1 4315 78 MICRORNAS AS NEW TARGETS OF DIETARY POLYPHENOLS. IN THE LASTS YEARS IT HAS BECOME EVIDENT THAT POLYPHENOLS MODIFY CELL FUNCTIONALITY THROUGH EPIGENETIC MECHANISMS, SUCH AS MODULATING MICRORNA (MIRNA) LEVELS. MIRNAS ARE SMALL NON-CODING RNAS OF ABOUT 22 NUCLEOTIDES IN LENGTH, THAT MODULATE GENE EXPRESSION AT THE POST-TRANSCRIPTIONAL LEVEL. MIRNAS ARE INVOLVED IN ALMOST ALL BIOLOGICAL PROCESSES, AFFECT MOST METABOLIC PATHWAYS AND RECENT EVIDENCE SUGGESTS THEIR DYSREGULATION IN A NUMBER OF METABOLIC DISORDERS AND DISEASES. IN THIS SENSE, MIRNAS ARE EMERGING AS POTENTIAL BIOMARKERS OF NUMEROUS PATHOLOGIES AND THEREFORE AS NEW THERAPEUTIC TARGETS. POLYPHENOLIC MODULATION OF MIRNAS IS VERY ATTRACTIVE AS A STRATEGY TO TARGET NUMEROUS CELL PROCESSES AND POTENTIALLY REDUCE THE RISK OF CHRONIC DISEASES. 2014 2 4460 24 MOLECULAR MECHANISMS OF ENVIRONMENTAL EXPOSURES AND HUMAN DISEASE. A SUBSTANTIAL PROPORTION OF DISEASE RISK FOR COMMON COMPLEX DISORDERS IS ATTRIBUTABLE TO ENVIRONMENTAL EXPOSURES AND POLLUTANTS. AN APPRECIATION OF HOW ENVIRONMENTAL POLLUTANTS ACT ON OUR CELLS TO PRODUCE DELETERIOUS HEALTH EFFECTS HAS LED TO ADVANCES IN OUR UNDERSTANDING OF THE MOLECULAR MECHANISMS UNDERLYING THE PATHOGENESIS OF CHRONIC DISEASES, INCLUDING CANCER AND CARDIOVASCULAR, NEURODEGENERATIVE AND RESPIRATORY DISEASES. HERE, WE DISCUSS EMERGING RESEARCH ON THE INTERPLAY OF ENVIRONMENTAL POLLUTANTS WITH THE HUMAN GENOME AND EPIGENOME. WE REVIEW EVIDENCE SHOWING THE ENVIRONMENTAL IMPACT ON GENE EXPRESSION THROUGH EPIGENETIC MODIFICATIONS, INCLUDING DNA METHYLATION, HISTONE MODIFICATION AND NON-CODING RNAS. WE ALSO HIGHLIGHT RECENT STUDIES THAT EVALUATE RECENTLY DISCOVERED MOLECULAR PROCESSES THROUGH WHICH THE ENVIRONMENT CAN EXERT ITS EFFECTS, INCLUDING EXTRACELLULAR VESICLES, THE EPITRANSCRIPTOME AND THE MITOCHONDRIAL GENOME. FINALLY, WE DISCUSS CURRENT CHALLENGES WHEN STUDYING THE EXPOSOME - THE CUMULATIVE MEASURE OF ENVIRONMENTAL INFLUENCES OVER THE LIFESPAN - AND ITS INTEGRATION INTO FUTURE ENVIRONMENTAL HEALTH RESEARCH. 2023 3 5071 31 PHYSICAL EXERCISE AND EPIGENETIC ADAPTATIONS OF THE CARDIOVASCULAR SYSTEM. DURING THE LAST DECADE, EPIGENETICS BECAME ONE OF THE FASTEST GROWING RESEARCH FIELDS IN NUMEROUS CLINICAL AND BASIC SCIENCE DISCIPLINES. EVIDENCE SUGGESTS THAT CHROMATIN MODIFICATIONS (E.G., HISTONE MODIFICATIONS AND DNA METHYLATION) AS WELL AS THE EXPRESSION OF MICRO-RNA MOLECULES PLAY A CRUCIAL ROLE IN THE PATHOGENESIS OF SEVERAL CARDIOVASCULAR DISEASES. ON THE ONE HAND, THEY ARE INVOLVED IN THE DEVELOPMENT OF GENERAL RISK FACTORS LIKE CHRONIC INFLAMMATION, BUT ON THE OTHER HAND, EPIGENETIC MODIFICATIONS ARE CONDUCIVE TO SMOOTH MUSCLE CELL, CARDIOMYOCYTE, AND ENDOTHELIAL PROGENITOR CELL PROLIFERATION/DIFFERENTIATION AS WELL AS TO EXTRACELLULAR MATRIX PROCESSING AND ENDOTHELIAL FUNCTION (E.G., ENDOTHELIAL NITRIC OXIDE SYNTHASE REGULATION). THEREFORE, EPIGENETIC MEDICAL DRUGS HAVE GAINED INCREASED ATTENTION AND PROVIDED THE FIRST PROMISING RESULTS IN THE CONTEXT OF CARDIOVASCULAR MALIGNANCIES. BESIDE OTHER LIFESTYLE FACTORS, PHYSICAL ACTIVITY AND SPORTS ESSENTIALLY CONTRIBUTE TO CARDIOVASCULAR HEALTH AND REGENERATION. IN THIS REVIEW WE FOCUS ON RECENT RESEARCH PROPOSING PHYSICAL ACTIVITY AS A POTENT EPIGENETIC REGULATOR THAT HAS THE POTENTIAL TO COUNTERACT PATHOPHYSIOLOGICAL ALTERATIONS IN ALMOST ALL THE AFOREMENTIONED CARDIOVASCULAR CELLS AND TISSUES. AS WITH EPIGENETIC MEDICAL DRUGS, MORE KNOWLEDGE ABOUT THE MOLECULAR MECHANISMS AND DOSE-RESPONSE RELATIONSHIPS OF EXERCISE IS NEEDED TO OPTIMIZE THE OUTCOME OF PREVENTIVE AND REHABILITATIVE EXERCISE PROGRAMS AND RECOMMENDATIONS. 2015 4 1415 29 DIETARY POLYPHENOLS AND THEIR RELATIONSHIP TO THE MODULATION OF NON-COMMUNICABLE CHRONIC DISEASES AND EPIGENETIC MECHANISMS: A MINI-REVIEW. CHRONIC NON-COMMUNICABLE DISEASES (NCDS) HAVE BEEN CONSIDERED A GLOBAL HEALTH PROBLEM, CHARACTERIZED AS DISEASES OF MULTIPLE FACTORS, WHICH ARE DEVELOPED THROUGHOUT LIFE, AND REGARDLESS OF GENETICS AS A RISK FACTOR OF IMPORTANT RELEVANCE, THE INCREASE IN MORTALITY ATTRIBUTED TO THE DISEASE TO ENVIRONMENTAL FACTORS AND THE LIFESTYLE ONE LEADS. ALTHOUGH THE REACTIVE SPECIES (ROS/RNS) ARE NECESSARY FOR SEVERAL PHYSIOLOGICAL PROCESSES, THEIR OVERPRODUCTION IS DIRECTLY RELATED TO THE PATHOGENESIS AND AGGRAVATION OF NCDS. IN CONTRAST, DIETARY POLYPHENOLS HAVE BEEN WIDELY ASSOCIATED WITH MINIMIZING OXIDATIVE STRESS AND INFLAMMATION. IN ADDITION TO THEIR ANTIOXIDANT POWER, POLYPHENOLS HAVE ALSO DRAWN ATTENTION FOR BEING ABLE TO MODULATE BOTH GENE EXPRESSION AND MODIFY EPIGENETIC ALTERATIONS, SUGGESTING AN ESSENTIAL INVOLVEMENT IN THE PREVENTION AND/OR DEVELOPMENT OF SOME PATHOLOGIES. THEREFORE, THIS REVIEW BRIEFLY EXPLAINED THE MECHANISMS IN THE DEVELOPMENT OF SOME NCDS, FOLLOWED BY A SUMMARY OF SOME EVIDENCE RELATED TO THE INTERACTION OF POLYPHENOLS IN OXIDATIVE STRESS, AS WELL AS THE MODULATION OF EPIGENETIC MECHANISMS INVOLVED IN THE MANAGEMENT OF NCDS. 2023 5 6738 21 WHAT'S YOUR CUP OF TEA? THE ROLE OF HERBAL COMPOUNDS IN THE MANAGEMENT OF MULTIPLE SCLEROSIS. MULTIPLE SCLEROSIS (MS) IS A CHRONIC, INFLAMMATORY, NEURODEGENERATIVE DISEASE THAT IS CHARACTERIZED BY A COMPLEX ETIOLOGY. EFFORTS TOWARDS THE MANAGEMENT OF MS HAVE LONG BEEN DIRECTED TOWARDS SYMPTOMATIC RELIEF, AS WELL AS THE USE OF IMMUNE-MODULATORY, DISEASE MODIFYING THERAPIES; HOWEVER, INCONSISTENT TREATMENT RESPONSES STILL PREVAIL, INCREASING THE RISK FOR DISEASE PROGRESSION. WHILE A GREAT DEAL OF RESEARCH ATTEMPTED TO UNRAVEL THE COMPLEXITY OF TREATMENT RESPONSES IN LIGHT OF EPIGENETIC VARIABILITY, PARALLEL EFFORTS IN THE DIRECTION OF ALTERNATIVE MEDICINE MAY BE AS PARAMOUNT. HERBAL COMPOUNDS HAVE LONG BEEN REGARDED AS SAFE AND VERSATILE OPTIONS FOR AIDING IN VARIOUS DISORDERS, INCLUDING NEURODEGENERATIVE CONDITIONS LIKE MS. NUMEROUS STUDIES HAVE TAKEN INTEREST IN A MYRIAD OF HERBAL PLANTS FOR THEIR POTENTIAL BENEFIT IN ALLEVIATING SOME OF THE MOST COMMON MS SYMPTOMS SUCH AS SPASTICITY AND FATIGUE, DELAYING THE PROGRESSION OF THE DISEASE, AS WELL AS INFLUENCING THE OVERALL QUALITY OF LIFE FOR MS PATIENTS. THIS REVIEW AIMS TO PROVIDE A COMPREHENSIVE OVERVIEW OF RECENT CLINICAL STUDIES EXAMINING THE EFFECTS OF VARIOUS HERBAL PLANTS ON DIFFERENT ASPECTS OF MS, IN AN ATTEMPT TO SHED LIGHT ON AN IMPORTANT TOOL FOR AIDING IN THE MANAGEMENT OF THIS COMPLEX AND MULTIFACTORIAL DISEASE. 2023 6 6287 24 THE POTENTIAL ROLE OF ENVIRONMENTAL FACTORS IN MODULATING MITOCHONDRIAL DNA EPIGENETIC MARKS. MANY STUDIES IMPLICATE MITOCHONDRIAL DYSFUNCTION IN THE DEVELOPMENT AND PROGRESSION OF NUMEROUS CHRONIC DISEASES. MITOCHONDRIA ARE RESPONSIBLE FOR MOST CELLULAR ENERGY PRODUCTION, AND UNLIKE OTHER CYTOPLASMIC ORGANELLES, MITOCHONDRIA CONTAIN THEIR OWN GENOME. MOST RESEARCH TO DATE, THROUGH INVESTIGATING MITOCHONDRIAL DNA COPY NUMBER, HAS FOCUSED ON LARGER STRUCTURAL CHANGES OR ALTERATIONS TO THE ENTIRE MITOCHONDRIAL GENOME AND THEIR ROLE IN HUMAN DISEASE. USING THESE METHODS, MITOCHONDRIAL DYSFUNCTION HAS BEEN LINKED TO CANCERS, CARDIOVASCULAR DISEASE, AND METABOLIC HEALTH. HOWEVER, LIKE THE NUCLEAR GENOME, THE MITOCHONDRIAL GENOME MAY EXPERIENCE EPIGENETIC ALTERATIONS, INCLUDING DNA METHYLATION THAT MAY PARTIALLY EXPLAIN SOME OF THE HEALTH EFFECTS OF VARIOUS EXPOSURES. RECENTLY, THERE HAS BEEN A MOVEMENT TO UNDERSTAND HUMAN HEALTH AND DISEASE WITHIN THE CONTEXT OF THE EXPOSOME, WHICH AIMS TO DESCRIBE AND QUANTIFY THE ENTIRETY OF ALL EXPOSURES PEOPLE ENCOUNTER THROUGHOUT THEIR LIVES. THESE INCLUDE, AMONG OTHERS, ENVIRONMENTAL POLLUTANTS, OCCUPATIONAL EXPOSURES, HEAVY METALS, AND LIFESTYLE AND BEHAVIORAL FACTORS. IN THIS CHAPTER, WE SUMMARIZE THE CURRENT RESEARCH ON MITOCHONDRIA AND HUMAN HEALTH, PROVIDE AN OVERVIEW OF THE CURRENT KNOWLEDGE ON MITOCHONDRIAL EPIGENETICS, AND DESCRIBE THE EXPERIMENTAL AND EPIDEMIOLOGIC STUDIES THAT HAVE INVESTIGATED PARTICULAR EXPOSURES AND THEIR RELATIONSHIPS WITH MITOCHONDRIAL EPIGENETIC MODIFICATIONS. WE CONCLUDE THE CHAPTER WITH SUGGESTIONS FOR FUTURE DIRECTIONS IN EPIDEMIOLOGIC AND EXPERIMENTAL RESEARCH THAT IS NEEDED TO ADVANCE THE GROWING FIELD OF MITOCHONDRIAL EPIGENETICS. 2023 7 4716 19 NON-GENETIC RATS MODELS FOR ATHEROSCLEROSIS RESEARCH: FROM PAST TO PRESENT. ATHEROSCLEROSIS IS AN INFLAMMATORY, PROGRESSIVE, AND CHRONIC ILLNESS THAT INVOLVES SEVERAL MOLECULAR AND EPIGENETIC FACTORS. DESPITE TREATMENT LIMITATIONS, CLINICAL AND THERAPEUTIC APPROACHES HAVE UNDENIABLY CHANGED RADICALLY IN RECENT DECADES THROUGH BETTER KNOWLEDGE OF THE PATHOPHYSIOLOGICAL BASIS OF THE DISEASE, WHICH HAS CONSIDERABLY IMPROVED PATIENTS' SURVIVAL AND QUALITY OF LIFE. SOME OF THESE ADVANCES ARE ATTRIBUTABLE TO BASIC BIOMEDICAL RESEARCH THAT PROVIDES INSIGHTS INTO A BETTER UNDERSTANDING AND IDENTIFICATION OF NEW MOLECULAR AND CELLULAR TARGETS FOR ATHEROSCLEROSIS TREATMENT. ALTHOUGH RODENT MODELS HAVE CONTRIBUTED SUBSTANTIALLY TO A BETTER UNDERSTANDING OF THE DEVELOPMENT OF ATHEROSCLEROSIS, THE ACCURACY OF THESE MODELS REMAINS CONTROVERSIAL. RESEARCH THAT UTILIZES GENETIC RODENT MODELS IS WELL ESTABLISHED, BUT THE USE OF SPECIFIC DIETS THAT ARE ASSOCIATED WITH OTHER RISK FACTORS (E.G., HYPERTENSION, HORMONE DEPRIVATION, AND PHARMACOLOGICAL TOOLS) IS STILL DEBATABLE. THE PRESENT REVIEW PROVIDES AN UPDATE ON NON-GENETIC RAT MODELS OF ATHEROSCLEROSIS AND AN OVERVIEW OF THE MAIN METHODOLOGIES THAT ARE CURRENTLY AVAILABLE. 2019 8 2459 18 EPIGENETIC THERAPIES FOR NON-ONCOLOGY INDICATIONS. CHRONIC AND DEGENERATIVE DISORDERS ARE A MAJOR, AND GROWING, HUMAN HEALTH BURDEN, AND CURRENT TREATMENTS ARE IN MANY CASES INADEQUATE OR VERY EXPENSIVE. EPIGENETIC THERAPIES ARE ATTRACTIVE OPTIONS FOR TREATING SUCH DISORDERS BECAUSE THEY MANIPULATE THE PROCESSES THAT MAINTAIN CELLS IN AN ABNORMAL TRANSCRIPTIONAL STATE. THE CHALLENGES LIE IN IDENTIFYING THE MOST APPROPRIATE DISEASES AND THE ENZYMES THAT SHOULD BE TARGETED. THIS REVIEW DESCRIBES THE DIFFERENT APPROACHES THAT CAN BE USED TO ADDRESS THIS PROBLEM, FOCUSING PARTICULARLY ON CNS DISORDERS (ESPECIALLY MENTAL RETARDATION, NEURODEGENERATIVE DISEASE, PSYCHIATRIC DISORDERS AND DRUG ADDICTION), DIABETES AND DIABETIC COMPLICATIONS, AND AUTOIMMUNITY AND INFLAMMATORY DISEASES. 2010 9 3421 17 HUMAN MATTERS IN ASTHMA: CONSIDERING THE MICROBIOME IN PULMONARY HEALTH. MICROBIAL COMMUNITIES FORM AN IMPORTANT SYMBIOTIC ECOSYSTEM WITHIN HUMANS AND HAVE DIRECT EFFECTS ON HEALTH AND WELL-BEING. NUMEROUS EXOGENOUS FACTORS INCLUDING AIRBORNE TRIGGERS, DIET, AND DRUGS IMPACT THESE ESTABLISHED, BUT FRAGILE COMMUNITIES ACROSS THE HUMAN LIFESPAN. CROSSTALK BETWEEN THE MUCOSAL MICROBIOTA AND THE IMMUNE SYSTEM AS WELL AS THE GUT-LUNG AXIS HAVE DIRECT CORRELATIONS TO IMMUNE BIAS THAT MAY PROMOTE CHRONIC DISEASES LIKE ASTHMA. ASTHMA INITIATION AND PATHOGENESIS ARE MULTIFACETED AND COMPLEX WITH INPUT FROM GENETIC, EPIGENETIC, AND ENVIRONMENTAL COMPONENTS. IN THIS REVIEW, WE SUMMARIZE AND DISCUSS THE ROLE OF THE AIRWAY MICROBIOME IN ASTHMA, AND HOW THE ENVIRONMENT, DIET AND THERAPEUTICS IMPACT THIS LOW BIOMASS COMMUNITY OF MICROORGANISMS. WE ALSO FOCUS THIS REVIEW ON THE PEDIATRIC AND BLACK POPULATIONS AS HIGH-RISK GROUPS REQUIRING SPECIAL ATTENTION, EMPHASIZING THAT THE WHOLE PATIENT MUST BE CONSIDERED DURING TREATMENT. ALTHOUGH NEW CULTURE-INDEPENDENT TECHNIQUES HAVE BEEN DEVELOPED AND ARE MORE ACCESSIBLE TO RESEARCHERS, THE EXACT CONTRIBUTION THE AIRWAY MICROBIOME MAKES IN ASTHMA PATHOGENESIS IS NOT WELL UNDERSTOOD. UNDERSTANDING HOW THE AIRWAY MICROBIOME, AS A LIVING ENTITY IN THE RESPIRATORY TRACT, PARTICIPATES IN LUNG IMMUNITY DURING THE DEVELOPMENT AND PROGRESSION OF ASTHMA MAY LEAD TO CRITICAL NEW TREATMENTS FOR ASTHMA, INCLUDING POPULATION-TARGETED INTERVENTIONS, OR EVEN MORE EFFECTIVE ADMINISTRATION OF CURRENTLY AVAILABLE THERAPEUTICS. 2022 10 554 30 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 11 2226 27 EPIGENETIC MODIFICATIONS INDUCED BY NUTRIENTS IN EARLY LIFE PHASES: GENDER DIFFERENCES IN METABOLIC ALTERATION IN ADULTHOOD. METABOLIC CHRONIC DISEASES, ALSO NAMED NONCOMMUNICABLE DISEASES (NCDS), ARE CONSIDERED MULTIFACTORIAL PATHOLOGIES, WHICH ARE DRAMATICALLY INCREASED DURING THE LAST DECADES. NONCOMMUNICABLE DISEASES SUCH AS CARDIOVASCULAR DISEASES, OBESITY, DIABETES MELLITUS, CANCERS, AND CHRONIC RESPIRATORY DISEASES MARKEDLY INCREASE MORBIDITY, MORTALITY, AND SOCIOECONOMIC COSTS. MOREOVER, NCDS INDUCE SEVERAL AND COMPLEX CLINICAL MANIFESTATIONS THAT LEAD TO A GRADUAL DETERIORATION OF HEALTH STATUS AND QUALITY OF LIFE OF AFFECTED INDIVIDUALS. MULTIPLE FACTORS ARE INVOLVED IN THE DEVELOPMENT AND PROGRESSION OF THESE DISEASES SUCH AS SEDENTARY BEHAVIOR, SMOKING, POLLUTION, AND UNHEALTHY DIET. INDEED, NUTRITION HAS A PIVOTAL ROLE IN MAINTAINING HEALTH, AND DIETARY IMBALANCES REPRESENT MAJOR DETERMINANTS FAVORING CHRONIC DISEASES THROUGH METABOLIC HOMEOSTASIS ALTERATIONS. IN PARTICULAR, IT APPEARS THAT SPECIFIC NUTRIENTS AND ADEQUATE NUTRITION ARE IMPORTANT IN ALL PERIODS OF LIFE, BUT THEY ARE ESSENTIAL DURING SPECIFIC TIMES IN EARLY LIFE SUCH AS PRENATAL AND POSTNATAL PHASES. INDEED, EPIDEMIOLOGIC AND EXPERIMENTAL STUDIES REPORT THE DELETERIOUS EFFECTS OF AN INCORRECT NUTRITION ON HEALTH STATUS SEVERAL DECADES LATER IN LIFE. DURING THE LAST DECADE, A GROWING INTEREST ON THE POSSIBLE ROLE OF EPIGENETIC MECHANISMS AS LINK BETWEEN NUTRITIONAL IMBALANCES AND NCDS DEVELOPMENT HAS BEEN OBSERVED. FINALLY, BECAUSE OF THE PIVOTAL ROLE OF THE HORMONES IN FAT, CARBOHYDRATE, AND PROTEIN METABOLISM REGULATION THROUGHOUT LIFE, IT IS EXPECTED THAT ANY HORMONAL MODIFICATION OF THESE PROCESSES CAN IMBALANCE METABOLISM AND FAT STORAGE. THEREFORE, A PARTICULAR INTEREST TO SEVERAL CHEMICALS ABLE TO ACT AS ENDOCRINE DISRUPTORS HAS BEEN RECENTLY DEVELOPED. IN THIS REVIEW, WE WILL PROVIDE AN OVERVIEW AND DISCUSS THE EPIGENETIC ROLE OF SOME SPECIFIC NUTRIENTS AND CHEMICALS IN THE MODULATION OF PHYSIOLOGICAL AND PATHOLOGICAL MECHANISMS. 2019 12 3689 22 INFLAMMATORY AUTO-IMMUNE DISEASES OF THE INTESTINE AND THEIR MANAGEMENT BY NATURAL BIOACTIVE COMPOUNDS. AUTOIMMUNE DISEASES ARE CAUSED BY THE OVERACTIVITY OF THE IMMUNE SYSTEM TOWARDS SELF-CONSTITUENTS. RISK FACTORS OF AUTOIMMUNE DISEASES ARE MULTIPLE AND INCLUDE GENETIC, EPIGENETIC, ENVIRONMENTAL, AND PSYCHOLOGICAL. AUTOIMMUNE CHRONIC INFLAMMATORY BOWEL DISEASES, INCLUDING CELIAC AND INFLAMMATORY DISEASES (CROHN'S DISEASE AND ULCERATIVE COLITIS), CONSTITUTE A SIGNIFICANT HEALTH PROBLEM WORLDWIDE. BESIDES THE COMPLEXITY OF THE SYMPTOMS OF THESE DISEASES, THEIR TREATMENTS HAVE ONLY BEEN PALLIATIVE. NUMEROUS INVESTIGATIONS SHOWED THAT NATURAL PHYTOCHEMICALS COULD BE PROMISING STRATEGIES TO FIGHT AGAINST THESE AUTOIMMUNE DISEASES. IN THIS RESPECT, PLANT-DERIVED NATURAL COMPOUNDS SUCH AS FLAVONOIDS, PHENOLIC ACIDS, AND TERPENOIDS EXHIBITED SIGNIFICANT EFFECTS AGAINST THREE AUTOIMMUNE DISEASES AFFECTING THE INTESTINE, PARTICULARLY BOWEL DISEASES. THIS REVIEW FOCUSES ON THE ROLE OF NATURAL COMPOUNDS OBTAINED FROM MEDICINAL PLANTS IN MODULATING INFLAMMATORY AUTO-IMMUNE DISEASES OF THE INTESTINE. IT COVERS THE MOST RECENT LITERATURE RELATED TO THE EFFECT OF THESE NATURAL COMPOUNDS IN THE TREATMENT AND PREVENTION OF AUTO-IMMUNE DISEASES OF THE INTESTINE. 2022 13 6021 15 THE BENEFICIAL AND DEBILITATING EFFECTS OF ENVIRONMENTAL AND MICROBIAL TOXINS, DRUGS, ORGANIC SOLVENTS AND HEAVY METALS ON THE ONSET AND PROGRESSION OF MULTIPLE SCLEROSIS. MULTIPLE SCLEROSIS (MS), A CHRONIC INFLAMMATORY DISEASE OF THE CENTRAL NERVOUS SYSTEM IS COMMON AMONGST YOUNG ADULTS, LEADING TO MAJOR PERSONAL AND SOCIOECONOMIC BURDENS. HOWEVER, IT IS STILL CONSIDERED COMPLEX AND CHALLENGING TO UNDERSTAND AND TREAT, IN SPITE OF THE EFFORTS MADE TO EXPLAIN ITS ETIOPATHOLOGY. DESPITE THE DISCOVERY OF MANY GENETIC AND ENVIRONMENTAL FACTORS THAT MIGHT BE RELATED TO ITS ETIOLOGY, NO CLEAR ANSWER WAS FOUND ABOUT THE CAUSES OF THE ILLNESS AND NEITHER ABOUT THE DETAILED MECHANISM OF THESE ENVIRONMENTAL TRIGGERS THAT MAKE INDIVIDUALS SUSCEPTIBLE TO MS. IN THIS REVIEW, WE WILL ATTEMPT TO EXPLORE THE MAJOR CONTRIBUTORS TO MS AUTOIMMUNITY INCLUDING GENETIC, EPIGENETIC AND ECOLOGICAL FACTORS WITH A PARTICULAR FOCUS ON TOXINS, CHEMICALS OR DRUGS THAT MAY TRIGGER, MODIFY OR PREVENT MS DISEASE. 2019 14 4676 23 NEW INSIGHTS TOWARD THE PATHOGENESIS OF ANKYLOSING SPONDYLITIS; GENETIC VARIATIONS AND EPIGENETIC MODIFICATIONS. ANKYLOSING SPONDYLITIS (AS) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE, CHARACTERIZED BY TYPICALLY AN AXIAL ARTHRITIS. AS IS THE PROTOTYPE OF A GROUP OF DISORDERS CALLED SPONDYLOARTHROPATHIES, WHICH IS BELIEVED TO HAVE COMMON CLINICAL MANIFESTATIONS AND GENETIC PREDISPOSITION. TO DATE, THE EXACT ETIOLOGY OF AS REMAINS UNCLEAR. OVER THE PAST FEW YEARS, HOWEVER, THE ROLE OF GENETIC SUSCEPTIBILITY AND EPIGENETIC MODIFICATIONS CAUSED THROUGH ENVIRONMENTAL FACTORS HAVE BEEN EXTENSIVELY SURVEYED WITH RESPECT TO THE PATHOGENESIS OF AS, RESULTED IN IMPORTANT ADVANCES. THIS REVIEW ARTICLE FOCUSES ON THE RECENT ADVANCES IN THE FIELD OF AS RESEARCH, INCLUDING HLA AND NON-HLA SUSCEPTIBILITY GENES IDENTIFIED IN GENOME-WIDE ASSOCIATION STUDIES (GWAS), AND ABERRANT EPIGENETIC MODIFICATIONS OF GENE LOCI ASSOCIATED WITH AS. HLA GENES MOST SIGNIFICANTLY LINKED WITH AS SUSCEPTIBILITY INCLUDE HLA-B27 AND ITS SUBTYPES. NUMEROUS NON-HLA GENES SUCH AS THOSE IN UBIQUITINATION, AMINOPEPTIDASES AND MHC CLASS I PRESENTATION MOLECULES LIKE ERAP-1 WERE ALSO REPORTED. MOREOVER, EPIGENETIC MODIFICATIONS OCCURRED IN AS HAS BEEN SUMMARIZED. TAKEN TOGETHER, THE FINDINGS PRESENTED IN THIS REVIEW ATTEMPT TO EXPLAIN THE CIRCUMSTANCE BY WHICH BOTH GENETIC VARIATIONS AND EPIGENETIC MODIFICATIONS ARE INVOLVED IN TRIGGERING AND DEVELOPMENT OF AS. NONETHELESS, SEVERAL UNANSWERED DARK SIDES CONTINUE TO CLOG OUR EXHAUSTIVE UNDERSTANDING OF AS. FUTURE RESEARCHES IN THE FIELD OF EPIGENETICS SHOULD BE CARRIED OUT TO EXTEND OUR VISION OF AS ETIOPATHOGENESIS. 2017 15 6913 20 [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 16 838 25 CHEMISTRY MEETS BIOLOGY IN COLITIS-ASSOCIATED CARCINOGENESIS. THE INTESTINE COMPRISES AN EXCEPTIONAL VENUE FOR A DYNAMIC AND COMPLEX INTERPLAY OF NUMEROUS CHEMICAL AND BIOLOGICAL PROCESSES. HERE, MULTIPLE CHEMICAL AND BIOLOGICAL SYSTEMS, INCLUDING THE INTESTINAL TISSUE ITSELF, ITS ASSOCIATED IMMUNE SYSTEM, THE GUT MICROBIOTA, XENOBIOTICS, AND METABOLITES MEET AND INTERACT TO FORM A SOPHISTICATED AND TIGHTLY REGULATED STATE OF TISSUE HOMOEOSTASIS. DISTURBANCE OF THIS HOMEOSTASIS CAN CAUSE INFLAMMATORY BOWEL DISEASE (IBD)-A CHRONIC DISEASE OF MULTIFACTORIAL ETIOLOGY THAT IS STRONGLY ASSOCIATED WITH INCREASED RISK FOR CANCER DEVELOPMENT. THIS REVIEW ADDRESSES RECENT DEVELOPMENTS IN RESEARCH INTO CHEMICAL AND BIOLOGICAL MECHANISMS UNDERLYING THE ETIOLOGY OF INFLAMMATION-INDUCED COLON CANCER. BEGINNING WITH A GENERAL OVERVIEW OF REACTIVE CHEMICAL SPECIES GENERATED DURING COLONIC INFLAMMATION, THE MECHANISTIC INTERPLAY BETWEEN CHEMICAL AND BIOLOGICAL MEDIATORS OF INFLAMMATION, THE ROLE OF GENETIC TOXICOLOGY, AND MICROBIAL PATHOGENESIS IN DISEASE DEVELOPMENT ARE DISCUSSED. WHEN POSSIBLE, WE SYSTEMATICALLY COMPARE EVIDENCE FROM STUDIES UTILIZING HUMAN IBD PATIENTS WITH EXPERIMENTAL INVESTIGATIONS IN MICE. THE COMPARISON REVEALS THAT MANY STRONG PATHOLOGICAL AND MECHANISTIC CORRELATES EXIST BETWEEN MOUSE MODELS OF COLITIS-ASSOCIATED CANCER, AND THE CLINICALLY RELEVANT SITUATION IN HUMANS. WE ALSO SUMMARIZE SEVERAL EMERGING ISSUES IN THE FIELD, SUCH AS THE CARCINOGENIC POTENTIAL OF NOVEL INFLAMMATION-RELATED DNA ADDUCTS AND GENOTOXIC MICROBIAL FACTORS, THE SYSTEMIC DIMENSION OF INFLAMMATION-INDUCED GENOTOXICITY, AND THE COMPLEX ROLE OF GENOME MAINTENANCE MECHANISMS DURING THESE PROCESSES. TAKEN TOGETHER, CURRENT EVIDENCE POINTS TO THE INDUCTION OF GENETIC AND EPIGENETIC ALTERATIONS BY CHEMICAL AND BIOLOGICAL INFLAMMATORY STIMULI ULTIMATELY LEADING TO CANCER FORMATION. 2013 17 4342 23 MINIREVIEW: EPIGENETICS OF OBESITY AND DIABETES IN HUMANS. UNDERSTANDING THE DETERMINANTS OF HUMAN HEALTH AND DISEASE IS OVERWHELMINGLY COMPLEX, PARTICULARLY FOR COMMON, LATE-ONSET, CHRONIC DISORDERS, SUCH AS OBESITY AND DIABETES. ELUCIDATING THE GENETIC AND ENVIRONMENTAL FACTORS THAT INFLUENCE SUSCEPTIBILITY TO DISRUPTIONS IN ENERGY HOMEOSTASIS AND METABOLIC REGULATION REMAIN A CHALLENGE, AND PROGRESS WILL ENTAIL THE INTEGRATION OF MULTIPLE ASSESSMENTS OF TEMPORALLY DYNAMIC ENVIRONMENTAL EXPOSURES IN THE CONTEXT OF EACH INDIVIDUAL'S GENOTYPE. TO MEET THIS CHALLENGE, RESEARCHERS ARE INCREASINGLY EXPLORING THE EPIGENOME, WHICH IS THE MALLEABLE INTERFACE OF GENE-ENVIRONMENT INTERACTIONS. EPIGENETIC VARIATION, WHETHER INNATE OR INDUCED, CONTRIBUTES TO VARIATION IN GENE EXPRESSION, THE RANGE OF POTENTIAL INDIVIDUAL RESPONSES TO INTERNAL AND EXTERNAL CUES, AND RISK FOR METABOLIC DISEASE. ULTIMATELY, ADVANCEMENT IN OUR UNDERSTANDING OF CHRONIC DISEASE SUSCEPTIBILITY IN HUMANS WILL DEPEND ON REFINEMENT OF EXPOSURE ASSESSMENT TOOLS AND SYSTEMS BIOLOGY APPROACHES TO INTERPRETATION. IN THIS REVIEW, WE PRESENT RECENT PROGRESS IN EPIGENETICS OF HUMAN OBESITY AND DIABETES, EXISTING CHALLENGES, AND THE POTENTIAL FOR NEW APPROACHES TO UNRAVEL THE COMPLEX BIOLOGY OF METABOLIC DYSREGULATION. 2012 18 6204 25 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 19 6630 18 UNDERSTANDING THE INTERPLAY BETWEEN HEALTH DISPARITIES AND EPIGENOMICS. SOCIAL EPIGENOMICS HAS EMERGED AS AN INTEGRATIVE FIELD OF RESEARCH FOCUSED ON IDENTIFICATION OF SOCIO-ENVIRONMENTAL FACTORS, THEIR INFLUENCE ON HUMAN BIOLOGY THROUGH EPIGENOMIC MODIFICATIONS, AND HOW THEY CONTRIBUTE TO CURRENT HEALTH DISPARITIES. SEVERAL HEALTH DISPARITIES STUDIES HAVE BEEN PUBLISHED USING GENETIC-BASED APPROACHES; HOWEVER, INCREASING ACCESSIBILITY AND AFFORDABILITY OF MOLECULAR TECHNOLOGIES HAVE ALLOWED FOR AN IN-DEPTH INVESTIGATION OF THE INFLUENCE OF EXTERNAL FACTORS ON EPIGENETIC MODIFICATIONS (E.G., DNA METHYLATION, MICRO-RNA EXPRESSION). CURRENTLY, RESEARCH IS FOCUSED ON EPIGENETIC CHANGES IN RESPONSE TO ENVIRONMENT, AS WELL AS TARGETED EPIGENETIC THERAPIES AND ENVIRONMENTAL/SOCIAL STRATEGIES FOR POTENTIALLY MINIMIZING CERTAIN HEALTH DISPARITIES. HERE, WE WILL REVIEW RECENT FINDINGS IN THIS FIELD PERTAINING TO CONDITIONS AND DISEASES OVER LIFE SPAN ENCOMPASSING PRENATAL TO ADULT STAGES. 2020 20 2100 21 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