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 3920 23 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 3 6276 31 THE PATHOGENIC ROLE OF DYSREGULATED EPIGENETIC MODIFICATIONS IN AUTOIMMUNE DISEASES. AUTOIMMUNE DISEASES CAN BE CHRONIC WITH RELAPSE OF INFLAMMATORY SYMPTOMS, BUT IT CAN BE ALSO ACUTE AND LIFE-THREATENING IF IMMUNE CELLS DESTROY LIFE-SUPPORTING ORGANS, SUCH AS LUPUS NEPHRITIS. THE ETIOPATHOGENESIS OF AUTOIMMUNE DISEASES HAS BEEN REVEALED AS THAT GENETICS AND ENVIRONMENTAL FACTORS-MEDIATED DYSREGULATED IMMUNE RESPONSES CONTRIBUTE TO THE INITIATION AND DEVELOPMENT OF AUTOIMMUNE DISORDERS. HOWEVER, THE CURRENT UNDERSTANDING OF PATHOGENESIS IS LIMITED AND THE UNDERLYING MECHANISM HAS NOT BEEN WELL DEFINED, WHICH LOWS THE DEVELOPMENT OF NOVEL BIOMARKERS AND NEW THERAPEUTIC STRATEGIES FOR AUTOIMMUNE DISEASES. TO IMPROVE THIS, BROADENING AND DEEPENING OUR UNDERSTANDING OF PATHOGENESIS IS AN UNMET NEED. AS GENETIC SUSCEPTIBILITY CANNOT EXPLAIN THE LOW ACCORDANCE RATE OF INCIDENCE IN HOMOZYGOUS TWINS, EPIGENETIC REGULATIONS MIGHT BE AN ADDITIONAL EXPLANATION. THEREFORE, THIS REVIEW WILL SUMMARIZE CURRENT PROGRESS OF STUDIES ON EPIGENETIC DYSREGULATIONS CONTRIBUTING TO AUTOIMMUNE DISEASES, INCLUDING SLE, RHEUMATOID ARTHRITIS (RA), PSORIASIS, TYPE 1 DIABETES (T1D), AND SYSTEMIC SCLEROSIS (SSC), HOPEFULLY PROVIDING OPINIONS ON ORIENTATION OF FUTURE RESEARCH, AS WELL AS DISCUSSING THE CLINICAL UTILIZATION OF POTENTIAL BIOMARKERS AND THERAPEUTIC STRATEGIES FOR THESE DISEASES. 2019 4 258 30 ADVANCES IN PATHOGENESIS AND NANOPARTICLES (NPS)-MEDIATED TREATMENT OF PSORIASIS. PSORIASIS IS A CHRONIC PAPULOSQUAMOUS SKIN DISEASE WITH AN AUTOIMMUNE PATHOGENIC TRAITS AND STRONG GENETIC PREDISPOSITION. IN THE PAST FEW DECADES, WITH THE RAPID DEVELOPMENT OF MOLECULAR BIOLOGY AND CELL BIOLOGY, THE INHERENT PATHOGENESIS OF PSORIASIS HAS BEEN GRADUALLY ELUCIDATED, IN WHICH CYTOKINE INFLAMMATORY LOOPS, CELL SIGNALING PATHWAYS, AND EPIGENETIC FACTORS SUCH AS MIRNAS HAVE BEEN DEMONSTRATED TO PLAY IMPORTANT ROLES IN REGULATING THE DEVELOPMENT AND PROGRESSION OF PSORIASIS. MORE IMPORTANTLY, UNDERSTANDING THE PATHOGENESIS OF PSORIASIS HAS PROMOTED THE DEVELOPMENT OF EFFECTIVE TREATMENT FOR PSORIASIS. IN THIS REVIEW, WE SYSTEMICALLY SUMMARIZED THE MOLECULAR MECHANISMS REGULATING THE DEVELOPMENT AND PROGRESSION PSORIASIS, INTRODUCED VARIOUS THERAPEUTICS USED FOR CLINICAL PSORIASIS THERAPY, AND HIGHLIGHTED THE RECENT ADVANCES IN NANOPARTICLES (NPS)-MEDIATED DRUG DELIVERY FOR PSORIASIS TREATMENT. 2022 5 2686 16 EVIDENCE FOR THE INVOLVEMENT OF EPIGENETICS IN THE PROGRESSION OF RENAL FIBROGENESIS. EPIGENETICS ARE OMNIPRESENT IN EUKARYOTIC CELLS AND INFLUENCE CELL DIFFERENTIATION AND MAINTENANCE OF CELL METABOLISM IN HEALTH AND DISEASE. HERE, WE DISCUSS HOW THE 'SECOND GENETIC CODE' IMPACTS THE FATE OF THE INJURED KIDNEY. WE PROVIDE A GLIMPSE OF HOW RECENT INSIGHTS INTO EPIGENETIC MECHANISMS OF CHRONIC KIDNEY DISEASE MIGHT LEAD TO NOVEL DIAGNOSTIC AND THERAPEUTIC TOOLS. 2014 6 3173 21 GUT MICROBIOTA-MICRORNA INTERACTIONS IN ANKYLOSING SPONDYLITIS. ANKYLOSING SPONDYLITIS (AS) IS A CHRONIC AUTOIMMUNE INFLAMMATORY DISABILITY THAT IS PART OF THE RHEUMATIC DISEASE GROUP OF SPONDYLOARTHROPATHIES. AS COMMONLY INFLUENCES THE JOINTS OF THE AXIAL SKELETON. THE CONTRIBUTIONS TO AS PATHOGENESIS OF GENETIC SUSCEPTIBILITY (PARTICULARLY HLA-B27 AND ERAP-1) AND EPIGENETIC MODIFICATIONS, LIKE NON-CODING RNAS, AS WELL AS ENVIRONMENTAL FACTORS, HAVE BEEN INVESTIGATED OVER THE LAST FEW YEARS. BUT THE FUNDAMENTAL ETIOLOGY OF AS REMAINS ELUSIVE TO DATE. THE EVIDENCE SUMMARIZED HERE INDICATES THAT IN THE IMMUNOPATHOGENESIS OF AS, MICRORNAS AND THE GUT MICROBIOME PERFORM CRITICAL FUNCTIONS. WE DISCUSS SIGNIFICANT ADVANCES IN THE IMMUNOLOGICAL MECHANISMS UNDERLYING AS AND ADDRESS POTENTIAL CROSS-TALK BETWEEN THE GUT MICROBIOME AND HOST MICRORNAS. THIS CRITICAL INTERACTION IMPLICATES A CO-EVOLUTIONARY SYMBIOTIC LINK BETWEEN HOST IMMUNITY AND THE GUT MICROBIOME. 2021 7 6784 19 [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 8 1243 20 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 9 1879 26 EMERGING ROLES OF NON-CODING RNAS IN PSORIASIS PATHOGENESIS. PSORIASIS IS A COMPLEX GENETIC SKIN DISORDER TYPICALLY MANIFESTED BY RED, SCALY, AND ITCHY PLAQUES MOST COMMONLY OVER THE SCALP, TRUNK, ELBOWS, AND KNEES. HISTOPATHOLOGICAL FEATURES INCLUDE THICKENING OF THE EPIDERMAL LAYER DUE TO HYPER-PROLIFERATION AND ABNORMAL DIFFERENTIATION OF EPIDERMAL KERATINOCYTES ALONG WITH INFILTRATION OF IMMUNE CELLS IN THE PSORIATIC SKIN. IT IS A CHRONIC INFLAMMATORY RELAPSING DISEASE, AND THERE IS CURRENTLY NO PERMANENT CURE FOR PSORIASIS. PROPER MEDICATIONS CAN REDUCE THE SEVERITY OF THE DISEASE AND IMPROVE THE QUALITY OF LIFE OF THE PATIENTS. WHILE THE GENETIC COMPONENTS OF PSORIASIS PATHOGENESIS ARE WELL EXPLORED, THE FULL UNDERSTANDING OF ITS EPIGENETIC COMPONENT REMAINS ELUSIVE. NON-CODING RNAS (NCRNAS) ARE DOCUMENTED TO REGULATE VARIOUS EPIGENETIC PROCESSES THAT LEAD TO THE PATHOGENESIS OF DIFFERENT DISEASES INCLUDING PSORIASIS. IN THIS REVIEW, WE HAVE DISCUSSED THE MOLECULAR INTERPLAY OF DIFFERENT NCRNAS IN PSORIASIS PATHOGENESIS. THE ROLES OF MICRORNAS (MIRNAS) IN PSORIASIS ARE PRETTY WELL STUDIED, WHEREAS THE ROLES OF LONG NONCODING RNAS (LNCRNAS) AND CIRCULAR RNAS (CIRCRNAS) ARE EMERGING. THIS REVIEW PROVIDES IDEAS COVERING SOME OF THE LATEST FINDINGS OF DIFFERENT MODES OF FUNCTIONS PLAYED BY THOSE DIFFERENT NCRNAS DOCUMENTED IN THE LITERATURE. AS AN EVER-EVOLVING TOPIC, SOME WORKS ARE STILL ONGOING AS WELL AS THERE ARE SEVERAL FIELDS THAT NEED RIGOROUS SCIENTIFIC VENTURES. WE HAVE PROPOSED THE AREAS WHICH CLAIM MORE EXPLORATIONS TO BETTER UNDERSTAND THE ROLES PLAYED BY THE NCRNAS IN PSORIASIS PATHOGENESIS. 2023 10 3776 26 INTERACTIONS BETWEEN DYSLIPIDEMIA AND THE IMMUNE SYSTEM AND THEIR RELEVANCE AS PUTATIVE THERAPEUTIC TARGETS IN ATHEROSCLEROSIS. CARDIOVASCULAR DISEASE (CVD) CONTINUES TO BE A LEADING CAUSE OF DEATH WORLDWIDE WITH ATHEROSCLEROSIS BEING THE MAJOR UNDERLYING PATHOLOGY. THE INTERPLAY BETWEEN LIPIDS AND IMMUNE CELLS IS BELIEVED TO BE A DRIVING FORCE IN THE CHRONIC INFLAMMATION OF THE ARTERIAL WALL DURING ATHEROGENESIS. ATHEROSCLEROSIS IS INITIATED AS LIPID PARTICLES ACCUMULATE AND BECOME TRAPPED IN VESSEL WALLS. THE SUBSEQUENT IMMUNE RESPONSE, INVOLVING BOTH ADAPTIVE AND IMMUNE CELLS, PROGRESSES PLAQUE DEVELOPMENT, WHICH MAY BE EXACERBATED UNDER DYSLIPIDEMIC CONDITIONS. BROAD EVIDENCE, ESPECIALLY FROM ANIMAL MODELS, CLEARLY DEMONSTRATES THE EFFECT OF LIPIDS ON IMMUNE CELLS FROM THEIR DEVELOPMENT IN THE BONE MARROW TO THEIR PHENOTYPIC SWITCHING IN CIRCULATION. INTERESTINGLY, RECENT RESEARCH HAS ALSO SHOWN A LONG-LASTING EPIGENETIC SIGNATURE FROM LIPIDS ON IMMUNE CELLS. TRADITIONALLY, CARDIOVASCULAR THERAPIES HAVE APPROACHED ATHEROSCLEROSIS THROUGH LIPID-LOWERING MEDICATIONS BECAUSE, UNTIL RECENTLY, ANTI-INFLAMMATORY THERAPIES HAVE BEEN LARGELY UNSUCCESSFUL IN CLINICAL TRIALS. HOWEVER, THE RECENT CANAKINUMAB ANTIINFLAMMATORY THROMBOSIS OUTCOMES STUDY (CANTOS) PROVIDED PIVOTAL SUPPORT OF THE INFLAMMATORY HYPOTHESIS OF ATHEROSCLEROSIS IN MAN SPURRING ON ANTI-INFLAMMATORY STRATEGIES TO TREAT ATHEROSCLEROSIS. IN THIS REVIEW, WE DESCRIBE THE INTERACTIONS BETWEEN LIPIDS AND IMMUNE CELLS ALONG WITH THEIR SPECIFIC OUTCOMES AS WELL AS DISCUSS THEIR FUTURE PERSPECTIVE AS POTENTIAL CARDIOVASCULAR TARGETS. 2019 11 539 14 ATHEROSCLEROSIS IS AN EPIGENETIC DISEASE. ATHEROSCLEROSIS IS A CHRONIC INFLAMMATORY AND LIPID-DEPOSITORY DISEASE THAT EVENTUALLY LEADS TO ACUTE CARDIOVASCULAR EVENTS. EMERGING EVIDENCE SUPPORTS THAT EPIGENETIC PROCESSES SUCH AS DNA METHYLATION, HISTONE MODIFICATION, AND NONCODING RNAS PLAY AN IMPORTANT ROLE IN PLAQUE PROGRESSION AND VULNERABILITY, HIGHLIGHTING THE THERAPEUTIC POTENTIAL OF EPIGENETIC DRUGS IN CARDIOVASCULAR THERAPEUTICS. 2018 12 6152 18 THE FUNCTION OF NCRNAS IN RHEUMATIC DISEASES. RHEUMATIC DISEASES ARE A GROUP OF CHRONIC HETEROGENEOUS AUTOIMMUNE DISORDERS CHARACTERIZED BY ABNORMAL REGULATION OF THE INNATE AND ADAPTIVE IMMUNE SYSTEMS. DESPITE EXTENSIVE EFFORTS, THE FULL SPECTRUM OF MOLECULAR FACTORS THAT CONTRIBUTE TO THE PATHOGENESIS OF RHEUMATIC DISEASES REMAINS UNCLEAR. NCRNAS CAN GOVERN GENE EXPRESSION AT THE TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL LEVELS IN MULTIPLE DISEASES. RECENT STUDIES HAVE DEMONSTRATED AN IMPORTANT ROLE FOR NCRNAS, SUCH AS MIRNAS AND LNCRNAS, IN THE DEVELOPMENT OF IMMUNE CELLS AND RHEUMATIC DISEASES. HERE, WE FOCUS ON THE EPIGENETIC REGULATORY ROLES OF NCRNAS IN THE PATHOGENESIS OF RHEUMATIC DISEASES AND AS BIOMARKERS OF DISEASE STATE. 2019 13 4844 28 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 14 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 15 2460 30 EPIGENETIC THERAPIES FOR OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS AN AGE-ASSOCIATED DISEASE CHARACTERIZED BY CHRONIC JOINT PAIN RESULTING FROM DEGRADATION OF ARTICULAR CARTILAGE, INFLAMMATION OF THE SYNOVIAL LINING, AND CHANGES TO THE SUBCHONDRAL BONE. DESPITE THE WIDE PREVALENCE, NO FDA-APPROVED DISEASE-MODIFYING DRUGS EXIST. RECENT EVIDENCE HAS DEMONSTRATED THAT EPIGENETIC DYSREGULATION OF MULTIPLE MOLECULAR PATHWAYS UNDERLIES OA PATHOGENESIS, PROVIDING A NEW MECHANISTIC AND THERAPEUTIC AXIS WITH THE ADVANTAGE OF TARGETING MULTIPLE DEREGULATED PATHWAYS SIMULTANEOUSLY. IN THIS REVIEW, WE FOCUS ON THE EPIGENETIC REGULATORS THAT HAVE BEEN IMPLICATED IN OA, THEIR INDIVIDUAL ROLES, AND POTENTIAL CROSSTALK. FINALLY, WE DISCUSS THE PHARMACOLOGICAL MOLECULES THAT CAN MODULATE THEIR ACTIVITIES AND DISCUSS THE POTENTIAL ADVANTAGES AND CHALLENGES ASSOCIATED WITH EPIGENOME-BASED THERAPEUTICS FOR OA. 2020 16 4145 27 MECHANISMS OF VASCULAR AGING. AGING OF THE VASCULATURE PLAYS A CENTRAL ROLE IN MORBIDITY AND MORTALITY OF OLDER PEOPLE. TO DEVELOP NOVEL TREATMENTS FOR AMELIORATION OF UNSUCCESSFUL VASCULAR AGING AND PREVENTION OF AGE-RELATED VASCULAR PATHOLOGIES, IT IS ESSENTIAL TO UNDERSTAND THE CELLULAR AND FUNCTIONAL CHANGES THAT OCCUR IN THE VASCULATURE DURING AGING. IN THIS REVIEW, THE PATHOPHYSIOLOGICAL ROLES OF FUNDAMENTAL CELLULAR AND MOLECULAR MECHANISMS OF AGING, INCLUDING OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, IMPAIRED RESISTANCE TO MOLECULAR STRESSORS, CHRONIC LOW-GRADE INFLAMMATION, GENOMIC INSTABILITY, CELLULAR SENESCENCE, EPIGENETIC ALTERATIONS, LOSS OF PROTEIN HOMEOSTASIS, DEREGULATED NUTRIENT SENSING, AND STEM CELL DYSFUNCTION IN THE VASCULAR SYSTEM ARE CONSIDERED IN TERMS OF THEIR CONTRIBUTION TO THE PATHOGENESIS OF BOTH MICROVASCULAR AND MACROVASCULAR DISEASES ASSOCIATED WITH OLD AGE. THE IMPORTANCE OF PROGERONIC AND ANTIGERONIC CIRCULATING FACTORS IN RELATION TO DEVELOPMENT OF VASCULAR AGING PHENOTYPES ARE DISCUSSED. FINALLY, FUTURE DIRECTIONS AND OPPORTUNITIES TO DEVELOP NOVEL INTERVENTIONS TO PREVENT/DELAY AGE-RELATED VASCULAR PATHOLOGIES BY TARGETING FUNDAMENTAL CELLULAR AND MOLECULAR AGING PROCESSES ARE PRESENTED. 2018 17 5359 24 REBOOTING REGULATORY T CELL AND DENDRITIC CELL FUNCTION IN IMMUNE-MEDIATED INFLAMMATORY DISEASES: BIOMARKER AND THERAPY DISCOVERY UNDER A MULTI-OMICS LENS. IMMUNE-MEDIATED INFLAMMATORY DISEASES (IMIDS) ARE A GROUP OF AUTOIMMUNE AND CHRONIC INFLAMMATORY DISORDERS WITH CONSTANTLY INCREASING PREVALENCE IN THE MODERN WORLD. THE VAST MAJORITY OF IMIDS DEVELOP AS A CONSEQUENCE OF COMPLEX MECHANISMS DEPENDENT ON GENETIC, EPIGENETIC, MOLECULAR, CELLULAR, AND ENVIRONMENTAL ELEMENTS, THAT LEAD TO DEFECTS IN IMMUNE REGULATORY GUARDIANS OF TOLERANCE, SUCH AS DENDRITIC (DCS) AND REGULATORY T (TREGS) CELLS. AS A RESULT OF THIS DYSFUNCTION, IMMUNE TOLERANCE COLLAPSES AND PATHOGENESIS EMERGES. DEEPER UNDERSTANDING OF SUCH DISEASE DRIVING MECHANISMS REMAINS A MAJOR CHALLENGE FOR THE PREVENTION OF INFLAMMATORY DISORDERS. THE RECENT RENAISSANCE IN HIGH THROUGHPUT TECHNOLOGIES HAS ENABLED THE INCREASE IN THE AMOUNT OF DATA COLLECTED THROUGH MULTIPLE OMICS LAYERS, WHILE ADDITIONALLY NARROWING THE RESOLUTION DOWN TO THE SINGLE CELL LEVEL. IN LIGHT OF THE AFOREMENTIONED, THIS REVIEW FOCUSES ON DCS AND TREGS AND DISCUSSES HOW MULTI-OMICS APPROACHES CAN BE HARNESSED TO CREATE ROBUST CELL-BASED IMID BIOMARKERS IN HOPE OF LEADING TO MORE EFFICIENT AND PATIENT-TAILORED THERAPEUTIC INTERVENTIONS. 2022 18 3011 22 GENETICS AND EPIGENETICS IN THE FIBROGENIC EVOLUTION OF CHRONIC LIVER DISEASES. RECENT YEARS HAVE SEEN UNPRECEDENTED PROGRESS IN THE IDENTIFICATION AND CHARACTERIZATION OF GENETIC INFORMATION RELATED TO CHRONIC LIVER DISEASES (CLDS). HOWEVER, DESPITE THE CONCEPTUAL BENEFIT IN EARLY RECOGNITION OF AT-RISK POPULATIONS AMENABLE TO PRE-EMPTIVE TREATMENT AND/OR SURVEILLANCE STRATEGIES, RECENT GENOMIC RESEARCH IN THE FIELD HAS PLACED FOCUS ON UNRAVELLING THE GENETIC ARCHITECTURE OF DISEASE SUSCEPTIBILITY, WHILE DATA ON GENETIC MARKERS ANTICIPATING AN ACCELERATED FIBROGENESIS IN AN INDIVIDUAL ARE STILL LIMITED. LIKEWISE, SEQUENCE VARIATION ASSIGNING RAPID FIBROGENIC EVOLUTION COMMON TO CLDS IRRESPECTIVE OF ETIOLOGY ARE POORLY DEFINED ASIDE FROM PNPLA3 (ADIPONUTRIN) AS A PROMINENT EXCEPTION. THE EMERGING FIELD OF EPIGENETICS IN HEPATOLOGY HAS MOSTLY BEEN STUDIED UNDER THE PERSPECTIVE OF GENE REGULATION, LESS SO AS A HERITABLE ALTERATION IN GENE ACTIVITY. IN THIS ARTICLE WE WILL CRITICALLY DISCUSS RECENT FINDINGS IN GENOMIC HEPATOLOGY WITH SPECIAL FOCUS ON THE (EPI)GENETIC CONTRIBUTION TO THE FIBROGENIC EVOLUTION OF CLDS. 2011 19 6101 20 THE EMERGING ROLE OF EPIGENETICS IN THE IMMUNE RESPONSE TO VACCINATION AND INFECTION: A SYSTEMATIC REVIEW. EXTENSIVE RESEARCH HAS HIGHLIGHTED THE ROLE OF INFECTION-INDUCED EPIGENETIC EVENTS IN THE DEVELOPMENT OF CANCER. MORE RECENTLY, ATTENTION HAS FOCUSED ON THE ABILITY OF NON-CARCINOGENIC INFECTIONS, AS WELL AS VACCINES, TO MODIFY THE HUMAN EPIGENOME AND MODULATE THE IMMUNE RESPONSE. THIS REVIEW EXPLORES THIS RAPIDLY EVOLVING AREA OF INVESTIGATION AND OUTLINES THE MANY AND VARIED WAYS IN WHICH VACCINATION AND NATURAL INFECTION CAN INFLUENCE THE HUMAN EPIGENOME FROM MODULATION OF THE INNATE AND ADAPTIVE IMMUNE RESPONSE, TO BIOLOGICAL AGEING AND MODIFICATION OF DISEASE RISK. THE IMPLICATIONS OF THESE EPIGENETIC CHANGES ON IMMUNE REGULATION AND THEIR POTENTIAL APPLICATION TO THE DIAGNOSIS AND TREATMENT OF CHRONIC INFECTION AND VACCINE DEVELOPMENT ARE ALSO DISCUSSED. 2020 20 6454 28 THIRD JESUS CULEBRAS LECTURE - MOLECULAR BIOLOGY AND CLINICAL NUTRITION; WHERE DO WE STAND AND WHERE DO WE GO? NUTRITION PLAYS A FUNDAMENTAL ROLE IN THE MAINTENANCE OF HEALTH AND THE TREATMENT OF DISEASE, AND SERVES AS THE CROSSROADS FOR MANY DISCIPLINES. BIOCHEMISTRY AND MOLECULAR BIOLOGY REPRESENTS A KEY BRAND OF SCIENCE TO ASCERTAIN THE MECHANISM OF ACTION OF NUTRIENTS AND OTHER FOOD BIOACTIVE COMPOUNDS IN HEALTH AND DISEASE. THE AIM OF THE PRESENT JESUS M. CULEBRAS LECTURE IS TO CONSIDER THE FUTURE OF THE RELATIONSHIPS BETWEEN MOLECULAR BIOLOGY AND CLINICAL NUTRITION AND TO DISCUSS THE USE OF MOLECULAR AND GENETIC TOOLS TO STUDY MOLECULAR RESPONSES TO DIETARY FACTORS AND THE METABOLIC CONSEQUENCES OF FOOD AND TO CONSIDER MAJOR CHALLENGES ON HUMAN NUTRITION SCIENCES IN THE 21(ST) CENTURY. PARTICULAR EMPHASIS IS GIVEN TO THE IDENTIFICATION AND USE OF NOVEL BIOMARKERS IN INFLAMMATORY DISEASES. LIKEWISE, THE IMPORTANCE OF THE HUMAN MICROBIOME AND HOW MICROORGANISMS CAN BE SAFELY UTILIZED IN THE PREVENTION AND MANAGEMENT OF INFECTIOUS AND CHRONIC DISEASES ARE DISCUSSED. MOREOVER, THE KEY ROLE OF NUTRIGENETICS, NUTRIGENOMICS AND EPIGENETICS IN THE NEW ERA OF NUTRITION IS CONSIDERED. NUTRIGENETICS REFERS TO THE ROLE OF DNA SEQUENCE VARIATION IN THE RESPONSES TO NUTRIENTS, WHEREAS NUTRIGENOMICS IS THE STUDY OF THE ROLE OF NUTRIENTS IN GENE EXPRESSION. EPIGENETICS IS THE STUDY OF MITOTICALLY HERITABLE ALTERATIONS IN GENE EXPRESSION POTENTIAL THAT ARE NOT CAUSED BY DNA SEQUENCE ALTERATIONS. IN THE PAST DECADE, IT HAS INCREASINGLY BEEN RECOGNIZED THAT DYSREGULATION OF EPIGENETIC MECHANISMS MAY PLAY AN IMPORTANT ROLE IN HUMAN DISEASE. INDEED, THERE IS INCREASING INTEREST IN EPIGENETIC MECHANISMS UNDERLYING PHENOTYPE MODIFICATION MODULATED BY NUTRIENTS. FURTHER RESEARCH IN THOSE AREAS SHOULD CONTRIBUTE TO EVALUATE FUNCTIONALITY OF SPECIFIC NUTRIENTS AND BIOACTIVE COMPOUNDS IN CLINICAL NUTRITION AND ALLOW PERSONALIZED NUTRITIONAL ADVICE. 2013