1 2578 163 EPIGENETICS OF INFLAMMATORY BOWEL DISEASES. INFLAMMATORY BOWEL DISEASES ARE MULTIFACTORIAL, CHRONIC, CONTINUOUS, RELAPSING, AND IMMUNE-MEDIATED DISEASES OF THE GASTROINTESTINAL TRACT. IT HAS BEEN BELIEVED THAT MECHANISMS UNDERLYING INFLAMMATORY BOWEL DISEASES INCLUDE GENETIC PREDISPOSITION, ENVIRONMENTAL FACTORS, AND ALTERED IMMUNE RESPONSE TO THE GUT MICROBIOME. THE EPIGENETIC MODULATION TAKES PLACE VIA CHROMATIN MODIFICATIONS, INCLUDING PHOSPHORYLATION, ACETYLATION, METHYLATION, SUMOYLATION, AND UBIQUITINATION. THE METHYLATION LEVELS OF COLONIC TISSUE WERE FOUND WELL CORRELATED TO BLOOD SAMPLES IN INFLAMMATORY BOWEL DISEASES. MOREOVER, THE METHYLATION LEVEL OF SPECIFIC GENES WAS DIFFERENT BETWEEN CROHN'S DISEASE AND ULCERATIVE COLITIS. IT HAS BEEN SHOWN THAT THE ENZYMES AFFECTING HISTONE MODIFICATIONS LIKE HISTONE DEACETYLASES AND HISTONE ACETYLTRANSFERASES DO NOT ACT SOLELY ON HISTONES BUT ALSO AFFECT THE ACETYLATION OF MANY PROTEINS SUCH AS P53 AND STAT3. IT HAS BEEN ALREADY SHOWN THAT A NONSELECTIVE HISTONE DEACETYLASE INHIBITOR, VORINOSTAT (SAHA), WHICH IS CURRENTLY BEING USED IN SEVERAL CANCER TREATMENTS, SHOWED ANTI-INFLAMMATORY ACTIVITIES IN MOUSE MODELS. AMONG EPIGENETIC ALTERATIONS, LONG NON-CODING RNAS AND MICRORNAS PLAY SIGNIFICANT ROLES IN T-CELL MATURATION, DIFFERENTIATION, ACTIVATION, AND SENILITY. THE LONG NON-CODING RNA AND MICRORNA EXPRESSION PROFILES CAN PERFECTLY SEPARATE INFLAMMATORY BOWEL DISEASE PATIENTS FROM HEALTHY CONTROLS AND ARE REMARKED AS BIOMARKERS OF INFLAMMATORY BOWEL DISEASES. OVERALL, MANY STUDIES HAVE SHOWN THAT EPIGENETIC INHIBITORS CAN TARGET SIGNIFICANT SIGNAL PATHWAYS IN THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASES, AND THE IMPACT OF EPIGENETIC INHIBITORS IS BEING STUDIED IN CLINICAL TRIALS. IN CONCLUSION, EXPLORING MORE EPIGENETIC PATHWAYS REGARDING INFLAMMATORY BOWEL DISEASE PATHOGENESIS WILL HELP US TO DISCOVER THERAPEUTIC TARGETS AND NEW DRUGS AND AGENTS TARGETING MIRNAS IN INFLAMMATORY BOWEL DISEASES. IN GENERAL, DISCOVERING EPIGENETIC TARGETS COULD IMPROVE THE DIAGNOSIS AND TREATMENT OF INFLAMMATORY BOWEL DISEASES. 2023 2 2233 51 EPIGENETIC MODIFICATIONS OF THE NUCLEAR FACTOR KAPPA B SIGNALLING PATHWAY AND ITS IMPACT ON INFLAMMATORY BOWEL DISEASE. BACKGROUND: INFLAMMATORY BOWEL DISEASE (IBD) IS A MULTIFACTORIAL CONDITION INFLUENCED BY THE IMMUNE SYSTEM, THE INTESTINAL MICROBIOTA, ENVIRONMENTAL FACTORS, GENETIC AND EPIGENETIC FACTORS. GENETIC- AND ENVIRONMENT- INDUCED DYSREGULATION OF THE NUCLEAR FACTOR-KAPPA B (NF-KAPPAB) TRANSCRIPTION FACTOR PATHWAY HAS BEEN LINKED TO IBD PATHOGENESIS. OBJECTIVE: TO ASSESS THE CURRENT EVIDENCE IN RELATION TO THE CONTRIBUTION OF THE CLASSICAL AND ALTERNATIVE NF-KAPPAB PATHWAYS IN IBD AND TO DISCUSS THE EPIGENETIC MECHANISMS THAT IMPACT ON NF-KAPPAB FUNCTION. METHODS: A MEDLINE SEARCH FOR 'NF-KAPPAB/NF-KAPPAB', IN COMBINATION WITH TERMS INCLUDING 'INFLAMMATORY BOWEL DISEASE/IBD', 'INTESTINAL INFLAMMATION', 'CROHN'S DISEASE', 'ULCERATIVE COLITIS', 'COLITIS'; 'EPIGENETICS', 'DNA METHYLATION', 'HISTONES', 'MICRORNAS/MIRNAS' AND 'SHORT NON-CODING/LONG NON-CODING RNAS' WAS PERFORMED. RESULTS: BOTH NF-KAPPAB PATHWAYS CONTRIBUTE TO THE CHRONIC INFLAMMATION UNDERLYING IBD BY REGULATING THE INFLAMMATORY IMMUNE RESPONSES AND HOMEOSTASIS OF THE INTESTINAL EPITHELIUM (CLASSICAL PATHWAY) OR REGULATING BOWEL INFLAMMATION AND EPITHELIAL MICROFOLD (M) CELL FUNCTION (ALTERNATIVE PATHWAY). DNA METHYLATION IS A COMMON EPIGENETIC MODIFICATION IN INTESTINAL INFLAMMATION, INCLUDING NFKB1 AND RELA LOCI. CONVERSELY, LITTLE IS UNDERSTOOD REGARDING EPIGENETIC EFFECTS ON GENES ENCODING OTHER NF-KAPPAB SUBUNITS, PARTICULARLY THOSE OF THE ALTERNATIVE PATHWAY, AND IN THE CONTEXT OF IBD. HOWEVER, NF-KAPPAB INTERACTION WITH CHROMATIN MODIFIERS IS ALSO SEEN TO BE AN ESSENTIAL MECHANISM OF REGULATION OF DOWNSTREAM TARGET GENES RELEVANT TO NF-KAPPAB-MEDIATED INFLAMMATORY RESPONSES. CONCLUSION: FURTHER RESEARCH IS CLEARLY WARRANTED IN THIS AREA, AS UNDERSTANDING THE CELL-SPECIFIC REGULATION OF THE NF-KAPPAB PATHWAYS WILL BRING RESEARCHERS INTO A POSITION TO ACHIEVE MORE EFFICIENT STRATIFICATION OF IBD PATIENTS, AND MORE TARGETED AND EFFECTIVE CHOICE OF TREATMENT. 2021 3 4670 43 NEW INSIGHTS INTO THE EPIGENETIC REGULATION OF INFLAMMATORY BOWEL DISEASE. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC INFLAMMATORY DISEASE OF THE COLONIC MUCOSA. ENVIRONMENTAL FACTORS, GENETICS, INTESTINAL MICROBIOTA, AND THE IMMUNE SYSTEM ARE ALL INVOLVED IN THE PATHOPHYSIOLOGY OF IBD. LATELY, ACCUMULATING EVIDENCE HAS SHOWN THAT ABNORMAL EPIGENETIC CHANGES IN DNA METHYLATION, HISTONE MARKERS, AND NON-CODING RNA EXPRESSION GREATLY CONTRIBUTE TO THE DEVELOPMENT OF THE ENTIRE DISEASE. EPIGENETICS REGULATES MANY FUNCTIONS, SUCH AS MAINTAINING THE HOMEOSTASIS OF THE INTESTINAL EPITHELIUM AND REGULATING THE IMMUNE SYSTEM OF THE IMMUNE CELLS. IN THE PRESENT STUDY, WE SYSTEMATICALLY SUMMARIZED THE LATEST ADVANCES IN EPIGENETIC MODIFICATION OF IBD AND HOW EPIGENETICS REVEALS NEW MECHANISMS OF IBD. OUR PRESENT REVIEW PROVIDED NEW INSIGHTS INTO THE PATHOPHYSIOLOGY OF IBD. MOREOVER, EXPLORING THE PATTERNS OF DNA METHYLATION AND HISTONE MODIFICATION THROUGH EPIGENETICS CAN NOT ONLY BE USED AS BIOMARKERS OF IBD BUT ALSO AS A NEW TARGET FOR THERAPEUTIC INTERVENTION IN IBD PATIENTS. 2022 4 2601 46 EPIGENETICS, DNA ORGANIZATION, AND INFLAMMATORY BOWEL DISEASE. INFLAMMATORY BOWEL DISEASES (IBDS) ARE CHRONIC INFLAMMATORY DISORDERS AFFECTING THE GASTROINTESTINAL TRACT. THE INCIDENCE OF IBD IS INCREASING, WITH MORE CASES OCCURRING IN DEVELOPED COUNTRIES. MULTIPLE FACTORS SUCH AS GENETICS, ENVIRONMENTAL CHANGES, GUT MICROBIOTA, AND IMMUNE ABNORMALITIES HAVE BEEN ASSOCIATED WITH DEVELOPMENT OF IBD. IN RECENT YEARS, IT HAS BECOME INCREASINGLY APPARENT THAT EPIGENETIC MODIFICATIONS OF CHROMATIN AND THE MANNER IN WHICH CHROMATIN IS ORGANIZED IN THE NUCLEUS ARE ADDITIONALLY IMPORTANT ELEMENTS THAT CAN INFLUENCE RESPONSES INDUCED BY THE FACTORS DESCRIBED ABOVE, AND MAY THEREFORE CONTRIBUTE TO THE ONSET AND PATHOGENESIS OF IBD. EPIGENETICS AND CHROMATIN ORGANIZATION REGULATE DIVERSE FUNCTIONS THAT INCLUDE MAINTENANCE OF HOMEOSTASIS IN THE INTESTINAL EPITHELIUM, THE DEVELOPMENT AND DIFFERENTIATION OF IMMUNE CELLS, AND MODULATION OF RESPONSES GENERATED BY THE IMMUNE SYSTEM TO DEFEND AGAINST POTENTIAL PATHOGENS. FURTHERMORE, CHANGES IN EPIGENETIC CHROMATIN MARKS AND IN CHROMATIN ORGANIZATION HAVE NOW BEEN LINKED TO DIFFERENTIAL GENE EXPRESSION IN IBD PATIENT CELLS. ALTHOUGH DIRECT EVIDENCE FOR A ROLE OF HISTONE MODIFICATIONS IN IBD IS CURRENTLY VERY LIMITED, IN THIS REVIEW, WE SUMMARIZE THE LINKS BETWEEN VARIOUS EPIGENETIC MODIFICATIONS, THE PROTEINS THAT CATALYZE OR RECOGNIZE THESE MODIFICATIONS, AND THE DEVELOPMENT OR PROGRESSION OF IBD IN HUMAN AND EXPERIMENTAL IBD. WE ALSO DISCUSS HOW EPIGENETICS INFLUENCE THE ORGANIZATION OF DNA CONTACTS TO REGULATE GENE EXPRESSION AND THE IMPLICATIONS THIS MAY HAVE FOR DIAGNOSING AND TREATING IBD. 2019 5 6340 44 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 6 5528 35 RNA MODIFICATION IN INFLAMMATORY BOWEL DISEASES. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC INFLAMMATORY DISORDER CHARACTERIZED BY DAMAGE TO THE INTESTINAL MUCOSA, WHICH IS CAUSED BY A COMBINATION OF FACTORS. THESE INCLUDE GENETIC AND EPIGENETIC ALTERATIONS, ENVIRONMENTAL INFLUENCE, MICROORGANISM INTERACTIONS, AND IMMUNE CONDITIONS. SOME POPULATIONS WITH IBD SHOW A CANCER-PRONE PHENOTYPE. RECENT STUDIES HAVE PROVIDED INSIGHT INTO THE INVOLVEMENT OF RNA MODIFICATIONS IN THE SPECIFIC PATHOGENESIS OF IBD THROUGH REGULATION OF RNA BIOLOGY IN EPITHELIAL AND IMMUNE CELLS. STUDIES OF SEVERAL RNA MODIFICATION-TARGETING REAGENTS HAVE SHOWN PREFERABLE OUTCOMES IN PATIENTS WITH COLITIS. HERE, WE NOTE A NEW AWARENESS OF RNA MODIFICATION IN THE TARGETING OF IBD AND RELATED DISEASES, WHICH WILL CONTRIBUTE TO EARLY DIAGNOSIS, DISEASE MONITORING, AND POSSIBLE CONTROL BY INNOVATIVE THERAPEUTIC APPROACHES. 2022 7 3703 32 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 3541 46 IMMUNOEPIGENETIC REGULATION OF INFLAMMATORY BOWEL DISEASE: CURRENT INSIGHTS INTO NOVEL EPIGENETIC MODULATIONS OF THE SYSTEMIC IMMUNE RESPONSE. THE IMMUNE SYSTEM AND ENVIRONMENTAL FACTORS ARE INVOLVED IN VARIOUS DISEASES, SUCH AS INFLAMMATORY BOWEL DISEASE (IBD), THROUGH THEIR EFFECT ON GENETICS, WHICH MODULATES IMMUNE CELLS. IBD ENCOMPASSES TWO MAIN PHENOTYPES, CROHN'S DISEASE, AND ULCERATIVE COLITIS, WHICH ARE MANIFESTED AS CHRONIC AND SYSTEMIC RELAPSE-REMITTING GASTROINTESTINAL TRACT DISORDERS WITH RISING GLOBAL INCIDENCE AND PREVALENCE. THE PATHOPHYSIOLOGY OF IBD IS COMPLEX AND NOT FULLY UNDERSTOOD. EPIGENETIC RESEARCH HAS RESULTED IN VALUABLE INFORMATION FOR UNRAVELING THE ETIOLOGY OF THIS IMMUNE-MEDIATED DISEASE. THUS, THE MAIN OBJECTIVE OF THE PRESENT REVIEW IS TO SUMMARIZE THE CURRENT FINDINGS ON THE ROLE OF EPIGENETIC MECHANISMS IN IBD TO SHED LIGHT ON THEIR POTENTIAL CLINICAL RELEVANCE. THIS REVIEW FOCUSES ON THE LATEST EVIDENCE REGARDING PERIPHERAL BLOOD MONONUCLEAR CELLS AND EPIGENETIC CHANGES IN HISTONE MODIFICATION, DNA METHYLATION, AND TELOMERE SHORTENING IN IBD. THE VARIOUS IDENTIFIED EPIGENETIC DNA PROFILES WITH CLINICAL VALUE IN IBD COULD BE USED AS BIOMARKERS FOR MORE ACCURATELY PREDICTING DISEASE DEVELOPMENT, TREATMENT RESPONSE, AND THERAPY-RELATED ADVERSE EVENTS. ULTIMATELY, THE INFORMATION PRESENTED HERE COULD BE OF POTENTIAL RELEVANCE FOR FUTURE CLINICAL PRACTICE IN DEVELOPING MORE EFFICIENT AND PRECISE MEDICINE TO IMPROVE THE QUALITY OF LIFE FOR PATIENTS WITH IBD. 2023 9 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 10 6353 32 THE ROLE OF GENETIC AND EPIGENETIC REGULATION IN INTESTINAL FIBROSIS IN INFLAMMATORY BOWEL DISEASE: A DESCENDING PROCESS OR A PROGRAMMED CONSEQUENCE? INFLAMMATORY BOWEL DISEASES (IBDS) ARE A GROUP OF CHRONIC DISEASES CHARACTERIZED BY RECURRING PERIODS OF EXACERBATION AND REMISSION. FIBROSIS OF THE INTESTINE IS ONE OF THE MOST COMMON COMPLICATIONS OF IBD. BASED ON CURRENT ANALYSES, IT IS EVIDENT THAT GENETIC FACTORS AND MECHANISMS, AS WELL AS EPIGENETIC FACTORS, PLAY A ROLE IN THE INDUCTION AND PROGRESSION OF INTESTINAL FIBROSIS IN IBD. KEY GENETIC FACTORS AND MECHANISMS THAT APPEAR TO BE SIGNIFICANT INCLUDE NOD2, TGF-BETA, TLRS, IL23R, AND ATG16L1. DEOXYRIBONUCLEIC ACID (DNA) METHYLATION, HISTONE MODIFICATION, AND RIBONUCLEIC ACID (RNA) INTERFERENCE ARE THE PRIMARY EPIGENETIC MECHANISMS. GENETIC AND EPIGENETIC MECHANISMS, WHICH SEEM TO BE IMPORTANT IN THE PATHOPHYSIOLOGY AND PROGRESSION OF IBD, MAY POTENTIALLY BE USED IN TARGETED THERAPY IN THE FUTURE. THEREFORE, THE AIM OF THIS STUDY WAS TO GATHER AND DISCUSS SELECTED MECHANISMS AND GENETIC FACTORS, AS WELL AS EPIGENETIC FACTORS. 2023 11 4330 49 MICRORNAS: AN EPIGENETIC TOOL TO STUDY CELIAC DISEASE. THIS ARTICLE SUMMARIZES RECENT FINDINGS ON THE ROLE OF MICRORNAS (MIRNAS) IN BIOLOGICAL PROCESSES ASSOCIATED WITH THE REGULATION OF CHRONIC INFLAMMATION AND AUTOIMMUNITY. MIRNAS ARE SMALL NON-CODING RNA MOLECULES THAT HAVE BEEN RECENTLY EMERGED AS A NEW CLASS OF MODULATORS OF GENE EXPRESSION AT THE POST-TRANSCRIPTIONAL LEVEL. MIRNAS BIND TO COMPLEMENTARY SEQUENCES OF SPECIFIC TARGETS OF MESSENGERS RNA, WHICH CAN INTERFERE WITH PROTEIN SYNTHESIS. WE REVIEWED STUDIES THAT EVALUATED THE EXPRESSION PATTERNS OF MIRNAS IN DIFFERENT AUTOIMMUNE DISEASES, ESPECIALLY IN CELIAC DISEASE (CD). CD IS A CHRONIC ENTEROPATHY TRIGGERED BY GLUTEN PROTEINS, CHARACTERIZED BY ALTERED IMMUNE RESPONSES IN GENETICALLY SUSCEPTIBLE INDIVIDUALS THAT RESULTS IN DAMAGE TO THE BOWEL MUCOSA. CD HAS A HIGH PREVALENCE AND AN EFFECTIVE TREATMENT BY A SPECIFIC DIET ("GLUTEN FREE DIET"). GENETIC FACTORS CONFER SUSCEPTIBILITY BUT DO NOT EXPLAIN THE WHOLE DISEASE, SUGGESTING THAT ENVIRONMENTAL FACTORS DO PLAY A RELEVANT ROLE IN THE DEVELOPMENT OF THE CONDITION.THE EVALUATION OF THE POTENTIAL ROLE OF MIRNA IS OF PARTICULAR INTEREST IN CD GIVEN THAT THESE EPIGENETIC MECHANISMS IN THE PATHOGENESIS OF AUTOIMMUNE AND INFLAMMATORY DISEASES HAVE BEEN RECENTLY DESCRIBED. IMPROVING OUR UNDERSTANDING OF MIRNAS IN CD WILL CONTRIBUTE TO CLARIFY THE ROLE OF ALTERED EPIGENETIC REGULATION IN THE DEVELOPMENT AND COURSE OF THIS DISEASE. 2014 12 3017 33 GENETICS AND EPIGENETICS OF INFLAMMATORY BOWEL DISEASE. THE RELEVANCE OF GENETIC AND EPIGENETIC ALTERATIONS IN THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE (IBD) IS STILL POORLY UNDERSTOOD. SO FAR, 240 RISK GENE LOCI HAVE BEEN ASSOCIATED WITH IBD. THEY ARE MAINLY INVOLVED IN REGULATING INNATE AND ADAPTIVE IMMUNITY, AS WELL AS MAINTAINING INTESTINAL EPITHELIAL BARRIER FUNCTION. HOWEVER, THE FUNCTIONAL CONSEQUENCES OF THE IDENTIFIED GENETIC POLYMORPHISMS FOR IBD PATHOGENESIS IN VIVO ARE OFTEN UNKNOWN. EVEN LESS IS KNOWN ABOUT THE ROLE FOR EPIGENETIC MODIFICATIONS IN IBD PATHOGENESIS. THOUGH A NUMBER OF EPIGENETIC EVENTS SEEM TO BE CAUSATIVELY INVOLVED IBD PATHOGENESIS, OUR KNOWLEDGE ABOUT THE FUNCTIONAL RELEVANCE OF THOSE EPIGENETIC MODIFICATIONS IS SCANTY. THIS OPENS UP A BROAD RESEARCH FIELD THAT GENERATES NOVEL INSIGHTS INTO THE PATHOPHYSIOLOGY OF INTESTINAL AND CHRONIC INFLAMMATORY DISEASE. PATTERNS OF DNA METHYLATION AND HISTONE MODIFICATIONS MIGHT SERVE NOT ONLY AS BIOMARKERS OF DISEASE ACTIVITY OR DISEASE COURSE, BUT ALSO AS NEW TARGETS IN THERAPEUTIC INTERVENTIONS IN IBD PATIENTS. 2018 13 2591 47 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 14 5561 42 ROLE OF HISTONE DEACETYLASES IN MONOCYTE FUNCTION IN HEALTH AND CHRONIC INFLAMMATORY DISEASES. HISTONE DEACETYLASES (HDACS) ARE A FAMILY OF 18 MEMBERS THAT PARTICIPATE IN THE EPIGENETIC REGULATION OF GENE EXPRESSION. IN ADDITION TO HISTONES, SOME HDACS ALSO DEACETYLATE TRANSCRIPTION FACTORS AND SPECIFIC CYTOPLASMIC PROTEINS.MONOCYTES, AS PART OF THE INNATE IMMUNE SYSTEM, MAINTAIN TISSUE HOMEOSTASIS AND HELP FIGHT INFECTIONS AND CANCER. IN THESE CELLS, HDACS ARE INVOLVED IN MULTIPLE PROCESSES INCLUDING PROLIFERATION, MIGRATION, DIFFERENTIATION, INFLAMMATORY RESPONSE, INFECTIONS, AND TUMORIGENESIS. HERE, A SYSTEMATIC DESCRIPTION OF THE ROLE THAT MOST HDACS PLAY IN THESE FUNCTIONS IS REVIEWED. SPECIFICALLY, SOME HDACS INDUCE A PRO-INFLAMMATORY RESPONSE AND PLAY MAJOR ROLES IN HOST DEFENSE. CONVERSELY, OTHER HDACS REPROGRAM MONOCYTES AND MACROPHAGES TOWARDS AN IMMUNOSUPPRESSIVE PHENOTYPE. THE RIGHT BALANCE BETWEEN BOTH TYPES HELPS MONOCYTES TO RESPOND CORRECTLY TO THE DIFFERENT PHYSIOLOGICAL/PATHOLOGICAL STIMULI. HOWEVER, ABERRANT EXPRESSIONS OR ACTIVITIES OF SPECIFIC HDACS ARE ASSOCIATED WITH AUTOIMMUNE DISEASES ALONG WITH OTHER CHRONIC INFLAMMATORY DISEASES, INFECTIONS, OR CANCER.THIS PAPER CRITICALLY REVIEWS THE INTERESTING AND EXTENSIVE KNOWLEDGE REGARDING THE ROLE OF SOME HDACS IN THESE PATHOLOGIES. IT ALSO SHOWS THAT AS YET, VERY LITTLE PROGRESS HAS BEEN MADE TOWARD THE GOAL OF FINDING EFFECTIVE HDAC-TARGETED THERAPIES. HOWEVER, GIVEN THEIR OBVIOUS POTENTIAL, WE CONCLUDE THAT IT IS WORTH THE EFFORT TO DEVELOP MONOCYTE-SPECIFIC DRUGS THAT SELECTIVELY TARGET HDAC SUBTYPES WITH THE AIM OF FINDING EFFECTIVE TREATMENTS FOR DISEASES IN WHICH OUR INNATE IMMUNE SYSTEM IS INVOLVED. 2021 15 3681 45 INFLAMMATION, DNA METHYLATION AND COLITIS-ASSOCIATED CANCER. INFLAMMATION CAN RESULT FROM A RANGE OF SOURCES INCLUDING MICROBIAL INFECTIONS, EXPOSURE TO ALLERGENS AND TOXIC CHEMICALS, AUTOIMMUNE DISEASE AND OBESITY. A WELL-BALANCED IMMUNE RESPONSE CAN BE ANTI-TUMORIGENIC; HOWEVER, A SUSTAINED OR CHRONIC INFLAMMATORY RESPONSE IS GENERALLY HARMFUL AS THE IMMUNE RESPONSE BECOMES DISTORTED. A CAUSAL LINK BETWEEN CHRONIC INFLAMMATION AND CANCER IS NOW WELL ACCEPTED AND MANY CHRONICALLY INFLAMED ORGANS OF THE GASTROINTESTINAL TRACT SHOW THIS ASSOCIATION. FOR EXAMPLE, PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD), INCLUDING BOTH ULCERATIVE COLITIS AND CROHN'S DISEASE, HAVE A 2- TO 3-FOLD GREATER LIFETIME RISK OF DEVELOPING COLORECTAL CANCER COMPARED WITH THE GENERAL POPULATION. THE DEVELOPMENT OF COLITIS-ASSOCIATED CANCER (CAC) IS THOUGHT TO BE MULTIFACETED AND IS PROBABLY DUE TO A COMBINATION OF GENETIC FACTORS, EPIGENETIC FACTORS AND THE DURATION, EXTENT AND SEVERITY OF DISEASE. RECENTLY, EPIGENETIC ALTERATIONS, IN PARTICULAR ALTERATIONS IN DNA METHYLATION, HAVE BEEN OBSERVED DURING INFLAMMATION AND INFLAMMATION-ASSOCIATED CARCINOGENESIS. THE MEDIATORS OF THIS, THE SIGNIFICANCE OF THESE CHANGES IN DNA METHYLATION AND THE EFFECT THIS HAS ON GENE EXPRESSION AND THE MALIGNANT TRANSFORMATION OF THE EPITHELIAL CELLS DURING IBD AND CAC ARE DISCUSSED IN THIS REVIEW. THE RECENT ADVANCES IN TECHNOLOGIES TO STUDY GENOME-WIDE DNA METHYLATION AND THE THERAPEUTIC POTENTIAL OF UNDERSTANDING THESE MOLECULAR MECHANISMS ARE ALSO HIGHLIGHTED. 2012 16 4365 39 MIRNA MOLECULES-LATE BREAKING TREATMENT FOR INFLAMMATORY BOWEL DISEASES? MICRORNAS (MIRNAS) ARE A GROUP OF NON-CODING RNAS THAT PLAY A CRITICAL ROLE IN REGULATING EPIGENETIC MECHANISMS IN INFLAMMATION-RELATED DISEASES. INFLAMMATORY BOWEL DISEASES (IBDS), WHICH PRIMARILY INCLUDE ULCERATIVE COLITIS (UC) AND CROHN'S DISEASE (CD), ARE CHARACTERIZED BY CHRONIC RECURRENT INFLAMMATION OF INTESTINAL TISSUES. DUE TO THE MULTIFACTORIAL ETIOLOGY OF THESE DISEASES, THE DEVELOPMENT OF INNOVATIVE TREATMENT STRATEGIES THAT CAN EFFECTIVELY MAINTAIN REMISSION AND ALLEVIATE DISEASE SYMPTOMS IS A MAJOR CHALLENGE. IN RECENT YEARS, EVIDENCE FOR THE REGULATORY ROLE OF MIRNAS IN THE PATHOGENETIC MECHANISMS OF VARIOUS DISEASES, INCLUDING IBD, HAS BEEN ACCUMULATING. IN LIGHT OF THESE FINDINGS, MIRNAS REPRESENT POTENTIAL INNOVATIVE CANDIDATES FOR THERAPEUTIC APPLICATION IN IBD. IN THIS REVIEW, WE DISCUSS RECENT FINDINGS ON THE ROLE OF MIRNAS IN REGULATING INFLAMMATORY RESPONSES, MAINTAINING INTESTINAL BARRIER INTEGRITY, AND DEVELOPING FIBROSIS IN CLINICAL AND EXPERIMENTAL IBD. THE FOCUS IS ON THE EXISTING LITERATURE, INDICATING POTENTIAL THERAPEUTIC APPLICATION OF MIRNAS IN BOTH PRECLINICAL EXPERIMENTAL IBD MODELS AND TRANSLATIONAL DATA IN THE CONTEXT OF CLINICAL IBD. TO DATE, A LARGE AND DIVERSE DATA SET, WHICH IS GROWING RAPIDLY, SUPPORTS THE POTENTIAL USE OF MIRNA-BASED THERAPIES IN CLINICAL PRACTICE, ALTHOUGH MANY QUESTIONS REMAIN UNANSWERED. 2023 17 2333 35 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 18 3350 38 HISTONE DEACETYLATION MEETS MIRNA: EPIGENETICS AND POST-TRANSCRIPTIONAL REGULATION IN CANCER AND CHRONIC DISEASES. INTRODUCTION: EPIGENETIC REGULATION VIA DNA METHYLATION, HISTONE ACETYLATION, AS WELL AS BY MICRORNAS (MIRNAS) IS CURRENTLY IN THE SCIENTIFIC FOCUS DUE TO ITS ROLE IN CARCINOGENESIS AND ITS INVOLVEMENT IN INITIATION, PROGRESSION AND METASTASIS. WHILE MANY TARGET GENES OF DNA METHYLATION, HISTONE ACETYLATION AND MIRNAS ARE KNOWN, EVEN LESS INFORMATION EXISTS AS TO HOW THESE MECHANISMS COOPERATE AND HOW THEY MAY REGULATE EACH OTHER IN A SPECIFIC PATHOLOGICAL CONTEXT. FOR FURTHER DEVELOPMENT OF THERAPEUTIC APPROACHES, THIS REVIEW PRESENTS THE CURRENT STATUS OF THE CROSSTALK OF HISTONE ACETYLATION AND MIRNAS IN HUMAN CARCINOGENESIS AND CHRONIC DISEASES. AREAS COVERED: THIS ARTICLE REVIEWS INFORMATION FROM COMPREHENSIVE PUBMED SEARCHES TO EVALUATE RELEVANT LITERATURE WITH A FOCUS ON POSSIBLE ASSOCIATION BETWEEN HISTONE ACETYLATION, MIRNAS AND THEIR TARGETS. OUR ANALYSIS IDENTIFIED SPECIFIC MIRNAS WHICH COLLABORATE WITH HISTONE DEACETYLASES (HDACS) AND COOPERATIVELY REGULATE SEVERAL RELEVANT TARGET GENES. EXPERT OPINION: FOURTEEN MIRNAS COULD BE LINKED TO THE EXPRESSION OF EIGHT HDACS INFLUENCING THE ALPHA-(1,6)-FUCOSYLTRANSFERASE, POLYCYSTIN-2 AND THE FIBROBLAST-GROWTH-FACTOR 2 PATHWAYS. FOCUSING ON THE COMPLEX LINKAGE OF MIRNA AND HDAC EXPRESSION COULD GIVE DEEPER INSIGHTS IN NEW 'DRUGGABLE' TARGETS AND MIGHT PROVIDE POSSIBLE NOVEL THERAPEUTIC APPROACHES IN FUTURE. 2015 19 5550 40 ROLE OF EPIGENETICS IN INFLAMMATION-ASSOCIATED DISEASES. THERE IS CONSIDERABLE EVIDENCE SUGGESTING THAT EPIGENETIC MECHANISMS MAY MEDIATE DEVELOPMENT OF CHRONIC INFLAMMATION BY MODULATING THE EXPRESSION OF PRO-INFLAMMATORY CYTOKINE TNF-ALPHA, INTERLEUKINS, TUMOR SUPPRESSOR GENES, ONCOGENES AND AUTOCRINE AND PARACRINE ACTIVATION OF THE TRANSCRIPTION FACTOR NF-KAPPAB. THESE MOLECULES ARE CONSTITUTIVELY PRODUCED BY A VARIETY OF CELLS UNDER CHRONIC INFLAMMATORY CONDITIONS, WHICH IN TURN LEADS TO THE DEVELOPMENT OF MAJOR DISEASES SUCH AS AUTOIMMUNE DISORDERS, CHRONIC OBSTRUCTIVE PULMONARY DISEASES, NEURODEGENERATIVE DISEASES AND CANCER. DISTINCT OR GLOBAL CHANGES IN THE EPIGENETIC LANDSCAPE ARE HALLMARKS OF CHRONIC INFLAMMATION DRIVEN DISEASES. EPIGENETICS INCLUDE CHANGES TO DISTINCT MARKERS ON THE GENOME AND ASSOCIATED CELLULAR TRANSCRIPTIONAL MACHINERY THAT ARE COPIED DURING CELL DIVISION (MITOSIS AND MEIOSIS). THESE CHANGES APPEAR FOR A SHORT SPAN OF TIME AND THEY NECESSARILY DO NOT MAKE PERMANENT CHANGES TO THE PRIMARY DNA SEQUENCE ITSELF. HOWEVER, THE MOST FREQUENTLY OBSERVED EPIGENETIC CHANGES INCLUDE ABERRANT DNA METHYLATION, AND HISTONE ACETYLATION AND DEACETYLATION. IN THIS CHAPTER, WE FOCUS ON PRO-INFLAMMATORY MOLECULES THAT ARE REGULATED BY ENZYMES INVOLVED IN EPIGENETIC MODIFICATIONS SUCH AS ARGININE AND LYSINE METHYL TRANSFERASES, DNA METHYLTRANSFERASE, HISTONE ACETYLTRANSFERASES AND HISTONE DEACETYLASES AND THEIR ROLE IN INFLAMMATION DRIVEN DISEASES. AGENTS THAT MODULATE OR INHIBIT THESE EPIGENETIC MODIFICATIONS, SUCH AS HAT OR HDAC INHIBITORS HAVE SHOWN GREAT POTENTIAL IN INHIBITING THE PROGRESSION OF THESE DISEASES. GIVEN THE PLASTICITY OF THESE EPIGENETIC CHANGES AND THEIR READINESS TO RESPOND TO INTERVENTION BY SMALL MOLECULE INHIBITORS, THERE IS A TREMENDOUS POTENTIAL FOR THE DEVELOPMENT OF NOVEL THERAPEUTICS THAT WILL SERVE AS DIRECT OR ADJUVANT THERAPEUTIC COMPOUNDS IN THE TREATMENT OF THESE DISEASES. 2013 20 2532 34 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