1 2591 127 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 2 1172 39 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 6340 34 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 4 6114 60 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 2070 39 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 6 6624 38 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 7 3703 36 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 4961 43 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 9 5932 45 TARGETING EPIGENETIC REGULATORS FOR INFLAMMATION: MECHANISMS AND INTERVENTION THERAPY. EMERGING EVIDENCE INDICATES THAT RESOLUTION OF INFLAMMATION IS A CRITICAL AND DYNAMIC ENDOGENOUS PROCESS FOR HOST TISSUES DEFENDING AGAINST EXTERNAL INVASIVE PATHOGENS OR INTERNAL TISSUE INJURY. IT HAS LONG BEEN KNOWN THAT AUTOIMMUNE DISEASES AND CHRONIC INFLAMMATORY DISORDERS ARE CHARACTERIZED BY DYSREGULATED IMMUNE RESPONSES, LEADING TO EXCESSIVE AND UNCONTROL TISSUE INFLAMMATION. THE DYSREGULATION OF EPIGENETIC ALTERATIONS INCLUDING DNA METHYLATION, POSTTRANSLATIONAL MODIFICATIONS TO HISTONE PROTEINS, AND NONCODING RNA EXPRESSION HAS BEEN IMPLICATED IN A HOST OF INFLAMMATORY DISORDERS AND THE IMMUNE SYSTEM. THE INFLAMMATORY RESPONSE IS CONSIDERED AS A CRITICAL TRIGGER OF EPIGENETIC ALTERATIONS THAT IN TURN INTERCEDE INFLAMMATORY ACTIONS. THUS, UNDERSTANDING THE MOLECULAR MECHANISM THAT DICTATES THE OUTCOME OF TARGETING EPIGENETIC REGULATORS FOR INFLAMMATORY DISEASE IS REQUIRED FOR INFLAMMATION RESOLUTION. IN THIS ARTICLE, WE ELUCIDATE THE CRITICAL ROLE OF THE NUCLEAR FACTOR-KAPPAB SIGNALING PATHWAY, JAK/STAT SIGNALING PATHWAY, AND THE NLRP3 INFLAMMASOME IN CHRONIC INFLAMMATORY DISEASES. AND WE FORMULATE THE RELATIONSHIP BETWEEN INFLAMMATION, CORONAVIRUS DISEASE 2019, AND HUMAN CANCERS. ADDITIONALLY, WE REVIEW THE MECHANISM OF EPIGENETIC MODIFICATIONS INVOLVED IN INFLAMMATION AND INNATE IMMUNE CELLS. ALL THAT MATTERS IS THAT WE PROPOSE AND DISCUSS THE REJUVENATION POTENTIAL OF INTERVENTIONS THAT TARGET EPIGENETIC REGULATORS AND REGULATORY MECHANISMS FOR CHRONIC INFLAMMATION-ASSOCIATED DISEASES TO IMPROVE THERAPEUTIC OUTCOMES. 2022 10 2333 34 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 11 6131 47 THE EPIGENETIC REGULATION OF WOUND HEALING. SIGNIFICANCE: EPIGENETIC REGULATORY MECHANISMS ARE ESSENTIAL FOR EPIDERMAL HOMEOSTASIS AND CONTRIBUTE TO THE PATHOGENESIS OF MANY SKIN DISEASES, INCLUDING SKIN CANCER AND PSORIASIS. HOWEVER, WHILE THE EPIGENETIC REGULATION OF EPIDERMAL HOMEOSTASIS IS NOW BECOMING ACTIVE AREA OF RESEARCH, THE EPIGENETIC MECHANISMS CONTROLLING THE WOUND HEALING RESPONSE REMAIN RELATIVELY UNTOUCHED. RECENT ADVANCES: SUBSTANTIAL PROGRESS ACHIEVED WITHIN THE LAST TWO DECADES IN UNDERSTANDING EPIGENETIC MECHANISMS CONTROLLING GENE EXPRESSION ALLOWED DEFINING SEVERAL LEVELS, INCLUDING COVALENT DNA AND HISTONE MODIFICATIONS, ATP-DEPENDENT AND HIGHER-ORDER CHROMATIN CHROMATIN REMODELING, AS WELL AS NONCODING RNA- AND MICRORNA-DEPENDENT REGULATION. RESEARCH PERTAINED OVER THE LAST FEW YEARS SUGGESTS THAT EPIGENETIC REGULATORY MECHANISMS PLAY A PIVOTAL ROLE IN THE REGULATION OF SKIN REGENERATION AND CONTROL AN EXECUTION OF REPARATIVE GENE EXPRESSION PROGRAMS IN BOTH SKIN EPITHELIUM AND MESENCHYME. CRITICAL ISSUES: EPIGENETIC REGULATORS APPEAR TO BE INHERENTLY INVOLVED IN THE PROCESSES OF SKIN REPAIR, AND ARE ABLE TO DYNAMICALLY REGULATE KERATINOCYTE PROLIFERATION, DIFFERENTIATION, AND MIGRATION, TOGETHER WITH INFLUENCING DERMAL REGENERATION AND NEOANGIOGENESIS. THIS IS ACHIEVED THROUGH A SERIES OF COMPLEX REGULATORY MECHANISMS THAT ARE ABLE TO BOTH STIMULATE AND REPRESS GENE ACTIVATION TO TRANSIENTLY ALTER CELLULAR PHENOTYPE AND BEHAVIOR, AND INTERACT WITH GROWTH FACTOR ACTIVITY. FUTURE DIRECTIONS: UNDERSTANDING THE MOLECULAR BASIS OF EPIGENETIC REGULATION IS A PRIORITY AS IT REPRESENTS POTENTIAL THERAPEUTIC TARGETS FOR THE TREATMENT OF BOTH ACUTE AND CHRONIC SKIN CONDITIONS. FUTURE RESEARCH IS, THEREFORE, IMPERATIVE TO HELP DISTINGUISH EPIGENETIC MODULATING DRUGS THAT CAN BE USED TO IMPROVE WOUND HEALING. 2014 12 4318 35 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 13 2945 38 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 14 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 15 6202 55 THE INFLAMMATORY RESPONSE IN PSORIASIS: A COMPREHENSIVE REVIEW. PSORIASIS IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE CHARACTERIZED BY AN EXCESSIVELY ABERRANT HYPERPROLIFERATION OF KERATINOCYTES. THE PATHOGENESIS OF PSORIASIS IS COMPLEX AND THE EXACT MECHANISM REMAINS ELUSIVE. HOWEVER, PSORIASIS IS THOUGHT TO RESULT FROM A COMBINATION OF GENETIC, EPIGENETIC, AND ENVIRONMENTAL INFLUENCES. RECENT STUDIES HAVE IDENTIFIED THAT EPIGENETIC FACTORS INCLUDING DYSREGULATED DNA METHYLATION LEVELS, ABNORMAL HISTONE MODIFICATION AND MICRORNAS EXPRESSIONS ARE INVOLVED IN THE DEVELOPMENT OF PSORIASIS. THE INTERPLAY OF IMMUNE CELLS AND CYTOKINES IS ANOTHER CRITICAL FACTOR IN THE PATHOGENESIS OF PSORIASIS. THESE FACTORS OR PATHWAYS INCLUDE TH1/TH2 HOMEOSTASIS, THE TH17/TREG BALANCE AND THE IL-23/TH17 AXIS. TH17 IS BELIEVED PARTICULARLY IMPORTANT IN PSORIASIS DUE TO ITS PRO-INFLAMMATORY EFFECTS AND ITS INVOLVEMENT IN AN INTEGRATED INFLAMMATORY LOOP WITH DENDRITIC CELLS AND KERATINOCYTES, CONTRIBUTING TO AN OVERPRODUCTION OF ANTIMICROBIAL PEPTIDES, INFLAMMATORY CYTOKINES, AND CHEMOKINES THAT LEADS TO AMPLIFICATION OF THE IMMUNE RESPONSE. IN ADDITION, OTHER PATHWAYS AND SIGNALING MOLECULES HAVE BEEN FOUND TO BE INVOLVED, INCLUDING TH9, TH22, REGULATORY T CELLS, GAMMADELTA T CELLS, CD8(+) T CELLS, AND THEIR RELATED CYTOKINES. UNDERSTANDING THE PATHOGENESIS OF PSORIASIS WILL ALLOW US TO DEVELOP INCREASINGLY EFFICIENT TARGETED TREATMENT BY BLOCKING RELEVANT INFLAMMATORY SIGNALING PATHWAYS AND MOLECULES. THERE IS NO CURE FOR PSORIASIS AT THE PRESENT TIME, AND MUCH OF THE TREATMENT INVOLVES MANAGING THE SYMPTOMS. THE BIOLOGICS, WHILE LACKING THE ADVERSE EFFECTS ASSOCIATED WITH SOME OF THE TRADITIONAL MEDICATIONS SUCH AS CORTICOSTEROIDS AND METHOTREXATE, HAVE THEIR OWN SET OF SIDE EFFECTS, WHICH MAY INCLUDE REACTIVATION OF LATENT INFECTIONS. SIGNIFICANT CHALLENGES REMAIN IN DEVELOPING SAFE AND EFFICACIOUS NOVEL TARGETED THERAPIES THAT DEPEND ON A BETTER UNDERSTANDING OF THE IMMUNOLOGICAL DYSFUNCTION IN PSORIASIS. 2016 16 2501 39 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 17 4883 37 OVERVIEW OF THE MOLECULAR DETERMINANTS CONTRIBUTING TO THE EXPRESSION OF PSORIASIS AND PSORIATIC ARTHRITIS PHENOTYPES. PSORIASIS AND PSORIATIC ARTHRITIS ARE MULTIFACTORIAL CHRONIC DISORDERS WHOSE ETIOPATHOGENESIS ESSENTIALLY DERIVES FROM THE ALTERATION OF SEVERAL SIGNALLING PATHWAYS AND THE CO-OCCURRENCE OF GENETIC, EPIGENETIC AND NON-GENETIC SUSCEPTIBILITY FACTORS THAT ALTOGETHER AFFECT THE FUNCTIONAL AND STRUCTURAL PROPERTY OF THE SKIN. ALTHOUGH SHARED AND DIFFERENTIAL SUSCEPTIBILITY GENES AND MOLECULAR PATHWAYS ARE KNOWN TO CONTRIBUTE TO THE ONSET OF PATHOLOGICAL PHENOTYPES, FURTHER RESEARCH IS NEEDED TO DISSECT THE MOLECULAR CAUSES OF PSORIATIC DISEASE AND ITS PROGRESSION TOWARDS PSORIATIC ARTHRITIS. THIS REVIEW WILL THEREFORE BE ADDRESSED TO EXPLORE DIFFERENCES AND SIMILARITIES IN THE ETIOPATHOGENESIS AND PROGRESSION OF BOTH DISORDERS, WITH A PARTICULAR FOCUS ON GENES INVOLVED IN THE MAINTENANCE OF THE SKIN STRUCTURE AND INTEGRITY (KERATINS AND COLLAGENS), MODULATION OF PATTERNS OF RECOGNITION (THROUGH TOLL-LIKE RECEPTORS AND DECTIN-1) AND IMMUNO-INFLAMMATORY RESPONSE (BY NLRP3-DEPENDENT INFLAMMASOME) TO MICROBIAL PATHOGENS. IN ADDITION, SPECIAL EMPHASIS WILL BE GIVEN TO THE CONTRIBUTION OF EPIGENETIC ELEMENTS (METHYLATION PATTERN, NON-CODING RNAS, CHROMATIN MODIFIERS AND 3D GENOME ORGANIZATION) TO THE ETIOPATHOGENESIS AND PROGRESSION OF PSORIASIS AND PSORIATIC ARTHRITIS. THE EVIDENCE DISCUSSED IN THIS REVIEW HIGHLIGHTS HOW THE KNOWLEDGE OF PATIENTS' CLINICAL AND (EPI)GENOMIC MAKE-UP COULD BE HELPFUL FOR IMPROVING THE AVAILABLE THERAPEUTIC STRATEGIES FOR PSORIASIS AND PSORIATIC ARTHRITIS TREATMENT. 2020 18 2027 47 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 19 2553 40 EPIGENETICS IN PSORIASIS: PERSPECTIVE OF DNA METHYLATION. PSORIASIS IS A CHRONIC INFLAMMATORY SKIN DISEASE CHARACTERIZED BY EXCESSIVE PROLIFERATION OF KERATINOCYTES (KCS). ONSET OF PSORIASIS IS RELATED TO GENETIC, IMMUNE AND ENVIRONMENTAL FACTORS. THE ENVIRONMENT CAN INTERACT WITH THE GENOME THROUGH EPIGENETIC MODIFICATIONS, INCLUDING DNA METHYLATION, AND THIS MODIFICATION IS INVOLVED IN THE PATHOGENESIS OF PSORIASIS. IN ADDITION TO A SKIN DISEASE, PSORIASIS IS ALSO CONSIDERED A SYSTEMIC DISEASE. WE REVIEWED THE CURRENT LITERATURE OF PSORIATIC DNA METHYLATION FOR STUDIES FROM SEVERAL ASPECTS ON THE DNA METHYLATION DISTRIBUTION PATTERNS IN DIFFERENT TISSUES/CELLS, SINGLE-NUCLEOTIDE POLYMORPHISMS, AND CANDIDATE DISEASE GENES AND IDENTIFIED TARGET GENES REGULATED BY DNA METHYLATION THAT HAVE BEEN DIRECTLY/INDIRECTLY VALIDATED. THIS REVIEW CONTRIBUTES TO A COMPREHENSIVE UNDERSTANDING OF THE IMPORTANT A ROLE THAT DNA METHYLATION PLAYS IN PSORIASIS FROM A HOLISTIC PERSPECTIVE AND WILL PROMOTE THE IMPLEMENTATION OF DNA METHYLATION IN DIAGNOSTIC AND THERAPEUTIC STRATEGIES FOR PSORIATIC PATIENTS. 2021 20 6344 30 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