1 258 76 ADVANCES IN PATHOGENESIS AND NANOPARTICLES (NPS)-MEDIATED TREATMENT OF PSORIASIS. PSORIASIS IS A CHRONIC PAPULOSQUAMOUS SKIN DISEASE WITH AN AUTOIMMUNE PATHOGENIC TRAITS AND STRONG GENETIC PREDISPOSITION. IN THE PAST FEW DECADES, WITH THE RAPID DEVELOPMENT OF MOLECULAR BIOLOGY AND CELL BIOLOGY, THE INHERENT PATHOGENESIS OF PSORIASIS HAS BEEN GRADUALLY ELUCIDATED, IN WHICH CYTOKINE INFLAMMATORY LOOPS, CELL SIGNALING PATHWAYS, AND EPIGENETIC FACTORS SUCH AS MIRNAS HAVE BEEN DEMONSTRATED TO PLAY IMPORTANT ROLES IN REGULATING THE DEVELOPMENT AND PROGRESSION OF PSORIASIS. MORE IMPORTANTLY, UNDERSTANDING THE PATHOGENESIS OF PSORIASIS HAS PROMOTED THE DEVELOPMENT OF EFFECTIVE TREATMENT FOR PSORIASIS. IN THIS REVIEW, WE SYSTEMICALLY SUMMARIZED THE MOLECULAR MECHANISMS REGULATING THE DEVELOPMENT AND PROGRESSION PSORIASIS, INTRODUCED VARIOUS THERAPEUTICS USED FOR CLINICAL PSORIASIS THERAPY, AND HIGHLIGHTED THE RECENT ADVANCES IN NANOPARTICLES (NPS)-MEDIATED DRUG DELIVERY FOR PSORIASIS TREATMENT. 2022 2 2553 27 EPIGENETICS IN PSORIASIS: PERSPECTIVE OF DNA METHYLATION. PSORIASIS IS A CHRONIC INFLAMMATORY SKIN DISEASE CHARACTERIZED BY EXCESSIVE PROLIFERATION OF KERATINOCYTES (KCS). ONSET OF PSORIASIS IS RELATED TO GENETIC, IMMUNE AND ENVIRONMENTAL FACTORS. THE ENVIRONMENT CAN INTERACT WITH THE GENOME THROUGH EPIGENETIC MODIFICATIONS, INCLUDING DNA METHYLATION, AND THIS MODIFICATION IS INVOLVED IN THE PATHOGENESIS OF PSORIASIS. IN ADDITION TO A SKIN DISEASE, PSORIASIS IS ALSO CONSIDERED A SYSTEMIC DISEASE. WE REVIEWED THE CURRENT LITERATURE OF PSORIATIC DNA METHYLATION FOR STUDIES FROM SEVERAL ASPECTS ON THE DNA METHYLATION DISTRIBUTION PATTERNS IN DIFFERENT TISSUES/CELLS, SINGLE-NUCLEOTIDE POLYMORPHISMS, AND CANDIDATE DISEASE GENES AND IDENTIFIED TARGET GENES REGULATED BY DNA METHYLATION THAT HAVE BEEN DIRECTLY/INDIRECTLY VALIDATED. THIS REVIEW CONTRIBUTES TO A COMPREHENSIVE UNDERSTANDING OF THE IMPORTANT A ROLE THAT DNA METHYLATION PLAYS IN PSORIASIS FROM A HOLISTIC PERSPECTIVE AND WILL PROMOTE THE IMPLEMENTATION OF DNA METHYLATION IN DIAGNOSTIC AND THERAPEUTIC STRATEGIES FOR PSORIATIC PATIENTS. 2021 3 2533 29 EPIGENETICS IN AUTOIMMUNE CONNECTIVE TISSUE DISEASES. BACKGROUND. AUTOIMMUNE CONNECTIVE TISSUE DISEASES (ACTDS) ENCOMPASS A HETEROGENEOUS GROUP OF CHRONIC IMMUNE-MEDIATED INFLAMMATORY DISORDERS, PRIMARILY AFFECTING CONNECTIVE TISSUES AND CLINICALLY CHARACTERIZED BY VARIABLE MULTISYSTEM MANIFESTATIONS, FREQUENTLY OVERLAPPING. ENVIRONMENTAL FACTORS ARE THOUGHT TO PROMOTE ACTD DEVELOPMENT IN GENETIC PREDISPOSING/ENDOCRINE PERMISSIVE BACKGROUND THROUGH THE INDUCTION OF EPIGENETIC MODIFICATIONS, CONSISTING OF STABLE, HERITABLE, BUT POTENTIALLY REVERSIBLE CHANGES IN GENE EXPRESSION, OCCURRING WITHOUT ALTERATIONS OF THE DNA SEQUENCE. ACTUALLY, EPIGENETIC MECHANISMS (SUCH AS HISTONE MODIFICATIONS, DNA METHYLATION, NUCLEOSOME POSITIONING, AND RNA INTERFERENCE) LINK GENOTYPE UPSTREAM AND PHENOTYPE DOWNSTREAM, AND, IF PERSISTENTLY ABERRANT, MAY CAUSE A VARIETY OF HUMAN DISEASES, INCLUDING ACTDS. WE AIMED TO REVIEW THE RECENT ADVANCES IN THE KNOWLEDGE OF THE ACTD EPIGENETIC ALTERATIONS. METHODS: A DETAILED SEARCH OF THE AVAILABLE LITERATURE WAS PERFORMED IN THE PUBMED (U.S. NATIONAL LIBRARY OF MEDICINE) DATABASE. RESULTS: GROWING EVIDENCE UNDERLINES THE RELEVANT ROLE OF EPIGENETIC DEFECTS IN THE ACTD PATHOGENESIS, AND SPECIFIC EPIGENETIC PATTERNS CAN REPRESENT DISEASE BIOMARKERS. IN PATIENTS WITH RHEUMATOID ARTHRITIS (RA), EPIGENETIC VARIATIONS INTERACT DETERMINING THE TYPICAL "AGGRESSIVE" PHENOTYPE DISPLAYED BY RA SYNOVIAL FIBROBLASTS. EPIGENETIC MODIFICATIONS ARE INVOLVED IN THE PROFIBROTIC PROCESS THAT CHARACTERIZES SYSTEMIC SCLEROSIS. IN SYSTEMIC LUPUS ERYTHEMATOSUS AND SJOGREN'S SYNDROME, COMPLEX EPIGENETIC CHANGES ALTERING GENE EXPRESSION HAVE BEEN DEMONSTRATED. CONCLUSIONS: COMPREHENSIVE STUDIES WILL CONTRIBUTE TO FURTHER DEFINE THE ABERRANT EPIGENETIC MECHANISMS INVOLVED IN THE ACTDS ETIOPATHOGENESIS. MOREOVER, BEING EPIGENETIC CHANGES POTENTIALLY REVERSIBLE, THE IDENTIFICATION OF ACTDS EPIGENETIC BIOMARKERS WILL ALLOW THE DEVELOPMENT OF THERAPEUTIC STRATEGIES ADDRESSED TO TARGET DYSREGULATED GENES AND CORRECT ABERRANT EPIGENOMIC ALTERATIONS. 2014 4 1879 31 EMERGING ROLES OF NON-CODING RNAS IN PSORIASIS PATHOGENESIS. PSORIASIS IS A COMPLEX GENETIC SKIN DISORDER TYPICALLY MANIFESTED BY RED, SCALY, AND ITCHY PLAQUES MOST COMMONLY OVER THE SCALP, TRUNK, ELBOWS, AND KNEES. HISTOPATHOLOGICAL FEATURES INCLUDE THICKENING OF THE EPIDERMAL LAYER DUE TO HYPER-PROLIFERATION AND ABNORMAL DIFFERENTIATION OF EPIDERMAL KERATINOCYTES ALONG WITH INFILTRATION OF IMMUNE CELLS IN THE PSORIATIC SKIN. IT IS A CHRONIC INFLAMMATORY RELAPSING DISEASE, AND THERE IS CURRENTLY NO PERMANENT CURE FOR PSORIASIS. PROPER MEDICATIONS CAN REDUCE THE SEVERITY OF THE DISEASE AND IMPROVE THE QUALITY OF LIFE OF THE PATIENTS. WHILE THE GENETIC COMPONENTS OF PSORIASIS PATHOGENESIS ARE WELL EXPLORED, THE FULL UNDERSTANDING OF ITS EPIGENETIC COMPONENT REMAINS ELUSIVE. NON-CODING RNAS (NCRNAS) ARE DOCUMENTED TO REGULATE VARIOUS EPIGENETIC PROCESSES THAT LEAD TO THE PATHOGENESIS OF DIFFERENT DISEASES INCLUDING PSORIASIS. IN THIS REVIEW, WE HAVE DISCUSSED THE MOLECULAR INTERPLAY OF DIFFERENT NCRNAS IN PSORIASIS PATHOGENESIS. THE ROLES OF MICRORNAS (MIRNAS) IN PSORIASIS ARE PRETTY WELL STUDIED, WHEREAS THE ROLES OF LONG NONCODING RNAS (LNCRNAS) AND CIRCULAR RNAS (CIRCRNAS) ARE EMERGING. THIS REVIEW PROVIDES IDEAS COVERING SOME OF THE LATEST FINDINGS OF DIFFERENT MODES OF FUNCTIONS PLAYED BY THOSE DIFFERENT NCRNAS DOCUMENTED IN THE LITERATURE. AS AN EVER-EVOLVING TOPIC, SOME WORKS ARE STILL ONGOING AS WELL AS THERE ARE SEVERAL FIELDS THAT NEED RIGOROUS SCIENTIFIC VENTURES. WE HAVE PROPOSED THE AREAS WHICH CLAIM MORE EXPLORATIONS TO BETTER UNDERSTAND THE ROLES PLAYED BY THE NCRNAS IN PSORIASIS PATHOGENESIS. 2023 5 5998 20 THE ABERRANT EPIGENETIC MODIFICATIONS IN THE PATHOGENESIS OF PSORIASIS. PSORIASIS IS A CHRONIC AND RECURRENT INFLAMMATORY SKIN DISEASE THAT IS CHARACTERIZED BY ABNORMAL KERATINOCYTE PROLIFERATION, VASCULAR HYPERPLASIA, AND INFILTRATION OF INFLAMMATORY CELLS INTO THE DERMIS AND EPIDERMIS. IT IS GENERALLY ACCEPTED THAT THE CENTRAL PATHOGENESIS OF PSORIASIS IS DYSFUNCTION OF T LYMPHOCYTES, WHICH ARE AFFECTED BY THE COMPLEX INTERPLAY BETWEEN GENETIC AND ENVIRONMENTAL FACTORS, INCLUDING TRAUMA, INFECTIONS, STRESS, DRUGS, SMOKING, AND ALCOHOL CONSUMPTION (NESTLE ET AL., 2009). THE ENVIRONMENTALLY INDUCED EPIGENETIC CHANGES, INCLUDING DNA METHYLATION, HISTONE MODIFICATION, AND MICRORNAS, HAVE BEEN SHOWN TO BE INVOLVED IN THE PATHOGENESIS OF THIS DISEASE (ZHANG ET AL., 2012). 2018 6 5359 29 REBOOTING REGULATORY T CELL AND DENDRITIC CELL FUNCTION IN IMMUNE-MEDIATED INFLAMMATORY DISEASES: BIOMARKER AND THERAPY DISCOVERY UNDER A MULTI-OMICS LENS. IMMUNE-MEDIATED INFLAMMATORY DISEASES (IMIDS) ARE A GROUP OF AUTOIMMUNE AND CHRONIC INFLAMMATORY DISORDERS WITH CONSTANTLY INCREASING PREVALENCE IN THE MODERN WORLD. THE VAST MAJORITY OF IMIDS DEVELOP AS A CONSEQUENCE OF COMPLEX MECHANISMS DEPENDENT ON GENETIC, EPIGENETIC, MOLECULAR, CELLULAR, AND ENVIRONMENTAL ELEMENTS, THAT LEAD TO DEFECTS IN IMMUNE REGULATORY GUARDIANS OF TOLERANCE, SUCH AS DENDRITIC (DCS) AND REGULATORY T (TREGS) CELLS. AS A RESULT OF THIS DYSFUNCTION, IMMUNE TOLERANCE COLLAPSES AND PATHOGENESIS EMERGES. DEEPER UNDERSTANDING OF SUCH DISEASE DRIVING MECHANISMS REMAINS A MAJOR CHALLENGE FOR THE PREVENTION OF INFLAMMATORY DISORDERS. THE RECENT RENAISSANCE IN HIGH THROUGHPUT TECHNOLOGIES HAS ENABLED THE INCREASE IN THE AMOUNT OF DATA COLLECTED THROUGH MULTIPLE OMICS LAYERS, WHILE ADDITIONALLY NARROWING THE RESOLUTION DOWN TO THE SINGLE CELL LEVEL. IN LIGHT OF THE AFOREMENTIONED, THIS REVIEW FOCUSES ON DCS AND TREGS AND DISCUSSES HOW MULTI-OMICS APPROACHES CAN BE HARNESSED TO CREATE ROBUST CELL-BASED IMID BIOMARKERS IN HOPE OF LEADING TO MORE EFFICIENT AND PATIENT-TAILORED THERAPEUTIC INTERVENTIONS. 2022 7 2591 35 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 8 6276 31 THE PATHOGENIC ROLE OF DYSREGULATED EPIGENETIC MODIFICATIONS IN AUTOIMMUNE DISEASES. AUTOIMMUNE DISEASES CAN BE CHRONIC WITH RELAPSE OF INFLAMMATORY SYMPTOMS, BUT IT CAN BE ALSO ACUTE AND LIFE-THREATENING IF IMMUNE CELLS DESTROY LIFE-SUPPORTING ORGANS, SUCH AS LUPUS NEPHRITIS. THE ETIOPATHOGENESIS OF AUTOIMMUNE DISEASES HAS BEEN REVEALED AS THAT GENETICS AND ENVIRONMENTAL FACTORS-MEDIATED DYSREGULATED IMMUNE RESPONSES CONTRIBUTE TO THE INITIATION AND DEVELOPMENT OF AUTOIMMUNE DISORDERS. HOWEVER, THE CURRENT UNDERSTANDING OF PATHOGENESIS IS LIMITED AND THE UNDERLYING MECHANISM HAS NOT BEEN WELL DEFINED, WHICH LOWS THE DEVELOPMENT OF NOVEL BIOMARKERS AND NEW THERAPEUTIC STRATEGIES FOR AUTOIMMUNE DISEASES. TO IMPROVE THIS, BROADENING AND DEEPENING OUR UNDERSTANDING OF PATHOGENESIS IS AN UNMET NEED. AS GENETIC SUSCEPTIBILITY CANNOT EXPLAIN THE LOW ACCORDANCE RATE OF INCIDENCE IN HOMOZYGOUS TWINS, EPIGENETIC REGULATIONS MIGHT BE AN ADDITIONAL EXPLANATION. THEREFORE, THIS REVIEW WILL SUMMARIZE CURRENT PROGRESS OF STUDIES ON EPIGENETIC DYSREGULATIONS CONTRIBUTING TO AUTOIMMUNE DISEASES, INCLUDING SLE, RHEUMATOID ARTHRITIS (RA), PSORIASIS, TYPE 1 DIABETES (T1D), AND SYSTEMIC SCLEROSIS (SSC), HOPEFULLY PROVIDING OPINIONS ON ORIENTATION OF FUTURE RESEARCH, AS WELL AS DISCUSSING THE CLINICAL UTILIZATION OF POTENTIAL BIOMARKERS AND THERAPEUTIC STRATEGIES FOR THESE DISEASES. 2019 9 4012 25 LOW-DENSITY GRANULOCYTES IN SYSTEMIC AUTOIMMUNITY AND AUTOINFLAMMATION. A BODY OF EVIDENCE HAS RE-ENERGIZED THE INTEREST ON THE ROLE NEUTROPHILS IN INFLAMMATORY AND AUTOIMMUNE CONDITIONS. FOR DECADES, NEUTROPHILS HAVE BEEN CONSIDERED A HOMOGENOUS POPULATION. NEVERTHELESS, ACCUMULATING EVIDENCE SUGGESTS THAT NEUTROPHILS ARE MORE VERSATILE AND HETEROGENEOUS THAN INITIALLY CONSIDERED. THE NOTION OF NEUTROPHIL HETEROGENEITY HAS BEEN SUPPORTED BY THE IDENTIFICATION OF LOW-DENSITY GRANULOCYTES (LDGS) IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) AND OTHER SYSTEMIC AUTOIMMUNE AND AUTOINFLAMMATORY CONDITIONS. TRANSCRIPTOMIC, EPIGENETIC, PROTEOMIC, AND FUNCTIONAL ANALYSES SUPPORT THAT LDGS ARE A DISTINCT SUBSET OF PROINFLAMMATORY NEUTROPHILS IMPLICATED IN THE PATHOGENESIS OF SLE AND OTHER AUTOIMMUNE DISEASES. IMPORTANTLY, IT REMAINS INCOMPLETELY CHARACTERIZED WHETHER LDGS DETECTED IN OTHER INFLAMMATORY/AUTOIMMUNE CONDITIONS DISPLAY THE SAME PHENOTYPE THAT THOSE PRESENT IN SLE. A SHARED FEATURE OF LDGS ACROSS DISEASES IS THEIR ASSOCIATION WITH VASCULAR DAMAGE, AN IMPORTANT CONTRIBUTOR TO MORBIDITY AND MORTALITY IN CHRONIC INFLAMMATORY CONDITIONS. ADDITIONALLY, THE LACK OF SPECIFIC MARKERS TO IDENTIFY LDGS IN CIRCULATION OR IN TISSUE, MAKES IT A CHALLENGE TO ELUCIDATE THEIR ROLE IN THE PATHOGENESIS OF INFLAMMATORY AND AUTOIMMUNE CONDITIONS. IN THIS REVIEW, WE AIM TO EXAMINE THE EVIDENCE ON THE BIOLOGY AND THE PUTATIVE PATHOGENIC ROLE OF LDGS IN SYSTEMIC AUTOIMMUNE DISEASES. 2023 10 395 27 AN UPDATE ON EPIGENETIC REGULATION IN AUTOIMMUNE DISEASES. AUTOIMMUNE DISEASES (AIDS) GENERALLY MANIFEST AS CHRONIC IMMUNE DISORDERS CHARACTERIZED BY SIGNIFICANT HETEROGENEITY AND COMPLEX SYMPTOMS. THE DISCORDANT INCIDENCE OF AIDS BETWEEN MONOZYGOTIC TWINS GUIDED PEOPLE TO ATTACH IMPORTANCE TO ENVIRONMENTAL FACTORS. EPIGENETICS IS ONE OF THE MAJOR WAYS TO BE INFLUENCED, SOME OF THEM CAN EVEN OCCUR YEARS BEFORE CLINICAL DIAGNOSIS. WITH THE ADVENT OF HIGH-THROUGHPUT OMICS TIMES, THE MYSTERIOUS VEIL OF EPIGENETIC MODIFICATION IN AIDS HAS BEEN GRADUALLY UNRAVELED, AND SOME PROGRESS HAS BEEN MADE IN UTILIZING IT AS INDICATORS OF DIAGNOSIS AND DISEASE ACTIVITY. FOR EXAMPLE, THE HYPOMETHYLATED IFI44L PROMOTER IN DIAGNOSING SYSTEMATIC LUPUS ERYTHEMATOSUS (SLE). MORE RECENTLY, NEWLY IDENTIFIED NONCODING RNAS (NCRNAS), INCLUDING LONG NONCODING RNAS (LNCRNAS) AND CIRCULAR RNAS (CIRCRNAS), ARE ALSO BELIEVED TO BE INVOLVED IN THE ETIOLOGY OF AIDS WHILE THE INITIAL FACTOR BEHIND THOSE EPIGENETIC ALTERATIONS CAN BE DIVERSE FROM METABOLISM TO MICROBIOTA. UPDATE AND COMPREHENSIVE INSIGHTS INTO EPIGENETICS IN AIDS CAN HELP US UNDERSTAND THE PATHOGENESIS AND FURTHER ORCHESTRATE IT TO BENEFIT PATIENTS IN THE FUTURE. THEREFORE, WE REVIEWED THE LATEST EPIGENETIC FINDINGS IN SLE, RHEUMATOID ARTHRITIS (RA), TYPE 1 DIABETES (T1D), SYSTEMIC SCLEROSIS (SSC) PRIMARILY FROM CELLULAR LEVELS. 2022 11 2461 30 EPIGENETIC THERAPY AS A PUTATIVE MOLECULAR TARGET TO MODULATE B CELL BIOLOGY AND BEHAVIOR IN THE CONTEXT OF IMMUNOLOGICAL DISORDERS. HISTONE DEACETYLASE- (HDAC-) DEPENDENT EPIGENETIC MECHANISMS HAVE BEEN WIDELY EXPLORED IN THE LAST DECADE IN DIFFERENT TYPES OF MALIGNANCIES IN PRECLINICAL STUDIES. THIS EFFORT LED TO THE DISCOVERY AND DEVELOPMENT OF A RANGE OF NEW HDAC INHIBITORS (IHDAC) WITH DIFFERENT CHEMICAL PROPERTIES AND SELECTIVE ABILITIES. IN FACT, HEMATOLOGICAL MALIGNANCIES WERE THE FIRST ONES TO HAVE NEW IHDACS APPROVED FOR CLINICAL USE, SUCH AS VORINOSTAT AND ROMIDEPSIN FOR CUTANEOUS T CELL LYMPHOMA AND PANOBINOSTAT FOR MULTIPLE MYELOMA. BESIDES THESE PROMISING ALREADY APPROVED IHDACS, WE HIGHLIGHT A RANGE OF STUDIES FOCUSING ON THE HDAC-DEPENDENT EPIGENETIC CONTROL OF B CELL DEVELOPMENT, BEHAVIOR, AND/OR FUNCTION. HERE, WE HIGHLIGHT 21 IHDACS WHICH HAVE BEEN STUDIED IN THE LITERATURE IN THE CONTEXT OF B CELL DEVELOPMENT AND/OR DYSFUNCTION MOSTLY FOCUSED ON B CELL LYMPHOMAGENESIS. REGARDLESS, WE HAVE IDENTIFIED 55 CLINICAL TRIALS USING 6 OUT OF 21 IHDACS TO APPROACH THEIR PUTATIVE ROLES ON B CELL MALIGNANCIES; NONE OF THEM FOCUSES ON PERITONEAL B CELL POPULATIONS. SINCE CELLS BELONGING TO THIS PECULIAR BODY COMPARTMENT, NAMED B1 CELLS, MAY CONTRIBUTE TO THE DEVELOPMENT OF AUTOIMMUNE PATHOLOGIES, SUCH AS LUPUS, A BETTER UNDERSTANDING OF THE HDAC-DEPENDENT EPIGENETIC MECHANISMS THAT CONTROL ITS BIOLOGY AND BEHAVIOR MIGHT SHED LIGHT ON IHDAC USE TO MANAGE THESE IMMUNOLOGICAL DYSFUNCTIONS. IN THIS SENSE, IHDACS MIGHT EMERGE AS A PROMISING NEW APPROACH FOR TRANSLATIONAL STUDIES IN THIS FIELD. IN THIS REVIEW, WE DISCUSS A PUTATIVE ROLE OF IHDACS IN THE MODULATION OF PERITONEAL B CELL SUBPOPULATION'S BALANCE AS WELL AS THEIR ROLE AS THERAPEUTIC AGENTS IN THE CONTEXT OF CHRONIC DISEASES MEDIATED BY PERITONEAL B CELLS. 2020 12 6624 33 UNDERSTANDING PSORIASIS: ROLE OF MIRNAS. PSORIASIS IS A CHRONIC, IMMUNE-MEDIATED INFLAMMATORY SKIN DISEASE, WITH A MULTIFACTORIAL ETIOLOGY AND IMPORTANT IMMUNOLOGIC, GENETIC AND ENVIRONMENTAL COMPONENTS. PSORIASIS VULGARIS REPRESENTS ITS MOST COMMON FORM, WITH A VARIABLE PREVALENCE ACROSS THE GLOBE. ALTHOUGH ITS PATHOGENESIS REMAINS TO BE FULLY ELUCIDATED, A LACK OF BALANCE IN THE EPIGENETIC NETWORK HAS BEEN SHOWN TO TRIGGER CERTAIN ELEMENTS OF THIS DISEASE, POSSIBLY ALTERING ITS OUTCOME. MICRORNAS ARE SMALL NON-CODING RNA MOLECULES INVOLVED IN RNA-SILENCING AND THE POST-TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION, WHICH ALSO APPEAR TO MEDIATE THE IMMUNE DYSFUNCTION IN PSORIASIS. ALTHOUGH MICRORNA RESEARCH IS A NEW FIELD IN DERMATOLOGY AND PSORIASIS, THERE IS RAPIDLY ACCUMULATING EVIDENCE FOR ITS MAJOR CONTRIBUTION IN THE PATHOGENESIS OF CHRONIC INFLAMMATORY CONDITIONS, INCLUDING PSORIASIS AND OTHER DERMATOLOGICAL DISORDERS. FURTHERMORE, CIRCULATING MIRNAS IDENTIFIED IN PATIENTS' BLOOD SAMPLES HAVE BEEN IDENTIFIED AS PROMISING BIOMARKERS OF DIAGNOSIS, PROGNOSIS OR TREATMENT RESPONSE. EXTENDED INVESTIGATIONS IN THIS FIELD ARE REQUIRED, AS UNTIL NOW, THE EXACT INVOLVEMENT OF MIRNAS IN PSORIASIS HAVE REMAINED TO BE ENTIRELY ELUCIDATED. THIS SHORT REVIEW HIGHLIGHTS A NUMBER OF THE ROLES OF MIRNAS FOUND IN DIFFERENT STAGES OF PSORIASIS. 2018 13 4452 28 MOLECULAR MECHANISMS AND MANAGEMENT OF A CUTANEOUS INFLAMMATORY DISORDER: PSORIASIS. PSORIASIS IS A COMPLEX CHRONIC INFLAMMATORY CUTANEOUS DISORDER. TO DATE, ROBUST MOLECULAR MECHANISMS OF PSORIASIS HAVE BEEN REPORTED. AMONG DIVERSE ABERRANT IMMUNOPATHOGENETIC MECHANISMS, THE CURRENT MODEL EMPHASIZES THE ROLE OF TH1 AND THE IL-23/TH17 AXIS, SKIN-RESIDENT IMMUNE CELLS AND MAJOR SIGNAL TRANSDUCTION PATHWAYS INVOLVED IN PSORIASIS. THE MULTIPLE GENETIC RISK LOCI FOR PSORIASIS HAVE BEEN RAPIDLY REVEALED WITH THE ADVENT OF A NOVEL TECHNOLOGY. MOREOVER, IDENTIFYING EPIGENETIC MODIFICATIONS COULD BRIDGE THE GAP BETWEEN GENETIC AND ENVIRONMENTAL RISK FACTORS IN PSORIASIS. THIS REVIEW WILL PROVIDE A BETTER UNDERSTANDING OF THE PATHOGENESIS OF PSORIASIS BY UNRAVELING THE COMPLICATED INTERPLAY AMONG IMMUNOLOGICAL ABNORMALITIES, GENETIC RISK FOCI, EPIGENETIC MODIFICATION AND ENVIRONMENTAL FACTORS OF PSORIASIS. WITH ADVANCES IN MOLECULAR BIOLOGY, DIVERSE NEW TARGETS ARE UNDER INVESTIGATION TO MANAGE PSORIASIS. THE RECENT ADVANCES IN TREATMENT MODALITIES FOR PSORIASIS BASED ON TARGETED MOLECULES ARE ALSO DISCUSSED. 2017 14 6255 26 THE MICROBIOTA AND EPIGENETIC REGULATION OF T HELPER 17/REGULATORY T CELLS: IN SEARCH OF A BALANCED IMMUNE SYSTEM. IMMUNE CELLS NOT ONLY AFFECT TISSUE HOMEOSTASIS AT THE SITE OF INFLAMMATION BUT ALSO EXERT SYSTEMIC EFFECTS CONTRIBUTING TO MULTIPLE CHRONIC CONDITIONS. RECENT EVIDENCE CLEARLY SUPPORTS AN ALTERED T HELPER 17/REGULATORY T CELL (TH17/TREG) BALANCE LEADING TO THE DEVELOPMENT AND PROGRESSION OF INFLAMMATORY DISEASES THAT NOT ONLY AFFECT THE GASTROINTESTINAL TRACT BUT ALSO HAVE WHOLE-BODY MANIFESTATIONS, INCLUDING INSULIN RESISTANCE. EPIGENETIC MECHANISMS ARE AMENABLE TO BOTH ENVIRONMENTAL AND CIRCULATING FACTORS AND CONTRIBUTE TO DETERMINING THE T CELL LANDSCAPE. THE RECENTLY IDENTIFIED PARTICIPATION OF THE GUT MICROBIOTA IN THE REMODELING OF THE EPIGENOME OF IMMUNE CELLS HAS TRIGGERED A PARADIGM SHIFT IN OUR UNDERSTANDING OF THE ETIOLOGY OF VARIOUS INFLAMMATORY DISEASES AND OPENED NEW PATHS TOWARD THERAPEUTIC STRATEGIES. IN THIS REVIEW, WE PROVIDE AN OVERVIEW OF THE CONTRIBUTION OF THE TH17/TREG BALANCE IN THE DEVELOPMENT AND PROGRESSION OF INFLAMMATORY BOWEL DISEASES AND METABOLIC DISEASES. WE DISCUSS THE INVOLVEMENT OF EPIGENETIC MECHANISMS IN THE REGULATION OF T CELL FUNCTION IN THE PARTICULAR CONTEXT OF DYSBIOSIS. FINALLY, WE EXAMINE THE POTENTIAL FOR NUTRITIONAL INTERVENTIONS AFFECTING THE GUT MICROBIOTA TO RESHAPE THE T CELL EPIGENOME AND ADDRESS THE INFLAMMATORY COMPONENT OF VARIOUS DISEASES. 2017 15 4883 27 OVERVIEW OF THE MOLECULAR DETERMINANTS CONTRIBUTING TO THE EXPRESSION OF PSORIASIS AND PSORIATIC ARTHRITIS PHENOTYPES. PSORIASIS AND PSORIATIC ARTHRITIS ARE MULTIFACTORIAL CHRONIC DISORDERS WHOSE ETIOPATHOGENESIS ESSENTIALLY DERIVES FROM THE ALTERATION OF SEVERAL SIGNALLING PATHWAYS AND THE CO-OCCURRENCE OF GENETIC, EPIGENETIC AND NON-GENETIC SUSCEPTIBILITY FACTORS THAT ALTOGETHER AFFECT THE FUNCTIONAL AND STRUCTURAL PROPERTY OF THE SKIN. ALTHOUGH SHARED AND DIFFERENTIAL SUSCEPTIBILITY GENES AND MOLECULAR PATHWAYS ARE KNOWN TO CONTRIBUTE TO THE ONSET OF PATHOLOGICAL PHENOTYPES, FURTHER RESEARCH IS NEEDED TO DISSECT THE MOLECULAR CAUSES OF PSORIATIC DISEASE AND ITS PROGRESSION TOWARDS PSORIATIC ARTHRITIS. THIS REVIEW WILL THEREFORE BE ADDRESSED TO EXPLORE DIFFERENCES AND SIMILARITIES IN THE ETIOPATHOGENESIS AND PROGRESSION OF BOTH DISORDERS, WITH A PARTICULAR FOCUS ON GENES INVOLVED IN THE MAINTENANCE OF THE SKIN STRUCTURE AND INTEGRITY (KERATINS AND COLLAGENS), MODULATION OF PATTERNS OF RECOGNITION (THROUGH TOLL-LIKE RECEPTORS AND DECTIN-1) AND IMMUNO-INFLAMMATORY RESPONSE (BY NLRP3-DEPENDENT INFLAMMASOME) TO MICROBIAL PATHOGENS. IN ADDITION, SPECIAL EMPHASIS WILL BE GIVEN TO THE CONTRIBUTION OF EPIGENETIC ELEMENTS (METHYLATION PATTERN, NON-CODING RNAS, CHROMATIN MODIFIERS AND 3D GENOME ORGANIZATION) TO THE ETIOPATHOGENESIS AND PROGRESSION OF PSORIASIS AND PSORIATIC ARTHRITIS. THE EVIDENCE DISCUSSED IN THIS REVIEW HIGHLIGHTS HOW THE KNOWLEDGE OF PATIENTS' CLINICAL AND (EPI)GENOMIC MAKE-UP COULD BE HELPFUL FOR IMPROVING THE AVAILABLE THERAPEUTIC STRATEGIES FOR PSORIASIS AND PSORIATIC ARTHRITIS TREATMENT. 2020 16 5309 30 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 17 5288 22 PROSPECTS FOR EPIGENETIC COMPOUNDS IN THE TREATMENT OF AUTOIMMUNE DISEASE. THERE IS GROWING EVIDENCE FOR A ROLE FOR EPIGENETIC MECHANISMS IN THE DEVELOPMENT OF AUTOIMMUNE DISEASES. IN MOST CASES OFAUTOIMMUNE DISEASE THE PRECISE EPIGENETIC MECHANISM INVOLVED REMAINS TO BE RESOLVED, HOWEVER DNA HYPOMETHYLATION ACCOMPANIED BY HYPOACETYLATION OFHISTONE H3/H4 IS COMMONLY OBSERVED. DUE TO THE REVERSIBLE NATURE OF EPIGENETIC MARKS THEIR MAINTENANCE ENZYMES SUCH AS DNA METHYLTRANSFERASES (DNMTS), HISTONE DEACETYLASES (HDACS) AND HISTONE LYSINE METHYLTRANSFERASES (HKMT) ARE ATTRACTIVE DRUG TARGETS. SMALL MOLECULE INHIBITORS OF HISTONE MODIFICATION AND DNA METHYLATION MAINTENANCE ARE INCREASINGLY BECOMING AVAILABLE AND WILL BE USEFUL CHEMICAL BIOLOGICAL TOOLS TO DISSECT EPIGENETIC MECHANISMS IN THESE DISEASES. HOWEVER, ALTHOUGH EPIGENETIC THERAPIES USED IN CANCER TREATMENT ARE A PROMISING STARTING POINT FOR THE EXPLORATION OF AUTOIMMUNE DISEASE TREATMENT, THERE IS A REQUIREMENT FOR MORE SPECIFIC AND LESS TOXIC AGENTS FOR THESE CHRONIC DISEASES OR FOR USE AS CHEMOPREVENTATIVE AGENTS. 2011 18 6200 26 THE INFLAMMATORY EFFECT OF EPIGENETIC FACTORS AND MODIFICATIONS IN TYPE 2 DIABETES. INFLAMMATION HAS A CENTRAL ROLE IN THE ETIOLOGY OF TYPE 2 DIABETES (T2D) AND ITS COMPLICATIONS. BOTH GENETIC AND EPIGENETIC FACTORS HAVE BEEN IMPLICATED IN THE DEVELOPMENT OF T2D-ASSOCIATED INFLAMMATION. EPIGENETIC MECHANISMS REGULATE THE FUNCTION OF SEVERAL COMPONENTS OF THE IMMUNE SYSTEM. DIABETIC CONDITIONS TRIGGER ABERRANT EPIGENETIC ALTERATIONS THAT CONTRIBUTE TO THE PROGRESSION OF INSULIN RESISTANCE AND BETA-CELL DYSFUNCTION BY INDUCTION OF INFLAMMATORY RESPONSES. THUS, TARGETING EPIGENETIC FACTORS AND MODIFICATIONS, AS ONE OF THE UNDERLYING CAUSES OF INFLAMMATION, COULD LEAD TO THE DEVELOPMENT OF NOVEL IMMUNE-BASED STRATEGIES FOR THE TREATMENT OF T2D. THE AIM OF THIS REVIEW IS TO PROVIDE AN OVERVIEW OF THE EPIGENETIC MECHANISMS INVOLVED IN THE PROPAGATION AND PERPETUATION OF CHRONIC INFLAMMATION IN T2D. WE ALSO DISCUSS THE POSSIBLE ANTI-INFLAMMATORY APPROACHES THAT TARGET EPIGENETIC FACTORS FOR THE TREATMENT OF T2D. 2020 19 1838 26 EFFECTS OF POLYPHENOLS ON NCRNAS IN CANCER-AN UPDATE. IN RECENT YEARS, ONCOTHERAPY HAS RECEIVED CONSIDERABLE ATTENTION CONCERNING PLANT POLYPHENOLS. INCREASING EVIDENCE SUGGESTS THAT BECAUSE OF THE EFFICIENCY OF POLYPHENOLS, THEY MAY HAVE ANTI-TUMOUR EFFECTS IN VARIOUS CANCERS. HOWEVER, THEIR REGULATORY STRUCTURES REMAIN ELUSIVE. LONG NON-CODING RNAS (LNCRNAS) HAVE BEEN IDENTIFIED IN THE REGULATION OF VARIOUS FORMS OF TUMORIGENESIS AND TUMOUR DEVELOPMENT. LONG NON-CODING RNAS HAVE RECENTLY EMERGED AS REGULATORY EUKARYOTIC TRANSCRIPTS AND THERAPEUTIC TARGETS WITH IMPORTANT AND DIVERSE FUNCTIONS IN HEALTH AND DISEASES. LNCRNAS MAY BE ASSOCIATED WITH THE INITIATION, DEVELOPMENT, AND PROGRESSION OF CANCER. THIS REVIEW SUMMARIZES THE RESEARCH ON THE MODULATORY EFFECTS OF INCRNAS AND THEIR ROLES IN MEDIATING CELLULAR PROCESSES. THE MECHANISMS OF ACTION OF POLYPHENOLS UNDERLYING THEIR THERAPEUTIC EFFECTS ON CANCERS ARE ALSO DISCUSSED. BASED ON OUR REVIEW, POLYPHENOLS MIGHT FACILITATE A SIGNIFICANT EPIGENETIC MODIFICATION AS PART OF THEIR TISSUE- AND/OR CELL-RELATED BIOLOGICAL EFFECTS. THIS FINDING MAY BE ATTRIBUTED TO THEIR INTERACTION WITH CELLULAR SIGNALLING PATHWAYS INVOLVED IN CHRONIC DISEASES. CERTAIN LNCRNAS MIGHT BE THE TARGET OF SPECIFIC POLYPHENOLS, AND SOME CRITICAL SIGNALLING PROCESSES INVOLVED IN THE INTERVENTION OF CANCERS MIGHT MEDIATE THE THERAPEUTIC ROLES OF POLYPHENOLS. 2022 20 2289 21 EPIGENETIC REGULATION IN MONOCYTE/MACROPHAGE: A KEY PLAYER DURING ATHEROSCLEROSIS. ATHEROSCLEROSIS IS A CHRONIC INFLAMMATORY DISEASE. RECENTLY, A GROWING BODY OF EVIDENCE EMPHASIZES THAT THE MONOCYTE AND MACROPHAGE DIFFERENTIATION AND ACTIVATION ARE KEY PROCESSES IN THE DEVELOPMENT OF ATHEROSCLEROSIS. HOWEVER, THE REGULATORY MECHANISM THAT MANIPULATES THE FUNCTION OF MONOCYTE AND MACROPHAGE IS STILL UNCLEAR. RECENT YEARS, EPIGENETIC MECHANISMS HAVE RECEIVED A WIDE ATTENTION AND BRING US A NEW FIELD OF VISION. MORE AND MORE EVIDENCE SHOWS THAT EPIGENETICS WEIGHS HEAVILY IN ATHEROSCLEROSIS BY REGULATING THE FUNCTION AND DIFFERENTIATION STATES OF MONOCYTE AND MACROPHAGE. IN THIS REVIEW, WE ILLUMINATE THE EPIGENETIC REGULATION MECHANISMS IN MONOCYTE AND MACROPHAGE AND THEIR CONTRIBUTIONS TO INFLAMMATORY PROCESSES OF ATHEROSCLEROSIS TO PROVIDE NEW THOUGHTS AND FIND NOVEL TARGETS OR BIOMARKERS FOR ATHEROSCLEROSIS. 2017