1 6340 107 THE ROLE OF EPIGENETIC FACTORS IN PSORIASIS. PSORIASIS IS A CHRONIC, SYSTEMIC, IMMUNE-MEDIATED DISEASE WITH AN INCIDENCE OF APPROXIMATELY 2%. THE PATHOGENESIS OF THE DISEASE IS COMPLEX AND NOT YET FULLY UNDERSTOOD. GENETIC FACTORS PLAY A SIGNIFICANT ROLE IN THE PATHOGENESIS OF THE DISEASE. IN PREDISPOSED INDIVIDUALS, MULTIPLE TRIGGER FACTORS MAY CONTRIBUTE TO DISEASE ONSET AND EXACERBATIONS OF SYMPTOMS. ENVIRONMENTAL FACTORS (STRESS, INFECTIONS, CERTAIN MEDICATIONS, NICOTINISM, ALCOHOL, OBESITY) PLAY A SIGNIFICANT ROLE IN THE PATHOGENESIS OF PSORIASIS. IN ADDITION, EPIGENETIC MECHANISMS ARE CONSIDERED RESULT IN MODULATION OF INDIVIDUAL GENE EXPRESSION AND AN INCREASED LIKELIHOOD OF THE DISEASE. STUDIES HIGHLIGHT THE SIGNIFICANT ROLE OF EPIGENETIC FACTORS IN THE ETIOLOGY AND PATHOGENESIS OF PSORIASIS. EPIGENETIC MECHANISMS IN PSORIASIS INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS AND NON-CODING RNAS. EPIGENETIC MECHANISMS INDUCE GENE EXPRESSION CHANGES UNDER THE INFLUENCE OF CHEMICAL MODIFICATIONS OF DNA AND HISTONES, WHICH ALTER CHROMATIN STRUCTURE AND ACTIVATE TRANSCRIPTION FACTORS OF SELECTED GENES, THUS LEADING TO TRANSLATION OF NEW MRNA WITHOUT AFFECTING THE DNA SEQUENCE. EPIGENETIC FACTORS CAN REGULATE GENE EXPRESSION AT THE TRANSCRIPTIONAL (VIA HISTONE MODIFICATION, DNA METHYLATION) AND POSTTRANSCRIPTIONAL LEVELS (VIA MICRORNAS AND LONG NON-CODING RNAS). THIS STUDY AIMS TO PRESENT AND DISCUSS THE DIFFERENT EPIGENETIC MECHANISMS IN PSORIASIS BASED ON A REVIEW OF THE AVAILABLE LITERATURE. 2021 2 1172 40 CONTRIBUTION OF THE ENVIRONMENT, EPIGENETIC MECHANISMS AND NON-CODING RNAS IN PSORIASIS. DESPITE THE INCREASING RESEARCH AND CLINICAL INTEREST IN THE PREDISPOSITION OF PSORIASIS, A CHRONIC INFLAMMATORY SKIN DISEASE, THE MULTITUDE OF GENETIC AND ENVIRONMENTAL FACTORS INVOLVED IN ITS PATHOGENESIS REMAIN UNCLEAR. THIS COMPLEXITY IS FURTHER EXACERBATED BY THE SEVERAL CELL TYPES THAT ARE IMPLICATED IN PSORIASIS'S PROGRESSION, INCLUDING KERATINOCYTES, MELANOCYTES AND VARIOUS IMMUNE CELL TYPES. THE OBSERVED INTERACTIONS BETWEEN THE GENETIC SUBSTRATE AND THE ENVIRONMENT LEAD TO EPIGENETIC ALTERATIONS THAT DIRECTLY OR INDIRECTLY AFFECT GENE EXPRESSION. CHANGES IN DNA METHYLATION AND HISTONE MODIFICATIONS THAT ALTER DNA-BINDING SITE ACCESSIBILITY, AS WELL AS NON-CODING RNAS IMPLICATED IN THE POST-TRANSCRIPTIONAL REGULATION, ARE MECHANISMS OF GENE TRANSCRIPTIONAL ACTIVITY MODIFICATION AND THEREFORE AFFECT THE PATHWAYS INVOLVED IN THE PATHOGENESIS OF PSORIASIS. IN THIS REVIEW, WE SUMMARIZE THE RESEARCH CONDUCTED ON THE ENVIRONMENTAL FACTORS CONTRIBUTING TO THE DISEASE ONSET, EPIGENETIC MODIFICATIONS AND NON-CODING RNAS EXHIBITING DEREGULATION IN PSORIASIS, AND WE FURTHER CATEGORIZE THEM BASED ON THE UNDER-STUDY CELL TYPES. WE ALSO ASSESS THE RECENT LITERATURE CONSIDERING THERAPEUTIC APPLICATIONS TARGETING MOLECULES THAT COMPROMISE THE EPIGENOME, AS A WAY TO SUPPRESS THE INFLAMMATORY CUTANEOUS CASCADE. 2022 3 2591 34 EPIGENETICS OF PSORIASIS. PSORIASIS IS A CHRONIC AND RECURRENT INFLAMMATORY SKIN DISEASE, INVOLVING THE RAPID PROLIFERATION AND ABNORMAL DIFFERENTIATION OF KERATINOCYTES AND ACTIVATION OF T CELLS. IT IS GENERALLY ACCEPTED THAT THE CENTRAL PATHOGENESIS OF PSORIASIS IS A T CELL-DOMINANT IMMUNE DISORDER AFFECTED BY MULTIPLE FACTORS INCLUDING GENETIC SUSCEPTIBILITY, ENVIRONMENTAL FACTORS, INNATE AND ADAPTIVE IMMUNE RESPONSES, ETC. HOWEVER, THE EXACT ETIOLOGY IS LARGELY UNKNOWN. IN RECENT YEARS, EPIGENETIC INVOLVEMENTS, SUCH AS THE DNA METHYLATION, CHROMATIN MODIFICATIONS, AND NONCODING RNA REGULATION ARE REPORTED TO BE CRITICAL FOR THE PATHOGENESIS OF PSORIASIS. HOWEVER, THE INTERPLAY BETWEEN THESE FACTORS HAS ONLY RECENTLY BEEN STARTED TO BE UNRAVELED. NOTABLY, INHIBITORS OF ENZYMES THAT WORK IN EPIGENETIC MODIFICATIONS, SUCH AS DNA METHYLTRANSFERASES AND HISTONE DEACETYLASES, ARE BEGINNING TO APPEAR IN THE CLINICAL SETTING TO RESTORE NORMAL EPIGENETIC PATTERNS (GENERALI ET AL. IN J AUTOIMMUN 83:51-61, 2017), PROVIDING NOVEL THERAPEUTIC POTENTIAL AS NOVEL TREATMENT TARGETS FOR PSORIASIS. INDEED, MEDICATIONS PREVIOUSLY USED TO TREAT AUTOIMMUNE DISEASES HAVE LATER BEEN DISCOVERED TO EXERT THEIR ACTION VIA EPIGENETIC MECHANISMS. HEREIN, WE REVIEW THE FINDINGS ON EPIGENETICS ASSOCIATED WITH PSORIASIS, AND DISCUSS FUTURE PERSPECTIVES IN THIS FIELD. 2020 4 6114 46 THE EPIGENETIC CONTRIBUTION TO THE PATHOGENESIS OF PSORIASIS: RECENT ADVANCES. PSORIASIS IS DEFINED AS A CHRONIC AUTOIMMUNE DISORDER OF THE SKIN IN WHICH ABNORMAL PROLIFERATION AND DIFFERENTIATION OF KERATINOCYTES ARE BLAMED AS THE CENTRAL CULPRIT OF DISEASE ETIOPATHOGENESIS. A COMPLEX INTERPLAY BETWEEN ENVIRONMENTAL FACTORS AND GENETIC RISK FACTORS HAS BEEN SUGGESTED TO TRIGGER THE DISEASE. HOWEVER, EPIGENETIC REGULATION APPEARS TO CONNECT EXTERNAL STIMULI AND GENETIC ABNORMALITIES IN THE DEVELOPMENT OF PSORIASIS. THE DISCORDANCE IN THE PREVALENCE OF PSORIASIS BETWEEN MONOZYGOTIC TWINS AND ENVIRONMENTAL FACTORS THAT CONTRIBUTE TO ITS ONSET HAVE CAUSED A PARADIGM SHIFT REGARDING THE MECHANISMS UNDERLYING THE PATHOGENESIS OF THIS DISEASE. EPIGENETIC DYSREGULATION MAY BE INVOLVED IN ABERRANCIES OF KERATINOCYTE DIFFERENTIATION, T-CELL ACTIVATION, AND OTHER PLAUSIBLE CELLS, LEADING TO THE INITIATION AND PERPETUATION OF PSORIASIS. EPIGENETICS IS CHARACTERIZED BY HERITABLE ALTERATIONS IN THE TRANSCRIPTION OF GENES WITHOUT NUCLEOTIDE CHANGE AND IS COMMONLY CONSIDERED AT THREE LEVELS, I.E., DNA METHYLATION, HISTONE MODIFICATIONS, AND MICRORNAS. TO DATE, SCIENTIFIC EVIDENCE HAS INDICATED ABNORMAL DNA METHYLATION, HISTONE MODIFICATIONS, AND NON-CODING RNA TRANSCRIPTION IN PSORIATIC PATIENTS. IN ORDER TO REVERSE ABERRANT EPIGENETIC CHANGES IN PSORIASIS PATIENTS, SEVERAL COMPOUNDS AND DRUGS (EPI-DRUGS) HAVE BEEN DEVELOPED TO AFFECT THE MAJOR ENZYMES INVOLVED IN THE METHYLATION OF DNA, OR THE ACETYLATION OF HISTONES, WHICH AIM TO CORRECT THE ABERRANT METHYLATION AND ACETYLATION PATTERNS. A NUMBER OF CLINICAL TRIALS HAVE SUGGESTED THE THERAPEUTIC POTENTIAL OF SUCH DRUGS IN THE TREATMENT OF PSORIASIS. IN THE PRESENT REVIEW, WE ATTEMPT TO CLARIFY RECENT FINDINGS WITH RESPECT TO EPIGENETIC IRREGULARITIES IN PSORIASIS AND DISCUSS FUTURE CHALLENGES. 2023 5 2333 36 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 6 2070 29 EPIGENETIC CONTROL OF SKIN IMMUNITY. EPIGENETICS HAS BEEN WELL UNDERSTOOD FOR ITS ROLE IN CELL DEVELOPMENT; HOWEVER, IT IS NOW KNOWN TO REGULATE MANY PROCESSES INVOLVED IN IMMUNE CELL ACTIVATION IN A VARIETY OF CELLS. THE SKIN MAINTAINS HOMEOSTASIS VIA CROSSTALK BETWEEN IMMUNE AND NON-IMMUNE CELLS. DISRUPTION OF NORMAL EPIGENETIC REGULATION IN THESE CELLS MAY ALTER THE TRANSCRIPTION OF IMMUNE-REGULATORY FACTORS AND AFFECT THE IMMUNOLOGICAL BALANCE IN THE SKIN. THIS REVIEW SUMMARIZES RECENT EVIDENCE FOR THE EPIGENETIC REGULATION OF SKIN IMMUNITY. MUCH OF WHAT IS KNOWN ABOUT EPIGENETIC INVOLVEMENT IN SKIN IMMUNITY IS ASSOCIATED WITH DNA METHYLATION. THIS REVIEW FOCUSES ON EPIGENETIC REGULATION OF HISTONE MODIFICATION AND CHROMATIN REMODELING AND DESCRIBES THEIR ROLE IN THE TRANSCRIPTIONAL REGULATION OF IMMUNE-REGULATORY FACTORS. WHILE MUCH IS STILL UNKNOWN REGARDING THE REGULATION OF SKIN IMMUNITY VIA HISTONE MODIFICATION OR CHROMATIN REMODELING, THESE PROCESSES MAY UNDERLIE THE PATHOGENESIS OF CHRONIC CUTANEOUS IMMUNE DISORDERS. 2023 7 3703 24 INFLAMMATORY SIGNALLING AS MEDIATOR OF EPIGENETIC MODULATION IN TISSUE-SPECIFIC CHRONIC INFLAMMATION. RECENT SUCCESSES OF THERAPEUTIC INTERVENTION IN CHRONIC INFLAMMATORY DISEASES USING EPIGENETIC MODIFIERS SUCH AS HISTONE DEACETYLASE INHIBITORS AND INHIBITORS OF DNA METHYLATION SUGGEST THAT EPIGENETIC REPROGRAMMING PLAYS A ROLE IN THE AETIOLOGY OF THESE DISEASES. THE EPIGENETIC SIGNATURE OF A GIVEN IMMUNE CELL IS REFLECTED IN THE HISTORY OF MODIFICATIONS FROM DIFFERENT SIGNALS THE CELL HAS BEEN SUBJECTED TO DURING DIFFERENTIATION. LIKE OTHER CELLS, DIFFERENTIATING IMMUNE CELLS ARE DEPENDENT ON A COMPLEX COMBINATION OF INTER- AND INTRACELL SIGNALLING AS WELL AS TRANSCRIPTION MACHINERIES TO MODULATE THEIR EPIGENOMES IN ORDER TO MEDIATE DIFFERENTIATION. DESPITE EXTENSIVE RESEARCH INTO THESE PROCESSES, THE LINK BETWEEN CELLULAR SIGNALLING AND EPIGENETIC MODULATION REMAINS POORLY UNDERSTOOD. HERE, WE REVIEW RECENT PROGRESS AND DISCUSS KEY FACTORS DRIVING EPIGENETIC MODULATION IN CHRONIC INFLAMMATION. 2009 8 2523 39 EPIGENETICS AND THE TRANSITION FROM ACUTE TO CHRONIC PAIN. OBJECTIVE: THE OBJECTIVE OF THIS STUDY WAS TO REVIEW THE EPIGENETIC MODIFICATIONS INVOLVED IN THE TRANSITION FROM ACUTE TO CHRONIC PAIN AND TO IDENTIFY POTENTIAL TARGETS FOR THE DEVELOPMENT OF NOVEL, INDIVIDUALIZED PAIN THERAPEUTICS. BACKGROUND: EPIGENETICS IS THE STUDY OF HERITABLE MODIFICATIONS IN GENE EXPRESSION AND PHENOTYPE THAT DO NOT REQUIRE A CHANGE IN GENETIC SEQUENCE TO MANIFEST THEIR EFFECTS. ENVIRONMENTAL TOXINS, MEDICATIONS, DIET, AND PSYCHOLOGICAL STRESSES CAN ALTER EPIGENETIC PROCESSES SUCH AS DNA METHYLATION, HISTONE ACETYLATION, AND RNA INTERFERENCE. AS EPIGENETIC MODIFICATIONS POTENTIALLY PLAY AN IMPORTANT ROLE IN INFLAMMATORY CYTOKINE METABOLISM, STEROID RESPONSIVENESS, AND OPIOID SENSITIVITY, THEY ARE LIKELY KEY FACTORS IN THE DEVELOPMENT OF CHRONIC PAIN. ALTHOUGH OUR KNOWLEDGE OF THE HUMAN GENETIC CODE AND DISEASE-ASSOCIATED POLYMORPHISMS HAS GROWN SIGNIFICANTLY IN THE PAST DECADE, WE HAVE NOT YET BEEN ABLE TO ELUCIDATE THE MECHANISMS THAT LEAD TO THE DEVELOPMENT OF PERSISTENT PAIN AFTER NERVE INJURY OR SURGERY. DESIGN: THIS IS A FOCUSED LITERATURE REVIEW OF EPIGENETIC SCIENCE AND ITS RELATIONSHIP TO CHRONIC PAIN. RESULTS: SIGNIFICANT LABORATORY AND CLINICAL DATA SUPPORT THE NOTION THAT EPIGENETIC MODIFICATIONS ARE AFFECTED BY THE ENVIRONMENT AND LEAD TO DIFFERENTIAL GENE EXPRESSION. SIMILAR TO MECHANISMS INVOLVED IN THE DEVELOPMENT OF CANCER, NEURODEGENERATIVE DISEASE, AND INFLAMMATORY DISORDERS, THE LITERATURE ENDORSES AN IMPORTANT POTENTIAL ROLE FOR EPIGENETICS IN CHRONIC PAIN. CONCLUSIONS: EPIGENETIC ANALYSIS MAY IDENTIFY MECHANISMS CRITICAL TO THE DEVELOPMENT OF CHRONIC PAIN AFTER INJURY, AND MAY PROVIDE NEW PATHWAYS AND TARGET MECHANISMS FOR FUTURE DRUG DEVELOPMENT AND INDIVIDUALIZED MEDICINE. 2012 9 2501 36 EPIGENETICS AND ITS ROLE IN PERIODONTAL DISEASES: A STATE-OF-THE-ART REVIEW. THE IMMUNE RESPONSE TO ORAL BACTERIA AND THE SUBSEQUENT ACTIVATION OF INFLAMMATORY SIGNALING IS NOT ONLY DEPENDENT ON GENETIC FACTORS. THE IMPORTANCE OF SO-CALLED EPIGENETIC MECHANISMS PRESENTS ADDITIONAL REGULATORY PATHWAYS OF GENES INVOLVED IN MAINTAINING CHRONIC INFLAMMATION, INCLUDING GINGIVITIS AND PERIODONTITIS. THE TERM EPIGENETICS RELATES TO CHANGES IN GENE EXPRESSION THAT ARE NOT ENCODED IN THE DNA SEQUENCE ITSELF AND INCLUDE CHEMICAL ALTERATIONS OF DNA AND ITS ASSOCIATED PROTEINS. THESE CHANGES LEAD TO REMODELING OF THE CHROMATIN AND SUBSEQUENT ACTIVATION OR INACTIVATION OF A GENE. EPIGENETIC MECHANISMS HAVE BEEN FOUND TO CONTRIBUTE TO DISEASE, INCLUDING CANCER AND AUTOIMMUNE OR INFLAMMATORY DISEASES. IN THIS STATE-OF-THE ART REVIEW, THE AUTHORS PROVIDE THE LATEST FINDINGS ON THE INVOLVEMENT OF EPIGENETIC MODIFICATIONS IN THE DEVELOPMENT OF PERIODONTAL DISEASE AND PRESENT EMERGING THERAPEUTIC STRATEGIES AIMED AT EPIGENETIC TARGETS (EPIDRUGS) ASSOCIATED WITH THE DISRUPTION OF TISSUE HOMEOSTASIS AND THE DEVELOPMENT OF PERIODONTITIS. 2015 10 2532 37 EPIGENETICS IN ATHEROSCLEROSIS AND INFLAMMATION. ATHEROSCLEROSIS IS A MULTIFACTORIAL DISEASE WITH A SEVERE BURDEN ON WESTERN SOCIETY. RECENT INSIGHTS INTO THE PATHOGENESIS OF ATHEROSCLEROSIS UNDERSCORE THE IMPORTANCE OF CHRONIC INFLAMMATION IN BOTH THE INITIATION AND PROGRESSION OF VASCULAR REMODELLING. EXPRESSION OF IMMUNOREGULATORY MOLECULES BY VASCULAR WALL COMPONENTS WITHIN THE ATHEROSCLEROTIC LESIONS IS ACCORDINGLY THOUGHT TO CONTRIBUTE TO THE ONGOING INFLAMMATORY PROCESS. BESIDES GENE REGULATORY PROTEINS (TRANSCRIPTION FACTORS), EPIGENETIC MECHANISMS ALSO PLAY AN ESSENTIAL AND FUNDAMENTAL ROLE IN THE TRANSCRIPTIONAL CONTROL OF GENE EXPRESSION. THESE EPIGENETIC MECHANISMS CHANGE THE ACCESSIBILITY OF CHROMATIN BY DNA METHYLATION AND HISTONE MODIFICATIONS. EPIGENETIC MODULATORS ARE THUS CRITICALLY INVOLVED IN THE REGULATION OF VASCULAR, IMMUNE AND TISSUE-SPECIFIC GENE EXPRESSION WITHIN THE ATHEROSCLEROTIC LESION. IMPORTANTLY, EPIGENETIC PROCESSES ARE REVERSIBLE AND MAY PROVIDE AN EXCELLENT THERAPEUTIC TARGET. THE CONCEPT OF EPIGENETIC REGULATION IS GRADUALLY BEING RECOGNIZED AS AN IMPORTANT FACTOR IN THE PATHOGENESIS OF ATHEROSCLEROSIS. RECENT RESEARCH PROVIDES AN ESSENTIAL LINK BETWEEN INFLAMMATION AND REPROGRAMMING OF THE EPIGENOME. IN THIS REVIEW WE THEREFORE DISCUSS THE BASIS OF EPIGENETIC REGULATION - AND THE CONTRIBUTION THEREOF IN THE REGULATION OF INFLAMMATORY PROCESSES IN GENERAL AND DURING ATHEROSCLEROSIS IN PARTICULAR. MOREOVER WE HIGHLIGHT POTENTIAL THERAPEUTIC INTERVENTIONS BASED ON EPIGENETIC MECHANISMS. 2010 11 6288 41 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 12 5325 33 PULMONARY PATHOGEN-INDUCED EPIGENETIC MODIFICATIONS. EPIGENETICS GENERALLY INVOLVES GENETIC CONTROL BY FACTORS OTHER THAN OUR OWN DNA SEQUENCE. RECENT RESEARCH HAS FOCUSED ON DELINEATING THE MECHANISMS OF TWO MAJOR EPIGENETIC PHENOMENA: DNA METHYLATION AND HISTONE MODIFICATION. AS EPIGENETICS INVOLVES MANY CELLULAR PROCESSES, IT IS NO SURPRISE THAT IT CAN ALSO INFLUENCE DISEASE-ASSOCIATED GENE EXPRESSION. A DIRECT LINK BETWEEN RESPIRATORY INFECTIONS, HOST CELL EPIGENETIC REGULATIONS, AND CHRONIC LUNG DISEASES IS STILL UNKNOWN. RECENT STUDIES HAVE REVEALED BACTERIUM- OR VIRUS-INDUCED EPIGENETIC CHANGES IN THE HOST CELLS. IN THIS REVIEW, WE FOCUSED ON RESPIRATORY PATHOGENS (VIRUSES, BACTERIA, AND FUNGI) INDUCED EPIGENETIC MODULATIONS (DNA METHYLATION AND HISTONE MODIFICATION) THAT MAY CONTRIBUTE TO LUNG DISEASE PATHOPHYSIOLOGY BY PROMOTING HOST DEFENSE OR ALLOWING PATHOGEN PERSISTENCE. 2023 13 4961 37 PATHOGENESIS OF PSORIASIS IN THE "OMIC" ERA. PART II. GENETIC, GENOMIC AND EPIGENETIC CHANGES IN PSORIASIS. PSORIASIS IS A MULTIFACTORIAL DISEASE IN WHICH GENETIC, ENVIRONMENTAL AND EPIGENETIC FACTORS REGULATING GENE EXPRESSION PLAY A KEY ROLE. IN THE "GENOMIC ERA", GENOME-WIDE ASSOCIATION STUDIES TOGETHER WITH TARGET GENOTYPING PLATFORMS PERFORMED IN DIFFERENT ETHNIC POPULATIONS HAVE FOUND MORE THAN 50 GENETIC SUSCEPTIBLE MARKERS ASSOCIATED WITH THE RISK OF PSORIASIS WHICH HAVE BEEN IDENTIFIED SO FAR. UP TILL NOW, THE STRONGEST ASSOCIATION WITH THE RISK OF THE DISEASE HAS BEEN PROVED FOR HLA-C*06 GENE. THE MAJORITY OF OTHER PSORIASIS RISK SNPS ARE SITUATED NEAR THE GENES ENCODING MOLECULES INVOLVED IN ADAPTIVE AND INNATE IMMUNITY, AND SKIN BARRIER FUNCTION. MANY CONTEMPORARY STUDIES INDICATE THAT THE EPIGENETIC CHANGES: HISTONE MODIFICATION, PROMOTER METHYLATIONS, LONG NON-CODING AND MICRO-RNA HYPEREXPRESSION ARE CONSIDERED AS FACTORS CONTRIBUTING TO PSORIASIS PATHOGENESIS AS THEY REGULATE ABNORMAL KERATINOCYTE DIFFERENTIATION AND PROLIFERATION, ABERRANT KERATINOCYTES - INFLAMMATORY CELLS COMMUNICATION, NEOANGIOGENESIS AND CHRONIC INFLAMMATION. THE CIRCULATING MIRNAS DETECTED IN THE BLOOD MAY BECOME SPECIFIC MARKERS IN THE DIAGNOSIS, PROGNOSIS AND RESPONSE TO THE TREATMENT OF THE DISEASE. THE INHIBITION OF EXPRESSION IN SELECTED MIRNAS MAY BE A NEW PROMISING THERAPY OPTION FOR PATIENTS WITH PSORIASIS. 2020 14 6533 35 TRANSCRIPTIONAL REGULATION OF INFLAMMATORY GENES ASSOCIATED WITH SEVERE ASTHMA. THE 10% OF PATIENTS WITH THE MOST SEVERE ASTHMA ARE RESPONSIBLE FOR A LARGE PART OF HEALTHCARE EXPENDITURE AND MORBIDITY. UNDERSTANDING THE PROCESSES INVOLVED IS KEY IF NEW THERAPEUTIC APPROACHES ARE TO BE DEVELOPED. EVIDENCE IS ACCUMULATING THAT CHRONIC DISEASES SUCH AS ASTHMA ARE ASSOCIATED WITH TEMPORAL AND SPATIAL ALTERATIONS IN THE PATTERN OF INFLAMMATORY GENE EXPRESSION WITHIN THE AIRWAYS. EXPRESSION OF THESE GENES CAN BE REGULATED BY TRANSCRIPTIONAL, POSTTRANSCRIPTIONAL, TRANSLATIONAL AND EPIGENETIC MECHANISMS. IT IS WELL ESTABLISHED THAT BINDING OF ACTIVATED TRANSCRIPTION FACTORS TO SPECIFIC INDUCIBLE GENE PROMOTER SITES IS TIGHTLY CONTROLLED BY CHROMATIN STATE AS A RESULT OF HISTONE MODIFICATIONS, PARTICULARLY THE BALANCE BETWEEN HISTONE ACETYLATION AND DEACETYLATION [1]. THE INTERACTION BETWEEN TRANSCRIPTION FACTORS AND THE PROMOTER IS KEY TO THE DIVERSIFICATION OF GENE EXPRESSION IN A TIME DEPENDENT MANNER LEADING TO ALTERED GENE EXPRESSION PROFILES. ALTERATIONS OF THE ACCESSIBILITY OF TRANSCRIPTION FACTORS TO THE DNA CAN HAVE RESIDING EFFECTS UPON GENE TRANSCRIPTION. THIS REVIEW WILL FOCUS ON THE REGULATION OF SEVERAL GROUPS OF KEY GENES WHICH ARE INVOLVED IN CHRONIC AIRWAY INFLAMMATION AND REMODELLING IN ASTHMA DRAWING MAINLY FROM OUR EXPERIENCE OF STUDYING THESE PROCESSES IN AIRWAY SMOOTH MUSCLE CELLS. AN OVERVIEW IS SHOWN IN FIGURE 1. 2011 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 6344 26 THE ROLE OF EPIGENETICS IN AGING AND AUTOIMMUNITY. THE DECLINE IN IMMUNOCOMPETENCE WITH AGE IS ACCOMPANIED BY THE INCREASE IN THE INCIDENCE OF AUTOIMMUNE DISEASES. AGING OF THE IMMUNE SYSTEM, OR IMMUNOSENESCENCE, IS CHARACTERIZED BY A DECLINE OF BOTH T AND B CELL FUNCTION, AND PARADOXICALLY THE PRESENCE OF LOW-GRADE CHRONIC INFLAMMATION. THERE IS GROWING EVIDENCE THAT EPIGENETICS, THE STUDY OF INHERITED CHANGES IN GENE EXPRESSION THAT ARE NOT ENCODED BY THE DNA SEQUENCE ITSELF, CHANGES WITH AGING. INTERESTINGLY, EMERGING EVIDENCE SUGGESTS A KEY ROLE FOR EPIGENETICS IN HUMAN PATHOLOGIES, INCLUDING INFLAMMATORY AND NEOPLASTIC DISORDERS. HERE, WE WILL REVIEW THE POTENTIAL MECHANISMS THAT CONTRIBUTE TO THE INCREASE IN AUTOIMMUNE RESPONSES IN AGING. IN PARTICULAR, WE WILL DISCUSS HOW EPIGENETIC ALTERATIONS, ESPECIALLY DNA METHYLATION AND HISTONE ACETYLATION, ARE ACCUMULATED DURING AGING AND HOW THESE EVENTS CONTRIBUTE TO AUTOIMMUNITY RISK. 2010 17 4318 33 MICRORNAS IN ANKYLOSING SPONDYLITIS: FUNCTION, POTENTIAL AND CHALLENGES. EPIGENETIC MECHANISMS SUCH AS DNA METHYLATION, HISTONE MODIFICATIONS AND NON-CODING RNA, ARE CONSIDERED THE ESSENTIAL CONNECTION BETWEEN A DISORDER'S ONSET AND THE ENVIRONMENT, ON A PERMISSIVE GENETIC BACKGROUND. AMONG AUTOIMMUNE AND INFLAMMATORY-MEDIATED DISORDERS, ANKYLOSING SPONDYLITIS (AS), A CHRONIC ARTHRITIS OF THE SPINE, IS A VERY GOOD EXAMPLE FOR THE WEIGHT OF EPIGENETICS' CONTRIBUTION. MICRORNAS (MIRNAS) ARE SINGLE-STRANDED NUCLEOTIDES WHICH REGULATE GENE EXPRESSION AND ARE INVOLVED IN PATHOLOGICAL AND PHYSIOLOGICAL PROCESSES. IN THIS MANUSCRIPT WE PROVIDE A CLARIFICATION ON THE ROLE OF MICRORNAS IN AS, WITH A FOCUS ON THE MECHANISMS OF PATHOGENESIS. IN SPECIFIC, WE HAVE EXAMINED THE CONTRIBUTION OF MIRNAS IN THE PROCESSES OF INFLAMMATION, NEW BONE FORMATION AND T-CELL FUNCTION, AND THE PATHWAYS (I.E. WNT, BMP, TGFBETA SIGNALLING ETC.) THEY REGULATE. THE UTILITY OF MIRNAS IN BETTER UNDERSTANDING AS PATHOGENESIS IS UNDISPUTED AND THEIR UTILITY AS THERAPEUTIC OPPORTUNITY IS STRONGLY INCREASING. 2020 18 2945 32 GENETIC AND EPIGENETIC BASIS OF PSORIASIS PATHOGENESIS. PSORIASIS IS A CHRONIC INFLAMMATORY SKIN DISEASE WHOSE PREVALENCE VARIES AMONG DIFFERENT POPULATIONS WORLDWIDE. IT IS A COMPLEX MULTI-FACTORIAL DISEASE AND THE EXACT ETIOLOGY IS LARGELY UNKNOWN. FAMILY BASED STUDIES HAVE INDICATED A GENETIC PREDISPOSITION; HOWEVER THEY CANNOT FULLY EXPLAIN THE DISEASE PATHOGENESIS. IN ADDITION TO GENETIC SUSCEPTIBILITY, ENVIRONMENTAL AS WELL AS GENDER AND AGE RELATED FACTORS WERE ALSO BEEN FOUND TO BE ASSOCIATED. RECENTLY, IMBALANCES IN EPIGENETIC NETWORKS ARE INDICATED TO BE CAUSATIVE ELEMENTS IN PSORIASIS. THE PRESENT KNOWLEDGE OF EPIGENETIC INVOLVEMENT, MAINLY THE DNA METHYLATION, CHROMATIN MODIFICATIONS AND MIRNA DEREGULATION IS SURVEYED HERE. AN INTEGRATED APPROACH CONSIDERING GENETIC AND EPIGENETIC ANOMALIES IN THE LIGHT OF IMMUNOLOGICAL NETWORK MAY EXPLORE THE PATHOGENESIS OF PSORIASIS. 2015 19 6624 35 UNDERSTANDING PSORIASIS: ROLE OF MIRNAS. PSORIASIS IS A CHRONIC, IMMUNE-MEDIATED INFLAMMATORY SKIN DISEASE, WITH A MULTIFACTORIAL ETIOLOGY AND IMPORTANT IMMUNOLOGIC, GENETIC AND ENVIRONMENTAL COMPONENTS. PSORIASIS VULGARIS REPRESENTS ITS MOST COMMON FORM, WITH A VARIABLE PREVALENCE ACROSS THE GLOBE. ALTHOUGH ITS PATHOGENESIS REMAINS TO BE FULLY ELUCIDATED, A LACK OF BALANCE IN THE EPIGENETIC NETWORK HAS BEEN SHOWN TO TRIGGER CERTAIN ELEMENTS OF THIS DISEASE, POSSIBLY ALTERING ITS OUTCOME. MICRORNAS ARE SMALL NON-CODING RNA MOLECULES INVOLVED IN RNA-SILENCING AND THE POST-TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION, WHICH ALSO APPEAR TO MEDIATE THE IMMUNE DYSFUNCTION IN PSORIASIS. ALTHOUGH MICRORNA RESEARCH IS A NEW FIELD IN DERMATOLOGY AND PSORIASIS, THERE IS RAPIDLY ACCUMULATING EVIDENCE FOR ITS MAJOR CONTRIBUTION IN THE PATHOGENESIS OF CHRONIC INFLAMMATORY CONDITIONS, INCLUDING PSORIASIS AND OTHER DERMATOLOGICAL DISORDERS. FURTHERMORE, CIRCULATING MIRNAS IDENTIFIED IN PATIENTS' BLOOD SAMPLES HAVE BEEN IDENTIFIED AS PROMISING BIOMARKERS OF DIAGNOSIS, PROGNOSIS OR TREATMENT RESPONSE. EXTENDED INVESTIGATIONS IN THIS FIELD ARE REQUIRED, AS UNTIL NOW, THE EXACT INVOLVEMENT OF MIRNAS IN PSORIASIS HAVE REMAINED TO BE ENTIRELY ELUCIDATED. THIS SHORT REVIEW HIGHLIGHTS A NUMBER OF THE ROLES OF MIRNAS FOUND IN DIFFERENT STAGES OF PSORIASIS. 2018 20 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