1 4272 135 MICROBIOME AND BEHCET'S DISEASE: A SYSTEMATIC REVIEW. THE AIM OF THIS REVIEW WAS TO DESCRIBE THE CHANGES IN THE MICROBIOTA OF PATIENTS WITH BEHCET'S DISEASE (BD) AND THE MECHANISMS INVOLVED IN THE RELATIONSHIP BETWEEN THE MICROBIOME AND IMMUNITY IN BD. A SYSTEMATIC SEARCH FOR RELEVANT ARTICLES WAS MADE ON PUBMED AND THE COCHRANE LIBRARY DATABASE USING THE FOLLOWING TERMS: "MICROBIOTA AND BEHCET'S DISEASE" OR "MICROBIOME AND BEHCET'S DISEASE". SIXTEEN ARTICLES WERE INCLUDED IN A QUALITATIVE SYNTHESIS. THIS SYSTEMATIC REVIEW ON THE MICROBIOME AND BEHCET'S DISEASE UNDERLINES THE PRESENCE OF GUT DYSBIOSIS IN BD PATIENTS. THIS DYSBIOSIS IS MARKED BY (I) A DECREASE IN BUTYRATE-PRODUCING BACTERIA, WHICH COULD AFFECT T CELL DIFFERENTIATION AND EPIGENETIC REGULATION OF IMMUNE-RELATED GENES, (II) A MODIFICATION OF TRYPTOPHAN-METABOLISING BACTERIA, WHICH COULD BE LINKED TO DYSREGULATED IL-22 SECRETION, AND (III) A DECREASE IN BACTERIA KNOWN TO HAVE ANTI-INFLAMMATORY PROPERTIES. REGARDING ORAL MICROBIOTA, THIS REVIEW UNDERLINES THE POSSIBLE ROLE OF STREPTOCOCCUS SANGUINIS THROUGH MOLECULAR MIMICRY AND NETOSIS. CLINICAL STUDIES OF BD HAVE SHOWN THAT (I) NEED FOR DENTISTRY IS ASSOCIATED WITH A MORE SEVERE COURSE IN BD, AND (II) ANTIBIOTIC-SUPPLEMENTED MOUTHWASH REDUCES PAIN AND ULCERS. FECAL TRANSPLANTATION OF BD PATIENTS' MICROBIOTA INTO MOUSE MODELS LED TO DECREASED SCFA PRODUCTION, NEUTROPHIL ACTIVATION, AND TH1/TH17 RESPONSES.RECIPIENT MICE SHOWED EXACERBATED EXPERIMENTAL AUTOIMMUNE UVEITIS (EAU) AND EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS (EAE). IN HERPES VIRUS SIMPLEX-1 (HSV-1) INFECTED MICE MIMICKING BD, ADMINISTRATION OF BUTYRATEPRODUCING BACTERIA IMPROVED SYMPTOMS AND IMMUNE VARIABLES. THE MICROBIOME MAY THUS BE INVOLVED IN BD THROUGH IMMUNITY REGULATION AND EPIGENETIC MODIFICATIONS. 2023 2 1226 32 CRITICAL ROLE OF GUT MICROBIOTA AND EPIGENETIC FACTORS IN THE PATHOGENESIS OF BEHCET'S DISEASE. BEHCET'S DISEASE (BD) IS A CHRONIC REFRACTORY MULTISYSTEM AUTOINFLAMMATORY DISEASE, CHARACTERIZED BY TYPICAL CLINICAL FEATURES OF NON-SPECIFIC VASCULITIS, ORAL AND GENITAL ULCERS, UVEITIS, AS WELL AS SKIN LESIONS. THE EXACT ETIOPATHOGENESIS OF BD REMAINS UNKNOWN, EXISTING STUDIES HAVE INDICATED THAT GENETICS AND ENVIRONMENTAL FACTORS CONTRIBUTE TO THE INCREASED DEVELOPMENT OF BD. RECENTLY, SEVERAL STUDIES HAVE SHOWN THAT EXTERNAL ENVIRONMENTAL FACTORS CAN AFFECT THE PROCESS OF EPIGENETIC MODIFICATION, AND ABNORMALITIES OF EPIGENETIC FACTORS HAVE BEEN CONFIRMED TO BE INVOLVED IN THE OCCURRENCE OF BD. AT THE SAME TIME, ABNORMALITIES OF GUT MICROBIOTA (GM) IN THE BODY, HAVE ALSO BEEN CONFIRMED TO PARTICIPATE IN THE PATHOGENESIS OF BD BY REGULATING THE BALANCE OF TH17/TREGS. THIS ARTICLE REVIEWS THE PATHOGENESIS OF BD AND SUMMARIZES NUMEROUS CLINICAL STUDIES, FOCUSING ON THE MECHANISM OF GM AND EPIGENETIC FACTORS IMPACTING ON BD, AND PROVIDING NEW IDEAS FOR FURTHER ELUCIDATING THE PATHOGENESIS OF BD. 2021 3 3023 33 GENETICS AND IMMUNODYSFUNCTION UNDERLYING BEHCET'S DISEASE AND IMMUNOMODULANT TREATMENT APPROACHES. BEHCET'S DISEASE (BD) IS A CHRONIC AUTOIMMUNE CONDITION PRIMARILY PREVALENT IN POPULATIONS ALONG THE MEDITERRANEAN SEA. THE EXACT ETIOLOGY OF BD HAS NOT BEEN FULLY EXPLAINED YET, BUT THE DISEASE OCCURRENCE IS ASSOCIATED WITH A GENETIC FACTOR, HUMAN LEUKOCYTE ANTIGEN (HLA)-B51 ANTIGEN. AMONG THE VARIOUS IMMUNODYSFUNCTIONS THAT ARE FOUND IN BD, PATIENTS ARE INCREASED NEUTROPHIL MOTILITY AND SUPEROXIDE PRODUCTION, AS WELL AS ELEVATED PRODUCTION OF TUMOR NECROSIS FACTOR (TNF)-ALPHA AND DECREASED PRODUCTION OF INTERLEUKIN (IL)-10. ELEVATED LEVELS OF INFLAMMATORY CYTOKINES LIKE IL-1 AND IL-17 IN BD HAVE BEEN FOUND ASSOCIATED WITH ABERRANT EXPRESSION OF MICRORNA. GENE POLYMORPHISMS IN BD PATIENTS HAVE BEEN OBSERVED IN MOLECULES INVOLVED IN RESPONSES TO PATHOGENS THAT CAN ULTIMATELY MODULATE THE HOST ANTIMICROBIAL RESPONSE. MOREOVER, SEVERAL SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) HAVE BEEN REPORTED IN GENES ENCODING CHEMOKINES AND ADHESION MOLECULES; MANY OF THESE CHANGES MANIFEST AS INCREASES IN VASCULAR INFLAMMATION AND VASCULAR DAMAGE. LASTLY, GENETIC AND EPIGENETIC CHANGES HAVE BEEN SUGGESTED AS INVOLVED IN THE PATHOGENESIS OF BD. MODIFICATIONS IN DNA METHYLATION HAVE BEEN FOUND IN BD PATIENT MONOCYTES AND LYMPHOCYTES, LEADING TO ADVERSE FUNCTION OF THESE CELLS. THIS REVIEW PRESENTS A COMPREHENSIVE COMPILATION OF THE LITERATURE WITH REGARD TO THE IMMUNODYSFUNCTION UNDERLYING BD, AS WELL AS OF THE GENETICS, NEWLY DESCRIBED CLINICAL SPECIFICATIONS AND NOVEL TREATMENT STRATEGIES USING IMMUNOMODULANTS BASED ON THE CURRENT UNDERSTANDING OF BD. 2017 4 1979 33 EPIGENETIC ALTERATIONS IN CHRONIC DISEASE FOCUSING ON BEHCET'S DISEASE: REVIEW. OBJECTIVE: 'EPIGENETICS' IS SPECIFIED AS THE INHERITABLE CHANGES IN GENE EXPRESSION WITH NO ALTERATIONS IN DNA SEQUENCES. EPIGENETICS IS A RAPIDLY OVERSPREADING SCIENTIFIC FIELD, AND THE STUDY OF EPIGENETIC REGULATION IN CHRONIC DISEASE IS EMERGING. THIS STUDY AIMS TO EVALUATE EPIGENETIC CHANGES INCLUDING DNA METHYLATION, HISTONE MODIFICATION, AND NON-CODING RNAS (NCRNAS) IN INFLAMMATORY DISEASE, WITH FOCUS ON BEHCET'S DISEASE. IN THIS REVIEW, FIRST WE DESCRIBE THE HISTORY AND CLASSIFICATION OF EPIGENETIC CHANGES, AND THEN THE ROLE OF EPIGENETIC ALTERATIONS IN CHRONIC DISEASES IS EXPLAINED. METHODS: SYSTEMATIC SEARCH OF MEDLINE, EMBASE, AND COCHRANE LIBRARY WAS CONDUCTED FOR ALL COMPARATIVE STUDIES SINCE 2000 TO 2015 WITH THE LIMITATIONS OF THE ENGLISH LANGUAGE. RESULTS: FOR A NOTABLE PERIOD OF TIME, RESEARCHERS HAVE MAINLY FOCUSED ON THE EPIGENETIC PATHWAYS THAT ARE INVOLVED IN THE MODULATION OF INFLAMMATORY AND ANTI-INFLAMMATORY GENES. RECENT STUDIES HAVE PROPOSED A CENTRAL ROLE FOR CHRONIC INFLAMMATION IN THE PATHOGENESIS OF CHRONIC DISEASE, INCLUDING BEHCET'S DISEASE. CONCLUSION: STUDIES HAVE BEEN REPORTED ON THE EPIGENETIC OF BD SHOWED THE ROLE OF ALTERATIONS IN THE METHYLATION LEVEL OF IRS ELEMENTS; HISTONE MODIFICATIONS SUCH AS H3K4ME27 AND H3K4ME3; UP REGULATION OF MIR-182 AND MIR-3591-3P; DOWN REGULATION OF MIR-155, MIR-638 AND MIR-4488 IN THE PATHOGENESIS OF THE DISEASE. 2017 5 2534 38 EPIGENETICS IN BIPOLAR DISORDER: A CRITICAL REVIEW OF THE LITERATURE. INTRODUCTION: BIPOLAR DISORDER (BD) IS A CHRONIC, DISABLING DISEASE CHARACTERISED BY ALTERNATE MOOD EPISODES, SWITCHING THROUGH DEPRESSIVE AND MANIC/HYPOMANIC PHASES. MOOD STABILIZERS, IN PARTICULAR LITHIUM SALTS, CONSTITUTE THE CORNERSTONE OF THE TREATMENT IN THE ACUTE PHASE AS WELL AS FOR THE PREVENTION OF RECURRENCES. THE PATHOPHYSIOLOGY OF BD AND THE MECHANISMS OF ACTION OF MOOD STABILIZERS REMAIN LARGELY UNKNOWN BUT SEVERAL PIECES OF EVIDENCE POINT TO GENE X ENVIRONMENT INTERACTIONS. EPIGENETICS, DEFINED AS THE REGULATION OF GENE EXPRESSION WITHOUT GENETIC CHANGES, COULD BE THE MOLECULAR SUBSTRATE OF THESE INTERACTIONS. IN THIS LITERATURE REVIEW, WE SUMMARIZE THE MAIN EPIGENETIC FINDINGS ASSOCIATED WITH BD AND RESPONSE TO MOOD STABILIZERS. METHODS: WE SEARCHED PUBMED, AND EMBASE DATABASES AND CLASSIFIED THE ARTICLES DEPENDING ON THE EPIGENETIC MECHANISMS (DNA METHYLATION, HISTONE MODIFICATIONS AND NON-CODING RNAS). RESULTS: WE PRESENT THE DIFFERENT EPIGENETIC MODIFICATIONS ASSOCIATED WITH BD OR WITH MOOD-STABILIZERS. THE MAJOR REPORTED MECHANISMS WERE DNA METHYLATION, HISTONE METHYLATION AND ACETYLATION, AND NON-CODING RNAS. OVERALL, THE ASSESSMENTS ARE POORLY HARMONIZED AND THE RESULTS ARE MORE LIMITED THAN IN OTHER PSYCHIATRIC DISORDERS (E.G. SCHIZOPHRENIA). HOWEVER, THE NATURE OF BD AND ITS TREATMENT OFFER EXCELLENT OPPORTUNITIES FOR EPIGENETIC RESEARCH: CLEAR IMPACT OF ENVIRONMENTAL FACTORS, CLINICAL VARIATION BETWEEN MANIC OR DEPRESSIVE EPISODES RESULTING IN POSSIBLE IDENTIFICATION OF STATE AND TRAITS BIOMARKERS, DOCUMENTED IMPACT OF MOOD-STABILIZERS ON THE EPIGENOME. CONCLUSION: EPIGENETIC IS A GROWING AND PROMISING FIELD IN BD THAT MAY SHED LIGHT ON ITS PATHOPHYSIOLOGY OR BE USEFUL AS BIOMARKERS OF RESPONSE TO MOOD-STABILIZER. 2021 6 3026 30 GENETICS OF BEHCET'S DISEASE: FUNCTIONAL GENETIC ANALYSIS AND ESTIMATING DISEASE HERITABILITY. BEHCET'S DISEASE IS A CHRONIC MULTISYSTEMIC INFLAMMATORY DISORDER CHARACTERIZED BY RECURRENT ORAL AND GENITAL ULCERS. ALTHOUGH ITS ETIOLOGY REMAINS UNCLEAR, IT IS THOUGHT THAT BOTH GENETIC AND ENVIRONMENTAL FACTORS CONTRIBUTE TO THE ONSET AND PROGRESSION OF BEHCET'S DISEASE. HERE, WE PROVIDE AN UPDATED VIEW OF THE GENETIC LANDSCAPE AND ARCHITECTURE OF BEHCET'S DISEASE. LARGE-SCALE GENETIC STUDIES PERFORMED TO DATE REVEALED 21 GENETIC SUSCEPTIBILITY LOCI ASSOCIATED WITH THE DISEASE AT A GWAS LEVEL OF SIGNIFICANCE (P-VALUE = 5 X 10(-8)). WE PERFORMED EPIGENETIC PATTERN ENRICHMENT ANALYSIS IN BEHCET'S DISEASE ASSOCIATED LOCI, PROVIDING NEW INSIGHTS INTO THE MOLECULAR MECHANISMS UNDERLYING ITS PATHOPHYSIOLOGY. OUR DATA SUGGEST THE CRUCIAL INVOLVEMENT OF SEVERAL IMMUNE CELL TYPES, INCLUDING NATURAL KILLER CELLS, MONOCYTES, AND B CELLS IN THE PATHOGENESIS OF THE DISEASE. PATHWAY ENRICHMENT ANALYSIS IDENTIFIED IMPORTANT BIOLOGICAL PROCESSES INVOLVED. USING LARGE-SCALE GENETIC DATA AVAILABLE FROM ~200 IMMUNE-RELATED LOCI (IMMUNOCHIP), WE ESTIMATE BEHCET'S DISEASE HERITABILITY TO BE AT LEAST 16%. WE FURTHER USED THE SAME APPROACH TO ESTIMATE THE HERITABILITY EXPLAINED BY THE KNOWN BEHCET'S DISEASE-ASSOCIATED LOCI, SUGGESTING THAT THEY EXPLAIN ~ 60% OF THE GENETIC COMPONENT UNDERLYING BEHCET'S DISEASE. THESE RESULTS INDICATE A SIGNIFICANT ROLE OF NON-GENETIC FACTORS IN CAUSING BEHCET'S DISEASE AND THAT ADDITIONAL GENETIC VARIATION INFLUENCING THE RISK OF BEHCET'S DISEASE REMAINS TO BE IDENTIFIED. FINALLY, WE CALCULATED A CUMULATIVE GENETIC RISK SCORE ACROSS POPULATIONS REINFORCING THE LINK BETWEEN GEOGRAPHIC VARIATIONS IN DISEASE PREVALENCE WITH ITS GENETIC COMPONENT. 2021 7 4328 24 MICRORNAS, STEM CELLS IN BIPOLAR DISORDER, AND LITHIUM THERAPEUTIC APPROACH. BIPOLAR DISORDER (BD) IS A SEVERE, CHRONIC, AND DISABLING NEUROPSYCHIATRIC DISORDER CHARACTERIZED BY RECURRENT MOOD DISTURBANCES (MANIA/HYPOMANIA AND DEPRESSION, WITH OR WITHOUT MIXED FEATURES) AND A CONSTELLATION OF COGNITIVE, PSYCHOMOTOR, AUTONOMIC, AND ENDOCRINE ABNORMALITIES. THE ETIOLOGY OF BD IS MULTIFACTORIAL, INCLUDING BOTH BIOLOGICAL AND EPIGENETIC FACTORS. RECENTLY, MICRORNAS (MIRNAS), A CLASS OF EPIGENETIC REGULATORS OF GENE EXPRESSION PLAYING A CENTRAL ROLE IN BRAIN DEVELOPMENT AND PLASTICITY, HAVE BEEN RELATED TO SEVERAL NEUROPSYCHIATRIC DISORDERS, INCLUDING BD. MOREOVER, AN ALTERATION IN THE NUMBER/DISTRIBUTION AND DIFFERENTIATION POTENTIAL OF NEURAL STEM CELLS HAS ALSO BEEN DESCRIBED, SIGNIFICANTLY AFFECTING BRAIN HOMEOSTASIS AND NEUROPLASTICITY. THIS REVIEW AIMED TO EVALUATE THE MOST RELIABLE SCIENTIFIC EVIDENCE ON MIRNAS AS BIOMARKERS FOR THE DIAGNOSIS OF BD AND ASSESS THEIR IMPLICATIONS IN RESPONSE TO MOOD STABILIZERS, SUCH AS LITHIUM. NEURAL STEM CELL DISTRIBUTION, REGULATION, AND DYSFUNCTION IN THE ETIOLOGY OF BD ARE ALSO DISSECTED. 2022 8 4439 31 MOLECULAR GENETIC AND EPIGENETIC BASIS OF MULTIPLE SCLEROSIS. MULTIPLE SCLEROSIS (MS) IS A CHRONIC IMMUNE-MEDIATED DISEASE OF SPINAL CORD AND BRAIN. THE INITIAL EVENT IN MS OCCURS WHEN ACTIVATED CD4(+) T CELLS IN PERIPHERY EXACERBATES IMMUNE RESPONSES BY STIMULATING IMMUNE CELLS SUCH AS B CELLS, CD8(+) CELLS, MAST CELLS, GRANULOCYTES AND MONOCYTES. THESE PROINFLAMMATORY CELLS PASS BLOOD BRAIN BARRIER BY SECRETING PROINFLAMMATORY CYTOKINES INCLUDING TNF-ALPHA AND INF-(GAMMA) WHICH ACTIVATE ADHESION FACTORS. APCS (ANTIGEN-PRESENTING CELLS) REACTIVATE CD4(+) T CELLS AFTER INFILTRATING THE CNS AND CD4(+) T CELLS PRODUCE CYTOKINES AND CHEMOKINES. THESE PROINFLAMMATORY CYTOKINES AGGRAVATE INFLAMMATION BY INDUCING MYELIN PHAGOCYTOSIS THROUGH MICROGLIA AND ASTROCYTES ACTIVATION. MS IS BELIEVED TO HAVE A MULTIFACTORIAL ORIGIN THAT INCLUDES A COMBINATION OF MULTIPLE GENETIC, ENVIRONMENTAL AND STOCHASTIC FACTORS. ALTHOUGH THE EXACT COMPONENT OF MS RISKS THAT CAN BE EXPLAINED BY THESE FACTORS IS DIFFICULT TO DETERMINE, ESTIMATES BASED ON GENETIC AND EPIDEMIOLOGICAL STUDIES SUGGEST THAT UP TO 60-70 % OF THE TOTAL RISK OF MS MAY BE CONTRIBUTE TO GENETIC FACTORS. IN CONTINUE, FIRSTLY WE PROVIDE AN OVERVIEW OF THE CURRENT UNDERSTANDING OF EPIGENETIC MECHANISMS, AND SO PRESENT EVIDENCE OF HOW THE EPIGENETIC MODIFICATIONS CONTRIBUTE TO INCREASED SUSCEPTIBILITY OF MS. WE ALSO EXPLAIN HOW SPECIFIED EPIGENETIC MODIFICATIONS MAY INFLUENCE THE PATHOPHYSIOLOGY AND KEY ASPECTS OF DISEASE IN MS (DEMYELINATION, REMYELINATION, INFLAMMATION, AND NEURODEGENERATION). FINALLY, WE TEND TO DISCUSS HOW ENVIRONMENTAL FACTORS AND EPIGENETIC MECHANISMS MAY INTERACT TO HAVE AN EFFECT ON MS RISK AND CLINICAL OUTCOME AND RECOMMEND NEW THERAPEUTIC INTERVENTIONS THAT MIGHT MODULATE PATIENTS' EPIGENETIC PROFILES. 2017 9 3549 33 IMMUNOSENESCENCE AND MULTIPLE SCLEROSIS. CHANGES IN THE IMMUNE SYSTEM ASSOCIATED WITH AGEING ARE KNOWN AS IMMUNOSENESCENCE. THIS IS CHARACTERISED BY A DECLINE IN IMMUNE RESPONSE, CHRONIC INFLAMMATION AND AN INCREASED RISK OF AUTOIMMUNE DISEASES. A CHRONIC INFLAMMATORY PROCESS WITH PERSISTENT PRODUCTION OF PROINFLAMMATORY MEDIATORS INCREASES THE RISK FOR MORBIDITY AND MORTALITY RELATED TO AGE, AND HAS BEEN DUBBED 'INFLAMM-AGEING'. IMMUNOSENESCENCE IS ASSOCIATED WITH A DECREASE IN THE NUMBER OF NAIVE T AND B CELLS, NK CELLS AND DISRUPTION OF THE PRO- AND ANTI-INFLAMMATORY BALANCE BY CHANGES IN THE PRODUCTION OF CYTOKINES. IN FACT, AGEING OF THE IMMUNE SYSTEM HAS A COMPLEX NETWORK OF UNDERLYING CAUSES WHICH INCLUDE NOT ONLY NATURAL MECHANISMS OF SENESCENCE BUT ALSO CHRONIC DISORDERS, LIFESTYLE, ENVIRONMENTAL AND EPIGENETIC FACTORS, AND INFECTIONS. MOREOVER, IMMUNOSENESCENCE HAS AN INFLUENCE ON THE COURSE OF CHRONIC DISEASES WHICH HAVE AN ONSET IN YOUNG ADULTS, SUCH AS MULTIPLE SCLEROSIS (MS). CURRENT DISEASE MODIFYING THERAPIES (DMTS) IN MS AIM TO REDUCE THE FREQUENCY OF RELAPSES AND TO SLOW DISEASE PROGRESSION, BUT THEY DO NOT NECESSARILY STOP THE ACCUMULATION OF DISABILITY RELATED TO DISEASE PROGRESSION. SOME FEATURES OF IMMUNOSENESCENCE FOUND IN AGED HEALTHY CONTROLS ARE ALREADY OBSERVED IN MS PATIENTS AT A YOUNGER AGE. THE OLDER POPULATION IS CHARACTERISED BY AN INCREASED SUSCEPTIBILITY TO INFECTIONS, A POOR RESPONSE TO VACCINATIONS, AND A HIGHER RISK OF DEVELOPING CANCER, VASCULAR DISEASES AND NEURODEGENERATION. IMMUNOSENESCENCE IS AN IMPORTANT FACTOR INFLUENCING THE COURSE OF MS, AND THE SAFETY AND EFFECTIVENESS OF DMTS. THE RELATIONSHIP BETWEEN THE PATHOGENIC PROCESS UNDERLYING THE DEVELOPMENT OF MS AND IMMUNOSENESCENCE REQUIRES FURTHER INVESTIGATION. 2022 10 6791 22 [DOES THE NUMBER OF PATIENTS WITH AUTOIMMUNE DISORDERS AND THE FREQUENCY OF AUTOIMMUNE DISEASES INCREASE?]. AUTOIMMUNE DISEASES GENERALLY BELONG TO THE RARE DISEASES, HOWEVER, SOME OF THEM ARE FREQUENT IN THE POPULATION. IN THE PRESENT WORK THE AUTHORS ANALYSE WHETHER CAN ANY INCREASE BE OBSERVED IN THE NUMBER OF PATIENTS SUFFERING FROM AUTOIMMUNE DISEASES AND WHETHER DO THE FREQUENCY OF CERTAIN AUTOIMMUNE DISORDERS INCREASE. DUE MAINLY TO EPIGENETIC FACTORS THE INCIDENCE OF AUTOIMMUNE DISEASES ARE INCREASING, THEREFORE THERE ARE MORE PATIENTS RECOGNISED WITH PARTICULAR DISORDERS. ON THE OTHER HAND THE INCIDENCE IS INCREASED BY IMPROVING DIAGNOSTIC POSSIBILITIES, BY THE USE OF MORE SPECIFIC AND SENSITIVE CLASSIFICATION CRITERIA AND MORE SOPHISTICATED LABORATORY TESTS, RESULTED IN THE RECOGNITION OF MILDER AND ATYPICAL DISEASE VARIANTS AS WELL. THE PREVALENCE IS ALSO INCREASING IN CONSEQUENCE OF NOVEL IMMUNE SUPPRESSIVE THERAPEUTIC POSSIBILITIES AND THE CONSEQUENT IMPROVEMENT OF SURVIVAL IN THE MOST OF THESE DISEASES. BESIDES, MORE AND MORE DISEASES HAVE BEEN REVEALED TO HAVE AUTOIMMUNE BACKGROUND, AND LOT OF NEW AUTOIMMUNE SYNDROMES, DISEASES HAVE BEEN CHARACTERISED RECENTLY. THIS INCREASES THE NUMBER OF THE KNOWN AUTOIMMUNE RHEUMATIC DISORDERS WITH A CONSEQUENT INCREASE IN THE NUMBER OF AUTOIMMUNE PATIENTS. ASSIGNED TO THE INCREASING NUMBER OF VARIABLE CHRONIC AUTOIMMUNE DISORDERS, AND THE INCREASING NUMBER OF DISABLED PATIENTS WITH SUCH DISEASES INCREASING MEDICAL AND SOCIAL ATTENTION HAS TO BE FOCUSED ON. 2007 11 3692 32 INFLAMMATORY BOWEL DISEASES: THE ROLE OF GUT MICROBIOTA. INFLAMMATORY BOWEL DISEASES (IBD) ARE CHRONIC MULTIFACTORIAL DISEASES CHARACTERIZED BY PARTIALLY UNCLEAR PATHOGENIC MECHANISMS INCLUDING CHANGES IN INTESTINAL MICROBIOTA. DESPITE THE MICROBIOTA, ALTERATION IS WELL ESTABLISHED IN IBD PATIENTS, AS REPORTED BY 16RNA SEQUENCING ANALYSIS, AN IMPORTANT GOAL IS TO DEFINE IF IT IS JUST A CONSEQUENCE OF THE DISEASE PROGRESSION OR A TRIGGER FACTOR OF THE DISEASE ITSELF. TO DATE, GUT MICROBIOTA COMPOSITION AND GUT MICROBIOTA-RELATED METABOLITES SEEM TO AFFECT THE HOST HEALTHY STATE BOTH BY MODULATING METABOLIC PATHWAYS OR ACTING ON THE EXPRESSION OF DIFFERENT GENES THROUGH EPIGENETIC EFFECTS. BECAUSE OF THIS, IT HAS BEEN SUGGESTED THAT INTESTINAL MICROBIOTA MIGHT REPRESENT A PROMISING THERAPEUTIC TARGET FOR IBD PATIENTS. THE AIM OF THIS REVIEW IS TO SUMMARIZE BOTH THE MOST RECENT ACQUISITIONS IN THE FIELD OF GUT MICROBIOTA AND ITS INVOLVEMENT IN INTESTINAL INFLAMMATION TOGETHER WITH THE AVAILABLE STRATEGIES FOR THE MODULATION OF MICROBIOTA, SUCH AS PREBIOTICS AND/OR PROBIOTICS ADMINISTRATION OR FECAL MICROBIOTA TRANSPLANTATION. 2020 12 1149 39 CONNECTING THE IMMUNE SYSTEM, SYSTEMIC CHRONIC INFLAMMATION AND THE GUT MICROBIOME: THE ROLE OF SEX. UNRESOLVED LOW GRADE SYSTEMIC INFLAMMATION REPRESENTS THE UNDERLYING PATHOLOGICAL MECHANISM DRIVING IMMUNE AND METABOLIC PATHWAYS INVOLVED IN AUTOIMMUNE DISEASES (AID). MECHANISTIC STUDIES IN ANIMAL MODELS OF AID AND OBSERVATIONAL STUDIES IN PATIENTS HAVE FOUND ALTERATIONS IN GUT MICROBIOTA COMMUNITIES AND THEIR METABOLITES, SUGGESTING A MICROBIAL CONTRIBUTION TO THE ONSET OR PROGRESSION OF AID. THE GUT MICROBIOTA AND ITS METABOLITES HAVE BEEN SHOWN TO INFLUENCE IMMUNE FUNCTIONS AND IMMUNE HOMEOSTASIS BOTH WITHIN THE GUT AND SYSTEMATICALLY. MICROBIAL DERIVED-SHORT CHAIN FATTY ACID (SCFA) AND BIO-TRANSFORMED BILE ACID (BA) HAVE BEEN SHOWN TO INFLUENCE THE IMMUNE SYSTEM ACTING AS LIGANDS SPECIFIC CELL SIGNALING RECEPTORS LIKE GPRCS, TGR5 AND FXR, OR VIA EPIGENETIC PROCESSES. SIMILARLY, INTESTINAL PERMEABILITY (LEAKY GUT) AND BACTERIAL TRANSLOCATION ARE IMPORTANT CONTRIBUTORS TO CHRONIC SYSTEMIC INFLAMMATION AND, WITHOUT REPAIR OF THE INTESTINAL BARRIER, MIGHT REPRESENT A CONTINUOUS INFLAMMATORY STIMULUS CAPABLE OF TRIGGERING AUTOIMMUNE PROCESSES. RECENT STUDIES INDICATE GENDER-SPECIFIC DIFFERENCES IN IMMUNITY, WITH THE GUT MICROBIOTA SHAPING AND BEING CONCOMITANTLY SHAPED BY THE HORMONAL MILIEU GOVERNING DIFFERENCES BETWEEN THE SEXES. A BI-DIRECTIONAL CROSS-TALK BETWEEN MICROBIOTA AND THE ENDOCRINE SYSTEM IS EMERGING WITH BACTERIA BEING ABLE TO PRODUCE HORMONES (E.G. SEROTONIN, DOPAMINE AND SOMATOSTATINE), RESPOND TO HOST HORMONES (E.G. ESTROGENS) AND REGULATE HOST HORMONES' HOMEOSTASIS (E.G BY INHIBITING GENE PROLACTIN TRANSCRIPTION OR CONVERTING GLUCOCORTICOIDS TO ANDROGENS). WE REVIEW HEREIN HOW GUT MICROBIOTA AND ITS METABOLITES REGULATE IMMUNE FUNCTION, INTESTINAL PERMEABILITY AND POSSIBLY AID PATHOLOGICAL PROCESSES. FURTHER, WE DESCRIBE THE DYSBIOSIS WITHIN THE GUT MICROBIOTA OBSERVED IN DIFFERENT AID AND SPECULATE HOW RESTORING GUT MICROBIOTA COMPOSITION AND ITS REGULATORY METABOLITES BY DIETARY INTERVENTION INCLUDING PREBIOTICS AND PROBIOTICS COULD HELP IN PREVENTING OR AMELIORATING AID. FINALLY, WE SUGGEST THAT, GIVEN CONSISTENT OBSERVATIONS OF MICROBIOTA DYSBIOSIS ASSOCIATED WITH AID AND THE ABILITY OF SCFA AND BA TO REGULATE INTESTINAL PERMEABILITY AND INFLAMMATION, FURTHER MECHANISTIC STUDIES, EXAMINING HOW DIETARY MICROBIOTA MODULATION CAN PROTECT AGAINST AID, HOLD CONSIDERABLE POTENTIAL TO TACKLE INCREASED INCIDENCE OF AID AT THE POPULATION LEVEL. 2018 13 6136 31 THE EPIGENETICS OF MULTIPLE SCLEROSIS AND OTHER RELATED DISORDERS. MULTIPLE SCLEROSIS (MS) IS A DEMYELINATING DISEASE CHARACTERIZED BY CHRONIC INFLAMMATION OF THE CENTRAL NERVOUS SYSTEM (CNS) GRAY AND WHITE MATTER. ALTHOUGH THE CAUSE OF MS IS UNKNOWN, IT IS WIDELY APPRECIATED THAT INNATE AND ADAPTIVE IMMUNE PROCESSES CONTRIBUTE TO ITS PATHOGENESIS. THESE INCLUDE MICROGLIA/MACROPHAGE ACTIVATION, PRO-INFLAMMATORY T-CELL (TH1) RESPONSES AND HUMORAL RESPONSES. ADDITIONALLY, THERE IS EVIDENCE INDICATING THAT MS HAS A NEURODEGENERATIVE COMPONENT SINCE NEURONAL AND AXONAL LOSS OCCURS EVEN IN THE ABSENCE OF OVERT INFLAMMATION. THESE ASPECTS ALSO FORM THE RATIONALE FOR CLINICAL MANAGEMENT OF THE DISEASE. HOWEVER, THE CURRENTLY AVAILABLE THERAPIES TO CONTROL THE DISEASE ARE ONLY PARTIALLY EFFECTIVE AT BEST INDICATING THAT MORE EFFECTIVE THERAPEUTIC SOLUTIONS ARE URGENTLY NEEDED. IT IS APPRECIATED THAT IN THE IMMUNE-DRIVEN AND NEURODEGENERATIVE PROCESSES MS-SPECIFIC DEREGULATION OF GENE EXPRESSIONS AND RESULTING PROTEIN DYSFUNCTION ARE THOUGHT TO PLAY A CENTRAL ROLE. THESE DEVIATIONS IN GENE EXPRESSION PATTERNS CONTRIBUTE TO THE INFLAMMATORY RESPONSE IN THE CNS, AND TO NEURONAL OR AXONAL LOSS. EPIGENETIC MECHANISMS CONTROL TRANSCRIPTION OF MOST, IF NOT ALL GENES, IN NUCLEATED CELLS INCLUDING CELLS OF THE CNS AND IN HAEMATOPOIETIC CELLS. MS-SPECIFIC ALTERATIONS IN EPIGENETIC REGULATION OF GENE EXPRESSION MAY THEREFORE LIE AT THE HEART OF THE DEREGULATION OF GENE EXPRESSION IN MS. AS SUCH, EPIGENETIC MECHANISMS MOST LIKELY PLAY AN IMPORTANT ROLE IN DISEASE PATHOGENESIS. IN THIS REVIEW WE DISCUSS A ROLE FOR MS-SPECIFIC DEREGULATION OF EPIGENETIC FEATURES THAT CONTROL GENE EXPRESSION IN THE CNS AND IN THE PERIPHERY. FURTHERMORE, WE DISCUSS THE APPLICATION OF SMALL MOLECULE INHIBITORS THAT TARGET THE EPIGENETIC MACHINERY TO AMELIORATE DISEASE IN EXPERIMENTAL ANIMAL MODELS, INDICATING THAT SUCH APPROACHES MAY BE APPLICABLE TO MS PATIENTS. 2014 14 4536 27 MULTIPLE SCLEROSIS - RISK FACTORS. MULTIPLE SCLEROSIS (MS) IS A CHRONIC AUTOIMMUNOLOGICAL CONDITION OF THE CENTRAL NERVOUS SYSTEM (CNS) AFFECTING MAINLY YOUNG ADULT INDIVIDUALS. THE PREVALENCE RANGES APPROXIMATELY BETWEEN 50 AND 300 PER 100000 INDIVIDUALS. IT IS CHARACTERIZED BY AN INFLAMMATORY PROCESS, DEMYELINATION AND AXONAL LOSS. IMMUNOLOGICAL MECHANISMS RESULTING IN THE DAMAGE TO THE MYELIN SHEATH EFFECTING THEN IN IMPAIRED NERVE IMPULSE CONDUCTION HAVE THE KEY ROLE IN MS PATHOGENESIS. THE ROLE OF INFLAMMATORY FACTORS HAS ALSO BEEN PROVED. HOWEVER, IT HAS NOT BEEN EXPLICITLY SHOWN WHETHER SUCH AN INFLAMMATORY PROCESS IS THE TRIGGERING FACTOR OR SECONDARY TO A YET UNKNOWN INFECTIOUS FACTOR OR A DEGENERATIVE PROCESS OF THE CNS. THEREFORE, RECOGNITION OF THE EPIGENETIC RISK FACTORS, SUCH AS: GEOGRAPHICAL LATITUDE, VITAMIN D LEVEL, HYGIENE HYPOTHESIS, EPSTEIN-BARR VIRUS (EBV) INFECTION AND OTHERS MAY CONTRIBUTE TO BETTER UNDERSTANDING OF THE MECHANISM UNDERLYING MULTIPLE SCLEROSIS. ADDITIONALLY, THEY MAY PROVIDE GUIDELINES FOR MORE EFFICIENT THERAPIES AND BETTER PREVENTION OF THE DISEASE. AIM OF THIS REVIEW IS TO PRESENT MOST CURRENT DATA ON MULTIPLE SCLEROSIS RISK FACTORS, CONSIDERING THOSE LESS KNOWN. 2020 15 1935 28 ENVIRONMENTAL RISK FACTORS AND EPIGENETIC ALTERNATIONS IN PSORIASIS. INTRODUCTION AND OBJECTIVE: PSORIASIS ISA QUITE COMMON, CHRONIC AND IMMUNE-MEDIATED SKIN DISORDER. THE PREVALENCE OF PSORIASIS DIFFERS IN VARIOUS COUNTRIES, BUT IT IS SAID TO AFFECT 2% OF THE WORLD'S POPULATION IN GENERAL. PSORIASIS HAS MANY DIFFERENT CLINICAL FEATURES BUT ALL LESIONS HAVE THE SAME CHARACTERISTIC: ERYTHEMA, THICKENING AND SCALE, ALTHOUGH OTHER CLINICAL FEATURES ARE ALSO CONNECTED, SUCH AS PSORIATIC ARTHRITIS, OBESITY AND METABOLIC SYNDROME. ALL OF THESE MAY LEAD TO CONDITIONS IMPAIRING THE QUALITY OF LIFE. THIS REVIEW IS AN ATTEMPT TO SUMMARIZE RECENT DATA REGARDING ENVIRONMENTAL FACTORS, TOGETHER WITH EPIGENETIC MARKERS AND PROCESSES PLAYING AN IMPORTANT ROLE IN PSORIASIS. STATE OF KNOWLEDGE: MANY DIFFERENT ENVIRONMENTAL FACTORS PLAY A ROLE IN GENETICALLY PREDISPOSED PATIENTS. THIS IS CAUSES EPIGENETIC ALTERNATIONS WHICH MAY BE A LINKING PART IN THE WHOLE PROCESS. MANY STUDIES HAVE INDICATED A CONNECTION BETWEEN PSORIASIS AND VARIOUS GENES AND ANTIGENS. THE PRESENCE OF HLA-CW6 IS COMMON AS WELL A STRONG LINK BETWEEN ITS PRESENCE AND THE ONSET OF PSORIASIS BEING OBSERVED. THE MAIN ALTERNATIONS ARE DNA METHYLATION, HISTONE'S MODIFICATIONS AND THE ROLE OF MICRORNA. EXCESSIVE REACTION IS USUALLY NOT PRESENT WITHOUT A TRIGGERING FACTOR. ENVIRONMENTAL FACTORS ARE MOSTLY RATED, SUCH AS DRUGS, LIFE STYLE AND HABITS (SMOKING, ALCOHOL), DIET, PHYSICAL TRAUMA (SKIN INJURY PROVOKING KOEBNER PHENOMENON), STRESS, MICROORGANISM AND INFECTIONS. CONCLUSIONS: THE CORRELATION BETWEEN PATHOGENESIS OF PSORIASIS AND ENVIRONMENTAL RISK FACTORS, TOGETHER WITH EPIGENETIC ALTERNATIONS STILL REQUIRE MORE INVESTIGATION. EDUCATION ABOUT DIET HABITS, NUTRITION, WEIGHT LOSS AND HEALTHY LIFESTYLE SEEMS TO BE IMPORTANT DURING THE TREATMENT OF PSORIASIS. 2020 16 5003 39 PERIODONTITIS IS AN INFLAMMATORY DISEASE OF OXIDATIVE STRESS: WE SHOULD TREAT IT THAT WAY. PERIODONTITIS IS A HIGHLY PREVALENT DISEASE. AS IT PROGRESSES, IT CAUSES SERIOUS MORBIDITY IN THE FORM OF PERIODONTAL ABSCESSES AND TOOTH LOSS AND, IN THE LATTER STAGES, PAIN. IT IS ALSO NOW KNOWN THAT PERIODONTITIS IS STRONGLY ASSOCIATED WITH SEVERAL NONORAL DISEASES. THUS, PATIENTS WITH PERIODONTITIS ARE AT GREATER RISK FOR THE DEVELOPMENT AND/OR EXACERBATION OF DIABETES, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, AND CARDIOVASCULAR DISEASES, AMONG OTHER CONDITIONS. ALTHOUGH IT IS WITHOUT QUESTION THAT SPECIFIC GROUPS OF ORAL BACTERIA WHICH POPULATE DENTAL PLAQUE PLAY A CAUSATIVE ROLE IN THE DEVELOPMENT OF PERIODONTITIS, IT IS NOW THOUGHT THAT ONCE THIS DISEASE HAS BEEN TRIGGERED, OTHER FACTORS PLAY AN EQUAL, AND POSSIBLY MORE IMPORTANT, ROLE IN ITS PROGRESSION, PARTICULARLY IN SEVERE CASES OR IN CASES THAT PROVE DIFFICULT TO TREAT. IN THIS REGARD, WE ALLUDE TO THE HOST RESPONSE, SPECIFICALLY THE NOTION THAT THE HOST, ONCE INFECTED WITH ORAL PERIODONTAL PATHOGENIC BACTERIA, WILL MOUNT A DEFENSE RESPONSE MEDIATED LARGELY THROUGH THE INNATE IMMUNE SYSTEM. THE MOST ABUNDANT CELL TYPE OF THE INNATE IMMUNE SYSTEM - POLYMORPHONUCLEAR NEUTROPHILS - CAN, WHEN PROTECTING THE HOST FROM MICROBIAL INVASION, MOUNT A RESPONSE THAT INCLUDES UPREGULATION OF PROINFLAMMATORY CYTOKINES, MATRIX METALLOPROTEINASES, AND REACTIVE OXYGEN SPECIES, ALL OF WHICH THEN CONTRIBUTE TO THE TISSUE DAMAGE AND LOSS OF TEETH COMMONLY ASSOCIATED WITH PERIODONTITIS. OF THE MECHANISMS REFERRED TO HERE, WE SUGGEST THAT UPREGULATION OF REACTIVE OXYGEN SPECIES MIGHT PLAY ONE OF THE MOST IMPORTANT ROLES IN THE ESTABLISHMENT AND PROGRESSION OF PERIODONTITIS (AS WELL AS IN OTHER DISEASES OF INFLAMMATION) THROUGH THE DEVELOPMENT OF OXIDATIVE STRESS. IN THIS OVERVIEW, WE DISCUSS BOTH INNATE AND EPIGENETIC FACTORS (EG, DIABETES, SMOKING) THAT LEAD TO THE DEVELOPMENT OF OXIDATIVE STRESS. THIS OXIDATIVE STRESS THEN PROVIDES AN ENVIRONMENT CONDUCIVE TO THE DESTRUCTIVE PROCESSES OBSERVED IN PERIODONTITIS. THEREFORE, WE SHALL DESCRIBE SOME OF THE FUNDAMENTAL CHARACTERISTICS OF OXIDATIVE STRESS AND ITS EFFECTS ON THE PERIODONTIUM, DISCUSS THE DISEASES AND OTHER FACTORS THAT CAUSE OXIDATIVE STRESS, AND, FINALLY, REVIEW POTENTIALLY NOVEL THERAPEUTIC APPROACHES FOR THE MANAGEMENT (AND POSSIBLY EVEN THE REVERSAL) OF PERIODONTITIS, WHICH RELY ON THE USE OF THERAPIES, SUCH AS RESVERATROL AND OTHER ANTIOXIDANTS, THAT PROVIDE INCREASED ANTIOXIDANT ACTIVITY IN THE HOST. 2020 17 3541 33 IMMUNOEPIGENETIC REGULATION OF INFLAMMATORY BOWEL DISEASE: CURRENT INSIGHTS INTO NOVEL EPIGENETIC MODULATIONS OF THE SYSTEMIC IMMUNE RESPONSE. THE IMMUNE SYSTEM AND ENVIRONMENTAL FACTORS ARE INVOLVED IN VARIOUS DISEASES, SUCH AS INFLAMMATORY BOWEL DISEASE (IBD), THROUGH THEIR EFFECT ON GENETICS, WHICH MODULATES IMMUNE CELLS. IBD ENCOMPASSES TWO MAIN PHENOTYPES, CROHN'S DISEASE, AND ULCERATIVE COLITIS, WHICH ARE MANIFESTED AS CHRONIC AND SYSTEMIC RELAPSE-REMITTING GASTROINTESTINAL TRACT DISORDERS WITH RISING GLOBAL INCIDENCE AND PREVALENCE. THE PATHOPHYSIOLOGY OF IBD IS COMPLEX AND NOT FULLY UNDERSTOOD. EPIGENETIC RESEARCH HAS RESULTED IN VALUABLE INFORMATION FOR UNRAVELING THE ETIOLOGY OF THIS IMMUNE-MEDIATED DISEASE. THUS, THE MAIN OBJECTIVE OF THE PRESENT REVIEW IS TO SUMMARIZE THE CURRENT FINDINGS ON THE ROLE OF EPIGENETIC MECHANISMS IN IBD TO SHED LIGHT ON THEIR POTENTIAL CLINICAL RELEVANCE. THIS REVIEW FOCUSES ON THE LATEST EVIDENCE REGARDING PERIPHERAL BLOOD MONONUCLEAR CELLS AND EPIGENETIC CHANGES IN HISTONE MODIFICATION, DNA METHYLATION, AND TELOMERE SHORTENING IN IBD. THE VARIOUS IDENTIFIED EPIGENETIC DNA PROFILES WITH CLINICAL VALUE IN IBD COULD BE USED AS BIOMARKERS FOR MORE ACCURATELY PREDICTING DISEASE DEVELOPMENT, TREATMENT RESPONSE, AND THERAPY-RELATED ADVERSE EVENTS. ULTIMATELY, THE INFORMATION PRESENTED HERE COULD BE OF POTENTIAL RELEVANCE FOR FUTURE CLINICAL PRACTICE IN DEVELOPING MORE EFFICIENT AND PRECISE MEDICINE TO IMPROVE THE QUALITY OF LIFE FOR PATIENTS WITH IBD. 2023 18 6879 32 [RELATIONSHIP BETWEEN INTESTINAL HYPERPERMEABILITY AND OBESITY]. OBESITY IS A COMBINATION OF GENETIC, ENVIRONMENTAL FACTORS, AND SYSTEMIC INFLAMMATION OF ADIPOSE TISSUE. IN THE LAST DECADE, MORE AND MORE EVIDENCE SUGGESTS THAT INTESTINAL MICROBIOTA IS AN ENVIRONMENTAL FACTOR THAT PLAYS A CRUCIAL ROLE IN OBESITY AND ASSOCIATED METABOLIC DISORDERS. HERE, WE REVIEW THE ASSOCIATION BETWEEN INTESTINAL MICROBIOTA AND OBESITY BASED ON THE LITERATURE DATA AVAILABLE TO US. THE INTESTINAL FLORA, IN THE EQUILIBRIUM STATE OF CONVENTIONAL BACTERIA, PROTECTS THE HEALTH OF THE HOST AND HELPS THE DEVELOPMENT OF THE IMMUNE SYSTEM. THE GENOME, DIET, LIFESTYLE, AND EPIGENETIC CHANGES OF THE HOST CAN PATHOLOGICALLY ALTER THE COMPOSITION OF THE MICROBIOTA. IN DYSBIOSIS, THE DEVELOPMENT OF THE GUT-ASSOCIATED LYMPHOID TISSUE (GALT) ASSOCIATED WITH THE INTESTINAL TRACT IS IMPAIRED AND THE INTEGRITY OF THE INTESTINAL BARRIER IS IMPAIRED. DUE TO THE CONSEQUENT INTESTINAL HYPERPERMEABILITY, COMPONENTS OF PATHOGENIC PATHOGENS SUCH AS LIPOPOLYSACCHARIDES ENTER THE BLOODSTREAM. THESE COMPONENTS BIND TO RECEPTORS ON ADIPOSE TISSUE IMMUNE CELLS AS LIGANDS FOR MOLECULAR SAMPLES WITH PATHOGENIC PROPERTIES AND INDUCE ADIPOSE TISSUE DYSFUNCTION. THE SECRETION OF INFLAMMATORY CYTOKINES IN ADIPOSE TISSUE IS INCREASED. THIS INDUCES PERSISTENT LOW CHRONIC INFLAMMATION, WHICH IS RESPONSIBLE FOR THE DEVELOPMENT OF OBESITY. THE DAMAGE TO HEALTH CAUSED BY THE HYPERPERMEABILITY OF THE INTESTINAL BARRIER CAN BE REDUCED BY INTERVENTIONS, OR RESTORED EARLY IN THE PROCESS. KNOWING THE RELATIONSHIPS WILL HELP PREVENT AND TREAT OBESITY. 2022 19 6345 29 THE ROLE OF EPIGENETICS IN AUTOIMMUNE/INFLAMMATORY DISEASE. HISTORICALLY, SYSTEMIC SELF-INFLAMMATORY CONDITIONS WERE CLASSIFIED AS EITHER AUTOINFLAMMATORY AND CAUSED BY THE INNATE IMMUNE SYSTEM OR AUTOIMMUNE AND DRIVEN BY ADAPTIVE IMMUNE RESPONSES. HOWEVER, IT BECAME CLEAR THAT REALITY IS MUCH MORE COMPLEX AND THAT AUTOIMMUNE/INFLAMMATORY CONDITIONS RANGE ALONG AN "INFLAMMATORY SPECTRUM" WITH PRIMARILY AUTOINFLAMMATORY VS. AUTOIMMUNE CONDITIONS RESEMBLING EXTREMES AT EITHER END. EPIGENETIC MODIFICATIONS INFLUENCE GENE EXPRESSION AND ALTER CELLULAR FUNCTIONS WITHOUT MODIFYING THE GENOMIC SEQUENCE. METHYLATION OF CPG DNA DINUCLEOTIDES AND/OR THEIR HYDROXYMETHYLATION, POST-TRANSLATIONAL MODIFICATIONS TO AMINO TERMINI OF HISTONE PROTEINS, AND NON-CODING RNA EXPRESSION ARE MAIN EPIGENETIC EVENTS. THE PATHOPHYSIOLOGY OF AUTOIMMUNE/INFLAMMATORY DISEASES HAS BEEN CLOSELY LINKED WITH DISEASE CAUSING GENE MUTATIONS (RARE) OR A COMBINATION OF GENETIC SUSCEPTIBILITY AND EPIGENETIC MODIFICATIONS ARISING FROM EXPOSURE TO THE ENVIRONMENT (MORE COMMON). OVER RECENT YEARS, PROGRESS HAS BEEN MADE IN UNDERSTANDING MOLECULAR MECHANISMS INVOLVED IN SYSTEMIC INFLAMMATION AND THE CONTRIBUTION OF INNATE AND ADAPTIVE IMMUNE RESPONSES. EPIGENETIC EVENTS HAVE BEEN IDENTIFIED AS (I) CENTRAL PATHOPHYSIOLOGICAL FACTORS IN ADDITION TO GENETIC DISEASE PREDISPOSITION AND (II) AS CO-FACTORS DETERMINING CLINICAL PICTURES AND OUTCOMES IN INDIVIDUALS WITH MONOGENIC DISEASE. THUS, A COMPLETE UNDERSTANDING OF EPIGENETIC CONTRIBUTORS TO AUTOIMMUNE/INFLAMMATORY DISEASE WILL RESULT IN APPROACHES TO PREDICT INDIVIDUAL DISEASE OUTCOMES AND THE INTRODUCTION OF EFFECTIVE, TARGET-DIRECTED, AND TOLERABLE THERAPIES. HERE, WE SUMMARIZE RECENT FINDINGS THAT SIGNIFY THE IMPORTANCE OF EPIGENETIC MODIFICATIONS IN AUTOIMMUNE/INFLAMMATORY DISORDERS ALONG THE INFLAMMATORY SPECTRUM CHOOSING THREE EXAMPLES: THE AUTOINFLAMMATORY BONE CONDITION CHRONIC NONBACTERIAL OSTEOMYELITIS (CNO), THE "MIXED PATTERN" DISORDER PSORIASIS, AND THE AUTOIMMUNE DISEASE SYSTEMIC LUPUS ERYTHEMATOSUS (SLE). 2019 20 2591 31 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