1 6784 87 [CHRONIC STRESS AND EPIGENETICS. RELATION BETWEEN ACADEMIC SCIENCES AND THEOLOGY]. THE AUTHOR GIVES A SHORT ACCOUNT ON THE PRINCIPLES OF SELYE'S STRESS THEORY, AND DISCUSSES SIMILARITIES AND DISSIMILARITIES OF ACUTE AND CHRONIC STRESS. BOTH THE EXTERNAL, AND THE INTERNAL ENVIRONMENT, AS WELL AS THE PSYCHO-MENTAL STATUS ARE INVOLVED IN THE NOTION OF THE ENVIRONMENT. BASIC PRINCIPLES OF EPIGENETICS ARE REVIEWED: INTERACTION BETWEEN ENVIRONMENT AND GENES, NEUROENDOCRINE AND ENZYMATIC MECHANISMS INVOLVED IN SILENCING AND ACTIVATION OF GENES, NOTIONS OF PHENOTYPIC PLASTICITY, AND EPIGENETIC REPROGRAMMING ARE DISCUSSED. EPIGENETIC MECHANISMS OF INTERRELATION BETWEEN PATHOLOGICAL CLINICAL STATES (DISEASES) AND THE CHARACTERISTIC PHENOTYPES, CAUSATIVE ROLE OF PSYCHO-MENTAL STATUS IN EVOKING PATHOLOGICAL SOMATIC ALTERATIONS, AND THE POTENTIAL THERAPEUTIC CONSEQUENCES ARE BRIEFLY DISCUSSED. THE ETIOLOGICAL ROLE OF CHRONIC, CIVILIZATION STRESS IN PRODUCING THE WORLDWIDE INCREMENT OF CARDIOVASCULAR MORBIDITY IS CITED, ARGUMENTATION AND CRITICISM OF THE CURRENT THERAPEUTICAL PRACTICE IS DISCUSSED. THE AUTHOR CONCLUDES THAT RECENT ADVANCES IN EPIGENETIC KNOWLEDGE SEEM TO SOLVE THE CONTROVERSY BETWEEN THE ACADEMIC AND THEOLOGICAL SCIENCES. 2012 2 4534 22 MULTIPLE REGULATIONS OF KEAP1/NRF2 SYSTEM BY DIETARY PHYTOCHEMICALS. KEAP1/NRF2 SYSTEM PLAYS A CRITICAL ROLE ON CELLULAR PROTECTION BY REGULATING MANY ANTIOXIDANT AND DETOXIFICATION ENZYME GENES THROUGH THE ANTIOXIDANT RESPONSE ELEMENT (ARE). THUS, IT MUST WORK CONSTANTLY TO PREVENT THE ACCUMULATION OF REACTIVE OXYGEN SPECIES (ROS) BECAUSE EXCESS ROS ARE ASSOCIATED WITH MANY DISEASES SUCH AS CANCER, CARDIOVASCULAR COMPLICATIONS, INFLAMMATION, AND NEURODEGENERATION. DIETARY PHYTOCHEMICALS WIDELY DISTRIBUTING IN FRUITS AND VEGETABLES HAVE BEEN CONSIDERED TO POSSESS CANCER CHEMOPREVENTIVE POTENTIAL THROUGH THE INDUCTION OF KEAP1/NRF2 SYSTEM-MEDIATED ANTIOXIDANT AND DETOXIFICATION ENZYMES IN A VARIETY OF MANNERS. THE DATA ARE EXTENSIVE AND ARE NOT WELL CLASSIFIED ON THE MOLECULAR MECHANISMS. IN THIS REVIEW, WE FIRST BRIEFLY INTRODUCE THE CURRENT KNOWLEDGE ON KEAP1/NRF2 SYSTEM REGULATION INCLUDING KEAP1-DEPENDENT AND KEAP1-INDEPENDENT CASCADES, AND EPIGENETIC PATHWAY. THEN, WE SUMMARIZE THE MOLECULAR TARGETS OF KEAP1/NRF2 SYSTEM BY DIETARY PHYTOCHEMICALS, AND FINALLY REVIEW THE CROSSTALK BETWEEN KEAP1/NRF2 SYSTEM AND OTHER CELLULAR SIGNALING PATHWAYS TO REGULATE DIVERSE CHRONIC DISEASES BY DIETARY PHYTOCHEMICALS. THESE COMPREHENSIVE DATA WILL HELP US TO UNDERSTAND THE POTENTIAL EFFECTS OF DIETARY PHYTOCHEMICALS ON THE PREVENTION OF CHRONIC DISEASES AND MAINTENANCE OF HUMAN HEALTH. 2016 3 6786 20 [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 4 1415 24 DIETARY POLYPHENOLS AND THEIR RELATIONSHIP TO THE MODULATION OF NON-COMMUNICABLE CHRONIC DISEASES AND EPIGENETIC MECHANISMS: A MINI-REVIEW. CHRONIC NON-COMMUNICABLE DISEASES (NCDS) HAVE BEEN CONSIDERED A GLOBAL HEALTH PROBLEM, CHARACTERIZED AS DISEASES OF MULTIPLE FACTORS, WHICH ARE DEVELOPED THROUGHOUT LIFE, AND REGARDLESS OF GENETICS AS A RISK FACTOR OF IMPORTANT RELEVANCE, THE INCREASE IN MORTALITY ATTRIBUTED TO THE DISEASE TO ENVIRONMENTAL FACTORS AND THE LIFESTYLE ONE LEADS. ALTHOUGH THE REACTIVE SPECIES (ROS/RNS) ARE NECESSARY FOR SEVERAL PHYSIOLOGICAL PROCESSES, THEIR OVERPRODUCTION IS DIRECTLY RELATED TO THE PATHOGENESIS AND AGGRAVATION OF NCDS. IN CONTRAST, DIETARY POLYPHENOLS HAVE BEEN WIDELY ASSOCIATED WITH MINIMIZING OXIDATIVE STRESS AND INFLAMMATION. IN ADDITION TO THEIR ANTIOXIDANT POWER, POLYPHENOLS HAVE ALSO DRAWN ATTENTION FOR BEING ABLE TO MODULATE BOTH GENE EXPRESSION AND MODIFY EPIGENETIC ALTERATIONS, SUGGESTING AN ESSENTIAL INVOLVEMENT IN THE PREVENTION AND/OR DEVELOPMENT OF SOME PATHOLOGIES. THEREFORE, THIS REVIEW BRIEFLY EXPLAINED THE MECHANISMS IN THE DEVELOPMENT OF SOME NCDS, FOLLOWED BY A SUMMARY OF SOME EVIDENCE RELATED TO THE INTERACTION OF POLYPHENOLS IN OXIDATIVE STRESS, AS WELL AS THE MODULATION OF EPIGENETIC MECHANISMS INVOLVED IN THE MANAGEMENT OF NCDS. 2023 5 1246 24 CURRENT EPIGENETIC ASPECTS THE CLINICAL KIDNEY RESEARCHER SHOULD EMBRACE. CHRONIC KIDNEY DISEASE (CKD), AFFECTING 10-12% OF THE WORLD'S ADULT POPULATION, IS ASSOCIATED WITH A CONSIDERABLY ELEVATED RISK OF SERIOUS COMORBIDITIES, IN PARTICULAR, PREMATURE VASCULAR DISEASE AND DEATH. ALTHOUGH A WIDE SPECTRUM OF CAUSATIVE FACTORS HAS BEEN IDENTIFIED AND/OR SUGGESTED, THERE IS STILL A LARGE GAP OF KNOWLEDGE REGARDING THE UNDERLYING MECHANISMS AND THE COMPLEXITY OF THE CKD PHENOTYPE. EPIGENETIC FACTORS, WHICH CALIBRATE THE GENETIC CODE, ARE EMERGING AS IMPORTANT PLAYERS IN THE CKD-ASSOCIATED PATHOPHYSIOLOGY. IN THIS ARTICLE, WE REVIEW SOME OF THE CURRENT KNOWLEDGE ON EPIGENETIC MODIFICATIONS AND ASPECTS ON THEIR ROLE IN THE PERTURBED URAEMIC MILIEU, AS WELL AS THE PROSPECT OF APPLYING EPIGENOTYPE-BASED DIAGNOSTICS AND PREVENTIVE AND THERAPEUTIC TOOLS OF CLINICAL RELEVANCE TO CKD PATIENTS. THE PRACTICAL REALIZATION OF SUCH A PARADIGM WILL REQUIRE THAT RESEARCHERS APPLY A HOLISTIC APPROACH, INCLUDING THE FULL SPECTRUM OF THE EPIGENETIC LANDSCAPE AS WELL AS THE VARIABILITY BETWEEN AND WITHIN TISSUES IN THE URAEMIC MILIEU. 2017 6 1977 16 EPIGENETIC ALTERATIONS IN ACUTE KIDNEY INJURY. ACUTE KIDNEY INJURY (AKI) IS A RISK FACTOR FOR CHRONIC KIDNEY DISEASE AND DEATH. DESPITE PROGRESS MADE IN UNDERSTANDING THE CELLULAR AND MOLECULAR BASIS OF AKI PATHOGENESIS THERE HAS BEEN NO IMPROVEMENT IN THE HIGH MORTALITY RATE FROM THIS DISEASE IN DECADES. EPIGENETICS IS ONE OF THE MOST INTENSIVELY STUDIED FIELDS OF BIOLOGY TODAY AND REPRESENTS A NEW PARADIGM FOR UNDERSTANDING THE PATHOPHYSIOLOGY OF DISEASE. ALTHOUGH EPIGENETICS OF AKI IS A NASCENT FIELD, THE AVAILABLE INFORMATION ALREADY IS PROVIDING COMPELLING EVIDENCE THAT CHROMATIN BIOLOGY PLAYS A CRITICAL ROLE IN THIS DISEASE. IN THIS ARTICLE WE EXPLORE WHAT IS KNOWN ABOUT THE CONTRIBUTION OF EPIGENETIC MECHANISMS TO THE PATHOPHYSIOLOGY OF AKI AND HOW THIS KNOWLEDGE ALREADY IS GUIDING THE DEVELOPMENT OF NEW DIAGNOSTIC TOOLS AND EPIGENETIC THERAPIES. 2013 7 6254 20 THE MICROBIOME AND IRRITABLE BOWEL SYNDROME - A REVIEW ON THE PATHOPHYSIOLOGY, CURRENT RESEARCH AND FUTURE THERAPY. IRRITABLE BOWEL SYNDROME (IBS) IS A FUNCTIONAL DISORDER WHICH AFFECTS A LARGE PROPORTION OF THE POPULATION GLOBALLY. THE PRECISE ETIOLOGY OF IBS IS STILL UNKNOWN, ALTHOUGH CONSENSUS UNDERSTANDING PROPOSES IBS TO BE OF MULTIFACTORIAL ORIGIN WITH YET UNDEFINED SUBTYPES. GENETIC AND EPIGENETIC FACTORS, STRESS-RELATED NERVOUS AND ENDOCRINE SYSTEMS, IMMUNE DYSREGULATION AND THE BRAIN-GUT AXIS SEEM TO BE CONTRIBUTING FACTORS THAT PREDISPOSE INDIVIDUALS TO IBS. IN ADDITION TO FOOD HYPERSENSITIVITY, TOXINS AND ADVERSE LIFE EVENTS, CHRONIC INFECTIONS AND DYSBIOTIC GUT MICROBIOTA HAVE BEEN SUGGESTED TO TRIGGER IBS SYMPTOMS IN TANDEM WITH THE PREDISPOSING FACTORS. THIS REVIEW WILL SUMMARIZE THE PATHOPHYSIOLOGY OF IBS AND THE ROLE OF GUT MICROBIOTA IN RELATION TO IBS. CURRENT METHODOLOGIES FOR MICROBIOME STUDIES IN IBS SUCH AS GENOME SEQUENCING, METAGENOMICS, CULTUROMICS AND ANIMAL MODELS WILL BE DISCUSSED. THE MYRIAD OF THERAPY OPTIONS SUCH AS IMMUNOGLOBULINS (IMMUNE-BASED THERAPY), PROBIOTICS AND PREBIOTICS, DIETARY MODIFICATIONS INCLUDING FODMAP RESTRICTION DIET AND GLUTEN-FREE DIET, AS WELL AS FECAL TRANSPLANTATION WILL BE REVIEWED. FINALLY THIS REVIEW WILL HIGHLIGHT FUTURE DIRECTIONS IN IBS THERAPY RESEARCH, INCLUDING IDENTIFICATION OF NEW MOLECULAR TARGETS, APPLICATION OF 3-D GUT MODEL, GUT-ON-A-CHIP AND PERSONALIZED THERAPY. 2019 8 4589 24 NANOPARTICLES IN THE DIAGNOSIS AND TREATMENT OF VASCULAR AGING AND RELATED DISEASES. AGING-INDUCED ALTERNATIONS OF VASCULATURE STRUCTURES, PHENOTYPES, AND FUNCTIONS ARE KEY IN THE OCCURRENCE AND DEVELOPMENT OF VASCULAR AGING-RELATED DISEASES. MULTIPLE MOLECULAR AND CELLULAR EVENTS, SUCH AS OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, VASCULAR INFLAMMATION, CELLULAR SENESCENCE, AND EPIGENETIC ALTERATIONS ARE HIGHLY ASSOCIATED WITH VASCULAR AGING PHYSIOPATHOLOGY. ADVANCES IN NANOPARTICLES AND NANOTECHNOLOGY, WHICH CAN REALIZE SENSITIVE DIAGNOSTIC MODALITIES, EFFICIENT MEDICAL TREATMENT, AND BETTER PROGNOSIS AS WELL AS LESS ADVERSE EFFECTS ON NON-TARGET TISSUES, PROVIDE AN AMAZING WINDOW IN THE FIELD OF VASCULAR AGING AND RELATED DISEASES. THROUGHOUT THIS REVIEW, WE PRESENTED CURRENT KNOWLEDGE ON CLASSIFICATION OF NANOPARTICLES AND THE RELATIONSHIP BETWEEN VASCULAR AGING AND RELATED DISEASES. IMPORTANTLY, WE COMPREHENSIVELY SUMMARIZED THE POTENTIAL OF NANOPARTICLES-BASED DIAGNOSTIC AND THERAPEUTIC TECHNIQUES IN VASCULAR AGING AND RELATED DISEASES, INCLUDING CARDIOVASCULAR DISEASES, CEREBROVASCULAR DISEASES, AS WELL AS CHRONIC KIDNEY DISEASES, AND DISCUSSED THE ADVANTAGES AND LIMITATIONS OF THEIR CLINICAL APPLICATIONS. 2022 9 3169 25 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 10 424 21 ANTHOCYANINS: FROM MECHANISMS OF REGULATION IN PLANTS TO HEALTH BENEFITS IN FOODS. ANTHOCYANINS REPRESENT THE MAJOR RED, PURPLE, AND BLUE PIGMENTS IN MANY FLOWERS, FRUITS, VEGETABLES, AND CEREALS. THEY ARE ALSO RECOGNIZED AS IMPORTANT HEALTH-PROMOTING COMPONENTS IN THE HUMAN DIET WITH PROTECTIVE EFFECTS AGAINST MANY CHRONIC DISEASES, INCLUDING CARDIOVASCULAR DISEASES, OBESITY, AND CANCER. ANTHOCYANIN BIOSYNTHESIS HAS BEEN STUDIED EXTENSIVELY, AND BOTH BIOSYNTHETIC AND KEY REGULATORY GENES HAVE BEEN ISOLATED IN MANY PLANT SPECIES. HERE, WE WILL PROVIDE AN OVERVIEW OF RECENT PROGRESS IN UNDERSTANDING THE ANTHOCYANIN BIOSYNTHETIC PATHWAY IN PLANTS, FOCUSING ON THE TRANSCRIPTION FACTORS CONTROLLING ACTIVATION OR REPRESSION OF ANTHOCYANIN ACCUMULATION IN CEREALS AND FRUITS OF DIFFERENT PLANT SPECIES, WITH SPECIAL EMPHASIS ON THE DIFFERENCES IN MOLECULAR MECHANISMS BETWEEN MONOCOT AND DICOT PLANTS. RECENTLY, NEW INSIGHT INTO THE TRANSCRIPTIONAL REGULATION OF THE ANTHOCYANIN BIOSYNTHESIS, INCLUDING POSITIVE AND NEGATIVE FEEDBACK CONTROL AS WELL AS EPIGENETIC AND POST-TRANSLATIONAL REGULATION OF MYB-BHLH-WD40 COMPLEXES, HAS BEEN GAINED. WE WILL CONSIDER HOW KNOWLEDGE OF REGULATORY MECHANISMS HAS HELPED TO PRODUCE ANTHOCYANIN-ENRICHED FOODS THROUGH CONVENTIONAL BREEDING AND METABOLIC ENGINEERING. ADDITIONALLY, WE WILL BRIEFLY DISCUSS THE BIOLOGICAL ACTIVITIES OF ANTHOCYANINS AS COMPONENTS OF THE HUMAN DIET AND RECENT FINDINGS DEMONSTRATING THE IMPORTANT HEALTH BENEFITS OF ANTHOCYANIN-RICH FOODS AGAINST CHRONIC DISEASES. 2021 11 4716 21 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 12 4520 22 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 13 5309 19 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 14 3920 18 LINKING IMMUNITY, EPIGENETICS, AND CANCER IN INFLAMMATORY BOWEL DISEASE. MOST OF WHAT IS KNOWN ABOUT THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE (IBD) PERTAINS TO COMPLEX INTERPLAY BETWEEN HOST GENETICS, IMMUNITY, AND ENVIRONMENTAL FACTORS. EPIGENETIC MODIFICATIONS PLAY PIVOTAL ROLES IN INTESTINAL IMMUNITY AND MUCOSAL HOMEOSTASIS AS WELL AS MEDIATING GENE-ENVIRONMENT INTERACTIONS. IN THIS ARTICLE, WE PROVIDE A HISTORICAL ACCOUNT OF EPIGENETIC RESEARCH EITHER DIRECTLY RELATED OR PERTINENT TO THE PATHOGENESIS AND MANAGEMENT OF IBD. WE FURTHER COLLATE EMERGING EVIDENCE SUPPORTING ROLES FOR EPIGENETIC MECHANISMS IN RELEVANT ASPECTS OF IBD BIOLOGY, INCLUDING DEREGULATED IMMUNITY, HOST-PATHOGEN RECOGNITION AND MUCOSAL INTEGRITY. FINALLY, WE HIGHLIGHT KEY EPIGENETIC MECHANISMS THAT LINK CHRONIC INFLAMMATION TO SPECIFIC IBD COMORBIDITIES, INCLUDING COLITIS-ASSOCIATED CANCER AND DISCUSS THEIR POTENTIAL UTILITY AS NOVEL BIOMARKERS OR PHARMACOLOGIC TARGETS IN IBD THERAPY. 2014 15 6860 19 [OBESITY EPIDEMIC: CURRENT EVIDENCE, CHALLENGES AND FUTURE DIRECTIONS]. THE OBESITY EPIDEMIC IS A PHENOMENON THAT HAS BEEN WIDELY STUDIED IN RECENT DECADES BUT IS STILL INCOMPLETELY UNDERSTOOD, AND ITS CONTROL IS FAR FROM THE DESIRABLE LEVEL IN VIEW OF THE INCREASING PREVALENCE FIGURES OBSERVED WORLDWIDE. THIS PAPER CONDUCTS A NARRATIVE REVIEW WITH THE AIM OF PROVIDING UPDATED EVIDENCE ON THE GLOBAL OBESITY EPIDEMIC, AND PARTICULARLY ON THE SITUATION IN LATIN AMERICA AND ARGENTINA, IDENTIFYING THE MAIN CHALLENGES AND FUTURE DIRECTIONS FOR ADDRESSING THIS PUBLIC HEALTH PROBLEM. IT FIRST DESCRIBES THE CURRENT BURDEN AND INCREASING TRENDS IN THE PREVALENCE OF OBESITY, IN THE OVERALL POPULATION AND BY POPULATION GROUPS, AND ITS POSSIBLE ASSOCIATION WITH GENETIC AND EPIGENETIC ASPECTS. IT ALSO SUMMARIZES THE DIRECT AND INDIRECT SOCIOECONOMIC CONSEQUENCES OF THIS EPIDEMIC, AS WELL AS RECENT STRATEGIES AND INITIATIVES FOCUSED ON OBESITY PREVENTION, WITH SPECIAL ATTENTION TO THOSE REPORTED AS THE MOST EFFICIENT IN THE LATIN AMERICAN CONTEXT. THIS REVIEW IDENTIFIED SOME PENDING CHALLENGES IN THE REGION, THE INTEGRATED APPROACH TO THE DOUBLE BURDEN OF MALNUTRITION AND THE GROWING CHILDHOOD OVERWEIGHT; AND IT POINTS OUT SOME EMERGING APPROACHES, SUCH AS THE SYNDEMIC APPROACH, AS POTENTIALLY USEFUL TO UNDERSTAND AND ADDRESS THIS COMPLEX PROBLEM IN THE CURRENT CONTEXT. IN CONCLUSION, IT HIGHLIGHTS THE IMPORTANCE OF IMPLEMENTING RENEWED, MORE EFFICIENT AND EVIDENCE-BASED STRATEGIES TO CONTROL THE GROWING PREVALENCE OF OBESITY, WHICH WOULD ALSO IMPACT ON THE BURDEN OF RELATED CHRONIC DISEASES, AND THUS ON THE ECONOMY AND WELL-BEING OF LATIN AMERICAN SOCIETIES. 2023 16 617 17 BIOACTIVE FOOD COMPOUNDS, EPIGENETICS AND CHRONIC DISEASE PREVENTION: FOCUS ON EARLY-LIFE INTERVENTIONS WITH POLYPHENOLS. CONSUMPTION OF BIOACTIVE COMPOUNDS SUCH AS POLYPHENOLS, ISOTHIOCYANATES, SULFUR-CONTAINING COMPOUNDS AND TERPENOIDS, FOUND IN FRUITS AND VEGETABLES, IS ASSOCIATED WITH PREVENTION OF CHRONIC DISEASE. THESE BIOACTIVE FOOD COMPOUNDS ELICIT THEIR PROTECTIVE EFFECTS THROUGH COMPLEX MECHANISMS AT THE CELLULAR AND MOLECULAR, INCLUDING EPIGENETIC LEVELS. ACCORDING TO THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) PARADIGM, IN UTERO EXPOSURE TO STRESSORS SUCH AS MALNUTRITION THROUGH MATERNAL DIET WOULD IMPAIR FETAL DEVELOPMENT AND EPIGENETICALLY PROGRAM INCREASED RISK OF METABOLIC DISEASES AND SOME CANCERS IN ADULT LIFE. IN ADDITION, A ROLE FOR FATHERS DIET DURING PRECONCEPTION ON THEIR OFFSPRING HEALTH AND CHRONIC DISEASE SUSCEPTIBILITY HAS ALSO EMERGED. THIS HIGHLIGHTS EARLY LIFE AS A PROMISING WINDOW OF OPPORTUNITY FOR STARTING DIETARY INTERVENTIONS FOCUSING ON PREVENTING CHRONIC DISEASES. HOWEVER, KNOWLEDGE ON THE POTENTIAL BENEFICIAL IMPACT OF EARLY LIFE EXPOSURE TO BIOACTIVE FOOD COMPOUNDS IS LIMITED. AMONG THE STUDIES THAT HAVE INVESTIGATED BIOACTIVE FOOD COMPOUNDS IN THE CONTEXT OF DOHAD, MOST HAVE FOCUSED ON THE IMPACT OF DIETARY POLYPHENOLS. THUS, IN THIS REVIEW WE DISCUSS EXPERIMENTAL EVIDENCE SUPPORTING A ROLE FOR THE DIETARY POLYPHENOLS RESVERATROL, GENISTEIN, EPIGALLOCATECHIN-3-GALLATE AND ANTHOCYANINS IN CHRONIC DISEASE PREVENTION CONSIDERING A PERSPECTIVE FROM EARLY-LIFE INTERVENTIONS THROUGH MATERNAL AND PATERNAL DIETS AND FOCUSING ON EPIGENETICS AS A POTENTIAL UNDERLYING MECHANISM. 2019 17 2543 23 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 18 498 21 ASSOCIATION BETWEEN DIABETES AND CANCER. CURRENT MECHANISTIC INSIGHTS INTO THE ASSOCIATION AND FUTURE CHALLENGES. COMPELLING PIECES OF EPIDEMIOLOGICAL, CLINICAL, AND EXPERIMENTAL RESEARCH HAVE DEMONSTRATED THAT DIABETES MELLITUS (DM) IS A MAJOR RISK FACTOR ASSOCIATED WITH INCREASED CANCER INCIDENCE AND MORTALITY IN MANY HUMAN NEOPLASMS. IN THE PATHOPHYSIOLOGY CONTEXT OF DM, MANY OF THE MAIN CLASSICAL ACTORS ARE RELEVANT ELEMENTS THAT CAN FUEL THE DIFFERENT STEPS OF THE CARCINOGENESIS PROCESS. HYPERGLYCEMIA, HYPERINSULINEMIA, METABOLIC INFLAMMATION, AND DYSLIPIDEMIA ARE AMONG THE CLASSIC CONTRIBUTORS TO THIS ASSOCIATION. FURTHERMORE, NEW EMERGING ACTORS HAVE RECEIVED PARTICULAR ATTENTION IN THE LAST FEW YEARS, AND COMPELLING DATA SUPPORT THAT THE MICROBIOME, THE EPIGENETIC CHANGES, THE RETICULUM ENDOPLASMIC STRESS, AND THE INCREASED GLYCOLYTIC INFLUX ALSO PLAY IMPORTANT ROLES IN PROMOTING THE DEVELOPMENT OF MANY CANCER TYPES. THE ARSENAL OF GLUCOSE-LOWERING THERAPEUTIC AGENTS USED FOR TREATING DIABETES IS WIDE AND DIVERSE, AND A GROWING BODY OF DATA RAISED DURING THE LAST TWO DECADES HAS TRIED TO CLARIFY THE CONTRIBUTION OF THERAPEUTIC AGENTS TO THIS ASSOCIATION. HOWEVER, THIS RESEARCH AREA REMAINS CONTROVERSIAL, BECAUSE SOME ANTI-DIABETIC DRUGS ARE NOW CONSIDERED AS EITHER PROMOTORS OR PROTECTING ELEMENTS. IN THE PRESENT REVIEW, WE INTEND TO HIGHLIGHT THE COMPELLING EPIDEMIOLOGICAL SHREDS OF EVIDENCE THAT SUPPORT THIS ASSOCIATION, AS WELL AS THE MECHANISTIC CONTRIBUTIONS OF MANY OF THESE POTENTIAL PATHOLOGICAL MECHANISMS, SOME CONTROVERSIAL POINTS AS WELL AS FUTURE CHALLENGES. 2023 19 757 18 CARTILAGE REPAIR BY MESENCHYMAL STEM CELLS: CLINICAL TRIAL UPDATE AND PERSPECTIVES. OSTEOARTHRITIS IS A DEGENERATIVE DISEASE OF JOINTS WITH DESTRUCTION OF ARTICULAR CARTILAGE ASSOCIATED WITH SUBCHONDRAL BONE HYPERTROPHY AND INFLAMMATION. OA IS THE LEADING CAUSE OF JOINT PAIN RESULTING IN SIGNIFICANT WORSENING OF THE QUALITY-OF-LIFE IN THE ELDERLY. NUMEROUS EFFORTS HAVE BEEN SPENT TO OVERCOME THE INHERENTLY POOR HEALING ABILITY OF ARTICULAR CARTILAGE. MESENCHYMAL STEM CELLS (MSCS) HAVE BEEN IN THE LIMELIGHT OF CELL-BASED THERAPIES TO PROMOTE CARTILAGE REPAIR. DESPITE PROGRESSIVE ADVANCEMENTS IN MSC MANIPULATION AND THE INTRODUCTION OF VARIOUS BIOACTIVE SCAFFOLDS AND GROWTH FACTORS IN PRECLINICAL STUDIES, CURRENT CLINICAL TRIALS ARE STILL AT EARLY STAGES WITH PRELIMINARY AIMS TO EVALUATE SAFETY, FEASIBILITY AND EFFICACY. THIS REVIEW SUMMARISES RECENTLY REPORTED MSC-BASED CLINICAL TRIALS AND DISCUSSES NEW RESEARCH DIRECTIONS WITH PARTICULAR FOCUS ON THE POTENTIAL APPLICATION OF MSC-DERIVED EXTRACELLULAR VEHICLES, MIRNAS AND ADVANCED GENE EDITING TECHNIQUES WHICH MAY SHED LIGHT ON THE DEVELOPMENT OF NOVEL TREATMENT STRATEGIES. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: THIS REVIEW SUMMARISES RECENT MSC-RELATED CLINICAL RESEARCH THAT FOCUSES ON CARTILAGE REPAIR. WE ALSO PROPOSE A NOVEL POSSIBLE TRANSLATIONAL DIRECTION FOR HYALINE CARTILAGE FORMATION AND A NEW PARADIGM MAKING USE OF EXTRA-CELLULAR SIGNALLING AND EPIGENETIC REGULATION IN THE APPLICATION OF MSCS FOR CARTILAGE REPAIR. 2017 20 1867 19 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