1 5309 83 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 2 4519 31 MULTI-OMICS IN CROHN'S DISEASE: NEW INSIGHTS FROM INSIDE. CROHN'S DISEASE (CD) IS AN INFLAMMATORY BOWEL DISEASE (IBD) WITH COMPLEX CLINICAL MANIFESTATIONS SUCH AS CHRONIC DIARRHEA, WEIGHT LOSS AND HEMATOCHEZIA. DESPITE THE INCREASING INCIDENCE WORLDWIDE, CURE OF CD REMAINS EXTREMELY DIFFICULT. THE RAPID DEVELOPMENT OF HIGH-THROUGHPUT SEQUENCING TECHNOLOGY WITH INTEGRATED-OMICS ANALYSES IN RECENT YEARS HAS PROVIDED A NEW MEANS FOR EXPLORING THE PATHOGENESIS, MINING THE BIOMARKERS AND DESIGNING TARGETED PERSONALIZED THERAPEUTICS OF CD. HOST GENOMICS AND EPIGENOMICS UNVEIL HEREDITY-RELATED MECHANISMS OF SUSCEPTIBLE INDIVIDUALS, WHILE MICROBIOME AND METABOLOMICS MAP HOST-MICROBE INTERACTIONS IN CD PATIENTS. PROTEOMICS SHOWS GREAT POTENTIAL IN SEARCHING FOR PROMISING BIOMARKERS. NONETHELESS, SINGLE OMICS TECHNOLOGY CANNOT HOLISTICALLY CONNECT THE MECHANISMS WITH HETEROGENEITY OF PATHOLOGICAL BEHAVIOR IN CD. THE RISE OF MULTI-OMICS ANALYSIS INTEGRATES GENETIC/EPIGENETIC PROFILES WITH PROTEIN/MICROBIAL METABOLITE FUNCTIONALITY, PROVIDING NEW HOPE FOR COMPREHENSIVE AND IN-DEPTH EXPLORATION OF CD. HEREIN, WE EMPHASIZED THE DIFFERENT OMICS FEATURES AND APPLICATIONS OF CD AND DISCUSSED THE CURRENT RESEARCH AND LIMITATIONS OF MULTI-OMICS IN CD. THIS REVIEW WILL UPDATE AND DEEPEN OUR UNDERSTANDING OF CD FROM INTEGRATION OF BROAD OMICS SPECTRA AND WILL PROVIDE NEW EVIDENCE FOR TARGETED INDIVIDUALIZED THERAPEUTICS. 2023 3 4832 27 OMICS BIOMARKERS IN OBESITY: NOVEL ETIOLOGICAL INSIGHTS AND TARGETS FOR PRECISION PREVENTION. PURPOSE OF REVIEW: OMICS-BASED TECHNOLOGIES WERE SUGGESTED TO PROVIDE AN ADVANCED UNDERSTANDING OF OBESITY ETIOLOGY AND ITS METABOLIC CONSEQUENCES. THIS REVIEW HIGHLIGHTS THE RECENT DEVELOPMENTS IN "OMICS"-BASED RESEARCH AIMED TO IDENTIFY OBESITY-RELATED BIOMARKERS. RECENT FINDINGS: RECENT ADVANCES IN OBESITY AND METABOLISM RESEARCH INCREASINGLY RELY ON NEW TECHNOLOGIES TO IDENTIFY MECHANISMS IN THE DEVELOPMENT OF OBESITY USING VARIOUS "OMICS" PLATFORMS. GENETIC AND EPIGENETIC BIOMARKERS THAT TRANSLATE INTO CHANGES IN TRANSCRIPTOME, PROTEOME, AND METABOLOME COULD SERVE AS TARGETS FOR OBESITY PREVENTION. DESPITE A NUMBER OF PROMISING CANDIDATE BIOMARKERS, THERE IS AN INCREASED DEMAND FOR LARGER PROSPECTIVE COHORT STUDIES TO VALIDATE FINDINGS AND DETERMINE BIOMARKER REPRODUCIBILITY BEFORE THEY CAN FIND APPLICATIONS IN PRIMARY CARE AND PUBLIC HEALTH. "OMICS" BIOMARKERS HAVE ADVANCED OUR KNOWLEDGE ON THE ETIOLOGY OF OBESITY AND ITS LINKS WITH CHRONIC DISEASES. THEY BRING SUBSTANTIAL PROMISE IN IDENTIFYING EFFECTIVE PUBLIC HEALTH STRATEGIES THAT PAVE THE WAY TOWARDS PATIENT STRATIFICATION AND PRECISION PREVENTION. 2020 4 4716 30 NON-GENETIC RATS MODELS FOR ATHEROSCLEROSIS RESEARCH: FROM PAST TO PRESENT. ATHEROSCLEROSIS IS AN INFLAMMATORY, PROGRESSIVE, AND CHRONIC ILLNESS THAT INVOLVES SEVERAL MOLECULAR AND EPIGENETIC FACTORS. DESPITE TREATMENT LIMITATIONS, CLINICAL AND THERAPEUTIC APPROACHES HAVE UNDENIABLY CHANGED RADICALLY IN RECENT DECADES THROUGH BETTER KNOWLEDGE OF THE PATHOPHYSIOLOGICAL BASIS OF THE DISEASE, WHICH HAS CONSIDERABLY IMPROVED PATIENTS' SURVIVAL AND QUALITY OF LIFE. SOME OF THESE ADVANCES ARE ATTRIBUTABLE TO BASIC BIOMEDICAL RESEARCH THAT PROVIDES INSIGHTS INTO A BETTER UNDERSTANDING AND IDENTIFICATION OF NEW MOLECULAR AND CELLULAR TARGETS FOR ATHEROSCLEROSIS TREATMENT. ALTHOUGH RODENT MODELS HAVE CONTRIBUTED SUBSTANTIALLY TO A BETTER UNDERSTANDING OF THE DEVELOPMENT OF ATHEROSCLEROSIS, THE ACCURACY OF THESE MODELS REMAINS CONTROVERSIAL. RESEARCH THAT UTILIZES GENETIC RODENT MODELS IS WELL ESTABLISHED, BUT THE USE OF SPECIFIC DIETS THAT ARE ASSOCIATED WITH OTHER RISK FACTORS (E.G., HYPERTENSION, HORMONE DEPRIVATION, AND PHARMACOLOGICAL TOOLS) IS STILL DEBATABLE. THE PRESENT REVIEW PROVIDES AN UPDATE ON NON-GENETIC RAT MODELS OF ATHEROSCLEROSIS AND AN OVERVIEW OF THE MAIN METHODOLOGIES THAT ARE CURRENTLY AVAILABLE. 2019 5 2932 27 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 6 1290 27 DECODING THE GENETIC AND EPIGENETIC BASIS OF ASTHMA. ASTHMA IS A COMPLEX AND HETEROGENEOUS CHRONIC INFLAMMATORY DISEASE OF THE AIRWAYS. ALONGSIDE ENVIRONMENTAL FACTORS, ASTHMA SUSCEPTIBILITY IS STRONGLY INFLUENCED BY GENETICS. GIVEN ITS HIGH PREVALENCE AND OUR INCOMPLETE UNDERSTANDING OF THE MECHANISMS UNDERLYING DISEASE SUSCEPTIBILITY, ASTHMA IS FREQUENTLY STUDIED IN GENOME-WIDE ASSOCIATION STUDIES (GWAS), WHICH HAVE IDENTIFIED THOUSANDS OF GENETIC VARIANTS ASSOCIATED WITH ASTHMA DEVELOPMENT. VIRTUALLY ALL THESE GENETIC VARIANTS RESIDE IN NON-CODING GENOMIC REGIONS, WHICH HAS OBSCURED THE FUNCTIONAL IMPACT OF ASTHMA-ASSOCIATED VARIANTS AND THEIR TRANSLATION INTO DISEASE-RELEVANT MECHANISMS. RECENT ADVANCES IN GENOMICS TECHNOLOGY AND EPIGENETICS NOW OFFER METHODS TO LINK GENETIC VARIANTS TO GENE REGULATORY ELEMENTS EMBEDDED WITHIN NON-CODING REGIONS, WHICH HAVE STARTED TO UNRAVEL THE MOLECULAR MECHANISMS UNDERLYING THE COMPLEX (EPI)GENETICS OF ASTHMA. HERE, WE PROVIDE AN INTEGRATED OVERVIEW OF (EPI)GENETIC VARIANTS ASSOCIATED WITH ASTHMA, FOCUSING ON EFFORTS TO LINK THESE DISEASE ASSOCIATIONS TO BIOLOGICAL INSIGHT INTO ASTHMA PATHOPHYSIOLOGY USING STATE-OF-THE-ART GENOMICS METHODOLOGY. FINALLY, WE PROVIDE A PERSPECTIVE AS TO HOW DECODING THE GENETIC AND EPIGENETIC BASIS OF ASTHMA HAS THE POTENTIAL TO TRANSFORM CLINICAL MANAGEMENT OF ASTHMA AND TO PREDICT THE RISK OF ASTHMA DEVELOPMENT. 2023 7 944 26 CHRONIC LYMPHOCYTIC LEUKEMIA: FROM MOLECULAR PATHOGENESIS TO NOVEL THERAPEUTIC STRATEGIES. CHRONIC LYMPHOCYTIC LEUKEMIA IS A WELL-DEFINED LYMPHOID NEOPLASM WITH VERY HETEROGENEOUS BIOLOGICAL AND CLINICAL BEHAVIOR. THE LAST DECADE HAS BEEN REMARKABLY FRUITFUL IN NOVEL FINDINGS ELUCIDATING MULTIPLE ASPECTS OF THE PATHOGENESIS OF THE DISEASE INCLUDING MECHANISMS OF GENETIC SUSCEPTIBILITY, INSIGHTS INTO THE RELEVANCE OF IMMUNOGENETIC FACTORS DRIVING THE DISEASE, PROFILING OF GENOMIC ALTERATIONS, EPIGENETIC SUBTYPES, GLOBAL EPIGENOMIC TUMOR CELL REPROGRAMMING, MODULATION OF TUMOR CELL AND MICROENVIRONMENT INTERACTIONS, AND DYNAMICS OF CLONAL EVOLUTION FROM EARLY STEPS IN MONOCLONAL B CELL LYMPHOCYTOSIS TO PROGRESSION AND TRANSFORMATION INTO DIFFUSE LARGE B-CELL LYMPHOMA. ALL THIS KNOWLEDGE HAS OFFERED NEW PERSPECTIVES THAT ARE BEING EXPLOITED THERAPEUTICALLY WITH NOVEL TARGET AGENTS AND MANAGEMENT STRATEGIES. IN THIS REVIEW WE PROVIDE AN OVERVIEW OF THESE NOVEL ADVANCES AND HIGHLIGHT QUESTIONS AND PERSPECTIVES THAT NEED FURTHER PROGRESS TO TRANSLATE INTO THE CLINICS THE BIOLOGICAL KNOWLEDGE AND IMPROVE THE OUTCOME OF THE PATIENTS. 2020 8 3682 23 INFLAMMATION, FIBROSIS AND CANCER: MECHANISMS, THERAPEUTIC OPTIONS AND CHALLENGES. UNCONTROLLED INFLAMMATION IS A SALIENT FACTOR IN MULTIPLE CHRONIC INFLAMMATORY DISEASES AND CANCERS. IN THIS REVIEW, WE PROVIDED AN IN-DEPTH ANALYSIS OF THE RELATIONSHIPS AND DISTINCTIONS BETWEEN UNCONTROLLED INFLAMMATION, FIBROSIS AND CANCERS, WHILE EMPHASIZING THE CHALLENGES AND OPPORTUNITIES OF DEVELOPING NOVEL THERAPIES FOR THE TREATMENT AND/OR MANAGEMENT OF THESE DISEASES. WE DESCRIBED HOW DRUG DELIVERY SYSTEMS, COMBINATION THERAPY AND THE INTEGRATION OF TISSUE-TARGETED AND/OR PATHWAYS SELECTIVE STRATEGIES COULD OVERCOME THE CHALLENGES OF CURRENT AGENTS FOR MANAGING AND/OR TREATING CHRONIC INFLAMMATORY DISEASES AND CANCERS. WE ALSO RECOGNIZED THE VALUE OF THE RE-EVALUATION OF THE DISEASE-SPECIFIC ROLES OF MULTIPLE PATHWAYS IMPLICATED IN THE PATHOPHYSIOLOGY OF CHRONIC INFLAMMATORY DISEASES AND CANCERS-AS WELL AS THE APPLICATION OF DATA FROM SINGLE-CELL RNA SEQUENCING IN THE SUCCESS OF FUTURE DRUG DISCOVERY ENDEAVORS. 2022 9 3399 27 HOW CAN GENETICS AND EPIGENETICS HELP THE NEPHROLOGIST IMPROVE THE DIAGNOSIS AND TREATMENT OF CHRONIC KIDNEY DISEASE PATIENTS? DISCOVERY OF NOVEL IMPROVED TOOLS FOR DIAGNOSIS, PREVENTION AND THERAPY OF CHRONIC KIDNEY DISEASE (CKD) IS AN IMPORTANT TASK FOR THE NEPHROLOGY COMMUNITY AND IT IS LIKELY THAT SCIENTIFIC BREAKTHROUGHS, TO A LARGE EXTENT, WILL BE BASED ON GENOMICS. THE RAPID GROWTH OF THE NUMBER OF GENOME-WIDE ASSOCIATION STUDIES, MAJOR ADVANCES IN DNA SEQUENCING AND OMICS PROFILING, AND ACCELERATING BIOMEDICAL RESEARCH EFFORTS IN THIS AREA HAVE GREATLY EXPANDED THE KNOWLEDGE BASE NEEDED FOR APPLIED GENOMICS. HOWEVER, TRANSLATING AND IMPLEMENTING GENOTYPE-PHENOTYPE DATA INTO GENE-BASED MEDICINE IN CKD POPULATIONS IS STILL IN AN EARLY PHASE AND WILL REQUIRE CONTINUOUS RESEARCH EFFORTS WITH INTEGRATED APPROACHES AND INTENSIFIED INVESTIGATIONS THAT FOCUS ON THE BIOLOGICAL PATHWAYS, WHICH CAUSATIVELY LINK A GENETIC VARIANT WITH THE DISEASE PHENOTYPE. IN THIS ARTICLE, WE REVIEW SOME CURRENT STRATEGIES TO UNRAVEL THESE TRANSLATIONAL GAPS AS WELL AS PROSPECTS FOR THE IMPLEMENTATION OF GENETIC AND EPIGENETIC METHODS INTO NOVEL CLINICAL PRACTICE. 2014 10 97 21 A PRIMER ON THE EPIGENETICS OF KIDNEY FIBROSIS. DESPITE EXTENSIVE KNOWLEDGE OF THE VARIOUS MOLECULAR PATHWAYS THAT CONTRIBUTE TO TUBULOINTERSTITIAL FIBROSIS, IT REMAINS AN UNSOLVED QUESTION WHY THE PROGRESSION RATE OF CHRONIC KIDNEY DISEASE VARIES SUBSTANTIALLY FROM PATIENT TO PATIENT, EVEN AMONG PATIENTS WITH COMMON UNDERLYING NEPHROPATHIES AND COMORBIDITIES. POSSIBLE EXPLANATIONS FOR DIFFERENT SUSCEPTIBILITIES OF INDIVIDUAL PATIENTS TO DEVELOP END-STAGE RENAL FAILURE INCLUDE GENETIC OR EPIGENETIC VARIATIONS, WHICH MODIFY HOW INDIVIDUAL PATIENTS RESPOND TO KIDNEY INJURY. HERE WE REVIEW PRINCIPLES OF EPIGENETIC MECHANISMS IN CONTEXT OF CHRONIC KIDNEY DISEASE AND DISCUSS HOW SUCH INSIGHTS MAY BE UTILIZED FOR FUTURE THERAPEUTIC STRATEGIES AND MAY LEAD TO NOVEL DIAGNOSTIC TOOLS IN THE FUTURE. 2012 11 459 26 APPLYING SINGLE-CELL TECHNOLOGIES TO CLINICAL PATHOLOGY: PROGRESS IN NEPHROPATHOLOGY. CELLS REPRESENT THE BASIC BUILDING BLOCKS OF LIVING ORGANISMS. ACCURATE CHARACTERISATION OF CELLULAR PHENOTYPE, INTERCELLULAR SIGNALLING NETWORKS, AND THE SPATIAL ORGANISATION OF CELLS WITHIN ORGANS IS CRUCIAL TO DELIVER A BETTER UNDERSTANDING OF THE PROCESSES UNDERPINNING PHYSIOLOGY, AND THE PERTURBATIONS THAT LEAD TO DISEASE. SINGLE-CELL METHODOLOGIES HAVE INCREASED RAPIDLY IN SCALE AND SCOPE IN RECENT YEARS AND ARE SET TO GENERATE IMPORTANT INSIGHTS INTO HUMAN DISEASE. HERE, WE REVIEW CURRENT PRACTICES IN NEPHROPATHOLOGY, WHICH ARE DOMINATED BY RELATIVELY SIMPLE MORPHOLOGICAL DESCRIPTIONS OF TISSUE BIOPSIES BASED ON THEIR APPEARANCE USING LIGHT MICROSCOPY. BULK TRANSCRIPTOMICS HAVE MORE RECENTLY BEEN USED TO EXPLORE GLOMERULAR AND TUBULOINTERSTITIAL KIDNEY DISEASE, RENAL CANCER, AND THE RESPONSES TO INJURY AND ALLOIMMUNITY IN KIDNEY TRANSPLANTATION, GENERATING NOVEL DISEASE INSIGHTS AND PROGNOSTIC BIOMARKERS. THESE STUDIES SET THE STAGE FOR SINGLE-CELL TRANSCRIPTOMIC APPROACHES THAT REVEAL CELL-TYPE-SPECIFIC GENE EXPRESSION PATTERNS IN HEALTH AND DISEASE. THESE TECHNOLOGIES ALLOW GENOME-WIDE DISEASE SUSCEPTIBILITY GENES TO BE INTERPRETED WITH THE KNOWLEDGE OF THE SPECIFIC CELL POPULATIONS WITHIN ORGANS THAT EXPRESS THEM, IDENTIFYING CANDIDATE CELL TYPES FOR FURTHER STUDY. SINGLE-CELL TECHNOLOGIES ARE ALSO MOVING BEYOND ASSAYING INDIVIDUAL CELLULAR TRANSCRIPTOMES, TO MEASURING THE EPIGENETIC LANDSCAPE OF SINGLE CELLS. SINGLE-CELL ANTIGEN-RECEPTOR GENE SEQUENCING ALSO ENABLES SPECIFIC T- AND B-CELL CLONES TO BE TRACKED IN DIFFERENT TISSUES AND DISEASE STATES. IN THE COMING YEARS THESE RICH 'MULTI-OMIC' DESCRIPTIONS OF KIDNEY DISEASE WILL ENABLE HISTOPATHOLOGICAL DESCRIPTIONS TO BE COMPREHENSIVELY INTEGRATED WITH MOLECULAR PHENOTYPES, ENABLING BETTER DISEASE CLASSIFICATION AND PROGNOSTICATION AND THE APPLICATION OF PERSONALISED TREATMENT STRATEGIES. (C) 2020 THE AUTHORS. THE JOURNAL OF PATHOLOGY PUBLISHED BY JOHN WILEY & SONS LTD ON BEHALF OF PATHOLOGICAL SOCIETY OF GREAT BRITAIN AND IRELAND. 2020 12 4422 37 MOLECULAR AND GENETIC INFLAMMATION NETWORKS IN MAJOR HUMAN DISEASES. IT HAS BEEN WELL-RECOGNIZED THAT INFLAMMATION ALONGSIDE TISSUE REPAIR AND DAMAGE MAINTAINING TISSUE HOMEOSTASIS DETERMINES THE INITIATION AND PROGRESSION OF COMPLEX DISEASES. ALBEIT WITH THE ACCOMPLISHMENT OF HAVING CAPTURED THE MOST CRITICAL INFLAMMATION-INVOLVED MOLECULES, GENETIC SUSCEPTIBILITIES, EPIGENETIC FACTORS, AND ENVIRONMENTAL FACTORS, OUR SCHEMATA ON THE ROLE OF INFLAMMATION IN COMPLEX DISEASES REMAIN LARGELY PATCHY, IN PART DUE TO THE SUCCESS OF REDUCTIONISM IN TERMS OF RESEARCH METHODOLOGY PER SE. OMICS DATA ALONGSIDE THE ADVANCES IN DATA INTEGRATION TECHNOLOGIES HAVE ENABLED RECONSTRUCTION OF MOLECULAR AND GENETIC INFLAMMATION NETWORKS WHICH SHED LIGHT ON THE UNDERLYING PATHOPHYSIOLOGY OF COMPLEX DISEASES OR CLINICAL CONDITIONS. GIVEN THE PROVEN BENEFICIAL ROLE OF ANTI-INFLAMMATION IN CORONARY HEART DISEASE AS WELL AS OTHER COMPLEX DISEASES AND IMMUNOTHERAPY AS A REVOLUTIONARY TRANSITION IN ONCOLOGY, IT BECOMES TIMELY TO REVIEW OUR CURRENT UNDERSTANDING OF THE MOLECULAR AND GENETIC INFLAMMATION NETWORKS UNDERLYING MAJOR HUMAN DISEASES. IN THIS REVIEW, WE FIRST BRIEFLY DISCUSS THE COMPLEXITY OF INFECTIOUS DISEASES AND THEN HIGHLIGHT RECENTLY UNCOVERED MOLECULAR AND GENETIC INFLAMMATION NETWORKS IN OTHER MAJOR HUMAN DISEASES INCLUDING OBESITY, TYPE II DIABETES, CORONARY HEART DISEASE, LATE ONSET ALZHEIMER'S DISEASE, PARKINSON'S DISEASE, AND SPORADIC CANCER. THE COMMONALITY AND SPECIFICITY OF THESE MOLECULAR NETWORKS ARE ADDRESSED IN THE CONTEXT OF GENETICS BASED ON GENOME-WIDE ASSOCIATION STUDY (GWAS). THE DOUBLE-SWORD ROLE OF INFLAMMATION, SUCH AS HOW THE ABERRANT TYPE 1 AND/OR TYPE 2 IMMUNITY LEADS TO CHRONIC AND SEVERE CLINICAL CONDITIONS, REMAINS OPEN IN TERMS OF THE INFLAMMASOME AND THE CORE INFLAMMATOME NETWORK FEATURES. INCREASINGLY AVAILABLE LARGE OMICS AND CLINICAL DATA IN TANDEM WITH SYSTEMS BIOLOGY APPROACHES HAVE OFFERED AN EXCITING YET CHALLENGING OPPORTUNITY TOWARD RECONSTRUCTION OF MORE COMPREHENSIVE AND DYNAMIC MOLECULAR AND GENETIC INFLAMMATION NETWORKS, WHICH HOLD GREAT PROMISE IN TRANSITING NETWORK SNAPSHOTS TO VIDEO-STYLE MULTI-SCALE INTERPLAYS OF DISEASE MECHANISMS, IN TURN LEADING TO EFFECTIVE CLINICAL INTERVENTION. 2016 13 4743 25 NOVEL INSIGHTS FROM GENETIC AND EPIGENETIC STUDIES IN UNDERSTANDING THE COMPLEX URAEMIC PHENOTYPE. LIKE IN MANY OTHER COMMON COMPLEX DISORDERS, STUDIES OF CHRONIC KIDNEY DISEASE (CKD) CAN NOW MAKE USE OF THE INCREASING KNOWLEDGE OF THE HUMAN GENOME, ITS VARIATIONS AND IMPACT ON DISEASE SUSCEPTIBILITY, INITIATION, PROGRESSION AND COMPLICATIONS. SUCH STUDIES ARE FACILITATED BY NOVEL READILY AVAILABLE HIGH THROUGH-PUT GENOTYPING METHODS AND SOPHISTICATED ANALYTICAL APPROACHES TO SCAN THE GENOME FOR DNA VARIATIONS AND EPIGENETIC MODIFICATIONS. HERE, WE REVIEW SOME OF THE RECENT DISCOVERIES THAT HAVE EMERGED FROM THESE STUDIES AND EXPANDED OUR KNOWLEDGE OF GENETIC RISK LOCI AND EPIGENETIC MARKERS IN CKD PATHOPHYSIOLOGY. OBSTACLES AND PRACTICAL ISSUES IN THIS FIELD ARE DISCUSSED. 2014 14 2394 20 EPIGENETIC REPROGRAMMING IN LIVER FIBROSIS AND CANCER. NOVEL INSIGHTS INTO THE EPIGENETIC CONTROL OF CHRONIC LIVER DISEASES ARE NOW EMERGING. RECENT ADVANCES IN OUR UNDERSTANDING OF THE CRITICAL ROLES OF DNA METHYLATION, HISTONE MODIFICATIONS AND NCRNA MAY NOW BE EXPLOITED TO IMPROVE MANAGEMENT OF FIBROSIS/CIRRHOSIS AND CANCER. FURTHERMORE, IMPROVED TECHNOLOGIES FOR THE DETECTION OF EPIGENETIC MARKERS FROM PATIENTS' BLOOD AND TISSUES WILL VASTLY IMPROVE DIAGNOSIS, TREATMENT OPTIONS AND PROGNOSTIC TRACKING. THE AIM OF THIS REVIEW IS TO PRESENT RECENT FINDINGS FROM THE FIELD OF LIVER EPIGENETICS AND TO EXPLORE THEIR POTENTIAL FOR TRANSLATION INTO THERAPEUTICS TO PREVENT DISEASE PROMOTING EPIGENOME REPROGRAMMING AND REVERSE EPIGENETIC CHANGES. 2017 15 3169 27 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 16 2543 27 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 6630 22 UNDERSTANDING THE INTERPLAY BETWEEN HEALTH DISPARITIES AND EPIGENOMICS. SOCIAL EPIGENOMICS HAS EMERGED AS AN INTEGRATIVE FIELD OF RESEARCH FOCUSED ON IDENTIFICATION OF SOCIO-ENVIRONMENTAL FACTORS, THEIR INFLUENCE ON HUMAN BIOLOGY THROUGH EPIGENOMIC MODIFICATIONS, AND HOW THEY CONTRIBUTE TO CURRENT HEALTH DISPARITIES. SEVERAL HEALTH DISPARITIES STUDIES HAVE BEEN PUBLISHED USING GENETIC-BASED APPROACHES; HOWEVER, INCREASING ACCESSIBILITY AND AFFORDABILITY OF MOLECULAR TECHNOLOGIES HAVE ALLOWED FOR AN IN-DEPTH INVESTIGATION OF THE INFLUENCE OF EXTERNAL FACTORS ON EPIGENETIC MODIFICATIONS (E.G., DNA METHYLATION, MICRO-RNA EXPRESSION). CURRENTLY, RESEARCH IS FOCUSED ON EPIGENETIC CHANGES IN RESPONSE TO ENVIRONMENT, AS WELL AS TARGETED EPIGENETIC THERAPIES AND ENVIRONMENTAL/SOCIAL STRATEGIES FOR POTENTIALLY MINIMIZING CERTAIN HEALTH DISPARITIES. HERE, WE WILL REVIEW RECENT FINDINGS IN THIS FIELD PERTAINING TO CONDITIONS AND DISEASES OVER LIFE SPAN ENCOMPASSING PRENATAL TO ADULT STAGES. 2020 18 6843 19 [MEDICAL APPLICATIONS OF GENOME DISCOVERY]. THE DISCOVERY OF THE COMPLETE BASE SEQUENCE OF HUMAN GENOME UNVEILS SEVERAL PERSPECTIVES TO UNDERSTAND HUMAN DISEASES AND DEVELOP NEW THERAPIES. HUMAN GENOME CONTAINS APPROXIMATELY 39,000 GENES OF WHICH 26,000 CODE SPECIFIC PROTEINS THAT HAVE BEEN IDENTIFIED. THERE ARE APPROXIMATELY 1,500 DISEASES WITH IDENTIFIED MOLECULAR DISTURBANCES. GENES CAN MODIFY SIGNS AND SYMPTOMS OF COMMON DISEASES. THUS, THERE ARE NO PURE MONOGENIC DISEASES. CHRONIC DISEASES OF ADULTS ARE COMPLEX AND DEPENDENT ON MULTIPLE FACTORS. SEVERAL GENES THAT PREDISPOSE TO CHRONIC DEGENERATIVE DISEASES HAVE BEEN IDENTIFIED. THIS IS REVEALING THE COMPLEX NATURE AND THE INTERACTION OF THESE AILMENTS WITH THE ENVIRONMENT. THE DISCOVERY OF BACTERIAL AND VIRAL GENOMIC SEQUENCES WILL ALLOW THE MANUFACTURING OF NEW VACCINES AND SPECIFIC MOLECULAR ANTIMICROBIALS. THE NEW PHARMACOGENOMICS WILL DEVISE TREATMENTS FOR EACH SUBJECT ACCORDING TO HER SPECIFIC GENOMIC PROFILE. THE NEW APPLICATIONS OF GENOMIC TECHNOLOGY IS CREATING NEW PARADIGMS IN BIOMEDICAL RESEARCH SUCH AS FUNCTIONAL GENOMICS, PROTEONOMICS, EPIGENETIC REGULATION. GENE DIAGNOSIS AND THERAPY WILL CONSIDERABLY IMPROVE THE FUTURE OF MEDICINE. 2001 19 2544 23 EPIGENETICS IN LIVER DISEASE: FROM BIOLOGY TO THERAPEUTICS. KNOWLEDGE OF THE FUNDAMENTAL EPIGENETIC MECHANISMS GOVERNING GENE EXPRESSION AND CELLULAR PHENOTYPE ARE SUFFICIENTLY ADVANCED THAT NOVEL INSIGHTS INTO THE EPIGENETIC CONTROL OF CHRONIC LIVER DISEASE ARE NOW EMERGING. HEPATOLOGISTS ARE IN THE PROCESS OF SHEDDING LIGHT ON THE ROLES PLAYED BY DNA METHYLATION, HISTONE/CHROMATIN MODIFICATIONS AND NON-CODING RNAS IN SPECIFIC LIVER PATHOLOGIES. ALONGSIDE THESE DISCOVERIES ARE ADVANCES IN THE TECHNOLOGIES FOR THE DETECTION AND QUANTIFICATION OF EPIGENETIC BIOMARKERS, EITHER DIRECTLY FROM PATIENT TISSUE OR FROM BODY FLUIDS. THE PREMISE FOR THIS REVIEW IS TO SURVEY THE RECENT ADVANCES IN THE FIELD OF LIVER EPIGENETICS AND TO EXPLORE THEIR POTENTIAL FOR TRANSLATION BY INDUSTRY AND CLINICAL HEPATOLOGISTS FOR THE DESIGN OF NOVEL THERAPEUTICS AND DIAGNOSTIC/PROGNOSTIC BIOMARKERS. IN PARTICULAR, WE PRESENT FINDINGS IN THE CONTEXT OF HEPATOCELLULAR CARCINOMA, FIBROSIS AND NON-ALCOHOLIC FATTY LIVER DISEASE, WHERE THERE IS URGENT UNMET NEED FOR NEW CLINICAL INTERVENTIONS AND BIOMARKERS. 2016 20 4452 29 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