1 6451 116 THERAPIES TARGETING EPIGENETIC ALTERATIONS IN ACUTE KIDNEY INJURY-TO-CHRONIC KIDNEY DISEASE TRANSITION. ACUTE KIDNEY INJURY (AKI) WAS PREVIOUSLY THOUGHT TO BE A MERELY TRANSIENT EVENT; HOWEVER, RECENT EPIDEMIOLOGICAL EVIDENCE SUPPORTS THE EXISTENCE OF A CAUSAL RELATIONSHIP BETWEEN AKI EPISODES AND SUBSEQUENT PROGRESSION TO CHRONIC KIDNEY DISEASE (CKD). ALTHOUGH THE PATHOPHYSIOLOGY OF THIS AKI-TO-CKD TRANSITION IS NOT FULLY UNDERSTOOD, IT IS MEDIATED BY THE INTERPLAY AMONG MULTIPLE COMPONENTS OF THE KIDNEY INCLUDING TUBULAR EPITHELIAL CELLS, ENDOTHELIAL CELLS, PERICYTES, INFLAMMATORY CELLS, AND MYOFIBROBLASTS. EPIGENETIC ALTERATIONS INCLUDING HISTONE MODIFICATION, DNA METHYLATION, NON-CODING RNAS, AND CHROMATIN CONFORMATIONAL CHANGES, ARE ALSO EXPECTED TO BE LARGELY INVOLVED IN THE PATHOPHYSIOLOGY AS A "MEMORY" OF THE INITIAL INJURY THAT CAN PERSIST AND PREDISPOSE TO CHRONIC PROGRESSION OF FIBROSIS. EACH EPIGENETIC MODIFICATION HAS A GREAT POTENTIAL AS A THERAPEUTIC TARGET OF AKI-TO-CKD TRANSITION; TIMELY AND TARGET-SPECIFIC EPIGENETIC INTERVENTIONS TO THE VARIOUS TEMPORAL STAGES OF AKI-TO-CKD TRANSITION WILL BE THE KEY TO FUTURE THERAPEUTIC APPLICATIONS IN CLINICAL PRACTICE. THIS REVIEW ELABORATES ON THE LATEST KNOWLEDGE OF EACH MECHANISM AND THE CURRENTLY AVAILABLE THERAPEUTIC AGENTS THAT TARGET EPIGENETIC MODIFICATION IN THE CONTEXT OF AKI-TO-CKD TRANSITION. FURTHER STUDIES WILL ELUCIDATE MORE DETAILED MECHANISMS AND NOVEL THERAPEUTIC TARGETS OF AKI-TO-CKD TRANSITION. 2022 2 2178 25 EPIGENETIC MECHANISMS OF MACROPHAGE ACTIVATION IN TYPE 2 DIABETES. THE ALARMING RISE OF OBESITY AND TYPE 2 DIABETES (T2D) HAS PUT A TREMENDOUS STRAIN ON GLOBAL HEALTHCARE SYSTEMS. OVER THE PAST DECADE EXTENSIVE RESEARCH HAS FOCUSED ON THE ROLE OF MACROPHAGES AS KEY MEDIATORS OF INFLAMMATION IN T2D. THE INFLAMMATORY ENVIRONMENT IN THE OBESE ADIPOSE TISSUE AND PANCREATIC BETA-CELL ISLETS CREATES AND PERPETUATES IMBALANCED INFLAMMATORY MACROPHAGE ACTIVATION. CONSEQUENCES OF THIS CHRONIC LOW-GRADE INFLAMMATION INCLUDE INSULIN RESISTANCE IN THE ADIPOSE TISSUE AND PANCREATIC BETA-CELL DYSFUNCTION. RECENTLY, THE EMERGING FIELD OF EPIGENETICS HAS PROVIDED NEW INSIGHTS INTO THE PATHOGENESIS OF T2D, WHILE ALSO AFFORDING POTENTIAL NEW OPPORTUNITIES FOR TREATMENT. IN MACROPHAGES, EPIGENETIC MECHANISMS ARE INCREASINGLY BEING RECOGNIZED AS CRUCIAL CONTROLLERS OF THEIR PHENOTYPE. HERE, WE FIRST DESCRIBE THE ROLE OF MACROPHAGES IN T2D. THEN WE ELABORATE ON EPIGENETIC MECHANISMS THAT REGULATE MACROPHAGE ACTIVATION, THEREBY FOCUSING ON T2D. NEXT, WE HIGHLIGHT HOW DIABETIC CONDITIONS SUCH AS HYPERLIPIDEMIA AND HYPERGLYCEMIA COULD INDUCE EPIGENETIC CHANGES THAT PROMOTE AN INFLAMMATORY MACROPHAGE PHENOTYPE. IN CONCLUSION WE DISCUSS POSSIBLE THERAPEUTIC INTERVENTIONS BY TARGETING MACROPHAGE EPIGENETICS AND SPECULATE ON FUTURE RESEARCH DIRECTIONS. 2017 3 2788 45 FACTORS AFFECTING THE TRANSITION OF ACUTE KIDNEY INJURY TO CHRONIC KIDNEY DISEASE: POTENTIAL MECHANISMS AND FUTURE PERSPECTIVES. ACUTE KIDNEY INJURY (AKI) IS DEFINED AS A RAPID LOSS OF KIDNEY FUNCTION CHARACTERISED BY INFLAMMATION AND CELL DEATH, ULTIMATELY LEADING TO FURTHER FUNCTIONAL AND STRUCTURAL RENAL ALTERATIONS. BASED ON EXPERIMENTAL AND EPIDEMIOLOGICAL PIECES OF EVIDENCE, AKI MAY PROGRESS TO CHRONIC KIDNEY DISEASE (CKD) EVEN AFTER A RECOVERY PERIOD DUE TO MALADAPTIVE REPAIR AND OTHER UNDERLYING MECHANISMS SUCH AS HEIGHTENED WNT SIGNALLING, OVERSTIMULATION OF THE RENIN-ANGIOTENSIN-ALDOSTERONE-SYSTEM (RAAS) PATHWAY, EPIGENETIC ALTERATIONS AND INHIBITION OF HYPOXIA-INDUCIBLE FACTOR (HIF) DEPENDENT DEFENCES. IT HAS BEEN REPORTED THAT RAAS ACTIVATION SUBSEQUENT TO RENAL INSULT MEDIATES INFLAMMATORY AND FIBROTIC MECHANISMS, WHICH ARE A HALLMARK OF CKD. MOREOVER, INTERESTING EVIDENCE REGARDING THE EXPOSURE-DEPENDENT DUAL ROLE OF WNT SIGNALLING IN BOTH INJURY AND REPAIR, EPIGENETIC CHANGES UNDERLYING KIDNEY DISEASE SUGGEST A POTENTIAL THERAPEUTIC ROLE OF THESE PATHWAYS IN AKI TO CKD CONTINUUM. IN ADDITION, THE HYPOXIA-INDEPENDENT RENAL BENEFITS OF ERYTHROPOIETIN SUCH AS ANTI-APOPTOSIS AND TUBULAR REGENERATION ALSO PRESENT AN AUSPICIOUS TARGET WHICH COULD BE USEFUL IN CLINICAL SETTINGS. IN THIS REVIEW, THE SPECIFIC ROLES OF THESE PATHWAYS IN KIDNEY DISEASE, THEIR PATHOLOGICAL MECHANISMS AND THERAPEUTIC STRATEGIES ARE DISCUSSED. MOREOVER, NOTABLE REPORTS CONCERNING STEM CELL THERAPY WHICH HOLD PROMISE IN HALTING AKI-CKD CONTINUUM WILL BE ELABORATED. 2019 4 6732 18 WESTERN DIET AND THE IMMUNE SYSTEM: AN INFLAMMATORY CONNECTION. THE CONSUMPTION OF WESTERN-TYPE CALORICALLY RICH DIETS COMBINED WITH CHRONIC OVERNUTRITION AND A SEDENTARY LIFESTYLE IN WESTERN SOCIETIES EVOKES A STATE OF CHRONIC METABOLIC INFLAMMATION, TERMED METAFLAMMATION. METAFLAMMATION CONTRIBUTES TO THE DEVELOPMENT OF MANY PREVALENT NON-COMMUNICABLE DISEASES (NCDS), AND THESE LIFESTYLE-ASSOCIATED PATHOLOGIES REPRESENT A RISING PUBLIC HEALTH PROBLEM WITH GLOBAL EPIDEMIC DIMENSIONS. A BETTER UNDERSTANDING OF HOW MODERN LIFESTYLE AND WESTERN DIET (WD) ACTIVATE IMMUNE CELLS IS ESSENTIAL FOR THE DEVELOPMENT OF EFFICIENT PREVENTIVE AND THERAPEUTIC STRATEGIES FOR COMMON NCDS. HERE, WE REVIEW THE CURRENT MECHANISTIC UNDERSTANDING OF HOW THE WESTERN LIFESTYLE CAN INDUCE METAFLAMMATION, AND WE DISCUSS HOW THIS KNOWLEDGE CAN BE TRANSLATED TO PROTECT THE PUBLIC FROM THE HEALTH BURDEN ASSOCIATED WITH THEIR SELECTED LIFESTYLE. 2019 5 5951 28 TARGETING THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM TO PREVENT HYPERTENSION AND KIDNEY DISEASE OF DEVELOPMENTAL ORIGINS. THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS) IS IMPLICATED IN HYPERTENSION AND KIDNEY DISEASE. THE DEVELOPING KIDNEY CAN BE PROGRAMMED BY VARIOUS EARLY-LIFE INSULTS BY SO-CALLED RENAL PROGRAMMING, RESULTING IN HYPERTENSION AND KIDNEY DISEASE IN ADULTHOOD. THIS THEORY IS KNOWN AS DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD). CONVERSELY, EARLY RAAS-BASED INTERVENTIONS COULD REVERSE PROGRAM PROCESSES TO PREVENT A DISEASE FROM OCCURRING BY SO-CALLED REPROGRAMMING. IN THE CURRENT REVIEW, WE MAINLY SUMMARIZE (1) THE CURRENT KNOWLEDGE ON THE RAAS IMPLICATED IN RENAL PROGRAMMING; (2) CURRENT EVIDENCE SUPPORTING THE CONNECTIONS BETWEEN THE ABERRANT RAAS AND OTHER MECHANISMS BEHIND RENAL PROGRAMMING, SUCH AS OXIDATIVE STRESS, NITRIC OXIDE DEFICIENCY, EPIGENETIC REGULATION, AND GUT MICROBIOTA DYSBIOSIS; AND (3) AN OVERVIEW OF HOW RAAS-BASED REPROGRAMMING INTERVENTIONS MAY PREVENT HYPERTENSION AND KIDNEY DISEASE OF DEVELOPMENTAL ORIGINS. TO ACCELERATE THE TRANSITION OF RAAS-BASED INTERVENTIONS FOR PREVENTION OF HYPERTENSION AND KIDNEY DISEASE, AN EXTENDED COMPREHENSION OF THE RAAS IMPLICATED IN RENAL PROGRAMMING IS NEEDED, AS WELL AS A GREATER FOCUS ON FURTHER CLINICAL TRANSLATION. 2021 6 1241 29 CURRENT AND FUTURE NUTRITIONAL STRATEGIES TO MODULATE INFLAMMATORY DYNAMICS IN METABOLIC DISORDERS. OBESITY, TYPE 2 DIABETES, AND OTHER METABOLIC DISORDERS HAVE A LARGE IMPACT ON GLOBAL HEALTH, ESPECIALLY IN WESTERN COUNTRIES. AN IMPORTANT HALLMARK OF METABOLIC DISORDERS IS CHRONIC LOW-GRADE INFLAMMATION. A KEY PLAYER IN CHRONIC LOW-GRADE INFLAMMATION IS DYSMETABOLISM, WHICH IS DEFINED AS THE INABILITY TO KEEP HOMEOSTASIS RESULTING IN LOSS OF LIPID CONTROL, OXIDATIVE STRESS, INFLAMMATION, AND INSULIN RESISTANCE. ALTHOUGH OFTEN NOT YET DETECTABLE IN THE CIRCULATION, CHRONIC LOW-GRADE INFLAMMATION CAN BE PRESENT IN ONE OR MULTIPLE ORGANS. THE RESPONSE TO A METABOLIC CHALLENGE CONTAINING LIPIDS MAY MAGNIFY DYSFUNCTIONALITIES AT THE TISSUE LEVEL, CAUSING AN OVERFLOW OF INFLAMMATORY MARKERS INTO THE CIRCULATION AND HENCE ALLOW DETECTION OF EARLY LOW-GRADE INFLAMMATION. HERE, WE SUMMARIZE THE EVIDENCE OF SUCCESSFUL APPLICATION OF METABOLIC CHALLENGE TESTS IN TYPE 2 DIABETES, METABOLIC SYNDROME, OBESITY, AND UNHEALTHY AGING. WE ALSO REVIEW HOW METABOLIC CHALLENGE TESTS HAVE BEEN SUCCESSFULLY APPLIED TO EVALUATE NUTRITIONAL INTERVENTION EFFECTS, INCLUDING AN "ANTI-INFLAMMATORY" MIXTURE, DARK CHOCOLATE, WHOLE GRAIN WHEAT AND OVERFEEDING. ADDITIONALLY, WE ELABORATE ON FUTURE STRATEGIES TO (RE)GAIN INFLAMMATORY FLEXIBILITY. THROUGH EPIGENETIC AND METABOLIC REGULATION, THE INFLAMMATORY RESPONSE MAY BE TRAINED BY REGULAR MILD AND METABOLIC TRIGGERS, WHICH CAN BE UNDERSTOOD FROM THE PERSPECTIVE OF TRAINED IMMUNITY, HORMESIS AND PRO-RESOLUTION. NEW STRATEGIES TO OPTIMIZE DYNAMICS OF INFLAMMATION MAY BECOME AVAILABLE. 2019 7 6786 26 [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 8 5309 26 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 9 4381 40 MITOCHONDRIAL DYSFUNCTION AND THE AKI-TO-CKD TRANSITION. ACUTE KIDNEY INJURY (AKI) HAS BEEN WIDELY RECOGNIZED AS AN IMPORTANT RISK FACTOR FOR THE OCCURRENCE AND DEVELOPMENT OF CHRONIC KIDNEY DISEASE (CKD). EVEN MILDER AKI HAS ADVERSE CONSEQUENCES AND COULD PROGRESS TO RENAL FIBROSIS, WHICH IS THE ULTIMATE COMMON PATHWAY FOR VARIOUS TERMINAL KIDNEY DISEASES. THUS, IT IS URGENT TO DEVELOP A STRATEGY TO HINDER THE TRANSITION FROM AKI TO CKD. SOME MECHANISMS OF THE AKI-TO-CKD TRANSITION HAVE BEEN REVEALED, SUCH AS NEPHRON LOSS, CELL CYCLE ARREST, PERSISTENT INFLAMMATION, ENDOTHELIAL INJURY WITH VASCULAR RAREFACTION, AND EPIGENETIC CHANGES. PREVIOUS STUDIES HAVE ELUCIDATED THE PIVOTAL ROLE OF MITOCHONDRIA IN ACUTE INJURIES AND DEMONSTRATED THAT THE FITNESS OF THIS ORGANELLE IS A MAJOR DETERMINANT IN BOTH THE PATHOGENESIS AND RECOVERY OF ORGAN FUNCTION. RECENT RESEARCH HAS SUGGESTED THAT DAMAGE TO MITOCHONDRIAL FUNCTION IN EARLY AKI IS A CRUCIAL FACTOR LEADING TO TUBULAR INJURY AND PERSISTENT RENAL INSUFFICIENCY. DYSREGULATION OF MITOCHONDRIAL HOMEOSTASIS, ALTERATIONS IN BIOENERGETICS, AND ORGANELLE STRESS CROSS TALK CONTRIBUTE TO THE AKI-TO-CKD TRANSITION. IN THIS REVIEW, WE FOCUS ON THE PATHOPHYSIOLOGY OF MITOCHONDRIA IN RENAL RECOVERY AFTER AKI AND PROGRESSION TO CKD, CONFIRMING THAT TARGETING MITOCHONDRIA REPRESENTS A POTENTIALLY EFFECTIVE THERAPEUTIC STRATEGY FOR THE PROGRESSION OF AKI TO CKD. 2020 10 4589 25 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 11 1243 22 CURRENT CONCEPTS IN CHRONIC INFLAMMATORY DISEASES: INTERACTIONS BETWEEN MICROBES, CELLULAR METABOLISM, AND INFLAMMATION. RECENT RESEARCH INDICATES THAT CHRONIC INFLAMMATORY DISEASES, INCLUDING ALLERGIES AND AUTOIMMUNE AND NEUROPSYCHIATRIC DISEASES, SHARE COMMON PATHWAYS OF CELLULAR AND MOLECULAR DYSREGULATION. IT WAS THE AIM OF THE INTERNATIONAL VON-BEHRING-RONTGEN SYMPOSIUM (OCTOBER 16-18, 2014, IN MARBURG, GERMANY) TO DISCUSS RECENT DEVELOPMENTS IN THIS FIELD. THESE INCLUDE A CONCEPT OF BIODIVERSITY; THE CONTRIBUTION OF URBANIZATION, LIFESTYLE FACTORS, AND NUTRITION (EG, VITAMIN D); AND NEW MECHANISMS OF METABOLIC AND IMMUNE DYSREGULATION, SUCH AS EXTRACELLULAR AND INTRACELLULAR RNAS AND CELLULAR AND MITOCHONDRIAL STRESS. EPIGENETIC MECHANISMS CONTRIBUTE FURTHER TO ALTERED GENE EXPRESSION AND THEREFORE TO THE DEVELOPMENT OF CHRONIC INFLAMMATION. THESE NOVEL FINDINGS PROVIDE THE FOUNDATION FOR FURTHER DEVELOPMENT OF PREVENTIVE AND THERAPEUTIC STRATEGIES. 2016 12 2459 18 EPIGENETIC THERAPIES FOR NON-ONCOLOGY INDICATIONS. CHRONIC AND DEGENERATIVE DISORDERS ARE A MAJOR, AND GROWING, HUMAN HEALTH BURDEN, AND CURRENT TREATMENTS ARE IN MANY CASES INADEQUATE OR VERY EXPENSIVE. EPIGENETIC THERAPIES ARE ATTRACTIVE OPTIONS FOR TREATING SUCH DISORDERS BECAUSE THEY MANIPULATE THE PROCESSES THAT MAINTAIN CELLS IN AN ABNORMAL TRANSCRIPTIONAL STATE. THE CHALLENGES LIE IN IDENTIFYING THE MOST APPROPRIATE DISEASES AND THE ENZYMES THAT SHOULD BE TARGETED. THIS REVIEW DESCRIBES THE DIFFERENT APPROACHES THAT CAN BE USED TO ADDRESS THIS PROBLEM, FOCUSING PARTICULARLY ON CNS DISORDERS (ESPECIALLY MENTAL RETARDATION, NEURODEGENERATIVE DISEASE, PSYCHIATRIC DISORDERS AND DRUG ADDICTION), DIABETES AND DIABETIC COMPLICATIONS, AND AUTOIMMUNITY AND INFLAMMATORY DISEASES. 2010 13 1977 28 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 14 4844 29 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 15 1387 33 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 16 4966 31 PATHOGENOMICS OF ENDOMETRIOSIS DEVELOPMENT. FOR OVER 100 YEARS, ENDOMETRIOSIS, AS A CHRONIC, ESTROGEN-DEPENDENT, INFLAMMATORY, HERITABLE DISEASE AFFECTING APPROXIMATELY 5(-)10% OF WOMEN IN REPRODUCTIVE AGE HAS BEEN THE FOCUS OF CLINICIANS AND SCIENTISTS. IN SPITE OF NUMEROUS ENVIRONMENTAL, GENETIC, EPIGENETIC, ENDOCRINE, AND IMMUNOLOGICAL STUDIES, OUR KNOWLEDGE OF ENDOMETRIOSIS IS STILL FRAGMENTARY, AND ITS PRECISE PATHOPHYSIOLOGY AND PATHOGENOMICS REMAIN A MYSTERY. THE IMPLEMENTATION OF NEW TECHNOLOGIES HAS PROVIDED TREMENDOUS PROGRESS IN UNDERSTANDING THE MANY INTRINSIC MOLECULAR MECHANISMS IN THE DEVELOPMENT OF ENDOMETRIOSIS, WITH PROGENITOR AND STEM CELLS (SCS) OF THE EUTOPIC ENDOMETRIUM AS THE STARTING PLAYERS AND ENDOMETRIOTIC LESIONS AS THE FINAL PATHOMORPHOLOGICAL TRAIT. NOVEL DATA ON THE MOLECULAR, GENETIC, AND EPIGENETIC MECHANISMS OF THE DISEASE ARE BRIEFLY OUTLINED. WE HYPOTHESIZE THE EXISTENCE OF AN ENDOMETRIOSIS DEVELOPMENT GENETIC PROGRAM (EMDP) THAT GOVERNS THE ORIGIN OF ENDOMETRIUM STEM CELLS PROGRAMMED FOR ENDOMETRIOSIS (1), THEIR TRANSITION (METAPLASIA) INTO MESENCHYMAL SCS (2), AND THEIR INVASION OF THE PERITONEUM AND PROGRESSION TO ENDOMETRIOTIC LESIONS (3). THE PROS AND CONS OF THE RECENT UNIFYING THEORY OF ENDOMETRIOSIS ARE ALSO DISCUSSED. COMPLEX GENOMIC AND EPIGENETIC INTERACTIONS AT DIFFERENT STAGES OF THE ENDOMETRIOSIS PROCESS RESULT IN DIFFERENT FORMS OF THE DISEASE, WITH SPECIFIC FEATURES AND CLINICAL MANIFESTATIONS. THE SIGNIFICANCE OF THE EMDP IN ELABORATING A NEW STRATEGY FOR ENDOMETRIOSIS PREDICTION, PREVENTION, AND TREATMENT IS DISCUSSED. 2018 17 3920 26 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 18 4520 35 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 19 1233 30 CROSSTALK BETWEEN KIDNEY AND LIVER IN NON-ALCOHOLIC FATTY LIVER DISEASE: MECHANISMS AND THERAPEUTIC APPROACHES. LIVER AND KIDNEY ARE VITAL ORGANS THAT MAINTAIN HOMEOSTASIS AND INJURY TO EITHER OF THEM TRIGGERS PATHOGENIC PATHWAYS AFFECTING THE OTHER. FOR EXAMPLE, NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) PROMOTES THE PROGRESSION OF CHRONIC KIDNEY DISEASE (CKD), VICE VERSA ACUTE KIDNEY INJURY (AKI) ENDORSES THE INDUCTION AND PROGRESSION OF LIVER DYSFUNCTION. PROGRESS IN CLINICAL AND BASIC RESEARCH SUGGEST A ROLE OF EXCESSIVE FRUCTOSE INTAKE, INSULIN RESISTANCE, INFLAMMATORY CYTOKINES PRODUCTION, ACTIVATION OF THE RENIN-ANGIOTENSIN SYSTEM, REDOX IMBALANCE, AND THEIR IMPACT ON EPIGENETIC REGULATION OF GENE EXPRESSION IN THIS CONTEXT. RECENT DEVELOPMENTS IN EXPERIMENTAL AND CLINICAL RESEARCH HAVE IDENTIFIED SEVERAL BIOCHEMICAL AND MOLECULAR PATHWAYS FOR AKI-LIVER INTERACTION, INCLUDING ALTERED LIVER ENZYMES PROFILE, METABOLIC ACIDOSIS, OXIDATIVE STRESS, ACTIVATION OF INFLAMMATORY AND REGULATED CELL DEATH PATHWAYS. THIS REVIEW FOCUSES ON THE CURRENT PRECLINICAL AND CLINICAL FINDINGS ON KIDNEY-LIVER CROSSTALK IN NAFLD-CKD AND AKI-LIVER DYSFUNCTION SETTINGS AND HIGHLIGHTS POTENTIAL MOLECULAR MECHANISMS AND THERAPEUTIC TARGETS. 2022 20 1366 27 DEVELOPMENTAL ORIGINS OF CHRONIC KIDNEY DISEASE: SHOULD WE FOCUS ON EARLY LIFE? CHRONIC KIDNEY DISEASE (CKD) IS BECOMING A GLOBAL BURDEN, DESPITE RECENT ADVANCES IN MANAGEMENT. CKD CAN BEGIN IN EARLY LIFE BY SO-CALLED "DEVELOPMENTAL PROGRAMMING" OR "DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE" (DOHAD). EARLY-LIFE INSULTS CAUSE STRUCTURAL AND FUNCTIONAL CHANGES IN THE DEVELOPING KIDNEY, WHICH IS CALLED RENAL PROGRAMMING. EPIDEMIOLOGICAL AND EXPERIMENTAL EVIDENCE SUPPORTS THE PROPOSITION THAT EARLY-LIFE ADVERSE EVENTS LEAD TO RENAL PROGRAMMING AND MAKE SUBJECTS VULNERABLE TO DEVELOPING CKD AND ITS COMORBIDITIES IN LATER LIFE. IN ADDITION TO LOW NEPHRON ENDOWMENT, SEVERAL MECHANISMS HAVE BEEN PROPOSED FOR RENAL PROGRAMMING. THE DOHAD CONCEPT OPENS A NEW WINDOW TO OFFSET THE PROGRAMMING PROCESS IN EARLY LIFE TO PREVENT THE DEVELOPMENT OF ADULT KIDNEY DISEASE, NAMELY REPROGRAMMING. HERE, WE REVIEW THE KEY THEMES ON THE DEVELOPMENTAL ORIGINS OF CKD. WE HAVE PARTICULARLY FOCUSED ON THE FOLLOWING AREAS: EVIDENCE FROM HUMAN STUDIES SUPPORT FETAL PROGRAMMING OF KIDNEY DISEASE; INSIGHT FROM ANIMAL MODELS OF RENAL PROGRAMMING; HYPOTHETICAL MECHANISMS OF RENAL PROGRAMMING; ALTERATIONS OF RENAL TRANSCRIPTOME IN RESPONSE TO EARLY-LIFE INSULTS; AND THE APPLICATION OF REPROGRAMMING INTERVENTIONS TO PREVENT THE PROGRAMMING OF KIDNEY DISEASE. 2017