1 302 159 AIR POLLUTION EXPOSURE AND AUTO-INFLAMMATORY AND AUTOIMMUNE DISEASES OF THE MUSCULOSKELETAL SYSTEM: A REVIEW OF EPIDEMIOLOGIC AND MECHANISTIC EVIDENCE. AUTO-INFLAMMATORY AND AUTOIMMUNE DISEASES OF THE MUSCULOSKELETAL SYSTEM CAN BE PERCEIVED AS A SPECTRUM OF RHEUMATIC DISEASES, WITH THE JOINTS AND CONNECTIVE TISSUES ARE ERODED SEVERELY THAT PROGRESSIVELY DEVELOP CHRONIC INFLAMMATION AND LESION. A WIDE RANGE OF RISK FACTORS REPRESENTED BY GENETIC AND ENVIRONMENTAL FACTORS HAVE BEEN UNCOVERED BY POPULATION-BASED SURVEYS AND EXPERIMENTAL STUDIES. LATELY, THE EXPOSURE TO AIR POLLUTION HAS BEEN FOUND TO BE POTENTIALLY INVOLVED IN THE MECHANISMS OF OCCURRENCE OR DEVELOPMENT OF SUCH DISEASES, PRINCIPALLY MANIFEST IN OXIDATIVE STRESS, LOCAL AND SYSTEMIC INFLAMMATION, AND EPIGENETIC MODIFICATIONS, AS WELL AS THE MITOCHONDRIAL DYSFUNCTION, WHICH HAS BEEN REPORTED TO PARTICIPATE IN THE INTERMEDIATE LINKS. THE LUNGS MIGHT SERVE AS A STARTING AREA OF AIR POLLUTANTS, WHICH WOULD CAUSE OXIDATIVE STRESS-INDUCED BRONCHIAL-ASSOCIATED LYMPHOID TISSUE (IBALT) TO FURTHER TO INFLUENCE T, B CELLS, AND THE SECRETION OF PRO-INFLAMMATORY CYTOKINES. THE BINDING OF AROMATIC HYDROCARBON RECEPTOR (AHR) TO THE CORRESPONDING CONTAMINANT LIGANDS TENDS TO REGULATE THE REACTION OF TH17 AND TREGS. FURTHERMORE, AIR POLLUTION COMPONENTS MIGHT SPUR ON IMMUNE AND INFLAMMATORY RESPONSES BY DAMAGING MITOCHONDRIA THAT COULD INTERACT WITH AND EXACERBATE OXIDATIVE STRESS AND PRO-INFLAMMATORY CYTOKINES. IN THIS REVIEW, WE FOCUSED ON THE ASSOCIATION BETWEEN AIR POLLUTION AND TYPICAL AUTO-INFLAMMATORY AND AUTOIMMUNE DISEASES OF THE MUSCULOSKELETAL SYSTEM, MAINLY INCLUDING OSTEOARTHRITIS (OA), RHEUMATOID ARTHRITIS (RA), SPONDYLOARTHRITIS (SPA) AND JUVENILE IDIOPATHIC ARTHRITIS (JIA), AND AIM TO COLLATE THE MECHANISMS INVOLVED AND THE POTENTIAL CHANNELS. A COMPLETE SUMMARY AND IN-DEPTH UNDERSTANDING OF THE AUTOIMMUNE AND INFLAMMATORY EFFECTS OF AIR POLLUTION EXPOSURE SHOULD HOPEFULLY CONTRIBUTE NEW PERSPECTIVES ON HOW TO FORMULATE BETTER PUBLIC HEALTH POLICIES TO ALLEVIATE THE ADVERSE HEALTH EFFECTS OF AIR POLLUTANTS. 2023 2 6683 44 UV RADIATION AND AIR POLLUTION AS DRIVERS OF MAJOR AUTOIMMUNE CONDITIONS. AUTOIMMUNE DISEASES COMPRISE A VERY HETEROGENEOUS GROUP OF DISORDERS CHARACTERIZED BY DISRUPTIVE IMMUNE RESPONSES AGAINST SELF-ANTIGENS, CHRONIC MORBIDITY AND INCREASED MORTALITY. THE INCIDENCE AND PREVALENCE OF MAJOR AUTOIMMUNE CONDITIONS ARE PARTICULARLY HIGH IN THE WESTERN WORLD, AT NORTHERN LATITUDES, AND IN INDUSTRIALIZED COUNTRIES. THIS STUDY WILL MAINLY FOCUS ON FIVE MAJOR AUTOIMMUNE CONDITIONS, NAMELY TYPE 1 DIABETES, MULTIPLE SCLEROSIS, INFLAMMATORY BOWEL DISEASES, RHEUMATOID ARTHRITIS, AND AUTOIMMUNE THYROID DISORDERS. EPIDEMIOLOGICAL AND EXPERIMENTAL EVIDENCE SUGGESTS A PROTECTIVE ROLE OF SUNLIGHT EXPOSURE ON THE ETIOLOGY OF MAJOR AUTOIMMUNE CONDITIONS MEDIATED BY THE ENDOGENOUS PRODUCTION OF VITAMIN D AND NITRIC OXIDE. A HISTORICAL PERSPECTIVE SHOWS HOW THE RISE OF ANTHROPOGENIC AIR POLLUTANTS IS TEMPORALLY ASSOCIATED WITH DRAMATIC INCREASES IN INCIDENCE OF THESE CONDITIONS. THE SCATTERING CAUSED BY AMBIENT PARTICULATE MATTER AND THE PRESENCE OF TROPOSPHERIC OZONE CAN REDUCE THE ENDOGENOUS PRODUCTION OF VITAMIN D AND NITRIC OXIDE, WHICH ARE IMPLICATED IN MAINTAINING THE IMMUNE HOMEOSTASIS. AIR POLLUTANTS HAVE DIRECT DETRIMENTAL EFFECTS ON THE HUMAN BODY AND ARE DEEMED RESPONSIBLE OF AN INCREASINGLY HIGHER PORTION OF THE ANNUAL BURDEN OF HUMAN MORBIDITY AND MORTALITY. AIR POLLUTION CONTRIBUTES IN SYSTEMIC INFLAMMATION, ACTIVATES OXIDATIVE PATHWAYS, INDUCES EPIGENETIC ALTERATIONS, AND MODULATES THE FUNCTION AND PHENOTYPE OF DENDRITIC CELLS, TREGS, AND T-CELLS. IN THIS REVIEW, WE PROVIDE EPIDEMIOLOGICAL AND MECHANISTIC INSIGHTS REGARDING THE ROLE OF UV-MEDIATED EFFECTS IN IMMUNITY AND HOW ANTHROPIC-DERIVED AIR POLLUTION MAY AFFECT MAJOR AUTOIMMUNE CONDITIONS THROUGH DIRECT AND INDIRECT MECHANISMS. 2023 3 6034 41 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 4 2027 42 EPIGENETIC CHANGES IN CHRONIC INFLAMMATORY DISEASES. THE NUMBER OF PEOPLE DIAGNOSED WITH CHRONIC INFLAMMATORY DISEASES HAS INCREASED NOTEWORTHY IN THE LAST 40 YEARS. SPONDYLOARTHRITIS (SPA), INFLAMMATORY BOWEL DISEASES (IBD), AND PSORIASIS ARE THE MOST FREQUENT CHRONIC INFLAMMATORY DISEASES, RESULTING FROM A COMBINATION OF GENETIC PREDISPOSITION AND ENVIRONMENTAL FACTORS. EPIGENETIC MODIFICATIONS INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS, AND SMALL AND LONG NONCODING RNAS. THEY ARE INFLUENCED BY ENVIRONMENTAL EXPOSURE, LIFE-STYLE, AND AGING AND HAVE RECENTLY BEEN SHOWN TO BE ALTERED IN MANY COMPLEX DISEASES INCLUDING INFLAMMATORY DISEASES. WHILE EPIGENETIC MODIFICATIONS HAVE BEEN WELL CHARACTERIZED IN OTHER DISEASES SUCH AS CANCER AND AUTOIMMUNE DISEASES, KNOWLEDGE ON CHANGES IN INFLAMMATORY DISEASES IS LAGGING BEHIND WITH SOME DISEASE-SPECIFIC DIFFERENCES. WHILE THE DNA METHYLATION PROFILE OF DIFFERENT CELL TYPES IN PATIENTS WITH IBD HAS BEEN RELATIVELY WELL DESCRIBED, LESS IS KNOWN ON CHANGES IMPLICATED IN PSORIASIS, AND NO SYSTEMATIC GENOME-WIDE STUDIES HAVE SO FAR BEEN PERFORMED IN SPA. IN THIS CHAPTER, WE REVIEW IN DETAIL THE REPORTED CHANGES IN PATTERNS OF DNA METHYLATION AND POSTTRANSLATIONAL HISTONE MODIFICATIONS IN CHRONIC INFLAMMATORY DISEASES HIGHLIGHTING POTENTIAL CONNECTIONS BETWEEN DISEASE-ASSOCIATED PATHOPHYSIOLOGICAL CHANGES SUCH AS THE DYSBIOSIS OF THE MICROBIOME OR GENETIC VARIATIONS ASSOCIATED WITH DISEASE SUSCEPTIBILITY AND THE EPIGENOME. WE ALSO DISCUSS IMPORTANT PARAMETERS OF MEANINGFUL EPIGENETIC STUDIES SUCH AS THE USE OF WELL DEFINED, DISEASE-RELEVANT CELL POPULATIONS, AND ELUDE ON THE POTENTIAL FUTURE OF ENGINEERING OF THE EPIGENOME IN INFLAMMATORY DISEASES. 2017 5 3421 40 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 6 4896 42 OXIDATIVE STRESS IN AIRWAY DISEASES. AIRWAY OXIDATIVE STRESS IS BROADLY DEFINED AS AN IMBALANCE BETWEEN PROOXIDATIVE AND ANTIOXIDATIVE PROCESSES IN THE AIRWAY. GIVEN ITS DIRECT EXPOSURE TO THE ENVIRONMENT, THE LUNG HAS SEVERAL MECHANISMS TO PREVENT AN EXCESSIVE DEGREE OF OXIDATIVE STRESS. BOTH ENZYMATIC AND NONENZYMATIC SYSTEMS CAN BUFFER A WIDE RANGE OF REACTIVE OXIDATIVE SPECIES AND OTHER COMPOUNDS WITH OXIDATIVE POTENTIAL. IN DISEASES LIKE ASTHMA AND CHRONIC OBSTRUCTIVE LUNG DISEASE, AIRWAY OXIDATIVE STRESS CAN OCCUR FROM A NUMBER OF SOURCES, INCLUDING GREATER EXPOSURE TO ENVIRONMENTAL PROOXIDANTS, AIRWAY INFILTRATION OF INFLAMMATORY CELLS, METABOLIC DEREGULATION, AND REDUCED LEVELS OF ANTIOXIDANTS. AIRWAY OXIDATIVE STRESS HAS BEEN ASSOCIATED WITH WORSE DISEASE SEVERITY, REDUCED LUNG FUNCTION, AND EPIGENETIC CHANGES THAT CAN DIMINISH RESPONSE TO STEROIDS. ALTHOUGH OXIDATIVE STRESS HAS BEEN LINKED TO A WIDE RANGE OF ADVERSE BIOLOGICAL EFFECTS, IT HAS ALSO BEEN ASSOCIATED WITH ADAPTIVE RESPONSES AND WITH RESOLUTION OF INFLAMMATION. THEREFORE, MORE THAN BEING AN IMBALANCE WITH A PREDICTABLE THRESHOLD AFTER WHICH DISEASE OR INJURY ENSUES, OXIDATIVE STRESS IS A DYNAMIC AND CONTINUOUS PROCESS. THIS MIGHT EXPLAIN WHY SUPPLEMENTING ANTIOXIDANTS HAS LARGELY FAILED TO IMPROVE DISEASES SUCH AS ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. HOWEVER, THE THERAPEUTIC POTENTIAL OF ANTIOXIDANTS COULD BE GREATLY IMPROVED BY TAKING AN APPROACH THAT CONSIDERS INDIVIDUAL AND ENVIRONMENTAL RISK FACTORS, INSTEAD OF TREATING OXIDATIVE AIRWAY STRESS BROADLY. 2013 7 874 38 CHRONIC ALLERGY SIGNALING: IS IT ALL STRESSED-OUT MITOCHONDRIA? ALLERGIC DISEASES IN GENERAL, AND CHRONIC ALLERGIC INFLAMMATION IN PARTICULAR, ARE ON THE RISE IN THE UNITED STATES AND OTHER DEVELOPED COUNTRIES. THE IDEA OF CHRONIC ALLERGIC DISEASE AS A CHRONIC TYPE 2 IMMUNE RESPONSE HAS BEEN AROUND FOR SEVERAL DECADES. HOWEVER, DATA SUGGEST THAT OTHER MECHANISMS MAY BE IMPORTANT IN CHRONIC DISEASE. THEREFORE, WE BELIEVE IT IS TIME FOR A PARADIGM SHIFT IN UNDERSTANDING THE MECHANISTIC CAUSES OF DISEASE SYMPTOMS IN THESE DISEASES. IN THIS REVIEW, WE HAVE AVOIDED THE CLASSIC CANONICAL PATHWAYS AND FOCUSED ON THE EMERGING IDEA THAT OXIDATIVE STRESS, CHANGES IN IMMUNO-METABOLISM, MITOCHONDRIAL DYSFUNCTION, AND EPIGENETIC CHANGES (PARTICULARLY MICRORNA PROFILE) MAY BE WORKING CONCURRENTLY OR SYNERGISTICALLY TO POTENTIATE ALLERGIC DISEASE SYMPTOMS. FURTHERMORE, WE HAVE ADDRESSED HOW THE EPIDEMIC OF OBESITY EXACERBATES ALLERGIC DISEASE VIA THE DYSREGULATION OF THE AFOREMENTIONED FACTORS. 2022 8 5003 49 PERIODONTITIS IS AN INFLAMMATORY DISEASE OF OXIDATIVE STRESS: WE SHOULD TREAT IT THAT WAY. PERIODONTITIS IS A HIGHLY PREVALENT DISEASE. AS IT PROGRESSES, IT CAUSES SERIOUS MORBIDITY IN THE FORM OF PERIODONTAL ABSCESSES AND TOOTH LOSS AND, IN THE LATTER STAGES, PAIN. IT IS ALSO NOW KNOWN THAT PERIODONTITIS IS STRONGLY ASSOCIATED WITH SEVERAL NONORAL DISEASES. THUS, PATIENTS WITH PERIODONTITIS ARE AT GREATER RISK FOR THE DEVELOPMENT AND/OR EXACERBATION OF DIABETES, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, AND CARDIOVASCULAR DISEASES, AMONG OTHER CONDITIONS. ALTHOUGH IT IS WITHOUT QUESTION THAT SPECIFIC GROUPS OF ORAL BACTERIA WHICH POPULATE DENTAL PLAQUE PLAY A CAUSATIVE ROLE IN THE DEVELOPMENT OF PERIODONTITIS, IT IS NOW THOUGHT THAT ONCE THIS DISEASE HAS BEEN TRIGGERED, OTHER FACTORS PLAY AN EQUAL, AND POSSIBLY MORE IMPORTANT, ROLE IN ITS PROGRESSION, PARTICULARLY IN SEVERE CASES OR IN CASES THAT PROVE DIFFICULT TO TREAT. IN THIS REGARD, WE ALLUDE TO THE HOST RESPONSE, SPECIFICALLY THE NOTION THAT THE HOST, ONCE INFECTED WITH ORAL PERIODONTAL PATHOGENIC BACTERIA, WILL MOUNT A DEFENSE RESPONSE MEDIATED LARGELY THROUGH THE INNATE IMMUNE SYSTEM. THE MOST ABUNDANT CELL TYPE OF THE INNATE IMMUNE SYSTEM - POLYMORPHONUCLEAR NEUTROPHILS - CAN, WHEN PROTECTING THE HOST FROM MICROBIAL INVASION, MOUNT A RESPONSE THAT INCLUDES UPREGULATION OF PROINFLAMMATORY CYTOKINES, MATRIX METALLOPROTEINASES, AND REACTIVE OXYGEN SPECIES, ALL OF WHICH THEN CONTRIBUTE TO THE TISSUE DAMAGE AND LOSS OF TEETH COMMONLY ASSOCIATED WITH PERIODONTITIS. OF THE MECHANISMS REFERRED TO HERE, WE SUGGEST THAT UPREGULATION OF REACTIVE OXYGEN SPECIES MIGHT PLAY ONE OF THE MOST IMPORTANT ROLES IN THE ESTABLISHMENT AND PROGRESSION OF PERIODONTITIS (AS WELL AS IN OTHER DISEASES OF INFLAMMATION) THROUGH THE DEVELOPMENT OF OXIDATIVE STRESS. IN THIS OVERVIEW, WE DISCUSS BOTH INNATE AND EPIGENETIC FACTORS (EG, DIABETES, SMOKING) THAT LEAD TO THE DEVELOPMENT OF OXIDATIVE STRESS. THIS OXIDATIVE STRESS THEN PROVIDES AN ENVIRONMENT CONDUCIVE TO THE DESTRUCTIVE PROCESSES OBSERVED IN PERIODONTITIS. THEREFORE, WE SHALL DESCRIBE SOME OF THE FUNDAMENTAL CHARACTERISTICS OF OXIDATIVE STRESS AND ITS EFFECTS ON THE PERIODONTIUM, DISCUSS THE DISEASES AND OTHER FACTORS THAT CAUSE OXIDATIVE STRESS, AND, FINALLY, REVIEW POTENTIALLY NOVEL THERAPEUTIC APPROACHES FOR THE MANAGEMENT (AND POSSIBLY EVEN THE REVERSAL) OF PERIODONTITIS, WHICH RELY ON THE USE OF THERAPIES, SUCH AS RESVERATROL AND OTHER ANTIOXIDANTS, THAT PROVIDE INCREASED ANTIOXIDANT ACTIVITY IN THE HOST. 2020 9 396 32 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 10 6811 42 [EPIGENETICS, ENVIRONMENT AND ASTHMA]. ASTHMA IS A CHRONIC INFLAMMATORY DISEASE OF THE RESPIRATORY TRACT WITH A COMPLEX GENETIC BACKGROUND INFLUENCED BY THE EXPOSITION TO A SERIES OF ENVIRONMENTAL FACTORS. GENETIC STUDIES CAN ONLY ELUCIDATE PART OF THE HERITABILITY AND SUSCEPTIBILITY OF ASTHMA AND EVEN THOUGH SEVERAL DISEASES HAVE AN EVIDENT GENETIC ETIOLOGY, ONLY A FRACTION OF THE GENES INVOLVED IN THEIR PATHOGENICITY HAVE BEEN IDENTIFIED. THE EPIGENETIC REGULATION OF THE LATTER IS A FACT ONE SHOULD BEAR IN MIND IN ORDER TO EXPLAIN THE MAJOR TRIGGERS OF DISEASES WHOSE UNDERSTANDING IS COMPLICATED, SUCH AS ALLERGIES AND ASTHMA. EXTERNAL STIMULUS SUCH AS NOURISHMENT, STRESS, PHYSICAL ACTIVITY, ATMOSPHERIC POLLUTION, TOBACCO SMOKING AND ALCOHOL DRINKING CAN INDUCE EITHER GENE SILENCING OR GENE EXPRESSION. IN THIS REGARD, EPIGENETICS CAN EXPLAIN HOW THESE ENVIRONMENTAL FACTORS INFLUENCE OUR GENETIC INHERITANCE. THERE IS GROWING EVIDENCE THAT BACKS-UP THE FACT THAT DNA METHYLATION, HISTONE POST-TRANSLATIONAL MODIFICATION AND MICRORNA EXPRESSION ARE INFLUENCED BY THE ENVIRONMENT. THIS HELPS EXPLAINING HOW SEVERAL OF THE RISK FACTORS MENTIONED CONTRIBUTE TO THE DEVELOPMENT AND INHERITANCE OF ASTHMA. IN THIS REVIEW, DIFFERENT ENVIRONMENTAL FACTORS AND THEIR RELATION WITH THE MAIN EPIGENETIC REGULATORY MECHANISMS WILL BE ANALYZED, AS WELL AS THEIR POSSIBLE ROLE IN THE DEVELOPMENT OF ASTHMA. 2014 11 4844 38 ONE YEAR IN REVIEW 2019: PATHOGENESIS OF RHEUMATOID ARTHRITIS. RHEUMATOID ARTHRITIS (RA) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE INFLUENCED BY BOTH GENETIC AND ENVIRONMENTAL FACTORS. OVER THE LAST FEW YEARS, PARTICULAR ATTENTION HAS BEEN GIVEN TO NOVEL GENES AND TO THE CLOSE INTERACTION BETWEEN GENETIC FACTORS AND EPIGENETIC MECHANISMS. RESEARCH HAS ALSO FOCUSED ON THE INFLUENCE OF ENVIRONMENTAL FACTORS ON DISEASE DEVELOPMENT, AND ON NEW MECHANISMS OF THE INNATE AND ADAPTIVE IMMUNE SYSTEM THAT CAN INFLUENCE THE DIFFERENT STAGES OF RA. HOWEVER, THERE ARE STILL SEVERAL ASPECTS OF THE DISEASE THAT NEED FURTHER INVESTIGATION. SHEDDING SOME LIGHT ON THE DIFFERENT ASPECTS OF RA PATHOGENESIS WILL HELP TO IMPROVE THE CURRENT DIAGNOSTIC TOOLS AND TO IDENTIFY NEW TARGETS FOR THE DEVELOPMENT OF DISEASE-MODIFYING THERAPIES. THUS, IN THIS REVIEW WE SUMMARISE THE NEW INSIGHTS IN RA PATHOGENESIS, RESULTING FROM LITERATURE RESEARCH DATA PUBLISHED IN THE LAST YEAR. 2019 12 3402 39 HOW DOES AGE DETERMINE THE DEVELOPMENT OF HUMAN IMMUNE-MEDIATED ARTHRITIS? DOES AGE SUBSTANTIALLY AFFECT THE EMERGENCE OF HUMAN IMMUNE-MEDIATED ARTHRITIS? CHILDREN DO NOT USUALLY DEVELOP IMMUNE-MEDIATED ARTICULAR INFLAMMATION DURING THEIR FIRST YEAR OF LIFE. IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS, THIS APPARENT 'IMMUNE PRIVILEGE' DISINTEGRATES, AND CHRONIC INFLAMMATION IS ASSOCIATED WITH VARIABLE AUTOANTIBODY SIGNATURES AND PATTERNS OF DISEASE THAT RESEMBLE ADULT ARTHRITIS PHENOTYPES. NUMEROUS MECHANISMS MIGHT BE INVOLVED IN THIS SHIFT, INCLUDING GENETIC AND EPIGENETIC PREDISPOSING FACTORS, MATURATION OF THE IMMUNE SYSTEM WITH A PROGRESSIVE MODULATION OF PUTATIVE TOLEROGENIC CONTROLS, PARALLEL DEVELOPMENT OF MICROBIAL DYSBIOSIS, ACCUMULATION OF A PRO-INFLAMMATORY BURDEN DRIVEN BY ENVIRONMENTAL EXPOSURES (THE EXPOSOME) AND COMORBIDITY-RELATED DRIVERS. BY EXPLORING THESE MECHANISMS, WE EXPAND THE DISCUSSION OF THREE (NOT MUTUALLY EXCLUSIVE) HYPOTHESES ON HOW THESE FACTORS CAN CONTRIBUTE TO THE DIFFERENCES AND SIMILARITIES BETWEEN THE LOSS OF IMMUNE TOLERANCE IN CHILDREN AND THE DEVELOPMENT OF ESTABLISHED IMMUNE-MEDIATED ARTHRITIS IN ADULTS. THESE THREE HYPOTHESES RELATE TO A CRITICAL WINDOW IN GENETICS AND EPIGENETICS, IMMUNE MATURATION, AND THE ACCUMULATION OF BURDEN. THE VARIED MANIFESTATION OF THE UNDERLYING MECHANISMS AMONG INDIVIDUALS IS ONLY BEGINNING TO BE CLARIFIED, BUT THE ESTABLISHMENT OF A FRAMEWORK CAN FACILITATE THE DEVELOPMENT OF AN INTEGRATED UNDERSTANDING OF THE PATHOGENESIS OF ARTHRITIS ACROSS ALL AGES. 2022 13 4393 35 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 14 1453 31 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 15 5033 45 PESTICIDES AND HUMAN CHRONIC DISEASES: EVIDENCES, MECHANISMS, AND PERSPECTIVES. ALONG WITH THE WIDE USE OF PESTICIDES IN THE WORLD, THE CONCERNS OVER THEIR HEALTH IMPACTS ARE RAPIDLY GROWING. THERE IS A HUGE BODY OF EVIDENCE ON THE RELATION BETWEEN EXPOSURE TO PESTICIDES AND ELEVATED RATE OF CHRONIC DISEASES SUCH AS DIFFERENT TYPES OF CANCERS, DIABETES, NEURODEGENERATIVE DISORDERS LIKE PARKINSON, ALZHEIMER, AND AMYOTROPHIC LATERAL SCLEROSIS (ALS), BIRTH DEFECTS, AND REPRODUCTIVE DISORDERS. THERE IS ALSO CIRCUMSTANTIAL EVIDENCE ON THE ASSOCIATION OF EXPOSURE TO PESTICIDES WITH SOME OTHER CHRONIC DISEASES LIKE RESPIRATORY PROBLEMS, PARTICULARLY ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), CARDIOVASCULAR DISEASE SUCH AS ATHEROSCLEROSIS AND CORONARY ARTERY DISEASE, CHRONIC NEPHROPATHIES, AUTOIMMUNE DISEASES LIKE SYSTEMIC LUPUS ERYTHEMATOUS AND RHEUMATOID ARTHRITIS, CHRONIC FATIGUE SYNDROME, AND AGING. THE COMMON FEATURE OF CHRONIC DISORDERS IS A DISTURBANCE IN CELLULAR HOMEOSTASIS, WHICH CAN BE INDUCED VIA PESTICIDES' PRIMARY ACTION LIKE PERTURBATION OF ION CHANNELS, ENZYMES, RECEPTORS, ETC., OR CAN AS WELL BE MEDIATED VIA PATHWAYS OTHER THAN THE MAIN MECHANISM. IN THIS REVIEW, WE PRESENT THE HIGHLIGHTED EVIDENCE ON THE ASSOCIATION OF PESTICIDE'S EXPOSURE WITH THE INCIDENCE OF CHRONIC DISEASES AND INTRODUCE GENETIC DAMAGES, EPIGENETIC MODIFICATIONS, ENDOCRINE DISRUPTION, MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, ENDOPLASMIC RETICULUM STRESS AND UNFOLDED PROTEIN RESPONSE (UPR), IMPAIRMENT OF UBIQUITIN PROTEASOME SYSTEM, AND DEFECTIVE AUTOPHAGY AS THE EFFECTIVE MECHANISMS OF ACTION. 2013 16 5552 37 ROLE OF EPIGENETICS IN THE PATHOGENESIS OF ASTHMA. ASTHMA IS A COMPLEX, HETEROGENEOUS AND CHRONIC AIRWAY INFLAMMATORY DISEASE WITH DIFFERENT CLINICAL PHENOTYPES CAUSED BY DIVERSE TRIGGERS AND PATHOPHYSIOLOGICAL MECHANISMS. ASTHMA HERITABILITY HAS BEEN ESTABLISHED IN MANY GENETIC STUDIES BUT IT IS EVIDENT THAT ONLY GENETIC ELEMENTS ARE NOT RESPONSIBLE FOR THE DEVELOPMENT OF ASTHMA. INCREASING RATE OF ASTHMA INCIDENCE DURING PAST DECADES HAS IMPLICATED THE ROLE OF EPIGENETICS IN DEVELOPMENT OF ASTHMA. ENVIRONMENTAL FACTORS PERFORM AS INITIATOR SIGNALS THROUGH EPIGENETIC MECHANISMS. THREE EPIGENETIC MECHANISMS HAVE BEEN IDENTIFIED, INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS, AND SMALL NONCODING RNAS. THESE MECHANISMS REGULATE THE IMMUNE RESPONSES AND INFLAMMATORY GENES EXPRESSION IN ASTHMA AND ALLERGY. THIS REVIEW EXPLAINS THE ROLE OF EPIGENETIC MODIFICATIONS IN CONTROLLING TH2 RESPONSE AND IGE PRODUCTION IN ASTHMA AND ALSO BRIEFLY OVERVIEWS THE ROLE OF ENVIRONMENTAL FACTORS SUCH AS POLLUTIONS, ALLERGENS, PRENATAL EXPOSURES AND DIET IN DEVELOPING ASTHMA. RECOGNIZING ENVIRONMENTAL RISK FACTORS AND THEIR EFFECTS ON EPIGENETIC MECHANISMS WOULD BE OF GREAT INTEREST FOR PROGNOSTIC AND PREVENTIVE ASPECT IN TREATMENT OF ASTHMA. 2017 17 4273 40 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 18 838 39 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 19 3123 40 GETTING AN INSIGHT INTO THE COMPLEXITY OF MAJOR CHRONIC INFLAMMATORY AND DEGENERATIVE DISEASES: A POTENTIAL NEW SYSTEMIC APPROACH TO THEIR TREATMENT. AS THE MODERN SOCIETY IS TROUBLED BY MULTI-FACTORIAL DISEASES, RESEARCH HAS BEEN CONDUCTED ON COMPLEX REALITIES INCLUDING CHRONIC INFLAMMATION, CANCER, OBESITY, HIV INFECTION, METABOLIC SYNDROME AND ITS DETRIMENTAL CARDIOVASCULAR COMPLICATIONS AS WELL AS DEPRESSION AND OTHER BRAIN DISORDERS. DETERIORATION OF CRUCIAL HOMEOSTATIC MECHANISMS IN SUCH DISEASES INVARIABLY RESULTS IN ACTIVATION OF INFLAMMATORY MEDIATORS, CHRONIC INFLAMMATION, LOSS IN IMMUNOLOGICAL FUNCTION, INCREASED SUSCEPTIBILITY TO DISEASES, ALTERATION OF METABOLISM, DECREASE OF ENERGY PRODUCTION AND NEURO-COGNITIVE DECLINE. REGULATION OF GENES EXPRESSION BY EPIGENETIC CODE IS THE DOMINANT MECHANISM FOR THE TRANSDUCTION OF ENVIRONMENTAL INPUTS, SUCH AS STRESS AND INFLAMMATION TO LASTING PHYSIOLOGICAL CHANGES. ACUTE AND CHRONIC STRESS DETERMINES DNA METHYLATION AND HISTONE MODIFICATIONS IN BRAIN REGIONS WHICH MAY CONTRIBUTE TO NEURO-DEGENERATIVE DISORDERS. NUCLEAR GLUCOCORTICOIDS RECEPTOR INTERACTS WITH THE EPIGENOMA RESULTING IN A CORTISOL RESISTANCE STATUS ASSOCIATED WITH A DETERIORATION OF THE METABOLIC AND IMMUNE FUNCTIONS. GONADAL STEROIDS RECEPTORS HAVE A SIMILAR CAPACITY TO PRODUCE EPIGENOMIC REORGANIZATION OF CHROMATINE STRUCTURE. EPIGENOMIC-INDUCED REDUCTION IN IMMUNE CELLS TELOMERES LENGTH HAS BEEN OBSERVED IN MANY DEGENERATIVE DISEASES, INCLUDING ALL TYPES OF CANCER. THE FINAL RESULT OF THESE EPIGENETIC ALTERATIONS IS A SERIOUS DAMAGE TO THE NEURO-ENDOCRINE-IMMUNE-METABOLIC ADAPTIVE SYSTEMS. IN THIS STUDY, WE PROPOSE A TREATMENT WITH STEM CELLS DIFFERENTIATION STAGE FACTORS TAKEN FROM ZEBRAFISH EMBRYOS WHICH ARE ABLE TO REGULATE THE GENES EXPRESSION OF NORMAL AND PATHOLOGICAL STEM CELLS IN A DIFFERENT SPECIFIC WAY. 2015 20 4901 26 OXIDATIVE, INFLAMMATORY, GENETIC, AND EPIGENETIC BIOMARKERS ASSOCIATED WITH CHRONIC OBSTRUCTIVE PULMONARY DISORDER. A LARGE BODY OF EVIDENCE INDICATES THAT CHRONIC OBSTRUCTIVE PULMONARY DISORDER (COPD) IS ACCOMPANIED BY OXIDATIVE STRESS AND INFLAMMATORY AND GENETIC PATHWAYS. EPIDEMIOLOGICAL STUDIES INDICATE THAT COPD IS A MAJOR CAUSE OF MORTALITY AND MORBIDITY IN THE WORLD. RECENT RESEARCH DEVELOPMENT IN COPD FOCUSES ON ACCELERATED AGING AND VARIOUS OXIDATIVE STRESS BIOMARKERS. IT INVOLVES THE CLINICAL MANIFESTATION OF THE DISEASE PROCESS AND MAY ALSO CONTAIN BIOCHEMICAL, IMMUNOLOGICAL, PHYSIOLOGICAL, MORPHOLOGICAL, AND GENETIC ASPECTS THAT ADD TO THE PROGRESSIVENESS OF THE DISEASE. HEREIN, WE SUMMARIZE FINDINGS THAT HIGHLIGHT THE ROLE OF DIMENSIONS OF COPD IN THE INVESTIGATION OF OXIDATIVE STRESS, INFLAMMATORY RESPONSES, GENETIC AND EPIGENETIC STUDIES, AND PHARMACOLOGICAL AND DIETARY ANTIOXIDANT INTERVENTION. 2019