1 3545 80 IMMUNOMETABOLISM IN THE PATHOGENESIS OF SYSTEMIC LUPUS ERYTHEMATOSUS. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A TYPICAL AUTOIMMUNE DISEASE CHARACTERIZED BY CHRONIC INFLAMMATION AND PATHOGENIC AUTO-ANTIBODIES. APART FROM B CELLS, DYSREGULATION OF OTHER IMMUNE CELLS ALSO PLAYS AN ESSENTIAL ROLE IN THE PATHOGENESIS AND DEVELOPMENT OF THE DISEASE INCLUDING CD4(+)T CELLS, DENDRITIC CELLS, MACROPHAGES AND NEUTROPHILS. SINCE METABOLIC PROGRAMS CONTROL IMMUNE CELL FATE AND FUNCTION, THEY ARE CRITICAL CHECKPOINTS IN AN EFFECTIVE IMMUNE RESPONSE AND ARE INVOLVED IN THE ETIOLOGY OF AUTOIMMUNE DISEASE. IN ADDITION, MITOCHONDRIA AND OXIDATIVE STRESS ARE BOTH INVOLVED IN CELLULAR METABOLISM AND IS ALSO ESSENTIAL IN IMMUNE RESPONSE. IN THIS REVIEW, APART FROM THE DISTURBED IMMUNE SYSTEM, WE WILL DISCUSS MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, ABNORMAL METABOLISM (INCLUDING GLUCOSE, LIPID AND AMINO ACID METABOLISM) OF IMMUNE CELLS AS WELL AS EPIGENETIC CONTROL OF METABOLISM REPROGRAMMING TO ELUCIDATE THE UNDERLYING PATHOGENIC MECHANISMS OF SYSTEMIC LUPUS ERYTHEMATOSUS. 2020 2 4372 26 MIRNAS, OXIDATIVE STRESS, AND CANCER: A COMPREHENSIVE AND UPDATED REVIEW. OXIDATIVE STRESS REFERS TO ELEVATED LEVELS OF INTRACELLULAR REACTIVE OXYGEN SPECIES (ROS). ROS HOMEOSTASIS FUNCTIONS AS A SIGNALING PATHWAY FOR NORMAL CELL SURVIVAL AND APPROPRIATE CELL SIGNALING. CHRONIC INFLAMMATION INDUCED BY IMBALANCED LEVELS OF ROS CONTRIBUTES TO MANY DISEASES AND DIFFERENT TYPES OF CANCER. ROS CAN ALTER THE EXPRESSION OF ONCOGENES AND TUMOR SUPPRESSOR GENES THROUGH EPIGENETIC MODIFICATIONS, TRANSCRIPTION FACTORS, AND NON-CODING RNAS. MICRORNAS (MIRNAS) ARE SMALL NON-CODING RNAS THAT PLAY A KEY ROLE IN MOST BIOLOGICAL PATHWAYS. EACH MIRNA REGULATES HUNDREDS OF TARGET GENES BY INHIBITING PROTEIN TRANSLATION AND/OR PROMOTING MESSENGER RNA DEGRADATION. IN NORMAL CONDITIONS, MIRNAS PLAY A PHYSIOLOGICAL ROLE IN CELL PROLIFERATION, DIFFERENTIATION, AND APOPTOSIS. HOWEVER, DIFFERENT FACTORS THAT CAN DYSREGULATE CELL SIGNALING AND CELLULAR HOMEOSTASIS CAN ALSO AFFECT MIRNA EXPRESSION. THE ALTERATION OF MIRNA EXPRESSION CAN WORK AGAINST DISTURBING FACTORS OR MEDIATE THEIR EFFECTS. OXIDATIVE STRESS IS ONE OF THESE FACTORS. CONSIDERING THE COMPLEX INTERPLAY BETWEEN ROS LEVEL AND MIRNA REGULATION AND BOTH OF THESE WITH CANCER DEVELOPMENT, WE REVIEW THE ROLE OF MIRNAS IN CANCER, FOCUSING ON THEIR FUNCTION IN OXIDATIVE STRESS. 2020 3 1872 26 EMERGING ROLE OF LONG NON-CODING RNAS IN ENDOTHELIAL DYSFUNCTION AND THEIR MOLECULAR MECHANISMS. LONG NON-CODING RNAS (LNCRNAS) ARE THE NOVEL CLASS OF TRANSCRIPTS INVOLVED IN TRANSCRIPTIONAL, POST-TRANSCRIPTIONAL, TRANSLATIONAL, AND POST-TRANSLATIONAL REGULATION OF PHYSIOLOGY AND THE PATHOLOGY OF DISEASES. STUDIES HAVE EVIDENCED THAT THE IMPAIRMENT OF ENDOTHELIUM IS A CRITICAL EVENT IN THE PATHOGENESIS OF ATHEROSCLEROSIS AND ITS COMPLICATIONS. ENDOTHELIAL DYSFUNCTION IS CHARACTERIZED BY AN IMBALANCE IN VASODILATION AND VASOCONSTRICTION, OXIDATIVE STRESS, PROINFLAMMATORY FACTORS, AND NITRIC OXIDE BIOAVAILABILITY. DISRUPTION OF THE ENDOTHELIAL BARRIER PERMEABILITY, THE FIRST STEP IN DEVELOPING ATHEROSCLEROTIC LESIONS IS A CONSEQUENCE OF ENDOTHELIAL DYSFUNCTION. THOUGH SEVERAL FACTORS INTERFERE WITH THE NORMAL FUNCTIONING OF THE ENDOTHELIUM, INTRINSIC EPIGENETIC MECHANISMS GOVERNING ENDOTHELIAL FUNCTION ARE REGULATED BY LNCRNAS AND PERTURBATIONS CONTRIBUTE TO THE PATHOGENESIS OF THE DISEASE. THIS REVIEW COMPREHENSIVELY ADDRESSES THE BIOGENESIS OF LNCRNA AND MOLECULAR MECHANISMS UNDERLYING AND REGULATION IN ENDOTHELIAL FUNCTION. AN INSIGHT CORRELATING LNCRNAS AND ENDOTHELIAL DYSFUNCTION-ASSOCIATED DISEASES CAN POSITIVELY IMPACT THE DEVELOPMENT OF NOVEL BIOMARKERS AND THERAPEUTIC TARGETS IN ENDOTHELIAL DYSFUNCTION-ASSOCIATED DISEASES AND TREATMENT STRATEGIES. 2022 4 241 36 ADIPOCYTE, IMMUNE CELLS, AND MIRNA CROSSTALK: A NOVEL REGULATOR OF METABOLIC DYSFUNCTION AND OBESITY. OBESITY IS CHARACTERIZED AS A COMPLEX AND MULTIFACTORIAL EXCESS ACCRETION OF ADIPOSE TISSUE (AT) ACCOMPANIED WITH ALTERATIONS IN THE IMMUNE RESPONSE THAT AFFECTS VIRTUALLY ALL AGE AND SOCIOECONOMIC GROUPS AROUND THE GLOBE. THE ABNORMAL ACCUMULATION OF AT LEADS TO SEVERAL METABOLIC DISEASES, INCLUDING NONALCOHOLIC FATTY LIVER DISORDER (NAFLD), LOW-GRADE INFLAMMATION, TYPE 2 DIABETES MELLITUS (T2DM), CARDIOVASCULAR DISORDERS (CVDS), AND CANCER. AT IS AN ENDOCRINE ORGAN COMPOSED OF ADIPOCYTES AND IMMUNE CELLS, INCLUDING B-CELLS, T-CELLS AND MACROPHAGES. THESE IMMUNE CELLS SECRETE VARIOUS CYTOKINES AND CHEMOKINES AND CROSSTALK WITH ADIPOKINES TO MAINTAIN METABOLIC HOMEOSTASIS AND LOW-GRADE CHRONIC INFLAMMATION. A NOVEL FORM OF ADIPOKINES, MICRORNA (MIRS), IS EXPRESSED IN MANY DEVELOPING PERIPHERAL TISSUES, INCLUDING ATS, T-CELLS, AND MACROPHAGES, AND MODULATES THE IMMUNE RESPONSE. MIRS ARE ESSENTIAL FOR INSULIN RESISTANCE, MAINTAINING THE TUMOR MICROENVIRONMENT, AND OBESITY-ASSOCIATED INFLAMMATION (OAI). THE ABNORMAL REGULATION OF AT, T-CELLS, AND MACROPHAGE MIRS MAY CHANGE THE FUNCTION OF DIFFERENT ORGANS INCLUDING THE PANCREAS, HEART, LIVER, AND SKELETAL MUSCLE. SINCE OBESITY AND INFLAMMATION ARE CLOSELY ASSOCIATED, THE DYSREGULATED EXPRESSION OF MIRS IN INFLAMMATORY ADIPOCYTES, T-CELLS, AND MACROPHAGES SUGGEST THE IMPORTANCE OF MIRS IN OAI. THEREFORE, IN THIS REVIEW ARTICLE, WE HAVE ELABORATED THE ROLE OF MIRS AS EPIGENETIC REGULATORS AFFECTING ADIPOCYTE DIFFERENTIATION, IMMUNE RESPONSE, AT BROWNING, ADIPOGENESIS, LIPID METABOLISM, INSULIN RESISTANCE (IR), GLUCOSE HOMEOSTASIS, OBESITY, AND METABOLIC DISORDERS. FURTHER, WE WILL DISCUSS A SET OF ALTERED MIRS AS NOVEL BIOMARKERS FOR METABOLIC DISEASE PROGRESSION AND THERAPEUTIC TARGETS FOR OBESITY. 2021 5 5573 28 ROLE OF MICRORNA IN SEVERE ASTHMA. THE VARIOUS ROLES OF MICRORNAS (MIRNAS) IN THE EPIGENETIC REGULATION OF HUMAN DISEASE ARE GAINING IMPORTANCE AS AREAS OF RESEARCH, AND A BETTER UNDERSTANDING OF THESE ROLES MAY IDENTIFY TARGETS FOR DEVELOPMENT OF NOVEL THERAPIES FOR SEVERE ASTHMA. MIRNAS, A CLASS OF SMALL NON-CODING RNAS THAT SERVE AS POST-TRANSCRIPTIONAL GENE REPRESSORS, ARE RECOGNIZED AS CRITICAL COMPONENTS IN REGULATING TISSUE HOMEOSTASIS. ALTERATION IN MIRNA EXPRESSION DISRUPTS HOMEOSTASIS AND IS AN UNDERLYING MECHANISM FOR DEVELOPMENT OF CHRONIC RESPIRATORY DISEASES, INCLUDING ASTHMA. DIFFERENTIAL PROFILES OF MIRNA EXPRESSION ARE INVOLVED IN INFLAMMATION AND REMODELING PATHOGENICITY VIA ACTIVATING AIRWAY STRUCTURAL CELLS AND IMMUNE CELLS AND INDUCING CYTOKINE RELEASES. MIRNA ACTION LEADS TO ASTHMA PROGRESSION FROM MILD TO SEVERE STAGES. HERE, CURRENT KNOWLEDGE OF THE HETEROGENEOUS ROLES OF MIRNAS IN SEVERE ASTHMA, INCLUDING BIOLOGICAL MECHANISMS UNDERLYING TH2 AND MACROPHAGE POLARIZATION, TYPE 2 INNATE LYMPHOID CELL (ILC2) BIOLOGY REGULATION, STEROID-RESISTANT ASTHMA PHENOTYPE, AIRWAY SMOOTH MUSCLE (ASM) DYSFUNCTION, AND IMPAIRED ANTI-VIRAL INNATE IMMUNE, ARE REVIEWED. 2019 6 3965 30 LONG NONCODING RNAS IN THE METABOLIC CONTROL OF INFLAMMATION AND IMMUNE DISORDERS. THE METABOLIC CONTROL OF IMMUNE CELL DEVELOPMENT AND FUNCTION HAS BEEN SHOWN TO BE CRITICAL FOR THE MAINTENANCE OF IMMUNE HOMEOSTASIS AND IS ALSO INVOLVED IN THE PATHOGENESIS OF IMMUNE DISORDERS. PATHOGENIC INFECTIONS OR CANCERS MAY INDUCE METABOLIC REPROGRAMMING THROUGH DIFFERENT PATHWAYS TO MEET THE ENERGY AND METABOLITE DEMANDS FOR PATHOGEN PROPAGATION OR CANCER PROGRESSION. IN ADDITION, SOME DEREGULATED METABOLITES COULD TRIGGER OR REGULATE IMMUNE RESPONSES, THUS CAUSING CHRONIC INFLAMMATION OR IMMUNE DISORDERS, SUCH AS VIRAL INFECTION, CANCER AND OBESITY. THEREFORE, THE METHODS THROUGH WHICH METABOLISM IS REGULATED AND THE ROLE OF METABOLIC REGULATION IN INFLAMMATION AND IMMUNITY ATTRACT MUCH ATTENTION. EPIGENETIC REGULATION OF INFLAMMATION AND IMMUNITY IS AN EMERGING FIELD. LONG NONCODING RNAS (LNCRNAS) HAVE BEEN WELL DOCUMENTED TO PLAY CRUCIAL ROLES IN MANY BIOLOGICAL PROCESSES THROUGH DIVERSE MECHANISMS, INCLUDING IMMUNE REGULATION AND METABOLIC ALTERNATION. HERE, WE REVIEW THE FUNCTIONS AND MECHANISMS OF LNCRNAS IN THE METABOLIC REGULATION OF INFLAMMATORY IMMUNE DISORDERS, AIMING TO DEEPEN OUR UNDERSTANDING OF THE EPIGENETIC REGULATION OF INFLAMMATION AND IMMUNITY. 2019 7 6182 31 THE IMPACT OF ADIPOSE TISSUE-DERIVED MIRNAS IN METABOLIC SYNDROME, OBESITY, AND CANCER. OBESITY IS A MULTIFACTORIAL AND COMPLEX CONDITION THAT IS CHARACTERIZED BY ABNORMAL AND EXCESSIVE WHITE ADIPOSE TISSUE ACCUMULATION, WHICH CAN LEAD TO THE DEVELOPMENT OF METABOLIC DISEASES, SUCH AS TYPE 2 DIABETES MELLITUS, NONALCOHOLIC FATTY LIVER DISEASE, CARDIOVASCULAR DISEASES, AND SEVERAL TYPES OF CANCER. OBESITY IS CHARACTERIZED BY EXCESSIVE ADIPOSE TISSUE ACCUMULATION AND ASSOCIATED WITH ALTERATIONS IN IMMUNITY, DISPLAYING A CHRONIC LOW-GRADE INFLAMMATION PROFILE. ADIPOSE TISSUE IS A DYNAMIC AND COMPLEX ENDOCRINE ORGAN COMPOSED NOT ONLY BY ADIPOCYTES, BUT SEVERAL IMMUNOLOGICAL CELLS, WHICH CAN SECRETE HORMONES, CYTOKINES AND MANY OTHER FACTORS CAPABLE OF REGULATING METABOLIC HOMEOSTASIS AND SEVERAL CRITICAL BIOLOGICAL PATHWAYS. REMARKABLY, ADIPOSE TISSUE IS A MAJOR SOURCE OF CIRCULATING MICRORNAS (MIRNAS), RECENTLY DESCRIBED AS A NOVEL FORM OF ADIPOKINES. SEVERAL ADIPOSE TISSUE-DERIVED MIRNAS ARE DEEPLY ASSOCIATED WITH ADIPOCYTES DIFFERENTIATION AND HAVE BEEN IDENTIFIED WITH AN ESSENTIAL ROLE IN OBESITY-ASSOCIATED INFLAMMATION, INSULIN RESISTANCE, AND TUMOR MICROENVIRONMENT. DURING OBESITY, ADIPOSE TISSUE CAN COMPLETELY CHANGE THE PROFILE OF THE SECRETED MIRNAS, INFLUENCING CIRCULATING MIRNAS AND IMPACTING THE DEVELOPMENT OF DIFFERENT PATHOLOGICAL CONDITIONS, SUCH AS OBESITY, METABOLIC SYNDROME, AND CANCER. IN THIS REVIEW, WE DISCUSS HOW MIRNAS CAN ACT AS EPIGENETIC REGULATORS AFFECTING ADIPOGENESIS, ADIPOCYTE DIFFERENTIATION, LIPID METABOLISM, BROWNING OF THE WHITE ADIPOSE TISSUE, GLUCOSE HOMEOSTASIS, AND INSULIN RESISTANCE, IMPACTING DEEPLY OBESITY AND METABOLIC DISEASES. MOREOVER, WE CHARACTERIZE HOW MIRNAS CAN OFTEN ACT AS ONCOGENIC AND TUMOR SUPPRESSOR MOLECULES, SIGNIFICANTLY MODULATING CANCER ESTABLISHMENT AND PROGRESSION. FURTHERMORE, WE HIGHLIGHT IN THIS MANUSCRIPT HOW ADIPOSE TISSUE-DERIVED MIRNAS CAN FUNCTION AS IMPORTANT NEW THERAPEUTIC TARGETS. 2020 8 4620 23 NEURO-IMMUNE DYSFUNCTION DURING BRAIN AGING: NEW INSIGHTS IN MICROGLIAL CELL REGULATION. MICROGLIA, THE RESIDENT IMMUNE CELLS OF THE BRAIN, ARE AT THE CENTER OF COMMUNICATION BETWEEN THE CENTRAL NERVOUS SYSTEM AND IMMUNE SYSTEM. WHILE THESE BRAIN-IMMUNE INTERACTIONS ARE BALANCED IN HEALTHY ADULTHOOD, THE ABILITY TO MAINTAIN HOMEOSTASIS DURING AGING IS IMPAIRED. MICROGLIA DEVELOP A LOSS OF INTEGRATED REGULATORY NETWORKS INCLUDING ABERRANT SIGNALING FROM OTHER BRAIN CELLS, IMMUNE SENSORS, AND EPIGENETIC MODIFIERS. THE LOW-GRADE CHRONIC NEUROINFLAMMATION ASSOCIATED WITH THIS DYSFUNCTIONAL ACTIVITY LIKELY CONTRIBUTES TO COGNITIVE DEFICITS AND SUSCEPTIBILITY TO AGE-RELATED PATHOLOGIES. A BETTER UNDERSTANDING OF THE UNDERLYING MECHANISMS RESPONSIBLE FOR NEURO-IMMUNE DYSREGULATION WITH AGE IS CRUCIAL FOR PROVIDING TARGETED THERAPEUTIC STRATEGIES TO SUPPORT BRAIN REPAIR AND HEALTHY AGING. 2016 9 3949 29 LNCRNAS IN T LYMPHOCYTES: RNA REGULATION AT THE HEART OF THE IMMUNE RESPONSE. GENOME-WIDE ANALYSES IN THE LAST DECADE HAVE UNCOVERED THE PRESENCE OF A LARGE NUMBER OF LONG NON-PROTEIN-CODING TRANSCRIPTS THAT SHOW HIGHLY TISSUE- AND STATE-SPECIFIC EXPRESSION PATTERNS. HIGH-THROUGHPUT SEQUENCING ANALYSES IN DIVERSE SUBSETS OF IMMUNE CELLS HAVE REVEALED A COMPLEX AND DYNAMIC EXPRESSION PATTERN FOR THESE LONG NONCODING RNAS (LNCRNAS) THAT CORRELATE WITH THE FUNCTIONAL STATES OF IMMUNE CELLS. ALTHOUGH THE VAST MAJORITY OF LNCRNAS EXPRESSED IN IMMUNE CELLS REMAIN UNSTUDIED, FUNCTIONAL STUDIES PERFORMED ON A SMALL SUBSET HAVE INDICATED THAT THEIR STATE-SPECIFIC EXPRESSIONS PATTERN FREQUENTLY HAS A REGULATORY IMPACT ON THE FUNCTION OF IMMUNE CELLS. IN VIVO AND IN VITRO STUDIES HAVE POINTED TO THE INVOLVEMENT OF LNCRNAS IN A WIDE VARIETY OF CELLULAR PROCESSES, INCLUDING BOTH THE INNATE AND ADAPTIVE IMMUNE RESPONSE THROUGH MECHANISMS RANGING FROM EPIGENETIC AND TRANSCRIPTIONAL REGULATION TO SEQUESTRATION OF FUNCTIONAL MOLECULES IN SUBCELLULAR COMPARTMENTS. THIS REVIEW WILL FOCUS MAINLY ON THE ROLE OF LNCRNAS IN CD4(+) AND CD8(+) T CELLS, WHICH PLAY PIVOTAL ROLES IN ADAPTIVE IMMUNITY. RECENT STUDIES HAVE POINTED TO KEY PHYSIOLOGICAL FUNCTIONS FOR LNCRNAS DURING SEVERAL DEVELOPMENTAL AND FUNCTIONAL STAGES OF THE LIFE CYCLE OF LYMPHOCYTES. ALTHOUGH LNCRNAS PLAY IMPORTANT PHYSIOLOGICAL ROLES IN LYMPHOCYTIC RESPONSE TO ANTIGENIC STIMULATION, DIFFERENTIATION INTO EFFECTOR CELLS, AND SECRETION OF CYTOKINES, THEIR DYSREGULATED EXPRESSION CAN PROMOTE OR SUSTAIN PATHOLOGICAL STATES SUCH AS AUTOIMMUNITY, CHRONIC INFLAMMATION, CANCER, AND VIREMIA. THIS, TOGETHER WITH THEIR HIGHLY CELL TYPE-SPECIFIC EXPRESSION PATTERNS, MAKES LNCRNAS IDEAL THERAPEUTIC TARGETS AND UNDERSCORES THE NEED FOR ADDITIONAL STUDIES INTO THE ROLE OF THESE UNDERSTUDIED TRANSCRIPTS IN ADAPTIVE IMMUNE RESPONSE. 2021 10 3640 26 INCREASED EXTRACELLULAR MATRIX PROTEIN PRODUCTION IN CHRONIC DIABETIC COMPLICATIONS: IMPLICATIONS OF NON-CODING RNAS. MANAGEMENT OF CHRONIC DIABETIC COMPLICATIONS REMAINS A MAJOR MEDICAL CHALLENGE WORLDWIDE. ONE OF THE CHARACTERISTIC FEATURES OF ALL CHRONIC DIABETIC COMPLICATIONS IS AUGMENTED PRODUCTION OF EXTRACELLULAR MATRIX (ECM) PROTEINS. SUCH ECM PROTEINS ARE DEPOSITED IN ALL TISSUES AFFECTED BY CHRONIC COMPLICATIONS, ULTIMATELY CAUSING ORGAN DAMAGE AND DYSFUNCTION. A CONTRIBUTING FACTOR TO THIS PATHOGENETIC PROCESS IS GLUCOSE-INDUCED ENDOTHELIAL DAMAGE, WHICH INVOLVES PHENOTYPIC TRANSFORMATION OF ENDOTHELIAL CELLS (ECS). THIS PHENOTYPIC TRANSITION OF ECS, FROM A QUIESCENT STATE TO AN ACTIVATED DYSFUNCTIONAL STATE, CAN BE MEDIATED THROUGH ALTERATIONS IN THE SYNTHESIS OF CELLULAR PROTEINS. IN THIS REVIEW, WE DISCUSSED THE ROLES OF NON-CODING RNAS, SPECIFICALLY MICRORNAS (MIRNAS) AND LONG NON-CODING RNAS (LNCRNAS), IN SUCH PROCESSES. WE FURTHER OUTLINED OTHER EPIGENETIC MECHANISMS REGULATING THE BIOGENESIS AND/OR FUNCTION OF NON-CODING RNAS. OVERALL, WE BELIEVE THAT BETTER UNDERSTANDING OF SUCH MOLECULAR PROCESSES MAY LEAD TO THE DEVELOPMENT OF NOVEL BIOMARKERS AND THERAPEUTIC STRATEGIES IN THE FUTURE. 2019 11 3834 23 INVOLVEMENTS OF LONG NONCODING RNAS IN OBESITY-ASSOCIATED INFLAMMATORY DISEASES. OBESITY IS ASSOCIATED WITH CHRONIC LOW-GRADE INFLAMMATION THAT AFFECTS THE PHENOTYPE OF MULTIPLE TISSUES AND THEREFORE IS IMPLICATED IN THE DEVELOPMENT AND PROGRESSION OF SEVERAL AGE-RELATED CHRONIC INFLAMMATORY DISORDERS. IMPORTANTLY, A NEW FAMILY OF NONCODING RNAS, TERMED LONG NONCODING RNAS (LNCRNAS), HAVE BEEN IDENTIFIED AS KEY REGULATORS OF INFLAMMATORY SIGNALLING PATHWAYS THAT CAN MEDIATE BOTH PRETRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL GENE REGULATION. FURTHERMORE, SEVERAL LNCRNAS HAVE BEEN IDENTIFIED, WHICH ARE DIFFERENTIALLY EXPRESSED IN MULTIPLE TISSUE TYPES IN INDIVIDUALS WHO ARE OBESE OR IN PRECLINICAL MODELS OF OBESITY. IN THIS REVIEW, WE EXAMINE THE EVIDENCE FOR THE ROLE OF SEVERAL OF THE MOST WELL-STUDIED LNCRNAS IN THE REGULATION OF INFLAMMATORY PATHWAYS ASSOCIATED WITH OBESITY. WE HIGHLIGHT THE EVIDENCE FOR THEIR DIFFERENTIAL EXPRESSION IN THE OBESE STATE AND IN AGE-RELATED CONDITIONS INCLUDING INSULIN RESISTANCE, TYPE 2 DIABETES (T2D), SARCOPENIA, OSTEOARTHRITIS AND RHEUMATOID ARTHRITIS, WHERE OBESITY PLAYS A SIGNIFICANT ROLE. DETERMINING THE EXPRESSION AND FUNCTIONAL ROLE OF LNCRNAS IN MEDIATING OBESITY-ASSOCIATED CHRONIC INFLAMMATION WILL ADVANCE OUR UNDERSTANDING OF THE EPIGENETIC REGULATORY PATHWAYS THAT UNDERLIE AGE-RELATED INFLAMMATORY DISEASES AND MAY ALSO ULTIMATELY IDENTIFY NEW TARGETS FOR THERAPEUTIC INTERVENTION. 2021 12 4368 29 MIRNA-DEPENDENT CD4(+) T CELL DIFFERENTIATION IN THE PATHOGENESIS OF MULTIPLE SCLEROSIS. MULTIPLE SCLEROSIS (MS) IS CHARACTERIZED BY MULTIFOCAL LESIONS, CHRONIC INFLAMMATORY CONDITION, AND DEGENERATIVE PROCESSES WITHIN THE CENTRAL NERVOUS SYSTEM (CNS) LEADING TO DEMYELINATION. THE MOST IMPORTANT CELLS INVOLVED IN ITS PATHOGENESIS ARE THOSE WHICH ARE CD4(+), PARTICULARLY PROINFLAMMATORY TH1/TH17 AND REGULATORY TREG. SIGNAL CASCADES ASSOCIATED WITH CD4(+) DIFFERENTIATION ARE REGULATED BY MICRORNAS (MIRNAS): SHORT, SINGLE-STRANDED RNAS, RESPONSIBLE FOR NEGATIVE REGULATION OF GENE EXPRESSION AT THE POSTTRANSCRIPTIONAL LEVEL. SEVERAL MIRNAS HAVE BEEN CONSISTENTLY REPORTED AS SHOWING DYSREGULATED EXPRESSION IN MS, AND THEIR EXPRESSION PATTERNS MAY BE ELEVATED OR DECREASED, DEPENDING ON THE FUNCTION OF SPECIFIC MIRNA IN THE IMMUNE SYSTEM. STUDIES IN MS PATIENTS INDICATE THAT, AMONG OTHERS, MIR-141, MIR-200A, MIR-155, MIR-223, AND MIR-326 ARE UPREGULATED, WHILE MIR-15B, MIR-20B, MIR-26A, AND MIR-30A ARE DOWNREGULATED. DYSREGULATION OF THESE MIRNAS MAY CONTRIBUTE TO THE IMBALANCE BETWEEN PRO- AND ANTI-INFLAMMATORY PROCESSES, SINCE THEIR TARGETS ARE ASSOCIATED WITH THE REGULATION OF TH1/TH17 AND TREG CELL DIFFERENTIATION. HIGHLY EXPRESSED MIRNAS CAN IN TURN SUPPRESS TRANSLATION OF KEY TH1/TH17 DIFFERENTIATION INHIBITORS. MIRNA DYSREGULATION MAY RESULT FROM THE IMPACT OF VARIOUS FACTORS AT EACH STAGE OF THEIR BIOGENESIS. IMMATURE MIRNA UNDERGOES MULTISTAGE TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL MODIFICATIONS; THEREFORE, ANY PROTEIN INVOLVED IN THE PROCESSING OF MIRNAS CAN POTENTIALLY LEAD TO DISTURBANCES IN THEIR EXPRESSION. EPIGENETIC MODIFICATIONS THAT HAVE A DIRECT IMPACT ON MIRNA GENE TRANSCRIPTION MAY ALSO PLAY AN IMPORTANT ROLE. 2021 13 1716 30 DYSREGULATED CD4+ T CELLS AND MICRORNAS IN MYOCARDITIS. MYOCARDITIS IS A POLYMORPHIC DISEASE COMPLICATED WITH INDETERMINATE ETIOLOGY AND PATHOGENESIS, AND REPRESENTS ONE OF THE MOST CHALLENGING CLINICAL PROBLEMS LACKING SPECIFIC DIAGNOSIS AND EFFECTIVE THERAPY. IT IS CAUSED BY A COMPLEX INTERPLAY OF ENVIRONMENTAL AND GENETIC FACTORS, AND CAUSAL LINKS BETWEEN DYSREGULATED MICRORIBONUCLEIC ACIDS (MIRNAS) AND MYOCARDITIS HAVE ALSO BEEN SUPPORTED BY RECENT EPIGENETIC RESEARCHES. BOTH DYSREGULATED CD4+ T CELLS AND MIRNAS PLAY CRITICAL ROLES IN THE PATHOGENESIS OF MYOCARDITIS, AND THE CLASSIC TRIPHASIC MODEL OF ITS PATHOGENESIS CONSISTS OF THE ACUTE INFECTIOUS, SUBACUTE IMMUNE, AND RECOVERY/CHRONIC MYOPATHIC PHASE. CD4+ T CELLS ARE KEY PATHOGENIC FACTORS UNDERLYING THE DEVELOPMENT AND PROGRESSION OF MYOCARDITIS, AND THE EFFECTOR AND REGULATORY SUBSETS, RESPECTIVELY, PROMOTE AND INHIBIT AUTOIMMUNE RESPONSES. FURTHERMORE, THE RECIPROCAL INTERPLAY OF THESE SUBSETS INFLUENCES THE PATHOGENESIS AS WELL. DYSREGULATED MIRNAS ALONG WITH THEIR MRNA AND PROTEIN TARGETS HAVE BEEN IDENTIFIED IN HEART BIOPSIES (INTRACELLULAR MIRNAS) AND BODY FLUIDS (CIRCULATING MIRNAS) DURING MYOCARDITIS. THESE MIRNAS SHOW PHASE-DEPENDENT CHANGES, AND CORRELATE WITH VIRAL INFECTION, IMMUNE STATUS, FIBROSIS, DESTRUCTION OF CARDIOMYOCYTES, ARRHYTHMIAS, CARDIAC FUNCTIONS, AND OUTCOMES. THUS, MIRNAS ARE PROMISING DIAGNOSTIC MARKERS AND THERAPEUTIC TARGETS IN MYOCARDITIS. IN THIS REVIEW, WE REVIEW MYOCARDITIS WITH AN EMPHASIS ON ITS PATHOGENESIS, AND PRESENT A SUMMARY OF CURRENT KNOWLEDGE OF DYSREGULATED CD4+ T CELLS AND MIRNAS IN MYOCARDITIS. 2020 14 6800 34 [EPIGENETIC DISTURBANCES IN SYSTEMIC LUPUS ERYTHEMATOSUS]. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE THAT RESULTS IN UNCONTROLLED IMMUNE SYSTEM ACTIVATION AND OVERPRODUCTION OF AUTOANTIBODIES. THE PATHOGENESIS OF THE DISEASE IS COMPLEX AND NOT FULLY UNDERSTOOD, NEVERTHELESS, GENETIC AND ENVIRONMENTAL FACTORS PLAY AN IMPORTANT ROLE. SO FAR, ABOUT 30 GENES HAVE BEEN IDENTIFIED TO BE INVOLVED IN THE SLE PATHOMECHANISM. HOWEVER, NOT ALL GENETICALLY PREDISPOSED INDIVIDUALS DEVELOP THE DISEASE. THIS PHENOMENON CAN BE ASSOCIATED WITH EPIGENETIC CHANGES THAT OCCUR UNDER THE INFLUENCE OF ENVIRONMENTAL FACTORS. THEY CAN AFFECT GENE EXPRESSION AND ARE POTENTIALLY HEREDITARY, BUT DO NOT LEAD TO CHANGES IN THE NUCLEOTIDE SEQUENCE. EPIGENETIC DYSFUNCTIONS, IDENTIFIED IN THE COURSE OF THE DISEASE, LEAD TO CHANGES IN THE EXPRESSION OF GENES THAT PLAY A KEY ROLE IN MAINTAINING THE BODY'S IMMUNE TOLERANCE. MAJOR MECHANISMS OF EPIGENETIC VARIABILITY ARE: DNA METHYLATION, HISTONE PROTEIN MODIFICATION, NON-CODING RNA EXPRESSION, AS WELL AS GENE IMPRINTING. THE MAJOR EPIGENETIC DYSFUNCTIONS AFFECTING THE PATHOGENESIS OF THE DISEASE ARE GLOBAL HYPOMETHYLATION ON CD4+ T CELLS RESULTING FROM ERK SIGNALING PATHWAY REGULATION, HISTONE HYPOACETYLATION, HISTONE H3 LYSINE METHYLATION, AND REACTIVATION OF INACTIVE CHROMOSOME X. IN LUPUS PATIENTS, VARIOUS EPIGENETIC MECHANISMS INTERACT WITH EACH OTHER, ENHANCING THE EXPRESSION OR SILENCING OF GENES RESPONSIBLE FOR THE PRODUCTION OF PRO-INFLAMMATORY AND ANTI-INFLAMMATORY CYTOKINES AND ACTIVATION OF AUTOREACTIVE B-LYMPHOCYTES. 2018 15 5932 33 TARGETING EPIGENETIC REGULATORS FOR INFLAMMATION: MECHANISMS AND INTERVENTION THERAPY. EMERGING EVIDENCE INDICATES THAT RESOLUTION OF INFLAMMATION IS A CRITICAL AND DYNAMIC ENDOGENOUS PROCESS FOR HOST TISSUES DEFENDING AGAINST EXTERNAL INVASIVE PATHOGENS OR INTERNAL TISSUE INJURY. IT HAS LONG BEEN KNOWN THAT AUTOIMMUNE DISEASES AND CHRONIC INFLAMMATORY DISORDERS ARE CHARACTERIZED BY DYSREGULATED IMMUNE RESPONSES, LEADING TO EXCESSIVE AND UNCONTROL TISSUE INFLAMMATION. THE DYSREGULATION OF EPIGENETIC ALTERATIONS INCLUDING DNA METHYLATION, POSTTRANSLATIONAL MODIFICATIONS TO HISTONE PROTEINS, AND NONCODING RNA EXPRESSION HAS BEEN IMPLICATED IN A HOST OF INFLAMMATORY DISORDERS AND THE IMMUNE SYSTEM. THE INFLAMMATORY RESPONSE IS CONSIDERED AS A CRITICAL TRIGGER OF EPIGENETIC ALTERATIONS THAT IN TURN INTERCEDE INFLAMMATORY ACTIONS. THUS, UNDERSTANDING THE MOLECULAR MECHANISM THAT DICTATES THE OUTCOME OF TARGETING EPIGENETIC REGULATORS FOR INFLAMMATORY DISEASE IS REQUIRED FOR INFLAMMATION RESOLUTION. IN THIS ARTICLE, WE ELUCIDATE THE CRITICAL ROLE OF THE NUCLEAR FACTOR-KAPPAB SIGNALING PATHWAY, JAK/STAT SIGNALING PATHWAY, AND THE NLRP3 INFLAMMASOME IN CHRONIC INFLAMMATORY DISEASES. AND WE FORMULATE THE RELATIONSHIP BETWEEN INFLAMMATION, CORONAVIRUS DISEASE 2019, AND HUMAN CANCERS. ADDITIONALLY, WE REVIEW THE MECHANISM OF EPIGENETIC MODIFICATIONS INVOLVED IN INFLAMMATION AND INNATE IMMUNE CELLS. ALL THAT MATTERS IS THAT WE PROPOSE AND DISCUSS THE REJUVENATION POTENTIAL OF INTERVENTIONS THAT TARGET EPIGENETIC REGULATORS AND REGULATORY MECHANISMS FOR CHRONIC INFLAMMATION-ASSOCIATED DISEASES TO IMPROVE THERAPEUTIC OUTCOMES. 2022 16 6907 23 [THE ROLE OF THE CIRCULAR RNAS IN MULTIPLE SCLEROSIS AND OTHER NEUROIMMUNE DISORDERS]. IN RECENT YEARS NON-CODING RNAS HAVE RECEIVED INCREASING ATTENTION AS AN IMPORTANT EPIGENETIC MECHANISM, WITH PARTICULAR ROLE OF MICRO RNAS. AS THE REGULATION OF MIRNA EXPRESSION IS HIGHLY DYNAMIC AND COMPLEX, GROWING EVIDENCE SUGGESTS THE EXISTENCE OF ANOTHER HIGHER LEVEL OF REGULATORY MECHANISM INVOLVED IN MIRNA ACTIVITY - CIRCULAR RNAS (CIRCRNAS). CIRCRNAS REPRESENT NOVEL, UNIQUE CLASS OF ENDOGENOUS NCRNAS CONTROLLING THE EXPRESSION AND FUNCTION OF MIRNA. THEY ARE CALLED NATURAL MIRNA "SPONGES". ACCUMULATING EVIDENCE REVEALS CIRCRNAS ROLE IN PHYSIOLOGICAL AND PATHOLOGICAL PROCESSES INCLUDING CNS AND IMMUNE REGULATION. PREVIOUS STUDIES IMPLICATED MIRNAS IN REGULATION OF AUTOIMMUNE DEMYELINATION IN MS. MULTIPLE SCLEROSIS IS A CHRONIC NEUROLOGICAL INFLAMMATORY DEMYELINATING DISORDER OF THE CENTRAL NERVOUS SYSTEM. WHILE THE ETIOLOGY OF MS IS STILL NOT FULLY UNDERSTOOD, ACCUMULATING EVIDENCE SUGGESTS THAT IT IS A MULTIFACTORIAL ENTITY WITH SIGNIFICANT INVOLVEMENT OF AUTOIMMUNE PROCESSES. 2022 17 4333 29 MICRORNAS: KEY PLAYERS IN MICROGLIA AND ASTROCYTE MEDIATED INFLAMMATION IN CNS PATHOLOGIES. THE SIGNIFICANCE OF MICROGLIA AND ASTROCYTES IN NEURAL DEVELOPMENT, IN MAINTAINING SYNAPTIC CONNECTIONS AND HOMEOSTASIS IN THE HEALTHY BRAIN IS WELL ESTABLISHED. MICROGLIA ARE DYNAMIC IMMUNE CELLS OF THE BRAIN THAT ELICIT AN IMMUNE RESPONSE DURING BRAIN DAMAGE AND ALSO PARTICIPATE IN TISSUE REPAIR AND REGENERATION, WHILE ASTROCYTES CONTRIBUTE TO THE LOCAL INFLAMMATORY RESPONSE BY PRODUCING PROINFLAMMATORY CYTOKINES AND RESOLVING NEURONAL DAMAGE THROUGH PRODUCTION OF ANTI-INFLAMMATORY CYTOKINES AND NEUROTROPHIC FACTORS. RECENT EFFORTS HAVE FOCUSED ON ELUCIDATING THE EPIGENETIC MECHANISMS WHICH REGULATE GLIAL CELL BEHAVIOR IN NORMAL AND PATHOLOGIC STATES. AN IMPORTANT CLASS OF EPIGENETIC REGULATORS IS MICRORNAS (MIRNAS) WHICH ARE SMALL NON-CODING RNA MOLECULES THAT REGULATE GENE EXPRESSION POSTTRANSCRIPTIONALLY. CERTAIN DYSREGULATED MIRNAS CONTRIBUTE TO CHRONIC MICROGLIAL INFLAMMATION IN THE BRAIN, THEREBY LEADING TO PROGRESSION OF NEUROLOGICAL DISEASES LIKE ALZHEIMER'S DISEASE, TRAUMATIC INJURY, AMYOTROPHIC LATERAL SCLEROSIS AND STROKE. FURTHER, SEVERAL MIRNAS ARE DIFFERENTIALLY EXPRESSED IN ASTROCYTES AFTER ISCHEMIA AND SPINAL CORD INJURY. DESPITE KNOWLEDGE ABOUT MIRNAS IN NEUROINFLAMMATION, LITTLE IS KNOWN ABOUT EFFECTIVE DELIVERY ROUTES AND PHARMACOKINETIC DATA FOR MIRNA BASED THERAPEUTICS. THIS REVIEW SUMMARIZES THE CURRENT RESEARCH ON THE ROLE OF MIRNAS IN PROMOTING AND INHIBITING INFLAMMATORY RESPONSE OF MICROGLIA AND ASTROCYTES IN A DISEASE-SPECIFIC MANNER. IN ADDITION, MIRNA DELIVERY AS A THERAPEUTIC STRATEGY TO TREAT NEUROINFLAMMATION IS DISCUSSED. 2016 18 3772 23 INTERACTION BETWEEN MICRORNA AND DNA METHYLATION IN ATHEROSCLEROSIS. ATHEROSCLEROSIS (AS) IS A CHRONIC INFLAMMATORY DISEASE ACCOMPANIED BY COMPLEX PATHOLOGICAL CHANGES, SUCH AS ENDOTHELIAL DYSFUNCTION, FOAM CELL FORMATION, AND VASCULAR SMOOTH MUSCLE CELL PROLIFERATION. MANY APPROACHES, INCLUDING REGULATING AS-RELATED GENE EXPRESSION IN THE TRANSCRIPTIONAL OR POST-TRANSCRIPTIONAL LEVEL, CONTRIBUTE TO ALLEVIATING AS DEVELOPMENT. THE DNA METHYLATION IS A CRUCIAL EPIGENETIC MODIFICATION IN REGULATING CELL FUNCTION BY SILENCING THE RELATIVE GENE EXPRESSION. THE MICRORNA (MIRNA) IS A TYPE OF NONCODING RNA THAT PLAYS AN IMPORTANT ROLE IN GENE POST-TRANSCRIPTIONAL REGULATION AND DISEASE DEVELOPMENT. THE DNA METHYLATION AND THE MIRNA ARE IMPORTANT EPIGENETIC FACTORS IN AS. HOWEVER, RECENT STUDIES HAVE FOUND A MUTUAL REGULATION BETWEEN THESE TWO FACTORS IN AS DEVELOPMENT. IN THIS STUDY, RECENT INSIGHTS INTO THE ROLES OF MIRNA AND DNA METHYLATION AND THEIR INTERACTION IN THE AS PROGRESSION ARE REVIEWED. 2021 19 4384 26 MITOCHONDRIAL EPIGENETICS REGULATING INFLAMMATION IN CANCER AND AGING. INFLAMMATION IS A DEFINING FACTOR IN DISEASE PROGRESSION; EPIGENETIC MODIFICATIONS OF THIS FIRST LINE OF DEFENCE PATHWAY CAN AFFECT MANY PHYSIOLOGICAL AND PATHOLOGICAL CONDITIONS, LIKE AGING AND TUMORIGENESIS. INFLAMMAGEING, ONE OF THE HALLMARKS OF AGING, REPRESENTS A CHRONIC, LOW KEY BUT A PERSISTENT INFLAMMATORY STATE. OXIDATIVE STRESS, ALTERATIONS IN MITOCHONDRIAL DNA (MTDNA) COPY NUMBER AND MIS-LOCALIZED EXTRA-MITOCHONDRIAL MTDNA ARE SUGGESTED TO DIRECTLY INDUCE VARIOUS IMMUNE RESPONSE PATHWAYS. THIS COULD ULTIMATELY PERTURB CELLULAR HOMEOSTASIS AND LEAD TO PATHOLOGICAL CONSEQUENCES. EPIGENETIC REMODELLING OF MTDNA BY DNA METHYLATION, POST-TRANSLATIONAL MODIFICATIONS OF MTDNA BINDING PROTEINS AND REGULATION OF MITOCHONDRIAL GENE EXPRESSION BY NUCLEAR DNA OR MTDNA ENCODED NON-CODING RNAS, ARE SUGGESTED TO DIRECTLY CORRELATE WITH THE ONSET AND PROGRESSION OF VARIOUS TYPES OF CANCER. MITOCHONDRIA ARE ALSO CAPABLE OF REGULATING IMMUNE RESPONSE TO VARIOUS INFECTIONS AND TISSUE DAMAGE BY PRODUCING PRO- OR ANTI-INFLAMMATORY SIGNALS. THIS OCCURS BY ALTERING THE LEVELS OF MITOCHONDRIAL METABOLITES AND REACTIVE OXYGEN SPECIES (ROS) LEVELS. SINCE MITOCHONDRIA ARE KNOWN AS THE GUARDIANS OF THE INFLAMMATORY RESPONSE, IT IS PLAUSIBLE THAT MITOCHONDRIAL EPIGENETICS MIGHT PLAY A PIVOTAL ROLE IN INFLAMMATION. HENCE, THIS REVIEW FOCUSES ON THE INTRICATE DYNAMICS OF EPIGENETIC ALTERATIONS OF INFLAMMATION, WITH EMPHASIS ON MITOCHONDRIA IN CANCER AND AGING. 2022 20 4278 29 MICROGLIAL INNATE MEMORY AND EPIGENETIC REPROGRAMMING IN NEUROLOGICAL DISORDERS. MICROGLIA ARE MYELOID-DERIVED CELLS RECOGNIZED AS BRAIN-RESIDENT MACROPHAGES. THEY ACT AS THE FIRST AND MAIN LINE OF IMMUNE DEFENSE IN THE CENTRAL NERVOUS SYSTEM (CNS). MICROGLIA HAVE HIGH PHENOTYPIC PLASTICITY AND ARE ESSENTIAL FOR REGULATING HEALTHY BRAIN HOMEOSTASIS, AND THEIR DYSREGULATION UNDERLIES THE ONSET AND PROGRESSION OF SEVERAL CNS PATHOLOGIES THROUGH IMPAIRED INFLAMMATORY RESPONSES. ABERRANT MICROGLIAL ACTIVATION, FOLLOWING AN INFLAMMATORY INSULT, IS ASSOCIATED WITH EPIGENETIC DYSREGULATION IN VARIOUS CNS PATHOLOGIES. EMERGING DATA SUGGEST THAT CERTAIN STIMULI TO MYELOID CELLS DETERMINE ENHANCED OR ATTENUATED RESPONSES TO SUBSEQUENT STIMULI. THESE PHENOMENA, GENERALLY TERMED INNATE IMMUNE MEMORY (IIM), ARE HIGHLY DEPENDENT ON EPIGENETIC REPROGRAMMING. MICROGLIAL PRIMING HAS BEEN REPORTED IN SEVERAL NEUROLOGICAL DISEASES AND CORRESPONDS TO A STATE OF INCREASED PERMISSIVENESS OR EXACERBATED RESPONSE, PROMOTED BY CONTINUOUS EXPOSURE TO A CHRONIC PRO-INFLAMMATORY ENVIRONMENT. IN THIS ARTICLE, WE PROVIDE EXTENSIVE EVIDENCE OF THESE EPIGENETIC-MEDIATED PHENOMENA UNDER NEUROLOGICAL CONDITIONS AND DISCUSS THEIR CONTRIBUTION TO PATHOGENESIS AND THEIR CLINICAL IMPLICATIONS, INCLUDING THOSE CONCERNING POTENTIAL NOVEL THERAPEUTIC APPROACHES. 2021