1 5562 101 ROLE OF HISTONE DEACETYLASES IN PANCREAS: IMPLICATIONS FOR PATHOGENESIS AND THERAPY. IN THE LAST YEARS, OUR KNOWLEDGE OF THE PATHOGENESIS IN ACUTE AND CHRONIC PANCREATITIS (AP/CP) AS WELL AS IN PANCREATIC CANCEROGENESIS HAS SIGNIFICANTLY DIVERSIFIED. NEVERTHELESS, THE MEDICINAL THERAPEUTIC OPTIONS ARE STILL LIMITED AND THERAPEUTIC SUCCESS AND PATIENT OUTCOME ARE POOR. EPIGENETIC DEREGULATION OF GENE EXPRESSION IS KNOWN TO CONTRIBUTE TO DEVELOPMENT AND PROGRESSION OF AP AND CP AS WELL AS OF PANCREATIC CANCER. THEREFORE, THE SELECTIVE INHIBITION OF ABERRANTLY ACTIVE EPIGENETIC REGULATORS CAN BE AN EFFECTIVE OPTION FOR FUTURE THERAPIES. HISTONE DEACETYLASES (HDACS) ARE ENZYMES THAT REMOVE AN ACETYL GROUP FROM HISTONE TAILS, THEREBY CAUSING CHROMATIN COMPACTION AND REPRESSION OF TRANSCRIPTION. IN THIS REVIEW WE PRESENT AN OVERVIEW OF THE CURRENTLY AVAILABLE LITERATURE ADDRESSING THE ROLE OF HDACS IN THE PANCREAS AND IN PANCREATIC DISEASES. IN PANCREATIC CANCEROGENESIS, HDACS PLAY A ROLE IN THE IMPORTANT PROCESS OF EPITHELIAL-MESENCHYMAL-TRANSITION, UBIQUITIN-PROTEASOME PATHWAY AND, HYPOXIA-INDUCIBLE-FACTOR-1-ANGIOGENESIS. FINALLY, WE FOCUS ON HDACS AS POTENTIAL THERAPEUTIC TARGETS BY SUMMARIZING CURRENTLY AVAILABLE HISTONE DEACETYLASE INHIBITORS. 2015 2 834 36 CHEMICAL BIOLOGY OF LYSINE DEMETHYLASES. ABNORMAL LEVELS OF DNA METHYLATION AND/OR HISTONE MODIFICATIONS ARE OBSERVED IN PATIENTS WITH A WIDE VARIETY OF CHRONIC DISEASES. METHYLATION OF LYSINES WITHIN HISTONE TAILS IS A KEY MODIFICATION THAT CONTRIBUTES TO INCREASED GENE EXPRESSION OR REPRESSION DEPENDING ON THE SPECIFIC RESIDUE AND DEGREE OF METHYLATION, WHICH IS IN TURN CONTROLLED BY THE INTERPLAY OF LYSINE METHYL TRANSFERASES AND DEMETHYLASES. DRUGS THAT TARGET THESE AND OTHER ENZYMES CONTROLLING CHROMATIN MODIFICATIONS CAN MODULATE THE EXPRESSION OF CLUSTERS OF GENES, POTENTIALLY OFFERING HIGHER THERAPEUTIC EFFICACY THAN CLASSICAL AGENTS ACTING ON DOWNSTREAM BIOCHEMICAL PATHWAYS THAT ARE SUSCEPTIBLE TO DEGENERACY. LYSINE DEMETHYLASES, FIRST DISCOVERED IN 2004, ARE THE SUBJECT OF INCREASING INTEREST AS THERAPEUTIC TARGETS. THIS REVIEW PROVIDES AN OVERVIEW OF RECENT FINDINGS IMPLICATING LYSINE DEMETHYLASES IN A RANGE OF THERAPEUTIC AREAS INCLUDING ONCOLOGY, IMMUNOINFLAMMATION, METABOLIC DISORDERS, NEUROSCIENCE, VIROLOGY AND REGENERATIVE MEDICINE, TOGETHER WITH A SUMMARY OF RECENT ADVANCES IN STRUCTURAL BIOLOGY AND SMALL MOLECULE INHIBITOR DISCOVERY, SUPPORTING THE TRACTABILITY OF THE PROTEIN FAMILY FOR THE DEVELOPMENT OF SELECTIVE DRUGLIKE INHIBITORS. 2011 3 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 4 3197 36 HDAC INHIBITORS: TARGETS FOR TUMOR THERAPY, IMMUNE MODULATION AND LUNG DISEASES. HISTONE DEACETYLASES (HDACS) ARE ENZYMES THAT PLAY A KEY ROLE IN THE EPIGENETIC REGULATION OF GENE EXPRESSION BY REMODELING CHROMATIN. INHIBITION OF HDACS IS A PROSPECTIVE THERAPEUTIC APPROACH FOR REVERSING EPIGENETIC ALTERATION IN SEVERAL DISEASES. IN PRECLINICAL RESEARCH, NUMEROUS TYPES OF HDAC INHIBITORS WERE DISCOVERED TO EXHIBIT POWERFUL AND SELECTIVE ANTICANCER PROPERTIES. HOWEVER, SUCH RESEARCH HAS REVEALED THAT THE EFFECTS OF HDAC INHIBITORS MAY BE FAR BROADER AND MORE INTRICATE THAN PREVIOUSLY THOUGHT. THIS REVIEW WILL PROVIDE INSIGHT INTO THE HDAC INHIBITORS AND THEIR MECHANISM OF ACTION WITH SPECIAL EMPHASIS ON THE SIGNIFICANCE OF HDAC INHIBITORS IN THE TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND LUNG CANCER. NANOCARRIER-MEDIATED HDAC INHIBITOR DELIVERY AND NEW APPROACHES FOR TARGETING HDACS ARE ALSO DISCUSSED. 2022 5 5937 35 TARGETING HISTONE DEACETYLASE ACTIVITY IN RHEUMATOID ARTHRITIS AND ASTHMA AS PROTOTYPES OF INFLAMMATORY DISEASE: SHOULD WE KEEP OUR HATS ON? CELLULAR ACTIVATION, PROLIFERATION AND SURVIVAL IN CHRONIC INFLAMMATORY DISEASES IS REGULATED NOT ONLY BY ENGAGEMENT OF SIGNAL TRANS-DUCTION PATHWAYS THAT MODULATE TRANSCRIPTION FACTORS REQUIRED FOR THESE PROCESSES, BUT ALSO BY EPIGENETIC REGULATION OF TRANSCRIPTION FACTOR ACCESS TO GENE PROMOTER REGIONS. HISTONE ACETYL TRANSFERASES COORDINATE THE RECRUITMENT AND ACTIVATION OF TRANSCRIPTION FACTORS WITH CONFORMATIONAL CHANGES IN HISTONES THAT ALLOW GENE PROMOTER EXPOSURE. HISTONE DEACETYLASES (HDACS) COUNTERACT HISTONE ACETYL TRANSFERASE ACTIVITY THROUGH THE TARGETING OF BOTH HISTONES AS WELL AS NONHISTONE SIGNAL TRANSDUCTION PROTEINS IMPORTANT IN INFLAMMATION. NUMEROUS STUDIES HAVE INDICATED THAT DEPRESSED HDAC ACTIVITY IN PATIENTS WITH INFLAMMATORY AIRWAY DISEASES MAY CONTRIBUTE TO LOCAL PROINFLAMMATORY CYTOKINE PRODUCTION AND DIMINISH PATIENT RESPONSES TO CORTICOSTEROID TREATMENT. RECENT OBSERVATIONS THAT HDAC ACTIVITY IS DEPRESSED IN RHEUMATOID ARTHRITIS PATIENT SYNOVIAL TISSUE HAVE PREDICTED THAT STRATEGIES RESTORING HDAC FUNCTION MAY BE THERAPEUTIC IN THIS DISEASE AS WELL. PHARMACOLOGICAL INHIBITORS OF HDAC ACTIVITY, HOWEVER, HAVE DEMONSTRATED POTENT THERAPEUTIC EFFECTS IN ANIMAL MODELS OF ARTHRITIS AND OTHER CHRONIC INFLAMMATORY DISEASES. IN THE PRESENT REVIEW WE ASSESS AND RECONCILE THESE OUTWARDLY PARADOXICAL STUDY RESULTS TO PROVIDE A WORKING MODEL FOR HOW ALTERATIONS IN HDAC ACTIVITY MAY CONTRIBUTE TO PATHOLOGY IN RHEUMATOID ARTHRITIS, AND HIGHLIGHT KEY QUESTIONS TO BE ANSWERED IN THE PRECLINICAL EVALUATION OF COMPOUNDS MODULATING THESE ENZYMES. 2008 6 3703 26 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 7 5550 33 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 8 5561 35 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 9 3350 37 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 10 2254 33 EPIGENETIC MODULATION: RESEARCH PROGRESS ON HISTONE ACETYLATION LEVELS IN MAJOR DEPRESSIVE DISORDERS. DEPRESSION IS A SERIOUS MENTAL ILLNESS AND A PREVALENT CONDITION WITH MULTIPLE AETIOLOGIES. THE IMPACT OF THE CURRENT THERAPEUTIC STRATEGIES IS LIMITED AND THE PATHOGENESIS OF THE ILLNESS IS NOT WELL UNDERSTOOD. ACCORDING TO PREVIOUS STUDIES, DEPRESSION ONSET IS INFLUENCED BY A VARIETY OF ENVIRONMENTAL AND GENETIC FACTORS, INCLUDING CHRONIC STRESS, ABERRANT CHANGES IN GENE EXPRESSION, AND HEREDITARY PREDISPOSITION. TRANSCRIPTIONAL REGULATION IN EUKARYOTES IS CLOSELY RELATED TO CHROMOSOME PACKING AND IS CONTROLLED BY HISTONE POST-TRANSLATIONAL MODIFICATIONS. THE DEVELOPMENT OF NEW ANTIDEPRESSANTS MAY PROCEED ALONG A NEW PATH WITH MEDICATIONS THAT TARGET EPIGENETICS. HISTONE DEACETYLASE INHIBITORS (HDACIS) ARE A CLASS OF COMPOUNDS THAT INTERFERE WITH THE FUNCTION OF HISTONE DEACETYLASES (HDACS). THIS REVIEW EXPLORES THE RELATIONSHIP BETWEEN HDACS AND DEPRESSION AND FOCUSES ON THE CURRENT KNOWLEDGE ON THEIR REGULATORY MECHANISM IN DEPRESSION AND THE POTENTIAL THERAPEUTIC USE OF HDACIS WITH ANTIDEPRESSANT EFFICACY IN PRECLINICAL RESEARCH. FUTURE RESEARCH ON INHIBITORS IS ALSO PROPOSED AND DISCUSSED. 2023 11 6131 41 THE EPIGENETIC REGULATION OF WOUND HEALING. SIGNIFICANCE: EPIGENETIC REGULATORY MECHANISMS ARE ESSENTIAL FOR EPIDERMAL HOMEOSTASIS AND CONTRIBUTE TO THE PATHOGENESIS OF MANY SKIN DISEASES, INCLUDING SKIN CANCER AND PSORIASIS. HOWEVER, WHILE THE EPIGENETIC REGULATION OF EPIDERMAL HOMEOSTASIS IS NOW BECOMING ACTIVE AREA OF RESEARCH, THE EPIGENETIC MECHANISMS CONTROLLING THE WOUND HEALING RESPONSE REMAIN RELATIVELY UNTOUCHED. RECENT ADVANCES: SUBSTANTIAL PROGRESS ACHIEVED WITHIN THE LAST TWO DECADES IN UNDERSTANDING EPIGENETIC MECHANISMS CONTROLLING GENE EXPRESSION ALLOWED DEFINING SEVERAL LEVELS, INCLUDING COVALENT DNA AND HISTONE MODIFICATIONS, ATP-DEPENDENT AND HIGHER-ORDER CHROMATIN CHROMATIN REMODELING, AS WELL AS NONCODING RNA- AND MICRORNA-DEPENDENT REGULATION. RESEARCH PERTAINED OVER THE LAST FEW YEARS SUGGESTS THAT EPIGENETIC REGULATORY MECHANISMS PLAY A PIVOTAL ROLE IN THE REGULATION OF SKIN REGENERATION AND CONTROL AN EXECUTION OF REPARATIVE GENE EXPRESSION PROGRAMS IN BOTH SKIN EPITHELIUM AND MESENCHYME. CRITICAL ISSUES: EPIGENETIC REGULATORS APPEAR TO BE INHERENTLY INVOLVED IN THE PROCESSES OF SKIN REPAIR, AND ARE ABLE TO DYNAMICALLY REGULATE KERATINOCYTE PROLIFERATION, DIFFERENTIATION, AND MIGRATION, TOGETHER WITH INFLUENCING DERMAL REGENERATION AND NEOANGIOGENESIS. THIS IS ACHIEVED THROUGH A SERIES OF COMPLEX REGULATORY MECHANISMS THAT ARE ABLE TO BOTH STIMULATE AND REPRESS GENE ACTIVATION TO TRANSIENTLY ALTER CELLULAR PHENOTYPE AND BEHAVIOR, AND INTERACT WITH GROWTH FACTOR ACTIVITY. FUTURE DIRECTIONS: UNDERSTANDING THE MOLECULAR BASIS OF EPIGENETIC REGULATION IS A PRIORITY AS IT REPRESENTS POTENTIAL THERAPEUTIC TARGETS FOR THE TREATMENT OF BOTH ACUTE AND CHRONIC SKIN CONDITIONS. FUTURE RESEARCH IS, THEREFORE, IMPERATIVE TO HELP DISTINGUISH EPIGENETIC MODULATING DRUGS THAT CAN BE USED TO IMPROVE WOUND HEALING. 2014 12 3855 27 IS THERE ANY THERAPEUTIC VALUE FOR THE USE OF HISTONE DEACETYLASE INHIBITORS FOR CHRONIC PAIN? CHRONIC PAIN IS A COMPLEX CLINICAL CONDITION THAT REDUCES THE QUALITY OF LIFE FOR BILLIONS OF PEOPLE. IN RECENT YEARS, THE ROLE OF EPIGENETIC MODULATION IN THE CONTROL OF LONG-TERM NEURONAL PLASTICITY HAS ATTRACTED THE ATTENTION OF PAIN RESEARCHERS. THE EPIGENETIC MECHANISMS INCLUDE COVALENT MODIFICATIONS OF DNA AND/OR HISTONE PROTEINS. MOUNTING EVIDENCE SUGGESTS THAT THE ACTIVITY OF HISTONE DEACETYLASES (HDACS) AND LEVELS OF HISTONE ACETYLATION ARE DYNAMIC AND THAT THESE ENZYMES MODULATE PAIN-RELATED SYNAPTIC PLASTICITY. THEREFORE, HDACS PLAY ESSENTIAL ROLES IN CHRONIC PAIN DEVELOPMENT AND MAINTENANCE. IN THIS MINI REVIEW, WE WILL DISCUSS THE ROLE OF HDACS IN THE PATHOGENESIS OF CHRONIC PAIN AND WILL CONSIDER THE THERAPEUTIC VALUE OF HDAC INHIBITORS IN TREATING CHRONIC PAIN. 2016 13 2341 27 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 14 6244 28 THE MECHANISMS OF HSC ACTIVATION AND EPIGENETIC REGULATION OF HSCS PHENOTYPES. EPIGENETICS IS A DYNAMICALLY EXPANDING FIELD OF SCIENCE ENTAILING NUMEROUS REGULATORY MECHANISMS CONTROLLING CHANGES OF GENE EXPRESSION IN RESPONSE TO ENVIRONMENTAL FACTORS. OVER THE RECENT YEARS THERE HAS BEEN A GREAT INTEREST IN EPIGENETIC MARKS AS A POTENTIAL DIAGNOSTIC AND PROGNOSTIC TOOL OR FUTURE TARGET FOR TREATMENT OF VARIOUS HUMAN DISEASES. THERE IS AN INCREASING BODY OF PUBLISHED RESEARCH TO SUGGEST THAT EPIGENETIC EVENTS REGULATE PROGRESSION OF CHRONIC LIVER DISEASE. EXPERIMENTAL MANIPULATION OF EPIGENETIC SIGNATURES SUCH AS DNA METHYLATION, HISTONE ACETYLATION / METHYLATION AND THE ACTIVITIES OF PROTEINS THAT EITHER ANNOTATE OR INTERPRET THESE EPIGENETIC MARKS CAN HAVE PROFOUND EFFECTS ON THE ACTIVATION AND PHENOTYPE OF HSC, KEY CELLS RESPONSIBLE FOR ONSET AND PROGRESSION OF LIVER FIBROSIS. THIS REVIEW PRESENTS RECENT ADVANCES IN EPIGENETIC ALTERATIONS, WHICH COULD PROVIDE MECHANISTIC INSIGHT INTO THE PATHOGENESIS OF CHRONIC LIVER DISEASE AND PROVIDE NOVEL CLINICAL APPLICATIONS. 2014 15 3333 28 HISTONE DEACETYLASE INHIBITORS AND DIABETIC KIDNEY DISEASE. DESPITE RECENT CLINICAL TRIAL ADVANCES AND IMPROVEMENTS IN CLINICAL CARE, KIDNEY DISEASE DUE TO DIABETES REMAINS THE MOST COMMON CAUSE OF CHRONIC KIDNEY FAILURE WORLDWIDE. IN THE SEARCH FOR NEW TREATMENTS, RECENT ATTENTIONS HAVE TURNED TO DRUG REPURPOSING OPPORTUNITIES, INCLUDING STUDY OF THE HISTONE DEACETYLASE (HDAC) INHIBITOR CLASS OF AGENTS. HDACS ARE A GROUP OF ENZYMES THAT REMOVE FUNCTIONAL ACETYL GROUPS FROM HISTONE AND NON-HISTONE PROTEINS AND THEY CAN AFFECT CELLULAR FUNCTION THROUGH BOTH EPIGENETIC AND NON-EPIGENETIC MEANS. OVER THE PAST DECADE, SEVERAL HDAC INHIBITORS HAVE BEEN ADOPTED INTO CLINICAL PRACTICE, PRIMARILY FOR THE TREATMENT OF HEMATOLOGICAL MALIGNANCY, WHEREAS OTHER EXISTING THERAPIES (FOR INSTANCE VALPROATE) HAVE BEEN FOUND TO HAVE HDAC INHIBITORY EFFECTS. HERE WE REVIEW THE CURRENT HDAC INHIBITORS IN THE CLINIC AND UNDER DEVELOPMENT; THE LITERATURE EVIDENCE SUPPORTING THE RENOPROTECTIVE EFFECTS OF HDAC INHIBITORS IN EXPERIMENTAL DIABETIC KIDNEY DISEASE; AND THE ADVERSE EFFECT PROFILES THAT MAY PREVENT EXISTING THERAPIES FROM ENTERING THE CLINIC FOR THIS INDICATION. WHEREAS RECENT RESEARCH EFFORTS HAVE SHED LIGHT ON THE FUNDAMENTAL ACTIONS OF HDACS IN THE DIABETIC KIDNEY, WHETHER THESE EFFORTS WILL TRANSLATE INTO NOVEL THERAPIES FOR PATIENTS WILL REQUIRE MORE SPECIFIC AND BETTER-TOLERATED THERAPIES. 2018 16 2532 33 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 17 2070 25 EPIGENETIC CONTROL OF SKIN IMMUNITY. EPIGENETICS HAS BEEN WELL UNDERSTOOD FOR ITS ROLE IN CELL DEVELOPMENT; HOWEVER, IT IS NOW KNOWN TO REGULATE MANY PROCESSES INVOLVED IN IMMUNE CELL ACTIVATION IN A VARIETY OF CELLS. THE SKIN MAINTAINS HOMEOSTASIS VIA CROSSTALK BETWEEN IMMUNE AND NON-IMMUNE CELLS. DISRUPTION OF NORMAL EPIGENETIC REGULATION IN THESE CELLS MAY ALTER THE TRANSCRIPTION OF IMMUNE-REGULATORY FACTORS AND AFFECT THE IMMUNOLOGICAL BALANCE IN THE SKIN. THIS REVIEW SUMMARIZES RECENT EVIDENCE FOR THE EPIGENETIC REGULATION OF SKIN IMMUNITY. MUCH OF WHAT IS KNOWN ABOUT EPIGENETIC INVOLVEMENT IN SKIN IMMUNITY IS ASSOCIATED WITH DNA METHYLATION. THIS REVIEW FOCUSES ON EPIGENETIC REGULATION OF HISTONE MODIFICATION AND CHROMATIN REMODELING AND DESCRIBES THEIR ROLE IN THE TRANSCRIPTIONAL REGULATION OF IMMUNE-REGULATORY FACTORS. WHILE MUCH IS STILL UNKNOWN REGARDING THE REGULATION OF SKIN IMMUNITY VIA HISTONE MODIFICATION OR CHROMATIN REMODELING, THESE PROCESSES MAY UNDERLIE THE PATHOGENESIS OF CHRONIC CUTANEOUS IMMUNE DISORDERS. 2023 18 3826 33 INVESTIGATION OF EPIGENETICS IN KIDNEY CELL BIOLOGY. EPIGENETICS IS THE STUDY OF HERITABLE CHANGES IN DNA OR ITS ASSOCIATED PROTEINS EXCEPT MUTATIONS IN GENE SEQUENCE. EPIGENETIC REGULATION PLAYS FUNDAMENTAL ROLES IN THE PROCESSES OF KIDNEY CELL BIOLOGY THROUGH THE ACTION OF DNA METHYLATION, CHROMATIN MODIFICATIONS VIA EPIGENETIC REGULATORS AND INTERACTION VIA TRANSCRIPTION FACTORS, AND NONCODING RNA SPECIES. KIDNEY DISEASES, INCLUDING ACUTE KIDNEY INJURY, CHRONIC KIDNEY DISEASE, NEPHRITIC AND NEPHROTIC SYNDROMES, PYELONEPHRITIS AND POLYCYSTIC KIDNEY DISEASES ARE DRIVEN BY ABERRANT ACTIVITY IN NUMEROUS SIGNALING PATHWAYS IN EVEN INDIVIDUAL KIDNEY CELL. EPIGENETIC ALTERATIONS, INCLUDING DNA METHYLATION, HISTONE ACETYLATION AND METHYLATION, NONCODING RNAS, AND PROTEIN POSTTRANSLATIONAL MODIFICATIONS, COULD DISRUPT ESSENTIAL PATHWAYS THAT PROTECT THE RENAL CELLS FROM UNCONTROLLED GROWTH, APOPTOSIS AND ESTABLISHMENT OF OTHER RENAL ASSOCIATED SYNDROMES, WHICH HAVE BEEN RECOGNIZED AS ONE OF THE CRITICAL MECHANISMS FOR REGULATING FUNCTIONAL CHANGES THAT DRIVE AND MAINTAIN THE KIDNEY DISEASE PHENOTYPE. IN THIS CHAPTER, WE BRIEFLY SUMMARIZE THE EPIGENETIC MECHANISMS IN KIDNEY CELL BIOLOGY AND EPIGENETIC BASIS OF KIDNEY DEVELOPMENT, AND INTRODUCE EPIGENETIC TECHNIQUES THAT CAN BE USED IN INVESTIGATING THE MOLECULAR MECHANISM OF KIDNEY CELL BIOLOGY AND KIDNEYS DISEASES, PRIMARILY FOCUSING ON THE INTEGRATION OF DNA METHYLATION AND CHROMATIN IMMUNOPRECIPITATION TECHNOLOGIES INTO KIDNEY DISEASE ASSOCIATED STUDIES. FUTURE STUDIES USING THESE EMERGING TECHNOLOGIES WILL ELUCIDATE HOW ALTERATIONS IN THE RENAL CELL EPIGENOME COOPERATE WITH GENETIC ABERRATIONS FOR KIDNEY DISEASE INITIATION AND PROGRESSION. INCORPORATING EPIGENOMIC TESTING INTO THE CLINICAL RESEARCH IS ESSENTIAL TO FUTURE STUDIES WITH EPIGENETICS BIOMARKERS AND PRECISION MEDICINE USING EMERGING EPIGENETIC THERAPIES. 2019 19 6896 30 [TARGETED EPIGENETIC THERAPY OF CANCER. ACHIEVEMENTS AND PERSPECTIVES]. IN THIS REVIEW, WE PROVIDE AN OVERVIEW OF THE PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL EPIGENETIC CHANGES OF NORMAL CELLS AND CANCER CELLS, AND EMPHASIZE THE ACHIEVEMENTS AND THE PERSPECTIVES OF CANCER EPIGENETIC THERAPY. CANCER EPIGENETIC ALTERATIONS CORRESPOND FOREMOST TO HYPERMETHYLATION OF TUMOR SUPPRESSOR GENES PROMOTORS, GLOBAL DNA HYPOMETHYLATION, AND OVEREXPRESSION AND ACTIVITY OF HISTONE DEACETYLASES. THE PURPOSE OF EPIGENETIC THERAPY IS TO REVERT THE EPIGENETIC ALTERATIONS IN CANCER CELLS AND OBTAIN THE "NORMAL EPIGENOME" RESTORATION. EPIGENETIC TARGETS IN CANCER THERAPY HAVE FOCUSED ON HDACS AND DNMTS INHIBITION. THE AZACITIDINE AND THE DECITABINE, THE VORINOSTAT AND THE ROMIDEPSIN WERE APPROVED BY US-FDA FOR TREATMENT OF MYELODYSPLASTIC SYNDROME, AND CUTANEOUS T-CELL LYMPHOMA, RESPECTIVELY. EPIGENETIC AND EPIGENOMIC CHANGES IN SINGLE OR MULTIPLE GENES HAVE SHOWED POTENTIAL IMPACT IN CANCER AS EARLY DETECTION, PROGNOSIS AND PREDICTIVE MARKS. THE EPIGENETIC REVOLUTION HAS ARRIVED FOR BIOLOGY. THE SIGNIFICANT PROGRESS IN EPIGENETIC STUDIES HAVE ALLOWED US, TO UNDERSTAND NEW LOOKS IN THE PHYSIOLOGY AND PATHOPHYSIOLOGY OF EMBRYONIC DEVELOPMENT, CANCER AND OTHER CHRONIC DISEASES. SPECIFIC MOLECULAR EPIGENETIC ALTERATIONS IN DIFFERENT CANCER TYPES, GIVE US NEW STRATEGIES TO DESIGN IMPROVED CANCER THERAPY. THE CHALLENGE FOR EPIGENETIC INVESTIGATORS IS DESIGN MORE SPECIFIC EPIDRUGS WITH LESSER SIDE EFFECTS. 2012 20 3326 37 HISTONE DEACETYLASE 3 (HDAC3) AS AN IMPORTANT EPIGENETIC REGULATOR OF KIDNEY DISEASES. DEVELOPMENT AND PROGRESSION OF MANY KIDNEY DISEASES ARE SUBSTANTIALLY INFLUENCED BY ABERRANT PROTEIN ACETYLATION MODIFICATIONS OF GENE EXPRESSION CRUCIAL FOR KIDNEY FUNCTIONS. HISTONE DEACETYLASE (HDAC) EXPRESSION ALTERATIONS ARE DETECTED FROM RENAL SAMPLES OF PATIENTS AND ANIMAL MODELS OF VARIOUS KIDNEY DISEASES, AND THE ADMINISTRATIONS OF HDAC INHIBITORS DISPLAY IMPRESSIVE RENAL PROTECTIVE EFFECTS IN VITRO AND IN VIVO. HOWEVER, WHEN THE EXPRESSION ALTERATIONS OF MULTIPLE HDACS OCCUR, NOT ALL THE HDACS CAUSALLY AFFECT THE DISEASE ONSET OR PROGRESSION. IDENTIFICATION OF A SINGLE HDAC AS A DISEASE-CAUSING FACTOR WILL ALLOW SUBTYPE-TARGETED INTERVENTION WITH LESS SIDE EFFECT. HDAC3 IS A UNIQUE HDAC WITH DISTINCT STRUCTURAL AND SUBCELLULAR DISTRIBUTION FEATURES AND CO-REPRESSOR DEPENDENCY. HDAC3 IS REQUIRED FOR KIDNEY DEVELOPMENT AND ITS ABERRATIONS ACTIVELY PARTICIPATE IN MANY PATHOLOGICAL PROCESSES, SUCH AS CANCER, CARDIOVASCULAR DISEASES, DIABETES, AND NEURODEGENERATIVE DISORDERS, AND CONTRIBUTE SIGNIFICANTLY TO THE PATHOGENESIS OF KIDNEY DISEASES. THIS REVIEW WILL DISCUSS THE RECENT STUDIES THAT INVESTIGATE THE CRITICAL ROLES OF HDAC3 ABERRATIONS IN KIDNEY DEVELOPMENT, RENAL AGING, RENAL CELL CARCINOMA, RENAL FIBROSIS, CHRONIC KIDNEY DISEASE, POLYCYSTIC KIDNEY DISEASE, GLOMERULAR PODOCYTE INJURY, AND DIABETIC NEPHROPATHY. THESE STUDIES REVEAL THE DISTINCT CHARACTERS OF HDAC3 ABERRATIONS THAT ACT ON DIFFERENT MOLECULES/SIGNALING PATHWAYS UNDER VARIOUS RENAL PATHOLOGICAL CONDITIONS, WHICH MIGHT SHED LIGHTS INTO THE EPIGENETIC MECHANISMS OF RENAL DISEASES AND THE POTENTIALLY THERAPEUTIC STRATEGIES. 2022