1 4520 131 MULTI-OMICS NUTRITIONAL APPROACHES TARGETING METABOLIC-ASSOCIATED FATTY LIVER DISEASE. CURRENTLY, METABOLIC-ASSOCIATED FATTY LIVER DISEASE (MAFLD) IS A LEADING GLOBAL CAUSE OF CHRONIC LIVER DISEASE, AND IS EXPECTED TO BECOME ONE OF THE MOST COMMON INDICATIONS OF LIVER TRANSPLANTATION. MAFLD IS ASSOCIATED WITH OBESITY, INVOLVING MULTIPLE MECHANISMS SUCH AS ALTERATIONS IN LIPID METABOLISM, INSULIN RESISTANCE, HYPERINFLAMMATION, MITOCHONDRIAL DYSFUNCTION, CELL APOPTOSIS, OXIDATIVE STRESS, AND EXTRACELLULAR MATRIX FORMATION. HOWEVER, THE ONSET AND PROGRESSION OF MAFLD IS VARIABLE AMONG INDIVIDUALS, BEING INFLUENCED BY INTRINSIC (PERSONAL) AND EXTERNAL ENVIRONMENTAL FACTORS. IN THIS CONTEXT, SEQUENCE STRUCTURAL VARIANTS ACROSS THE HUMAN GENOME, EPIGENETIC PHENOMENA (I.E., DNA METHYLATION, HISTONE MODIFICATIONS, AND LONG NON-CODING RNAS) AFFECTING GENE EXPRESSION, GUT MICROBIOTA DYSBIOSIS, AND METABOLOMICS/LIPIDOMIC FINGERPRINTS MAY ACCOUNT FOR DIFFERENCES IN MAFLD OUTCOMES THROUGH INTERACTIONS WITH NUTRITIONAL FEATURES. THIS KNOWLEDGE MAY CONTRIBUTE TO GAINING A DEEPER UNDERSTANDING OF THE MOLECULAR AND PHYSIOLOGICAL PROCESSES UNDERLYING MAFLD PATHOGENESIS AND PHENOTYPE HETEROGENEITY, AS WELL AS FACILITATING THE IDENTIFICATION OF BIOMARKERS OF DISEASE PROGRESSION AND THERAPEUTIC TARGETS FOR THE IMPLEMENTATION OF TAILORED NUTRITIONAL STRATEGIES. THIS COMPREHENSIVE LITERATURE REVIEW HIGHLIGHTS THE POTENTIAL OF NUTRIGENETIC, NUTRIEPIGENETIC, NUTRIMETAGENOMIC, NUTRITRANSCRIPTOMICS, AND NUTRIMETABOLOMIC APPROACHES FOR THE PREVENTION AND MANAGEMENT OF MAFLD IN HUMANS THROUGH THE LENS OF PRECISION NUTRITION. 2022 2 5544 31 ROLE OF EPIGENETIC ABNORMALITIES AND INTERVENTION IN OBSTRUCTIVE SLEEP APNEA TARGET ORGANS. OBSTRUCTIVE SLEEP APNEA (OSA) IS A COMMON CONDITION THAT HAS CONSIDERABLE IMPACTS ON HUMAN HEALTH. EPIGENETICS HAS BECOME A RAPIDLY DEVELOPING AND EXCITING AREA IN BIOLOGY, AND IT IS DEFINED AS HERITABLE ALTERATIONS IN GENE EXPRESSION AND HAS REGULATORY EFFECTS ON DISEASE PROGRESSION. HOWEVER, THE PUBLISHED LITERATURE THAT IS INTEGRATING BOTH OF THEM IS NOT SUFFICIENT. THE PURPOSE OF THIS ARTICLE IS TO EXPLORE THE RELATIONSHIP BETWEEN OSA AND EPIGENETICS AND TO OFFER BETTER DIAGNOSTIC METHODS AND TREATMENT OPTIONS. EPIGENETIC MODIFICATIONS MAINLY MANIFEST AS POST-TRANSLATIONAL MODIFICATIONS IN DNA AND HISTONE PROTEINS AND REGULATION OF NON-CODING RNAS. CHRONIC INTERMITTENT HYPOXIA-MEDIATED EPIGENETIC ALTERATIONS ARE INVOLVED IN THE PROGRESSION OF OSA AND DIVERSE MULTIORGAN INJURIES, INCLUDING CARDIOVASCULAR DISEASE, METABOLIC DISORDERS, PULMONARY HYPERTENSION, NEURAL DYSFUNCTION, AND EVEN TUMORS. THIS ARTICLE PROVIDES DEEPER INSIGHTS INTO THE DISEASE MECHANISM OF OSA AND POTENTIAL APPLICATIONS OF TARGETED DIAGNOSIS, TREATMENT, AND PROGNOSIS IN OSA COMPLICATIONS. 2023 3 2932 29 GENES AND EPIGENETIC PROCESSES AS PROSPECTIVE PAIN TARGETS. CHRONIC PAIN AFFECTS APPROXIMATELY ONE IN FIVE ADULTS, RESULTING IN A GREATLY REDUCED QUALITY OF LIFE AND A HIGHER RISK OF DEVELOPING CO-MORBIDITIES SUCH AS DEPRESSION. AVAILABLE TREATMENTS OFTEN PROVIDE INADEQUATE PAIN RELIEF, BUT IT IS HOPED THAT THROUGH DEEPER UNDERSTANDING OF THE MOLECULAR MECHANISMS UNDERLYING CHRONIC PAIN STATES WE CAN DISCOVER NEW AND IMPROVED THERAPIES. ALTHOUGH GENETIC RESEARCH HAS FLOURISHED OVER THE PAST DECADE AND HAS IDENTIFIED MANY KEY GENES IN PAIN PROCESSING, THE BUDDING FIELD OF EPIGENETICS PROMISES TO PROVIDE NEW INSIGHTS AND A MORE DYNAMIC VIEW OF PAIN REGULATION. THIS REVIEW GIVES AN OVERVIEW OF BASIC MECHANISMS AND CURRENT THERAPIES TO TREAT PAIN, AND DISCUSSES THE CLINICAL AND PRECLINICAL EVIDENCE FOR THE CONTRIBUTION OF GENETIC AND EPIGENETIC FACTORS, WITH A FOCUS ON HOW THIS KNOWLEDGE CAN AFFECT DRUG DEVELOPMENT. 2013 4 6048 31 THE CONCEPTS OF ASTHMA ENDOTYPES AND PHENOTYPES TO GUIDE CURRENT AND NOVEL TREATMENT STRATEGIES. ASTHMA, A COMMON, NON-COMMUNICABLE CHRONIC DISEASE AFFECTS OVER 300 MILLION INDIVIDUALS WORLDWIDE. THE WESTERN WORLD LIFESTYLE IS CLAIMED TO BE RESPONSIBLE FOR THIS HIGH AND INCREASING PREVALENCE. ASTHMA HAS BEEN DEFINED AS A SYNDROME WITH VARIOUS PHENOTYPES AND ENDOTYPES, ALLERGIC ASTHMA AND TYPE 2 ASTHMA BEING THE MOST FREQUENT. A GREAT INCREASE IN PREVALENCE OF ALLERGIC DISEASES HAS NECESSITATED INTENSIVE INVESTIGATIONS BOTH FOR UNDERSTANDING THE UNDERLYING MECHANISMS AND FOR THE DEVELOPMENT OF NOVEL THERAPY OPTIONS WITH LONG-TERM EFFICACY AND LIMITED SIDE-EFFECTS. ALLERGIC PATIENTS DEMONSTRATE UNIQUE PRESENTATIONS WITH VARIABLE VISIBLE CHARACTERISTICS AND DISEASE OUTCOMES DEPENDING ON DIFFERENT MOLECULAR MECHANISMS, RELATED TO INFLUENCE OF GENES AND EPIGENETIC CONTROL BY MICRO- AND MACRO-ENVIRONMENT. AREAS COVERED: THIS ARTICLE REVIEWS THE DEFINITION OF ASTHMA PHENOTYPES AND POSSIBLE ENDOTYPES, ADVANCES IN ALLERGY-IMMUNOLOGY FIELD AND CONTEMPORARY PERSONALIZED THERAPY OPTIONS FOR ASTHMA. EXPERT COMMENTARY: BETTER UNDERSTANDING OF THE COMPLEX IMMUNE NETWORK OF ALLERGIC INFLAMMATION AND KEY PLAYERS OF IMMUNITY IS CONTINUOUSLY BEING PROVIDED FOR CLARIFICATION OF ASTHMA SUB-TYPES. SUCCESSFUL THERAPY OF ASTHMA REQUIRES BETTER DEFINITION OF UNDERLYING PATHOGENESIS, WHICH SEQUENTIALLY COULD END UP WITH 'CUSTOM-TAILORED' INDIVIDUALIZED, EVIDENCE-BASED AND MORE PRECISE THERAPY OPTIONS; A NEW ERA TERMED AS 'PRECISION MEDICINE'. ENDOTYPE, PHENOTYPE, THERATYPE AND BIOMARKER TERMS ARISE AS MAJOR KEYWORDS IN PRECISION/PERSONALIZED MEDICINE. 2018 5 3169 39 GUIDE FOR CURRENT NUTRIGENETIC, NUTRIGENOMIC, AND NUTRIEPIGENETIC APPROACHES FOR PRECISION NUTRITION INVOLVING THE PREVENTION AND MANAGEMENT OF CHRONIC DISEASES ASSOCIATED WITH OBESITY. CHRONIC DISEASES, INCLUDING OBESITY, ARE MAJOR CAUSES OF MORBIDITY AND MORTALITY IN MOST COUNTRIES. THE ADVERSE IMPACTS OF OBESITY AND ASSOCIATED COMORBIDITIES ON HEALTH REMAIN A MAJOR CONCERN DUE TO THE LACK OF EFFECTIVE INTERVENTIONS FOR PREVENTION AND MANAGEMENT. PRECISION NUTRITION IS AN EMERGING THERAPEUTIC APPROACH THAT TAKES INTO ACCOUNT AN INDIVIDUAL'S GENETIC AND EPIGENETIC INFORMATION, AS WELL AS AGE, GENDER, OR PARTICULAR PHYSIOPATHOLOGICAL STATUS. ADVANCES IN GENOMIC SCIENCES ARE CONTRIBUTING TO A BETTER UNDERSTANDING OF THE ROLE OF GENETIC VARIANTS AND EPIGENETIC SIGNATURES AS WELL AS GENE EXPRESSION PATTERNS IN THE DEVELOPMENT OF DIVERSE CHRONIC CONDITIONS, AND HOW THEY MAY MODIFY THERAPEUTIC RESPONSES. THIS KNOWLEDGE HAS LED TO THE SEARCH FOR GENETIC AND EPIGENETIC BIOMARKERS TO PREDICT THE RISK OF DEVELOPING CHRONIC DISEASES AND PERSONALIZING THEIR PREVENTION AND TREATMENT. ADDITIONALLY, ORIGINAL NUTRITIONAL INTERVENTIONS BASED ON NUTRIENTS AND BIOACTIVE DIETARY COMPOUNDS THAT CAN MODIFY EPIGENETIC MARKS AND GENE EXPRESSION HAVE BEEN IMPLEMENTED. ALTHOUGH CAUTION MUST BE EXERCISED, THESE SCIENTIFIC INSIGHTS ARE PAVING THE WAY FOR THE DESIGN OF INNOVATIVE STRATEGIES FOR THE CONTROL OF CHRONIC DISEASES ACCOMPANYING OBESITY. THIS DOCUMENT PROVIDES A NUMBER OF EXAMPLES OF THE HUGE POTENTIAL OF UNDERSTANDING NUTRIGENETIC, NUTRIGENOMIC, AND NUTRIEPIGENETIC ROLES IN PRECISION NUTRITION. 2017 6 5309 23 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 7 4720 33 NONCODING RNAS AS ADDITIONAL MEDIATORS OF EPIGENETIC REGULATION IN NONALCOHOLIC FATTY LIVER DISEASE. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) HAS EMERGED AS THE MOST COMMON CAUSE OF CHRONIC LIVER DISORDER WORLDWIDE. IT REPRESENTS A SPECTRUM THAT INCLUDES A CONTINUUM OF DIFFERENT CLINICAL ENTITIES RANGING FROM SIMPLE STEATOSIS TO NONALCOHOLIC STEATOHEPATITIS, WHICH CAN EVOLVE TO CIRRHOSIS AND IN SOME CASES TO HEPATOCELLULAR CARCINOMA, ULTIMATELY LEADING TO LIVER FAILURE. THE PATHOGENESIS OF NAFLD AND THE MECHANISMS UNDERLYING ITS PROGRESSION TO MORE PATHOLOGICAL STAGES ARE NOT COMPLETELY UNDERSTOOD. BESIDES GENETIC FACTORS, EVIDENCE INDICATES THAT EPIGENETIC MECHANISMS OCCURRING IN RESPONSE TO ENVIRONMENTAL STIMULI ALSO CONTRIBUTE TO THE DISEASE RISK. NONCODING RNAS (NCRNAS), INCLUDING MICRORNAS, LONG NONCODING RNAS, AND CIRCULAR RNAS, ARE ONE OF THE EPIGENETIC FACTORS THAT PLAY KEY REGULATORY ROLES IN THE DEVELOPMENT OF NAFLD. AS THE FIELD OF NCRNAS IS RAPIDLY EVOLVING, THE PRESENT REVIEW AIMS TO EXPLORE THE CURRENT STATE OF KNOWLEDGE ON THE ROLES OF THESE RNA SPECIES IN THE PATHOGENESIS OF NAFLD, HIGHLIGHT RELEVANT MECHANISMS BY WHICH SOME NCRNAS CAN MODULATE REGULATORY NETWORKS IMPLICATED IN NAFLD, AND DISCUSS KEY CHALLENGES AND FUTURE DIRECTIONS FACING CURRENT RESEARCH IN THE HOPES OF DEVELOPING NCRNAS AS NEXT-GENERATION NON-INVASIVE DIAGNOSTICS AND THERAPIES IN NAFLD AND SUBSEQUENT PROGRESSION TO HEPATOCELLULAR CARCINOMA. 2022 8 4464 34 MOLECULAR MECHANISMS OF NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)/NONALCOHOLIC STEATOHEPATITIS (NASH). NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS ONE OF THE MOST COMMON CHRONIC LIVER DISEASES WORLDWIDE AND HAS GARNERED INCREASING ATTENTION IN RECENT DECADES. NAFLD IS CHARACTERIZED BY A WIDE RANGE OF LIVER CHANGES, FROM SIMPLE STEATOSIS TO NONALCOHOLIC STEATOHEPATITIS (NASH), CIRRHOSIS, AND HEPATOCELLULAR CARCINOMA. THE PATHOGENESIS OF NAFLD/NASH IS VERY COMPLICATED AND INVOLVES LIPID ACCUMULATION, INSULIN RESISTANCE, INFLAMMATION, AND FIBROGENESIS. IN ADDITION, NAFLD IS CLOSELY ASSOCIATED WITH COMPLICATIONS SUCH AS OBESITY, DYSLIPIDEMIA, AND TYPE 2 DIABETES. IN PARTICULAR, THE CLINICAL SPECTRUM, PATHOPHYSIOLOGY, AND THERAPEUTIC OPTIONS OF NAFLD SHARE MANY THINGS IN COMMON WITH DIABETES. INSULIN RESISTANCE IS AN UNDERLYING BASIS FOR THE PATHOGENESIS OF DIABETES AND NAFLD. THIS CHAPTER FOCUSES ON THE MOLECULAR MECHANISM INVOLVED IN THE PATHOGENESIS OF INSULIN RESISTANCE, DIABETES, AND NASH/NAFLD INCLUDING THOSE THAT DRIVE DISEASE PROGRESSION SUCH AS OXIDATIVE STRESS, GENETIC AND EPIGENETIC MECHANISMS, ADIPONECTIN, CYTOKINES, AND IMMUNE CELLS. 2021 9 6204 42 THE INFLUENCE OF EPIGENETICS AND INFLAMMATION ON CARDIOMETABOLIC RISKS. CARDIOMETABOLIC DISEASES INCLUDE METABOLIC SYNDROME, OBESITY, TYPE 2 DIABETES MELLITUS, AND HYPERTENSION. EPIGENETIC MODIFICATIONS PARTICIPATE IN CARDIOMETABOLIC DISEASES THROUGH SEVERAL PATHWAYS, INCLUDING INFLAMMATION, VASCULAR DYSFUNCTION, AND INSULIN RESISTANCE. EPIGENETIC MODIFICATIONS, WHICH ENCOMPASS ALTERATIONS TO GENE EXPRESSION WITHOUT MUTATING THE DNA SEQUENCE, HAVE GAINED MUCH ATTENTION IN RECENT YEARS, SINCE THEY HAVE BEEN CORRELATED WITH CARDIOMETABOLIC DISEASES AND MAY BE TARGETED FOR THERAPEUTIC INTERVENTIONS. EPIGENETIC MODIFICATIONS ARE GREATLY INFLUENCED BY ENVIRONMENTAL FACTORS, SUCH AS DIET, PHYSICAL ACTIVITY, CIGARETTE SMOKING, AND POLLUTION. SOME MODIFICATIONS ARE HERITABLE, INDICATING THAT THE BIOLOGICAL EXPRESSION OF EPIGENETIC ALTERATIONS MAY BE OBSERVED ACROSS GENERATIONS. MOREOVER, MANY PATIENTS WITH CARDIOMETABOLIC DISEASES PRESENT WITH CHRONIC INFLAMMATION, WHICH CAN BE INFLUENCED BY ENVIRONMENTAL AND GENETIC FACTORS. THE INFLAMMATORY ENVIRONMENT WORSENS THE PROGNOSIS OF CARDIOMETABOLIC DISEASES AND FURTHER INDUCES EPIGENETIC MODIFICATIONS, PREDISPOSING PATIENTS TO THE DEVELOPMENT OF OTHER METABOLISM-ASSOCIATED DISEASES AND COMPLICATIONS. A DEEPER UNDERSTANDING OF INFLAMMATORY PROCESSES AND EPIGENETIC MODIFICATIONS IN CARDIOMETABOLIC DISEASES IS NECESSARY TO IMPROVE OUR DIAGNOSTIC CAPABILITIES, PERSONALIZED MEDICINE APPROACHES, AND THE DEVELOPMENT OF TARGETED THERAPEUTIC INTERVENTIONS. FURTHER UNDERSTANDING MAY ALSO ASSIST IN PREDICTING DISEASE OUTCOMES, ESPECIALLY IN CHILDREN AND YOUNG ADULTS. THIS REVIEW DESCRIBES EPIGENETIC MODIFICATIONS AND INFLAMMATORY PROCESSES UNDERLYING CARDIOMETABOLIC DISEASES, AND FURTHER DISCUSSES ADVANCES IN THE RESEARCH FIELD WITH A FOCUS ON SPECIFIC POINTS FOR INTERVENTIONAL THERAPY. 2023 10 2731 33 EXPLORING THE COMPLEX RELATIONSHIP BETWEEN MICROBIOTA AND SYSTEMIC LUPUS ERYTHEMATOSUS. PURPOSE OF REVIEW: SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC AUTOIMMUNE DISEASE CHARACTERIZED BY VARIOUS AUTOANTIBODIES AND MULTI-ORGAN. MICROBIOTA DYSBIOSIS IN THE GUT, SKIN, ORAL, AND OTHER SURFACES HAS A SIGNIFICANT IMPACT ON SLE DEVELOPMENT. THIS ARTICLE SUMMARIZES RELEVANT RESEARCH AND PROVIDES NEW MICROBIOME-RELATED STRATEGIES FOR EXPLORING THE MECHANISMS AND TREATING PATIENTS WITH SLE. RECENT FINDINGS: SLE PATIENTS HAVE DISRUPTIONS IN MULTIPLE MICROBIOMES, WITH THE GUT MICROBIOTA (BACTERIA, VIRUSES, AND FUNGI) AND THEIR METABOLITES BEING THE MOST THOROUGHLY RESEARCHED. THIS DYSBIOSIS CAN PROMOTE SLE PROGRESSION THROUGH MECHANISMS SUCH AS THE LEAKY GUT, MOLECULAR MIMICRY, AND EPIGENETIC REGULATION. NOTWITHSTANDING STUDY CONSTRAINTS ON THE RELATIONSHIP BETWEEN MICROBIOTA AND SLE, SPECIFIC INTERVENTIONS TARGETING THE GUT MICROBIOTA, SUCH AS PROBIOTICS, DIETARY MANAGEMENT, AND FECAL MICROBIOTA TRANSPLANTATION, HAVE EMERGED AS PROMISING SLE THERAPEUTICS. 2023 11 6882 23 [RESEARCH PROGRESS ON NON-CODING RNAS IN THE MOLECULAR PATHOGENESIS OF HEPATOCELLULAR CARCINOMA]. PRIMARY LIVER CANCER ARISES FROM CHRONIC LIVER DISEASE, AND CIRRHOTIC LIVER GRADUALLY DEVELOPS INTO DYSPLASTIC NODULES THAT EVENTUALLY FORM MALIGNANT TUMORS. IN RECENT YEARS, MOLECULAR BIOTECHNOLOGY DEVELOPMENT HAS DEEPENED PEOPLE'S UNDERSTANDING ON THE PATHOGENESIS OF LIVER CANCER. EPIGENETIC MODIFICATIONS PLAY A SIGNIFICANT ROLE IN DNA METHYLATION, NON-CODING RNAS, CHROMATIN REMODELING, AND HISTONE MODIFICATION. THIS REVIEW FOCUSES ON THE PROGRESS OF CURRENTLY IMPLICATED NON-CODING RNAS IN THE MOLECULAR PATHOGENESIS OF HEPATOCELLULAR CARCINOMA, AND ITS POTENTIAL APPLICATION IN IMPROVING THE DIAGNOSIS AND TREATMENT. 2018 12 4722 45 NONCODING RNAS IN NONALCOHOLIC FATTY LIVER DISEASE: POTENTIAL DIAGNOSIS AND PROGNOSIS BIOMARKERS. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS CURRENTLY THE MOST COMMON CHRONIC LIVER DISEASE WORLDWIDE IN PART DUE TO THE CONCOMITANT OBESITY PANDEMIC AND INSULIN RESISTANCE (IR). IT IS INCREASINGLY BECOMING EVIDENT THAT NAFLD IS A DISEASE AFFECTING NUMEROUS EXTRAHEPATIC VITAL ORGANS AND REGULATORY PATHWAYS. THE MOLECULAR MECHANISMS UNDERLYING THE NONALCOHOLIC STEATOSIS FORMATION ARE POORLY UNDERSTOOD, AND LITTLE INFORMATION IS AVAILABLE ON THE PATHWAYS THAT ARE RESPONSIBLE FOR THE PROGRESSIVE HEPATOCELLULAR DAMAGE THAT FOLLOWS LIPID ACCUMULATION. RECENTLY, MUCH RESEARCH HAS FOCUSED ON THE IDENTIFICATION OF THE EPIGENETIC MODIFICATIONS THAT CONTRIBUTE TO NAFLD PATHOGENESIS. NONCODING RNAS (NCRNAS) ARE ONE OF SUCH EPIGENETIC FACTORS THAT COULD BE IMPLICATED IN THE NAFLD DEVELOPMENT AND PROGRESSION. IN THIS REVIEW, WE SUMMARIZE THE CURRENT KNOWLEDGE OF THE GENETIC AND EPIGENETIC FACTORS POTENTIALLY UNDERLYING THE DISEASE. PARTICULAR EMPHASIS WILL BE PUT ON THE CONTRIBUTION OF MICRORNAS (MIRNAS), LONG NONCODING RNAS (LNCRNAS), AND CIRCULAR RNAS (CIRCRNAS) TO THE PATHOPHYSIOLOGY OF NAFLD AS WELL AS THEIR POTENTIAL USE AS THERAPEUTIC TARGETS OR AS MARKERS FOR THE PREDICTION AND THE PROGRESSION OF THE DISEASE. 2020 13 5372 33 RECENT ADVANCES IN UNDERSTANDING THE PATHOGENESIS OF RHEUMATOID ARTHRITIS: NEW TREATMENT STRATEGIES. RHEUMATOID ARTHRITIS (RA) IS CONSIDERED A CHRONIC SYSTEMIC, MULTI-FACTORIAL, INFLAMMATORY, AND PROGRESSIVE AUTOIMMUNE DISEASE AFFECTING MANY PEOPLE WORLDWIDE. WHILE PATIENTS SHOW VERY INDIVIDUAL COURSES OF DISEASE, WITH RA FOCUSING ON THE MUSCULOSKELETAL SYSTEM, JOINTS ARE OFTEN SEVERELY AFFECTED, LEADING TO LOCAL INFLAMMATION, CARTILAGE DESTRUCTION, AND BONE EROSION. TO PREVENT JOINT DAMAGE AND PHYSICAL DISABILITY AS ONE OF MANY SYMPTOMS OF RA, EARLY DIAGNOSIS IS CRITICAL. AUTO-ANTIBODIES PLAY A PIVOTAL CLINICAL ROLE IN PATIENTS WITH SYSTEMIC RA. AS BIOMARKERS, THEY COULD HELP TO MAKE A MORE EFFICIENT DIAGNOSIS, PROGNOSIS, AND TREATMENT DECISION. BESIDES AUTO-ANTIBODIES, SEVERAL OTHER FACTORS ARE INVOLVED IN THE PROGRESSION OF RA, SUCH AS EPIGENETIC ALTERATIONS, POST-TRANSLATIONAL MODIFICATIONS, GLYCOSYLATION, AUTOPHAGY, AND T-CELLS. UNDERSTANDING THE INTERPLAY BETWEEN THESE FACTORS WOULD CONTRIBUTE TO A DEEPER INSIGHT INTO THE CAUSES, MECHANISMS, PROGRESSION, AND TREATMENT OF THE DISEASE. IN THIS REVIEW, THE LATEST RA RESEARCH FINDINGS ARE DISCUSSED TO BETTER UNDERSTAND THE PATHOGENESIS, AND FINALLY, TREATMENT STRATEGIES FOR RA THERAPY ARE PRESENTED, INCLUDING BOTH CONVENTIONAL APPROACHES AND NEW METHODS THAT HAVE BEEN DEVELOPED IN RECENT YEARS OR ARE CURRENTLY UNDER INVESTIGATION. 2021 14 1867 25 EMERGING GENE-EDITING MODALITIES FOR OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS A PATHOLOGICAL DEGENERATIVE CONDITION OF THE JOINTS THAT IS WIDELY PREVALENT WORLDWIDE, RESULTING IN SIGNIFICANT PAIN, DISABILITY, AND IMPAIRED QUALITY OF LIFE. THE DIVERSE ETIOLOGY AND PATHOGENESIS OF OA CAN EXPLAIN THE PAUCITY OF VIABLE PREVENTIVE AND DISEASE-MODIFYING STRATEGIES TO COUNTER IT. ADVANCES IN GENOME-EDITING TECHNIQUES MAY IMPROVE DISEASE-MODIFYING SOLUTIONS BY ADDRESSING INHERITED PREDISPOSING RISK FACTORS AND THE ACTIVITY OF INFLAMMATORY MODULATORS. RECENT PROGRESS ON TECHNOLOGIES SUCH AS CRISPR/CAS9 AND CELL-BASED GENOME-EDITING THERAPIES TARGETING THE GENETIC AND EPIGENETIC ALTERNATIONS IN OA OFFER PROMISING AVENUES FOR EARLY DIAGNOSIS AND THE DEVELOPMENT OF PERSONALIZED THERAPIES. THE PURPOSE OF THIS LITERATURE REVIEW WAS TO CONCISELY SUMMARIZE THE GENOME-EDITING OPTIONS AGAINST CHRONIC DEGENERATIVE JOINT CONDITIONS SUCH AS OA WITH A FOCUS ON THE MORE RECENTLY EMERGING MODALITIES, ESPECIALLY CRISPR/CAS9. FUTURE ADVANCEMENTS IN NOVEL GENOME-EDITING THERAPIES MAY IMPROVE THE EFFICACY OF SUCH TARGETED TREATMENTS. 2020 15 3011 23 GENETICS AND EPIGENETICS IN THE FIBROGENIC EVOLUTION OF CHRONIC LIVER DISEASES. RECENT YEARS HAVE SEEN UNPRECEDENTED PROGRESS IN THE IDENTIFICATION AND CHARACTERIZATION OF GENETIC INFORMATION RELATED TO CHRONIC LIVER DISEASES (CLDS). HOWEVER, DESPITE THE CONCEPTUAL BENEFIT IN EARLY RECOGNITION OF AT-RISK POPULATIONS AMENABLE TO PRE-EMPTIVE TREATMENT AND/OR SURVEILLANCE STRATEGIES, RECENT GENOMIC RESEARCH IN THE FIELD HAS PLACED FOCUS ON UNRAVELLING THE GENETIC ARCHITECTURE OF DISEASE SUSCEPTIBILITY, WHILE DATA ON GENETIC MARKERS ANTICIPATING AN ACCELERATED FIBROGENESIS IN AN INDIVIDUAL ARE STILL LIMITED. LIKEWISE, SEQUENCE VARIATION ASSIGNING RAPID FIBROGENIC EVOLUTION COMMON TO CLDS IRRESPECTIVE OF ETIOLOGY ARE POORLY DEFINED ASIDE FROM PNPLA3 (ADIPONUTRIN) AS A PROMINENT EXCEPTION. THE EMERGING FIELD OF EPIGENETICS IN HEPATOLOGY HAS MOSTLY BEEN STUDIED UNDER THE PERSPECTIVE OF GENE REGULATION, LESS SO AS A HERITABLE ALTERATION IN GENE ACTIVITY. IN THIS ARTICLE WE WILL CRITICALLY DISCUSS RECENT FINDINGS IN GENOMIC HEPATOLOGY WITH SPECIAL FOCUS ON THE (EPI)GENETIC CONTRIBUTION TO THE FIBROGENIC EVOLUTION OF CLDS. 2011 16 2543 40 EPIGENETICS IN LIVER DISEASE. EPIGENETICS IS A TERM THAT ENCOMPASSES A VARIETY OF REGULATORY PROCESSES THAT ARE ABLE TO CROSSTALK IN ORDER TO INFLUENCE GENE EXPRESSION AND CELL PHENOTYPE IN RESPONSE TO ENVIRONMENTAL CUES. A DEEP UNDERSTANDING OF EPIGENETICS OFFERS THE POTENTIAL FOR FRESH INSIGHTS INTO THE BASIS FOR COMPLEX CHRONIC DISEASES AND IMPROVED DIAGNOSTIC AND PROGNOSTIC TOOLS. MOREOVER, AS EPIGENETIC MODIFICATIONS ARE HIGHLY PLASTIC AND RESPONSIVE TO THE ENVIRONMENT, THERE IS MUCH EXCITEMENT AROUND THE THEME OF EPIGENETIC THERAPEUTICS, INCLUDING NOT ONLY NEW DRUGS BUT ALSO MORE INFORMED PATIENT ADVICE ON LIFESTYLE CHOICES AND THEIR IMPACT ON PATHOLOGY. THIS REVIEW BRIEFLY EXPLAINS THE MOLECULAR NATURE OF THE INDIVIDUAL REGULATORY PROCESS THAT CONSTITUTE EPIGENETICS, INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS, CHROMATIN REMODELING, TRANSCRIPTIONAL CONTROL, AND NONCODING RNAS. THE WAYS IN WHICH THESE EPIGENETIC MECHANISMS INFLUENCE LIVER PHYSIOLOGY AND DISEASE WILL BE CONSIDERED IN DETAIL, PARTICULARLY IN THE CONTEXT OF CANCER, FIBROSIS, AND NONALCOHOLIC STEATOHEPATITIS. THE CURRENT LIMITATIONS ASSOCIATED WITH EPIGENETIC PROFILING AND THERAPEUTICS IN LIVER DISEASE ARE DISCUSSED, AS IS THE INTRIGUING POSSIBILITY THAT ENVIRONMENTAL-INDUCED EPIGENETIC CHANGES MAY BECOME STABLE AND HERITABLE. CONCLUSION: THE AIM OF THE REVIEW IS TO INFORM HEPATOLOGISTS OF THE EMERGING KEY EPIGENETIC IDEAS OF RELEVANCE TO LIVER DISEASES THAT ARE HIGHLY LIKELY TO FORM A COMPONENT OF PATIENT MANAGEMENT AND CARE IN THE NEXT DECADE. 2014 17 1387 35 DIABETIC GUT MICROBIOTA DYSBIOSIS AS AN INFLAMMAGING AND IMMUNOSENESCENCE CONDITION THAT FOSTERS PROGRESSION OF RETINOPATHY AND NEPHROPATHY. THE INCREASED PREVALENCE OF TYPE 2 DIABETES MELLITUS (T2DM) AND LIFE EXPECTANCY OF DIABETIC PATIENTS FOSTERS THE WORLDWIDE PREVALENCE OF RETINOPATHY AND NEPHROPATHY, TWO MAJOR MICROVASCULAR COMPLICATIONS THAT HAVE BEEN DIFFICULT TO TREAT WITH CONTEMPORARY GLUCOSE-LOWERING MEDICATIONS. THE GUT MICROBIOTA (GM) HAS BECOME A LIVELY FIELD RESEARCH IN THE LAST YEARS; THERE IS A GROWING RECOGNITION THAT ALTERED INTESTINAL MICROBIOTA COMPOSITION AND FUNCTION CAN DIRECTLY IMPACT THE PHENOMENON OF AGEING AND AGE-RELATED DISORDERS. IN FACT, HUMAN GM, ENVISAGED AS A POTENTIAL SOURCE OF NOVEL THERAPEUTICS, STRONGLY MODULATES HOST IMMUNITY AND METABOLISM. IT IS NOW CLEAR THAT GUT DYSBIOSIS AND THEIR PRODUCTS (E.G. P-CRESYL SULFATE, TRIMETHYLAMINE?N?OXIDE) DICTATE A SECRETORY ASSOCIATED SENESCENCE PHENOTYPE AND CHRONIC LOW-GRADE INFLAMMATION, FEATURES SHARED IN THE PHYSIOLOGICAL PROCESS OF AGEING ("INFLAMMAGING") AS WELL AS IN T2DM ("METAFLAMMATION") AND IN ITS MICROVASCULAR COMPLICATIONS. THIS REVIEW PROVIDES AN IN-DEPTH LOOK ON THE CROSSTALK BETWEEN GM, HOST IMMUNITY AND METABOLISM. FURTHER, IT CHARACTERIZES HUMAN GM SIGNATURES OF ELDERLY AND T2DM PATIENTS. FINALLY, A COMPREHENSIVE SCRUTINY OF RECENT MOLECULAR FINDINGS (E.G. EPIGENETIC CHANGES) UNDERLYING CAUSAL RELATIONSHIPS BETWEEN GM DYSBIOSIS AND DIABETIC RETINOPATHY/NEPHROPATHY COMPLICATIONS IS PINPOINTED, WITH THE ULTIMATE GOAL TO UNRAVEL POTENTIAL PATHOPHYSIOLOGICAL MECHANISMS THAT MAY BE EXPLORED, IN A NEAR FUTURE, AS PERSONALIZED DISEASE-MODIFYING THERAPEUTIC APPROACHES. 2019 18 2009 27 EPIGENETIC BASIS OF DIABETIC VASCULOPATHY. TYPE 2 DIABETES MELLITUS (T2DM) CAUSES PERIPHERAL VASCULAR DISEASE BECAUSE OF WHICH SEVERAL BLOOD-BORNE FACTORS, INCLUDING VITAL NUTRIENTS FAIL TO REACH THE AFFECTED TISSUE. TISSUE EPIGENOME IS SENSITIVE TO CHRONIC HYPERGLYCEMIA AND IS KNOWN TO CAUSE PATHOGENESIS OF MICRO- AND MACROVASCULAR COMPLICATIONS. THESE VASCULAR COMPLICATIONS OF T2DM MAY PERPETUATE THE ONSET OF ORGAN DYSFUNCTION. THE BURDEN OF DIABETES IS PRIMARILY BECAUSE OF A WIDE RANGE OF COMPLICATIONS OF WHICH NONHEALING DIABETIC ULCERS REPRESENT A MAJOR COMPONENT. THUS, IT IS IMPERATIVE THAT CURRENT RESEARCH HELP RECOGNIZE MORE EFFECTIVE METHODS FOR THE DIAGNOSIS AND MANAGEMENT OF EARLY VASCULAR INJURIES. THIS REVIEW ADDRESSES THE SIGNIFICANCE OF EPIGENETIC PROCESSES SUCH AS DNA METHYLATION AND HISTONE MODIFICATIONS IN THE EVOLUTION OF MACROVASCULAR AND MICROVASCULAR COMPLICATIONS OF T2DM. 2022 19 4844 26 ONE YEAR IN REVIEW 2019: PATHOGENESIS OF RHEUMATOID ARTHRITIS. RHEUMATOID ARTHRITIS (RA) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE INFLUENCED BY BOTH GENETIC AND ENVIRONMENTAL FACTORS. OVER THE LAST FEW YEARS, PARTICULAR ATTENTION HAS BEEN GIVEN TO NOVEL GENES AND TO THE CLOSE INTERACTION BETWEEN GENETIC FACTORS AND EPIGENETIC MECHANISMS. RESEARCH HAS ALSO FOCUSED ON THE INFLUENCE OF ENVIRONMENTAL FACTORS ON DISEASE DEVELOPMENT, AND ON NEW MECHANISMS OF THE INNATE AND ADAPTIVE IMMUNE SYSTEM THAT CAN INFLUENCE THE DIFFERENT STAGES OF RA. HOWEVER, THERE ARE STILL SEVERAL ASPECTS OF THE DISEASE THAT NEED FURTHER INVESTIGATION. SHEDDING SOME LIGHT ON THE DIFFERENT ASPECTS OF RA PATHOGENESIS WILL HELP TO IMPROVE THE CURRENT DIAGNOSTIC TOOLS AND TO IDENTIFY NEW TARGETS FOR THE DEVELOPMENT OF DISEASE-MODIFYING THERAPIES. THUS, IN THIS REVIEW WE SUMMARISE THE NEW INSIGHTS IN RA PATHOGENESIS, RESULTING FROM LITERATURE RESEARCH DATA PUBLISHED IN THE LAST YEAR. 2019 20 4958 29 PATHOGENESIS OF HUMAN SYSTEMIC LUPUS ERYTHEMATOSUS: A CELLULAR PERSPECTIVE. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC AUTOIMMUNE DISEASE AFFECTING MULTIPLE ORGANS. A COMPLEX INTERACTION OF GENETICS, ENVIRONMENT, AND HORMONES LEADS TO IMMUNE DYSREGULATION AND BREAKDOWN OF TOLERANCE TO SELF-ANTIGENS, RESULTING IN AUTOANTIBODY PRODUCTION, INFLAMMATION, AND DESTRUCTION OF END-ORGANS. EMERGING EVIDENCE ON THE ROLE OF THESE FACTORS HAS INCREASED OUR KNOWLEDGE OF THIS COMPLEX DISEASE, GUIDING THERAPEUTIC STRATEGIES AND IDENTIFYING PUTATIVE BIOMARKERS. RECENT FINDINGS INCLUDE THE CHARACTERIZATION OF GENETIC/EPIGENETIC FACTORS LINKED TO SLE, AS WELL AS CELLULAR EFFECTORS. NOVEL OBSERVATIONS HAVE PROVIDED AN IMPROVED UNDERSTANDING OF THE CONTRIBUTION OF TISSUE-SPECIFIC FACTORS AND ASSOCIATED DAMAGE, T AND B LYMPHOCYTES, AS WELL AS INNATE IMMUNE CELL SUBSETS AND THEIR CORRESPONDING ABNORMALITIES. THE INTRICATE WEB OF INVOLVED FACTORS AND PATHWAYS DICTATES THE ADOPTION OF TAILORED THERAPEUTIC APPROACHES TO CONQUER THIS DISEASE. 2017