1 3144 124 GLOBAL ORAL HEALTH INEQUALITIES: TASK GROUP--PERIODONTAL DISEASE. PERIODONTAL DISEASES CONSTITUTE ONE OF THE MAJOR GLOBAL ORAL HEALTH BURDENS, AND PERIODONTITIS REMAINS A MAJOR CAUSE OF TOOTH LOSS IN ADULTS WORLDWIDE. THE WORLD HEALTH ORGANIZATION RECENTLY REPORTED THAT SEVERE PERIODONTITIS EXISTS IN 5-20% OF ADULT POPULATIONS, AND MOST CHILDREN AND ADOLESCENTS EXHIBIT SIGNS OF GINGIVITIS. LIKELY REASONS TO ACCOUNT FOR THESE PREVALENT DISEASES INCLUDE GENETIC, EPIGENETIC, AND ENVIRONMENTAL RISK FACTORS, AS WELL AS INDIVIDUAL AND SOCIO-ECONOMIC DETERMINANTS. CURRENTLY, THERE ARE FUNDAMENTAL GAPS IN KNOWLEDGE OF SUCH FUNDAMENTAL ISSUES AS THE MECHANISMS OF INITIATION AND PROGRESSION OF PERIODONTAL DISEASES, WHICH ARE UNDEFINED; INABILITY TO IDENTIFY HIGH-RISK FORMS OF GINGIVITIS THAT PROGRESS TO PERIODONTITIS; LACK OF EVIDENCE ON HOW TO PREVENT THE DISEASES EFFECTIVELY; INABILITY TO DETECT DISEASE ACTIVITY AND PREDICT TREATMENT EFFICACY; AND LIMITED INFORMATION ON THE EFFECTS OF INTEGRATION OF PERIODONTAL HEALTH AS A PART OF THE HEALTH CARE PROGRAM DESIGNED TO PROMOTE GENERAL HEALTH AND PREVENT CHRONIC DISEASES. IN THE PRESENT REPORT, 12 BASIC, TRANSLATIONAL, AND APPLIED RESEARCH AREAS HAVE BEEN PROPOSED TO ADDRESS THE ISSUE OF GLOBAL PERIODONTAL HEALTH INEQUALITY. WE BELIEVE THAT THE ORAL HEALTH BURDEN CAUSED BY PERIODONTAL DISEASES COULD BE RELIEVED SIGNIFICANTLY IN THE NEAR FUTURE THROUGH AN EFFECTIVE GLOBAL COLLABORATION. 2011 2 4393 26 MODIFIABLE RISK FACTORS IN PERIODONTITIS: AT THE INTERSECTION OF AGING AND DISEASE. CHRONIC INFLAMMATION IS A PROMINENT FEATURE OF AGING AND OF COMMON AGE-RELATED DISEASES, INCLUDING ATHEROSCLEROSIS, CANCER AND PERIODONTITIS. THIS VOLUME EXAMINES MODIFIABLE RISK FACTORS FOR PERIODONTITIS AND OTHER CHRONIC INFLAMMATORY DISEASES. ORAL BACTERIAL COMMUNITIES AND VIRAL INFECTIONS, PARTICULARLY WITH CYTOMEGALOVIRUS AND OTHER HERPESVIRUSES, ELICIT DISTINCT IMMUNE RESPONSES AND ARE CENTRAL IN THE INITIATION OF PERIODONTAL DISEASES. RISK OF DISEASE IS DYNAMIC AND CHANGES IN RESPONSE TO COMPLEX INTERACTIONS OF GENETIC, ENVIRONMENTAL AND STOCHASTIC FACTORS OVER THE LIFESPAN. MANY MODIFIABLE RISK FACTORS, SUCH AS SMOKING AND EXCESS CALORIC INTAKE, CONTRIBUTE TO INCREASES IN SYSTEMIC MARKERS OF INFLAMMATION AND CAN MODIFY GENE REGULATION THROUGH A VARIETY OF BIOLOGIC MECHANISMS (E.G. EPIGENETIC MODIFICATIONS). PERIODONTITIS AND OTHER COMMON CHRONIC INFLAMMATORY DISEASES SHARE MULTIPLE MODIFIABLE RISK FACTORS, SUCH AS TOBACCO SMOKING, PSYCHOLOGICAL STRESS AND DEPRESSION, ALCOHOL CONSUMPTION, OBESITY, DIABETES, METABOLIC SYNDROME AND OSTEOPOROSIS. INTERVENTIONS THAT TARGET MODIFIABLE RISK FACTORS HAVE THE POTENTIAL TO IMPROVE RISK PROFILES FOR PERIODONTITIS AS WELL AS FOR OTHER COMMON CHRONIC DISEASES. 2014 3 2396 35 EPIGENETIC REPROGRAMMING IN PERIODONTAL DISEASE: DYNAMIC CROSSTALK WITH POTENTIAL IMPACT IN ONCOGENESIS. PERIODONTITIS IS A CHRONIC MULTIFACTORIAL IN FL AMMATORY DISEASE ASSOCIATED WITH MICROBIAL DYSBIOSIS AND CHARACTERIZED BY PROGRESSIVE DESTRUCTION OF THE PERIODONTAL TISSUES. SUCH CHRONIC INFECTIOUS INFLAMMATORY DISEASE IS RECOGNIZED AS A MAJOR PUBLIC HEALTH PROBLEM WORLDWIDE WITH MEASURABLE IMPACT IN SYSTEMIC HEALTH. IT HAS BECOME EVIDENT THAT THE PERIODONTAL DISEASE PHENOTYPES ARE NOT ONLY DETERMINED BY THE MICROBIOME EFFECT, BUT THE EXTENT OF THE TISSUE RESPONSE IS ALSO DRIVEN BY THE HOST GENOME AND EPIGENOME PATTERNS RESPONDING TO VARIOUS ENVIRONMENTAL EXPOSURES. MORE RECENTLY THERE IS MOUNTING EVIDENCE INDICATING THAT EPIGENETIC REPROGRAMMING IN RESPONSE TO COMBINED INTRINSIC AND ENVIRONMENTAL EXPOSURES, MIGHT BE PARTICULARLY RELEVANT DUE ITS PLASTICITY AND POTENTIAL APPLICATION TOWARDS PRECISION HEALTH. THE COMPLEX EPIGENETIC CROSSTALK IS REFLECTED IN THE PROGNOSIS AND PROGRESS OF PERIODONTAL DISEASES AND MAY ALSO LEAD TO A FAVORABLE LANDSCAPE FOR CANCER DEVELOPMENT. THIS REVIEW DISCUSSES EPIGENOMICS MODIFICATIONS FOCUSING ON THE ROLE OF DNA METHYLATION AND PATHWAYS LINKING MICROBIAL INFECTION AND INFLAMMATORY PATHWAYS, WHICH ARE ALSO ASSOCIATED WITH CARCINOGENESIS. THERE IS A MORE CLEAR VISION WHEREAS 'OMICS' TECHNOLOGIES APPLIED TO UNVEIL RELEVANT EPIGENETIC FACTORS COULD PLAY A SIGNIFICANT ROLE IN THE TREATMENT OF PERIODONTAL DISEASE IN A PERSONALIZED MODE, EVIDENCING THAT PUBLIC HEALTH APPROACH SHOULD COEXIST WITH PRECISION INDIVIDUALIZED TREATMENT. 2020 4 2651 37 EPIGENOMICS AND TRANSCRIPTOMICS IN THE PREDICTION AND DIAGNOSIS OF CHILDHOOD ASTHMA: ARE WE THERE YET? ASTHMA IS THE MOST COMMON NON-COMMUNICABLE CHRONIC DISEASE OF CHILDHOOD. DESPITE ITS HIGH PREVALENCE, TO DATE WE LACK METHODS THAT ARE BOTH EFFICIENT AND ACCURATE IN DIAGNOSING ASTHMA. MOST TRADITIONAL APPROACHES HAVE BEEN BASED ON GARNERING CLINICAL EVIDENCE, SUCH AS RISK FACTORS AND EXPOSURES. GIVEN THE HIGH HERITABILITY OF ASTHMA, MORE RECENT APPROACHES HAVE LOOKED AT GENETIC POLYMORPHISMS AS POTENTIAL "RISK FACTORS." HOWEVER, GENETIC VARIANTS EXPLAIN ONLY A SMALL PROPORTION OF ASTHMA RISK, AND HAVE BEEN LESS THAN OPTIMAL AT PREDICTING RISK FOR INDIVIDUAL SUBJECTS. EPIGENOMIC STUDIES OFFER SIGNIFICANT ADVANTAGES OVER PREVIOUS APPROACHES. EPIGENETIC REGULATION IS HIGHLY TISSUE-SPECIFIC, AND CAN INDUCE BOTH SHORT- AND LONG-TERM CHANGES IN GENE EXPRESSION. SUCH CHANGES CAN START IN UTERO, CAN VARY THROUGHOUT THE LIFE SPAN, AND IN SOME INSTANCES CAN BE PASSED ON FROM ONE GENERATION TO ANOTHER. MOST IMPORTANTLY, THE EPIGENOME CAN BE MODIFIED BY ENVIRONMENTAL FACTORS AND EXPOSURES, AND THUS EPIGENETIC AND TRANSCRIPTOMIC PROFILING MAY YIELD THE MOST ACCURATE RISK ESTIMATES FOR A GIVEN PATIENT BY INCORPORATING ENVIRONMENTAL (AND TREATMENT) EFFECTS THROUGHOUT THE LIFESPAN. HERE WE WILL REVIEW THE MOST RECENT ADVANCES IN THE USE OF EPIGENETIC AND TRANSCRIPTOMIC ANALYSIS FOR THE EARLY DIAGNOSIS OF ASTHMA AND ATOPY, AS WELL AS CHALLENGES AND FUTURE DIRECTIONS IN THE FIELD AS IT MOVES FORWARD. WE WILL PARTICULARLY FOCUS ON DNA METHYLATION, THE MOST STUDIED MECHANISM OF EPIGENETIC REGULATION. 2019 5 1248 37 CURRENT EVIDENCE FOR BIOLOGICAL BIOMARKERS AND MECHANISMS UNDERLYING ACUTE TO CHRONIC PAIN TRANSITION ACROSS THE PEDIATRIC AGE SPECTRUM. CHRONIC PAIN IS HIGHLY PREVALENT IN THE PEDIATRIC POPULATION. MANY FACTORS ARE INVOLVED IN THE TRANSITION FROM ACUTE TO CHRONIC PAIN. CURRENTLY, THERE ARE CONCEPTUAL MODELS PROPOSED, BUT THEY LACK A MECHANISTICALLY SOUND INTEGRATED THEORY CONSIDERING THE STAGES OF CHILD DEVELOPMENT. OBJECTIVE BIOMARKERS ARE CRITICALLY NEEDED FOR THE DIAGNOSIS, RISK STRATIFICATION, AND PROGNOSIS OF THE PATHOLOGICAL STAGES OF PAIN CHRONIFICATION. IN THIS ARTICLE, WE SUMMARIZE THE CURRENT EVIDENCE ON MECHANISMS AND BIOMARKERS OF ACUTE TO CHRONIC PAIN TRANSITIONS IN INFANTS AND CHILDREN THROUGH THE DEVELOPMENTAL LENS. THE GOAL IS TO IDENTIFY GAPS AND OUTLINE FUTURE DIRECTIONS FOR BASIC AND CLINICAL RESEARCH TOWARD A DEVELOPMENTALLY INFORMED THEORY OF PAIN CHRONIFICATION IN THE PEDIATRIC POPULATION. AT THE OUTSET, THE IMPORTANCE OF OBJECTIVE BIOMARKERS FOR CHRONIFICATION OF PAIN IN CHILDREN IS OUTLINED, FOLLOWED BY A SUMMARY OF THE CURRENT EVIDENCE ON THE MECHANISMS OF ACUTE TO CHRONIC PAIN TRANSITION IN ADULTS, IN ORDER TO CONTRAST WITH THE DEVELOPMENTAL MECHANISMS OF PAIN CHRONIFICATION IN THE PEDIATRIC POPULATION. EVIDENCE IS PRESENTED TO SHOW THAT CHRONIC PAIN MAY HAVE ITS ORIGIN FROM INSULTS EARLY IN LIFE, WHICH PRIME THE CHILD FOR THE DEVELOPMENT OF CHRONIC PAIN IN LATER LIFE. FURTHERMORE, AVAILABLE GENETIC, EPIGENETIC, PSYCHOPHYSICAL, ELECTROPHYSIOLOGICAL, NEUROIMAGING, NEUROIMMUNE, AND SEX MECHANISMS ARE DESCRIBED IN INFANTS AND OLDER CHILDREN. IN CONCLUSION, FUTURE DIRECTIONS ARE DISCUSSED WITH A FOCUS ON RESEARCH GAPS, TRANSLATIONAL AND CLINICAL IMPLICATIONS. UTILIZATION OF DEVELOPMENTAL MECHANISMS FRAMEWORK TO INFORM CLINICAL DECISION-MAKING AND STRATEGIES FOR PREVENTION AND MANAGEMENT OF ACUTE TO CHRONIC PAIN TRANSITIONS IN CHILDREN, IS HIGHLIGHTED. 2023 6 1453 29 DISCOVERING HOW ENVIRONMENTAL EXPOSURES ALTER GENES COULD LEAD TO NEW TREATMENTS FOR CHRONIC ILLNESSES. EMERGING RESEARCH DEMONSTRATES THAT DIET, POLLUTION, AND OTHER ENVIRONMENTAL TRIGGERS CAN ALTER BOTH THE FUNCTION AND EXPRESSION OF HUMAN GENES AND LEAD TO A HEIGHTENED DISEASE RISK. THESE ENVIRONMENT-GENE INTERACTIONS CAN CAUSE SO-CALLED EPIGENETIC CHANGES IN GENE EXPRESSION-PATTERNS OF WHICH GENES ARE SWITCHED "ON" OR "OFF"-THAT MAY ACCOUNT FOR THE RISING MORTALITY FROM CHRONIC DISEASES IN INDUSTRIALIZED NATIONS. IN THIS PAPER, WE CALL FOR A NEW TRANSDISCIPLINARY APPROACH TO PUBLIC HEALTH THAT WOULD EXAMINE HOW ENVIRONMENTAL EXPOSURES, BOTH PHYSICAL AND SOCIAL, INFLUENCE GENE EXPRESSION AND A PERSON'S SUSCEPTIBILITY TO CHRONIC DISEASE. THIS INITIATIVE COULD LEAD TO NEW WAYS TO PREVENT AND TREAT SUCH ILLNESSES. 2011 7 6288 31 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 8 3404 27 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 9 6905 24 [THE ROLE OF EPIGENETIC REGULATIONS IN EARLY CHILDHOOD DISEASES]. WITH THE ACCEPTANCE OF "THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE" CONCEPT IN THE 1990S, IT BECAME CLEAR THAT EPIGENETIC INHERITANCE, WHICH DO NOT INVOLVE CHANGES IN THE DNA SEQUENCE HAS IMPORTANT ROLE IN THE PATHOGENESIS OF DISEASES. EPIGENETIC REGULATION SERVES THE ADAPTATION TO THE CHANGING ENVIRONMENT AND MAINTAINS THE REPRODUCTIVE FITNESS EVEN ON THE DRAWBACK OF INCREASED RISK OF DISEASES IN LATER LIFE. THE ROLE OF EPIGENETIC MECHANISMS IN CHRONIC NON-COMMUNICABLE DISEASES HAS BEEN WELL ESTABLISHED. RECENT STUDIES HAVE REVEALED THAT EPIGENETIC CHANGES HAVE ALSO CAUSAL ROLE IN CERTAIN PEDIATRIC DISEASES. THE REVIEW EVALUATES THE RECENT EPIGENETIC FINDINGS IN THE PATHOMECHANISM OF COMMON PEDIATRIC DISEASES. THE WIDE RANGE AND LONG-LASTING DURATION OF EPIGENETIC REGULATIONS GIVE IMPORTANCE TO THE SUBJECT. METHODS ARE ALREADY AVAILABLE TO EVALUATE A PART OF THE EPIGENETIC CHANGES IN THE CLINICAL PRACTICE, PRESENTLY AIMING PRIMARILY THE ESTIMATION OF THE DISEASE RISK OR DEFINITION OF DIAGNOSIS. FURTHERMORE, THERE ARE ALREADY AVAILABLE LIMITED MEANS TO INFLUENCE THE EPIGENETIC REGULATION. 2019 10 3676 33 INFLAMMATION AND NEUTROPHIL IMMUNOSENESCENCE IN HEALTH AND DISEASE: TARGETED TREATMENTS TO IMPROVE CLINICAL OUTCOMES IN THE ELDERLY. DESPITE INCREASING LONGEVITY, MANY OLD PEOPLE ARE NOT IN GOOD HEALTH. THERE HAS BEEN AN INCREASE IN THE PREVALENCE OF AGE-ASSOCIATED MULTI-MORBIDITY (TWO OR MORE CHRONIC CONDITIONS IN THE SAME PERSON). ALSO, SEVERE INFECTIONS, SUCH AS PNEUMONIA, REMAIN SIGNIFICANT CAUSES OF MORTALITY AND MORBIDITY IN THIS AGING GROUP. MANY CHRONIC HEALTH CONDITIONS SHARE RISK FACTORS SUCH AS INCREASING AGE, SMOKING, A SEDENTARY LIFE STYLE AND BEING PART OF A LOWER SOCIOECONOMIC GROUP. HOWEVER, DESPITE THIS, MULTI-MORBIDITIES OFTEN CO-OCCUR MORE COMMONLY THAN WOULD BE PREDICTED. THIS HAS LED TO THE HYPOTHESIS THAT THEY SHARE COMMON UNDERLYING MECHANISMS. THIS IS AN IMPORTANT CONCEPT, FOR IF IT WERE TRUE, TREATMENTS COULD BE DEVISED WHICH TARGET THESE COMMON PATHWAYS AND IMPROVE A NUMBER OF AGE-ASSOCIATED HEALTH CONDITIONS. MANY CHRONIC ILLNESSES ASSOCIATED WITH MULTI-MORBIDITY AND SEVERE INFECTIONS ARE CHARACTERIZED BY AN ABNORMAL AND SUSTAINED INFLAMMATORY RESPONSE, WITH NEUTROPHILS BEING KEY EFFECTOR CELLS IN THE PATHOLOGICAL PROCESS. STUDIES HAVE DESCRIBED ABERRANT NEUTROPHIL FUNCTIONS ACROSS THESE CONDITIONS, AND SOME HAVE HIGHLIGHTED POTENTIAL MECHANISMS FOR ALTERED CELL BEHAVIOURS WHICH APPEAR SHARED ACROSS DISEASE STATES. IT HAS BEEN SUGGESTED THAT ALTERED FUNCTIONS MAY REPRESENT NEUTROPHIL "SENESCENCE". THIS REVIEW CONSIDERS HOW AND WHY NEUTROPHIL FUNCTIONS CHANGE AS THE CELL AGES, AND HOW AND WHY NEUTROPHIL FUNCTIONS CHANGE AS THE HOST AGES IN HEALTH AND DISEASE AND DISCUSSES WHETHER NEUTROPHIL FUNCTIONS COULD BE TARGETED TO IMPROVE HEALTH OUTCOMES IN OLDER ADULTS. 2018 11 1871 42 EMERGING ROLE OF EPIGENETICS IN EXPLAINING RELATIONSHIP OF PERIODONTITIS AND CARDIOVASCULAR DISEASES. CARDIOVASCULAR DISEASES SUCH AS ISCHEMIC HEART DISEASES OR STROKE ARE AMONG THE LEADING CAUSE OF DEATHS GLOBALLY, AND EVIDENCE SUGGESTS THAT THESE DISEASES ARE MODULATED BY A MULTIFACTORIAL AND COMPLEX INTERPLAY OF GENETIC, ENVIRONMENTAL, AND LIFESTYLE FACTORS. GENETIC PREDISPOSITION AND CHRONIC EXPOSURE TO MODIFIABLE RISK FACTORS HAVE BEEN EXPLORED TO BE INVOLVED IN THE PATHOPHYSIOLOGY OF CVD. ENVIRONMENTAL FACTORS CONTRIBUTE TO AN INDIVIDUAL'S PROPENSITY TO DEVELOP MAJOR CARDIOVASCULAR RISK FACTORS THROUGH EPIGENETIC MODIFICATIONS OF DNA AND HISTONES VIA MIRNA REGULATION OF PROTEIN TRANSLATION THAT ARE TYPES OF EPIGENETIC MECHANISMS AND PARTICIPATE IN DISEASE DEVELOPMENT. PERIODONTAL DISEASE (PD) IS ONE OF THE MOST COMMON ORAL DISEASES IN HUMANS THAT IS CHARACTERIZED BY LOW-GRADE INFLAMMATION AND HAS BEEN SHOWN TO INCREASE THE RISK OF CVDS. RISK FACTORS INVOLVED IN PD AND CVD ARE DETERMINED BOTH GENETICALLY AND BEHAVIORALLY. PERIODONTAL DISEASES SUCH AS CHRONIC INFLAMMATION PROMOTE DNA METHYLATION. EPIGENETIC MODIFICATIONS INVOLVED IN THE INITIATION AND PROGRESSION OF ATHEROSCLEROSIS PLAY AN ESSENTIAL ROLE IN PLAQUE DEVELOPMENT AND VULNERABILITY. EPIGENETICS HAS OPENED A NEW WORLD TO UNDERSTAND AND MANAGE HUMAN DISEASES, INCLUDING CVDS AND PERIODONTAL DISEASES. GENETIC MEDICINE HAS STARTED A NEW ERA OF EPIGENETICS TO OVERCOME HUMAN DISEASES WITH VARIOUS NEW METHODOLOGY. EPIGENETIC PROFILING MAY AID IN BETTER DIAGNOSIS AND STRATIFICATION OF PATIENTS SHOWING POTENTIAL PREDISPOSED STATES FOR DISEASE. A BETTER UNDERSTANDING OF THE EXACT REGULATORY MECHANISMS OF EPIGENETIC PATHWAYS DRIVING INFLAMMATION IS SLOWLY EMERGING AND WILL AID IN DEVELOPING NOVEL TOOLS FOR THE TREATMENT OF DISEASE. 2021 12 2570 26 EPIGENETICS OF CHRONIC INFLAMMATORY DISEASES. CHRONIC, NONCOMMUNICABLE, AND INFLAMMATION-ASSOCIATED DISEASES REMAIN THE LARGEST CAUSE OF MORBIDITY AND MORTALITY GLOBALLY AND WITHIN THE UNITED STATES. THIS IS MAINLY DUE TO OUR LIMITED UNDERSTANDING OF THE MOLECULAR MECHANISMS THAT UNDERLIE THESE COMPLEX PATHOLOGIES. THE AVAILABLE EVIDENCE INDICATES THAT STUDIES OF EPIGENETICS (TRADITIONALLY DEFINED AS THE HERITABLE CHANGES TO GENE EXPRESSION THAT ARE INDEPENDENT OF CHANGES TO DNA) ARE SIGNIFICANTLY ADVANCING OUR KNOWLEDGE OF THESE INFLAMMATORY CONDITIONS. THIS REVIEW WILL FOCUS ON EPIGENETIC STUDIES OF THREE DISEASES, THAT ARE AMONG THE MOST BURDENSOME GLOBALLY: CARDIOVASCULAR DISEASE, THE NUMBER ONE CAUSE OF DEATHS WORLDWIDE, TYPE 2 DIABETES AND, ALZHEIMER'S DISEASE. THE CURRENT STATUS OF EPIGENETIC RESEARCH, INCLUDING THE ABILITY TO PREDICT DISEASE RISK, AND KEY PATHOPHYSIOLOGICAL DEFECTS ARE DISCUSSED. THE SIGNIFICANCE OF DEFINING THE CONTRIBUTION OF EPIGENETIC DEFECTS TO NONRESOLVING INFLAMMATION AND AGING, EACH ASSOCIATED WITH THESE DISEASES, IS HIGHLIGHTED, AS THESE ARE LIKELY TO PROVIDE NEW INSIGHTS INTO INFLAMMATORY DISEASE PATHOGENESIS. 2019 13 269 33 AGE AND PERIODONTAL HEALTH - IMMUNOLOGICAL VIEW. PURPOSE OF THE REVIEW: AGING CLEARLY IMPACTS A WIDE ARRAY OF SYSTEMS, IN PARTICULAR THE BREADTH OF THE IMMUNE SYSTEM LEADING TO IMMUNOSENESCENCE, ALTERED IMMUNOACTIVATION, AND COINCIDENT INFLAMMAGING PROCESSES. THE NET RESULT OF THESE CHANGES LEADS TO INCREASED SUSCEPTIBILITY TO INFECTIONS, INCREASED NEOPLASTIC OCCURRENCES, AND ELEVATED FREQUENCY OF AUTOIMMUNE DISEASES WITH AGING. HOWEVER, AS THE BACTERIA IN THE ORAL MICROBIOME THAT CONTRIBUTE TO THE CHRONIC INFECTION OF PERIODONTITIS IS ACQUIRED EARLIER IN LIFE, THE CHARACTERISTICS OF THE INNATE AND ADAPTIVE IMMUNE SYSTEMS TO REGULATE THESE MEMBERS OF THE AUTOCHTHONOUS MICROBIOTA ACROSS THE LIFESPAN REMAINS ILL DEFINED. RECENT FINDINGS: CLEAR DATA DEMONSTRATE THAT BOTH CELLS AND MOLECULES OF THE INNATE AND ADAPTIVE IMMUNE RESPONSE ARE ADVERSELY IMPACTED BY AGING, INCLUDING IN THE ORAL CAVITY, YIELDING A REASONABLE TENET THAT THE INCREASED PERIODONTITIS NOTED IN AGING POPULATIONS IS REFLECTIVE OF THE AGE-ASSOCIATED IMMUNE DYSREGULATION. ADDITIONALLY, THIS FACET OF HOST-MICROBE INTERACTIONS AND DISEASE NEEDS TO ACCOMMODATE THE POPULATION VARIATION IN DISEASE ONSET AND PROGRESSION, WHICH MAY ALSO REFLECT AN ACCUMULATION OF ENVIRONMENTAL STRESSORS AND/OR DECREASED PROTECTIVE NUTRIENTS THAT COULD FUNCTION AT THE GENE LEVEL (IE. EPIGENETIC) OR TRANSLATIONAL LEVEL FOR PRODUCTION AND SECRETION OF IMMUNE SYSTEM MOLECULES. SUMMARY: FINALLY, THE MAJORITY OF STUDIES OF AGING AND PERIODONTITIS HAVE EMPHASIZED THE INCREASED PREVALENCE/SEVERITY OF DISEASE WITH AGING, ALL BASED UPON CHRONOLOGICAL AGE. HOWEVER, EVOLVING AREAS OF STUDY FOCUSING ON "BIOLOGICAL AGING" TO HELP ACCOUNT FOR POPULATION VARIATION IN DISEASE EXPRESSION, MAY SUGGEST THAT CHRONIC PERIODONTITIS REPRESENTS A CO-MORBIDITY THAT CONTRIBUTES TO "GEROVULNERABILITY" WITHIN THE POPULATION. 2018 14 5929 33 TARGETING EPIGENETIC MECHANISMS IN PERIODONTAL DISEASES. EPIGENETIC FACTORS ARE HERITABLE GENOME MODIFICATIONS THAT POTENTIALLY IMPACT GENE TRANSCRIPTION, CONTRIBUTING TO DISEASE STATES. EPIGENETIC MARKS PLAY AN IMPORTANT ROLE IN CHRONIC INFLAMMATORY CONDITIONS, AS OBSERVED IN PERIODONTAL DISEASES, BY ALLOWING MICROBIAL PERSISTENCE OR BY PERMITTING MICROBIAL INSULT TO PLAY A ROLE IN THE SO-CALLED 'HIT-AND-RUN' INFECTIOUS MECHANISM, LEADING TO LASTING PATHOGEN INTERFERENCE WITH THE HOST GENOME. EPIGENETICS ALSO AFFECTS THE HEALTH SCIENCES BY PROVIDING A DYNAMIC MECHANISTIC FRAMEWORK TO EXPLAIN THE WAY IN WHICH ENVIRONMENTAL AND BEHAVIORAL FACTORS INTERACT WITH THE GENOME TO ALTER DISEASE RISK. IN THIS ARTICLE WE REVIEW CURRENT KNOWLEDGE OF EPIGENOME REGULATION IN LIGHT OF THE MULTIFACTORIAL NATURE OF PERIODONTAL DISEASES. WE DISCUSS EPIGENETIC TAGGING IN IDENTIFIED GENES, AND CONSIDER THE POTENTIAL IMPLICATIONS OF EPIGENETIC CHANGES ON HOST-MICROBIOME DYNAMICS IN CHRONIC INFLAMMATORY STATES AND IN RESPONSE TO ENVIRONMENTAL STRESSORS. THE MOST RECENT ADVANCES IN GENOMIC TECHNOLOGIES HAVE PLACED US IN A POSITION TO ANALYZE INTERACTION EFFECTS (EG, BETWEEN PERIODONTAL DISEASE AND TYPE 2 DIABETES MELLITUS), WHICH CAN BE INVESTIGATED THROUGH EPIGENOME-WIDE ASSOCIATION ANALYSIS. FINALLY, BECAUSE OF THE INDIVIDUALIZED TRAITS OF EPIGENETIC BIOMARKERS, PHARMACOEPIGENOMIC PERSPECTIVES ARE ALSO CONSIDERED AS POTENTIALLY NOVEL THERAPEUTIC APPROACHES FOR IMPROVING PERIODONTAL DISEASE STATUS. 2018 15 2136 40 EPIGENETIC INFLUENCES IN THE OBESITY/COLORECTAL CANCER AXIS: A NOVEL THERAGNOSTIC AVENUE. THE WORLD HEALTH ORGANIZATION (WHO) CONSIDERS THAT OBESITY HAS REACHED PROPORTIONS OF PANDEMIC. EXPERTS ALSO INSIST ON THE IMPORTANCE OF CONSIDERING OBESITY AS A CHRONIC DISEASE AND ONE OF THE MAIN CONTRIBUTORS TO THE WORLDWIDE BURDEN OF OTHER NONTRANSMISSIBLE CHRONIC DISEASES, WHICH HAVE A GREAT IMPACT ON HEALTH, LIFESTYLE, AND ECONOMIC COST. ONE OF THE MOST CURRENT CHALLENGES OF BIOMEDICAL SCIENCE FACES IS TO UNDERSTAND THE ORIGIN OF THE CHRONIC NONTRANSMISSIBLE DISEASES, SUCH AS OBESITY AND CANCER. THERE IS A LARGE EVIDENCE, BOTH IN EPIDEMIOLOGICAL STUDIES IN HUMANS AND IN ANIMAL MODELS, OF THE ASSOCIATION BETWEEN OBESITY AND AN INCREASED RISK OF CANCER INCIDENCE. IN THE LAST YEARS, THE INITIAL DISCOVERY OF EPIGENETIC MECHANISMS REPRESENTS THE MOST RELEVANT FINDING TO EXPLAIN HOW THE GENOME INTERACTS WITH ENVIRONMENTAL FACTORS AND THE RIPPLE EFFECTS ON DISEASE PATHOGENESES. SINCE THEN, ALL EPIGENETIC PROCESS HAS BEEN INVESTIGATED BY THE SCIENTIFIC COMMUNITIES FOR NEARLY TWO DECADES TO DETERMINE WHICH COMPONENTS ARE INVOLVED IN THIS PROCESS. DNA/RNA METHYLATION AND MIRNA ARE CLASSIFIED AS TWO OF THE MOST IMPORTANT REPRESENTATIVE CLASSES OF SUCH EPIGENETIC MECHANISMS AND DYSREGULATED ACTIVITY OF SUCH MECHANISM CAN CERTAINLY CONTRIBUTE TO DISEASE PATHOGENESIS AND/OR PROGRESSION ESPECIALLY IN TUMORS. THIS REVIEW ARTICLE SERVES TO HIGHLIGHT THE IMPACT OF DNA/RNA METHYLATION AND MIRNA-BASED EPIGENETIC MECHANISM ACTIVITIES IN THE INTERPLAY BETWEEN OBESITY AND THE DEVELOPMENT AND CLINICAL SIGNIFICANCE OF COLORECTAL CANCER. 2019 16 396 33 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 17 6459 20 TIME TO CHANGE FROM A SIMPLE LINEAR MODEL TO A COMPLEX SYSTEMS MODEL. A SIMPLE LINEAR MODEL TO TEST THE HYPOTHESIS BASED ON ONE-ON-ONE RELATIONSHIP HAS BEEN USED TO FIND THE CAUSATIVE FACTORS OF DISEASES. HOWEVER, WE NOW KNOW THAT NOT JUST ONE, BUT MANY FACTORS FROM DIFFERENT SYSTEMS SUCH AS CHEMICAL EXPOSURE, GENES, EPIGENETIC CHANGES, AND PROTEINS ARE INVOLVED IN THE PATHOGENESIS OF CHRONIC DISEASES SUCH AS DIABETES MELLITUS. SO, WITH AVAILABILITY OF MODERN TECHNOLOGIES TO UNDERSTAND THE INTRICATE NATURE OF RELATIONS AMONG COMPLEX SYSTEMS, WE NEED TO MOVE FORWARD TO THE FUTURE BY TAKING COMPLEX SYSTEMS MODEL. 2016 18 2517 28 EPIGENETICS AND THE BURDEN OF NONCOMMUNICABLE DISEASE: A PAUCITY OF RESEARCH IN AFRICA. EPIDEMIOLOGICAL EVIDENCE SUGGESTS THAT AN ADVERSE IN UTERO ENVIRONMENT IS ASSOCIATED WITH AN INCREASED RISK FOR DEVELOPING ADULT ONSET DISEASES. THE MOLECULAR MECHANISMS FOR SUSCEPTIBILITY TO CHRONIC NONCOMMUNICABLE DISEASES ARE NOT FULLY UNDERSTOOD, ALTHOUGH RECENT RESEARCH HAS PROPOSED THAT EPIGENETIC MODIFICATIONS PLAY AN IMPORTANT ROLE IN FETAL PROGRAMMING. GENETIC AND ENVIRONMENTAL FACTORS CONTRIBUTE TO INTERINDIVIDUAL AND SPATIOTEMPORAL TISSUE-SPECIFIC METHYLATION PATTERNS. ALTHOUGH THE DIVERSE ENVIRONMENTS AND HIGH GENETIC DIVERSITY OF AFRICAN POPULATIONS PROVIDE UNPARALLELED POTENTIAL TO INVESTIGATE THE EFFECTS OF ENVIRONMENTAL CHANGE ON THE EPIGENETIC PROFILE IN HUMANS, ONLY A SMALL PERCENTAGE OF GENOMIC AND EPIGENETIC STUDIES HAVE FOCUSED ON POPULATIONS FROM THIS CONTINENT. THIS EMPHASIZES THE NEED TO BUILD CAPACITY IN AFRICA FOR RESEARCH THAT LEADS TO AN UNDERSTANDING OF THE ASSOCIATION BETWEEN GENETIC, EPIGENETIC AND ENVIRONMENTAL RISK FACTORS FOR NONCOMMUNICABLE DISEASES ON THE CONTINENT. 2015 19 4392 26 MODIFIABLE RISK FACTORS IN PERIODONTAL DISEASE: EPIGENETIC REGULATION OF GENE EXPRESSION IN THE INFLAMMATORY RESPONSE. EPIGENETICS AS A MODIFIABLE RISK FACTOR IN PERIODONTAL DISEASES HAS BEEN INVESTIGATED IN LIGHT OF THE CURRENT KNOWLEDGE OF HOW CHRONIC INFECTION AND INFLAMMATION CAN AFFECT GENE-SPECIFIC EPIGENETIC REPROGRAMMING IN PERIODONTAL TISSUES. EPIGENOMIC PROGRAMMING MIGHT BE PARTICULARLY SENSITIVE TO ENVIRONMENTAL INFLUENCES, AND A COMBINATION OF PHYSIOLOGICAL STRESSORS AND ENVIRONMENTAL EXPOSURES APPEARS TO AFFECT THE EPIGENOMIC PROGRAM ACQUIRED BY A CELL DURING DIFFERENTIATION AND THROUGHOUT THE CELLULAR LINEAGE LIFESPAN. VIRAL AND BACTERIAL INFECTIONS CAN ESTABLISH SEVERAL TYPES OF EPIGENETIC MODIFICATIONS, WHICH SOMETIMES ENGAGE IN A COMPLEX EPIGENETIC CROSSTALK ALSO REFLECTING IN THE ESTABLISHMENT AND PROGRESS OF PERIODONTAL DISEASES. THE INFLAMMATORY AND METABOLIC STATES OF THE PERIODONTAL TISSUES ARE DRIVEN BY THE INFECTIOUS STIMULI, AND THE MAGNITUDE OF THE CELLULAR AND MOLECULAR SIGNATURE RESPONSE IS FURTHER DICTATED BY THE HOST GENETIC AND EPIGENETIC TRAITS ASSOCIATED WITH VARIOUS SYSTEMIC EXPOSURES, INCLUDING SMOKING, OBESITY AND DIABETES/HYPERGLYCEMIA. THIS REVIEW DISCUSSES THE ADVANCES IN EPIGENETICS, FOCUSING ON THE ROLE OF DNA METHYLATION IN THE PATHOGENESIS OF PERIODONTAL DISEASE AND THE POTENTIAL OF EPIGENETIC THERAPY. 2014 20 6823 26 [GENERAL CONCEPTS OF EPIGENETICS: PROJECTIONS IN PAEDIATRICS]. CURRENT EVIDENCE SUPPORTS THE NOTION THAT ALTERATIONS IN INTRAUTERINE GROWTH AND DURING THE FIRST YEARS OF LIFE HAVE A SUBSTANTIAL EFFECT ON THE RISK FOR THE DEVELOPMENT OF CHRONIC DISEASE, WHICH IN SOME CASES IS EVEN HIGHER THAN THOSE DUE TO GENETIC FACTORS. THE PERSISTENCE AND REPRODUCIBILITY OF THE PHENOTYPES ASSOCIATED WITH ALTERED EARLY DEVELOPMENT SUGGEST THE PARTICIPATION OF MECHANISMS THAT WOULD RECORD ENVIRONMENTAL CUES, GENERATING A CELLULAR REPROGRAMMING (I.E., EPIGENETIC MECHANISMS). THIS REVIEW IS AN INTRODUCTION TO A SERIES OF FIVE ARTICLES FOCUSED ON THE PARTICIPATION OF EPIGENETIC MECHANISMS IN THE DEVELOPMENT OF HIGHLY PREVALENT CHRONIC DISEASES (I.E., CARDIOVASCULAR, METABOLIC, ASTHMA/ALLERGIES AND CANCER) AND THEIR ORIGINS IN THE FOETAL AND NEONATAL PERIOD. THIS SERIES OF ARTICLES AIMS TO SHOW THE STATE OF THE ART IN THIS RESEARCH AREA AND PRESENT THE UPCOMING CLUES AND CHALLENGES, IN WHICH PAEDIATRICIANS HAVE A PROMINENT ROLE, DEVELOPING STRATEGIES FOR THE PREVENTION, EARLY DETECTION AND FOLLOW-UP. 2016