1 6738 119 WHAT'S YOUR CUP OF TEA? THE ROLE OF HERBAL COMPOUNDS IN THE MANAGEMENT OF MULTIPLE SCLEROSIS. MULTIPLE SCLEROSIS (MS) IS A CHRONIC, INFLAMMATORY, NEURODEGENERATIVE DISEASE THAT IS CHARACTERIZED BY A COMPLEX ETIOLOGY. EFFORTS TOWARDS THE MANAGEMENT OF MS HAVE LONG BEEN DIRECTED TOWARDS SYMPTOMATIC RELIEF, AS WELL AS THE USE OF IMMUNE-MODULATORY, DISEASE MODIFYING THERAPIES; HOWEVER, INCONSISTENT TREATMENT RESPONSES STILL PREVAIL, INCREASING THE RISK FOR DISEASE PROGRESSION. WHILE A GREAT DEAL OF RESEARCH ATTEMPTED TO UNRAVEL THE COMPLEXITY OF TREATMENT RESPONSES IN LIGHT OF EPIGENETIC VARIABILITY, PARALLEL EFFORTS IN THE DIRECTION OF ALTERNATIVE MEDICINE MAY BE AS PARAMOUNT. HERBAL COMPOUNDS HAVE LONG BEEN REGARDED AS SAFE AND VERSATILE OPTIONS FOR AIDING IN VARIOUS DISORDERS, INCLUDING NEURODEGENERATIVE CONDITIONS LIKE MS. NUMEROUS STUDIES HAVE TAKEN INTEREST IN A MYRIAD OF HERBAL PLANTS FOR THEIR POTENTIAL BENEFIT IN ALLEVIATING SOME OF THE MOST COMMON MS SYMPTOMS SUCH AS SPASTICITY AND FATIGUE, DELAYING THE PROGRESSION OF THE DISEASE, AS WELL AS INFLUENCING THE OVERALL QUALITY OF LIFE FOR MS PATIENTS. THIS REVIEW AIMS TO PROVIDE A COMPREHENSIVE OVERVIEW OF RECENT CLINICAL STUDIES EXAMINING THE EFFECTS OF VARIOUS HERBAL PLANTS ON DIFFERENT ASPECTS OF MS, IN AN ATTEMPT TO SHED LIGHT ON AN IMPORTANT TOOL FOR AIDING IN THE MANAGEMENT OF THIS COMPLEX AND MULTIFACTORIAL DISEASE. 2023 2 6565 23 TRANSLATING EPIGENETICS INTO CLINIC: FOCUS ON LUPUS. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC RELAPSING-REMITTING AUTOIMMUNE DISEASE WITH HIGHLY HETEROGENEOUS PHENOTYPES. BIOMARKERS WITH HIGH SENSITIVITY AND SPECIFICITY ARE USEFUL FOR EARLY DIAGNOSIS AS WELL AS MONITORING DISEASE ACTIVITY AND LONG-TERM COMPLICATIONS. EPIGENETICS POTENTIALLY PROVIDE NOVEL BIOMARKERS IN AUTOIMMUNE DISEASES. THESE MAY INCLUDE DNA METHYLATION CHANGES IN RELEVANT LUPUS-PRONE GENES OR HISTONE MODIFICATIONS AND MICRORNAS TO UPREGULATE AND DOWNREGULATE RELEVANT GENE EXPRESSION. THE TIMING AND NATURE OF EPIGENETIC MODIFICATION PROVIDE SUCH CHANGES. IN LUPUS, DNA METHYLATION ALTERATIONS IN CYTOKINE GENES, SUCH AS IFN-RELATED GENE AND RETROVIRUS GENE, HAVE BEEN FOUND TO OFFER BIOMARKERS FOR LUPUS DIAGNOSIS. HISTONE MODIFICATIONS SUCH AS HISTONE METHYLATION AND ACETYLATION LEAD TO TRANSCRIPTIONAL ALTERATIONS OF SEVERAL GENES SUCH AS PTPN22, LRP1B, AND TNFSF70. THERE ARE VARIETIES OF MICRORNAS APPLIED AS LUPUS BIOMARKERS, INCLUDING DNMT1-RELATED MICRORNAS, RENAL FUNCTION-ASSOCIATED MICRORNAS, MICRORNAS INVOLVED IN THE IMMUNE SYSTEM, AND MICRORNAS FOR PHENOTYPE CLASSIFICATION. THUS, WE CONCLUDE A WIDE RANGE OF PROMISING ROLES OF EPIGENETIC BIOMARKERS AIDING IN THE DIAGNOSING AND MONITORING OF LUPUS DISEASES AND THE RISK OF ORGAN DAMAGE. 2017 3 2975 26 GENETIC AND MOLECULAR ALTERATIONS ASSOCIATED WITH ORAL SQUAMOUS CELL CANCER (REVIEW). THE DEVELOPMENT OF ORAL SQUAMOUS CELL CANCER (OSCC) IS A MULTISTEP PROCESS INVOLVING THE ACCUMULATION OF MULTIPLE GENETIC ALTERATIONS MODULATED BY GENETIC PRE-DISPOSITION AND ENVIRONMENTAL INFLUENCES SUCH AS TOBACCO AND ALCOHOL USE, CHRONIC INFLAMMATION, AND VIRAL INFECTIONS. ALL OF THESE FACTORS CAN LEAD TO A WIDE RANGE OF GENETIC AND MOLECULAR ALTERATIONS THAT CAN BE DETECTED USING A RANGE OF MOLECULAR STUDIES. THE ALTERATIONS MOSTLY AFFECT TWO LARGE GROUPS OF GENES: ONCOGENES AND TUMOR SUPPRESSOR GENES, WHICH CAN BE EITHER INACTIVATED OR OVEREXPRESSED THROUGH MUTATIONS, LOSS OF HETEROZYGOSITY, DELETIONS, OR EPIGENETIC MODIFICATIONS SUCH AS METHYLATION. OTHER MOLECULES THAT ARE CLOSELY ASSOCIATED WITH TUMOR PATHOGENESIS AND PROGNOSIS ALSO EXIST AND WARRANT FURTHER STUDY. IMPORTANT ADVANCES IN MOLECULAR BIOLOGY ARE HELPING TO SHED LIGHT ON ORAL CANCER AND THUS AIDING IN THE EARLY DIAGNOSIS AND DEVELOPMENT OF NEW PERSONALIZED TREATMENT APPROACHES. THE PURPOSE OF THE REVIEW IS TO EXPLORE THE GENETIC AND MOLECULAR ALTERATIONS ASSOCIATED WITH OSCC. 2009 4 5419 27 REGULATION OF GENE EXPRESSION AND PAIN STATES BY EPIGENETIC MECHANISMS. THE INDUCTION OF INFLAMMATORY OR NEUROPATHIC PAIN STATES IS KNOWN TO INVOLVE MOLECULAR ACTIVITY IN THE SPINAL SUPERFICIAL DORSAL HORN AND DORSAL ROOT GANGLIA, INCLUDING INTRACELLULAR SIGNALING EVENTS WHICH LEAD TO CHANGES IN GENE EXPRESSION. THESE CHANGES ULTIMATELY CAUSE ALTERATIONS IN MACROMOLECULAR SYNTHESIS, SYNAPTIC TRANSMISSION, AND STRUCTURAL ARCHITECTURE WHICH SUPPORT CENTRAL SENSITIZATION, A PROCESS REQUIRED FOR THE ESTABLISHMENT OF LONG-TERM PAIN STATES. EPIGENETIC MECHANISMS ARE ESSENTIAL FOR LONG-TERM SYNAPTIC PLASTICITY AND MODULATION OF GENE EXPRESSION. THIS IS BECAUSE EPIGENETIC MODIFICATIONS ARE KNOWN TO REGULATE GENE TRANSCRIPTION BY AIDING THE PHYSICAL RELAXATION OR CONDENSATION OF CHROMATIN. THESE PROCESSES ARE THEREFORE POTENTIAL REGULATORS OF THE MOLECULAR CHANGES UNDERLYING PERMANENT PAIN STATES. A HANDFUL OF STUDIES HAVE EMERGED IN THE FIELD OF PAIN EPIGENETICS; HOWEVER, THE FIELD IS STILL VERY MUCH IN ITS INFANCY. THIS CHAPTER DRAWS UPON OTHER SPECIALITIES WHICH HAVE EXTENSIVELY INVESTIGATED EPIGENETIC MECHANISMS, SUCH AS LEARNING AND MEMORY AND ONCOLOGY. AFTER DEFINING EPIGENETICS AS WELL AS THE RECENT FIELD OF "NEUROEPIGENETICS" AND THE MAIN MOLECULAR MECHANISMS INVOLVED, THIS CHAPTER DESCRIBES THE ROLE OF THESE MECHANISMS IN THE SYNAPTIC PLASTICITY SEEN IN LEARNING AND MEMORY, AND ADDRESS THOSE EPIGENETIC MECHANISMS THAT HAVE BEEN LINKED WITH THE DEVELOPMENT OF ACUTE AND PROLONGED PAIN STATES. FINALLY, THE IDEA THAT LONG-LASTING EPIGENETIC MODIFICATIONS COULD CONTRIBUTE TO THE TRANSITION FROM ACUTE TO CHRONIC PAIN STATES BY SUPPORTING MALADAPTIVE MOLECULAR CHANGES IS DISCUSSED. 2015 5 2257 19 EPIGENETIC PERSPECTIVES IN SYSTEMIC LUPUS ERYTHEMATOSUS: PATHOGENESIS, BIOMARKERS, AND THERAPEUTIC POTENTIALS. SYSTEM LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC AUTOIMMUNE DISEASE CHARACTERIZED BY THE PRODUCTION OF AUTOANTIBODIES THAT CAUSE WIDESPREAD TISSUE DAMAGE. THE UNDERLYING ETIOLOGY REMAINS LARGELY UNKNOWN. ABERRANT EPIGENETICS PLAYS ESSENTIAL ROLES IN THE PATHOGENESIS OF SLE. THIS REVIEW EXPLORES THE LINKS BETWEEN DNA METHYLATION, HISTONE MODIFICATIONS, AND MIRNAS IN SLE AND HIGHLIGHTS HOW THESE FACTORS MAY INTERACT IN SLE PATHOGENESIS. WE ALSO DISCUSS HOW FURTHERING OUR KNOWLEDGE OF EPIGENETICS IN LUPUS PROVIDES HOPE FOR FINDING NEW DIAGNOSTIC AND PROGNOSTIC BIOMARKERS AND NOVEL THERAPEUTIC TARGETS AND STRATEGIES. 2010 6 4665 28 NEW INSIGHTS AND ADVANCES IN PATHOGENESIS AND TREATMENT OF VERY EARLY ONSET INFLAMMATORY BOWEL DISEASE. VERY EARLY ONSET INFLAMMATORY BOWEL DISEASE (VEO-IBD) IS CHARACTERIZED BY MULTIFACTORIAL CHRONIC RECURRENT INTESTINAL INFLAMMATION. COMPARED WITH ELDERLY PATIENTS, THOSE WITH VEO-IBD HAVE A MORE SERIOUS CONDITION, NOT RESPONSIVE TO CONVENTIONAL TREATMENTS, WITH A POOR PROGNOSIS. RECENT STUDIES FOUND THAT GENETIC AND IMMUNOLOGIC ABNORMALITIES ARE CLOSELY RELATED TO VEO-IBD. INTESTINAL IMMUNE HOMEOSTASIS MONOGENIC DEFECTS (IIHMDS) ARE CHANGED THROUGH VARIOUS MECHANISMS. RECENT STUDIES HAVE ALSO REVEALED THAT ABNORMALITIES IN GENES AND IMMUNE MOLECULAR MECHANISMS ARE CLOSELY RELATED TO VEO-IBD. IIHMDS CHANGE THROUGH VARIOUS MECHANISMS. EPIGENETIC FACTORS CAN MEDIATE THE INTERACTION BETWEEN THE ENVIRONMENT AND GENOME, AND GENETIC FACTORS AND IMMUNE MOLECULES MAY BE INVOLVED IN THE PATHOGENESIS OF THE ENVIRONMENT AND GUT MICROBIOTA. THESE DISCOVERIES WILL PROVIDE NEW DIRECTIONS AND IDEAS FOR THE TREATMENT OF VEO-IBD. 2022 7 2559 33 EPIGENETICS IN SYSTEMIC LUPUS ERYTHEMATOSUS: LEADING THE WAY FOR SPECIFIC THERAPEUTIC AGENTS. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC AUTOIMMUNE DISORDER OF AN UNCLEARLY DETERMINED ETIOLOGY. PAST STUDIES, BOTH EPIDEMIOLOGICAL AND BIOLOGICAL, HAVE IMPLICATED EPIGENETIC INFLUENCES IN DISEASE ETIOLOGY AND PATHOGENESIS. EPIGENETICS DESCRIBES CHANGES IN GENE EXPRESSION NOT LINKED TO ALTERATIONS IN THE UNDERLYING GENOMIC SEQUENCE, AND IS MOST OFTEN TYPIFIED BY THREE MODIFICATIONS: METHYLATION OF DNA, ADDITION OF VARIOUS SIDE CHAINS TO HISTONE GROUPS AND TRANSCRIPTIONAL REGULATION VIA SHORT NCRNA SEQUENCES. THE PURPOSE OF THIS ARTICLE IS TO REVIEW THE MOST IMPORTANT ADVANCES THAT LINK EPIGENETIC CHANGES TO LUPUS. THE CONTRIBUTION OF DNA METHYLATION CHANGES TO LUPUS PATHOGENESIS IS DISCUSSED. THESE INCLUDE THE ROLE OF APOPTOTIC DNA, ULTRAVIOLET RADIATION, ENDOGENOUS RETROVIRUSES, DIETARY CONTRIBUTIONS AND AGING. HYPOMETHYLATION OF SPECIFIC GENES OVEREXPRESSED IN LUPUS T CELLS SUCH AS ITGAL (CD11A), CD40LG (CD40L), TNFSF7 (CD70), KIR2DL4 AND PRF1 (PERFORIN), AND CD5 IN LUPUS B CELLS SEEM TO PLAY AN IMPORTANT ROLE. MOREOVER, HISTONE MODIFICATIONS SUCH AS INCREASED GLOBAL H4 ACETYLATION IN MONOCYTES ARE HIGHLY ASSOCIATED WITH SLE. NCRNAS, ESPECIALLY MIR-21, MIR-148A AND MIR-126, CONTROL OTHER ELEMENTS OF EPIGENETIC REGULATION; PARTICULARLY, TRANSCRIPTION OF THE MAINTENANCE DNA METHYLATION ENZYME DNMT1. EPIGENETIC CONTRIBUTIONS TO SLE ETIOLOGY HAVE BEEN WELL ESTABLISHED, BUT MUCH IS STILL UNKNOWN. EPIGENOME-WIDE STUDIES COUPLED WITH FUNCTIONAL ANALYSIS OF THE EPIGENOMIC CHANGES DISCOVERED WILL UNCOVER NOVEL PATHWAYS IMPORTANT IN DISEASE PATHOGENESIS. EPIGENETIC THERAPIES FOR SLE MAY BE FEASIBLE IN THE FUTURE, PARTICULARLY IF THEY ARE DESIGNED TO TARGET SPECIFIC REGIONS WITHIN THE GENOME. 2011 8 258 26 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 9 4012 26 LOW-DENSITY GRANULOCYTES IN SYSTEMIC AUTOIMMUNITY AND AUTOINFLAMMATION. A BODY OF EVIDENCE HAS RE-ENERGIZED THE INTEREST ON THE ROLE NEUTROPHILS IN INFLAMMATORY AND AUTOIMMUNE CONDITIONS. FOR DECADES, NEUTROPHILS HAVE BEEN CONSIDERED A HOMOGENOUS POPULATION. NEVERTHELESS, ACCUMULATING EVIDENCE SUGGESTS THAT NEUTROPHILS ARE MORE VERSATILE AND HETEROGENEOUS THAN INITIALLY CONSIDERED. THE NOTION OF NEUTROPHIL HETEROGENEITY HAS BEEN SUPPORTED BY THE IDENTIFICATION OF LOW-DENSITY GRANULOCYTES (LDGS) IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) AND OTHER SYSTEMIC AUTOIMMUNE AND AUTOINFLAMMATORY CONDITIONS. TRANSCRIPTOMIC, EPIGENETIC, PROTEOMIC, AND FUNCTIONAL ANALYSES SUPPORT THAT LDGS ARE A DISTINCT SUBSET OF PROINFLAMMATORY NEUTROPHILS IMPLICATED IN THE PATHOGENESIS OF SLE AND OTHER AUTOIMMUNE DISEASES. IMPORTANTLY, IT REMAINS INCOMPLETELY CHARACTERIZED WHETHER LDGS DETECTED IN OTHER INFLAMMATORY/AUTOIMMUNE CONDITIONS DISPLAY THE SAME PHENOTYPE THAT THOSE PRESENT IN SLE. A SHARED FEATURE OF LDGS ACROSS DISEASES IS THEIR ASSOCIATION WITH VASCULAR DAMAGE, AN IMPORTANT CONTRIBUTOR TO MORBIDITY AND MORTALITY IN CHRONIC INFLAMMATORY CONDITIONS. ADDITIONALLY, THE LACK OF SPECIFIC MARKERS TO IDENTIFY LDGS IN CIRCULATION OR IN TISSUE, MAKES IT A CHALLENGE TO ELUCIDATE THEIR ROLE IN THE PATHOGENESIS OF INFLAMMATORY AND AUTOIMMUNE CONDITIONS. IN THIS REVIEW, WE AIM TO EXAMINE THE EVIDENCE ON THE BIOLOGY AND THE PUTATIVE PATHOGENIC ROLE OF LDGS IN SYSTEMIC AUTOIMMUNE DISEASES. 2023 10 4495 47 MORE GAIN, LESS PAIN: HOW RESISTANCE TRAINING AFFECTS IMMUNE SYSTEM FUNCTIONING IN MULTIPLE SCLEROSIS PATIENTS: A REVIEW. MULTIPLE SCLEROSIS (MS) IS CHARACTERIZED BY A COMPLEX ETIOLOGY THAT IS MIRRORED BY THE PERPLEXING AND INCONSISTENT TREATMENT RESPONSES OBSERVED ACROSS DIFFERENT PATIENTS. ALTHOUGH EPIGENETIC RESEARCH HAS GARNERED RIGHTFUL INTEREST IN ITS EFFORTS TOWARDS DEMYSTIFYING AND UNDERSTANDING ABERRANT RESPONSES TO TREATMENT, THE INTERIM UNDOUBTEDLY REQUIRES ALTERNATIVE NON-PHARMACOLOGICAL APPROACHES TOWARDS ATTAINING MORE EFFECTIVE MANAGEMENT STRATEGIES. OF PARTICULAR INTEREST IN THIS REVIEW IS RESISTANCE TRAINING (RT) AS A NON-PHARMACOLOGICAL EXERCISE-BASED INTERVENTIONAL STRATEGY AND ITS POTENTIAL ROLE AS A DISEASE-MODIFYING TOOL. RT HAS BEEN REPORTED ACROSS LITERATURE TO POSITIVELY INFLUENCE NUMEROUS ASPECTS IN THE QUALITY OF LIFE (QOL) AND FUNCTIONAL CAPACITY OF MS PATIENTS, AND ONE OF THE ATTRIBUTES OF THESE BENEFITS MAY BE A SHIFT IN THE IMMUNE SYSTEM OF THESE INDIVIDUALS. RT HAS ALSO BEEN PROVEN TO AFFECT DIFFERENT IMMUNE SYSTEM KEY PLAYERS ASSOCIATED WITH MS PATHOLOGY. ULTIMATELY, THIS BRIEF REVIEW AIMS TO PROVIDE A POTENTIAL YET CRUCIAL LINK BETWEEN RT, ALTERATIONS IN THE EXPRESSION PROFILE OF THE IMMUNE SYSTEM, AND FINALLY AN IMMINENT IMPROVEMENT IN THE OVERALL WELL-BEING AND QOL OF MS PATIENTS, SUGGESTING THAT UTILIZING RT AS AN INTERVENTIONAL EXERCISE MODALITY MAY BE AN EFFECTIVE STRATEGY THAT WOULD AID IN MANAGING SUCH A COMPLEX AND DEBILITATING DISEASE. 2023 11 6107 29 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 6147 29 THE EXPRESSION OF NON-CODING RNAS AND THEIR TARGET MOLECULES IN RHEUMATOID ARTHRITIS: A MOLECULAR BASIS FOR RHEUMATOID PATHOGENESIS AND ITS POTENTIAL CLINICAL APPLICATIONS. RHEUMATOID ARTHRITIS (RA) IS A TYPICAL AUTOIMMUNE-MEDIATED RHEUMATIC DISEASE PRESENTING AS A CHRONIC SYNOVITIS IN THE JOINT. THE CHRONIC SYNOVIAL INFLAMMATION IS CHARACTERIZED BY HYPER-VASCULARITY AND EXTRAVASATION OF VARIOUS IMMUNE-RELATED CELLS TO FORM LYMPHOID AGGREGATES WHERE AN INTIMATE CROSS-TALK AMONG INNATE AND ADAPTIVE IMMUNE CELLS TAKES PLACE. THESE INTERACTIONS FACILITATE PRODUCTION OF ABUNDANT PROINFLAMMATORY CYTOKINES, CHEMOKINES AND GROWTH FACTORS FOR THE PROLIFERATION/MATURATION/DIFFERENTIATION OF B LYMPHOCYTES TO BECOME PLASMA CELLS. FINALLY, THE AUTOANTIBODIES AGAINST DENATURED IMMUNOGLOBULIN G (RHEUMATOID FACTORS), EB VIRUS NUCLEAR ANTIGENS (EBNAS) AND CITRULLINATED PROTEIN (ACPAS) ARE PRODUCED TO TRIGGER THE DEVELOPMENT OF RA. FURTHERMORE, IT IS DOCUMENTED THAT GENE MUTATIONS, ABNORMAL EPIGENETIC REGULATION OF PEPTIDYLARGININE DEIMINASE GENES 2 AND 4 (PADI2 AND PADI4), AND THEREBY THE INDUCED AUTOANTIBODIES AGAINST PAD2 AND PAD4 ARE IMPLICATED IN ACPA PRODUCTION IN RA PATIENTS. THE ABERRANT EXPRESSIONS OF NON-CODING RNAS (NCRNAS) INCLUDING MICRORNAS (MIRS) AND LONG NON-CODING RNAS (LNCRNAS) IN THE IMMUNE SYSTEM UNDOUBTEDLY DERANGE THE MRNA EXPRESSIONS OF CYTOKINES/CHEMOKINES/GROWTH FACTORS. IN THE PRESENT REVIEW, WE WILL DISCUSS IN DETAIL THE EXPRESSION OF THESE NCRNAS AND THEIR TARGET MOLECULES PARTICIPATING IN DEVELOPING RA, AND THE POTENTIAL BIOMARKERS FOR THE DISEASE, ITS DIAGNOSIS, CARDIOVASCULAR COMPLICATIONS AND THERAPEUTIC RESPONSE. FINALLY, WE PROPOSE SOME PROSPECTIVE INVESTIGATIONS FOR UNRAVELING THE CONUNDRUMS OF RHEUMATOID PATHOGENESIS. 2021 13 1059 22 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 14 4958 24 PATHOGENESIS OF HUMAN SYSTEMIC LUPUS ERYTHEMATOSUS: A CELLULAR PERSPECTIVE. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC AUTOIMMUNE DISEASE AFFECTING MULTIPLE ORGANS. A COMPLEX INTERACTION OF GENETICS, ENVIRONMENT, AND HORMONES LEADS TO IMMUNE DYSREGULATION AND BREAKDOWN OF TOLERANCE TO SELF-ANTIGENS, RESULTING IN AUTOANTIBODY PRODUCTION, INFLAMMATION, AND DESTRUCTION OF END-ORGANS. EMERGING EVIDENCE ON THE ROLE OF THESE FACTORS HAS INCREASED OUR KNOWLEDGE OF THIS COMPLEX DISEASE, GUIDING THERAPEUTIC STRATEGIES AND IDENTIFYING PUTATIVE BIOMARKERS. RECENT FINDINGS INCLUDE THE CHARACTERIZATION OF GENETIC/EPIGENETIC FACTORS LINKED TO SLE, AS WELL AS CELLULAR EFFECTORS. NOVEL OBSERVATIONS HAVE PROVIDED AN IMPROVED UNDERSTANDING OF THE CONTRIBUTION OF TISSUE-SPECIFIC FACTORS AND ASSOCIATED DAMAGE, T AND B LYMPHOCYTES, AS WELL AS INNATE IMMUNE CELL SUBSETS AND THEIR CORRESPONDING ABNORMALITIES. THE INTRICATE WEB OF INVOLVED FACTORS AND PATHWAYS DICTATES THE ADOPTION OF TAILORED THERAPEUTIC APPROACHES TO CONQUER THIS DISEASE. 2017 15 4721 34 NONCODING RNAS IN MULTIPLE SCLEROSIS. MULTIPLE SCLEROSIS (MS), A CHRONIC INFLAMMATORY DEMYELINATING DISEASE OF THE CENTRAL NERVOUS SYSTEM, IS CHARACTERIZED BY AXONAL DEGENERATION AND GLIOSIS. ALTHOUGH THE CAUSES OF MS REMAIN UNKNOWN, GENE DYSREGULATION IN THE CENTRAL NERVOUS SYSTEM HAS BEEN ASSOCIATED WITH THE DISEASE PATHOGENESIS. AS SUCH, THE VARIOUS REGULATORS OF GENE EXPRESSION MAY BE CONTRIBUTING FACTORS. THE NONCODING (NC) RNAS HAVE PIQUED THE INTEREST OF MS RESEARCHERS DUE TO THEIR KNOWN FUNCTIONS IN HUMAN PHYSIOLOGY AND VARIOUS PATHOLOGICAL PROCESSES, DESPITE BEING GENERALLY CHARACTERIZED AS TRANSCRIPTS WITHOUT APPARENT PROTEIN-CODING CAPACITY. ACCUMULATING EVIDENCE HAS INDICATED THAT NCRNAS PARTICIPATE IN THE REGULATION OF MS BY ACTING AS EPIGENETIC FACTORS, ESPECIALLY THE LONG (L) NCRNAS AND THE MICRO (MI) RNAS, AND THEY ARE NOW RECOGNIZED AS KEY REGULATORY MOLECULES IN MS. IN THIS REVIEW, WE SUMMARIZE THE MOST CURRENT STUDIES ON THE CONTRIBUTION OF NCRNAS IN MS PATHOGENIC PROCESSES AND DISCUSS THEIR POTENTIAL APPLICATIONS IN THE DIAGNOSIS AND TREATMENT OF MS. 2018 16 3598 13 IMPLICATIONS ON HYPNOTHERAPY: NEUROPLASTICITY, EPIGENETICS AND PAIN. WE PROVIDE A BRIEF REVIEW ABOUT THE SIGNIFICANCE OF HYPNOSIS WITH RESPECT TO APPLICATIONS AND PHYSIOLOGICAL PROCESSES IN HYPNOTHERAPY. OUR REVIEW CONCLUDES THAT HYPNOSIS IS A PROMISING METHOD TO MANAGE ACUTE AND CHRONIC PAIN. IN ADDITION, WE DISCUSS INDICATIONS POINTING TOWARD THE VIEW THAT HYPNOSIS CAN INDUCE CHANGES IN NEUROPLASTICITY POSSIBLY INVOLVING EPIGENETIC MECHANISMS. 2021 17 4754 28 NOVEL THERAPEUTIC STRATEGIES FOR CHRONIC HEPATITIS B. THE LAST FEW YEARS HAVE SEEN A RESURGENCE OF ACTIVITY IN THE HEPATITIS B DRUG PIPELINE, WITH MANY COMPOUNDS IN VARIOUS STAGES OF DEVELOPMENT. THIS REVIEW AIMS TO PROVIDE A COMPREHENSIVE OVERVIEW OF THE LATEST ADVANCES IN THERAPEUTICS FOR CHRONIC HEPATITIS B (CHB). WE WILL DISCUSS THE BROAD SPECTRUM OF DIRECT-ACTING ANTIVIRALS IN CLINICAL DEVELOPMENT, INCLUDING CAPSIDS INHIBITORS, SIRNA, HBSAG AND POLYMERASE INHIBITORS. IN ADDITION, HOST-TARGETED THERAPIES (HTT) WILL BE EXTENSIVELY REVIEWED, FOCUSING ON THE LATEST PROGRESS IN IMMUNOTHERAPEUTICS SUCH AS TOLL-LIKE RECEPTORS AND RIG-1 AGONISTS, THERAPEUTIC VACCINES AND IMMUNE CHECKPOINTS MODULATORS. A GROWING NUMBER OF HTT IN PRE-CLINICAL DEVELOPMENT DIRECTLY TARGET THE KEY TO HBV PERSISTENCE, NAMELY THE COVALENTLY CLOSED CIRCULAR DNA (CCCDNA) AND HOLD GREAT PROMISE FOR HBV CURE. THIS EXCITING AREA OF HBV RESEARCH WILL BE HIGHLIGHTED, AND MOLECULES SUCH AS CYCLOPHILINS INHIBITORS, APOBEC3 DEAMINASES AND EPIGENETIC MODIFIERS WILL BE DISCUSSED. 2022 18 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 19 395 33 AN UPDATE ON EPIGENETIC REGULATION IN AUTOIMMUNE DISEASES. AUTOIMMUNE DISEASES (AIDS) GENERALLY MANIFEST AS CHRONIC IMMUNE DISORDERS CHARACTERIZED BY SIGNIFICANT HETEROGENEITY AND COMPLEX SYMPTOMS. THE DISCORDANT INCIDENCE OF AIDS BETWEEN MONOZYGOTIC TWINS GUIDED PEOPLE TO ATTACH IMPORTANCE TO ENVIRONMENTAL FACTORS. EPIGENETICS IS ONE OF THE MAJOR WAYS TO BE INFLUENCED, SOME OF THEM CAN EVEN OCCUR YEARS BEFORE CLINICAL DIAGNOSIS. WITH THE ADVENT OF HIGH-THROUGHPUT OMICS TIMES, THE MYSTERIOUS VEIL OF EPIGENETIC MODIFICATION IN AIDS HAS BEEN GRADUALLY UNRAVELED, AND SOME PROGRESS HAS BEEN MADE IN UTILIZING IT AS INDICATORS OF DIAGNOSIS AND DISEASE ACTIVITY. FOR EXAMPLE, THE HYPOMETHYLATED IFI44L PROMOTER IN DIAGNOSING SYSTEMATIC LUPUS ERYTHEMATOSUS (SLE). MORE RECENTLY, NEWLY IDENTIFIED NONCODING RNAS (NCRNAS), INCLUDING LONG NONCODING RNAS (LNCRNAS) AND CIRCULAR RNAS (CIRCRNAS), ARE ALSO BELIEVED TO BE INVOLVED IN THE ETIOLOGY OF AIDS WHILE THE INITIAL FACTOR BEHIND THOSE EPIGENETIC ALTERATIONS CAN BE DIVERSE FROM METABOLISM TO MICROBIOTA. UPDATE AND COMPREHENSIVE INSIGHTS INTO EPIGENETICS IN AIDS CAN HELP US UNDERSTAND THE PATHOGENESIS AND FURTHER ORCHESTRATE IT TO BENEFIT PATIENTS IN THE FUTURE. THEREFORE, WE REVIEWED THE LATEST EPIGENETIC FINDINGS IN SLE, RHEUMATOID ARTHRITIS (RA), TYPE 1 DIABETES (T1D), SYSTEMIC SCLEROSIS (SSC) PRIMARILY FROM CELLULAR LEVELS. 2022 20 3880 23 KETAMINE: REPURPOSING AND REDEFINING A MULTIFACETED DRUG. THIS SHORT REVIEW WILL HIGHLIGHT RECENT CLINICAL AND BASIC RESEARCH THAT SUPPORTS THE THERAPEUTIC UTILITY OF KETAMINE AS A RAPID-ACTING, LIFE-SAVING ANTIDEPRESSANT AND A VERSATILE ANALGESIC. AFTER 50 YEARS OF USE AS A DISSOCIATIVE ANESTHETIC AND MISUSE AS A STREET DRUG, KETAMINE HAS RE-EMERGED AS A USEFUL OFF-LABEL AGENT FOR AMELIORATING VARIOUS TYPES OF PAIN AND RESISTANT DEPRESSION. IN ADDITION TO ITS ABILITY TO INHIBIT N-METHYL-D-ASPARTATE (NMDA) RECEPTORS, THE DIVERSE ACTIONS OF KETAMINE MIGHT INVOLVE EPIGENETIC MECHANISMS SUCH AS MICRORNA REGULATION. THUS, KETAMINE IS TRANSITIONING FROM BEING THE PHARMACOLOGIST'S NIGHTMARE TO ONE OF THE MOST INTERESTING DEVELOPMENTS IN THE PHARMACOLOGY OF DEPRESSION AND PAIN. 2014