1 2569 95 EPIGENETICS OF ANKYLOSING SPONDYLITIS: RECENT DEVELOPMENTS. ANKYLOSING SPONDYLITIS (AS) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE WHICH MAINLY AFFECTS THE SPINE, SACROILIAC JOINT AND PERIPHERAL JOINTS. TO DATE, THE EXACT CAUSES AND PATHOGENESIS OF AS STILL REMAIN UNKNOWN. IT IS CONSIDERED THAT THE PATHOGENESIS OF AS IS ASSOCIATED WITH GENETIC, INFECTION, ENVIRONMENT, IMMUNITY AND OTHER FACTORS. AMONG THEM, THE ROLE OF GENETIC FACTORS IN THE PATHOGENESIS OF AS HAS BEEN STUDIED MOST DEEPLY. HOWEVER, OVER THE PAST FEW YEARS, THE FUNCTION OF ENVIRONMENTAL PREDISPOSITION AND EPIGENETIC MODIFICATION IN THE PATHOGENESIS OF AS HAS RECEIVED EXTENSIVE ATTENTION. THIS PAPER SUMMARIZES THE RECENT PROGRESS IN THE EPIGENETICS OF AS, INCLUDING ABNORMAL EPIGENETIC MODIFICATIONS AT AS-ASSOCIATED GENOMIC LOCI, SUCH AS DNA METHYLATION, HISTONE MODIFICATION, MICRORNA, AND SO ON. IN SUMMARY, THE FINDINGS OF THIS REVIEW ATTEMPT TO EXPLAIN THE ROLE OF EPIGENETIC MODIFICATION IN THE OCCURRENCE AND DEVELOPMENT OF AS. NEVERTHELESS, THERE ARE STILL UNKNOWN AND COMPLICATED ASPECTS WORTH EXPLORING TO DEEPEN OUR UNDERSTANDING OF THE PATHOGENESIS OF AS. 2021 2 2027 36 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 3 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 4 4676 52 NEW INSIGHTS TOWARD THE PATHOGENESIS OF ANKYLOSING SPONDYLITIS; GENETIC VARIATIONS AND EPIGENETIC MODIFICATIONS. ANKYLOSING SPONDYLITIS (AS) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE, CHARACTERIZED BY TYPICALLY AN AXIAL ARTHRITIS. AS IS THE PROTOTYPE OF A GROUP OF DISORDERS CALLED SPONDYLOARTHROPATHIES, WHICH IS BELIEVED TO HAVE COMMON CLINICAL MANIFESTATIONS AND GENETIC PREDISPOSITION. TO DATE, THE EXACT ETIOLOGY OF AS REMAINS UNCLEAR. OVER THE PAST FEW YEARS, HOWEVER, THE ROLE OF GENETIC SUSCEPTIBILITY AND EPIGENETIC MODIFICATIONS CAUSED THROUGH ENVIRONMENTAL FACTORS HAVE BEEN EXTENSIVELY SURVEYED WITH RESPECT TO THE PATHOGENESIS OF AS, RESULTED IN IMPORTANT ADVANCES. THIS REVIEW ARTICLE FOCUSES ON THE RECENT ADVANCES IN THE FIELD OF AS RESEARCH, INCLUDING HLA AND NON-HLA SUSCEPTIBILITY GENES IDENTIFIED IN GENOME-WIDE ASSOCIATION STUDIES (GWAS), AND ABERRANT EPIGENETIC MODIFICATIONS OF GENE LOCI ASSOCIATED WITH AS. HLA GENES MOST SIGNIFICANTLY LINKED WITH AS SUSCEPTIBILITY INCLUDE HLA-B27 AND ITS SUBTYPES. NUMEROUS NON-HLA GENES SUCH AS THOSE IN UBIQUITINATION, AMINOPEPTIDASES AND MHC CLASS I PRESENTATION MOLECULES LIKE ERAP-1 WERE ALSO REPORTED. MOREOVER, EPIGENETIC MODIFICATIONS OCCURRED IN AS HAS BEEN SUMMARIZED. TAKEN TOGETHER, THE FINDINGS PRESENTED IN THIS REVIEW ATTEMPT TO EXPLAIN THE CIRCUMSTANCE BY WHICH BOTH GENETIC VARIATIONS AND EPIGENETIC MODIFICATIONS ARE INVOLVED IN TRIGGERING AND DEVELOPMENT OF AS. NONETHELESS, SEVERAL UNANSWERED DARK SIDES CONTINUE TO CLOG OUR EXHAUSTIVE UNDERSTANDING OF AS. FUTURE RESEARCHES IN THE FIELD OF EPIGENETICS SHOULD BE CARRIED OUT TO EXTEND OUR VISION OF AS ETIOPATHOGENESIS. 2017 5 2945 31 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 6 6288 37 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 7 4319 26 MICRORNAS IN AXIAL SPONDYLARTHRITIS: AN OVERVIEW OF THE RECENT PROGRESSES IN THE FIELD WITH A FOCUS ON ANKYLOSING SPONDYLITIS AND PSORIATIC ARTHRITIS. PURPOSE OF REVIEW: TO HIGHLIGHT THE RECENT DISCOVERIES AND LINES OF EVIDENCE ON THE ROLE OF MICRORNAS IN ANKYLOSING SPONDYLITIS (AS) AND PSORIATIC ARTHRITIS (PSA), FOCUSING ON THEIR EXPRESSION PROFILING AND MECHANISMS OF ACTION. RECENT FINDINGS: AS AND PSA ARE CHRONIC INFLAMMATORY MUSCULOSKELETAL DISEASES WITH AXIAL MANIFESTATIONS AND REPRESENT AN EXCELLENT MODEL FOR STUDYING MICRORNAS CONTRIBUTION TO THE DISEASE PATHOGENESIS, PARTICULARLY THROUGH IMMUNOMODULATION, INFLAMMATION, AND BONE REMODELLING, OR THEIR VALUE AS CANDIDATE DIAGNOSTIC AND PROGNOSTIC BIOMARKERS. MICRORNAS ARE SINGLE-STRANDED NUCLEOTIDES ABLE TO REGULATE GENE EXPRESSION. THEY ARE A KEY COMPONENT OF THE EPIGENETIC MACHINERY, INVOLVED IN PHYSIOLOGICAL AND PATHOLOGICAL PROCESSES. THE CONTRIBUTION OF MICRORNAS IN AS AND PSA (SUCH AS MIR-29A IN REGULATING BONE METABOLISM) IS HIGHLIGHTED BY SEVERAL WORKS IN THE FIELD BUT THEIR UTILITY AS POSSIBLE MARKERS MUST BE STILL CONFIRMED, PARTICULARLY IN LARGER PATIENTS' COHORTS. 2021 8 1871 33 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 9 6624 30 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 10 2591 40 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 11 4844 33 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 2333 27 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 13 2224 32 EPIGENETIC MODIFICATIONS IN THE PATHOGENESIS OF SYSTEMIC SCLEROSIS. SYSTEMIC SCLEROSIS IS A RARE CHRONIC AUTOIMMUNE DISEASE, WHICH MAINLY MANIFESTS AS IMMUNE DISORDERS, VASCULAR DAMAGE, AND PROGRESSIVE FIBROSIS. THE ETIOLOGY OF SSC IS COMPLEX AND INVOLVES MULTIPLE FACTORS. BOTH GENETIC AND ENVIRONMENTAL FACTORS ARE INVOLVED IN ITS PATHOGENESIS. AS ONE OF THE MOLECULAR MECHANISMS OF ENVIRONMENTAL FACTORS, EPIGENETIC REGULATION PLAYS AN IMPORTANT ROLE IN THE OCCURRENCE AND DEVELOPMENT OF SYSTEMIC SCLEROSIS, WHICH INVOLVES DNA METHYLATION, HISTONE MODIFICATION AND NON-CODING RNA REGULATION. THIS REVIEW SUMMARIZES RESEARCH ADVANCES IN EPIGENETICS, INCLUDING EXOSOMES, LNCRNA, AND MENTIONS POSSIBLE BIOMARKERS AND THERAPEUTIC TARGETS AMONG THEM. 2022 14 1172 33 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 15 6340 31 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 16 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 17 6114 40 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 18 2309 30 EPIGENETIC REGULATION OF CHONDROCYTES AND SUBCHONDRAL BONE IN OSTEOARTHRITIS. THE AIM OF THIS REVIEW IS TO PROVIDE AN UPDATED REVIEW OF THE EPIGENETIC FACTORS INVOLVED IN THE ONSET AND DEVELOPMENT OF OSTEOARTHRITIS (OA). OA IS A PREVALENT DEGENERATIVE JOINT DISEASE CHARACTERIZED BY CHRONIC INFLAMMATION, ECTOPIC BONE FORMATION WITHIN THE JOINT, AND PHYSICAL AND PROTEOLYTIC CARTILAGE DEGRADATION WHICH RESULT IN CHRONIC PAIN AND LOSS OF MOBILITY. AT PRESENT, NO DISEASE-MODIFYING THERAPEUTICS EXIST FOR THE PREVENTION OR TREATMENT OF THE DISEASE. RESEARCH HAS IDENTIFIED SEVERAL OA RISK FACTORS INCLUDING MECHANICAL STRESSORS, PHYSICAL ACTIVITY, OBESITY, TRAUMATIC JOINT INJURY, GENETIC PREDISPOSITION, AND AGE. RECENTLY, THERE HAS BEEN INCREASED INTEREST IN IDENTIFYING EPIGENETIC FACTORS INVOLVED IN THE PATHOGENESIS OF OA. IN THIS REVIEW, WE DETAIL SEVERAL OF THESE EPIGENETIC MODIFICATIONS WITH KNOWN FUNCTIONS IN THE ONSET AND PROGRESSION OF THE DISEASE. WE ALSO REVIEW CURRENT THERAPEUTICS TARGETING ABERRANT EPIGENETIC REGULATION AS POTENTIAL OPTIONS FOR PREVENTIVE OR THERAPEUTIC TREATMENT. 2022 19 3706 32 INFLUENCE OF GENETICS ON DISEASE SUSCEPTIBILITY AND PROGRESSION. FOR MANY CHRONIC DISEASES, THE INFLUENCE OF GENETICS IS COMPLEX AND PHENOTYPES DO NOT CONFORM TO SIMPLE MENDELIAN PATTERNS OF INHERITANCE. DISCUSSED HERE ARE TWO TYPES OF GENETIC INFLUENCES ON HEALTHY AGING. THE FIRST INVOLVES VARIATION IN THE GENE SEQUENCE ITSELF AND HOW THIS MAY INFLUENCE DISEASE SUSCEPTIBILITY, PROGRESSION, AND SEVERITY, INTERACTING WITH OTHER RECOGNIZED RISK FACTORS. THE SECOND INVOLVES EPIGENETIC REGULATORY MECHANISMS THAT MAY POTENTIALLY PROVIDE INSIGHT INTO HOW ENVIRONMENTAL INFLUENCES AFFECT THE EXPRESSED GENOME, THUS IMPROVING OUR UNDERSTANDING OF THE GENETIC MECHANISMS UNDERLYING MULTIFACTORIAL DISEASES. THE INTERLEUKIN-1 FAMILY OF CYTOKINES CAN BE USED TO ILLUSTRATE HOW GENETIC SEQUENCE VARIATION MAY AFFECT SUCH DISEASES. THIS CYTOKINE FAMILY PLAYS A KEY ROLE IN MEDIATING INFLAMMATION, WHICH IS NOW UNDERSTOOD TO BE A CENTRAL COMPONENT OF A GROWING NUMBER OF CHRONIC DISEASES. RECENT WORK HAS REVEALED MANY SEQUENCE VARIATIONS IN THE REGULATORY DNA OF GENES ENCODING IMPORTANT MEMBERS OF THE INTERLEUKIN-1 FAMILY, AND THESE VARIATIONS ARE ASSOCIATED WITH DIFFERENTIAL EFFECTS ON THE INFLAMMATORY RESPONSE. THE INTERACTIONS OF ENVIRONMENTAL FACTORS WITH BOTH DNA SEQUENCE VARIATIONS AND EPIGENETIC MODIFICATIONS ARE LIKELY TO DETERMINE THE PHENOTYPES OF MULTIFACTORIAL DISEASES OF AGING AS WELL AS THE PHENOTYPE OF HEALTHY AGING. 2007 20 3108 25 GENOMICS OF PAIN IN OSTEOARTHRITIS. OSTEOARTHRITIS (OA) ACCOUNTS FOR THE MAJORITY OF THE DISEASE BURDEN FOR MUSCULOSKELETAL DISORDERS AND IS ONE OF THE LEADING CAUSES OF DISABILITY WORLDWIDE. THIS DISABILITY IS THE RESULT NOT OF THE CARTILAGE LOSS THAT DEFINES OA RADIOGRAPHICALLY, BUT OF THE CHRONIC PAIN WHOSE PRESENCE DEFINES SYMPTOMATIC OA. IT IS BECOMING CLEAR THAT MANY GENES, EACH WITH A SMALL EFFECT SIZE, CONTRIBUTE TO THE RISK OF DEVELOPING OA. HOWEVER, THE GENETICS OF OA PAIN ARE ONLY JUST STARTING TO BE EXPLORED. THIS REVIEW WILL DESCRIBE THE FIRST GENES TO HAVE BEEN IDENTIFIED IN GENOMIC STUDIES OF OA PAIN, AS WELL AS THE POSSIBLE DUAL ROLES OF GENES PREVIOUSLY IDENTIFIED IN GENOMIC STUDIES OF OA IN THE CONTEXT OF PAIN. DIFFICULTIES ASSOCIATED WITH ATTEMPTING TO CHARACTERISE THE GENETICS OF OA PAIN WILL BE DISCUSSED AND PROMISING FUTURE AVENUES OF RESEARCH INTO GENETIC AND EPIGENETIC FACTORS AFFECTING OA PAIN DESCRIBED. 2013