THE PRESENT REVIEW NOT ONLY SUMS UP THE AVAILABLE DATA ON THE ROLE OF VITAMINS AS POTENTIAL EPIGENETIC MODIFIERS BUT ALSO DISCUSSES THE IMPORTANCE OF NANO-ENGINEERED VITAMINS AS POTENTIAL EPIDRUGS FOR DIETARY AND PHARMACOLOGICAL INTERVENTION TO MITIGATE THE LONG-TERM EFFECTS OF AIR POLLUTION TOXICITY. 2023 3 644 25 BIOPHARMACEUTICAL MONOTARGETING VERSUS 'UNIVERSAL TARGETING' OF LATE-ONSET ALZHEIMER'S DISEASE USING MIXTURES OF PLEIOTROPIC NATURAL COMPOUNDS. A FIVE-YEAR CLOSE READING OF THE SCIENTIFIC LITERATURE ON LATE-ONSET ALZHEIMER'S DISEASE (AD) HAS PROMPTED THE INVENTION OF A NOVEL THERAPEUTIC METHOD THAT BIOMECHANISTICALLY TARGETS THE TARGETABLE DISEASE-PROCESS TARGETS OF AD WITH ONE OR ANOTHER MIXTURE OF NON-TOXIC PLEIOTROPIC NATURAL COMPOUNDS. THE FEATURED MIXTURE HEREIN IS COMPRISED OF CURCUMIN, RESVERATROL, AND EGCG. THE MIXTURE'S TARGETS INCLUDE CENTRAL PATHOLOGICAL ELEMENTS OF AD (INCLUDING AMYLOID, TAU, SYNAPTIC DYSFUNCTION, OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, AND ABERRANT NEUROINFLAMMATION), MODIFIABLE RISK FACTORS, COMORBIDITIES, AND EPIGENETIC ELEMENTS. THE FEATURED MIXTURE AND OTHER SUCH MIXTURES ARE SUITABLE FOR LONG-TERM USE, AND MAY BE APPLIED TO ANY STAGE OF AD, INCLUDING PRIMARY AND SECONDARY PREVENTION. SUCH MIXTURES ALSO WOULD BE AMENABLE FOR USE AS PRE-TREATMENT, CO-TREATMENT, AND POST-TREATMENT APPLICATIONS WITH CERTAIN BIOPHARMACEUTICAL AGENTS. THE TARGETING FOCUS HERE IS THE MAJOR CREDIBLE HYPOTHESES OF AD. THE FOCUS OF FUTURE SUCH ARTICLES WILL INCLUDE OTHER AD-RELATED TARGETS, MODIFIABLE RISK FACTORS AND COMORBIDITIES, APOE4, EPIGENETIC FACTORS, BIOAVAILABILITY, DOSE RESPONSE, AND IMPLICATIONS FOR CLINICAL TESTING. THE "UNIVERSAL TARGETING" METHOD DESCRIBED HEREIN-THAT IS, "TARGETING THE TARGETABLE TARGETS" OF AD USING CERTAIN MIXTURES OF NATURAL COMPOUNDS-IS REPROGRAMMABLE AND THUS IS APPLICABLE TO OTHER CHRONIC NEUROLOGICAL CONDITIONS, INCLUDING PARKINSON'S DISEASE, VASCULAR DEMENTIA, ISCHEMIC-STROKE PREVENTION AND RECOVERY, AND SPORTS-RELATED HEAD INJURIES AND SEQUELAE LEADING TO CHRONIC TRAUMATIC ENCEPHALOPATHY. 2019 4 4109 26 MECHANISMS AND DRUG THERAPY OF PULMONARY HYPERTENSION AT HIGH ALTITUDE. PULMONARY VASOCONSTRICTION REPRESENTS A PHYSIOLOGICAL ADAPTIVE MECHANISM TO HIGH ALTITUDE. IF EXAGGERATED, HOWEVER, IT IS ASSOCIATED WITH IMPORTANT MORBIDITY AND MORTALITY. RECENT MECHANISTIC STUDIES USING SHORT-TERM ACUTE HIGH ALTITUDE EXPOSURE HAVE PROVIDED INSIGHT INTO THE IMPORTANCE OF DEFECTIVE VASCULAR ENDOTHELIAL AND RESPIRATORY EPITHELIAL NITRIC OXIDE (NO) SYNTHESIS, INCREASED ENDOTHELIN-1 BIOAVAILABILITY, AND OVERACTIVATION OF THE SYMPATHETIC NERVOUS SYSTEM IN CAUSING EXAGGERATED HYPOXIC PULMONARY HYPERTENSION IN HUMANS. BASED ON THESE STUDIES, DRUGS THAT INCREASE NO BIOAVAILABILITY, ATTENUATE ENDOTHELIN-1 INDUCED PULMONARY VASOCONSTRICTION, OR PREVENT EXAGGERATED SYMPATHETIC ACTIVATION HAVE BEEN SHOWN TO BE USEFUL FOR THE TREATMENT/PREVENTION OF EXAGGERATED PULMONARY HYPERTENSION DURING ACUTE SHORT-TERM HIGH ALTITUDE EXPOSURE. THE MECHANISMS UNDERPINNING CHRONIC PULMONARY HYPERTENSION IN HIGH ALTITUDE DWELLERS ARE LESS WELL UNDERSTOOD, BUT RECENT EVIDENCE SUGGESTS THAT THEY DIFFER IN SOME ASPECTS FROM THOSE INVOLVED IN SHORT-TERM ADAPTATION TO HIGH ALTITUDE. THESE DIFFERENCES HAVE CONSEQUENCES FOR THE CHOICE OF THE TREATMENT FOR CHRONIC PULMONARY HYPERTENSION AT HIGH ALTITUDE. FINALLY, RECENT DATA INDICATE THAT FETAL PROGRAMMING OF PULMONARY VASCULAR DYSFUNCTION IN OFFSPRING OF PREECLAMPSIA AND CHILDREN GENERATED BY ASSISTED REPRODUCTIVE TECHNOLOGIES REPRESENTS A NOVEL AND FREQUENT CAUSE OF PULMONARY HYPERTENSION AT HIGH ALTITUDE. IN ANIMAL MODELS OF FETAL PROGRAMMING OF HYPOXIC PULMONARY HYPERTENSION, EPIGENETIC MECHANISMS PLAY A ROLE, AND TARGETING OF THESE MECHANISMS WITH DRUGS LOWERS PULMONARY ARTERY PRESSURE. IF EPIGENETIC MECHANISMS ALSO ARE OPERATIONAL IN THE FETAL PROGRAMMING OF PULMONARY VASCULAR DYSFUNCTION IN HUMANS, SUCH DRUGS MAY BECOME NOVEL TOOLS FOR THE TREATMENT OF HYPOXIC PULMONARY HYPERTENSION. 2013 5 6305 40 THE QUESTION IS WHETHER INTAKE OF FOLIC ACID FROM DIET ALONE DURING PREGNANCY IS SUFFICIENT. PREGNANCY AND FOLIC ACID: PREGNANCY IS THE MOST IMPORTANT PERIOD IN LIFE OF EVERY WOMAN, PARTIALLY FOR THE NUMBER OF PHYSIOLOGICAL ADAPTATIONS SHE IS GOING THROUGH, PARTIALLY FOR THE EXPECTANCE OF NEW LIFE. IN ADDITION, PREGNANCY IS THE "CRITICAL WINDOW" FOR DEVELOPMENT LATER IN CHILDHOOD, AS A PERIOD OF FOETAL PROGRAMMING DURING WHICH NUTRITION PLAYS ONE OF CRUCIAL ROLES. DESPITE THE GENERAL BELIEF THAT NUTRITION THROUGH PREGNANCY IS ADEQUATE AND CHARACTERIZED BY BETTER NUTRITIONAL HABITS, A NUMBER OF STUDIES DO NOT CORROBORATE THIS BELIEF. ROLE OF FOLIC ACID: AN ADEQUATE FOLATE BLOOD LEVEL IS NECESSARY FOR NORMAL CELL GROWTH, SYNTHESIS OF SEVERAL COMPOUNDS INCLUDING DEOXYRIBONUCLEIC ACID AND RIBONUCLEIC ACID, PROPER BRAIN AND NEUROLOGIC FUNCTIONS; IT IS INCLUDED IN THE REGULATION OF HOMOCYSTEINE LEVEL, AND CLOSELY RELATED TO THE VITAMIN B12 METABOLISM. FOLATE DEFICIENCY IN PREGNANCY IS RELATED TO NEURAL TUBE DEFECTS, OTHER NEUROLOGICAL DISORDERS, PRETERM DELIVERY AND LOW BIRTH WEIGHT. FOOD SOURCES: A CORRELATION BETWEEN FOLATE AND THE PREVENTION OF BROAD SPECTRUM OF CHRONIC DISEASES HAS BEEN CONFIRMED. EMERGING EVIDENCE FROM THE EPIGENETIC STUDIES IS NOW BRINGING EVEN MORE LIGHT ON THE LEVEL OF SIGNIFICANCE OF FOLIC ACID. A WIDE RANGE OF PLANT AND ANIMAL FOODS ARE THE NATURAL SOURCES OF FOLATE; LIVER, YEAST, MUSHROOMS, AND GREEN LEAFY VEGETABLES BEING THE MOST SIGNIFICANT. DIFFERENT WAYS OF FOOD PREPARATION INFLUENCE THE FOLATE STABILITY AND ITS BIOAVAILABILITY VARIES FROM 25 TO 50% FROM FOODS, 85% FROM ENRICHED FOODS OR 100% FROM SUPPLEMENTS. CONCLUSION: A GREAT AMOUNT OF SCIENTIFIC RESULTS HAS LED TO OFFICIAL RECOMMENDATIONS FOR FOLIC ACID SUPPLEMENTATION IN PREGNANT WOMEN AS WELL AS IN A NUMBER OF OBLIGATORY OR VOLUNTARY FORTIFICATION PROGRAMMES IN ORDER TO PREVENT THE FOLATE DEFICIENCY ON THE LEVEL OF DIFFERENT POPULATION GROUPS. NEVERTHELESS, THERE MUST BE A CERTAIN LEVEL OF PRECAUTION FOR ELDERLY BECAUSE FOLATE CAN MASK THE VITAMIN B12 DEFICIENCY WITH POSSIBLE FATAL OUTCOMES. 2014 6 4541 38 MULTISYSTEMIC ALTERATIONS IN HUMANS INDUCED BY BISPHENOL A AND PHTHALATES: EXPERIMENTAL, EPIDEMIOLOGICAL AND CLINICAL STUDIES REVEAL THE NEED TO CHANGE HEALTH POLICIES. A VAST AMOUNT OF EVIDENCE INDICATES THAT BISPHENOL A (BPA) AND PHTHALATES ARE WIDELY DISTRIBUTED IN THE ENVIRONMENT SINCE THESE COMPOUNDS ARE MASS-PRODUCED FOR THE MANUFACTURE OF PLASTICS AND PLASTICIZERS. THESE COMPOUNDS BELONG TO A LARGE GROUP OF SUBSTANCES TERMED ENDOCRINE-DISRUPTING CHEMICALS (EDC). IT IS WELL KNOWN THAT HUMANS AND LIVING ORGANISMS ARE UNAVOIDABLY AND UNINTENTIONALLY EXPOSED TO BPA AND PHTHALATES FROM FOOD PACKAGING MATERIALS AND MANY OTHER EVERYDAY PRODUCTS. BPA AND PHTHALATES EXERT THEIR EFFECT BY INTERFERING WITH HORMONE SYNTHESIS, BIOAVAILABILITY, AND ACTION, THEREBY ALTERING CELLULAR PROLIFERATION AND DIFFERENTIATION, TISSUE DEVELOPMENT, AND THE REGULATION OF SEVERAL PHYSIOLOGICAL PROCESSES. IN FACT, THESE EDC CAN ALTER FETAL PROGRAMMING AT AN EPIGENETIC LEVEL, WHICH CAN BE TRANSGENERATIONAL TRANSMITTED AND MAY BE INVOLVED IN THE DEVELOPMENT OF VARIOUS CHRONIC PATHOLOGIES LATER IN THE ADULTHOOD, INCLUDING METABOLIC, REPRODUCTIVE AND DEGENERATIVE DISEASES, AND CERTAIN TYPES OF CANCER. IN THIS REVIEW, WE DESCRIBE THE MOST RECENT PROPOSED MECHANISMS OF ACTION OF THESE EDC AND OFFER A COMPELLING SELECTION OF EXPERIMENTAL, EPIDEMIOLOGICAL AND CLINICAL STUDIES, WHICH SHOW EVIDENCE OF HOW EXPOSURE TO THESE POLLUTANTS AFFECTS OUR HEALTH DURING DEVELOPMENT, AND THEIR ASSOCIATION WITH A WIDE RANGE OF REPRODUCTIVE, METABOLIC AND NEUROLOGICAL DISEASES, AS WELL AS HORMONE-RELATED CANCERS. WE STRESS THE IMPORTANCE OF CONCERN IN THE GENERAL POPULATION AND THE URGENT NEED FOR THE MEDICAL HEALTH CARE SYSTEM TO CLOSELY MONITOR EDC LEVELS IN THE POPULATION DUE TO UNAVOIDABLE AND INVOLUNTARY EXPOSURE TO THESE POLLUTANTS AND THEIR IMPACT ON HUMAN HEALTH. 2021 7 1895 33 ENDOTHELIAL DYSFUNCTION IN INDIVIDUALS BORN AFTER FETAL GROWTH RESTRICTION: CARDIOVASCULAR AND RENAL CONSEQUENCES AND PREVENTIVE APPROACHES. INDIVIDUALS BORN AFTER INTRAUTERINE GROWTH RESTRICTION (IUGR) HAVE AN INCREASED RISK OF PERINATAL MORBIDITY/MORTALITY, AND THOSE WHO SURVIVE FACE LONG-TERM CONSEQUENCES SUCH AS CARDIOVASCULAR-RELATED DISEASES, INCLUDING SYSTEMIC HYPERTENSION, ATHEROSCLEROSIS, CORONARY HEART DISEASE AND CHRONIC KIDNEY DISEASE. IN ADDITION TO THE DEMONSTRATED LONG-TERM EFFECTS OF DECREASED NEPHRON ENDOWMENT AND HYPERACTIVITY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS, INDIVIDUALS BORN AFTER IUGR ALSO EXHIBIT EARLY ALTERATIONS IN VASCULAR STRUCTURE AND FUNCTION, WHICH HAVE BEEN IDENTIFIED AS KEY FACTORS OF THE DEVELOPMENT OF CARDIOVASCULAR-RELATED DISEASES. THE ENDOTHELIUM PLAYS A MAJOR ROLE IN MAINTAINING VASCULAR FUNCTION AND HOMEOSTASIS. THEREFORE, IT IS NOT SURPRISING THAT IMPAIRED ENDOTHELIAL FUNCTION CAN LEAD TO THE LONG-TERM DEVELOPMENT OF VASCULAR-RELATED DISEASES. ENDOTHELIAL DYSFUNCTION, PARTICULARLY IMPAIRED ENDOTHELIUM-DEPENDENT VASODILATION AND VASCULAR REMODELING, INVOLVES DECREASED NITRIC OXIDE (NO) BIOAVAILABILITY, IMPAIRED ENDOTHELIAL NO SYNTHASE FUNCTIONALITY, INCREASED OXIDATIVE STRESS, ENDOTHELIAL PROGENITOR CELLS DYSFUNCTION AND ACCELERATED VASCULAR SENESCENCE. PREVENTIVE APPROACHES SUCH AS BREASTFEEDING, SUPPLEMENTATION WITH FOLATE, VITAMINS, ANTIOXIDANTS, L-CITRULLINE, L-ARGININE AND TREATMENT WITH NO MODULATORS REPRESENT PROMISING STRATEGIES FOR IMPROVING ENDOTHELIAL FUNCTION, MITIGATING LONG-TERM OUTCOMES AND POSSIBLY PREVENTING IUGR OF VASCULAR ORIGIN. MOREOVER, THE IDENTIFICATION OF EARLY BIOMARKERS OF ENDOTHELIAL DYSFUNCTION, ESPECIALLY EPIGENETIC BIOMARKERS, COULD ALLOW EARLY SCREENING AND FOLLOW-UP OF INDIVIDUALS AT RISK OF DEVELOPING CARDIOVASCULAR AND RENAL DISEASES, THUS CONTRIBUTING TO THE DEVELOPMENT OF PREVENTIVE AND THERAPEUTIC STRATEGIES TO AVERT THE LONG-TERM EFFECTS OF ENDOTHELIAL DYSFUNCTION IN INFANTS BORN AFTER IUGR. 2017 8 617 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 9 4652 33 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 10 700 29 BROMODOMAIN-CONTAINING PROTEIN 4 (BRD4): A KEY PLAYER IN INFLAMMATORY BOWEL DISEASE AND POTENTIAL TO INSPIRE EPIGENETIC THERAPEUTICS. INTRODUCTION: INFLAMMATORY BOWEL DISEASES (IBDS) ARE DEBILITATING CHRONIC INFLAMMATORY DISORDERS WITH INCREASING PREVALENCE WORLDWIDE. EPIGENETIC REGULATOR BROMODOMAIN-CONTAINING PROTEIN 4 (BRD4) IS CRITICAL IN CONTROLLING GENE EXPRESSION OF IBD-ASSOCIATED INFLAMMATORY CYTOKINE NETWORKS. BRD4 AS A PROMISING THERAPEUTIC TARGET IS ALSO TIGHTLY ASSOCIATED WITH MANY OTHER DISEASES, SUCH AS AIRWAY INFLAMMATION AND FIBROSIS, CANCERS, INFECTIOUS DISEASES AND CENTRAL NERVOUS SYSTEM DISORDERS. AREAS COVERED: THIS REVIEW BRIEFLY SUMMARIZED THE CRITICAL ROLE OF BRD4 IN THE PATHOGENESIS OF IBDS AND THE CURRENT CLINICAL LANDSCAPE OF DEVELOPING BROMODOMAIN AND EXTRA TERMINAL DOMAIN (BET) INHIBITORS. THE CHALLENGES AND OPPORTUNITIES AS WELL AS FUTURE DIRECTIONS OF TARGETING BRD4 INHIBITION FOR POTENTIAL IBD MEDICATIONS WERE ALSO DISCUSSED. EXPERT OPINION: TARGETING BRD4 WITH POTENT AND SPECIFIC INHIBITORS MAY OFFER NOVEL EFFECTIVE THERAPEUTICS FOR IBD PATIENTS, PARTICULARLY THOSE WHO ARE REFRACTORY TO ANTI-TNFALPHA THERAPY AND IBD-RELATED PROFIBROTIC. DEVELOPING HIGHLY SPECIFIC BRD4 INHIBITORS FOR IBD MEDICATIONS MAY HELP ERASE THE DRAWBACKS OF MOST CURRENT PAN-BET/BRD4 INHIBITORS, SUCH AS OFF-TARGET EFFECTS, POOR ORAL BIOAVAILABILITY, AND LOW GUT MUCOSAL ABSORBANCE. NOVEL STRATEGIES SUCH AS COMBINATORIAL THERAPY, BRD4-BASED DUAL INHIBITORS AND PROTEOLYSIS TARGETING CHIMERAS (PROTACS) MAY ALSO HAVE GREAT POTENTIAL TO MITIGATE SIDE EFFECTS AND OVERCOME DRUG RESISTANCE DURING IBD TREATMENT. 2023 11 5048 38 PHARMACOLOGICAL APPROACHES IN EITHER INTERMITTENT OR PERMANENT HYPOXIA: A TALE OF TWO EXPOSURES. HYPOXIA INDUCES SEVERAL RESPONSES AT CARDIOVASCULAR, PULMONARY AND REPRODUCTIVE LEVELS, WHICH MAY LEAD TO CHRONIC DISEASES. THIS IS RELEVANT IN HUMAN POPULATIONS EXPOSED TO HIGH ALTITUDE (HA), IN EITHER CHRONIC CONTINUOUS (PERMANENT INHABITANTS) OR INTERMITTENT FASHION (HA WORKERS, TOURISTS AND MOUNTAINEERS). IN CHILE, IT IS ESTIMATED THAT 1.000.000 PEOPLE LIVE AT HIGHLANDS AND MORE THAN 55.000 WORK IN HA SHIFTS. INITIAL RESPONSES TO HYPOXIA ARE COMPENSATORY AND INDUCE ACTIVATION OF CARDIOPROTECTIVE MECHANISMS, SUCH AS THOSE SEEN UNDER INTERMITTENT HYPOBARIC (IH) HYPOXIA, EVENTS THAT COULD MEDIATE PRECONDITIONING. HOWEVER, WHENEVER HYPOXIA IS PROLONGED, THE CHRONIC ACTIVATION OF CELLULAR RESPONSES INDUCES LONG-LASTING MODIFICATIONS THAT MAY RESULT IN ACCLIMATIZATION OR PRODUCE MALADAPTIVE CHANGES WITH INCREASE IN CARDIOVASCULAR RISK. HA EXPOSURE DURING PREGNANCY INDUCES HYPOXIA AND OXIDATIVE STRESS, WHICH IN TURN MAY PROMOTE CELLULAR RESPONSES AND EPIGENETIC MODIFICATIONS RESULTING IN SEVERE IMPAIRMENT IN GROWTH AND DEVELOPMENT. SADLY, THIS CONDITION IS ACCOMPANIED WITH AN INCREASED FETAL AND NEONATAL MORBI-MORTALITY. FURTHER, DEVELOPMENTAL HYPOXIA MAY PROGRAM CARDIO-PULMONARY CIRCULATIONS LATER IN POSTNATAL LIFE, ENDING IN VASCULAR STRUCTURAL AND FUNCTIONAL ALTERATIONS WITH AUGMENTED RISK ON PULMONARY AND CARDIOVASCULAR FAILURE. ADDITIONALLY, PERMANENT HA INHABITANTS HAVE AUGMENTED RISK AND PREVALENCE OF CHRONIC HYPOXIC PULMONARY HYPERTENSION, RIGHT VENTRICULAR HYPERTROPHY AND CARDIOPULMONARY REMODELING. SIMILAR RESPONSES ARE SEEN IN ADULTS THAT ARE INTERMITTENTLY EXPOSED TO CHRONIC HYPOXIA (CH) SUCH AS SHIFT WORKERS IN HA AREAS. THE MECHANISMS INVOLVED DETERMINING THE IMMEDIATE, SHORT AND LONG-LASTING EFFECTS ARE STILL UNCLEAR. FOR SEVERAL YEARS, THE STUDY OF THE RESPONSES TO HYPOXIC INSULTS AND PHARMACOLOGICAL TARGETS HAS BEEN THE MOTIVATION OF OUR GROUP. THIS REVIEW DESCRIBES SOME OF THE MECHANISMS UNDERLYING HYPOXIC RESPONSES AND POTENTIAL THERAPEUTIC APPROACHES WITH ANTIOXIDANTS SUCH AS MELATONIN, ASCORBATE, OMEGA 3 (OMEGA3) OR COMPOUNDS THAT INCREASE THE NITRIC OXIDE (NO) BIOAVAILABILITY. 2015 12 4396 40 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 13 615 43 BIOACTIVE COMPONENTS AND POSSIBLE ACTIVITIES OF MEDICINAL MUSHROOMS IN ALLEVIATING THE PATHOGENESIS OF NONALCOHOLIC FATTY LIVER DISEASE (REVIEW). NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS A GLOBAL DISEASE THAT IS CLOSELY ASSOCIATED WITH OBESITY, TYPE 2 DIABETES MELLITUS, AND CARDIOVASCULAR DISEASE. EXCESSIVE FAT ACCUMULATION, FATTY DEGENERATION, AND CHRONIC INFLAMMATION OF THE LIVER ACTIVATE THE PROGRESSION OF NAFLD FROM SIMPLE STEATOSIS TO NONALCOHOLIC STEATOHEPATITIS AND FURTHER TO LIVER FIBROSIS, CIRRHOSIS, AND HEPATOCELLULAR CARCINOMA. THE UNDERLYING MECHANISM FOR THE DEVELOPMENT AND PROGRESSION OF NAFLD IS COMPLEX AND A MULTIPLE-HIT HYPOTHESIS INCLUDING DIETARY, ENVIRONMENTAL, GENETIC, AND EPIGENETIC FACTORS HAS BEEN RAISED. INCREASED DE NOVO LIPOGENESIS, DECREASED LIPOLYSIS, AND INSULIN RESISTANCE ARE ASSOCIATED WITH THE DEVELOPMENT OF NAFLD. CURRENTLY, NO EFFECTIVE DRUG THERAPIES ARE APPROVED FOR THE TREATMENT OF NAFLD. SEVERAL MEDICINAL MUSHROOMS HAVE BEEN FOUND TO HAVE SIGNIFICANT WEIGHT CONTROL AND GUT MICROBE MODULATION ACTIVITIES AND ANTIHYPERTRIGLYCERIDEMIC, ANTIHYPERGLYCEMIC, ANTIOXIDANT, AND ANTI-INFLAMMATORY EFFECTS, WHICH MAY BE USEFUL TO PREVENT AND ATTENUATE THE DEVELOPMENT AND PROGRESSION OF NAFLD. THESE BENEFICIAL EFFECTS ARE ASSOCIATED WITH MUSHROOMS' BIOACTIVE COMPONENTS, SUCH AS POLYSACCHARIDES, DIETARY FIBERS, ANTIOXIDANTS, AND OTHER COMPOUNDS DERIVED FROM FRUITING BODIES, CULTURED MYCELIUM, AND/OR BROTH OF MEDICINAL MUSHROOMS. THIS ARTICLE PRESENTS AN OVERVIEW OF MULTIPLE ASPECTS OF NAFLD, INCLUDING THE EPIDEMIOLOGY, PATHOGENESIS, MANAGEMENT, AND TREATMENT. THE BIOACTIVE COMPONENTS AND POSSIBLE ACTIVITIES OF MEDICINAL MUSHROOMS IN ALLEVIATING THE PATHOGENESIS OF NAFLD ARE ALSO REVIEWED. 2021 14 1636 20 DOES AGEING AFFECT ZINC HOMEOSTASIS AND DIETARY REQUIREMENTS? DIETARY INTAKES OF ZINC ARE LOWER IN THE ELDERLY BECAUSE OF REDUCED ENERGY REQUIREMENTS, AND IT IS NOT CLEAR WHETHER AGEING IMPACTS ON ADAPTIVE HOMEOSTATIC MECHANISMS, NAMELY ABSORPTIVE EFFICIENCY AND ENDOGENOUS LOSSES IN THE GI TRACT. PHYSIOLOGICAL REQUIREMENTS FOR ZINC ARE UNLIKELY TO CHANGE SIGNIFICANTLY, BUT THERE ARE SEVERAL ATTRIBUTES OF AGEING THAT MAY AFFECT ASPECTS OF ZINC METABOLISM (E.G. CHANGES IN GUT STRUCTURE AND FUNCTION, DISEASE STATES, CHRONIC INFLAMMATION, EPIGENETIC CHANGES IN GENES THAT EXPRESS ZINC-RELATED PROTEINS AND DRUG REGIMENS) THAT ARE WORTHY OF FURTHER INVESTIGATION. THERE IS, AS YET, NO INFORMATION ON THE EFFECTS OF AGEING ON ZINC TRANSPORTERS, AND THERE ARE NO SENSITIVE AND SPECIFIC MEASURES OF ZINC STATUS, THEREFORE DIETARY RECOMMENDATIONS FOR ZINC HAVE BEEN DERIVED FROM FACTORIAL CALCULATIONS USING INFORMATION ON ZINC ABSORPTION AND LOSS, AND ESTIMATES OF DIETARY BIOAVAILABILITY. 2008 15 2869 35 FUNCTIONAL FOODS AND HEALTH EFFECTS: A NUTRITIONAL BIOCHEMISTRY PERSPECTIVE. BACKGROUND: INCREASED CONSUMER S INTEREST IN HEALTH HAS DRIVEN THE DEVELOPMENT OF FOODS THAT OFFER SPECIFIC BENEFICIAL EFFECTS. THE LIST OF FOODS AND INGREDIENTS INCLUDES ESSENTIAL AND NON-ESSENTIAL NUTRIENTS, PLANT AND MARINE COMPONENTS, WHOLE FOODS, MICROORGANISMS, MICROALGAE AND TECHNOLOGICAL APPROACHES. TRADITIONALLY, HEALTH OUTCOMES FOCUSSED ON THE PREVENTION OF CHRONIC DISEASES BUT HEALTH TARGETS HAVE EXPANDED TO COVER AREAS SUCH AS BRAIN HEALTH, INFLAMMATION, EYE HEALTH, WOMEN S HEALTH, HEALTHY AGEING AND BEAUTY. OBJECTIVE: THIS REVIEW HIGHLIGHTS, FROM A NUTRITIONAL BIOCHEMISTRY PERSPECTIVE, DIFFERENTIAL ASPECTS ON DESIGNING AND INTERPRETING HUMAN STUDIES TO SUPPORT THE HEALTH EFFECTS OF FUNCTIONAL FOODS. RESULTS: DESPITE THE AVAILABLE EVIDENCE FROM IN VITRO, ANIMAL AND OBSERVATIONAL STUDIES, WELLDESIGNED HUMAN STUDIES ARE NECESSARY TO SUPPORT THE HEALTH EFFECTS OF FUNCTIONAL FOODS. INTERVENTION TRIALS WITH FOODS ARE COMPLEX AS THEY IMPLY LIMITATIONS DUE TO METHODOLOGICAL, FOOD-RELATED AND HOST-RELATED FACTORS. THE USE OF RESPONSIVE, VALIDATED AND CLINICALLY RELEVANT MARKERS BECOMES ESSENTIAL EVEN THOUGH THERE IS A LACK OF RELIABLE BIOMARKERS OF EXPOSURE FOR MANY BIOACTIVES. FURTHERMORE, THE EFFECT OF MODULATING FACTORS SUCH AS SUBCLINICAL INFLAMMATION, GUT MICROBIOTA AND GENETIC VARIABILITY SHOULD BE TAKEN INTO ACCOUNT. MULTIPLE INDICATORS MAY PROVIDE A MORE RELIABLE ALTERNATIVE TO ASSESS PHYSIOLOGICAL PROCESSES WHILE EMERGING BIOMARKERS (MICRORNAS, EPIGENETIC CHANGES) CONSTITUTE A PROMISING APPROACH. ADDITIONALLY, THE MAGNITUDE OF THE CHANGE IS CRITICAL TO SUPPORT ANY HEALTH EFFECT ALTHOUGH INTERVENTIONS MAY HAVE A LIMITED CLINICAL IMPACT BUT BE EPIDEMIOLOGICALLY RELEVANT. ALSO, BASED ON THE AVAILABLE DATA, THE PREMISE THAT BIOACTIVESCONTAINING FOODS ARE SAFE MAY BE QUESTIONABLE. CONCLUSION: AN INTEGRATED APPROACH INCLUDING MULTIPLE BIOMARKERS, GENETIC VARIABILITY, EFFECT OF GUT MICROBIOTA AND RISK/BENEFIT ASSESSMENT SHOULD BE USED TO SUPPORT THE POTENTIAL HEALTH EFFECTS OF FUNCTIONAL FOODS. 2016 16 554 41 AUTOPHAGY IN HUMAN HEALTH AND DISEASE: NOVEL THERAPEUTIC OPPORTUNITIES. SIGNIFICANCE: IN EUKARYOTES, AUTOPHAGY REPRESENTS A HIGHLY EVOLUTIONARY CONSERVED PROCESS, THROUGH WHICH MACROMOLECULES AND CYTOPLASMIC MATERIAL ARE DEGRADED INTO LYSOSOMES AND RECYCLED FOR BIOSYNTHETIC OR ENERGETIC PURPOSES. DYSFUNCTION OF THE AUTOPHAGIC PROCESS HAS BEEN ASSOCIATED WITH THE ONSET AND DEVELOPMENT OF MANY HUMAN CHRONIC PATHOLOGIES, SUCH AS CARDIOVASCULAR, METABOLIC, AND NEURODEGENERATIVE DISEASES AS WELL AS CANCER. RECENT ADVANCES: CURRENTLY, COMPREHENSIVE RESEARCH IS BEING CARRIED OUT TO DISCOVER NEW THERAPEUTIC AGENTS THAT ARE ABLE TO MODULATE THE AUTOPHAGIC PROCESS IN VIVO. RECENT EVIDENCE HAS SHOWN THAT A LARGE NUMBER OF NATURAL BIOACTIVE COMPOUNDS ARE INVOLVED IN THE REGULATION OF AUTOPHAGY BY MODULATING SEVERAL TRANSCRIPTIONAL FACTORS AND SIGNALING PATHWAYS. CRITICAL ISSUES: CRITICAL ISSUES THAT DESERVE PARTICULAR ATTENTION ARE THE INADEQUATE UNDERSTANDING OF THE COMPLEX ROLE OF AUTOPHAGY IN DISEASE PATHOGENESIS, THE LIMITED AVAILABILITY OF THERAPEUTIC DRUGS, AND THE LACK OF CLINICAL TRIALS. IN THIS CONTEXT, THE EFFECTS THAT NATURAL BIOACTIVE COMPOUNDS EXERT ON AUTOPHAGIC MODULATION SHOULD BE CLEARLY HIGHLIGHTED, SINCE THEY DEPEND ON THE TYPE AND STAGE OF THE PATHOLOGICAL CONDITIONS OF DISEASES. FUTURE DIRECTIONS: RESEARCH EFFORTS SHOULD NOW FOCUS ON UNDERSTANDING THE SURVIVAL-SUPPORTING AND DEATH-PROMOTING ROLES OF AUTOPHAGY, HOW NATURAL COMPOUNDS INTERACT EXACTLY WITH THE AUTOPHAGIC TARGETS SO AS TO INDUCE OR INHIBIT AUTOPHAGY AND ON THE EVALUATION OF THEIR PHARMACOLOGICAL EFFECTS IN A MORE IN-DEPTH AND MECHANISTIC WAY. IN ADDITION, CLINICAL STUDIES ON AUTOPHAGY-INDUCING NATURAL PRODUCTS ARE STRONGLY ENCOURAGED, ALSO TO HIGHLIGHT SOME FUNDAMENTAL ASPECTS, SUCH AS THE DOSE, THE DURATION, AND THE POSSIBLE SYNERGISTIC ACTION OF THESE COMPOUNDS WITH CONVENTIONAL THERAPY. 2019 17 1836 23 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 18 1410 34 DIETARY INTERVENTIONS FOR AUTISM SPECTRUM DISORDER: AN UPDATED SYSTEMATIC REVIEW OF HUMAN STUDIES. AUTISM IS A COMPLEX SPECTRUM OF DISORDERS WITH GENETIC, EPIGENETIC, AUTOIMMUNE, OXIDATIVE STRESS, AND ENVIRONMENTAL ETIOLOGIES. TREATMENT OF ASD USING DIETARY APPROACH IS A PROMISING STRATEGY, ESPECIALLY OWING TO ITS SAFETY AND AVAILABILITY. OUR STUDY CRITICALLY ANALYSED THE ROLES AND EFFICACY OF ANTIOXIDANTS, PROBIOTICS, PREBIOTICS, CAMEL MILK AND VITAMIN D. THIS SYSTEMATIC REVIEW PROVIDES AN UPDATED SYNOPSIS OF HUMAN STUDIES THAT INVESTIGATED THERAPEUTIC BENEFITS OF THESE DIETARY INTERVENTIONS IN AUTISM. A TOTAL OF 943 PAPERS WERE IDENTIFIED OUT OF WHICH 21 ARTICLES WERE INCLUDED IN THE SYSTEMATIC REVIEW. THE SELECTED STUDIES INVESTIGATED THE IMPACT OF 5 DIFFERENT DIETARY SUPPLEMENTATIONS IN ASD SYMPTOM AND BEHAVIOURS. THESE AGENTS INCLUDE; ANTIOXIDANTS/POLYPHENOLIC COMPOUNDS, PROBIOTICS, PREBIOTICS, CAMEL MILK AND VITAMIN D. FROM THE RESULTS OF THE PRESENT REVIEW, ANTIOXIDANTS/POLYPHENOLIC COMPOUNDS DECREASED THE LEVELS OF INFLAMMATORY CYTOKINES AND IMPROVED BEHAVIOURAL SYMPTOMS. PROBIOTICS IMPROVED BEHAVIOURAL AND GI SYMPTOMS AS WELL AS RESTORED GUT MICROBIOTA EQUILIBRIUM. PREBIOTICS DECREASED LEVELS OF INFLAMMATORY CYTOKINES, IMPROVED BEHAVIOURAL AND GI SYMPTOMS AND IMPROVED GUT MICROBIOTA. VITAMIN D IMPROVED BEHAVIOURAL SYMPTOMS AND OFFERED PROTECTIVE EFFECTS AGAINST NEUROTOXICITY. CAMEL MILK REDUCED INFLAMMATORY RESPONSES AND OXIDATIVE STRESS. GIVEN THE CHRONIC NATURE AS WELL AS EARLY ONSET OF ASD, DIETARY SUPPLEMENTS BECOME USEFUL TO COMPLEMENT NUTRITIONAL DEFICIENCIES IN CHILDREN WITH ASD. KEY BENEFITS OF THESE AGENTS STEM FROM THEIR ABILITY TO TARGET MULTIPLE PHYSIOLOGICAL AREAS VIA THE GUT BRAIN-AXIS AND ARE DEVOID OF POTENTIAL HARMFUL OR AGGRAVATING EFFECTS ON ASD PATIENTS. THE EVIDENCE COLLATED IN THIS REVIEW PROPOSE THAT DIETARY INTERVENTION MAY PROVIDE A NEW PLATFORM FOR THE MANAGEMENT OF AUTISM. 2022 19 4970 25 PATHOMECHANISMS OF PRENATALLY PROGRAMMED ADULT DISEASES. BASED ON EPIDEMIOLOGICAL OBSERVATIONS BARKER ET AL. PUT FORWARD THE HYPOTHESIS/CONCEPT THAT AN ADVERSE INTRAUTERINE ENVIRONMENT (INVOLVING AN INSUFFICIENT NUTRIENT SUPPLY, CHRONIC HYPOXIA, STRESS, AND TOXIC SUBSTANCES) IS AN IMPORTANT RISK FACTOR FOR THE DEVELOPMENT OF CHRONIC DISEASES LATER IN LIFE. THE FETUS RESPONDS TO THE UNFAVORABLE ENVIRONMENT WITH ADAPTIVE REACTIONS, WHICH ENSURE SURVIVAL IN THE SHORT RUN, BUT AT THE EXPENSE OF INITIATING PATHOLOGICAL PROCESSES LEADING TO ADULT DISEASES. IN THIS REVIEW, THE MAJOR MECHANISMS (INCLUDING TELOMERE DYSFUNCTION, EPIGENETIC MODIFICATIONS, AND CARDIOVASCULAR-RENAL-ENDOCRINE-METABOLIC REACTIONS) WILL BE OUTLINED, WITH A PARTICULAR EMPHASIS ON THE ROLE OF OXIDATIVE STRESS IN THE FETAL ORIGIN OF ADULT DISEASES. 2023 20 1710 33 DYSFUNCTIONAL IMMUNOMETABOLIC EFFECTS OF VITAMIN D DEFICIENCY, INCREASED CARDIOMETABOLIC RISK. POTENTIAL EPIDEMIOLOGICAL ALERT IN AMERICA? VITAMIN D DEFICIENCY IS A SERIOUS PUBLIC HEALTH PROBLEM WORLDWIDE THAT AFFECTS NOT ONLY SKELETAL HEALTH, BUT ALSO A WIDE RANGE OF ACUTE AND CHRONIC DISEASES. HOWEVER, THERE IS STILL SKEPTICISM BECAUSE OF THE LACK OF RANDOMIZED, CONTROLLED TRIALS TO SUPPORT ASSOCIATION STUDIES ON THE BENEFITS OF VITAMIN D FOR NON-SKELETAL HEALTH. THIS REVIEW WAS BASED ON ARTICLES PUBLISHED DURING THE 1980-2015 OBTAINED FROM THE COCHRANE CENTRAL REGISTER OF CONTROLLED TRIALS, MEDLINE AND PUBMED, AND FOCUSES ON RECENT CHALLENGES WITH REGARD TO THE DEFINITION OF VITAMIN D DEFICIENCY AND HOW TO ACHIEVE OPTIMAL SERUM 25-HYDROXYVITAMIN D LEVELS FROM DIETARY SOURCES, SUPPLEMENTS, AND SUN EXPOSURE. THE EFFECT OF VITAMIN D ON EPIGENETIC FETAL PROGRAMMING AND REGULATION OF GENES THAT MAY POTENTIALLY EXPLAIN WHY VITAMIN D COULD HAVE SUCH LIFELONG COMPREHENSIVE HEALTH BENEFITS IS REVIEWED. OPTIMIZATION OF VITAMIN D LEVELS IN CHILDREN AND ADULTS AROUND THE WORLD HAS POTENTIAL BENEFITS TO IMPROVE SKELETAL HEALTH AND TO REDUCE THE RISK OF CHRONIC DISEASES, INCLUDING SOME TYPES OF CANCER, AUTOIMMUNE DISEASES, INFECTIOUS DISEASES, TYPE 2 DIABETES MELLITUS, AND SEVERE CARDIOVASCULAR DISORDERS SUCH AS ATHEROTHROMBOSIS, NEUROCOGNITIVE DISORDERS, AND MORTALITY. 2017