1 1254 99 CURRENT PROGRESS ON THE MECHANISMS OF HYPERHOMOCYSTEINEMIA-INDUCED VASCULAR INJURY AND USE OF NATURAL POLYPHENOL COMPOUNDS. CARDIOVASCULAR DISEASE IS ONE OF THE MOST COMMON DISEASES IN THE ELDERLY POPULATION, AND ITS INCIDENCE HAS RAPIDLY INCREASED WITH THE PROLONGATION OF LIFE EXPECTANCY. HYPERHOMOCYSTEINEMIA IS AN INDEPENDENT RISK FACTOR FOR VARIOUS CARDIOVASCULAR DISEASES, INCLUDING ATHEROSCLEROSIS, AND DAMAGE TO VASCULAR FUNCTION PLAYS AN INITIAL ROLE IN ITS PATHOGENESIS. THIS REVIEW PRESENTS THE LATEST KNOWLEDGE ON THE MECHANISMS OF VASCULAR INJURY CAUSED BY HYPERHOMOCYSTEINEMIA, INCLUDING OXIDATIVE STRESS, ENDOPLASMIC RETICULUM STRESS, PROTEIN N-HOMOCYSTEINIZATION, AND EPIGENETIC MODIFICATION, AND DISCUSSES THE THERAPEUTIC TARGETS OF NATURAL POLYPHENOLS. STUDIES HAVE SHOWN THAT NATURAL POLYPHENOLS IN PLANTS CAN REDUCE HOMOCYSTEINE LEVELS AND REGULATE DNA METHYLATION BY ACTING ON OXIDATIVE STRESS AND ENDOPLASMIC RETICULUM STRESS-RELATED SIGNALING PATHWAYS, THUS IMPROVING HYPERHOMOCYSTEINEMIA-INDUCED VASCULAR INJURY. NATURAL POLYPHENOLS OBTAINED VIA DAILY DIET ARE SAFER AND HAVE MORE PRACTICAL SIGNIFICANCE IN THE PREVENTION AND TREATMENT OF CHRONIC DISEASES THAN TRADITIONAL DRUGS. 2021 2 2100 28 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 3 6913 24 [VARIOUS PATHWAYS LEADING TO THE PROGRESSION OF CHRONIC LIVER DISEASES]. AS THE RESULT OF VARIOUS EFFECTS (VIRUSES, METABOLIC DISEASES, NUTRITIONAL FACTORS, TOXIC AGENTS, AUTOIMMUNE PROCESSES) ABNORMAL LIVER FUNCTION, LIVER STEATOSIS AND CONNECTIVE TISSUE REMODELING MAY DEVELOP. PROGRESSION OF THIS PROCESS IS COMPLEX INCLUDING VARIOUS PATHWAYS AND A NUMBER OF FACTORS. THE AUTHORS SUMMARIZE THE FACTORS INVOLVED IN THE PROGRESSION OF CHRONIC LIVER DISEASE. THEY DESCRIBE THE ROLE OF CELLS AND THE PRODUCED INFLAMMATORY MEDIATORS AND CYTOKINES, AS WELL AS THE RELATIONSHIP BETWEEN THE DISEASE AND THE INTESTINAL FLORA. THEY EMPHASIZE THE ROLE OF OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION AND CELL DEATH IN DISEASE PROGRESSION. INSULIN RESISTANCE AND MICRO-ELEMENTS (IRON, COPPER) IN RELATION TO LIVER DAMAGE ARE ALSO DISCUSSED, AND GENETIC AND EPIGENETIC ASPECTS UNDERLYING DISEASE PROGRESSION ARE SUMMARIZED. DISCOVERY OF NOVEL TREATMENT OPTIONS, ASSESSMENT OF THE EFFECTIVENESS OF TREATMENT, AS WELL AS THE SUCCESS AND PROPER TIMING OF LIVER TRANSPLANTATION MAY DEPEND ON A BETTER UNDERSTANDING OF THE PROCESS OF DISEASE PROGRESSION. 2016 4 2163 25 EPIGENETIC MECHANISMS IN DIABETIC VASCULAR COMPLICATIONS. THERE HAS BEEN A RAPID INCREASE IN THE INCIDENCE OF DIABETES AS WELL THE ASSOCIATED VASCULAR COMPLICATIONS. BOTH GENETIC AND ENVIRONMENTAL FACTORS HAVE BEEN IMPLICATED IN THESE PATHOLOGIES. INCREASING EVIDENCE SUGGESTS THAT EPIGENETIC FACTORS PLAY A KEY ROLE IN THE COMPLEX INTERPLAY BETWEEN GENES AND THE ENVIRONMENT. ACTIONS OF MAJOR PATHOLOGICAL MEDIATORS OF DIABETES AND ITS COMPLICATIONS SUCH AS HYPERGLYCAEMIA, OXIDANT STRESS, AND INFLAMMATORY FACTORS CAN LEAD TO DYSREGULATED EPIGENETIC MECHANISMS THAT AFFECT CHROMATIN STRUCTURE AND GENE EXPRESSION. FURTHERMORE, PERSISTENCE OF THIS ALTERED STATE OF THE EPIGENOME MAY BE THE UNDERLYING MECHANISM CONTRIBUTING TO A 'METABOLIC MEMORY' THAT RESULTS IN CHRONIC INFLAMMATION AND VASCULAR DYSFUNCTION IN DIABETES EVEN AFTER ACHIEVING GLYCAEMIC CONTROL. FURTHER EXAMINATION OF EPIGENETIC MECHANISMS BY ALSO TAKING ADVANTAGE OF RECENTLY DEVELOPED NEXT-GENERATION SEQUENCING TECHNOLOGIES CAN PROVIDE NOVEL INSIGHTS INTO THE PATHOLOGY OF DIABETES AND ITS COMPLICATIONS AND LEAD TO THE DISCOVERY OF MUCH NEEDED NEW DRUG TARGETS FOR THESE DISEASES. IN THIS REVIEW, WE HIGHLIGHT THE ROLE OF EPIGENETICS IN DIABETES AND ITS VASCULAR COMPLICATIONS, AND RECENT TECHNOLOGICAL ADVANCES THAT HAVE SIGNIFICANTLY ACCELERATED THE FIELD. 2011 5 5390 29 REDOX-FIBROSIS: IMPACT OF TGFBETA1 ON ROS GENERATORS, MEDIATORS AND FUNCTIONAL CONSEQUENCES. FIBROSIS IS ONE OF THE MOST PREVALENT FEATURES OF AGE-RELATED DISEASES LIKE OBESITY, DIABETES, NON-ALCOHOLIC FATTY LIVER DISEASE, CHRONIC KIDNEY DISEASE, OR CARDIOMYOPATHY AND AFFECTS MILLIONS OF PEOPLE IN ALL COUNTRIES. ALTHOUGH THE UNDERSTANDING ABOUT THE PATHOPHYSIOLOGY OF FIBROSIS HAS IMPROVED A LOT DURING THE RECENT YEARS, A NUMBER OF MECHANISMS STILL REMAIN UNKNOWN. ALTHOUGH TGF-BETA1 SIGNALING, LOSS OF METABOLIC HOMEOSTASIS AND CHRONIC LOW-GRADE INFLAMMATION APPEAR TO PLAY IMPORTANT ROLES IN THE PATHOGENESIS OF FIBROSIS, RECENT EVIDENCE INDICATES THAT OXIDATIVE STRESS AND THE ANTIOXIDANT SYSTEM MAY ALSO BE CRUCIAL FOR FIBROSIS DEVELOPMENT AND PERSISTENCE. THESE FINDINGS POINT TO A CONCEPT OF A REDOX-FIBROSIS WHERE THE CELLULAR OXIDANT AND ANTIOXIDANT SYSTEM COULD BE POTENTIAL THERAPEUTIC TARGETS. THE CURRENT REVIEW AIMS TO SUMMARIZE THE EXISTING LINKS BETWEEN TGF-BETA1 SIGNALING, GENERATION AND ACTION OF REACTIVE OXYGEN SPECIES, EXPRESSION OF ANTIOXIDATIVE ENZYMES, AND FUNCTIONAL CONSEQUENCES INCLUDING EPIGENETIC REDOX-MEDIATED RESPONSES DURING FIBROSIS. 2015 6 2154 38 EPIGENETIC MECHANISMS AND KIDNEY DISEASES. IN RECENT YEARS, MOLECULAR RESEARCH HAS BROUGHT TO LIGHT A SERIES OF MECHANISMS INVOLVED IN THE REGULATION OF GENE FUNCTION WITHOUT ALTERING THE DNA SEQUENCE. THESE MECHANISMS ARE DESCRIBED WITH THE TERM "EPIGENETICS" AND INCLUDE MODIFICATIONS IN THE STRUCTURE OF THE HUMAN GENOME, LEADING TO HERITABLE AND POTENTIALLY REVERSIBLE CHANGES IN GENE EXPRESSION. THERE IS NOW INCREASING EVIDENCE SUGGESTING THAT SEVERAL CHARACTERISTIC FEATURES OF CHRONIC KIDNEY DISEASE SUCH AS HYPERHOMOCYSTEINEMIA, SUBCLINICAL INFLAMMATION, INCREASED OXIDATIVE STRESS AND OTHERS MAY AFFECT THE HUMAN EPIGENOME. IN ADDITION, ANIMAL STUDIES HAVE SUGGESTED A POSSIBLE LINK BETWEEN NUTRITION AND ENVIRONMENTAL EXPOSURE DURING THE PERICONCEPTIONAL PERIOD AND EPIGENETIC CHANGES IN THE EXPRESSION OF MAJOR GENES IMPLICATED IN KIDNEY ORGANOGENESIS; THESE CHANGES RESULT IN A DIMINISHED NUMBER OF NEPHRONS IN THE DEVELOPING KIDNEY, WHICH PREDISPOSES TO AN INCREASED RISK FOR HYPERTENSION AND CHRONIC KIDNEY DISEASE IN FUTURE LIFE. THE UNDERSTANDING OF THE ROLE OF EPIGENETIC PHENOMENA IN THE PATHOGENESIS OF CHRONIC KIDNEY DISEASE OPENS NEW AVENUES FOR FUTURE THERAPEUTIC STRATEGIES, THROUGH THE DEVELOPMENT OF PHARMACEUTICAL AGENTS THAT TARGET DIRECTLY WITH THE CHANGES IN THE HUMAN EPIGENOME. SUCH EPIGENETIC DRUGS ARE ALREADY IN CLINICAL USE FOR THE TREATMENT OF CANCER AS WELL AS UNDER INVESTIGATION FOR THE USE IN OTHER DISEASES. THIS REVIEW WILL SUMMARIZE THE EXISTING DATA ON THE LINK BETWEEN EPIGENETIC MECHANISMS AND CHRONIC UREMIC MILIEU, AS WELL AS THE PROMISING RESULTS OF ONGOING RESEARCH IN THE FIELD OF EPIGENETIC DRUGS THAT COULD REPRESENT ADDITIONAL OPTIONS IN OUR THERAPEUTIC ARMAMENTARIUM FOR PATIENTS WITH CHRONIC KIDNEY DISEASE. 2011 7 6258 35 THE MOLECULAR MECHANISM OF POLYPHENOLS IN THE REGULATION OF AGEING HALLMARKS. AGEING IS A COMPLEX PROCESS CHARACTERIZED MAINLY BY A DECLINE IN THE FUNCTION OF CELLS, TISSUES, AND ORGANS, RESULTING IN AN INCREASED RISK OF MORTALITY. THIS PROCESS INVOLVES SEVERAL CHANGES, DESCRIBED AS HALLMARKS OF AGEING, WHICH INCLUDE GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC CHANGES, LOSS OF PROTEOSTASIS, DYSREGULATED NUTRIENT SENSING, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, STEM CELL DEPLETION, AND ALTERED INTRACELLULAR COMMUNICATION. THE DETERMINING ROLE THAT ENVIRONMENTAL FACTORS SUCH AS DIET AND LIFESTYLE PLAY ON HEALTH, LIFE EXPECTANCY, AND SUSCEPTIBILITY TO DISEASES, INCLUDING CANCER AND NEURODEGENERATIVE DISEASES, IS WELLESTABLISHED. IN VIEW OF THE GROWING INTEREST IN THE BENEFICIAL EFFECTS OF PHYTOCHEMICALS IN THE PREVENTION OF CHRONIC DISEASES, SEVERAL STUDIES HAVE BEEN CONDUCTED, AND THEY STRONGLY SUGGEST THAT THE INTAKE OF DIETARY POLYPHENOLS MAY BRING NUMEROUS BENEFITS DUE TO THEIR ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES, AND THEIR INTAKE HAS BEEN ASSOCIATED WITH IMPAIRED AGEING IN HUMANS. POLYPHENOL INTAKE HAS BEEN SHOWN TO BE EFFECTIVE IN AMELIORATING SEVERAL AGE-RELATED PHENOTYPES, INCLUDING OXIDATIVE STRESS, INFLAMMATORY PROCESSES, IMPAIRED PROTEOSTASIS, AND CELLULAR SENESCENCE, AMONG OTHER FEATURES, WHICH CONTRIBUTE TO AN INCREASED RISK OF AGEING-ASSOCIATED DISEASES. THIS REVIEW AIMS TO ADDRESS, IN A GENERAL WAY, THE MAIN FINDINGS DESCRIBED IN THE LITERATURE ABOUT THE BENEFITS OF POLYPHENOLS IN EACH OF THE HALLMARKS OF AGEING, AS WELL AS THE MAIN REGULATORY MECHANISMS RESPONSIBLE FOR THE OBSERVED ANTIAGEING EFFECTS. 2023 8 6067 39 THE DIABETES MELLITUS-ATHEROSCLEROSIS CONNECTION: THE ROLE OF LIPID AND GLUCOSE METABOLISM AND CHRONIC INFLAMMATION. DIABETES MELLITUS COMPRISES A GROUP OF CARBOHYDRATE METABOLISM DISORDERS THAT SHARE A COMMON MAIN FEATURE OF CHRONIC HYPERGLYCEMIA THAT RESULTS FROM DEFECTS OF INSULIN SECRETION, INSULIN ACTION, OR BOTH. INSULIN IS AN IMPORTANT ANABOLIC HORMONE, AND ITS DEFICIENCY LEADS TO VARIOUS METABOLIC ABNORMALITIES IN PROTEINS, LIPIDS, AND CARBOHYDRATES. ATHEROSCLEROSIS DEVELOPS AS A RESULT OF A MULTISTEP PROCESS ULTIMATELY LEADING TO CARDIOVASCULAR DISEASE ASSOCIATED WITH HIGH MORBIDITY AND MORTALITY. ALTERATION OF LIPID METABOLISM IS A RISK FACTOR AND CHARACTERISTIC FEATURE OF ATHEROSCLEROSIS. POSSIBLE LINKS BETWEEN THE TWO CHRONIC DISORDERS DEPENDING ON ALTERED METABOLIC PATHWAYS HAVE BEEN INVESTIGATED IN NUMEROUS STUDIES. IT WAS SHOWN THAT BOTH TYPES OF DIABETES MELLITUS CAN ACTUALLY INDUCE ATHEROSCLEROSIS DEVELOPMENT OR FURTHER ACCELERATE ITS PROGRESSION. ELEVATED GLUCOSE LEVEL, DYSLIPIDEMIA, AND OTHER METABOLIC ALTERATIONS THAT ACCOMPANY THE DISEASE DEVELOPMENT ARE TIGHTLY INVOLVED IN THE PATHOGENESIS OF ATHEROSCLEROSIS AT ALMOST EVERY STEP OF THE ATHEROGENIC PROCESS. CHRONIC INFLAMMATION IS CURRENTLY CONSIDERED AS ONE OF THE KEY FACTORS IN ATHEROSCLEROSIS DEVELOPMENT AND IS PRESENT STARTING FROM THE EARLIEST STAGES OF THE PATHOLOGY INITIATION. IT MAY ALSO BE REGARDED AS ONE OF THE POSSIBLE LINKS BETWEEN ATHEROSCLEROSIS AND DIABETES MELLITUS. HOWEVER, THE DATA AVAILABLE SO FAR DO NOT ALLOW FOR DEVELOPING EFFECTIVE ANTI-INFLAMMATORY THERAPEUTIC STRATEGIES THAT WOULD STOP ATHEROSCLEROTIC LESION PROGRESSION OR INDUCE LESION REDUCTION. IN THIS REVIEW, WE SUMMARIZE THE MAIN ASPECTS OF DIABETES MELLITUS THAT POSSIBLY AFFECT THE ATHEROGENIC PROCESS AND ITS RELATIONSHIP WITH CHRONIC INFLAMMATION. WE ALSO DISCUSS THE ESTABLISHED PATHOPHYSIOLOGICAL FEATURES THAT LINK ATHEROSCLEROSIS AND DIABETES MELLITUS, SUCH AS OXIDATIVE STRESS, ALTERED PROTEIN KINASE SIGNALING, AND THE ROLE OF CERTAIN MIRNA AND EPIGENETIC MODIFICATIONS. 2020 9 5821 31 STRESS IN OBESITY AND ASSOCIATED METABOLIC AND CARDIOVASCULAR DISORDERS. OBESITY HAS SIGNIFICANT IMPLICATIONS FOR HEALTHCARE, SINCE IT IS A MAJOR RISK FACTOR FOR BOTH TYPE 2 DIABETES AND THE METABOLIC SYNDROME. THIS SYNDROME IS A COMMON AND COMPLEX DISORDER COMBINING OBESITY, DYSLIPIDEMIA, HYPERTENSION, AND INSULIN RESISTANCE. IT IS ASSOCIATED WITH HIGH ATHEROSCLEROTIC CARDIOVASCULAR RISK, WHICH CAN ONLY PARTIALLY BE EXPLAINED BY ITS COMPONENTS. THEREFORE, TO EXPLAIN HOW OBESITY CONTRIBUTES TO THE DEVELOPMENT OF METABOLIC AND CARDIOVASCULAR DISORDERS, MORE AND BETTER INSIGHT IS REQUIRED INTO THE EFFECTS OF PERSONAL AND ENVIRONMENTAL STRESS ON DISEASE PROCESSES. IN THIS PAPER, WE SHOW THAT OBESITY IS A CHRONIC INFLAMMATORY DISEASE, WHICH HAS MANY MOLECULAR MECHANISMS IN COMMON WITH ATHEROSCLEROSIS. FURTHERMORE, WE FOCUS ON THE ROLE OF OXIDATIVE STRESS ASSOCIATED WITH OBESITY IN THE DEVELOPMENT OF THE METABOLIC SYNDROME. WE DISCUSS HOW SEVERAL STRESS CONDITIONS ARE RELATED TO INFLAMMATION AND OXIDATIVE STRESS IN ASSOCIATION WITH OBESITY AND ITS COMPLICATIONS. WE ALSO EMPHASIZE THE RELATION BETWEEN STRESS CONDITIONS AND THE DEREGULATION OF EPIGENETIC CONTROL MECHANISMS BY MEANS OF MICRORNAS AND SHOW HOW THIS IMPAIRMENT FURTHER CONTRIBUTES TO THE DEVELOPMENT OF OBESITY, CLOSING THE VICIOUS CIRCLE. FINALLY, WE DISCUSS THE LIMITATIONS OF CURRENT ANTI-INFLAMMATION AND ANTIOXIDANT THERAPY TO TREAT OBESITY. 2012 10 183 29 ACCELERATED VASCULAR AGING IN CHRONIC KIDNEY DISEASE: THE POTENTIAL FOR NOVEL THERAPIES. THE PATHOPHYSIOLOGY OF VASCULAR DISEASE IS LINKED TO ACCELERATED BIOLOGICAL AGING AND A COMBINATION OF GENETIC, LIFESTYLE, BIOLOGICAL, AND ENVIRONMENTAL RISK FACTORS. WITHIN THE SCENARIO OF UNCONTROLLED ARTERY WALL AGING PROCESSES, CKD (CHRONIC KIDNEY DISEASE) STANDS OUT AS A VALID MODEL FOR DETAILED STRUCTURAL, FUNCTIONAL, AND MOLECULAR STUDIES OF THIS PROCESS. THE CARDIORENAL SYNDROME RELATES TO THE DETRIMENTAL BIDIRECTIONAL INTERPLAY BETWEEN THE KIDNEY AND THE CARDIOVASCULAR SYSTEM. IN ADDITION TO ESTABLISHED RISK FACTORS, THIS GROUP OF PATIENTS IS SUBJECTED TO A PLETHORA OF OTHER EMERGING VASCULAR RISK FACTORS, SUCH AS INFLAMMATION, OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, VITAMIN K DEFICIENCY, CELLULAR SENESCENCE, SOMATIC MUTATIONS, EPIGENETIC MODIFICATIONS, AND INCREASED APOPTOSIS. A BETTER UNDERSTANDING OF THE MOLECULAR MECHANISMS THROUGH WHICH THE UREMIC MILIEU TRIGGERS AND MAINTAINS EARLY VASCULAR AGING PROCESSES, HAS PROVIDED IMPORTANT NEW CLUES ON INFLAMMATORY PATHWAYS AND EMERGING RISK FACTORS ALIKE, AND TO THE ALTERED BEHAVIOR OF CELLS IN THE ARTERIAL WALL. ADVANCES IN THE UNDERSTANDING OF THE BIOLOGY OF UREMIC EARLY VASCULAR AGING OPENS AVENUES TO NOVEL PHARMACOLOGICAL AND NUTRITIONAL THERAPEUTIC INTERVENTIONS. SUCH STRATEGIES HOLD PROMISE TO IMPROVE FUTURE PREVENTION AND TREATMENT OF EARLY VASCULAR AGING NOT ONLY IN CKD BUT ALSO IN THE ELDERLY GENERAL POPULATION. 2023 11 4895 37 OXIDATIVE STRESS DRIVERS AND MODULATORS IN OBESITY AND CARDIOVASCULAR DISEASE: FROM BIOMARKERS TO THERAPEUTIC APPROACH. THIS REVIEW ARTICLE IS INTENDED TO DESCRIBE HOW OXIDATIVE STRESS REGULATES CARDIOVASCULAR DISEASE DEVELOPMENT AND PROGRESSION. EPIGENETIC MECHANISMS RELATED TO OXIDATIVE STRESS, AS WELL AS MORE RELIABLE BIOMARKERS OF OXIDATIVE STRESS, ARE EMERGING OVER THE LAST YEARS AS POTENTIALLY USEFUL TOOLS TO DESIGN THERAPEUTIC APPROACHES AIMED AT MODULATING ENHANCED OXIDATIVE STRESS "IN VIVO", THEREBY MITIGATING THE CONSEQUENT ATHEROSCLEROTIC BURDEN. AS A PARADIGM, WE DESCRIBE THE CASE OF OBESITY, IN WHICH THE INTERTWINING AMONG OXIDATIVE STRESS, DUE TO CALORIC OVERLOAD, CHRONIC LOW-GRADE INFLAMMATION INDUCED BY ADIPOSE TISSUE DYSFUNCTION, AND PLATELET ACTIVATION REPRESENTS A VICIOUS CYCLE FAVORING THE PROGRESSION OF ATHEROTHROMBOSIS. OXIDATIVE STRESS IS A MAJOR PLAYER IN THE PATHOBIOLOGY OF CARDIOVASCULAR DISEASE (CVD). REACTIVE OXYGEN SPECIES (ROS)- DEPENDENT SIGNALING PATHWAYS PROMPT TRANSCRIPTIONAL AND EPIGENETIC DYSREGULATION, INDUCING CHRONIC LOW-GRADE INFLAMMATION, PLATELET ACTIVATION AND ENDOTHELIAL DYSFUNCTION. IN ADDITION, SEVERAL OXIDATIVE BIOMARKERS HAVE BEEN PROPOSED WITH THE POTENTIAL TO IMPROVE CURRENT UNDERSTANDING OF THE MECHANISMS UNDERLYING CVD. THESE INCLUDE ROS-GENERATING AND/OR QUENCHING MOLECULES, AND ROS-MODIFIED COMPOUNDS, SUCH AS F2-ISOPROSTANES. THERE IS ALSO INCREASING EVIDENCE THAT NONCODING MICRO- RNA (MI-RNA) ARE CRITICALLY INVOLVED IN POST- TRANSCRIPTIONAL REGULATION OF CELL FUNCTIONS, INCLUDING ROS GENERATION, INFLAMMATION, REGULATION OF CELL PROLIFERATION, ADIPOCYTE DIFFERENTIATION, ANGIOGENESIS AND APOPTOSIS. THESE MOLECULES HAVE PROMISING TRANSLATIONAL POTENTIAL AS BOTH MARKERS OF DISEASE AND SITE OF TARGETED INTERVENTIONS. FINALLY, OXIDATIVE STRESS IS A CRITICAL TARGET OF SEVERAL CARDIOPROTECTIVE DRUGS AND NUTRACEUTICALS, INCLUDING ANTIDIABETIC AGENTS, STATINS, RENIN-ANGIOTENSIN SYSTEM BLOCKERS, POLYPHENOLS AND OTHER ANTIOXIDANTS. FURTHER UNDERSTANDING OF ROS-GENERATING MECHANISMS, THEIR BIOLOGICAL ROLE AS WELL AS POTENTIAL THERAPEUTIC IMPLICATIONS WOULD TRANSLATE INTO CONSISTENT BENEFITS FOR EFFECTIVE CV PREVENTION. 2015 12 3593 38 IMPLICATION OF THE MEDITERRANEAN DIET ON THE HUMAN EPIGENOME. EPIGENETICS, DEFINED AS "HEREDITARY CHANGES IN GENE EXPRESSION THAT OCCUR WITHOUT ANY CHANGE IN THE DNA SEQUENCE", CONSISTS OF VARIOUS EPIGENETIC MARKS, INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS, AND NON-CODING RNAS. THE EPIGENOME, WHICH HAS A DYNAMIC STRUCTURE IN RESPONSE TO INTRACELLULAR AND EXTRACELLULAR STIMULI, HAS A KEY ROLE IN THE CONTROL OF GENE ACTIVITY, SINCE IT IS LOCATED AT THE INTERSECTION OF CELLULAR INFORMATION ENCODED IN THE GENOME AND MOLECULAR/CHEMICAL INFORMATION OF EXTRACELLULAR ORIGIN. THE FOCUS SHIFT OF STUDIES TO EPIGENETIC REPROGRAMMING HAS LED TO THE FORMATION AND PROGRESSIVE IMPORTANCE OF A CONCEPT CALLED "NUTRIEPIGENETICS", WHOSE AIM IS TO PREVENT DISEASES BY INTERVENING ON NUTRITION STYLE. AMONG THE DIET TYPES ADOPTED IN THE WORLD, THE RENOWNED MEDITERRANEAN DIET (MD), BEING RICH IN UNSATURATED FATTY ACIDS AND CONTAINING HIGH LEVELS OF WHOLE GRAIN FOODS AND LARGE QUANTITIES OF FRUITS, VEGETABLES, AND LEGUMES, HAS SHOWN NUMEROUS ADVANTAGES IN EXCLUDING CHRONIC DISEASES. ADDITIONALLY, THE FACT THAT THIS DIET IS RICH IN POLYPHENOLS WITH HIGH ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES HAS AN UNDENIABLE EFFECT IN TURNING SOME CELLULAR PATHWAYS AGAINST THE DISEASE. IT IS ALSO APPARENT THAT THE EFFECTS OF POLYPHENOLS ON THE EPIGENOME CAUSE CHANGES IN MECHANISMS SUCH AS DNA METHYLATION AND HISTONE ACETYLATION/DEACETYLATION, WHICH HAVE A REGULATORY EFFECT ON GENE REGULATION. THIS REVIEW PRESENTS THE EFFECTS OF LONG-TERM CONSUMPTION OF NUTRIENTS FROM THE MD ON THE EPIGENOME AND DISCUSSES THE BENEFITS OF THIS DIET IN THE TREATMENT AND EVEN PREVENTION OF CHRONIC DISEASES. 2022 13 6034 33 THE CHALLENGE BY MULTIPLE ENVIRONMENTAL AND BIOLOGICAL FACTORS INDUCE INFLAMMATION IN AGING: THEIR ROLE IN THE PROMOTION OF CHRONIC DISEASE. THE AGING PROCESS IS DRIVEN BY MULTIPLE MECHANISMS THAT LEAD TO CHANGES IN ENERGY PRODUCTION, OXIDATIVE STRESS, HOMEOSTATIC DYSREGULATION AND EVENTUALLY TO LOSS OF FUNCTIONALITY AND INCREASED DISEASE SUSCEPTIBILITY. MOST AGED INDIVIDUALS DEVELOP CHRONIC LOW-GRADE INFLAMMATION, WHICH IS AN IMPORTANT RISK FACTOR FOR MORBIDITY, PHYSICAL AND COGNITIVE IMPAIRMENT, FRAILTY, AND DEATH. AT ANY AGE, CHRONIC INFLAMMATORY DISEASES ARE MAJOR CAUSES OF MORBIMORTALITY, AFFECTING UP TO 5-8% OF THE POPULATION OF INDUSTRIALIZED COUNTRIES. SEVERAL ENVIRONMENTAL FACTORS CAN PLAY AN IMPORTANT ROLE FOR MODIFYING THE INFLAMMATORY STATE. GENETICS ACCOUNTS FOR ONLY A SMALL FRACTION OF CHRONIC-INFLAMMATORY DISEASES, WHEREAS ENVIRONMENTAL FACTORS APPEAR TO PARTICIPATE, EITHER WITH A CAUSATIVE OR A PROMOTIONAL ROLE IN 50% TO 75% OF PATIENTS. SEVERAL OF THOSE CHANGES DEPEND ON EPIGENETIC CHANGES THAT WILL FURTHER MODIFY THE INDIVIDUAL RESPONSE TO ADDITIONAL STIMULI. THE INTERACTION BETWEEN INFLAMMATION AND THE ENVIRONMENT OFFERS IMPORTANT INSIGHTS ON AGING AND HEALTH. THESE CONDITIONS, OFTEN DEPENDING ON THE INDIVIDUAL'S SEX, APPEAR TO LEAD TO DECREASED LONGEVITY AND PHYSICAL AND COGNITIVE DECLINE. IN ADDITION TO BIOLOGICAL FACTORS, THE ENVIRONMENT IS ALSO INVOLVED IN THE GENERATION OF PSYCHOLOGICAL AND SOCIAL CONTEXT LEADING TO STRESS. POOR PSYCHOLOGICAL ENVIRONMENTS AND OTHER SOURCES OF STRESS ALSO RESULT IN INCREASED INFLAMMATION. HOWEVER, THE MECHANISMS UNDERLYING THE ROLE OF ENVIRONMENTAL AND PSYCHOSOCIAL FACTORS AND NUTRITION ON THE REGULATION OF INFLAMMATION, AND HOW THE RESPONSE ELICITED FOR THOSE FACTORS INTERACT AMONG THEM, ARE POORLY UNDERSTOOD. WHEREAS CERTAIN DELETERIOUS ENVIRONMENTAL FACTORS RESULT IN THE GENERATION OF OXIDATIVE STRESS DRIVEN BY AN INCREASED PRODUCTION OF REACTIVE OXYGEN AND NITROGEN SPECIES, ENDOPLASMIC RETICULUM STRESS, AND INFLAMMATION, OTHER FACTORS, INCLUDING NUTRITION (POLYUNSATURATED FATTY ACIDS) AND BEHAVIORAL FACTORS (EXERCISE) CONFER PROTECTION AGAINST INFLAMMATION, OXIDATIVE AND ENDOPLASMIC RETICULUM STRESS, AND THUS AMELIORATE THEIR DELETERIOUS EFFECT. HERE, WE DISCUSS PROCESSES AND MECHANISMS OF INFLAMMATION ASSOCIATED WITH ENVIRONMENTAL FACTORS AND BEHAVIOR, THEIR LINKS TO SEX AND GENDER, AND THEIR OVERALL IMPACT ON AGING. 2020 14 3749 34 INSIGHTS INTO THE ROLE OF PLASMATIC AND EXOSOMAL MICRORNAS IN OXIDATIVE STRESS-RELATED METABOLIC DISEASES. A COMMON DENOMINATOR OF METABOLIC DISEASES, INCLUDING TYPE 2 DIABETES MELLITUS, DYSLIPIDEMIA, AND ATHEROSCLEROSIS, ARE ELEVATED OXIDATIVE STRESS AND CHRONIC INFLAMMATION. THESE COMPLEX, MULTI-FACTORIAL DISEASES ARE CAUSED BY THE DETRIMENTAL INTERACTION BETWEEN THE INDIVIDUAL GENETIC BACKGROUND AND MULTIPLE ENVIRONMENTAL STIMULI. THE CELLS, INCLUDING THE ENDOTHELIAL ONES, ACQUIRE A PREACTIVATED PHENOTYPE AND METABOLIC MEMORY, EXHIBITING INCREASED OXIDATIVE STRESS, INFLAMMATORY GENE EXPRESSION, ENDOTHELIAL VASCULAR ACTIVATION, AND PROTHROMBOTIC EVENTS, LEADING TO VASCULAR COMPLICATIONS. THERE ARE DIFFERENT PATHWAYS INVOLVED IN THE PATHOGENESIS OF METABOLIC DISEASES, AND INCREASED KNOWLEDGE SUGGESTS A ROLE OF THE ACTIVATION OF THE NF-KB PATHWAY AND NLRP3 INFLAMMASOME AS KEY MEDIATORS OF METABOLIC INFLAMMATION. EPIGENETIC-WIDE ASSOCIATED STUDIES PROVIDE NEW INSIGHT INTO THE ROLE OF MICRORNAS IN THE PHENOMENON OF METABOLIC MEMORY AND THE DEVELOPMENT CONSEQUENCES OF VESSEL DAMAGE. IN THIS REVIEW, WE WILL FOCUS ON THE MICRORNAS RELATED TO THE CONTROL OF ANTI-OXIDATIVE ENZYMES, AS WELL AS MICRORNAS RELATED TO THE CONTROL OF MITOCHONDRIAL FUNCTIONS AND INFLAMMATION. THE OBJECTIVE IS THE SEARCH FOR NEW THERAPEUTIC TARGETS TO IMPROVE THE FUNCTIONING OF MITOCHONDRIA AND REDUCE OXIDATIVE STRESS AND INFLAMMATION, DESPITE THE ACQUIRED METABOLIC MEMORY. 2023 15 3547 35 IMMUNOMODULATORY ROLE OF NUTRIENTS: HOW CAN PULMONARY DYSFUNCTIONS IMPROVE? NUTRITION IS AN IMPORTANT TOOL THAT CAN BE USED TO MODULATE THE IMMUNE RESPONSE DURING INFECTIOUS DISEASES. IN ADDITION, THROUGH DIET, IMPORTANT SUBSTRATES ARE ACQUIRED FOR THE BIOSYNTHESIS OF REGULATORY MOLECULES IN THE IMMUNE RESPONSE, INFLUENCING THE PROGRESSION AND TREATMENT OF CHRONIC LUNG DISEASES, SUCH AS ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). IN THIS WAY, NUTRITION CAN PROMOTE LUNG HEALTH STATUS. A RANGE OF NUTRIENTS, SUCH AS VITAMINS (A, C, D, AND E), MINERALS (ZINC, SELENIUM, IRON, AND MAGNESIUM), FLAVONOIDS AND FATTY ACIDS, PLAY IMPORTANT ROLES IN REDUCING THE RISK OF PULMONARY CHRONIC DISEASES AND VIRAL INFECTIONS. THROUGH THEIR ANTIOXIDANT AND ANTI-INFLAMMATORY EFFECTS, NUTRIENTS ARE ASSOCIATED WITH BETTER LUNG FUNCTION AND A LOWER RISK OF COMPLICATIONS SINCE THEY CAN DECREASE THE HARMFUL EFFECTS FROM THE IMMUNE SYSTEM DURING THE INFLAMMATORY RESPONSE. IN ADDITION, BIOACTIVE COMPOUNDS CAN EVEN CONTRIBUTE TO EPIGENETIC CHANGES, INCLUDING HISTONE DEACETYLASE (HDAC) MODIFICATIONS THAT INHIBIT THE TRANSCRIPTION OF PROINFLAMMATORY CYTOKINES, WHICH CAN CONTRIBUTE TO THE MAINTENANCE OF HOMEOSTASIS IN THE CONTEXT OF INFECTIONS AND CHRONIC INFLAMMATORY DISEASES. THESE NUTRIENTS ALSO PLAY AN IMPORTANT ROLE IN ACTIVATING IMMUNE RESPONSES AGAINST PATHOGENS, WHICH CAN HELP THE IMMUNE SYSTEM DURING INFECTIONS. HERE, WE PROVIDE AN UPDATED OVERVIEW OF THE ROLES PLAYED BY DIETARY FACTORS AND HOW THEY CAN AFFECT RESPIRATORY HEALTH. THEREFORE, WE WILL SHOW THE ANTI-INFLAMMATORY ROLE OF FLAVONOIDS, FATTY ACIDS, VITAMINS AND MICROBIOTA, IMPORTANT FOR THE CONTROL OF CHRONIC INFLAMMATORY DISEASES AND ALLERGIES, IN ADDITION TO THE ANTIVIRAL ROLE OF VITAMINS, FLAVONOIDS, AND MINERALS DURING PULMONARY VIRAL INFECTIONS, ADDRESSING THE MECHANISMS INVOLVED IN EACH FUNCTION. THESE MECHANISMS ARE INTERESTING IN THE DISCUSSION OF PERSPECTIVES ASSOCIATED WITH SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) INFECTION AND ITS PULMONARY COMPLICATIONS SINCE PATIENTS WITH SEVERE DISEASE HAVE VITAMINS DEFICIENCY, ESPECIALLY VITAMIN D. IN ADDITION, RESEARCHES WITH THE USE OF FLAVONOIDS HAVE BEEN SHOWN TO DECREASE VIRAL REPLICATION IN VITRO. THIS WAY, A FULL UNDERSTANDING OF DIETARY INFLUENCES CAN IMPROVE THE LUNG HEALTH OF PATIENTS. 2021 16 554 33 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 2562 24 EPIGENETICS IN THE PRIMARY AND SECONDARY PREVENTION OF CARDIOVASCULAR DISEASE: INFLUENCE OF EXERCISE AND NUTRITION. INCREASING EVIDENCE LINKS CHANGES IN EPIGENETIC SYSTEMS, SUCH AS DNA METHYLATION, HISTONE MODIFICATION, AND NON-CODING RNA EXPRESSION, TO THE OCCURRENCE OF CARDIOVASCULAR DISEASE (CVD). THESE EPIGENETIC MODIFICATIONS CAN CHANGE GENETIC FUNCTION UNDER INFLUENCE OF EXOGENOUS STIMULI AND CAN BE TRANSFERRED TO NEXT GENERATIONS, PROVIDING A POTENTIAL MECHANISM FOR INHERITANCE OF BEHAVIOURAL INTERVENTION EFFECTS. THE BENEFITS OF EXERCISE AND NUTRITIONAL INTERVENTIONS IN THE PRIMARY AND SECONDARY PREVENTION OF CVD ARE WELL ESTABLISHED, BUT THE MECHANISMS ARE NOT COMPLETELY UNDERSTOOD. IN THIS REVIEW, WE DESCRIBE THE ACUTE AND CHRONIC EPIGENETIC EFFECTS OF PHYSICAL ACTIVITY AND DIETARY CHANGES. WE PROPOSE EXERCISE AND NUTRITION AS POTENTIAL TRIGGERS OF EPIGENETIC SIGNALS, PROMOTING THE RESHAPING OF TRANSCRIPTIONAL PROGRAMMES WITH EFFECTS ON CVD PHENOTYPES. FINALLY, WE HIGHLIGHT RECENT DEVELOPMENTS IN EPIGENETIC THERAPEUTICS WITH IMPLICATIONS FOR PRIMARY AND SECONDARY CVD PREVENTION. 2022 18 2704 27 EXERCISE AND COLORECTAL CANCER: PREVENTION AND MOLECULAR MECHANISMS. EXERCISE AND PHYSICAL ACTIVITY HAVE BEEN SHOWN TO BE STRONGLY ASSOCIATED WITH A DECREASED INCIDENCE RATE OF VARIOUS CHRONIC DISEASES ESPECIALLY NUMEROUS HUMAN MALIGNANCIES. A HUGE NUMBER OF CLINICAL TRIALS AND META-ANALYSIS HAVE DEMONSTRATED THAT EXERCISE IS SIGNIFICANTLY EFFECTIVE IN LOWERING THE RISK OF COLORECTAL CANCER. IN ADDITION, IT IS SUGGESTED AS AN EFFECTIVE THERAPEUTIC MODALITY AGAINST THIS CANCER TYPE. THEREFORE, IN THIS REVIEW, WE WILL REVIEW COMPREHENSIBLY THE EFFECTS OF EXERCISE IN PREVENTING, TREATING, AND ALLEVIATING THE ADVERSE EFFECTS OF CONVENTIONAL THERAPEUTIC OPTIONS IN COLORECTAL CANCER. MOREOVER, THE POSSIBLE MECHANISMS UNDERLYING THE POSITIVE EFFECTS OF EXERCISE AND PHYSICAL ACTIVITY IN COLORECTAL CANCER, INCLUDING REGULATION OF INFLAMMATION, APOPTOSIS, GROWTH FACTOR AXIS, IMMUNITY, EPIGENETIC, ETC. WILL BE ALSO DISCUSSED. 2022 19 6204 29 THE INFLUENCE OF EPIGENETICS AND INFLAMMATION ON CARDIOMETABOLIC RISKS. CARDIOMETABOLIC DISEASES INCLUDE METABOLIC SYNDROME, OBESITY, TYPE 2 DIABETES MELLITUS, AND HYPERTENSION. EPIGENETIC MODIFICATIONS PARTICIPATE IN CARDIOMETABOLIC DISEASES THROUGH SEVERAL PATHWAYS, INCLUDING INFLAMMATION, VASCULAR DYSFUNCTION, AND INSULIN RESISTANCE. EPIGENETIC MODIFICATIONS, WHICH ENCOMPASS ALTERATIONS TO GENE EXPRESSION WITHOUT MUTATING THE DNA SEQUENCE, HAVE GAINED MUCH ATTENTION IN RECENT YEARS, SINCE THEY HAVE BEEN CORRELATED WITH CARDIOMETABOLIC DISEASES AND MAY BE TARGETED FOR THERAPEUTIC INTERVENTIONS. EPIGENETIC MODIFICATIONS ARE GREATLY INFLUENCED BY ENVIRONMENTAL FACTORS, SUCH AS DIET, PHYSICAL ACTIVITY, CIGARETTE SMOKING, AND POLLUTION. SOME MODIFICATIONS ARE HERITABLE, INDICATING THAT THE BIOLOGICAL EXPRESSION OF EPIGENETIC ALTERATIONS MAY BE OBSERVED ACROSS GENERATIONS. MOREOVER, MANY PATIENTS WITH CARDIOMETABOLIC DISEASES PRESENT WITH CHRONIC INFLAMMATION, WHICH CAN BE INFLUENCED BY ENVIRONMENTAL AND GENETIC FACTORS. THE INFLAMMATORY ENVIRONMENT WORSENS THE PROGNOSIS OF CARDIOMETABOLIC DISEASES AND FURTHER INDUCES EPIGENETIC MODIFICATIONS, PREDISPOSING PATIENTS TO THE DEVELOPMENT OF OTHER METABOLISM-ASSOCIATED DISEASES AND COMPLICATIONS. A DEEPER UNDERSTANDING OF INFLAMMATORY PROCESSES AND EPIGENETIC MODIFICATIONS IN CARDIOMETABOLIC DISEASES IS NECESSARY TO IMPROVE OUR DIAGNOSTIC CAPABILITIES, PERSONALIZED MEDICINE APPROACHES, AND THE DEVELOPMENT OF TARGETED THERAPEUTIC INTERVENTIONS. FURTHER UNDERSTANDING MAY ALSO ASSIST IN PREDICTING DISEASE OUTCOMES, ESPECIALLY IN CHILDREN AND YOUNG ADULTS. THIS REVIEW DESCRIBES EPIGENETIC MODIFICATIONS AND INFLAMMATORY PROCESSES UNDERLYING CARDIOMETABOLIC DISEASES, AND FURTHER DISCUSSES ADVANCES IN THE RESEARCH FIELD WITH A FOCUS ON SPECIFIC POINTS FOR INTERVENTIONAL THERAPY. 2023 20 1414 34 DIETARY PHYTOCHEMICALS IN NEUROIMMUNOAGING: A NEW THERAPEUTIC POSSIBILITY FOR HUMANS? ALTHOUGH SEVERAL EFFORTS HAVE BEEN MADE IN THE SEARCH FOR GENETIC AND EPIGENETIC PATTERNS LINKED TO DISEASES, A COMPREHENSIVE EXPLANATION OF THE MECHANISMS UNDERLYING PATHOLOGICAL PHENOTYPIC PLASTICITY IS STILL FAR FROM BEING CLARIFIED. OXIDATIVE STRESS AND INFLAMMATION ARE TWO OF THE MAJOR TRIGGERS OF THE EPIGENETIC ALTERATIONS OCCURRING IN CHRONIC PATHOLOGIES, SUCH AS NEURODEGENERATIVE DISEASES. IN FACT, OVER THE LAST DECADE, REMARKABLE PROGRESS HAS BEEN MADE TO REALIZE THAT CHRONIC, LOW-GRADE INFLAMMATION IS ONE OF THE MAJOR RISK FACTOR UNDERLYING BRAIN AGING. ACCUMULATED DATA STRONGLY SUGGEST THAT PHYTOCHEMICALS FROM FRUITS, VEGETABLES, HERBS, AND SPICES MAY EXERT RELEVANT IMMUNOMODULATORY AND/OR ANTI-INFLAMMATORY ACTIVITIES IN THE CONTEXT OF BRAIN AGING. STARTING BY THE EVIDENCE THAT A COMMON DENOMINATOR OF AGING AND CHRONIC DEGENERATIVE DISEASES IS REPRESENTED BY INFLAMMATION, AND THAT SEVERAL DIETARY PHYTOCHEMICALS ARE ABLE TO POTENTIALLY INTERFERE WITH AND REGULATE THE NORMAL FUNCTION OF CELLS, IN PARTICULAR NEURONAL COMPONENTS, AIM OF THIS REVIEW IS TO SUMMARIZE RECENT STUDIES ON NEUROINFLAMMAGING PROCESSES AND PROOFS INDICATING THAT SPECIFIC PHYTOCHEMICALS MAY ACT AS POSITIVE MODULATORS OF NEUROINFLAMMATORY EVENTS. IN ADDITION, CRITICAL PATHWAYS INVOLVED IN MEDIATING PHYTOCHEMICALS EFFECTS ON NEUROINFLAMMAGING WERE DISCUSSED, EXPLORING THE REAL IMPACT OF THESE COMPOUNDS IN PRESERVING BRAIN HEALTH BEFORE THE ONSET OF SYMPTOMS LEADING TO INFLAMMATORY NEURODEGENERATION AND COGNITIVE DECLINE. 2016