1 1051 120 CLINICAL IMPLICATIONS OF EXOSOME-DERIVED NONCODING RNAS IN LIVER. EXOSOMES, ONE OF THREE MAIN TYPES OF EXTRACELLULAR VESICLES, ARE ~30-100 NM IN DIAMETER AND HAVE A LIPID BILAYER MEMBRANE. THEY ARE WIDELY DISTRIBUTED IN ALMOST ALL BODY FLUIDS. EXOSOMES HAVE THE POTENTIAL TO REGULATE UNKNOWN CELLULAR AND MOLECULAR MECHANISMS IN INTERCELLULAR COMMUNICATION, ORGAN HOMEOSTASIS, AND DISEASES. THEY ARE CRITICAL SIGNAL CARRIERS THAT TRANSFER NUCLEIC ACIDS, PROTEINS, LIPIDS, AND OTHER SUBSTANCES INTO RECIPIENT CELLS, PARTICIPATING IN CELLULAR SIGNAL TRANSDUCTION AND MATERIAL EXCHANGE. NCRNAS ARE NON-PROTEIN-CODING GENES THAT ACCOUNT FOR OVER 90% OF THE GENOME AND INCLUDE MICRORNAS (MIRNAS), LONG NCRNAS (LNCRNAS), AND CIRCULAR RNAS (CIRCRNAS). NCRNAS ARE CRUCIAL FOR PHYSIOLOGICAL AND PATHOLOGICAL ACTIVITIES IN THE LIVER BY PARTICIPATING IN GENE TRANSCRIPTION, POSTTRANSCRIPTIONAL EPIGENETIC REGULATION, AND CELLULAR PROCESSES THROUGH INTERACTING WITH DNA, RNA, OR PROTEINS. RECENT EVIDENCE FROM BOTH CLINICAL AND PRECLINICAL STUDIES INDICATES THAT EXOSOME-DERIVED NONCODING RNAS (NCRNAS) ARE HIGHLY INVOLVED IN THE PROGRESSION OF ACUTE AND CHRONIC LIVER DISEASES BY REGULATING HEPATIC LIPID METABOLISM, INNATE IMMUNITY, VIRAL INFECTION, FIBROSIS, AND CANCER. THEREFORE, EXOSOME-DERIVED NCRNAS HAVE PROMISING POTENTIAL AND CLINICAL IMPLICATIONS FOR THE EARLY DIAGNOSIS, TARGETED THERAPY, AND PROGNOSIS OF LIVER DISEASES. 2022 2 263 24 ADVANCES WITH LONG NON-CODING RNAS IN DIABETIC PERIPHERAL NEUROPATHY. LONG NON-CODING RNAS (?LNCRNAS) ?ARE A GROUP OF NON-CODING RNAS LONGER THAN 200 NUCLEOTIDES, WHICH ARE DEFINED AS TRANSCRIPTS. THE LNCRNAS ARE INVOLVED IN REGULATING GENE EXPRESSION AT EPIGENETIC, TRANSCRIPTIONAL, AND POST-TRANSCRIPTIONAL LEVELS. RECENT STUDIES HAVE FOUND THAT LNCRNA IS CLOSELY RELATED TO MANY DISEASES LIKE NEUROLOGICAL DISEASES, ENDOCRINE AND METABOLIC DISORDERS. DIABETIC PERIPHERAL NEUROPATHY (DPN) IS ONE OF THE MOST COMMON CHRONIC COMPLICATIONS OF DIABETES MELLITUS. IN THIS REVIEW, WE HIGHLIGHT THE LATEST RESEARCH RELATED TO LNCRNAS IN DPN. 2020 3 6882 20 [RESEARCH PROGRESS ON NON-CODING RNAS IN THE MOLECULAR PATHOGENESIS OF HEPATOCELLULAR CARCINOMA]. PRIMARY LIVER CANCER ARISES FROM CHRONIC LIVER DISEASE, AND CIRRHOTIC LIVER GRADUALLY DEVELOPS INTO DYSPLASTIC NODULES THAT EVENTUALLY FORM MALIGNANT TUMORS. IN RECENT YEARS, MOLECULAR BIOTECHNOLOGY DEVELOPMENT HAS DEEPENED PEOPLE'S UNDERSTANDING ON THE PATHOGENESIS OF LIVER CANCER. EPIGENETIC MODIFICATIONS PLAY A SIGNIFICANT ROLE IN DNA METHYLATION, NON-CODING RNAS, CHROMATIN REMODELING, AND HISTONE MODIFICATION. THIS REVIEW FOCUSES ON THE PROGRESS OF CURRENTLY IMPLICATED NON-CODING RNAS IN THE MOLECULAR PATHOGENESIS OF HEPATOCELLULAR CARCINOMA, AND ITS POTENTIAL APPLICATION IN IMPROVING THE DIAGNOSIS AND TREATMENT. 2018 4 6152 25 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 5 5264 29 PROMISING DIRECTIONS IN ATHEROSCLEROSIS TREATMENT BASED ON EPIGENETIC REGULATION USING MICRORNAS AND LONG NONCODING RNAS. ATHEROSCLEROSIS IS ONE OF THE LEADING CAUSES OF MORTALITY FROM CARDIOVASCULAR DISEASE (CVD) AND IS A CHRONIC INFLAMMATORY DISEASE OF THE MIDDLE AND LARGE ARTERIES CAUSED BY A DISRUPTION OF LIPID METABOLISM. NONCODING RNA (NCRNA), INCLUDING MICRORNA (MIRNA), SMALL INTERFERING RNA (SIRNA) AND LONG NONCODING RNA (LNCRNA), WAS INVESTIGATED FOR THE TREATMENT OF ATHEROSCLEROSIS. REGULATION OF THE EXPRESSION OF NONCODING RNA TARGETS THE CONSTITUENT ELEMENT OF THE PATHOGENESIS OF ATHEROSCLEROSIS. CURRENTLY, MIRNA THERAPY COMMONLY EMPLOYS MIRNA ANTAGONISTS AND MIMIC COMPOUNDS. IN THIS REVIEW, ATTENTION IS FOCUSED ON APPROACHES TO CORRECTING MOLECULAR DISORDERS BASED ON THE GENETIC REGULATION OF THE TRANSCRIPTION OF KEY GENES RESPONSIBLE FOR THE DEVELOPMENT OF ATHEROSCLEROSIS. PROMISING TECHNOLOGIES WERE CONSIDERED FOR THE TREATMENT OF ATHEROSCLEROSIS, AND EXAMPLES ARE GIVEN FOR TECHNOLOGIES THAT HAVE BEEN SHOWN TO BE EFFECTIVE IN CLINICAL TRIALS. 2019 6 2276 28 EPIGENETIC REGULATION AS A PROMISING TOOL FOR TREATMENT OF ATHEROSCLEROSIS. ATHEROSCLEROSIS IS ONE OF THE LEADING CAUSES OF DEATH FROM CARDIOVASCULAR DISEASE (CVD) THAT PRIMARILY INVOLVES MID SIZE AND LARGE ARTERIES. ATHEROSCLEROSIS IS ASSOCIATED WITH DISRUPTION OF LIPID METABOLISM AND CHRONIC INFLAMMATORY PROCESSES. ONE APPROACH FOR TREATMENT OF ATHEROSCLEROSIS IS BY VIRTUE OF EPIGENETIC CONTROL BY NONCODING RNAS (NCRNA) INCLUDING MIRNA, SIRNA AND LNCRNA, COMMONLY EMPLOYING MIRNA ANTAGONISTS AND MIMIC COMPOUNDS. HERE, WE REVIEW SUCH USAGES AS WELL AS OTHER APPROACHES FOR CORRECTING THE MOLECULAR LESIONS OF ATHEROSCLEROSIS INCLUDING SPECIFIC ACTIVATION OF ATHEROPROTECTIVE MIRNAS, AS WELL AS USE OF SIRNAS AND LCRNA TO CONTROL ABERRANT LIPID METABOLISM. WE ALSO DISCUSS SOME OF THESE TECHNOLOGIES THAT HAVE ALREADY SHOWN TO BE EFFECTIVE IN CLINICAL TRIALS AND ARE LIKELY TO ENTER THE CLINICAL ARENA. 2020 7 4720 30 NONCODING RNAS AS ADDITIONAL MEDIATORS OF EPIGENETIC REGULATION IN NONALCOHOLIC FATTY LIVER DISEASE. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) HAS EMERGED AS THE MOST COMMON CAUSE OF CHRONIC LIVER DISORDER WORLDWIDE. IT REPRESENTS A SPECTRUM THAT INCLUDES A CONTINUUM OF DIFFERENT CLINICAL ENTITIES RANGING FROM SIMPLE STEATOSIS TO NONALCOHOLIC STEATOHEPATITIS, WHICH CAN EVOLVE TO CIRRHOSIS AND IN SOME CASES TO HEPATOCELLULAR CARCINOMA, ULTIMATELY LEADING TO LIVER FAILURE. THE PATHOGENESIS OF NAFLD AND THE MECHANISMS UNDERLYING ITS PROGRESSION TO MORE PATHOLOGICAL STAGES ARE NOT COMPLETELY UNDERSTOOD. BESIDES GENETIC FACTORS, EVIDENCE INDICATES THAT EPIGENETIC MECHANISMS OCCURRING IN RESPONSE TO ENVIRONMENTAL STIMULI ALSO CONTRIBUTE TO THE DISEASE RISK. NONCODING RNAS (NCRNAS), INCLUDING MICRORNAS, LONG NONCODING RNAS, AND CIRCULAR RNAS, ARE ONE OF THE EPIGENETIC FACTORS THAT PLAY KEY REGULATORY ROLES IN THE DEVELOPMENT OF NAFLD. AS THE FIELD OF NCRNAS IS RAPIDLY EVOLVING, THE PRESENT REVIEW AIMS TO EXPLORE THE CURRENT STATE OF KNOWLEDGE ON THE ROLES OF THESE RNA SPECIES IN THE PATHOGENESIS OF NAFLD, HIGHLIGHT RELEVANT MECHANISMS BY WHICH SOME NCRNAS CAN MODULATE REGULATORY NETWORKS IMPLICATED IN NAFLD, AND DISCUSS KEY CHALLENGES AND FUTURE DIRECTIONS FACING CURRENT RESEARCH IN THE HOPES OF DEVELOPING NCRNAS AS NEXT-GENERATION NON-INVASIVE DIAGNOSTICS AND THERAPIES IN NAFLD AND SUBSEQUENT PROGRESSION TO HEPATOCELLULAR CARCINOMA. 2022 8 1021 31 CIRCULAR RNA AS AN EPIGENETIC REGULATOR IN CHRONIC LIVER DISEASES. CIRCULAR RNA (CIRCRNA) IS A TYPE OF NON-CODING RNA CHARACTERIZED BY A COVALENTLY CLOSED CONTINUOUS LOOP. CIRCRNA IS GENERATED BY PRE-MRNA THROUGH BACK-SPLICING AND IS PROBABLY CLEARED UP BY EXTRACELLULAR VESICLES. CIRCRNAS PLAY A PIVOTAL ROLE IN THE EPIGENETIC REGULATION OF GENE EXPRESSION AT TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL LEVELS. RECENTLY, CIRCRNAS HAVE BEEN DEMONSTRATED TO BE INVOLVED IN THE REGULATION OF LIVER HOMEOSTASIS AND DISEASES. HOWEVER, THE EPIGENETIC ROLE AND UNDERLYING MECHANISMS OF CIRCRNAS IN CHRONIC LIVER DISEASES REMAIN UNCLEAR. THIS REVIEW DISCUSSED THE ROLE OF CIRCRNAS IN NON-NEOPLASTIC CHRONIC LIVER DISEASES, INCLUDING ALCOHOLIC LIVER DISEASE (ALD), METABOLIC-ASSOCIATED FATTY LIVER DISEASE (MAFLD), VIRAL HEPATITIS, LIVER INJURY AND REGENERATION, LIVER CIRRHOSIS, AND AUTOIMMUNE LIVER DISEASE. THE REVIEW ALSO HIGHLIGHTED THAT FURTHER EFFORTS ARE URGENTLY NEEDED TO DEVELOP CIRCRNAS AS NOVEL DIAGNOSTICS AND THERAPEUTICS FOR CHRONIC LIVER DISEASES. 2021 9 6289 25 THE POTENTIAL ROLE OF GENETICS, ENVIRONMENTAL FACTORS, AND GUT DYSBIOSIS IN THE ABERRANT NON-CODING RNA EXPRESSION TO MEDIATE INFLAMMATION AND OSTEOCLASTOGENIC/OSTEOGENIC DIFFERENTIATION IN ANKYLOSING SPONDYLITIS. ANKYLOSING SPONDYLITIS (AS) OR RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS IS A CHRONIC IMMUNE-MEDIATED RHEUMATIC DISORDER CHARACTERIZED BY THE INFLAMMATION IN THE AXIAL SKELETON, PERIPHERAL JOINTS, AND SOFT TISSUES (ENTHESIS, FASCIA, AND LIGAMENT). IN ADDITION, THE EXTRA-SKELETAL COMPLICATIONS INCLUDING ANTERIOR UVEITIS, INTERSTITIAL LUNG DISEASES AND AORTITIS ARE FOUND. THE PATHOGENESIS OF AS IMPLICATES AN INTRICATE INTERACTION AMONG HLA (HLA-B27) AND NON-HLA LOCI [ENDOPLASMIC RETICULUM AMINOPEPTIDASE 1 (ERAP1), AND INTERLEUKIN-23 RECEPTOR (IL23R), GUT DYSBIOSIS, IMMUNE PLASTICITY, AND NUMEROUS ENVIRONMENTAL FACTORS (INFECTIONS, HEAVY METALS, STRESS, CIGARETTE SMOKING, ETC.) THE LATTER MULTIPLE NON-GENETIC FACTORS MAY EXERT A POWERFUL STRESS ON EPIGENETIC REGULATIONS. THESE EPIGENETIC REGULATIONS OF GENE EXPRESSION CONTAIN DNA METHYLATION/DEMETHYLATION, HISTONE MODIFICATIONS AND ABERRANT NON-CODING RNAS (NCRNAS) EXPRESSION, LEADING TO INFLAMMATION AND IMMUNE DYSFUNCTIONS. IN THE PRESENT REVIEW, WE SHALL DISCUSS THESE CONTRIBUTORY FACTORS THAT ARE INVOLVED IN AS PATHOGENESIS, ESPECIALLY THE ABERRANT NCRNA EXPRESSION AND ITS EFFECTS ON THE PROINFLAMMATORY CYTOKINE PRODUCTIONS (TNF-ALPHA, IL-17 AND IL-23), T CELL SKEWING TO TH1/TH17, AND OSTEOCLASTOGENIC/OSTEOGENIC DIFFERENTIATION. FINALLY, SOME POTENTIAL INVESTIGATORY APPROACHES ARE RAISED FOR SOLVING THE PUZZLES IN AS PATHOGENESIS. 2021 10 1879 30 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 11 6107 35 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 12 1059 20 CLINICAL PERSPECTIVES OF NON-CODING RNA IN ORAL INFLAMMATORY DISEASES AND NEUROPATHIC PAIN: A NARRATIVE REVIEW. NON-CODING RNAS (NCRNAS) REPRESENT A RESEARCH HOTSPOT BY PLAYING A KEY ROLE IN EPIGENETIC AND TRANSCRIPTIONAL REGULATION OF DIVERSE BIOLOGICAL FUNCTIONS AND DUE TO THEIR INVOLVEMENT IN DIFFERENT DISEASES, INCLUDING ORAL INFLAMMATORY DISEASES. BASED ON NCRNAS' SUITABILITY FOR SALIVARY BIOMARKERS AND THEIR INVOLVEMENT IN NEUROPATHIC PAIN AND TISSUE REGENERATION SIGNALING PATHWAYS, THE PRESENT NARRATIVE REVIEW AIMS TO HIGHLIGHT THE POTENTIAL CLINICAL APPLICATIONS OF NCRNAS IN ORAL INFLAMMATORY DISEASES, WITH AN EMPHASIS ON SALIVARY DIAGNOSTICS, REGENERATIVE DENTISTRY, AND PRECISION MEDICINE FOR NEUROPATHIC OROFACIAL PAIN. 2022 13 3957 24 LONG NON-CODING RNAS AS EMERGING REGULATORS OF MIRNAS AND EPIGENETICS IN DIABETES-RELATED CHRONIC KIDNEY DISEASE. DIABETES IS ONE OF THE MAJOR CAUSE OF CHRONIC KIDNEY DISEASE (CKD), INCLUDING "DIABETIC NEPHROPATHY," AND IS AN INCREASINGLY PREVALENT ACCELERATOR OF THE PROGRESSION OF NON-DIABETIC FORMS OF CKD. THE LONG NON-CODING RNAS (LNCRNAS) HAVE COME INTO THE LIMELIGHT IN THE PAST FEW YEARS AS ONE OF THE EMERGING WEAPONS AGAINST CKD IN DIABETES. AVAILABLE DATA OVER THE PAST FEW YEARS DEMONSTRATE THE INTERACTION OF LNCRNAS WITH MIRNAS AND EPIGENETIC MACHINERY. INTERESTINGLY, THE EVOLVING DATA SUGGEST THAT LNCRNAS PLAY A VITAL ROLE IN DIABETES-ASSOCIATED CKD BY REGULATION OF EPIGENETIC ENZYMES SUCH AS DNA METHYLTRANSFERASE, HISTONE DEACETYLASES, AND HISTONE METHYLTRANSFERASES. LNCRNAS ARE ALSO ENGAGED IN THE REGULATION OF SEVERAL MIRNAS IN DIABETIC NEPHROPATHY. HENCE THIS REVIEW WILL ELABORATE ON THE ASSOCIATION BETWEEN LNCRNAS AND THEIR INTERACTION WITH EPIGENETIC REGULATORS INVOLVED IN DIFFERENT ASPECTS AND THUS THE PROGRESSION OF CKD IN DIABETES. 2022 14 4722 33 NONCODING RNAS IN NONALCOHOLIC FATTY LIVER DISEASE: POTENTIAL DIAGNOSIS AND PROGNOSIS BIOMARKERS. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS CURRENTLY THE MOST COMMON CHRONIC LIVER DISEASE WORLDWIDE IN PART DUE TO THE CONCOMITANT OBESITY PANDEMIC AND INSULIN RESISTANCE (IR). IT IS INCREASINGLY BECOMING EVIDENT THAT NAFLD IS A DISEASE AFFECTING NUMEROUS EXTRAHEPATIC VITAL ORGANS AND REGULATORY PATHWAYS. THE MOLECULAR MECHANISMS UNDERLYING THE NONALCOHOLIC STEATOSIS FORMATION ARE POORLY UNDERSTOOD, AND LITTLE INFORMATION IS AVAILABLE ON THE PATHWAYS THAT ARE RESPONSIBLE FOR THE PROGRESSIVE HEPATOCELLULAR DAMAGE THAT FOLLOWS LIPID ACCUMULATION. RECENTLY, MUCH RESEARCH HAS FOCUSED ON THE IDENTIFICATION OF THE EPIGENETIC MODIFICATIONS THAT CONTRIBUTE TO NAFLD PATHOGENESIS. NONCODING RNAS (NCRNAS) ARE ONE OF SUCH EPIGENETIC FACTORS THAT COULD BE IMPLICATED IN THE NAFLD DEVELOPMENT AND PROGRESSION. IN THIS REVIEW, WE SUMMARIZE THE CURRENT KNOWLEDGE OF THE GENETIC AND EPIGENETIC FACTORS POTENTIALLY UNDERLYING THE DISEASE. PARTICULAR EMPHASIS WILL BE PUT ON THE CONTRIBUTION OF MICRORNAS (MIRNAS), LONG NONCODING RNAS (LNCRNAS), AND CIRCULAR RNAS (CIRCRNAS) TO THE PATHOPHYSIOLOGY OF NAFLD AS WELL AS THEIR POTENTIAL USE AS THERAPEUTIC TARGETS OR AS MARKERS FOR THE PREDICTION AND THE PROGRESSION OF THE DISEASE. 2020 15 6229 29 THE LNCRNAS IN HBV-RELATED HCCS: TARGETING CHROMATIN DYNAMICS AND BEYOND. HEPATOCELLULAR CARCINOMA (HCC) REPRESENTS THE FOURTH LEADING AND FASTEST RISING CAUSE OF CANCER DEATH (841,000 NEW CASES AND 782,000 DEATHS ANNUALLY), AND HEPATITIS B (HBV), WITH 250 MILLION PEOPLE CHRONICALLY INFECTED AT RISK OF DEVELOPING HCC, ACCOUNTS FOR >50% OF THE CASES WORLDWIDE. LONG NON-CODING RNAS (LNCRNAS), UNTRANSLATED TRANSCRIPTS LONGER THAN 200 NUCLEOTIDES, ARE IMPLICATED IN GENE REGULATION AT THE TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL LEVELS, EXERTING THEIR ACTIVITIES BOTH IN THE NUCLEAR AND CYTOPLASMIC COMPARTMENTS. THANKS TO HIGH-THROUGHPUT SEQUENCING TECHNIQUES, SEVERAL LNCRNAS HAVE BEEN SHOWN TO FAVOR THE ESTABLISHMENT OF CHRONIC HBV INFECTION, TO CHANGE THE HOST TRANSCRIPTOME TO ESTABLISH A PRO-CARCINOGENIC ENVIRONMENT, AND TO DIRECTLY PARTICIPATE IN HCC DEVELOPMENT AND PROGRESSION. IN THIS REVIEW, WE SUMMARIZE CURRENT KNOWLEDGE ON THE ROLE OF LNCRNAS IN HBV INFECTION AND HBV-RELATED LIVER CARCINOGENESIS AND DISCUSS THE POTENTIAL OF LNCRNAS AS PREDICTIVE OR DIAGNOSTIC BIOMARKERS. 2021 16 2188 32 EPIGENETIC MECHANISMS UNDERLYING THE BENEFITS OF FLAVONOIDS IN CARDIOVASCULAR HEALTH AND DISEASES: ARE LONG NON-CODING RNAS RISING STARS? CARDIOVASCULAR DISEASES (CVDS) RANK AS THE FIRST LEADING CAUSE OF DEATH GLOBALLY. HIGH DIETARY POLYPHENOL (ESPECIALLY FLAVONOIDS) INTAKE HAS STRONGLY BEEN ASSOCIATED WITH LOW INCIDENCE OF THE PRIMARY OUTCOME, OVERALL MORTALITY, BLOOD PRESSURE, INFLAMMATORY BIOMARKERS, ONSET OF NEW-ONSET TYPE 2 DIABETES MELLITUS (T2DM), AND OBESITY. PHYTOGENIC FLAVONOIDS AFFECT THE PHYSIOLOGICAL AND PATHOLOGICAL PROCESSES OF CVDS BY MODULATING VARIOUS BIOCHEMICAL SIGNALING PATHWAYS. NON-CODING RNAS (NCRNAS) HAVE ATTRACTED INCREASING ATTENTION AS FUNDAMENTAL REGULATOR OF GENE EXPRESSION INVOLVED IN CVDS. AMONG THE DIFFERENT NCRNA SUBGROUPS, LONG NCRNAS (LNCRNAS) HAVE RECENTLY EMERGED AS REGULATORY EUKARYOTIC TRANSCRIPTS AND THERAPEUTIC TARGETS WITH IMPORTANT AND DIVERSE FUNCTIONS IN HEALTH AND DISEASES. LNCRNAS MAY BE ASSOCIATED WITH THE INITIATION, DEVELOPMENT AND PROGRESSION OF CVDS BY MODULATING ACUTE AND CHRONIC INFLAMMATION, ADIPOGENESIS AND LIPID METABOLISM, AND CELLULAR PHYSIOLOGY. THIS REVIEW SUMMARIZES THIS RESEARCH ON THE MODULATORY EFFECTS OF LNCRNAS AND THEIR ROLES IN MEDIATING CELLULAR PROCESSES. THE MECHANISMS OF ACTION OF FLAVONOIDS UNDERLYING THEIR THERAPEUTIC EFFECTS ON CVDS ARE ALSO DISCUSSED. BASED ON OUR REVIEW, FLAVONOIDS MIGHT FACILITATE A SIGNIFICANT EPIGENETIC MODIFICATION AS PART (IF NOT FULL) OF THEIR TISSUE-/CELL-RELATED BIOLOGICAL EFFECTS. THIS FINDING MAY BE ATTRIBUTED TO THEIR INTERACTION WITH CELLULAR SIGNALING PATHWAYS INVOLVED IN CHRONIC DISEASES. CERTAIN LNCRNAS MIGHT BE THE TARGET OF SPECIFIC FLAVONOIDS, AND SOME CRITICAL SIGNALING PROCESSES INVOLVED IN THE INTERVENTION OF CVDS MIGHT MEDIATE THE THERAPEUTIC ROLES OF FLAVONOIDS. 2022 17 1480 28 DIVERSITY OF DYSREGULATED LONG NON-CODING RNAS IN HBV-RELATED HEPATOCELLULAR CARCINOMA. INFECTION WITH THE HEPATITIS B VIRUS (HBV) CONTINUES TO POSE A MAJOR THREAT TO PUBLIC HEALTH AS APPROXIMATELY 292 MILLION PEOPLE WORLDWIDE ARE CURRENTLY LIVING WITH THE CHRONIC FORM OF THE DISEASE, FOR WHICH TREATMENT IS NON-CURATIVE. CHRONIC HBV INFECTIONS OFTEN PROGRESS TO HEPATOCELLULAR CARCINOMA (HCC) WHICH IS ONE OF THE WORLD'S LEADING CAUSES OF CANCER-RELATED DEATHS. ALTHOUGH THE PROCESS OF HEPATOCARCINOGENESIS IS MULTIFACETED AND HAS YET TO BE FULLY ELUCIDATED, SEVERAL STUDIES HAVE IMPLICATED NUMEROUS LONG NON-CODING RNAS (LNCRNAS) AS CONTRIBUTORS TO THE DEVELOPMENT OF HCC. THESE HOST-DERIVED LNCRNAS, WHICH ARE OFTEN DYSREGULATED AS A CONSEQUENCE OF VIRAL INFECTION, HAVE BEEN SHOWN TO FUNCTION AS SIGNALS, DECOYS, GUIDES, OR SCAFFOLDS, TO MODULATE GENE EXPRESSION AT EPIGENETIC, TRANSCRIPTIONAL, POST-TRANSCRIPTIONAL AND EVEN POST-TRANSLATIONAL LEVELS. THESE LNCRNAS MAINLY FUNCTION TO PROMOTE HBV REPLICATION AND ONCOGENE EXPRESSION OR DOWNREGULATE TUMOR SUPPRESSORS. VERY FEW LNCRNAS ARE KNOWN TO SUPPRESS TUMORIGENESIS AND THESE ARE OFTEN DOWNREGULATED IN HCC. IN THIS REVIEW, WE DESCRIBE THE MECHANISMS BY WHICH LNCRNA DYSREGULATION IN HBV-RELATED HCC PROMOTES TUMORIGENESIS AND CANCER PROGRESSION. 2022 18 2014 22 EPIGENETIC BIOMARKERS FOR THE DIAGNOSIS AND TREATMENT OF LIVER DISEASE. RESEARCH IN THE LAST DECADES HAS DEMONSTRATED THE RELEVANCE OF EPIGENETICS IN CONTROLLING GENE EXPRESSION TO MAINTAIN CELL HOMEOSTASIS, AND THE IMPORTANT ROLE PLAYED BY EPIGENOME ALTERATIONS IN DISEASE DEVELOPMENT. MOREOVER, THE REVERSIBILITY OF EPIGENETIC MARKS CAN BE HARNESSED AS A THERAPEUTIC STRATEGY, AND EPIGENETIC MARKS CAN BE USED AS DIAGNOSIS BIOMARKERS. EPIGENETIC ALTERATIONS IN DNA METHYLATION, HISTONE POST-TRANSLATIONAL MODIFICATIONS (PTMS), AND NON-CODING RNA (NCRNA) EXPRESSION HAVE BEEN ASSOCIATED WITH THE PROCESS OF HEPATOCARCINOGENESIS. HERE, WE SUMMARIZE EPIGENETIC ALTERATIONS INVOLVED IN THE PATHOGENESIS OF CHRONIC LIVER DISEASE (CLD), PARTICULARLY FOCUSING ON DNA METHYLATION. WE ALSO DISCUSS THEIR UTILITY AS EPIGENETIC BIOMARKERS IN LIQUID BIOPSY FOR THE DIAGNOSIS AND PROGNOSIS OF HEPATOCELLULAR CARCINOMA (HCC). FINALLY, WE DISCUSS THE POTENTIAL OF EPIGENETIC THERAPEUTIC STRATEGIES FOR HCC TREATMENT. 2021 19 3960 36 LONG NON-CODING RNAS: A DOUBLE-EDGED SWORD IN AGING KIDNEY AND RENAL DISEASE. AGING AS ONE OF INTRINSIC BIOLOGICAL PROCESSES IS A RISK FACTOR FOR MANY CHRONIC DISEASES. KIDNEY DISEASE IS A GLOBAL PROBLEM AND HEALTH CARE BURDEN WORLDWIDE. THE DIAGNOSIS OF KIDNEY DISEASE IS CURRENTLY BASED ON SERUM CREATININE AND UREA LEVELS. NOVEL BIOMARKERS MAY IMPROVE DIAGNOSTIC ACCURACY, THEREBY ALLOWING EARLY PREVENTION AND TREATMENT. OVER THE PAST FEW YEARS, ADVANCES IN GENOME ANALYSES HAVE IDENTIFIED AN EMERGING CLASS OF NONCODING RNAS THAT PLAY CRITICAL ROLES IN THE REGULATION OF GENE EXPRESSION AND EPIGENETIC REPROGRAMMING. LONG NONCODING RNAS (LNCRNAS) ARE PERVASIVELY TRANSCRIBED IN THE GENOME AND COULD BIND DNA, RNA AND PROTEIN. EMERGING EVIDENCE HAS DEMONSTRATED THAT LNCRNAS PLAYED AN IMPORTANT ROLE IN ALL STAGES OF KIDNEY DISEASE. TO DATE, ONLY SOME LNCRNAS WERE WELL IDENTIFIED AND CHARACTERIZED, BUT THE COMPLEXITY OF MULTILEVEL REGULATION OF TRANSCRIPTIONAL PROGRAMS INVOLVED IN THESE PROCESSES REMAINS UNDEFINED. IN THIS REVIEW, WE SUMMARIZED THE LNCRNA EXPRESSION PROFILING OF LARGE-SCALE IDENTIFIED LNCRNAS ON KIDNEY DISEASES INCLUDING ACUTE KIDNEY INJURY, CHRONIC KIDNEY DISEASE, DIABETIC NEPHROPATHY AND KIDNEY TRANSPLANTATION. WE FURTHER DISCUSSED A NUMBER OF ANNOTATED LNCRNAS LINKING WITH COMPLEX ETIOLOGY OF KIDNEY DISEASES. FINALLY, SEVERAL LNCRNAS WERE HIGHLIGHTED AS DIAGNOSTIC BIOMARKERS AND THERAPEUTIC TARGETS. TARGETING LNCRNAS MAY REPRESENT A PRECISE THERAPEUTIC STRATEGY FOR PROGRESSIVE RENAL FIBROSIS. 2021 20 4335 38 MICRORNAS: SMALL MOLECULES WITH SIGNIFICANT FUNCTIONS, PARTICULARLY IN THE CONTEXT OF VIRAL HEPATITIS B AND C INFECTION. A MICRORNA (MIRNA) IS DEFINED AS A SMALL MOLECULE OF NON-CODING RNA (NCRNA). ITS MOLECULAR SIZE IS ABOUT 20 NUCLEOTIDES (NT), AND IT ACTS ON GENE EXPRESSION'S REGULATION AT THE POST-TRANSCRIPTION LEVEL THROUGH BINDING TO THE 3'UNTRANSLATED REGIONS (UTR), CODING SEQUENCES, OR 5'UTR OF THE TARGET MESSENGER RNAS (MRNAS), WHICH LEADS TO THE SUPPRESSION OR DEGRADATION OF THE MRNA. IN RECENT YEARS, A HUGE EVOLUTION HAS IDENTIFIED THE ORIGIN AND FUNCTION OF MIRNAS, FOCUSING ON THEIR IMPORTANT EFFECTS IN RESEARCH AND CLINICAL APPLICATIONS. FOR EXAMPLE, MICRORNAS ARE KEY PLAYERS IN HCV INFECTION AND HAVE IMPORTANT HOST CELLULAR FACTORS REQUIRED FOR HCV REPLICATION AND CELL GROWTH. ALTERED EXPRESSION OF MIRNAS AFFECTS THE PATHOGENICITY ASSOCIATED WITH HCV INFECTION THROUGH REGULATING DIFFERENT SIGNALING PATHWAYS THAT CONTROL HCV/IMMUNITY INTERACTIONS, PROLIFERATION, AND CELL DEATH. ON THE OTHER HAND, CIRCULATING MIRNAS CAN BE USED AS NOVEL BIOMARKERS AND DIAGNOSTIC TOOLS FOR HCV PATHOGENESIS AND EARLY THERAPEUTIC RESPONSE. MOREOVER, MICRORNAS (MIRNA) HAVE BEEN INVOLVED IN HEPATITIS B VIRUS (HBV) GENE EXPRESSION AND ADVANCED ANTIVIRAL DISCOVERY. THEY REGULATE HBV/HCV REPLICATION AND PATHOGENESIS WITH DIFFERENT PATHWAYS INVOLVING FACILITATION, INHIBITION, ACTIVATION OF THE IMMUNE SYSTEM (INNATE AND ADAPTIVE), AND EPIGENETIC MODIFICATIONS. IN THIS SHORT REVIEW, WE WILL DISCUSS HOW MICRORNAS CAN BE USED AS PROGNOSTIC, DIAGNOSTIC, AND THERAPEUTIC TOOLS, ESPECIALLY FOR CHRONIC HEPATITIS VIRUSES (HBV AND HCV), AS WELL AS HOW THEY COULD BE USED AS NEW BIOMARKERS DURING INFECTION AND ADVANCED TREATMENT. 2023