1 4266 122 MICRO-RNAS: CROSSROADS BETWEEN THE EXPOSURE TO ENVIRONMENTAL PARTICULATE POLLUTION AND THE OBSTRUCTIVE PULMONARY DISEASE. ENVIRONMENTAL POLLUTION HAS REACHED A GLOBAL ECHO AND REPRESENTS A SERIOUS PROBLEM FOR HUMAN HEALTH. AIR POLLUTION ENCOMPASSES A SET OF HAZARDOUS SUBSTANCES, SUCH AS PARTICULATE MATTER AND HEAVY METALS (E.G., CADMIUM, LEAD, AND ARSENIC), AND HAS A STRONG IMPACT ON THE ENVIRONMENT BY AFFECTING GROUNDWATER, SOIL, AND AIR. AN ADAPTIVE RESPONSE TO ENVIRONMENTAL CUES IS ESSENTIAL FOR HUMAN SURVIVAL, WHICH IS ASSOCIATED WITH THE INDUCTION OF ADAPTIVE PHENOTYPES. THE EPIGENETIC MECHANISMS REGULATING THE EXPRESSION PATTERNS OF SEVERAL GENES ARE PROMISING CANDIDATES TO PROVIDE MECHANISTIC AND PROGNOSTIC INSIGHTS INTO THIS. MICRO-RNAS (MIRNAS) FULFIL THESE FEATURES GIVEN THEIR ABILITY TO RESPOND TO ENVIRONMENTAL FACTORS AND THEIR CRITICAL ROLE IN DETERMINING PHENOTYPES. THESE MOLECULES ARE PRESENT IN EXTRACELLULAR FLUIDS, AND THEIR EXPRESSION PATTERNS ARE ORGAN-, TISSUE-, OR CELL-SPECIFIC. MOREOVER, THE EXPERIMENTAL SETTINGS FOR THEIR QUANTITATIVE AND QUALITATIVE ANALYSIS ARE ROBUST, STANDARDIZED, AND INEXPENSIVE. IN THIS REVIEW, WE PROVIDE AN UPDATE ON THE ROLE OF MIRNAS AS SUITABLE TOOLS FOR UNDERSTANDING THE MECHANISMS BEHIND THE PHYSIOPATHOLOGICAL RESPONSE TO TOXICANTS AND THE PROGNOSTIC VALUE OF THEIR EXPRESSION PATTERN ASSOCIABLE WITH SPECIFIC EXPOSURES. WE LOOK AT THE MECHANISTIC EVIDENCE ASSOCIABLE TO THE ROLE OF MIRNAS IN THE PROCESSES LEADING TO ENVIRONMENTAL-INDUCED PULMONARY DISEASE (I.E., CHRONIC OBSTRUCTIVE PULMONARY DISEASE). 2020 2 396 37 AN UPDATE ON EPIGENETICS AND CHILDHOOD RESPIRATORY DISEASES. EPIGENETIC MECHANISMS, DEFINED AS CHANGES IN PHENOTYPE OR GENE EXPRESSION CAUSED BY MECHANISMS OTHER THAN CHANGES IN THE UNDERLYING DNA SEQUENCE, HAVE BEEN PROPOSED TO CONSTITUTE A LINK BETWEEN GENETIC AND ENVIRONMENTAL FACTORS THAT AFFECT COMPLEX DISEASES. RECENT STUDIES SHOW THAT DNA METHYLATION, ONE OF THE KEY EPIGENETIC MECHANISMS, IS ALTERED IN CHILDREN EXPOSED TO AIR POLLUTANTS AND ENVIRONMENTAL TOBACCO SMOKE EARLY IN LIFE. SEVERAL CANDIDATE GENE STUDIES ON EPIGENETICS HAVE BEEN PUBLISHED TO DATE, BUT IT IS ONLY RECENTLY THAT GLOBAL METHYLATION ANALYSES HAVE BEEN PERFORMED FOR RESPIRATORY DISORDERS SUCH AS ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. HOWEVER, LARGE-SCALE STUDIES WITH ADEQUATE POWER ARE YET TO BE PRESENTED IN CHILDREN, AND IMPLICATIONS FOR CLINICAL USE REMAIN TO BE EVALUATED. IN THIS REVIEW, WE SUMMARIZE THE RECENT ADVANCES IN EPIGENETICS AND RESPIRATORY DISORDERS IN CHILDREN, WITH A MAIN FOCUS ON METHODOLOGICAL CHALLENGES AND ANALYSES RELATED TO PHENOTYPE AND EXPOSURE USING GLOBAL METHYLATION APPROACHES. 2014 3 2282 40 EPIGENETIC REGULATION IN EXPOSOME-INDUCED TUMORIGENESIS: EMERGING ROLES OF NCRNAS. ENVIRONMENTAL FACTORS, INCLUDING POLLUTANTS AND LIFESTYLE, CONSTITUTE A SIGNIFICANT ROLE IN SEVERE, CHRONIC PATHOLOGIES WITH AN ESSENTIAL SOCIETAL, ECONOMIC BURDEN. THE MEASUREMENT OF ALL ENVIRONMENTAL EXPOSURES AND ASSESSING THEIR CORRELATION WITH EFFECTS ON INDIVIDUAL HEALTH IS DEFINED AS THE EXPOSOME, WHICH INTERACTS WITH OUR UNIQUE CHARACTERISTICS SUCH AS GENETICS, PHYSIOLOGY, AND EPIGENETICS. EPIGENETICS INVESTIGATES MODIFICATIONS IN THE EXPRESSION OF GENES THAT DO NOT DEPEND ON THE UNDERLYING DNA SEQUENCE. SOME STUDIES HAVE CONFIRMED THAT ENVIRONMENTAL FACTORS MAY PROMOTE DISEASE IN INDIVIDUALS OR SUBSEQUENT PROGENY THROUGH EPIGENETIC ALTERATIONS. VARIATIONS IN THE EPIGENETIC MACHINERY CAUSE A SPECTRUM OF DIFFERENT DISORDERS SINCE THESE MECHANISMS ARE MORE SENSITIVE TO THE ENVIRONMENT THAN THE GENOME, DUE TO THE INHERENT REVERSIBLE NATURE OF THE EPIGENETIC LANDSCAPE. SEVERAL EPIGENETIC MECHANISMS, INCLUDING MODIFICATIONS IN DNA (E.G., METHYLATION), HISTONES, AND NONCODING RNAS CAN CHANGE GENOME EXPRESSION UNDER THE EXOGENOUS INFLUENCE. NOTABLY, THE ROLE OF LONG NONCODING RNAS IN EPIGENETIC PROCESSES HAS NOT BEEN WELL EXPLORED IN THE CONTEXT OF EXPOSOME-INDUCED TUMORIGENESIS. IN THE PRESENT REVIEW, OUR SCOPE IS TO PROVIDE RELEVANT EVIDENCE INDICATING THAT EPIGENETIC ALTERATIONS MEDIATE THOSE DETRIMENTAL EFFECTS CAUSED BY EXPOSURE TO ENVIRONMENTAL TOXICANTS, FOCUSING MAINLY ON A MULTI-STEP REGULATION BY DIVERSE NONCODING RNAS SUBTYPES. 2022 4 4460 32 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 5 3404 34 HOW EPIGENETICS IMPACTS ON HUMAN DISEASES. EPIGENETICS IS A RAPIDLY GROWING FIELD OF BIOLOGY THAT STUDIES THE CHANGES IN GENE EXPRESSION THAT ARE NOT DUE TO ALTERATIONS IN THE DNA SEQUENCE BUT RATHER THE CHEMICAL MODIFICATIONS OF DNA AND ITS ASSOCIATED PROTEINS. EPIGENETIC MECHANISMS CAN PROFOUNDLY INFLUENCE GENE EXPRESSION, CELL DIFFERENTIATION, TISSUE DEVELOPMENT, AND DISEASE SUSCEPTIBILITY. UNDERSTANDING EPIGENETIC CHANGES IS ESSENTIAL TO ELUCIDATE THE MECHANISMS UNDERLYING THE INCREASINGLY RECOGNIZED ROLE OF ENVIRONMENTAL AND LIFESTYLE FACTORS IN HEALTH AND DISEASE AND THE INTERGENERATIONAL TRANSMISSION OF PHENOTYPES. RECENT STUDIES SUGGEST EPIGENETICS MAY BE CRITICAL IN VARIOUS DISEASES, FROM CARDIOVASCULAR DISEASE AND CANCER TO NEURODEVELOPMENTAL AND NEURODEGENERATIVE DISORDERS. EPIGENETIC MODIFICATIONS ARE POTENTIALLY REVERSIBLE AND COULD PROVIDE NEW THERAPEUTIC AVENUES FOR TREATING THESE DISEASES USING EPIGENETIC MODULATORS. MOREOVER, EPIGENETICS PROVIDE INSIGHT INTO DISEASE PATHOGENESIS AND BIOMARKERS FOR DISEASE DIAGNOSIS AND RISK STRATIFICATION. NEVERTHELESS, EPIGENETIC INTERVENTIONS HAVE THE POTENTIAL FOR UNINTENDED CONSEQUENCES AND MAY POTENTIALLY LEAD TO INCREASED RISKS OF UNEXPECTED OUTCOMES, SUCH AS ADVERSE DRUG REACTIONS, DEVELOPMENTAL ABNORMALITIES, AND CANCER. THEREFORE, RIGOROUS STUDIES ARE ESSENTIAL TO MINIMIZE THE RISKS ASSOCIATED WITH EPIGENETIC THERAPIES AND TO DEVELOP SAFE AND EFFECTIVE INTERVENTIONS FOR IMPROVING HUMAN HEALTH. THIS ARTICLE PROVIDES A SYNTHETIC AND HISTORICAL VIEW OF THE ORIGIN OF EPIGENETICS AND SOME OF THE MOST RELEVANT ACHIEVEMENTS. 2023 6 3100 34 GENOMIC IMPACT OF CIGARETTE SMOKE, WITH APPLICATION TO THREE SMOKING-RELATED DISEASES. THERE IS CONSIDERABLE EVIDENCE THAT INHALED TOXICANTS SUCH AS CIGARETTE SMOKE CAN CAUSE BOTH IRREVERSIBLE CHANGES TO THE GENETIC MATERIAL (DNA MUTATIONS) AND PUTATIVELY REVERSIBLE CHANGES TO THE EPIGENETIC LANDSCAPE (CHANGES IN THE DNA METHYLATION AND CHROMATIN MODIFICATION STATE). THE DISEASES THAT ARE BELIEVED TO INVOLVE GENETIC AND EPIGENETIC PERTURBATIONS INCLUDE LUNG CANCER, CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), AND CARDIOVASCULAR DISEASE (CVD), ALL OF WHICH ARE STRONGLY LINKED EPIDEMIOLOGICALLY TO CIGARETTE SMOKING. IN THIS REVIEW, WE HIGHLIGHT THE SIGNIFICANCE OF GENOMICS AND EPIGENOMICS IN THESE MAJOR SMOKING-RELATED DISEASES. WE ALSO SUMMARIZE THE IN VITRO AND IN VIVO FINDINGS ON THE SPECIFIC PERTURBATIONS THAT SMOKE AND ITS CONSTITUENT COMPOUNDS CAN INFLICT UPON THE GENOME, PARTICULARLY ON THE PULMONARY SYSTEM. FINALLY, WE REVIEW STATE-OF-THE-ART GENOMICS AND NEW TECHNIQUES SUCH AS HIGH-THROUGHPUT SEQUENCING AND GENOME-WIDE CHROMATIN ASSAYS, RAPIDLY EVOLVING TECHNIQUES WHICH HAVE ALLOWED EPIGENETIC CHANGES TO BE CHARACTERIZED AT THE GENOME LEVEL. THESE TECHNIQUES HAVE THE POTENTIAL TO SIGNIFICANTLY IMPROVE OUR UNDERSTANDING OF THE SPECIFIC MECHANISMS BY WHICH EXPOSURE TO ENVIRONMENTAL CHEMICALS CAUSES DISEASE. SUCH MECHANISTIC KNOWLEDGE PROVIDES A VARIETY OF OPPORTUNITIES FOR ENHANCED PRODUCT SAFETY ASSESSMENT AND THE DISCOVERY OF NOVEL THERAPEUTIC INTERVENTIONS. 2012 7 6183 36 THE IMPACT OF ENVIRONMENTAL FACTORS IN INFLUENCING EPIGENETICS RELATED TO OXIDATIVE STATES IN THE CARDIOVASCULAR SYSTEM. OXIDATIVE STATES EXERT A SIGNIFICANT INFLUENCE ON A WIDE RANGE OF BIOLOGICAL AND MOLECULAR PROCESSES AND FUNCTIONS. WHEN THEIR BALANCE IS SHIFTED TOWARDS ENHANCED AMOUNTS OF FREE RADICALS, PATHOLOGICAL PHENOMENA CAN OCCUR, AS THE GENERATION OF REACTIVE OXYGEN SPECIES (ROS) IN TISSUE MICROENVIRONMENT OR IN THE SYSTEMIC CIRCULATION CAN BE DETRIMENTAL. EPIDEMIC CHRONIC DISEASES OF WESTERN SOCIETIES, SUCH AS CARDIOVASCULAR DISEASE, OBESITY, AND DIABETES CORRELATE WITH THE IMBALANCE OF REDOX HOMEOSTASIS. CURRENT ADVANCES IN OUR UNDERSTANDING OF EPIGENETICS HAVE REVEALED A PARALLEL SCENARIO SHOWING THE INFLUENCE OF OXIDATIVE STRESS AS A MAJOR REGULATOR OF EPIGENETIC GENE REGULATION VIA MODIFICATION OF DNA METHYLATION, HISTONES, AND MICRORNAS. THIS HAS PROVIDED BOTH THE BIOLOGICAL LINK AND A POTENTIAL MOLECULAR EXPLANATION BETWEEN OXIDATIVE STRESS AND CARDIOVASCULAR/METABOLIC PHENOMENA. ACCORDINGLY, IN THIS REVIEW, WE WILL PROVIDE CURRENT INSIGHTS ON THE PHYSIOLOGICAL AND PATHOLOGICAL IMPACT OF CHANGES IN OXIDATIVE STATES ON CARDIOVASCULAR DISORDERS, BY SPECIFICALLY FOCUSING ON THE INFLUENCE OF EPIGENETIC REGULATION. A SPECIAL EMPHASIS WILL HIGHLIGHT THE EFFECT ON EPIGENETIC REGULATION OF HUMAN'S CURRENT LIFE HABITS, EXTERNAL AND ENVIRONMENTAL FACTORS, INCLUDING FOOD INTAKE, TOBACCO, AIR POLLUTION, AND ANTIOXIDANT-BASED APPROACHES. ADDITIONALLY, THE STRATEGY TO QUANTIFY OXIDATIVE STATES IN HUMANS IN ORDER TO DETERMINE WHICH BIOLOGICAL MARKER COULD BEST MATCH A SUBJECT'S PROFILE WILL BE DISCUSSED. 2017 8 738 30 CANCER SUSCEPTIBILITY: EPIGENETIC MANIFESTATION OF ENVIRONMENTAL EXPOSURES. CANCER IS A DISEASE THAT RESULTS FROM BOTH GENETIC AND EPIGENETIC CHANGES. DISCORDANT PHENOTYPES AND VARYING INCIDENCES OF COMPLEX DISEASES SUCH AS CANCER IN MONOZYGOTIC TWINS AS WELL AS GENETICALLY IDENTICAL LABORATORY ANIMALS HAVE LONG BEEN ATTRIBUTED TO DIFFERENCES IN ENVIRONMENTAL EXPOSURES. ACCUMULATING EVIDENCE INDICATES, HOWEVER, THAT DISPARITIES IN GENE EXPRESSION RESULTING FROM VARIABLE MODIFICATIONS IN DNA METHYLATION AND CHROMATIN STRUCTURE IN RESPONSE TO THE ENVIRONMENT ALSO PLAY A ROLE IN DIFFERENTIAL SUSCEPTIBILITY TO DISEASE. DESPITE A GROWING CONSENSUS ON THE IMPORTANCE OF EPIGENETICS IN THE ETIOLOGY OF CHRONIC HUMAN DISEASES, THE GENES MOST PRONE TO EPIGENETIC DYSREGULATION ARE INCOMPLETELY DEFINED. MOREOVER, NEITHER THE ENVIRONMENTAL AGENTS MOST STRONGLY AFFECTING THE EPIGENOME NOR THE CRITICAL WINDOWS OF VULNERABILITY TO ENVIRONMENTALLY INDUCED EPIGENETIC ALTERATIONS ARE ADEQUATELY CHARACTERIZED. THESE MAJOR DEFICITS IN KNOWLEDGE MARKEDLY IMPAIR OUR ABILITY TO UNDERSTAND FULLY THE ETIOLOGY OF CANCER AND THE IMPORTANCE OF THE EPIGENOME IN DIAGNOSING AND PREVENTING THIS DEVASTATING DISEASE. 2007 9 3706 35 INFLUENCE OF GENETICS ON DISEASE SUSCEPTIBILITY AND PROGRESSION. FOR MANY CHRONIC DISEASES, THE INFLUENCE OF GENETICS IS COMPLEX AND PHENOTYPES DO NOT CONFORM TO SIMPLE MENDELIAN PATTERNS OF INHERITANCE. DISCUSSED HERE ARE TWO TYPES OF GENETIC INFLUENCES ON HEALTHY AGING. THE FIRST INVOLVES VARIATION IN THE GENE SEQUENCE ITSELF AND HOW THIS MAY INFLUENCE DISEASE SUSCEPTIBILITY, PROGRESSION, AND SEVERITY, INTERACTING WITH OTHER RECOGNIZED RISK FACTORS. THE SECOND INVOLVES EPIGENETIC REGULATORY MECHANISMS THAT MAY POTENTIALLY PROVIDE INSIGHT INTO HOW ENVIRONMENTAL INFLUENCES AFFECT THE EXPRESSED GENOME, THUS IMPROVING OUR UNDERSTANDING OF THE GENETIC MECHANISMS UNDERLYING MULTIFACTORIAL DISEASES. THE INTERLEUKIN-1 FAMILY OF CYTOKINES CAN BE USED TO ILLUSTRATE HOW GENETIC SEQUENCE VARIATION MAY AFFECT SUCH DISEASES. THIS CYTOKINE FAMILY PLAYS A KEY ROLE IN MEDIATING INFLAMMATION, WHICH IS NOW UNDERSTOOD TO BE A CENTRAL COMPONENT OF A GROWING NUMBER OF CHRONIC DISEASES. RECENT WORK HAS REVEALED MANY SEQUENCE VARIATIONS IN THE REGULATORY DNA OF GENES ENCODING IMPORTANT MEMBERS OF THE INTERLEUKIN-1 FAMILY, AND THESE VARIATIONS ARE ASSOCIATED WITH DIFFERENTIAL EFFECTS ON THE INFLAMMATORY RESPONSE. THE INTERACTIONS OF ENVIRONMENTAL FACTORS WITH BOTH DNA SEQUENCE VARIATIONS AND EPIGENETIC MODIFICATIONS ARE LIKELY TO DETERMINE THE PHENOTYPES OF MULTIFACTORIAL DISEASES OF AGING AS WELL AS THE PHENOTYPE OF HEALTHY AGING. 2007 10 6287 35 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 11 3106 37 GENOMICS AND THE RESPIRATORY EFFECTS OF AIR POLLUTION EXPOSURE. ADVERSE HEALTH EFFECTS FROM AIR POLLUTANTS REMAIN IMPORTANT, DESPITE IMPROVEMENT IN AIR QUALITY IN THE PAST FEW DECADES. THE EXACT MECHANISMS OF LUNG INJURY FROM EXPOSURE TO AIR POLLUTANTS ARE NOT YET FULLY UNDERSTOOD. STUDYING THE GENOME (E.G. SINGLE-NUCLEOTIDE POLYMORPHISMS (SNP) ), EPIGENOME (E.G. METHYLATION OF GENES), TRANSCRIPTOME (MRNA EXPRESSION) AND MICRORNAOME (MICRORNA EXPRESSION) HAS THE POTENTIAL TO IMPROVE OUR UNDERSTANDING OF THE ADVERSE EFFECTS OF AIR POLLUTANTS. GENOME-WIDE ASSOCIATION STUDIES OF SNP HAVE DETECTED SNP ASSOCIATED WITH RESPIRATORY PHENOTYPES; HOWEVER, TO DATE, ONLY CANDIDATE GENE STUDIES OF AIR POLLUTION EXPOSURE HAVE BEEN PERFORMED. CHANGES IN EPIGENETIC PROCESSES, SUCH DNA METHYLATION THAT LEADS TO GENE SILENCING WITHOUT ALTERING THE DNA SEQUENCE, OCCUR WITH AIR POLLUTANT EXPOSURE, ESPECIALLY GLOBAL AND GENE-SPECIFIC METHYLATION CHANGES. RESPIRATORY CELL LINE AND ANIMAL MODELS DEMONSTRATE DISTINCT GENE EXPRESSION SIGNATURES IN THE TRANSCRIPTOME, ARISING FROM EXPOSURE TO PARTICULATE MATTER OR OZONE. PARTICULATE MATTER AND OTHER ENVIRONMENTAL TOXINS ALTER EXPRESSION OF MICRORNA, WHICH ARE SHORT NON-CODING RNA THAT REGULATE GENE EXPRESSION. WHILE IT IS CLEARLY IMPORTANT TO CONTAIN RISING LEVELS OF AIR POLLUTION, STRATEGIES ALSO NEED TO BE DEVELOPED TO MINIMIZE THE DAMAGING EFFECTS OF AIR POLLUTANT EXPOSURE ON THE LUNG, ESPECIALLY FOR PATIENTS WITH CHRONIC LUNG DISEASE AND FOR PEOPLE AT RISK OF FUTURE LUNG DISEASE. CAREFUL STUDY OF GENOMIC RESPONSES WILL IMPROVE OUR UNDERSTANDING OF MECHANISMS OF LUNG INJURY FROM AIR POLLUTION AND ENABLE FUTURE CLINICAL TESTING OF INTERVENTIONS AGAINST THE TOXIC EFFECTS OF AIR POLLUTANTS. 2012 12 6809 28 [EPIGENETICS IN INFLAMMATORY SYSTEMIC DISEASES]. IN ADDITION TO ANALYSIS OF THE GENETIC CODE, IN RECENT YEARS MORE AND MORE STUDIES HAVE CONCENTRATED ON CHANGES IN THE EPIGENETIC CODE. EPIGENETIC MECHANISMS DETERMINE WHICH GENES IN A CELL ARE TRANSCRIBED AND THUS FORM THE PHENOTYPE OF A CELL. THE EPIGENETIC CODE CAN BE CHANGED BY ENVIRONMENTAL INFLUENCES, WHICH ALLOWS CELLS TO ADAPT TO LONGSTANDING CHANGES IN THE ENVIRONMENT. THEREFORE, IT IS FEASIBLE TO ASSUME THAT EPIGENETIC CHANGES ARE THE MOLECULAR BASIS FOR LONG-TERM EFFECTS OF THE ENVIRONMENT ON DISEASE DEVELOPMENT. IN PARTICULAR IN TUMORS AND CHRONIC INFLAMMATORY DISEASES EPIGENETIC CHANGES WERE FOUND TO CORRELATE WITH DISEASE SEVERITY AND PROGRESSION. KNOWLEDGE ABOUT THESE EPIGENETIC CHANGES MIGHT HELP THAT EPIGENETIC MODIFICATIONS CAN BE USED IN THE FUTURE AS BIOMARKERS, PROGNOSTIC FACTORS AND THERAPEUTIC TARGETS. 2014 13 4273 34 MICROBIOTA AND EPIGENETICS: HEALTH IMPACT. EPIGENETIC CHANGES ASSOCIATED WITH DISEASE DEVELOPMENT AND PROGRESSIONS ARE OF INCREASING IMPORTANCE BECAUSE OF THEIR POTENTIAL DIAGNOSTIC AND THERAPEUTIC APPLICATIONS. SEVERAL EPIGENETIC CHANGES ASSOCIATED WITH CHRONIC METABOLIC DISORDERS HAVE BEEN STUDIED IN VARIOUS DISEASES. EPIGENETIC CHANGES ARE MOSTLY MODULATED BY ENVIRONMENTAL FACTORS, INCLUDING THE HUMAN MICROBIOTA LIVING IN DIFFERENT PARTS OF OUR BODIES. THE MICROBIAL STRUCTURAL COMPONENTS AND THE MICROBIALLY DERIVED METABOLITES DIRECTLY INTERACT WITH HOST CELLS, THEREBY MAINTAINING HOMEOSTASIS. MICROBIOME DYSBIOSIS, ON THE OTHER HAND, IS KNOWN TO PRODUCE ELEVATED LEVELS OF DISEASE-LINKED METABOLITES, WHICH MAY DIRECTLY AFFECT A HOST METABOLIC PATHWAY OR INDUCE EPIGENETIC CHANGES THAT CAN LEAD TO DISEASE DEVELOPMENT. DESPITE THEIR IMPORTANT ROLE IN HOST PHYSIOLOGY AND SIGNAL TRANSDUCTION, THERE HAS BEEN LITTLE RESEARCH INTO THE MECHANICS AND PATHWAYS ASSOCIATED WITH EPIGENETIC MODIFICATIONS. THIS CHAPTER FOCUSES ON THE RELATIONSHIP BETWEEN MICROBES AND THEIR EPIGENETIC EFFECTS IN DISEASED PATHOLOGY, AS WELL AS ON THE REGULATION AND METABOLISM OF THE DIETARY OPTIONS AVAILABLE TO THE MICROBES. FURTHERMORE, THIS CHAPTER ALSO PROVIDES A PROSPECTIVE LINK BETWEEN THESE TWO IMPORTANT PHENOMENA, TERMED "MICROBIOME AND EPIGENETICS." 2023 14 2333 32 EPIGENETIC REGULATION OF INFLAMMATION: THE METABOLOMICS CONNECTION. EPIGENETIC FACTORS ARE CONSIDERED THE REGULATOR OF COMPLEX MACHINERY BEHIND INFLAMMATORY DISORDERS AND SIGNIFICANTLY CONTRIBUTED TO THE EXPRESSION OF INFLAMMATION-ASSOCIATED GENES. EPIGENETIC MODIFICATIONS MODULATE VARIATION IN THE EXPRESSION PATTERN OF TARGET GENES WITHOUT AFFECTING THE DNA SEQUENCE. THE CURRENT KNOWLEDGE OF EPIGENETIC RESEARCH FOCUSED ON THEIR ROLE IN THE PATHOGENESIS OF VARIOUS INFLAMMATORY DISEASES THAT CAUSES MORBIDITY AND MORTALITY WORLDWIDE. INFLAMMATORY DISEASES ARE CATEGORIZED AS ACUTE AND CHRONIC BASED ON THE DISEASE SEVERITY AND ARE REGULATED BY THE EXPRESSION PATTERN OF VARIOUS GENES. HENCE, UNDERSTANDING THE ROLE OF EPIGENETIC MODIFICATIONS DURING INFLAMMATION PROGRESSION WILL CONTRIBUTE TO THE DISEASE OUTCOMES AND THERAPEUTIC APPROACHES. THIS REVIEW ALSO FOCUSES ON THE METABOLOMICS APPROACH ASSOCIATED WITH THE STUDY OF INFLAMMATORY DISORDERS. INFLAMMATORY RESPONSES AND METABOLIC REGULATION ARE HIGHLY INTEGRATED AND VARIOUS ADVANCED TECHNIQUES ARE ADOPTED TO STUDY THE METABOLIC SIGNATURE MOLECULES. HERE WE DISCUSS SEVERAL METABOLOMICS APPROACHES USED TO LINK INFLAMMATORY DISORDERS AND EPIGENETIC CHANGES. WE PROPOSED THAT DECIPHERING THE MECHANISM BEHIND THE INFLAMMATION-METABOLISM LOOP MAY HAVE IMMENSE IMPORTANCE IN BIOMARKERS RESEARCH AND MAY ACT AS A PRINCIPAL COMPONENT IN DRUG DISCOVERY AS WELL AS THERAPEUTIC APPLICATIONS. 2022 15 6199 35 THE IMPORTANCE OF EPIGENETICS IN THE DEVELOPMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. IT IS GENERALLY ACCEPTED THAT GENETIC PREDISPOSITION PLAYS A ROLE IN COPD DEVELOPMENT IN SUSCEPTIBLE INDIVIDUALS. THEREFORE, MANY CANDIDATE GENES THAT COULD BE LINKED TO THE DEVELOPMENT OF DISEASE HAVE BEEN EXAMINED IN COPD. HOWEVER, INCONSISTENT RESULTS IN DIFFERENT STUDY POPULATIONS OFTEN LIMIT THIS APPROACH, SUGGESTING THAT NOT ONLY GENETICS, BUT ALSO OTHER FACTORS, MAY BE CONTRIBUTED TO THE SUSCEPTIBILITY TO COPD. EPIGENETIC MECHANISMS CAN AFFECT THE TRANSCRIPTIONAL ACTIVITY OF SPECIFIC GENES, AT DIFFERENT POINTS IN TIME, AND IN DIFFERENT ORGANS. MOREOVER, THESE MECHANISMS CAN HAVE AN EFFECT ON PEOPLE'S HEALTH. RECENTLY, THERE IS EMERGING EVIDENCE SUPPORTING A ROLE OF EPIGENETICS FOR THE REGULATION OF INFLAMMATORY GENES IN DISEASES SUCH AS ASTHMA AND COPD. MOREOVER, RECENT STUDIES SUGGEST THAT THE CURRENTLY USED TREATMENTS INCLUDING CORTICOSTEROIDS MAY WORK THROUGH EPIGENETIC MECHANISMS. EPIGENETIC REGULATION CAN BE REPROGRAMMED, POTENTIALLY AFFECTING THE RISK, AETIOLOGY AND TREATMENT OF VARIOUS DISEASE STATES. THE EPIGENETICALLY INFLUENCED PHENOTYPE COULD BE REVERSED WITH DEMETHYLATING OR DEACETYLATING AGENTS, CONSISTENT WITH EPIGENETIC PLASTICITY. THE POSTNATAL REVERSIBILITY OF THESE METHYLATION OR ACETYLATION EVENTS MAY THEREFORE PROVIDE GOOD OPPORTUNITIES FOR INTERVENTION. THE RECOGNITION OF THE ROLE OF GENETIC AND EPIGENETIC MECHANISMS IN THE DEVELOPMENT OF COPD MAY IDENTIFY NOVEL TARGETS THAT HATCH NEW THERAPIES FOR PATIENTS WITH COPD. 2011 16 3028 23 GENETICS OF COMPLEX AIRWAY DISEASE. THE PAST 3 YEARS HAVE SEEN HIGHLY SIGNIFICANT GENETIC EFFECTS IDENTIFIED FOR A WIDE VARIETY OF COMMON COMPLEX DISEASES, INCLUDING THE AIRWAY DISORDERS OF ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. IT APPEARS THAT ONLY A PORTION OF THE GENETICALLY MEDIATED SUSCEPTIBILITY TO COMPLEX DISEASES HAS BEEN IDENTIFIED, AND THERE IS MUCH LEFT TO BE DISCOVERED. THIS REVIEW BRIEFLY DESCRIBES THE RESULTS OF THE GENOME-WIDE ASSOCIATION STUDIES OF ASTHMA AND GIVES AN OVERVIEW OF THE PARALLEL AND INCREASINGLY LARGE-SCALE STUDIES THAT ARE TAKING PLACE WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE. THE FUTURE IMPACT IS DISCUSSED OF TECHNOLOGICAL ADVANCES THAT ALLOW INCREASINGLY LARGE-SCALE GENE EXPRESSION STUDIES, NEXT-GENERATION SEQUENCING, AND GENOME-WIDE TESTING FOR EPIGENETIC EFFECTS. THE USE OF GENETIC TECHNOLOGY TO EXAMINE THE AIRWAY MICROBIOTA THAT INTERACT WITH THE MUCOSA IN HEALTH AND DISEASE IS DESCRIBED. 2011 17 4780 43 NUTRIEPIGENOMICS AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE: POTENTIAL ROLE OF DIETARY AND EPIGENETICS FACTORS IN DISEASE DEVELOPMENT AND MANAGEMENT. OVER RECENT DECADES, A NUMBER OF STUDIES HAVE REVEALED THE POSSIBLE ROLE OF DIFFERENT TYPES OF DIETS, AS WELL AS THE NUTRITIONAL ELEMENTS THEY ARE MADE UP OF, IN THE PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). TO DATE, DIETARY FACTORS HAVE BEEN IDENTIFIED TO PLAY A ROLE IN THE PREVENTION OF COPD, WITH EVIDENCE FROM ANTIOXIDANT NUTRIENTS, VITAMINS, AND FIBER INTAKE. ADDITIONALLY, CERTAIN DIETARY PATTERNS SUCH AS THE MEDITERRANEAN DIET, TOGETHER WITH OTHER WESTERN DIETS, PROVIDE EVIDENCE OF THE INFLUENCE ON COPD DEVELOPMENT, PROMOTING LUNG HEALTH THROUGH NUTRITIONAL APPROACHES, AND GIVING US AN OPPORTUNITY FOR INTERVENTION. THE EFFECT OF DIET ON COPD IS CONVEYED BY 3 MECHANISMS: REGULATION OF INFLAMMATION, OXIDATIVE STRESS, AND CARBON DIOXIDE PRODUCED/OXYGEN INTAKE. CURRENT ADVANCES HAVE BEGUN TO HIGHLIGHT THE POSSIBLE ROLE OF DIET IN MODIFYING GENE EXPRESSION IN CERTAIN INDIVIDUALS THAT PREDISPOSES THEM TO COPD THROUGH EPIGENETIC MODIFICATIONS. THE RELATION BETWEEN DIETARY INTAKE AND EPIGENETIC FACTORS HAS THEREFORE OUTLINED NUTRIEPIGENOMICS AS A POSSIBLE MISSING LINK IN THE RELATION BETWEEN ENVIRONMENTAL EXPOSURE TO SMOKE AND THE APPEARANCE OF A SUBSEQUENT CHRONIC BRONCHIAL OBSTRUCTION. THIS REVIEW SUMMARIZES THE EVIDENCE REGARDING THE INFLUENCE OF DIETARY PATTERNS AND NUTRIENTS AND EPIGENETIC REGULATORY MECHANISMS ON COPD DEVELOPMENT AND PREVENTION WITH THE AIM OF ENCOURAGING CLINICAL RESEARCH ON THE IMPACT OF DIETARY MODIFICATIONS ON COPD-RELATED CLINICAL OUTCOMES. THIS REVIEW HIGHLIGHTS THE IMPORTANCE OF PROPOSING AND CARRYING OUT FUTURE STUDIES FOCUSED ON THE MODULATING EFFECTS OF CERTAIN NUTRIENTS ON EPIGENETIC CHANGES IN PATIENTS WITH SPECIFIC COPD PHENOTYPES (BRONCHIECTASIS, EMPHYSEMA, ASTHMA/COPD, CHRONIC BRONCHITIS), AND THEIR INDIVIDUAL RESPONSES TO CIGARETTE SMOKING, ENVIRONMENTAL POLLUTION, OR OTHER NOXIOUS PARTICLES. THE OBJECTIVES OF THESE FUTURE STUDIES MUST BE DIRECTED TO THE DEVELOPMENT OF NOVEL THERAPEUTIC APPROACHES AND PERSONALIZED MANAGEMENT OF COPD. 2021 18 6812 28 [EPIGENETICS, INTERFACE BETWEEN ENVIRONMENT AND GENES: ROLE IN COMPLEX DISEASES]. EPIGENETICS IS THE STUDY OF HERITABLE CHANGES IN GENE EXPRESSION OR CELLULAR PHENOTYPE CAUSED BY MECHANISMS OTHER THAN CHANGES IN THE UNDERLYING DNA SEQUENCE. EPIGENETICS IS ONE OF THE MAJOR MECHANISMS EXPLAINING THE "DEVELOPMENTAL ORIGIN OF HEALTH AND DISEASES" (DOHAD). BESIDES GENETIC BACKGROUND INHERITED FROM PARENTS, WHICH CONFERS SUSCEPTIBILITY TO CERTAIN PATHOLOGIES, EPIGENETIC CHANGES CONSTITUTE THE MEMORY OF PREVIOUS EVENTS, EITHER POSITIVE OR NEGATIVE, ALONG THE LIFE CYCLE, INCLUDING AT THE IN UTERO STAGE. THE LATER EXPOSITION TO HOSTILE ENVIRONMENT MAY REVEAL SUCH SUSCEPTIBILITY, WITH THE DEVELOPMENT OF VARIOUS PATHOLOGIES, AMONG THEM NUMEROUS CHRONIC COMPLEX DISEASES. THE DEMONSTRATION OF SUCH A SEQUENCE OF EVENTS HAS BEEN SHOWN FOR METABOLIC DISEASES AS OBESITY, METABOLIC SYNDROME AND TYPE 2 DIABETES, CARDIOVASCULAR DISEASE AND CANCER. IN CONTRAST TO GENETIC PREDISPOSITION, WHICH IS IRREVERSIBLE, EPIGENETIC CHANGES ARE POTENTIALLY REVERSIBLE, THUS GIVING TARGETS NOT ONLY FOR PREVENTION, BUT POSSIBLY ALSO FOR THE TREATMENT OF CERTAIN COMPLEX DISEASES. 2012 19 2330 29 EPIGENETIC REGULATION OF IMMUNE FUNCTION IN ASTHMA. ASTHMA IS A COMMON COMPLEX RESPIRATORY DISEASE CHARACTERIZED BY CHRONIC AIRWAY INFLAMMATION AND PARTIALLY REVERSIBLE AIRFLOW OBSTRUCTION RESULTING FROM GENETIC AND ENVIRONMENTAL DETERMINANTS. BECAUSE EPIGENETIC MARKS INFLUENCE GENE EXPRESSION AND CAN BE MODIFIED BY BOTH ENVIRONMENTAL EXPOSURES AND GENETIC VARIATION, THEY ARE INCREASINGLY RECOGNIZED AS RELEVANT TO THE PATHOGENESIS OF ASTHMA AND MAY BE A KEY LINK BETWEEN ENVIRONMENTAL EXPOSURES AND ASTHMA SUSCEPTIBILITY. UNLIKE CHANGES TO DNA SEQUENCE, EPIGENETIC SIGNATURES ARE DYNAMIC AND REVERSIBLE, CREATING AN OPPORTUNITY FOR NOT ONLY THERAPEUTIC TARGETS BUT MAY SERVE AS BIOMARKERS TO FOLLOW DISEASE COURSE AND IDENTIFY MOLECULAR SUBTYPES IN HETEROGENEOUS DISEASES SUCH AS ASTHMA. IN THIS REVIEW, WE WILL EXAMINE THE RELATIONSHIP BETWEEN ASTHMA AND 3 KEY EPIGENETIC PROCESSES THAT MODIFY GENE EXPRESSION: DNA METHYLATION, MODIFICATION OF HISTONE TAILS, AND NONCODING RNAS. IN ADDITION TO PRESENTING A COMPREHENSIVE ASSESSMENT OF THE EXISTING EPIGENETIC STUDIES FOCUSING ON IMMUNE REGULATION IN ASTHMA, WE WILL DISCUSS FUTURE DIRECTIONS FOR EPIGENETIC INVESTIGATION IN ALLERGIC AIRWAY DISEASE. 2022 20 6288 38 THE POTENTIAL ROLE OF EPIGENETIC MODIFICATIONS ON DIFFERENT FACETS IN THE PERIODONTAL PATHOGENESIS. PERIODONTITIS IS A CHRONIC INFLAMMATORY DISEASE THAT AFFECTS THE SUPPORTING STRUCTURES OF TEETH. IN THE LITERATURE, THE ASSOCIATION BETWEEN THE PATHOGENICITY OF BACTERIA AND ENVIRONMENTAL FACTORS IN THIS REGARD HAVE BEEN EXTENSIVELY EXAMINED. IN THE PRESENT STUDY, WE WILL SHED LIGHT ON THE POTENTIAL ROLE THAT EPIGENETIC CHANGE CAN PLAY ON DIFFERENT FACETS OF ITS PROCESS, MORE PARTICULARLY THE MODIFICATIONS CONCERNING THE GENES INVOLVED IN INFLAMMATION, DEFENSE, AND IMMUNE SYSTEMS. SINCE THE 1960S, THE ROLE OF GENETIC VARIANTS IN THE ONSET AND SEVERITY OF PERIODONTAL DISEASE HAS BEEN WIDELY DEMONSTRATED. THESE MAKE SOME PEOPLE MORE SUSCEPTIBLE TO DEVELOPING IT THAN OTHERS. IT HAS BEEN DOCUMENTED THAT THE WIDE VARIATION IN ITS FREQUENCY FOR VARIOUS RACIAL AND ETHNIC POPULATIONS IS DUE PRIMARILY TO THE COMPLEX INTERPLAY AMONG GENETIC FACTORS WITH THOSE AFFECTING THE ENVIRONMENT AND THE DEMOGRAPHY. IN MOLECULAR BIOLOGY, EPIGENETIC MODIFICATIONS ARE DEFINED AS ANY CHANGE IN THE PROMOTER FOR THE CPG ISLANDS, IN THE STRUCTURE OF THE HISTONE PROTEIN, AS WELL AS POST-TRANSLATIONAL REGULATION BY MICRORNAS (MIRNAS), BEING KNOWN TO CONTRIBUTE TO THE ALTERATION IN GENE EXPRESSION FOR COMPLEX MULTIFACTORIAL DISEASES SUCH AS PERIODONTITIS. THE KEY ROLE OF EPIGENETIC MODIFICATION IS TO UNDERSTAND THE MECHANISM INVOLVED IN THE GENE-ENVIRONMENT INTERACTION, AND THE DEVELOPMENT OF PERIODONTITIS IS NOW THE SUBJECT OF MORE AND MORE STUDIES THAT ATTEMPT TO IDENTIFY WHICH FACTORS ARE STIMULATING IT, BUT ALSO AFFECT THE REDUCED RESPONSE TO THERAPY. 2023