1 4716 105 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 2 6786 33 [CONSENSUS AND CONTROVERSY ON RESEARCH PROGRESS AND CLINICAL PRACTICE OF VASCULAR CALCIFICATION]. VASCULAR CALCIFICATION IS AN ACTIVE AND COMPLEX PATHOLOGICAL PROCESS REGULATED BY SEVERAL FACTORS. VASCULAR CALCIFICATION IS CLOSELY RELATED TO THE INCIDENCE AND MORTALITY OF THE CARDIOVASCULAR DISEASE, CHRONIC KIDNEY DISEASE AND OTHER DISEASES, WHICH AFFECTS MULTIPLE ORGANS AND SYSTEMS, THUS AFFECTING PEOPLE'S HEALTH. THEREFORE, MORE AND MORE ATTENTION IS PAID TO VASCULAR CALCIFICATION. AT PRESENT, THE PATHOGENESIS AND CLINICAL PRACTICE OF VASCULAR CALCIFICATION HAVE BEEN CONTINUOUSLY IMPROVED, WHICH MAINLY INCLUDES CALCIUM AND PHOSPHORUS IMBALANCE THEORY, VASCULAR SMOOTH MUSCLE CELL TRANSDIFFERENTIATION THEORY, BONE HOMEOSTASIS IMBALANCE THEORY, EPIGENETIC REGULATION THEORY, INFLAMMATION THEORY, EXTRACELLULAR MATRIX THEORY, NEW CELL FATE THEORY AND SO ON. HOWEVER, THERE ARE STILL MANY UNSOLVED PROBLEMS. SINCE THE OCCURRENCE AND DEVELOPMENT OF VASCULAR CALCIFICATION AFFECT MULTIPLE ORGANS AND SYSTEMS, THIS EXPERT CONSENSUS GATHERED CLINICIANS AND BASIC RESEARCH EXPERTS ENGAGED IN THE STUDY OF VASCULAR CALCIFICATION IN ORDER TO SUMMARIZE THE PROGRESS OF VARIOUS DISCIPLINES RELATED TO VASCULAR CALCIFICATION IN RECENT YEARS. THE PURPOSE OF THIS CONSENSUS IS TO SYSTEMATICALLY SUMMARIZE THE LATEST RESEARCH PROGRESS, TREATMENT CONSENSUS AND CONTROVERSY OF VASCULAR CALCIFICATION FROM THE ASPECTS OF EPIDEMIOLOGY, PATHOGENESIS, PREVENTION AND TREATMENT, SO AS TO PROVIDE THEORETICAL BASIS AND CLINICAL ENLIGHTENMENT FOR IN-DEPTH RESEARCH IN THIS FIELD. 2022 3 3399 35 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 4 1290 34 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 5 46 31 A CONCEPTUAL FRAMEWORK FOR THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE. IN THE LAST DECADES, THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) HAVE EMERGED AS A VIGOROUS FIELD COMBINING EXPERIMENTAL, CLINICAL, EPIDEMIOLOGICAL AND PUBLIC HEALTH RESEARCH. ITS GOAL IS TO UNDERSTAND HOW EVENTS IN EARLY LIFE SHAPE LATER MORBIDITY RISK, ESPECIALLY OF NON-COMMUNICABLE CHRONIC DISEASES. AS THESE DISEASES BECOME THE MAJOR CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE, RESEARCH ARISING FROM DOHAD IS LIKELY TO GAIN SIGNIFICANCE TO PUBLIC HEALTH AND ECONOMIC DEVELOPMENT. BUT ACTION MAY BE HINDERED BY THE LACK OF A FIRM MECHANISTIC EXPLANATION AND OF A CONCEPTUAL BASIS, ESPECIALLY REGARDING THE EVOLUTIONARY SIGNIFICANCE OF THE DOHAD PHENOMENON. IN THIS ARTICLE, WE PROVIDE A SUCCINCT HISTORICAL REVIEW OF THE RESEARCH INTO THE RELATIONSHIP BETWEEN DEVELOPMENT AND LATER DISEASE, CONSIDER THE EVOLUTIONARY AND DEVELOPMENTAL SIGNIFICANCE AND DISCUSS THE UNDERLYING MECHANISMS OF THE DOHAD PHENOMENON. DOHAD SHOULD BE VIEWED AS A PART OF A BROADER BIOLOGICAL MECHANISM OF PLASTICITY BY WHICH ORGANISMS, IN RESPONSE TO CUES SUCH AS NUTRITION OR HORMONES, ADAPT THEIR PHENOTYPE TO ENVIRONMENT. THESE RESPONSES MAY BE DIVIDED INTO THOSE FOR IMMEDIATE BENEFIT AND THOSE AIMED AT PREDICTION OF A FUTURE ENVIRONMENT: DISEASE OCCURS IN THE MISMATCH BETWEEN PREDICTED AND REALIZED FUTURE. THE LIKELY MECHANISMS THAT ENABLE PLASTICITY INVOLVE EPIGENETIC PROCESSES, AFFECTING THE EXPRESSION OF GENES ASSOCIATED WITH REGULATORY PATHWAYS. THERE IS NOW EVIDENCE THAT EPIGENETIC MARKS MAY BE INHERITED AND SO CONTRIBUTE TO NON-GENOMIC HERITABLE DISEASE RISK. WE END BY DISCUSSING THE GLOBAL SIGNIFICANCE OF THE DOHAD PHENOMENON AND ITS POTENTIAL APPLICATIONS FOR PUBLIC HEALTH PURPOSES. 2010 6 5163 35 PRECISION/PERSONALIZED MEDICINE IN ALLERGIC DISEASES AND ASTHMA. LIKE MANY OTHER CHRONIC DISEASES, EVERY ALLERGIC PATIENT HAS DIFFERENT CHARACTERISTICS BASED ON CLINICAL COURSE, TREATMENT RESPONSIVENESS AND DISEASE OUTCOMES, WHICH ARE ASSOCIATED WITH THE GENETIC AND EPIGENETIC CONTROL OF MOLECULAR MECHANISMS AND ENVIRONMENT. THIS VARIABILITY NECESSITATES THE ESTABLISHMENT OF PATIENT-TAILORED AND PRECISION APPROACHES IN HANDLING ALLERGIC DISORDERS. BETTER UNDERSTANDING OF THE UNDERLYING PATHOPHYSIOLOGICAL MECHANISMS FOR THE DEVELOPMENT OF ALLERGIC DISORDERS WILL PROVIDE MORE RATIONALE STRATEGIES BASED ON INDIVIDUAL CASES IN CONTROLLING AND TREATING THESE DISORDERS. ENDOTYPING, PHENOTYPING, GENOTYPING AND THERATYPING, AND BIOMARKERS ARE KEYWORDS IN THIS AREA AND HAVE BEEN GAINING LOTS OF ATTENTION IN THE FIELD OF PRECISION MEDICINE, WHICH AIMS TO REVOLUTIONIZE PATIENT CARE AND DEVELOP BETTER PREVENTION AND TREATMENT STRATEGIES. IN ADDITION, PRECISION HEALTH IS A NEW CONCEPT THAT BRINGS PRECISE APPROACHES TO THE SCENE FOR BEING HEALTHY AND PREVENTION OF ALLERGIC DISEASE AND ASTHMA. THE SPECIALTY OF ALLERGY HAS A LEADING ROLE IN THE FIELD, BECAUSE ALLERGEN-SPECIFIC IMMUNOTHERAPY STARTED 105 YEARS AGO, AND IS HISTORICALLY A LEADING PERSONALIZED/PRECISION MEDICINE APPROACH IN ALL MEDICINE DISCIPLINES PROVIDING THE POSSIBILITY OF CURE IN AN INDIVIDUALIZED MANNER INSTEAD OF CONVENTIONAL SYMPTOMATIC TREATMENTS. 2018 7 4832 30 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 8 4422 36 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 9 6630 28 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 10 357 31 ALTERNATIVE MODELS FOR TRANSGENERATIONAL EPIGENETIC INHERITANCE: MOLECULAR PSYCHIATRY BEYOND MICE AND MAN. MENTAL ILLNESS REMAINS THE GREATEST CHRONIC HEALTH BURDEN GLOBALLY WITH FEW IN-ROADS HAVING BEEN MADE DESPITE SIGNIFICANT ADVANCES IN GENOMIC KNOWLEDGE IN RECENT DECADES. THE FIELD OF PSYCHIATRY IS CONSTANTLY CHALLENGED TO BRING NEW APPROACHES AND TOOLS TO ADDRESS AND TREAT THE NEEDS OF VULNERABLE INDIVIDUALS AND SUBPOPULATIONS, AND THAT HAS TO BE SUPPORTED BY A CONTINUOUS GROWTH IN KNOWLEDGE. THE MAJORITY OF NEUROPSYCHIATRIC SYMPTOMS REFLECT COMPLEX GENE-ENVIRONMENT INTERACTIONS, WITH EPIGENETICS BRIDGING THE GAP BETWEEN GENETIC SUSCEPTIBILITY AND ENVIRONMENTAL STRESSORS THAT TRIGGER DISEASE ONSET AND DRIVE THE ADVANCEMENT OF SYMPTOMS. IT HAS MORE RECENTLY BEEN DEMONSTRATED IN PRECLINICAL MODELS THAT EPIGENETICS UNDERPINS THE TRANSGENERATIONAL INHERITANCE OF STRESS-RELATED BEHAVIOURAL PHENOTYPES IN BOTH PATERNAL AND MATERNAL LINEAGES, PROVIDING FURTHER SUPPORTING EVIDENCE FOR HERITABILITY IN HUMANS. HOWEVER, UNBIASED PROSPECTIVE STUDIES OF THIS NATURE ARE PRACTICALLY IMPOSSIBLE TO CONDUCT IN HUMANS SO PRECLINICAL MODELS REMAIN OUR BEST OPTION FOR RESEARCHING THE MOLECULAR PATHOPHYSIOLOGIES UNDERLYING MANY NEUROPSYCHIATRIC CONDITIONS. WHILE RODENTS WILL REMAIN THE DOMINANT MODEL SYSTEM FOR PRECLINICAL STUDIES (ESPECIALLY FOR ADDRESSING COMPLEX BEHAVIOURAL PHENOTYPES), THERE IS SCOPE TO EXPAND CURRENT RESEARCH OF THE MOLECULAR AND EPIGENETIC PATHOLOGIES BY USING INVERTEBRATE MODELS. HERE, WE WILL DISCUSS THE UTILITY AND ADVANTAGES OF TWO ALTERNATIVE MODEL ORGANISMS-CAENORHABDITIS ELEGANS AND DROSOPHILA MELANOGASTER-AND SUMMARISE THE COMPELLING INSIGHTS OF THE EPIGENETIC REGULATION OF TRANSGENERATIONAL INHERITANCE THAT ARE POTENTIALLY RELEVANT TO HUMAN PSYCHIATRY. 2021 11 2595 40 EPIGENETICS OF SPONDYLOARTHRITIS. SPONDYLOARTHRITIS (SPA) IS A CHRONIC INFLAMMATORY DISORDER RESULTING FROM A COMBINATION OF GENETIC PREDISPOSITION AND ENVIRONMENTAL FACTORS. DESPITE RECENT ADVANCES, A SUBSTANTIAL FRACTION OF ITS GENETIC BASIS REMAINS POORLY UNDERSTOOD. SEVERAL MECHANISMS HAVE BEEN PROPOSED TO ACCOUNT FOR THIS UNEXPLAINED HERITABILITY, INCLUDING EPIGENETICS WHICH CAN PLAY A ROLE AT THE INTERFACE BETWEEN GENETIC AND ENVIRONMENTAL SUSCEPTIBILITY FACTORS. EPIGENETICS REFERS TO CHANGES IN GENE EXPRESSION THAT ARE NOT ENCODED IN THE DNA SEQUENCE ITSELF. SUCH MECHANISMS MAY INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS AND NON-CODING RNAS. DISRUPTION OF ONE OF THESE SYSTEMS CAN LEAD TO INAPPROPRIATE GENE EXPRESSION, WHICH IN TURN MIGHT FAVOUR THE DEVELOPMENT OF DISEASE. THANKS TO RECENT TECHNOLOGICAL PROGRESS, THERE HAS BEEN A GROWING INTEREST IN THE FIELD OF EPIGENETICS IN COMPLEX DISEASES, INCLUDING SPA. HOWEVER, EPIGENETIC STUDIES FACE SOME METHODOLOGICAL LIMITATIONS THAT HAMPER INTERPRETATION OF THEIR RESULTS: SMALL SAMPLE SIZE, ABSENCE OF BIOLOGICAL REPLICATION, LACK OF ADEQUATE CONTROLS FOR POTENTIAL CONFOUNDERS, STUDIES NOT PERFORMED IN THE MOST RELEVANT CELL/TISSUES. IN THE FUTURE, INTEGRATION OF EPIGENETICS WITH OTHER "OMICS" DATA WILL PROBABLY BE NECESSARY TO IMPROVE OUR UNDERSTANDING OF SPA PATHOGENESIS. THESE ISSUES NEED TO BE ADDRESSED BEFORE CONSIDERING THE USE OF EPIGENETIC MARKS IN CLINICAL ROUTINE, AS BIOMARKERS OR AS DRUG TARGETS. 2020 12 1037 16 CLASSIFICATION AND DIAGNOSIS OF TEMPOROMANDIBULAR DISORDERS AND TEMPOROMANDIBULAR DISORDER PAIN. DESIGNING CLASSIFICATION SYSTEMS AND DEVELOPING DIAGNOSTIC CRITERIA FOR TEMPOROMANDIBULAR DISORDERS IS DIFFICULT. AN APPRECIATION OF THE UTILITY AND APPLICABILITY OF THESE ENTITIES REQUIRES AN UNDERSTANDING OF THE IMPORTANCE OF EACH, THE DIFFERENCES BETWEEN THE TWO, AND HOW THEY MAY BE OPTIMALLY OPERATIONALIZED FOR BOTH CLINICAL AND RESEARCH ACTIVITIES IN LIGHT OF THEIR INHERENT ADVANTAGES AND LIMITATIONS. IN ADDITION, CONSIDERATION FOR ADOPTING NEWER APPROACHES, SUCH AS FOLLOWING ONTOLOGICAL AND PRECISION-BASED MEDICINE PRINCIPLES, ACCOUNTING FOR GENETICS/EPIGENETIC AND NEUROBIOLOGICAL FACTORS, AND THE INCLUSION OF BIOMARKERS WILL POTENTIALLY RESULT IN MORE THOROUGH AND COMPREHENSIVE CLASSIFICATION SYSTEMS AND DIAGNOSTIC CRITERIA. 2023 13 6295 34 THE PROMISES AND CHALLENGES OF TOXICO-EPIGENOMICS: ENVIRONMENTAL CHEMICALS AND THEIR IMPACTS ON THE EPIGENOME. BACKGROUND: IT HAS BEEN ESTIMATED THAT A SUBSTANTIAL PORTION OF CHRONIC AND NONCOMMUNICABLE DISEASES CAN BE CAUSED OR EXACERBATED BY EXPOSURE TO ENVIRONMENTAL CHEMICALS. MULTIPLE LINES OF EVIDENCE INDICATE THAT EARLY LIFE EXPOSURE TO ENVIRONMENTAL CHEMICALS AT RELATIVELY LOW CONCENTRATIONS COULD HAVE LASTING EFFECTS ON INDIVIDUAL AND POPULATION HEALTH. ALTHOUGH THE POTENTIAL ADVERSE EFFECTS OF ENVIRONMENTAL CHEMICALS ARE KNOWN TO THE SCIENTIFIC COMMUNITY, REGULATORY AGENCIES, AND THE PUBLIC, LITTLE IS KNOWN ABOUT THE MECHANISTIC BASIS BY WHICH THESE CHEMICALS CAN INDUCE LONG-TERM OR TRANSGENERATIONAL EFFECTS. TO ADDRESS THIS QUESTION, EPIGENETIC MECHANISMS HAVE EMERGED AS THE POTENTIAL LINK BETWEEN GENETIC AND ENVIRONMENTAL FACTORS OF HEALTH AND DISEASE. OBJECTIVES: WE PRESENT AN OVERVIEW OF EPIGENETIC REGULATION AND A SUMMARY OF REPORTED EVIDENCE OF ENVIRONMENTAL TOXICANTS AS EPIGENETIC DISRUPTORS. WE ALSO DISCUSS THE ADVANTAGES AND CHALLENGES OF USING EPIGENETIC BIOMARKERS AS AN INDICATOR OF TOXICANT EXPOSURE, USING MEASURES THAT CAN BE TAKEN TO IMPROVE RISK ASSESSMENT, AND OUR PERSPECTIVES ON THE FUTURE ROLE OF EPIGENETICS IN TOXICOLOGY. DISCUSSION: UNTIL RECENTLY, EFFORTS TO APPLY EPIGENOMIC DATA IN TOXICOLOGY AND RISK ASSESSMENT WERE RESTRICTED BY AN INCOMPLETE UNDERSTANDING OF EPIGENOMIC VARIABILITY ACROSS TISSUE TYPES AND POPULATIONS. THIS IS POISED TO CHANGE WITH THE DEVELOPMENT OF NEW TOOLS AND CONCERTED EFFORTS BY RESEARCHERS ACROSS DISCIPLINES THAT HAVE LED TO A BETTER UNDERSTANDING OF EPIGENETIC MECHANISMS AND COMPREHENSIVE MAPS OF EPIGENOMIC VARIATION. WITH THE FOUNDATIONS NOW IN PLACE, WE FORESEE THAT UNPRECEDENTED ADVANCEMENTS WILL TAKE PLACE IN THE FIELD IN THE COMING YEARS. HTTPS://DOI.ORG/10.1289/EHP6104. 2020 14 5025 37 PERSONALIZED MANAGEMENT OF CARDIOVASCULAR DISORDERS. PERSONALIZED MANAGEMENT OF CARDIOVASCULAR DISORDERS (CVD), ALSO REFERRED TO AS PERSONALIZED OR PRECISION CARDIOLOGY IN ACCORDANCE WITH GENERAL PRINCIPLES OF PERSONALIZED MEDICINE, IS SELECTION OF THE BEST TREATMENT FOR AN INDIVIDUAL PATIENT. IT INVOLVES THE INTEGRATION OF VARIOUS "OMICS" TECHNOLOGIES SUCH AS GENOMICS AND PROTEOMICS AS WELL AS OTHER NEW TECHNOLOGIES SUCH AS NANOBIOTECHNOLOGY. MOLECULAR DIAGNOSTICS AND BIOMARKERS ARE IMPORTANT FOR LINKING DIAGNOSIS WITH THERAPY AND MONITORING THERAPY. BECAUSE CVD INVOLVE PERTURBATIONS OF LARGE COMPLEX BIOLOGICAL NETWORKS, A SYSTEMS BIOLOGY APPROACH TO CVD RISK STRATIFICATION MAY BE USED FOR IMPROVING RISK-ESTIMATING ALGORITHMS, AND MODELING OF PERSONALIZED BENEFIT OF TREATMENT MAY BE HELPFUL FOR GUIDING THE CHOICE OF INTERVENTION. BIOINFORMATICS TOOLS ARE HELPFUL IN ANALYZING AND INTEGRATING LARGE AMOUNTS OF DATA FROM VARIOUS SOURCES. PERSONALIZED THERAPY IS CONSIDERED DURING DRUG DEVELOPMENT, INCLUDING METHODS OF TARGETED DRUG DELIVERY AND CLINICAL TRIALS. INDIVIDUALIZED RECOMMENDATIONS CONSIDER MULTIPLE FACTORS - GENETIC AS WELL AS EPIGENETIC - FOR PATIENTS' RISK OF HEART DISEASE. EXAMPLES OF PERSONALIZED TREATMENT ARE THOSE OF CHRONIC MYOCARDIAL ISCHEMIA, HEART FAILURE, AND HYPERTENSION. SIMILAR APPROACHES CAN BE USED FOR THE MANAGEMENT OF ATRIAL FIBRILLATION AND HYPERCHOLESTEROLEMIA, AS WELL AS THE USE OF ANTICOAGULANTS. PERSONALIZED MANAGEMENT INCLUDES PHARMACOTHERAPY, SURGERY, LIFESTYLE MODIFICATIONS, AND COMBINATIONS THEREOF. FURTHER PROGRESS IN UNDERSTANDING THE PATHOMECHANISM OF COMPLEX CARDIOVASCULAR DISEASES AND IDENTIFICATION OF CAUSATIVE FACTORS AT THE INDIVIDUAL PATIENT LEVEL WILL PROVIDE OPPORTUNITIES FOR THE DEVELOPMENT OF PERSONALIZED CARDIOLOGY. APPLICATION OF PRINCIPLES OF PERSONALIZED MEDICINE WILL IMPROVE THE CARE OF THE PATIENTS WITH CVD. 2017 15 3169 35 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 6892 23 [SIGNIFICANCE OF PREVENTING DEVELOPMENTAL ORIGINS OF DISEASES IN IMPROVING POPULATION QUALITY]. MORE STUDIES SHOW THAT VARIOUS DISEASES, ESPECIALLY CHRONIC NON-INFECTIOUS DISEASES, HAVE DEVELOPMENTAL ORIGIN. DEVELOPMENTAL ORIGINS OF DISEASES ARE MAINLY DUE TO GAMETES AND EARLY LIFE DEVELOPMENT STAGE BEING EXPOSED TO ADVERSE ENVIRONMENT, RESULTING IN ABNORMAL MODIFICATION OF EPIGENETIC AND STABLE INHERITANCE TO THE ADULT STAGE, WHICH COULD MAKE THE RISK OF VARIOUS LONG-TERM DISEASES OF INDIVIDUALS HIGH. THE THEORY OF DEVELOPMENTAL ORIGIN PROVIDES A NEW PERSPECTIVE FOR THE OCCURRENCE AND DEVELOPMENT OF DISEASES, AND ALSO PROVIDES A THEORETICAL BASIS FOR DISEASE PREVENTION. ATTACHING IMPORTANCE TO MATERNAL AND CHILD HEALTH CARE AND LIFE-CYCLE MANAGEMENT IS CONDUCIVE TO THE PREVENTION OF DEVELOPMENTAL DISEASES AND IS OF GREAT SIGNIFICANCE TO THE IMPROVEMENT OF POPULATION QUALITY. 2023 17 4342 28 MINIREVIEW: EPIGENETICS OF OBESITY AND DIABETES IN HUMANS. UNDERSTANDING THE DETERMINANTS OF HUMAN HEALTH AND DISEASE IS OVERWHELMINGLY COMPLEX, PARTICULARLY FOR COMMON, LATE-ONSET, CHRONIC DISORDERS, SUCH AS OBESITY AND DIABETES. ELUCIDATING THE GENETIC AND ENVIRONMENTAL FACTORS THAT INFLUENCE SUSCEPTIBILITY TO DISRUPTIONS IN ENERGY HOMEOSTASIS AND METABOLIC REGULATION REMAIN A CHALLENGE, AND PROGRESS WILL ENTAIL THE INTEGRATION OF MULTIPLE ASSESSMENTS OF TEMPORALLY DYNAMIC ENVIRONMENTAL EXPOSURES IN THE CONTEXT OF EACH INDIVIDUAL'S GENOTYPE. TO MEET THIS CHALLENGE, RESEARCHERS ARE INCREASINGLY EXPLORING THE EPIGENOME, WHICH IS THE MALLEABLE INTERFACE OF GENE-ENVIRONMENT INTERACTIONS. EPIGENETIC VARIATION, WHETHER INNATE OR INDUCED, CONTRIBUTES TO VARIATION IN GENE EXPRESSION, THE RANGE OF POTENTIAL INDIVIDUAL RESPONSES TO INTERNAL AND EXTERNAL CUES, AND RISK FOR METABOLIC DISEASE. ULTIMATELY, ADVANCEMENT IN OUR UNDERSTANDING OF CHRONIC DISEASE SUSCEPTIBILITY IN HUMANS WILL DEPEND ON REFINEMENT OF EXPOSURE ASSESSMENT TOOLS AND SYSTEMS BIOLOGY APPROACHES TO INTERPRETATION. IN THIS REVIEW, WE PRESENT RECENT PROGRESS IN EPIGENETICS OF HUMAN OBESITY AND DIABETES, EXISTING CHALLENGES, AND THE POTENTIAL FOR NEW APPROACHES TO UNRAVEL THE COMPLEX BIOLOGY OF METABOLIC DYSREGULATION. 2012 18 6843 29 [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 2543 31 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 20 5161 40 PRECISION AND PERSONALIZED MEDICINE: HOW GENOMIC APPROACH IMPROVES THE MANAGEMENT OF CARDIOVASCULAR AND NEURODEGENERATIVE DISEASE. LIFE EXPECTANCY HAS GRADUALLY GROWN OVER THE LAST CENTURY. THIS HAS DEEPLY AFFECTED HEALTHCARE COSTS, SINCE THE GROWTH OF AN AGING POPULATION IS CORRELATED TO THE INCREASING BURDEN OF CHRONIC DISEASES. THIS REPRESENTS THE INTERESTING CHALLENGE OF HOW TO MANAGE PATIENTS WITH CHRONIC DISEASES IN ORDER TO IMPROVE HEALTH CARE BUDGETS. EFFECTIVE PRIMARY PREVENTION COULD REPRESENT A PROMISING ROUTE. TO THIS END, PRECISION, TOGETHER WITH PERSONALIZED MEDICINE, ARE USEFUL INSTRUMENTS IN ORDER TO INVESTIGATE PATHOLOGICAL PROCESSES BEFORE THE APPEARANCE OF CLINICAL SYMPTOMS AND TO GUIDE PHYSICIANS TO CHOOSE A TARGETED THERAPY TO MANAGE THE PATIENT. CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES REPRESENT SUITABLE MODELS FOR TAKING FULL ADVANTAGE OF PRECISION MEDICINE TECHNOLOGIES APPLIED TO ALL STAGES OF DISEASE DEVELOPMENT. THE AVAILABILITY OF HIGH TECHNOLOGY INCORPORATING ARTIFICIAL INTELLIGENCE AND ADVANCEMENT PROGRESS MADE IN THE FIELD OF BIOMEDICAL RESEARCH HAVE BEEN SUBSTANTIAL TO UNDERSTAND HOW GENES, EPIGENETIC MODIFICATIONS, AGING, NUTRITION, DRUGS, MICROBIOME AND OTHER ENVIRONMENTAL FACTORS CAN IMPACT HEALTH AND CHRONIC DISORDERS. THE AIM OF THE PRESENT REVIEW IS TO ADDRESS HOW PRECISION AND PERSONALIZED MEDICINE CAN BRING GREATER CLARITY TO THE CLINICAL AND BIOLOGICAL COMPLEXITY OF THESE TYPES OF DISORDERS ASSOCIATED WITH HIGH MORTALITY, INVOLVING TREMENDOUS HEALTH CARE COSTS, BY DESCRIBING IN DETAIL THE METHODS THAT CAN BE APPLIED. THIS MIGHT OFFER PRECIOUS TOOLS FOR PREVENTIVE STRATEGIES AND POSSIBLE CLUES ON THE EVOLUTION OF THE DISEASE AND COULD HELP IN PREDICTING MORBIDITY, MORTALITY AND DETECTING CHRONIC DISEASE INDICATORS MUCH EARLIER IN THE DISEASE COURSE. THIS, OF COURSE, WILL HAVE A MAJOR EFFECT ON BOTH IMPROVING THE QUALITY OF CARE AND QUALITY OF LIFE OF THE PATIENTS AND REDUCING TIME EFFORTS AND HEALTHCARE COSTS. 2020