1 6799 48 [EPIGENETIC AND CURRENT TREATMENT APPROACHES IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE]. EPIGENETICS MECHANISMS SUCH AS DNA METHYLATION, HISTONE ACETYLATION AND NON-CODING RNAS MAY PLAY ARE A ROLE IN THE PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). RESEARCHS WITH REGARD EPIGENETIC IN COPD CAN SHED LIGHT ON PATHOGENES AND MAY BE RELEVANT IN THE DEVELOPMENT OF NOVEL TARGETED THERAPIES. THE AIM OF THIS ARTICLE IS TO REVIEW EPIGENETIC MECHANISMS NEW TREATMENTS APPROACHES IN COPD. 2016 2 1878 24 EMERGING ROLES OF LONG NONCODING RNA IN CHONDROGENESIS, OSTEOGENESIS, AND OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS THE MOST PREVALENT AGE-RELATED DEBILITATING JOINT DISEASE, AND IS CHARACTERIZED PRIMARILY BY ARTICULAR CARTILAGE DEGRADATION AND SUBCHONDRAL BONE LESIONS. IT IS ALSO THE LEADING CAUSE OF CHRONIC MORBIDITY IN OLDER POPULATIONS. THE ETIOLOGY OF OA IS MULTIFACTORIAL, WITH THE UNDERLYING REGULATORY MECHANISMS REMAINING LARGELY UNKNOWN. LONG NONCODING RNA (LNCRNA) IS A GROUP OF NONCODING RNAS DEFINED AS BEING >200 NUCLEOTIDES IN LENGTH. INCREASING EVIDENCE DEMONSTRATES THAT MANY LNCRNAS SERVE AS CRITICAL REGULATORS OF CHONDROGENESIS AND BONE AND CARTILAGE HOMEOSTASIS, THEREBY INFLUENCING OA DEVELOPMENT. IN THIS REVIEW, WE HIGHLIGHT THE CURRENT UNDERSTANDING CONCERNING LNCRNAS, INCLUDING THEIR PHYSICAL FEATURES, BIOLOGICAL FUNCTIONS, AND POTENTIAL ROLES IN CHONDROGENESIS, OSTEOGENESIS, AND OA. THIS INFORMATION MAY SHED NEW LIGHT ON THE EPIGENETIC REGULATION OF CARTILAGE AND SUBSTANTIATE LNCRNAS AS NOVEL THERAPEUTIC TARGETS IN OA. 2019 3 4130 20 MECHANISMS OF FERROPTOSIS AND EMERGING LINKS TO THE PATHOLOGY OF NEURODEGENERATIVE DISEASES. NEURODEGENERATIVE DISEASES ARE A DIVERSE CLASS OF DISEASES ATTRIBUTED TO CHRONIC PROGRESSIVE NEURONAL DEGENERATION AND SYNAPTIC LOSS IN THE BRAIN AND/OR SPINAL CORD, INCLUDING ALZHEIMER'S DISEASE, PARKINSON'S DISEASE, HUNTINGTON'S DISEASE, AMYOTROPHIC LATERAL SCLEROSIS AND MULTIPLE SCLEROSIS. THE PATHOGENESIS OF NEURODEGENERATIVE DISEASES IS COMPLEX AND DIVERSE, OFTEN INVOLVING MITOCHONDRIAL DYSFUNCTION, NEUROINFLAMMATION, AND EPIGENETIC CHANGES. HOWEVER, THE PATHOGENESIS OF NEURODEGENERATIVE DISEASES HAS NOT BEEN FULLY ELUCIDATED. RECENTLY, ACCUMULATING EVIDENCE REVEALED THAT FERROPTOSIS, A NEWLY DISCOVERED IRON-DEPENDENT AND LIPID PEROXIDATION-DRIVEN TYPE OF PROGRAMMED CELL DEATH, PROVIDES ANOTHER EXPLANATION FOR THE OCCURRENCE AND PROGRESSION OF NEURODEGENERATIVE DISEASES. HERE, WE PROVIDE AN OVERVIEW OF THE PROCESS AND REGULATION MECHANISMS OF FERROPTOSIS, AND SUMMARIZE CURRENT RESEARCH PROGRESSES THAT SUPPORT THE CONTRIBUTION OF FERROPTOSIS TO THE PATHOGENESIS OF NEURODEGENERATIVE DISEASES. A COMPREHENSIVE UNDERSTANDING OF THE EMERGING ROLES OF FERROPTOSIS IN NEURODEGENERATIVE DISEASES WILL SHED LIGHT ON THE DEVELOPMENT OF NOVEL THERAPEUTIC TECHNOLOGIES AND STRATEGIES FOR SLOWING DOWN THE PROGRESSION OF THESE DISEASES. 2022 4 6738 22 WHAT'S YOUR CUP OF TEA? THE ROLE OF HERBAL COMPOUNDS IN THE MANAGEMENT OF MULTIPLE SCLEROSIS. MULTIPLE SCLEROSIS (MS) IS A CHRONIC, INFLAMMATORY, NEURODEGENERATIVE DISEASE THAT IS CHARACTERIZED BY A COMPLEX ETIOLOGY. EFFORTS TOWARDS THE MANAGEMENT OF MS HAVE LONG BEEN DIRECTED TOWARDS SYMPTOMATIC RELIEF, AS WELL AS THE USE OF IMMUNE-MODULATORY, DISEASE MODIFYING THERAPIES; HOWEVER, INCONSISTENT TREATMENT RESPONSES STILL PREVAIL, INCREASING THE RISK FOR DISEASE PROGRESSION. WHILE A GREAT DEAL OF RESEARCH ATTEMPTED TO UNRAVEL THE COMPLEXITY OF TREATMENT RESPONSES IN LIGHT OF EPIGENETIC VARIABILITY, PARALLEL EFFORTS IN THE DIRECTION OF ALTERNATIVE MEDICINE MAY BE AS PARAMOUNT. HERBAL COMPOUNDS HAVE LONG BEEN REGARDED AS SAFE AND VERSATILE OPTIONS FOR AIDING IN VARIOUS DISORDERS, INCLUDING NEURODEGENERATIVE CONDITIONS LIKE MS. NUMEROUS STUDIES HAVE TAKEN INTEREST IN A MYRIAD OF HERBAL PLANTS FOR THEIR POTENTIAL BENEFIT IN ALLEVIATING SOME OF THE MOST COMMON MS SYMPTOMS SUCH AS SPASTICITY AND FATIGUE, DELAYING THE PROGRESSION OF THE DISEASE, AS WELL AS INFLUENCING THE OVERALL QUALITY OF LIFE FOR MS PATIENTS. THIS REVIEW AIMS TO PROVIDE A COMPREHENSIVE OVERVIEW OF RECENT CLINICAL STUDIES EXAMINING THE EFFECTS OF VARIOUS HERBAL PLANTS ON DIFFERENT ASPECTS OF MS, IN AN ATTEMPT TO SHED LIGHT ON AN IMPORTANT TOOL FOR AIDING IN THE MANAGEMENT OF THIS COMPLEX AND MULTIFACTORIAL DISEASE. 2023 5 1136 24 COMPREHENSIVE OVERVIEW OF MICRORNA FUNCTION IN RHEUMATOID ARTHRITIS. MICRORNAS (MIRNAS), A CLASS OF ENDOGENOUS SINGLE-STRANDED SHORT NONCODING RNAS, HAVE EMERGED AS VITAL EPIGENETIC REGULATORS OF BOTH PATHOLOGICAL AND PHYSIOLOGICAL PROCESSES IN ANIMALS. THEY DIRECT FUNDAMENTAL CELLULAR PATHWAYS AND PROCESSES BY FINE-TUNING THE EXPRESSION OF MULTIPLE GENES AT THE POSTTRANSCRIPTIONAL LEVEL. GROWING EVIDENCE SUGGESTS THAT MIRNAS ARE IMPLICATED IN THE ONSET AND DEVELOPMENT OF RHEUMATOID ARTHRITIS (RA). RA IS A CHRONIC INFLAMMATORY DISEASE THAT MAINLY AFFECTS SYNOVIAL JOINTS. THIS COMMON AUTOIMMUNE DISORDER IS CHARACTERIZED BY A COMPLEX AND MULTIFACETED PATHOGENESIS, AND ITS MORBIDITY, DISABILITY AND MORTALITY RATES REMAIN CONSISTENTLY HIGH. MORE IN-DEPTH INSIGHTS INTO THE UNDERLYING MECHANISMS OF RA ARE REQUIRED TO ADDRESS UNMET CLINICAL NEEDS AND OPTIMIZE TREATMENT. HEREIN, WE COMPREHENSIVELY REVIEW THE DEREGULATED MIRNAS AND IMPAIRED CELLULAR FUNCTIONS IN RA TO SHED LIGHT ON SEVERAL ASPECTS OF RA PATHOGENESIS, WITH A FOCUS ON EXCESSIVE INFLAMMATION, SYNOVIAL HYPERPLASIA AND PROGRESSIVE JOINT DAMAGE. THIS REVIEW ALSO PROVIDES PROMISING TARGETS FOR INNOVATIVE THERAPIES OF RA. IN ADDITION, WE DISCUSS THE REGULATORY ROLES AND CLINICAL POTENTIAL OF EXTRACELLULAR MIRNAS IN RA, HIGHLIGHTING THEIR PROSPECTIVE APPLICATIONS AS DIAGNOSTIC AND PREDICTIVE BIOMARKERS. 2023 6 1476 23 DIVERSE EPIGENETIC REGULATIONS OF MACROPHAGES IN ATHEROSCLEROSIS. EMERGING RESEARCH ON EPIGENETICS HAS RESULTED IN MANY NOVEL DISCOVERIES IN ATHEROSCLEROSIS (AS), AN INFLAMMAGING-ASSOCIATED DISEASE CHARACTERIZED BY CHRONIC INFLAMMATION PRIMARILY DRIVEN BY MACROPHAGES. THE BULK OF EVIDENCE HAS DEMONSTRATED THE CENTRAL ROLE OF EPIGENETIC MACHINERY IN MACROPHAGE POLARIZATION TO PRO- (M1-LIKE) OR ANTI-INFLAMMATORY (M2-LIKE) PHENOTYPE. AN INCREASING NUMBER OF EPIGENETIC ALTERATIONS AND THEIR MODIFIERS INVOLVED IN REPROGRAMMING MACROPHAGES BY REGULATING DNA METHYLATION OR HISTONE MODIFICATIONS (E.G., METHYLATION, ACETYLATION, AND RECENTLY LACTYLATION) HAVE BEEN IDENTIFIED. THEY MAY ACT TO DETERMINE OR SKEW THE DIRECTION OF MACROPHAGE POLARIZATION IN AS LESIONS, THEREBY REPRESENTING A PROMISING TARGET. HERE WE DESCRIBE THE CURRENT UNDERSTANDING OF THE EPIGENETIC MACHINERY INVOLVING MACROPHAGE POLARIZATION, TO SHED LIGHT ON CHRONIC INFLAMMATION-DRIVING ONSET AND PROGRESSION OF INFLAMMAGING-ASSOCIATED DISEASES, USING AS AS A PROTOTYPIC EXAMPLE, AND DISCUSS THE CHALLENGE FOR DEVELOPING EFFECTIVE THERAPIES TARGETING THE EPIGENETIC MODIFIERS AGAINST THESE DISEASES, PARTICULARLY HIGHLIGHTING A POTENTIAL STRATEGY BASED ON EPIGENETICALLY-GOVERNED REPOLARIZATION FROM M1-LIKE TO M2-LIKE PHENOTYPE. 2022 7 757 24 CARTILAGE REPAIR BY MESENCHYMAL STEM CELLS: CLINICAL TRIAL UPDATE AND PERSPECTIVES. OSTEOARTHRITIS IS A DEGENERATIVE DISEASE OF JOINTS WITH DESTRUCTION OF ARTICULAR CARTILAGE ASSOCIATED WITH SUBCHONDRAL BONE HYPERTROPHY AND INFLAMMATION. OA IS THE LEADING CAUSE OF JOINT PAIN RESULTING IN SIGNIFICANT WORSENING OF THE QUALITY-OF-LIFE IN THE ELDERLY. NUMEROUS EFFORTS HAVE BEEN SPENT TO OVERCOME THE INHERENTLY POOR HEALING ABILITY OF ARTICULAR CARTILAGE. MESENCHYMAL STEM CELLS (MSCS) HAVE BEEN IN THE LIMELIGHT OF CELL-BASED THERAPIES TO PROMOTE CARTILAGE REPAIR. DESPITE PROGRESSIVE ADVANCEMENTS IN MSC MANIPULATION AND THE INTRODUCTION OF VARIOUS BIOACTIVE SCAFFOLDS AND GROWTH FACTORS IN PRECLINICAL STUDIES, CURRENT CLINICAL TRIALS ARE STILL AT EARLY STAGES WITH PRELIMINARY AIMS TO EVALUATE SAFETY, FEASIBILITY AND EFFICACY. THIS REVIEW SUMMARISES RECENTLY REPORTED MSC-BASED CLINICAL TRIALS AND DISCUSSES NEW RESEARCH DIRECTIONS WITH PARTICULAR FOCUS ON THE POTENTIAL APPLICATION OF MSC-DERIVED EXTRACELLULAR VEHICLES, MIRNAS AND ADVANCED GENE EDITING TECHNIQUES WHICH MAY SHED LIGHT ON THE DEVELOPMENT OF NOVEL TREATMENT STRATEGIES. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: THIS REVIEW SUMMARISES RECENT MSC-RELATED CLINICAL RESEARCH THAT FOCUSES ON CARTILAGE REPAIR. WE ALSO PROPOSE A NOVEL POSSIBLE TRANSLATIONAL DIRECTION FOR HYALINE CARTILAGE FORMATION AND A NEW PARADIGM MAKING USE OF EXTRA-CELLULAR SIGNALLING AND EPIGENETIC REGULATION IN THE APPLICATION OF MSCS FOR CARTILAGE REPAIR. 2017 8 2550 30 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 9 2094 21 EPIGENETIC EFFECTS MEDIATED BY ANTIEPILEPTIC DRUGS AND THEIR POTENTIAL APPLICATION. AN EPIGENETIC EFFECT MAINLY REFERS TO A HERITABLE MODULATION IN GENE EXPRESSION IN THE SHORT TERM BUT DOES NOT INVOLVE ALTERATIONS IN THE DNA ITSELF. EPIGENETIC MOLECULAR MECHANISMS INCLUDE DNA METHYLATION, HISTONE MODIFICATION, AND UNTRANSLATED RNA REGULATION. ANTIEPILEPTIC DRUGS HAVE DRAWN ATTENTION TO BIOLOGICAL AND TRANSLATIONAL MEDICINE BECAUSE THEIR IMPACT ON EPIGENETIC MECHANISMS WILL LEAD TO THE IDENTIFICATION OF NOVEL BIOMARKERS AND POSSIBLE THERAPEUTIC STRATEGIES FOR THE PREVENTION AND TREATMENT OF VARIOUS DISEASES RANGING FROM NEUROPSYCHOLOGICAL DISORDERS TO CANCERS AND OTHER CHRONIC CONDITIONS. HOWEVER, THESE TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL ALTERATIONS CAN ALSO RESULT IN ADVERSE REACTIONS AND TOXICITY IN VITRO AND IN VIVO. HENCE, IN THIS REVIEW, WE FOCUS ON RECENT FINDINGS SHOWING EPIGENETIC PROCESSES MEDIATED BY ANTIEPILEPTIC DRUGS TO ELUCIDATE THEIR APPLICATION IN MEDICAL EXPERIMENTS AND SHED LIGHT ON EPIGENETIC RESEARCH FOR MEDICINAL PURPOSES. 2020 10 4365 25 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 11 5309 21 PSORIASIS PATHOGENESIS AND TREATMENT. RESEARCH ON PSORIASIS PATHOGENESIS HAS LARGELY INCREASED KNOWLEDGE ON SKIN BIOLOGY IN GENERAL. IN THE PAST 15 YEARS, BREAKTHROUGHS IN THE UNDERSTANDING OF THE PATHOGENESIS OF PSORIASIS HAVE BEEN TRANSLATED INTO TARGETED AND HIGHLY EFFECTIVE THERAPIES PROVIDING FUNDAMENTAL INSIGHTS INTO THE PATHOGENESIS OF CHRONIC INFLAMMATORY DISEASES WITH A DOMINANT IL-23/TH17 AXIS. THIS REVIEW DISCUSSES THE MECHANISMS INVOLVED IN THE INITIATION AND DEVELOPMENT OF THE DISEASE, AS WELL AS THE THERAPEUTIC OPTIONS THAT HAVE ARISEN FROM THE DISSECTION OF THE INFLAMMATORY PSORIATIC PATHWAYS. OUR DISCUSSION BEGINS BY ADDRESSING THE INFLAMMATORY PATHWAYS AND KEY CELL TYPES INITIATING AND PERPETUATING PSORIATIC INFLAMMATION. NEXT, WE DESCRIBE THE ROLE OF GENETICS, ASSOCIATED EPIGENETIC MECHANISMS, AND THE INTERACTION OF THE SKIN FLORA IN THE PATHOPHYSIOLOGY OF PSORIASIS. FINALLY, WE INCLUDE A COMPREHENSIVE REVIEW OF WELL-ESTABLISHED WIDELY AVAILABLE THERAPIES AND NOVEL TARGETED DRUGS. 2019 12 2283 22 EPIGENETIC REGULATION IN FIBROSIS PROGRESS. FIBROSIS, A COMMON PROCESS OF CHRONIC INFLAMMATORY DISEASES, IS DEFINED AS A REPAIR RESPONSE DISORDER WHEN ORGANS UNDERGO CONTINUOUS DAMAGE, ULTIMATELY LEADING TO SCAR FORMATION AND FUNCTIONAL FAILURE. AROUND THE WORLD, FIBROTIC DISEASES CAUSE HIGH MORTALITY, UNFORTUNATELY, WITH LIMITED TREATMENT MEANS IN CLINICAL PRACTICE. WITH THE DEVELOPMENT AND APPLICATION OF DEEP SEQUENCING TECHNOLOGY, COMPREHENSIVELY EXPLORING THE EPIGENETIC MECHANISM IN FIBROSIS HAS BEEN ALLOWED. EXTENSIVE REMODELING OF EPIGENETICS CONTROLLING VARIOUS CELLS PHENOTYPE AND MOLECULAR MECHANISMS INVOLVED IN FIBROGENESIS WAS SUBSEQUENTLY VERIFIED. IN THIS REVIEW, WE SUMMARIZE THE REGULATORY MECHANISMS OF DNA METHYLATION, HISTONE MODIFICATION, NONCODING RNAS (NCRNAS) AND N6-METHYLADENOSINE (M6A) MODIFICATION IN ORGAN FIBROSIS, FOCUSING ON HEART, LIVER, LUNG AND KIDNEY. ADDITIONALLY, WE EMPHASIZE THE DIVERSITY OF EPIGENETICS IN THE CELLULAR AND MOLECULAR MECHANISMS RELATED TO FIBROSIS. FINALLY, THE POTENTIAL AND PROSPECT OF TARGETED THERAPY FOR FIBROSIS BASED ON EPIGENETIC IS DISCUSSED. 2021 13 2508 19 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 14 5931 26 TARGETING EPIGENETIC MODIFIERS TO REPROGRAMME MACROPHAGES IN NON-RESOLVING INFLAMMATION-DRIVEN ATHEROSCLEROSIS. EPIGENOMIC AND EPIGENETIC RESEARCH HAS BEEN PROVIDING SEVERAL NEW INSIGHTS INTO A VARIETY OF DISEASES CAUSED BY NON-RESOLVING INFLAMMATION, INCLUDING CARDIOVASCULAR DISEASES. ATHEROSCLEROSIS (AS) HAS LONG BEEN RECOGNIZED AS A CHRONIC INFLAMMATORY DISEASE OF THE ARTERIAL WALLS, CHARACTERIZED BY LOCAL PERSISTENT AND STEPWISE ACCELERATING INFLAMMATION WITHOUT RESOLUTION, ALSO KNOWN AS UNCONTROLLED INFLAMMATION. THE PATHOGENESIS OF AS IS DRIVEN PRIMARILY BY HIGHLY PLASTIC MACROPHAGES VIA THEIR POLARIZATION TO PRO- OR ANTI-INFLAMMATORY PHENOTYPES AS WELL AS OTHER NOVEL SUBTYPES RECENTLY IDENTIFIED BY SINGLE-CELL SEQUENCING. ALTHOUGH EMERGING EVIDENCE HAS INDICATED THE KEY ROLE OF THE EPIGENETIC MACHINERY IN THE REGULATION OF MACROPHAGE PLASTICITY, THE INVESTIGATION OF EPIGENETIC ALTERATIONS AND MODIFIERS IN AS AND RELATED INFLAMMATION IS STILL IN ITS INFANCY. AN INCREASING NUMBER OF THE EPIGENETIC MODIFIERS (E.G. TET2, DNMT3A, HDAC3, HDAC9, JMJD3, KDM4A) HAVE BEEN IDENTIFIED IN EPIGENETIC REMODELLING OF MACROPHAGES THROUGH DNA METHYLATION OR HISTONE MODIFICATIONS (E.G. METHYLATION, ACETYLATION, AND RECENTLY LACTYLATION) IN INFLAMMATION. THESE OR MANY UNEXPLORED MODIFIERS FUNCTION TO DETERMINE OR SWITCH THE DIRECTION OF MACROPHAGE POLARIZATION VIA TRANSCRIPTIONAL REPROGRAMMING OF GENE EXPRESSION AND INTRACELLULAR METABOLIC REWIRING UPON MICROENVIRONMENTAL CUES, THEREBY REPRESENTING A PROMISING TARGET FOR ANTI-INFLAMMATORY THERAPY IN AS. HERE, WE REVIEW UP-TO-DATE FINDINGS INVOLVING THE EPIGENETIC REGULATION OF MACROPHAGES TO SHED LIGHT ON THE MECHANISM OF UNCONTROLLED INFLAMMATION DURING AS ONSET AND PROGRESSION. WE ALSO DISCUSS CURRENT CHALLENGES FOR DEVELOPING AN EFFECTIVE AND SAFE ANTI-AS THERAPY THAT TARGETS THE EPIGENETIC MODIFIERS AND PROPOSE A POTENTIAL ANTI-INFLAMMATORY STRATEGY THAT REPOLARIZES MACROPHAGES FROM PRO- TO ANTI-INFLAMMATORY PHENOTYPES. 2021 15 2527 21 EPIGENETICS APPROACHES TOWARD PRECISION MEDICINE FOR IDIOPATHIC PULMONARY FIBROSIS: FOCUS ON DNA METHYLATION. GENETIC INFORMATION IS NOT TRANSMITTED SOLELY BY DNA BUT BY THE EPIGENETICS PROCESS. EPIGENETICS DESCRIBES MOLECULAR MISSING LINK PATHWAYS THAT COULD BRIDGE THE GAP BETWEEN THE GENETIC BACKGROUND AND ENVIRONMENTAL RISK FACTORS THAT CONTRIBUTE TO THE PATHOGENESIS OF PULMONARY FIBROSIS. SPECIFIC EPIGENETIC PATTERNS, ESPECIALLY DNA METHYLATION, HISTONE MODIFICATIONS, LONG NON-CODING, AND MICRORNA (MIRNAS), AFFECT THE ENDOPHENOTYPES UNDERLYING THE DEVELOPMENT OF IDIOPATHIC PULMONARY FIBROSIS (IPF). AMONG ALL THE EPIGENETIC MARKS, DNA METHYLATION MODIFICATIONS HAVE BEEN THE MOST WIDELY STUDIED IN IPF. THIS REVIEW SUMMARIZES THE CURRENT KNOWLEDGE CONCERNING DNA METHYLATION CHANGES IN PULMONARY FIBROSIS AND DEMONSTRATES A PROMISING NOVEL EPIGENETICS-BASED PRECISION MEDICINE. 2023 16 2460 19 EPIGENETIC THERAPIES FOR OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS AN AGE-ASSOCIATED DISEASE CHARACTERIZED BY CHRONIC JOINT PAIN RESULTING FROM DEGRADATION OF ARTICULAR CARTILAGE, INFLAMMATION OF THE SYNOVIAL LINING, AND CHANGES TO THE SUBCHONDRAL BONE. DESPITE THE WIDE PREVALENCE, NO FDA-APPROVED DISEASE-MODIFYING DRUGS EXIST. RECENT EVIDENCE HAS DEMONSTRATED THAT EPIGENETIC DYSREGULATION OF MULTIPLE MOLECULAR PATHWAYS UNDERLIES OA PATHOGENESIS, PROVIDING A NEW MECHANISTIC AND THERAPEUTIC AXIS WITH THE ADVANTAGE OF TARGETING MULTIPLE DEREGULATED PATHWAYS SIMULTANEOUSLY. IN THIS REVIEW, WE FOCUS ON THE EPIGENETIC REGULATORS THAT HAVE BEEN IMPLICATED IN OA, THEIR INDIVIDUAL ROLES, AND POTENTIAL CROSSTALK. FINALLY, WE DISCUSS THE PHARMACOLOGICAL MOLECULES THAT CAN MODULATE THEIR ACTIVITIES AND DISCUSS THE POTENTIAL ADVANTAGES AND CHALLENGES ASSOCIATED WITH EPIGENOME-BASED THERAPEUTICS FOR OA. 2020 17 539 19 ATHEROSCLEROSIS IS AN EPIGENETIC DISEASE. ATHEROSCLEROSIS IS A CHRONIC INFLAMMATORY AND LIPID-DEPOSITORY DISEASE THAT EVENTUALLY LEADS TO ACUTE CARDIOVASCULAR EVENTS. EMERGING EVIDENCE SUPPORTS THAT EPIGENETIC PROCESSES SUCH AS DNA METHYLATION, HISTONE MODIFICATION, AND NONCODING RNAS PLAY AN IMPORTANT ROLE IN PLAQUE PROGRESSION AND VULNERABILITY, HIGHLIGHTING THE THERAPEUTIC POTENTIAL OF EPIGENETIC DRUGS IN CARDIOVASCULAR THERAPEUTICS. 2018 18 2544 22 EPIGENETICS IN LIVER DISEASE: FROM BIOLOGY TO THERAPEUTICS. KNOWLEDGE OF THE FUNDAMENTAL EPIGENETIC MECHANISMS GOVERNING GENE EXPRESSION AND CELLULAR PHENOTYPE ARE SUFFICIENTLY ADVANCED THAT NOVEL INSIGHTS INTO THE EPIGENETIC CONTROL OF CHRONIC LIVER DISEASE ARE NOW EMERGING. HEPATOLOGISTS ARE IN THE PROCESS OF SHEDDING LIGHT ON THE ROLES PLAYED BY DNA METHYLATION, HISTONE/CHROMATIN MODIFICATIONS AND NON-CODING RNAS IN SPECIFIC LIVER PATHOLOGIES. ALONGSIDE THESE DISCOVERIES ARE ADVANCES IN THE TECHNOLOGIES FOR THE DETECTION AND QUANTIFICATION OF EPIGENETIC BIOMARKERS, EITHER DIRECTLY FROM PATIENT TISSUE OR FROM BODY FLUIDS. THE PREMISE FOR THIS REVIEW IS TO SURVEY THE RECENT ADVANCES IN THE FIELD OF LIVER EPIGENETICS AND TO EXPLORE THEIR POTENTIAL FOR TRANSLATION BY INDUSTRY AND CLINICAL HEPATOLOGISTS FOR THE DESIGN OF NOVEL THERAPEUTICS AND DIAGNOSTIC/PROGNOSTIC BIOMARKERS. IN PARTICULAR, WE PRESENT FINDINGS IN THE CONTEXT OF HEPATOCELLULAR CARCINOMA, FIBROSIS AND NON-ALCOHOLIC FATTY LIVER DISEASE, WHERE THERE IS URGENT UNMET NEED FOR NEW CLINICAL INTERVENTIONS AND BIOMARKERS. 2016 19 3829 25 INVOLVEMENT OF EPIGENETICS IN OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS THE MOST PREVALENT CHRONIC AGE-RELATED ARTHRITIC DISEASE THAT MAINLY AFFECTS THE DIARTHRODIAL JOINTS. NEVERTHELESS, THERE IS NO TREATMENT CURRENTLY AVAILABLE THAT CAN EFFECTIVELY REDUCE SYMPTOMS OR SLOW DOWN OR STOP DISEASE PROGRESSION. THE LACK OF DISEASE-MODIFYING THERAPIES COULD BE EXPLAINED BY THE COMPLEX PATHOGENESIS OF OA, WHICH IS STILL NOT COMPLETELY UNDERSTOOD. INTERTWINED EPIGENETIC MECHANISMS SUCH AS DNA METHYLATION, HISTONE MODIFICATIONS, AND NONCODING RNAS (NCRNAS) HAVE BEEN INDICATED AS IMPORTANT CELLULAR TOOLS TO MAINTAIN TISSUE HOMEOSTASIS UPON ENVIRONMENTAL CHALLENGES. THE CURRENT REVIEW ILLUSTRATES THAT DYSFUNCTIONAL EPIGENETIC CONTROL MECHANISMS IN THE ARTICULAR CARTILAGE LIKELY PLAY AN IMPORTANT ROLE IN DRIVING OA PATHOPHYSIOLOGY. 2017 20 2224 22 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