1 2224 66 EPIGENETIC MODIFICATIONS IN THE PATHOGENESIS OF SYSTEMIC SCLEROSIS. SYSTEMIC SCLEROSIS IS A RARE CHRONIC AUTOIMMUNE DISEASE, WHICH MAINLY MANIFESTS AS IMMUNE DISORDERS, VASCULAR DAMAGE, AND PROGRESSIVE FIBROSIS. THE ETIOLOGY OF SSC IS COMPLEX AND INVOLVES MULTIPLE FACTORS. BOTH GENETIC AND ENVIRONMENTAL FACTORS ARE INVOLVED IN ITS PATHOGENESIS. AS ONE OF THE MOLECULAR MECHANISMS OF ENVIRONMENTAL FACTORS, EPIGENETIC REGULATION PLAYS AN IMPORTANT ROLE IN THE OCCURRENCE AND DEVELOPMENT OF SYSTEMIC SCLEROSIS, WHICH INVOLVES DNA METHYLATION, HISTONE MODIFICATION AND NON-CODING RNA REGULATION. THIS REVIEW SUMMARIZES RESEARCH ADVANCES IN EPIGENETICS, INCLUDING EXOSOMES, LNCRNA, AND MENTIONS POSSIBLE BIOMARKERS AND THERAPEUTIC TARGETS AMONG THEM. 2022 2 2557 26 EPIGENETICS IN RHEUMATOID ARTHRITIS; FIBROBLAST-LIKE SYNOVIOCYTES AS AN EMERGING PARADIGM IN THE PATHOGENESIS OF THE DISEASE. RHEUMATOID ARTHRITIS (RA) IS CHARACTERIZED BY IMMUNE DYSFUNCTIONS AND CHRONIC INFLAMMATION THAT MAINLY AFFECTS DIARTHRODIAL JOINTS. GENETICS HAS LONG BEEN SURVEYED IN SEARCHING FOR THE ETIOPATHOGENESIS OF THE DISEASE AND PARTIALLY CLARIFIED THE CONUNDRUMS WITHIN THIS CONTEXT. EPIGENETIC ALTERATIONS, SUCH AS DNA METHYLATION, HISTONE MODIFICATIONS, AND NONCODING RNAS, WHICH HAVE BEEN CONSIDERED TO BE INVOLVED IN RA PATHOGENESIS, LIKELY EXPLAIN THE NONGENETIC RISK FACTORS. EPIGENETIC MODIFICATIONS MAY INFLUENCE RA THROUGH FIBROBLAST-LIKE SYNOVIOCYTES (FLSS). IT HAS BEEN SHOWN THAT FLSS PLAY AN ESSENTIAL ROLE IN THE ONSET AND EXACERBATION OF RA, AND THEREFORE, THEY MAY ILLUSTRATE SOME ASPECTS OF RA PATHOGENESIS. THESE CELLS EXHIBIT A UNIQUE DNA METHYLATION PROFILE IN THE EARLY STAGE OF THE DISEASE THAT CHANGES WITH DISEASE PROGRESSION. HISTONE ACETYLATION PROFILE IN RA FLSS IS DISRUPTED THROUGH THE IMBALANCE OF HISTONE ACETYLTRANSFERASES AND HISTONE DEACETYLASE ACTIVITY. FURTHERMORE, DYSREGULATION OF MICRORNAS (MIRNAS) IS IMMENSE. MOST OF THESE MIRNAS HAVE SHOWN AN ABERRANT EXPRESSION IN FLSS THAT ARE INVOLVED IN PROLIFERATION AND CYTOKINE PRODUCTION. BESIDES, DYSREGULATION OF LONG NONCODING RNAS IN FLSS HAS BEEN REVEALED AND ATTRIBUTED TO RA PATHOGENESIS. FURTHER INVESTIGATIONS ARE NEEDED TO GET A BETTER VIEW OF EPIGENETIC ALTERATIONS AND THEIR INTERACTIONS. WE ALSO DISCUSS THE ROLE OF THESE EPIGENETIC ALTERATIONS IN RA PATHOGENESIS AND THEIR THERAPEUTIC POTENTIAL. 2020 3 6107 31 THE EMERGING ROLE OF NONCODING RNAS IN SYSTEMIC LUPUS ERYTHEMATOSUS: NEW INSIGHTS INTO THE MASTER REGULATORS OF DISEASE PATHOGENESIS. AUTO-IMMUNE DISEASES ARE A FORM OF CHRONIC DISORDERS IN WHICH THE IMMUNE SYSTEM DESTROYS THE BODY'S CELLS DUE TO A LOSS OF TOLERANCE TO SELF-ANTIGENS. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE), IDENTIFIED BY THE PRODUCTION OF AUTOANTIBODIES IN DIFFERENT BODY PARTS, IS ONE OF THE MOST WELL-KNOWN EXAMPLES OF THESE DISEASES. ALTHOUGH THE ETIOLOGY OF SLE IS UNCLEAR, THE DISEASE'S PROGRESSION MAY BE AFFECTED BY GENETIC AND ENVIRONMENTAL FACTORS. AS STUDIES IN TWINS PROVIDE ADEQUATE EVIDENCE FOR GENETIC INVOLVEMENT IN THE SLE, OTHER PHENOMENA SUCH AS METALLIZATION, HISTONE MODIFICATIONS, AND ALTERATIONS IN THE EXPRESSION OF NONCODING RNAS (NCRNAS) ALSO INDICATE THE INVOLVEMENT OF EPIGENETIC FACTORS IN THIS DISEASE. AMONG ALL THE EPIGENETIC ALTERATIONS, NCRNAS APPEAR TO HAVE THE MOST CRUCIAL CONTRIBUTION TO THE PATHOGENESIS OF SLE. THE NCRNAS' LENGTH AND SIZE ARE DIVIDED INTO THREE MAIN CLASSES: MICRO RNAS, LONG NONCODING RNAS (LNCRNA), AND CIRCULAR RNAS (CIRCRNAS). ACCUMULATING EVIDENCE SUGGESTS THAT DYSREGULATIONS IN THESE NCRNAS CONTRIBUTED TO THE PATHOGENESIS OF SLE. HENCE, CLARIFYING THE FUNCTION OF THESE GROUPS OF NCRNAS IN THE PATHOPHYSIOLOGY OF SLE PROVIDES A DEEPER UNDERSTANDING OF THE DISEASE. IT ALSO OPENS UP NEW OPPORTUNITIES TO DEVELOP TARGETED THERAPIES FOR THIS DISEASE. 2023 4 763 25 CAUSES OF PULMONARY FIBROSIS IN THE ELDERLY. IDIOPATHIC PULMONARY FIBROSIS (IPF) IS THE MOST COMMON AND MOST LETHAL TYPE OF IDIOPATHIC INTERSTITIAL PNEUMONIA. IT IS A CHRONIC, AGING-ASSOCIATED LUNG DISEASE CHARACTERIZED BY FIBROTIC FOCI AND INFLAMMATORY INFILTRATES, WITH NO CURE AND VERY LIMITED THERAPEUTIC OPTIONS. ALTHOUGH ITS ETIOLOGY IS UNKNOWN, SEVERAL PATHOGENIC PATHWAYS HAVE BEEN DESCRIBED THAT COULD EXPLAIN THIS PROCESS, INVOLVING AGING, ENVIRONMENTAL FACTORS, GENOMIC INSTABILITY, LOSS OF PROTEOSTASIS, TELOMERE ATTRITION, EPIGENETIC CHANGES, MITOCHONDRIAL DYSFUNCTION, CELL SENESCENCE, AND ALTERED INTERCELLULAR COMMUNICATION. ONE OF THE MAIN PROGNOSTIC FACTORS FOR THE DEVELOPMENT OF IPF IN BROAD EPIDEMIOLOGICAL STUDIES IS AGE. THE INCIDENCE INCREASES WITH AGE, MAKING THIS A DISEASE THAT PREDOMINANTLY AFFECTS THE ELDERLY POPULATION, BEING EXCEPTIONAL UNDER 45 YEARS OF AGE. HOWEVER, THE DEGREE TO WHICH EACH OF THESE MECHANISMS IS INVOLVED IN THE ETIOLOGY OF THE UNCONTROLLED FIBROGENESIS THAT DEFINES IPF IS STILL UNKNOWN. CLARIFYING THESE QUESTIONS IS CRUCIAL TO THE DEVELOPMENT OF POINTS OF INTERVENTION IN THE PATHOGENESIS OF THE DISEASE. THIS REVIEW BRIEFLY SUMMARIZES WHAT IS KNOWN ABOUT EACH POSSIBLE ETIOLOGICAL FACTOR, AND THE QUESTIONS THAT MOST URGENTLY NEED TO BE ADDRESSED. 2018 5 3829 26 INVOLVEMENT OF EPIGENETICS IN OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS THE MOST PREVALENT CHRONIC AGE-RELATED ARTHRITIC DISEASE THAT MAINLY AFFECTS THE DIARTHRODIAL JOINTS. NEVERTHELESS, THERE IS NO TREATMENT CURRENTLY AVAILABLE THAT CAN EFFECTIVELY REDUCE SYMPTOMS OR SLOW DOWN OR STOP DISEASE PROGRESSION. THE LACK OF DISEASE-MODIFYING THERAPIES COULD BE EXPLAINED BY THE COMPLEX PATHOGENESIS OF OA, WHICH IS STILL NOT COMPLETELY UNDERSTOOD. INTERTWINED EPIGENETIC MECHANISMS SUCH AS DNA METHYLATION, HISTONE MODIFICATIONS, AND NONCODING RNAS (NCRNAS) HAVE BEEN INDICATED AS IMPORTANT CELLULAR TOOLS TO MAINTAIN TISSUE HOMEOSTASIS UPON ENVIRONMENTAL CHALLENGES. THE CURRENT REVIEW ILLUSTRATES THAT DYSFUNCTIONAL EPIGENETIC CONTROL MECHANISMS IN THE ARTICULAR CARTILAGE LIKELY PLAY AN IMPORTANT ROLE IN DRIVING OA PATHOPHYSIOLOGY. 2017 6 2988 26 GENETIC FACTORS AND SYSTEMIC SCLEROSIS. SYSTEMIC SCLEROSIS (SSC) IS A RARE CONNECTIVE TISSUE DISEASE OF UNKNOWN ETIOLOGY CHARACTERIZED BY CHRONIC INFLAMMATION AND FIBROSIS OF THE SKIN, VASCULAR ABNORMALITIES, AND VARIABLE INVOLVEMENT OF ORGANS INCLUDING KIDNEYS, GASTROINTESTINAL TRACT, HEART, AND LUNGS. SSC SHOWS A COMPLEX ETIOLOGY IN WHICH BOTH ENVIRONMENTAL AND GENETIC FACTORS SEEM TO INFLUENCE THE ONSET AND OUTCOME OF THE DISEASE. WE PROVIDE AN EXTENSIVE OVERVIEW OF THE GENETIC FACTORS AND EPIGENETIC MODIFICATIONS AND WHAT THEIR KNOWLEDGE HAS REVEALED IN TERMS OF ETIOPATHOGENESIS OF SSC. 2016 7 1726 32 DYSREGULATION OF LNCRNAS IN RHEUMATOID ARTHRITIS: BIOMARKERS, PATHOGENESIS AND POTENTIAL THERAPEUTIC TARGETS. RHEUMATOID ARTHRITIS (RA) IS A CHRONIC AUTOIMMUNE DISEASE OF UNKNOWN ETIOLOGY, MAINLY MANIFESTED BY PERSISTENT ABNORMAL PROLIFERATION OF FIBROBLAST-LIKE SYNOVIOCYTES (FLSS), INFLAMMATION, SYNOVIAL HYPERPLASIA AND CARTILAGE EROSION, ACCOMPANIED BY JOINT SWELLING AND JOINT DESTRUCTION. ABNORMAL EXPRESSION OR FUNCTION OF LONG NONCODING RNAS (LNCRNAS) ARE CLOSELY RELATED TO HUMAN DISEASES, INCLUDING CANCERS, MENTAL DISEASES, AUTOIMMUNE DISEASES AND OTHERS. THE ABNORMAL SEQUENCE AND SPATIAL STRUCTURE OF LNCRNAS, THE DISORDER EXPRESSION AND THE ABNORMAL INTERACTION WITH THE BINDING PROTEIN WILL LEAD TO THE CHANGE OF GENE EXPRESSION IN THE WAY OF EPIGENETIC MODIFICATION. INCREASING EVIDENCE DEMONSTRATED THAT LNCRNAS WERE INVOLVED IN THE ACTIVATION OF FLSS, WHICH PLAYED A KEY ROLE IN THE PATHOGENESIS OF RA. IN THIS REVIEW, THE RESEARCH PROGRESS OF LNCRNAS IN THE PATHOGENESIS OF RA WAS SYSTEMATICALLY SUMMARIZED, INCLUDING THE ROLE OF LNCRNAS IN THE DIAGNOSIS OF RA, THE REGULATORY MECHANISM OF LNCRNAS IN THE PATHOGENESIS OF RA, AND THE INTERVENTION ROLE OF LNCRNAS IN THE TREATMENT OF RA. FURTHERMORE, THE ACTIVATED SIGNAL PATHWAYS, THE ROLE OF DNA METHYLATION AND OTHER MECHANISM HAVE ALSO BEEN OVERVIEW IN THIS REVIEW. 2021 8 6786 25 [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 9 4668 32 NEW INSIGHTS INTO MOLECULAR MECHANISMS OF EPIGENETIC REGULATION IN KIDNEY DISEASE. THE NUMBER OF PATIENTS WITH KIDNEY FAILURE HAS INCREASED IN RECENT YEARS. DIFFERENT FACTORS CONTRIBUTE TO THE PROGRESSION OF CHRONIC KIDNEY DISEASE, INCLUDING GLOMERULAR SCLEROSIS, ATHEROSCLEROSIS OF THE RENAL ARTERIES AND TUBULOINTERSTITIAL FIBROSIS. TUBULOINTERSTITIAL INJURY IS INDUCED BY HYPOXIA AND OTHER INFLAMMATORY SIGNALS, LEADING TO FIBROBLAST ACTIVATION. TECHNOLOGICAL ADVANCES USING HIGH-THROUGHPUT SEQUENCING HAS ENABLED THE DETERMINATION OF THE EXPRESSION PROFILE OF ALMOST ALL GENES, REVEALING THAT GENE EXPRESSION IS INTRICATELY REGULATED BY DNA METHYLATION, HISTONE MODIFICATION, CHANGES IN CHROMOSOME CONFORMATION, LONG NON-CODING RNAS AND MICRORNAS. THESE EPIGENETIC MODIFICATIONS ARE STORED AS CELLULAR EPIGENETIC MEMORY. EPIGENETIC MEMORY LEADS TO ADULT-ONSET DISEASE OR AGEING IN THE LONG TERM AND MAY POSSIBLY PLAY AN IMPORTANT ROLE IN THE KIDNEY DISEASE PROCESS. HEREIN WE EMPHASIZE THE IMPORTANCE OF CLARIFYING THE MOLECULAR MECHANISMS UNDERLYING EPIGENETIC MODIFICATIONS BECAUSE THIS MAY LEAD TO THE DEVELOPMENT OF NEW THERAPEUTIC TARGETS IN KIDNEY DISEASE. 2016 10 3674 19 INFLAMMATION AND DYSREGULATED FIBROBLAST PROLIFERATION--NEW MECHANISMS? IDIOPATHIC PULMONARY FIBROSIS (IPF) IS A DEVASTATING, AGE-RELATED LUNG DISEASE OF UNKNOWN CAUSE THAT HAS FEW TREATMENT OPTIONS. ONCE THOUGHT TO BE A CHRONIC INFLAMMATORY PROCESS, CURRENT EVIDENCE INDICATES THAT THE FIBROTIC RESPONSE MAY PRIMARILY BE DRIVEN BY ABNORMALLY ACTIVATED ALVEOLAR EPITHELIAL CELLS AND THE UNDERLYING MESENCHYME. THE MEDIATORS PRODUCED AND PRESENT IN THIS MICROENVIRONMENT INDUCE THE FORMATION OF FIBROBLAST FOCI THROUGH THE PROLIFERATION OF RESIDENT MESENCHYMAL CELLS, ATTRACTION OF CIRCULATING FIBROCYTES, AND STIMULATION OF EPITHELIAL TO MESENCHYMAL TRANSITION. THE FIBROBLAST AND MYOFIBROBLAST FOCI SECRETE EXCESSIVE AMOUNTS OF EXTRACELLULAR MATRIX, MAINLY COLLAGENS, RESULTING IN SCARRING AND DESTRUCTION OF THE LUNG ARCHITECTURE. THE DETAILED MECHANISMS THAT LINK IPF WITH AGEING AND ABERRANT EPITHELIAL ACTIVATION ARE UNKNOWN, BUT SOME EVIDENCE SUGGESTS THAT THE ABNORMAL RECAPITULATION OF DEVELOPMENTAL PATHWAYS AND EPIGENETIC CHANGES MAY PLAY A ROLE. THIS REVIEW PROVIDES A BRIEF SYNOPSIS OF HIGHLIGHTS IN THE CURRENT UNDERSTANDING OF THE PATHOPHYSIOLOGY OF IPF, AS WELL AS NOVEL THERAPEUTICS BEING EXPLORED IN CLINICAL TRIALS FOR THE TREATMENT OF THIS DEVASTATING DISEASE. 2013 11 6152 23 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 12 1136 28 COMPREHENSIVE OVERVIEW OF MICRORNA FUNCTION IN RHEUMATOID ARTHRITIS. MICRORNAS (MIRNAS), A CLASS OF ENDOGENOUS SINGLE-STRANDED SHORT NONCODING RNAS, HAVE EMERGED AS VITAL EPIGENETIC REGULATORS OF BOTH PATHOLOGICAL AND PHYSIOLOGICAL PROCESSES IN ANIMALS. THEY DIRECT FUNDAMENTAL CELLULAR PATHWAYS AND PROCESSES BY FINE-TUNING THE EXPRESSION OF MULTIPLE GENES AT THE POSTTRANSCRIPTIONAL LEVEL. GROWING EVIDENCE SUGGESTS THAT MIRNAS ARE IMPLICATED IN THE ONSET AND DEVELOPMENT OF RHEUMATOID ARTHRITIS (RA). RA IS A CHRONIC INFLAMMATORY DISEASE THAT MAINLY AFFECTS SYNOVIAL JOINTS. THIS COMMON AUTOIMMUNE DISORDER IS CHARACTERIZED BY A COMPLEX AND MULTIFACETED PATHOGENESIS, AND ITS MORBIDITY, DISABILITY AND MORTALITY RATES REMAIN CONSISTENTLY HIGH. MORE IN-DEPTH INSIGHTS INTO THE UNDERLYING MECHANISMS OF RA ARE REQUIRED TO ADDRESS UNMET CLINICAL NEEDS AND OPTIMIZE TREATMENT. HEREIN, WE COMPREHENSIVELY REVIEW THE DEREGULATED MIRNAS AND IMPAIRED CELLULAR FUNCTIONS IN RA TO SHED LIGHT ON SEVERAL ASPECTS OF RA PATHOGENESIS, WITH A FOCUS ON EXCESSIVE INFLAMMATION, SYNOVIAL HYPERPLASIA AND PROGRESSIVE JOINT DAMAGE. THIS REVIEW ALSO PROVIDES PROMISING TARGETS FOR INNOVATIVE THERAPIES OF RA. IN ADDITION, WE DISCUSS THE REGULATORY ROLES AND CLINICAL POTENTIAL OF EXTRACELLULAR MIRNAS IN RA, HIGHLIGHTING THEIR PROSPECTIVE APPLICATIONS AS DIAGNOSTIC AND PREDICTIVE BIOMARKERS. 2023 13 4981 29 PATHOPHYSIOLOGY OF SYSTEMIC SCLEROSIS: CURRENT UNDERSTANDING AND NEW INSIGHTS. INTRODUCTION: SYSTEMIC SCLEROSIS (SSC) IS A COMPLEX AUTOIMMUNE CONNECTIVE TISSUE DISEASE CHARACTERIZED BY CHRONIC AND PROGRESSIVE TISSUE AND ORGAN FIBROSIS WITH BROAD PATIENT-TO-PATIENT VARIABILITY. SOME RISK FACTORS ARE KNOWN AND INCLUDE COMBINATION OF PERSISTENT RAYNAUD'S PHENOMENON, STEROID HORMONE IMBALANCE, SELECTED CHEMICALS, THERMAL, OR OTHER INJURIES. ENDOGENOUS AND/OR EXOGENOUS ENVIRONMENTAL TRIGGER/RISK FACTORS PROMOTE EPIGENETIC MECHANISMS IN GENETICALLY PRIMED SUBJECTS. DISEASE PATHOGENESIS PRESENTS EARLY MICROVASCULAR CHANGES WITH ENDOTHELIAL CELL DYSFUNCTION, FOLLOWED BY THE ACTIVATION OF MECHANISMS PROMOTING THEIR TRANSITION INTO MYOFIBROBLASTS. A COMPLEX AUTOIMMUNE RESPONSE, INVOLVING INNATE AND ADAPTIVE IMMUNITY WITH SPECIFIC/FUNCTIONAL AUTOANTIBODY PRODUCTION, CHARACTERIZES THE DISEASE. PROGRESSIVE FIBROSIS AND ISCHEMIA INVOLVE SKIN AND VISCERAL ORGANS RESULTING IN THEIR IRREVERSIBLE DAMAGE/FAILURE. PROGENITOR CIRCULATING CELLS (MONOCYTES, FIBROCYTES), TOGETHER WITH GROWTH FACTORS AND CYTOKINES PARTICIPATE IN DISEASE DIFFUSION AND EVOLUTION. EPIGENETIC, VASCULAR AND IMMUNOLOGIC MECHANISMS IMPLICATED IN SYSTEMIC FIBROSIS, REPRESENT MAJOR TARGETS FOR INCOMING DISEASE MODIFYING THERAPEUTIC APPROACHES. AREAS COVERED: THIS REVIEW DISCUSSES CURRENT UNDERSTANDING AND NEW INSIGHTS OF SSC PATHOGENESIS, THROUGH AN OVERVIEW OF THE MOST RELEVANT ADVANCEMENTS TO PRESENT ASPECTS AND MECHANISMS INVOLVED IN DISEASE PATHOGENESIS. EXPERT OPINION: CONSIDERING SSC INTRICACY/HETEROGENEITY, EARLY COMBINATION THERAPY WITH VASODILATORS, IMMUNOSUPPRESSIVE AND ANTIFIBROTIC DRUGS SHOULD SUCCESSFULLY DOWNREGULATE THE DISEASE PROGRESSION, ESPECIALLY IF STARTED FROM THE BEGINNING. 2019 14 5565 26 ROLE OF HYPOXIA IN PROGRESSIVE CHRONIC KIDNEY DISEASE AND IMPLICATIONS FOR THERAPY. PURPOSE OF REVIEW: CHRONIC HYPOXIA IN THE TUBULOINTERSTITIUM HAS BEEN RECOGNIZED AS A FINAL COMMON PATHWAY THAT LEADS TO THE DEVELOPMENT OF END-STAGE RENAL DISEASE. HYPOXIA-INDUCIBLE FACTOR (HIF), A MASTER REGULATOR OF THE ADAPTIVE RESPONSE AGAINST HYPOXIA, IS INVOLVED IN THE PATHOGENESIS OF CHRONIC KIDNEY DISEASE (CKD). THIS REVIEW FOCUSES ON HIF AND NOVEL THERAPEUTIC STRATEGIES TARGETING HIF. RECENT FINDINGS: ALTHOUGH HIF UPREGULATION IS BENEFICIAL AGAINST HYPOXIC KIDNEY INJURY, IT MAY BE HARMFUL UNDER CERTAIN PATHOLOGICAL CONDITIONS. RECENT ADVANCES IN EPIGENETIC CHANGES PROVIDE AN ADDITIONAL LAYER OF COMPLEXITY TO OUR UNDERSTANDING OF GENE REGULATION IN RESPONSE TO HYPOXIA, WHICH IS MOST LIKELY INVOLVED IN THE PROGRESSION OF CKD. ON THE BASIS OF THIS NOVEL KNOWLEDGE, THE PHARMACOLOGICAL ACTIVATION AND MODULATION OF HIF IS EMERGING AS A NOVEL THERAPEUTIC TARGET. SUMMARY: HIF PLAYS A CRUCIAL ROLE IN THE PATHOPHYSIOLOGY OF CKD. THE UNDERLYING MOLECULAR MECHANISMS, INCLUDING EPIGENETICS, HAVE BEEN THOROUGHLY INVESTIGATED. ON THE BASIS OF THE EXPERIMENTAL DATA AVAILABLE TO DATE, THE PHARMACOLOGICAL ACTIVATION OF HIF IS LIKELY A NOVEL PROMISING THERAPY FOR CKD. 2014 15 3890 22 KLOTHO, PHOSPHATE AND INFLAMMATION/AGEING IN CHRONIC KIDNEY DISEASE. EVIDENCE IS EMERGING FOR THE INFLAMMATORY NATURE OF MANY AGEING-ASSOCIATED DISEASES, INCLUDING ATHEROSCLEROSIS, VASCULAR CALCIFICATION, DIABETES AND CHRONIC KIDNEY DISEASE (CKD), AMONG OTHERS. AGEING ITSELF RESULTS IN CHRONIC LOW-GRADE INFLAMMATION THAT PROMOTES END-ORGAN DAMAGE. INFLAMMATORY ORGAN DAMAGE, IN TURN, MAY CONTRIBUTE TO INFLAMMATION. RECENT RESEARCH HAS IDENTIFIED THE KIDNEY-SECRETED HORMONE KLOTHO AS A CENTRAL PLAYER AT THE AGEING-INFLAMMATION INTERFACE. THUS, SYSTEMIC OR LOCAL RENAL INFLAMMATION DECREASES KIDNEY KLOTHO EXPRESSION. KLOTHO DOWN-REGULATION MAY BE INDUCED BY SPECIFIC CYTOKINES SUCH AS TUMOUR NECROSIS FACTOR-ALPHA OR TWEAK THROUGH THE CANONICAL ACTIVATION OF THE INFLAMMATORY TRANSCRIPTION FACTOR NUCLEAR FACTOR KAPPA B (NFKAPPAB) AND, SPECIFICALLY RELA. IN ADDITION, INFLAMMATORY CYTOKINES LEAD TO THE EPIGENETIC INACTIVATION OF KLOTHO TRANSCRIPTION. KLOTHO ITSELF HAS ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES AND THE CANONICAL NFKAPPAB COMPONENT RELA IS ONE OF ITS TARGETS. KLOTHO IS A KEY REGULATOR OF PHOSPHATE BALANCE AND A ROLE OF PHOSPHATE IN AGEING HAS BEEN SHOWN. HOWEVER, THE POTENTIAL RELATIONSHIP BETWEEN PHOSPHATE AND INFLAMMATION REQUIRES FURTHER CLARIFICATION. A CORRECT UNDERSTANDING OF THESE INTERACTIONS MAY LEAD TO THE DESIGN OF NOVEL THERAPEUTIC APPROACHES TO CKD AND CKD-RELATED INFLAMMATORY AND AGEING FEATURES AS WELL AS TO INFLAMMATION/AGEING IN GENERAL. 2012 16 5265 25 PROMISING THERAPEUTIC TARGETS FOR TREATMENT OF RHEUMATOID ARTHRITIS. RHEUMATOID ARTHRITIS (RA) IS A SYSTEMIC POLY-ARTICULAR CHRONIC AUTOIMMUNE JOINT DISEASE THAT MAINLY DAMAGES THE HANDS AND FEET, WHICH AFFECTS 0.5% TO 1.0% OF THE POPULATION WORLDWIDE. WITH THE SUSTAINED DEVELOPMENT OF DISEASE-MODIFYING ANTIRHEUMATIC DRUGS (DMARDS), SIGNIFICANT SUCCESS HAS BEEN ACHIEVED FOR PREVENTING AND RELIEVING DISEASE ACTIVITY IN RA PATIENTS. UNFORTUNATELY, SOME PATIENTS STILL SHOW LIMITED RESPONSE TO DMARDS, WHICH PUTS FORWARD NEW REQUIREMENTS FOR SPECIAL TARGETS AND NOVEL THERAPIES. UNDERSTANDING THE PATHOGENETIC ROLES OF THE VARIOUS MOLECULES IN RA COULD FACILITATE DISCOVERY OF POTENTIAL THERAPEUTIC TARGETS AND APPROACHES. IN THIS REVIEW, BOTH EXISTING AND EMERGING TARGETS, INCLUDING THE PROTEINS, SMALL MOLECULAR METABOLITES, AND EPIGENETIC REGULATORS RELATED TO RA, ARE DISCUSSED, WITH A FOCUS ON THE MECHANISMS THAT RESULT IN INFLAMMATION AND THE DEVELOPMENT OF NEW DRUGS FOR BLOCKING THE VARIOUS MODULATORS IN RA. 2021 17 2020 28 EPIGENETIC CHANGES AND FUNCTIONS IN PNEUMOCONIOSIS. PNEUMOCONIOSIS IS ONE OF THE MOST COMMON OCCUPATIONAL DISEASES IN THE WORLD, AND SPECIFIC TREATMENT METHODS OF PNEUMOCONIOSIS ARE LACKING AT PRESENT, SO IT CARRIES GREAT SOCIAL AND ECONOMIC BURDENS. PNEUMOCONIOSIS, CORONAVIRUS DISEASE 2019, AND IDIOPATHIC PULMONARY FIBROSIS ALL HAVE SIMILAR TYPICAL PATHOLOGICAL CHANGES-PULMONARY FIBROSIS. PULMONARY FIBROSIS IS A CHRONIC LUNG DISEASE CHARACTERIZED BY EXCESSIVE DEPOSITION OF THE EXTRACELLULAR MATRIX AND REMODELING OF THE LUNG TISSUE STRUCTURE. CLARIFYING THE PATHOGENESIS OF PNEUMOCONIOSIS PLAYS AN IMPORTANT GUIDING ROLE IN ITS TREATMENT. THE OCCURRENCE AND DEVELOPMENT OF PNEUMOCONIOSIS ARE ACCOMPANIED BY EPIGENETIC FACTORS (E.G., DNA METHYLATION AND NONCODING RNA) CHANGES, WHICH IN TURN CAN PROMOTE OR INHIBIT THE PROCESS OF PNEUMOCONIOSIS. HERE, WE SUMMARIZE EPIGENETIC CHANGES AND FUNCTIONS IN THE SEVERAL KINDS OF EVIDENCE CLASSIFICATION (EPIDEMIOLOGICAL INVESTIGATION, IN VIVO, AND IN VITRO EXPERIMENTS) AND MAIN TYPES OF CELLS (MACROPHAGES, FIBROBLASTS, AND ALVEOLAR EPITHELIAL CELLS) TO PROVIDE SOME CLUES FOR FINDING SPECIFIC THERAPEUTIC TARGETS FOR PNEUMOCONIOSIS AND EVEN FOR PULMONARY FIBROSIS. 2022 18 2283 24 EPIGENETIC REGULATION IN FIBROSIS PROGRESS. FIBROSIS, A COMMON PROCESS OF CHRONIC INFLAMMATORY DISEASES, IS DEFINED AS A REPAIR RESPONSE DISORDER WHEN ORGANS UNDERGO CONTINUOUS DAMAGE, ULTIMATELY LEADING TO SCAR FORMATION AND FUNCTIONAL FAILURE. AROUND THE WORLD, FIBROTIC DISEASES CAUSE HIGH MORTALITY, UNFORTUNATELY, WITH LIMITED TREATMENT MEANS IN CLINICAL PRACTICE. WITH THE DEVELOPMENT AND APPLICATION OF DEEP SEQUENCING TECHNOLOGY, COMPREHENSIVELY EXPLORING THE EPIGENETIC MECHANISM IN FIBROSIS HAS BEEN ALLOWED. EXTENSIVE REMODELING OF EPIGENETICS CONTROLLING VARIOUS CELLS PHENOTYPE AND MOLECULAR MECHANISMS INVOLVED IN FIBROGENESIS WAS SUBSEQUENTLY VERIFIED. IN THIS REVIEW, WE SUMMARIZE THE REGULATORY MECHANISMS OF DNA METHYLATION, HISTONE MODIFICATION, NONCODING RNAS (NCRNAS) AND N6-METHYLADENOSINE (M6A) MODIFICATION IN ORGAN FIBROSIS, FOCUSING ON HEART, LIVER, LUNG AND KIDNEY. ADDITIONALLY, WE EMPHASIZE THE DIVERSITY OF EPIGENETICS IN THE CELLULAR AND MOLECULAR MECHANISMS RELATED TO FIBROSIS. FINALLY, THE POTENTIAL AND PROSPECT OF TARGETED THERAPY FOR FIBROSIS BASED ON EPIGENETIC IS DISCUSSED. 2021 19 5323 30 PULMONARY INVOLVEMENT IN SYSTEMIC SCLEROSIS: EXPLORING CELLULAR, GENETIC AND EPIGENETIC MECHANISMS. SYSTEMIC SCLEROSIS (SSC) IS A CHRONIC PROGRESSIVE AUTOIMMUNE DISEASE CHARACTERIZED BY IMMUNE INFLAMMATION, VASCULOPATHY, AND FIBROSIS. THERE ARE STILL NUMEROUS UNCERTAINTIES IN THE UNDERSTANDING OF DISEASE INITIATION AND PROGRESSION. PULMONARY INVOLVEMENT IN SSC, AND PARTICULARLY PULMONARY FIBROSIS, IS CRITICAL FOR ALL ORGAN SYSTEMS AFFECTIONS IN THIS DISEASE. THIS REVIEW IS AIMED TO DESCRIBE AND ANALYZE NEW FINDINGS IN THE PATHOPHYSIOLOGY OF SSC-ASSOCIATED PULMONARY INVOLVEMENT AND TO EXPLORE PERSPECTIVE DIAGNOSTIC AND THERAPEUTIC STRATEGIES. A MYRIAD OF CELLULAR INTERACTIONS IS EXPLORED IN THE DYNAMICS OF PROGRESSIVE INTERSTITIAL LUNG DISEASE (ILD) AND PULMONARY HYPERTENSION (PH) IN SSC. THE ROLE OF EXOSOMES, MICROVESICLES, AND APOPTOTIC BODIES IS EXAMINED AND THE IMPACT OF MICRO AND LONG NON-CODING RNAS, DNA METHYLATION, AND HISTONE MODIFICATION IN SSC IS DISCUSSED. 2020 20 4589 22 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