1 2223 121 EPIGENETIC MODIFICATIONS IN SPINAL LIGAMENT AGING. SPINAL STENOSIS IS A COMMON DEGENERATIVE SPINE DISORDER IN THE AGED POPULATION AND THE SPINAL LIGAMENT AGING IS A MAIN CONTRIBUTOR TO THIS CHRONIC DISEASE. HOWEVER, THE UNDERLYING MECHANISMS OF SPINAL LIGAMENT AGING REMAIN UNCLEAR. EPIGENETICS IS THE STUDY OF HERITABLE AND REVERSIBLE CHANGES IN THE FUNCTION OF A GENE OR GENOME THAT OCCUR WITHOUT ANY ALTERATION IN THE PRIMARY DNA SEQUENCE. EPIGENETIC ALTERATIONS HAVE BEEN DEMONSTRATED TO PLAY CRUCIAL ROLES IN AGE-RELATED DISEASES AND CONDITIONS, AND THEY ARE RECENTLY STUDIED AS BIOMARKERS AND THERAPEUTIC TARGETS IN THE FIELD OF CANCER RESEARCH. THE MAIN EPIGENETIC MODIFICATIONS, INCLUDING DNA METHYLATION ALTERATION, HISTONE MODIFICATIONS AS WELL AS DYSREGULATED NONCODING RNA MODULATION, HAVE ALL BEEN IMPLICATED IN SPINAL LIGAMENT AGING DISEASES. DNA METHYLATION MODULATES THE EXPRESSION OF CRITICAL GENES INCLUDING WNT5A, GDNF, ACSM5, MIR-497 AND MIR-195 DURING SPINAL LIGAMENT DEGENERATION. HISTONE MODIFICATIONS WIDELY AFFECT GENE EXPRESSION AND OBVIOUS HISTONE MODIFICATION ABNORMALITIES HAVE BEEN FOUND IN SPINAL LIGAMENT AGING. MICRORNAS (MIRNAS), LONG NONCODING RNAS (LNCRNAS) AND CIRCULAR RNAS (CIRCRNAS) EXERT CRUCIAL REGULATING EFFECTS ON SPINAL LIGAMENT AGING CONDITIONS VIA TARGETING VARIOUS OSTEOGENIC OR FIBROGENIC DIFFERENTIATION RELATED GENES. TO OUR KNOWLEDGE, THERE IS NO SYSTEMATIC REVIEW YET TO SUMMARIZE THE INVOLVEMENT OF EPIGENETIC MECHANISMS OF SPINAL LIGAMENT AGING IN DEGENERATIVE SPINAL DISEASES. IN THIS STUDY, WE SYSTEMATICALLY DISCUSSED THE DIFFERENT EPIGENETIC MODIFICATIONS AND THEIR POTENTIAL FUNCTIONS IN SPINAL LIGAMENT AGING PROCESS. 2022 2 6795 26 [EFFECT OF HISTONE ACETYLATION ON OSTEOGENIC DIFFERENTIATION OF PERIODONTAL LIGAMENT STEM CELLS DERIVED FROM PERIODONTITIS TISSUE]. EPIGENETICS IS DEFINED AS A CHANGE IN GENE EXPRESSION WITHOUT THE ALTERATION OF THE GENETIC SEQUENCE. SUCH A CHANGE WOULD BE INHERITED BY OFFSPRING. HISTONE ACETYLATION IS A TYPE OF EPIGENETICS. EXISTING STUDIES PROPOSED THAT CHRONIC PERIODONTITIS IS RELATED TO EPIGENETIC MODIFICATION. IN THIS REVIEW, WE SUMMARISED THE INFLUENCE OF CHRONIC PERIODONTITIS ON PERIODONTAL LIGAMENT STEM CELLS BY HISTONE ACETYLATION. 2019 3 2220 40 EPIGENETIC MODIFICATIONS IN NEUROPATHIC PAIN. NEUROPATHIC PAIN (NP) IS A COMMON SYMPTOM IN MANY DISEASES OF THE SOMATOSENSORY NERVOUS SYSTEM, WHICH SEVERELY AFFECTS THE PATIENT'S QUALITY OF LIFE. EPIGENETICS ARE HERITABLE ALTERATIONS IN GENE EXPRESSION THAT DO NOT CAUSE PERMANENT CHANGES IN THE DNA SEQUENCE. EPIGENETIC MODIFICATIONS CAN AFFECT GENE EXPRESSION AND FUNCTION AND CAN ALSO MEDIATE CROSSTALK BETWEEN GENES AND THE ENVIRONMENT. INCREASING EVIDENCE SHOWS THAT EPIGENETIC MODIFICATIONS, INCLUDING DNA METHYLATION, HISTONE MODIFICATION, NON-CODING RNA, AND RNA MODIFICATION, ARE INVOLVED IN THE DEVELOPMENT AND MAINTENANCE OF NP. IN THIS REVIEW, WE FOCUS ON THE CURRENT KNOWLEDGE OF EPIGENETIC MODIFICATIONS IN THE DEVELOPMENT AND MAINTENANCE OF NP. THEN, WE ILLUSTRATE DIFFERENT FACETS OF EPIGENETIC MODIFICATIONS THAT REGULATE GENE EXPRESSION AND THEIR CROSSTALK. FINALLY, WE DISCUSS THE BURGEONING EVIDENCE SUPPORTING THE POTENTIAL OF EMERGING EPIGENETIC THERAPIES, WHICH HAS BEEN VALUABLE IN UNDERSTANDING MECHANISMS AND OFFERS NOVEL AND POTENT TARGETS FOR NP THERAPY. 2021 4 3772 35 INTERACTION BETWEEN MICRORNA AND DNA METHYLATION IN ATHEROSCLEROSIS. ATHEROSCLEROSIS (AS) IS A CHRONIC INFLAMMATORY DISEASE ACCOMPANIED BY COMPLEX PATHOLOGICAL CHANGES, SUCH AS ENDOTHELIAL DYSFUNCTION, FOAM CELL FORMATION, AND VASCULAR SMOOTH MUSCLE CELL PROLIFERATION. MANY APPROACHES, INCLUDING REGULATING AS-RELATED GENE EXPRESSION IN THE TRANSCRIPTIONAL OR POST-TRANSCRIPTIONAL LEVEL, CONTRIBUTE TO ALLEVIATING AS DEVELOPMENT. THE DNA METHYLATION IS A CRUCIAL EPIGENETIC MODIFICATION IN REGULATING CELL FUNCTION BY SILENCING THE RELATIVE GENE EXPRESSION. THE MICRORNA (MIRNA) IS A TYPE OF NONCODING RNA THAT PLAYS AN IMPORTANT ROLE IN GENE POST-TRANSCRIPTIONAL REGULATION AND DISEASE DEVELOPMENT. THE DNA METHYLATION AND THE MIRNA ARE IMPORTANT EPIGENETIC FACTORS IN AS. HOWEVER, RECENT STUDIES HAVE FOUND A MUTUAL REGULATION BETWEEN THESE TWO FACTORS IN AS DEVELOPMENT. IN THIS STUDY, RECENT INSIGHTS INTO THE ROLES OF MIRNA AND DNA METHYLATION AND THEIR INTERACTION IN THE AS PROGRESSION ARE REVIEWED. 2021 5 6340 36 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 2508 36 EPIGENETICS AND OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS THE MOST COMMON FORM OF JOINT DISEASE AND THE LEADING CAUSE OF CHRONIC DISABILITY IN MIDDLE-AGED AND OLDER POPULATIONS. THE DEVELOPMENT OF DISEASE-MODIFYING THERAPY FOR OA CURRENTLY FACES MAJOR OBSTACLES LARGELY BECAUSE THE REGULATORY MECHANISMS FOR THE FUNCTION OF JOINT TISSUE CELLS REMAIN UNCLEAR. PREVIOUS STUDIES HAVE FOUND THAT THE ALTERATIONS IN GENE EXPRESSION OF SPECIFIC TRANSCRIPTION FACTORS (TFS), PRO- OR ANTI-INFLAMMATORY CYTOKINES, MATRIX PROTEINASES AND EXTRACELLULAR MATRIX (ECM) PROTEINS IN ARTICULAR CARTILAGE MAY BE INVOLVED IN THE DEVELOPMENT OF OA. HOWEVER, THE REGULATORY MECHANISMS FOR THE EXPRESSION OF THOSE GENES IN OA CHONDROCYTES ARE LARGELY UNKNOWN. THE RECENT ADVANCES IN EPIGENETIC STUDIES HAVE SHED LIGHTS ON THE IMPORTANCE OF EPIGENETIC REGULATION OF GENE EXPRESSION IN THE DEVELOPMENT OF OA. IN THIS REVIEW, WE SUMMARIZE AND DISCUSS THE RECENT STUDIES ON THE REGULATORY ROLES OF VARIOUS EPIGENETIC MECHANISMS IN THE EXPRESSION OF GENES FOR SPECIFIC TFS, CYTOKINES, ECM PROTEINS AND MATRIX PROTEINASES, AS WELL THE SIGNIFICANCE OF THESE EPIGENETIC MECHANISMS IN THE PATHOGENESIS OF OA. 2015 7 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 8 6802 20 [EPIGENETIC MECHANISMS IN MODELS OF CHRONIC PAIN - A TARGET FOR NOVEL THERAPY?]. EVIDENCE OF EPIGENETICS' ROLE IN PAIN RESPONSE IS ACCUMULATING IN RECENT YEARS. TIGHTLY REGULATED EPIGENETIC ALTERATIONS ON DNA AND HISTONES IN THE SENSORY CIRCUIT SHAPE THE PHYSIOLOGICAL RESPONSE TO INJURY. ALTERING THOSE EPIGENETIC PROCESSES HINDERS THERAPEUTIC POTENTIAL IN PAIN. THIS REVIEW PROVIDES AN OVERVIEW OF EPIGENOMIC MODIFICATION IN THE DEVELOPMENT OF CHRONIC PAIN, AND SUMMARIZES THE THERAPEUTIC POTENTIAL TO ALTER EPIGENETIC PROCESSES. 2018 9 4289 31 MICRORNA IN OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS THE MOST PREVALENT DEGENERATIVE JOINT DISEASE AND IS ACCOMPANIED BY PAIN AND JOINT DYSFUNCTION. ITS CLINICAL TREATMENT TENDS TO BE UNSATISFACTORY. NOVEL TARGETS IN OA INCLUDE GENES THAT ARE INVOLVED IN OA PATHOPHYSIOLOGY AND HAVE BEEN DISCOVERED USING GENE NETWORK, EPIGENETIC AND MICRORNA (MIRNA) APPROACHES. MIRNA HAS BEEN IMPLICATED IN IMPORTANT CELLULAR PROCESSES SUCH AS LIPID METABOLISM, APOPTOSIS, DIFFERENTIATION AND ORGAN DEVELOPMENT. THE IMPORTANCE OF MIRNA REGULATION IN CELLULAR FUNCTION IS BECOMING INCREASINGLY CLEAR AS NEW MIRNA TARGETS ARE REVEALED. THE PRESENT REVIEW SUMMARIZES THE CURRENT EVIDENCE OF THE IMPORTANT ROLE PLAYED BY MIRNA IN DETERMINING THE COMPLEX GENE EXPRESSION PATTERNS OF OA CHONDROCYTES AND THEIR ROLE IN THE REGULATION OF TRANSCRIPTION, AND POSSIBLE DEMETHYLATION MECHANISMS THAT MIGHT BE APPLICABLE IN OA. IN SUMMARY, MIRNA MAY HAVE IMPORTANT DIAGNOSTIC AND THERAPEUTIC POTENTIAL, AND MIGHT PROVIDE A NOVEL MEANS OF TREATING OA. 2011 10 2550 32 EPIGENETICS IN OSTEOARTHRITIS: POTENTIAL OF HDAC INHIBITORS AS THERAPEUTICS. OSTEOARTHRITIS (OA) IS THE MOST COMMON JOINT DISEASE AND THE LEADING CAUSE OF CHRONIC DISABILITY IN MIDDLE-AGED AND OLDER POPULATIONS WORLDWIDE. THE DEVELOPMENT OF DISEASE MODIFYING THERAPY FOR OA IS IN ITS INFANCY LARGELY BECAUSE THE REGULATORY MECHANISMS FOR THE MOLECULAR EFFECTORS OF OA PATHOGENESIS ARE POORLY UNDERSTOOD. RECENT STUDIES IDENTIFIED EPIGENETIC EVENTS AS A CRITICAL REGULATOR OF MOLECULAR PLAYERS INVOLVED IN THE INDUCTION AND DEVELOPMENT OF OA. EPIGENETIC MECHANISMS INCLUDE DNA METHYLATION, NON-CODING RNA AND HISTONE MODIFICATIONS. THE AIM OF THIS REVIEW IS TO BRIEFLY HIGHLIGHT THE RECENT ADVANCES IN THE EPIGENETICS OF CARTILAGE AND POTENTIAL OF HDACS (HISTONE DEACETYLASES) INHIBITORS IN THE THERAPEUTIC MANAGEMENT OF OA. WE SUMMARIZE THE RECENT STUDIES UTILIZING HDAC INHIBITORS AS POTENTIAL THERAPEUTICS FOR INHIBITING DISEASE PROGRESSION AND PREVENTING THE CARTILAGE DESTRUCTION IN OA. HDACS CONTROL NORMAL CARTILAGE DEVELOPMENT AND HOMEOSTASIS AND UNDERSTANDING THE IMPACT OF HDACS INHIBITORS ON THE DISEASE PATHOGENESIS IS OF INTEREST BECAUSE OF ITS IMPORTANCE IN AFFECTING OVERALL CARTILAGE HEALTH AND HOMEOSTASIS. THESE FINDINGS ALSO SHED NEW LIGHT ON CARTILAGE DISEASE PATHOPHYSIOLOGY AND PROVIDE SUBSTANTIAL EVIDENCE THAT HDACS MAY BE POTENTIAL NOVEL THERAPEUTIC TARGETS IN OA. 2018 11 2308 39 EPIGENETIC REGULATION OF CHEMOKINE (CC-MOTIF) LIGAND 2 IN INFLAMMATORY DISEASES. APPROPRIATE RESPONSES TO INFLAMMATION ARE CONDUCIVE TO PATHOGEN ELIMINATION AND TISSUE REPAIR, WHILE UNCONTROLLED INFLAMMATORY REACTIONS ARE LIKELY TO RESULT IN THE DAMAGE OF TISSUES. CHEMOKINE (CC-MOTIF) LIGAND 2 (CCL2) IS THE MAIN CHEMOKINE AND ACTIVATOR OF MONOCYTES, MACROPHAGES, AND NEUTROPHILS. CCL2 PLAYED A KEY ROLE IN AMPLIFYING AND ACCELERATING THE INFLAMMATORY CASCADE AND IS CLOSELY RELATED TO CHRONIC NON-CONTROLLABLE INFLAMMATION (CIRRHOSIS, NEUROPATHIC PAIN, INSULIN RESISTANCE, ATHEROSCLEROSIS, DEFORMING ARTHRITIS, ISCHEMIC INJURY, CANCER, ETC.). THE CRUCIAL REGULATORY ROLES OF CCL2 MAY PROVIDE POTENTIAL TARGETS FOR THE TREATMENT OF INFLAMMATORY DISEASES. THEREFORE, WE PRESENTED A REVIEW OF THE REGULATORY MECHANISMS OF CCL2. GENE EXPRESSION IS LARGELY AFFECTED BY THE STATE OF CHROMATIN. DIFFERENT EPIGENETIC MODIFICATIONS, INCLUDING DNA METHYLATION, POST-TRANSLATIONAL MODIFICATION OF HISTONES, HISTONE VARIANTS, ATP-DEPENDENT CHROMATIN REMODELLING, AND NON-CODING RNA, COULD AFFECT THE 'OPEN' OR 'CLOSED' STATE OF DNA, AND THEN SIGNIFICANTLY AFFECT THE EXPRESSION OF TARGET GENES. SINCE MOST EPIGENETIC MODIFICATIONS ARE PROVEN TO BE REVERSIBLE, TARGETING THE EPIGENETIC MECHANISMS OF CCL2 IS EXPECTED TO BE A PROMISING THERAPEUTIC STRATEGY FOR INFLAMMATORY DISEASES. THIS REVIEW FOCUSES ON THE EPIGENETIC REGULATION OF CCL2 IN INFLAMMATORY DISEASES. 2023 12 1172 42 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 13 2532 35 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 14 2341 34 EPIGENETIC REGULATION OF LIVER FIBROSIS. FIBROSIS IS A COMMON AND IMPORTANT PATHOLOGY ASSOCIATED WITH PROGRESSIVE CHRONIC LIVER DISEASES AND UNDERLIES THE DEVELOPMENT OF CIRRHOSIS AND HEPATOCELLULAR CARCINOMA. RESEARCH INTO THE MOLECULAR REGULATION OF FIBROSIS HAS DISCOVERED THAT IT IS UNDER THE CONTROL OF A NUMBER OF EPIGENETIC MECHANISMS INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS AND THE ACTIVITIES OF NON-CODING RNAS. A DEEPER UNDERSTANDING OF HOW EPIGENETIC REGULATORS SUCH AS DNA METHYLTRANSERASES, METHYL-DNA BINDING PROTEINS, HISTONE MODIFYING ENZYMES AND REGULATORY RNA MOLECULES IMPACT ON THE FIBROGENIC PROCESS IS EXPECTED TO RESULT IN NEW BIOMARKERS FOR DISEASE PROGRESSION AS WELL AS NOVEL THERAPEUTIC TARGETS. THE AIM OF THIS MINI-REVIEW IS TO BRIEFLY INTRODUCE THE READER TO THE MAJOR EPIGENETIC REGULATORS SO FAR IDENTIFIED AS BEING IMPLICATED IN FIBROSIS. 2015 15 1597 43 DNA METHYLATION REGULATED GENE EXPRESSION IN ORGAN FIBROSIS. DNA METHYLATION IS A MAJOR EPIGENETIC MECHANISM TO REGULATE GENE EXPRESSION. EPIGENETIC REGULATION, INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS AND RNA INTERFERENCE, RESULTS IN HERITABLE CHANGES IN GENE EXPRESSION INDEPENDENT OF ALTERATIONS IN DNA SEQUENCE. EPIGENETIC REGULATION OFTEN OCCURS IN RESPONSE TO AGING AND ENVIRONMENT STIMULI, INCLUDING EXPOSURES AND DIET. STUDIES HAVE SHOWN THAT DNA METHYLATION IS CRITICAL IN THE PATHOGENESIS OF FIBROSIS INVOLVING MULTIPLE ORGAN SYSTEMS, CONTRIBUTING TO SIGNIFICANT MORBIDITY AND MORTALITY. ABERRANT DNA METHYLATION CAN SILENCE OR ACTIVATE GENE EXPRESSION PATTERNS THAT DRIVE THE FIBROSIS PROCESS. FIBROSIS IS A PATHOLOGICAL WOUND HEALING PROCESS IN RESPONSE TO CHRONIC INJURY. IT IS CHARACTERIZED BY EXCESSIVE EXTRACELLULAR MATRIX PRODUCTION AND ACCUMULATION, WHICH EVENTUALLY AFFECTS ORGAN ARCHITECTURE AND RESULTS IN ORGAN FAILURE. FIBROSIS CAN AFFECT A WIDE RANGE OF ORGANS, INCLUDING THE HEART AND LUNGS, AND HAVE LIMITED THERAPEUTIC OPTIONS. DNA METHYLATION, LIKE OTHER EPIGENETIC PROCESS, IS REVERSIBLE, THEREFORE REGARDED AS ATTRACTIVE THERAPEUTIC INTERVENTIONS. ALTHOUGH EPIGENETIC MECHANISMS ARE HIGHLY INTERACTIVE AND OFTEN REINFORCING, THIS REVIEW DISCUSSES DNA METHYLATION-DEPENDENT MECHANISMS IN THE PATHOGENESIS OF ORGAN FIBROSIS, WITH FOCUS ON CARDIAC AND PULMONARY FIBROSIS. WE DISCUSS SPECIFIC PRO- AND ANTI-FIBROTIC GENES AND PATHWAYS REGULATED BY DNA METHYLATION IN ORGAN FIBROSIS; WE FURTHER HIGHLIGHT THE POTENTIAL BENEFITS AND SIDE-EFFECTS OF EPIGENETIC THERAPIES IN FIBROTIC DISORDERS. 2017 16 3675 33 INFLAMMATION AND HISTONE MODIFICATION IN CHRONIC PAIN. INCREASING EVIDENCE SUGGESTS THAT EPIGENETIC MECHANISMS HAVE GREAT POTENTIAL IN THE FIELD OF PAIN. THE CHANGES AND ROLES OF EPIGENETICS OF THE SPINAL CORD AND DORSAL ROOT GANGLIA IN THE CHRONIC PAIN PROCESS MAY PROVIDE BROAD INSIGHTS FOR FUTURE PAIN MANAGEMENT. PRO-INFLAMMATORY CYTOKINES AND CHEMOKINES RELEASED BY MICROGLIA AND ASTROCYTES, AS WELL AS BLOOD-DERIVED MACROPHAGES, PLAY CRITICAL ROLES IN INDUCING AND MAINTAINING CHRONIC PAIN, WHILE HISTONE MODIFICATIONS MAY PLAY AN IMPORTANT ROLE IN INFLAMMATORY METABOLISM. THIS REVIEW PROVIDES AN OVERVIEW OF NEUROINFLAMMATION AND CHRONIC PAIN, AND WE SYSTEMATICALLY DISCUSS THE REGULATION OF NEUROINFLAMMATION AND HISTONE MODIFICATIONS IN THE CONTEXT OF CHRONIC PAIN. SPECIFICALLY, WE ANALYZED THE ROLE OF EPIGENETICS IN ALLEVIATING OR EXACERBATING CHRONIC PAIN BY MODULATING MICROGLIA, ASTROCYTES, AND THE PROINFLAMMATORY MEDIATORS THEY RELEASE. THIS REVIEW AIMED TO CONTRIBUTE TO THE DISCOVERY OF NEW THERAPEUTIC TARGETS FOR CHRONIC PAIN. 2022 17 2354 18 EPIGENETIC REGULATION OF PERSISTENT PAIN. PERSISTENT OR CHRONIC PAIN IS TIGHTLY ASSOCIATED WITH VARIOUS ENVIRONMENTAL CHANGES AND LINKED TO ABNORMAL GENE EXPRESSION WITHIN CELLS PROCESSING NOCICEPTIVE SIGNALING. EPIGENETIC REGULATION GOVERNS GENE EXPRESSION IN RESPONSE TO ENVIRONMENTAL CUES. RECENT ANIMAL MODEL AND CLINICAL STUDIES INDICATE THAT EPIGENETIC REGULATION PLAYS AN IMPORTANT ROLE IN THE DEVELOPMENT OR MAINTENANCE OF PERSISTENT PAIN AND POSSIBLY THE TRANSITION OF ACUTE PAIN TO CHRONIC PAIN, THUS SHEDDING LIGHT IN A DIRECTION FOR DEVELOPMENT OF NEW THERAPEUTICS FOR PERSISTENT PAIN. 2015 18 6886 37 [ROLE OF EPIGENETIC MODIFICATION IN HIGHER BRAIN DYSFUNCTION AND AGING]. EPIGENETIC MECHANISMS TYPICALLY INVOLVE HERITABLE ALTERATIONS IN CHROMATIN STRUCTURE, WHICH, IN TURN, REGULATE GENE EXPRESSION. FUNDAMENTAL INSIGHTS ABOUT EPIGENETIC HERITABILITY HAVE COME FROM STUDIES OF CELL DIVISION AND DEVELOPMENT. HOWEVER, THERE IS INCREASING EVIDENCE THAT THE REGULATION OF CHROMATIN STRUCTURE THROUGH HISTONE MODIFICATIONS AND DNA METHYLATION MIGHT MEDIATE THE EXPRESSION OF KEY GENES INVOLVED IN ACQUIRED CHRONIC DISORDERS. THIS IDEA IS FASCINATING BECAUSE SIMILAR MECHANISMS ARE USED FOR TRIGGERING AND STORING LONG-TERM MEMORIES AT THE CELLULAR LEVEL DURING, FOR EXAMPLE, HIGHER-BRAIN DYSFUNCTION, STRESS DISEASE, DRUG DEPENDENCE, AGING, AND CHRONIC PAIN. THIS REVIEW WILL EXPLORE THE MOST CURRENT ISSUES IN THE FIELD OF EPIGENETICS, WITH A FOCUS ON NEXT LEVELS OF TRANSCRIPTIONAL MECHANISMS UNDERLYING AGING, ENRICHED ENVIRONMENT AND DRUG ADDICTION. EPIGENETIC MECHANISMS, WHICH ARE KEY CELLULAR AND MOLECULAR PROCESSES THAT INTEGRATE DIVERSE ENVIRONMENTAL STIMULI TO EXERT POTENT AND OFTEN LONG-LASTING CHANGES IN GENE EXPRESSION THROUGH THE REGULATION OF CHROMATIN STRUCTURE, CONTRIBUTE TO TRANSCRIPTIONAL AND BEHAVIORAL CHANGES. 2012 19 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 20 1020 30 CIRCRNAS IN ATHEROSCLEROSIS, WITH SPECIAL EMPHASIS ON THE SPONGY EFFECT OF CIRCRNAS ON MIRNAS. ATHEROSCLEROSIS (AS) IS A CHRONIC INFLAMMATORY DISEASE, WHICH LEADS TO ATHEROSCLEROTIC RUPTURE, LUMEN STENOSIS AND THROMBOSIS, AND OFTEN ENDANGERS LIFE. CIRCULAR RNAS (CIRCRNAS) ARE A SPECIAL CLASS OF NON-CODING RNA MOLECULES, WHOSE ABNORMAL EXPRESSION HAS BEEN PROVED TO BE CLOSELY RELATED TO HUMAN DISEASES, INCLUDING AS. BOTH THE ABNORMAL REGULATION OF CIRCRNAS AND THE SPONGING EFFECT ON MIRNAS WOULD LEAD TO CHANGES IN GENE EXPRESSION IN THE FORM OF EPIGENETIC MODIFICATION, ULTIMATELY LEADING TO THE FORMATION OF AS. CIRCRNAS CAN BE USED AS PERIPHERAL BLOOD MARKERS OF AS, AND PLAY AN IMPORTANT REGULATORY ROLE IN THE PROLIFERATION, MIGRATION, INFLAMMATION AND APOPTOSIS OF VASCULAR SMOOTH MUSCLE CELLS, ENDOTHELIAL CELLS AND MACROPHAGE, WHICH ARE KEY CELLS FOR THE DEVELOPMENT OF AS. THE IN-DEPTH UNDERSTANDING OF CIRCRNAS IN AS NOT ONLY PROVIDES A NEW METHOD FOR THE DIAGNOSIS OF AS, BUT ALSO PROVIDES A NEW IDEA FOR THE TREATMENT OF AS. 2023