1 3146 177 GLOBAL RESEARCH TRENDS ON EPIGENETICS AND NEUROPATHIC PAIN: A BIBLIOMETRIC ANALYSIS. OBJECTIVE: NEUROPATHIC PAIN (NP) IS A COMMON DISEASE THAT MANIFESTS WITH PATHOLOGICAL CHANGES IN THE SOMATOSENSORY SYSTEM. IN RECENT YEARS, THE INTERACTIONS OF NP WITH THE EPIGENETIC MECHANISM HAVE BEEN INCREASINGLY ELUCIDATED. HOWEVER, ONLY A FEW STUDIES HAVE USED BIBLIOMETRIC TOOLS TO SYSTEMATICALLY ANALYZE KNOWLEDGE IN THIS FIELD. THE OBJECTIVE OF THIS STUDY IS TO VISUALLY ANALYZE THE TRENDS, HOTSPOTS, AND FRONTIERS IN EPIGENETICS AND NP RESEARCH BY USING A BIBLIOMETRIC METHOD. METHODS: STUDIES RELATED TO EPIGENETICS AND NP WERE SEARCHED FROM THE SCIENCE CITATION INDEX-EXPANDED OF THE WEB OF SCIENCE CORE COLLECTION DATABASE. SEARCH TIME IS FROM INCEPTION TO NOVEMBER 30, 2022. NO RESTRICTIONS WERE PLACED ON LANGUAGE. ONLY ARTICLES AND REVIEWS WERE INCLUDED AS DOCUMENT TYPES. DATA ON INSTITUTIONS, COUNTRIES, AUTHORS, JOURNAL DISTRIBUTION, AND KEYWORDS WERE IMPORTED INTO CITESPACE SOFTWARE FOR VISUAL ANALYSIS. RESULTS: A TOTAL OF 867 PUBLICATIONS MET THE INCLUSION CRITERIA, WHICH SPANNED THE PERIOD FROM 2000 TO 2022. OVER THE YEARS, THE NUMBER OF PUBLICATIONS AND THE FREQUENCY OF CITATIONS EXHIBITED A CLEAR UPWARD TREND IN GENERAL, REACHING A PEAK IN 2021. THE MAJOR CONTRIBUTING COUNTRIES IN TERMS OF THE NUMBER OF PUBLICATIONS WERE CHINA, THE UNITED STATES, AND JAPAN. THE TOP THREE INSTITUTIONS WERE RUTGERS STATE UNIVERSITY, XUZHOU MEDICAL UNIVERSITY, AND NANJING MEDICAL UNIVERSITY. MOLECULAR PAIN, PAIN, AND JOURNAL OF NEUROINFLAMMATION CONTRIBUTED SIGNIFICANTLY TO THE VOLUME OF ISSUES. AMONG THE TOP 10 AUTHORS IN TERMS OF THE NUMBER OF PUBLICATIONS, TAO YUAN-XIANG CONTRIBUTED 30 ENTRIES, FOLLOWED BY ZHANG YI WITH 24 AND WU SHAO-GEN WITH 20. ON THE BASIS OF THE BURST AND CLUSTERS OF KEYWORDS, "DNA METHYLATION," "CIRCULAR RNA," "ACETYLATION," "LONG NON-CODING RNA," AND "MICROGLIA" ARE GLOBAL HOTSPOTS IN THE FIELD. CONCLUSION: THE BIBLIOMETRIC ANALYSIS INDICATES THAT THE NUMBER OF PUBLICATIONS RELATED TO EPIGENETICS AND NP IS EXHIBITING A RAPID INCREASE. KEYWORD ANALYSIS SHOWS THAT "DNA METHYLATION," "CIRCULAR RNA," "ACETYLATION," "LONG NON-CODING RNA" AND "MICROGLIA" ARE THE MOST INTERESTING TERMS FOR RESEARCHERS IN THE FIELD. MORE RIGOROUS CLINICAL TRIALS AND ADDITIONAL STUDIES THAT EXPLORE RELEVANT MECHANISMS ARE REQUIRED IN THE FUTURE. 2023 2 6127 41 THE EPIGENETIC OVERLAP BETWEEN OBESITY AND MOOD DISORDERS: A SYSTEMATIC REVIEW. (1) BACKGROUND: OBESITY AND MOOD DISORDERS ARE CONSIDERED AS THE MOST PREVALENT MORBIDITIES IN MANY COUNTRIES. WE SUPPOSE THAT EPIGENETIC MECHANISMS MAY INDUCE HIGHER RATES OF OBESITY IN SUBJECTS WHO SUFFER FROM MOOD DISORDERS. IN THIS SYSTEMATIC REVIEW, WE FOCUSED ON THE POTENTIAL ROLES OF DNA METHYLATION ON MOOD DISORDERS AND OBESITY DEVELOPMENT. (2) METHODS: THIS SYSTEMATIC REVIEW WAS CONDUCTED IN ACCORDANCE WITH THE PRISMA STATEMENT AND REGISTERED IN PROSPERO. A SYSTEMATIC SEARCH WAS CONDUCTED IN MEDLINE, SCOPUS, WEB OF SCIENCE, COCHRANE CENTRAL DATABASE, EMBASE, AND CINHAL. WE ALSO CONDUCTED A GREY LITERATURE SEARCH, SUCH AS GOOGLE SCHOLAR. (3) RESULTS: AFTER DEDUPLICATION, WE IDENTIFIED 198 POTENTIALLY RELATED CITATIONS. FINALLY, TEN UNIQUE STUDIES MET OUR INCLUSION CRITERIA. WE HAVE FOUND THREE OVERLAP GENES THAT SHOW SIGNIFICANT DNA METHYLATION CHANGES, BOTH IN OBESITY AND DEPRESSION. PATHWAY ANALYSIS INTERACTION FOR TAPBP, BDNF, AND SORBS2 CONFIRMED THE RELATION OF THESE GENES IN BOTH OBESITY AND MOOD DISORDERS. (4) CONCLUSIONS: WHILE MECHANISMS LINKING BOTH OBESITY AND MOOD DISORDERS TO EPIGENETIC RESPONSE ARE STILL UNKNOWN, WE HAVE ALREADY KNOWN CHRONIC INFLAMMATION INDUCES A NOVEL EPIGENETIC PROGRAM. AS THE RESULTS OF GENE ENRICHMENT, PATHWAYS ANALYSIS SHOWED THAT TAPBP, BDNF, AND SORBS2 LINKED TOGETHER BY INFLAMMATORY PATHWAYS. HYPERMETHYLATION IN THESE GENES MIGHT PLAY A CRUCIAL RULE IN THE CO-OCCURRENCE OF OBESITY AND MOOD DISORDERS. 2020 3 2585 49 EPIGENETICS OF OBSTRUCTIVE SLEEP APNEA SYNDROME: A SYSTEMATIC REVIEW. STUDY OBJECTIVES: OBSTRUCTIVE SLEEP APNEA (OSA) IS A CHRONIC AND WIDELY PREVALENT DISEASE ASSOCIATED WITH MULTIPLE HEALTH DISORDERS. CURRENT DIAGNOSTIC STRATEGIES FOR OSA ARE LIMITED BECAUSE OF COST, TIME, AND ACCESS. EPIGENETIC SIGNATURES OFFER INSIGHT INTO THE RELATIONSHIPS BETWEEN DISEASE AND ENVIRONMENT AND COULD PLAY A SIGNIFICANT ROLE IN DEVELOPING BOTH DIAGNOSTIC AND THERAPEUTIC TOOLS FOR OSA. IN THE CURRENT STUDY, A SYSTEMATIC LITERATURE SEARCH WAS CONDUCTED TO INVESTIGATE THE EXISTING EVIDENCE OF OSA-ASSOCIATED EPIGENETIC MODIFICATIONS. METHODS: A SYSTEMATIC LITERATURE SEARCH WAS PERFORMED USING ELECTRONIC ACADEMIC DATABASES INCLUDING PUBMED, CINAHL, SCOPUS, EMBASE, EBM REVIEWS, AND WEB OF SCIENCE. HOWEVER, THE CURRENT STUDY FOCUSED ON SCREENING FOR ORIGINAL, ENGLISH-LANGUAGE ARTICLES PERTAINING TO OSA AND ASSOCIATED EPIGENETIC MECHANISMS. TO PRODUCE UNBIASED RESULTS, SCREENING WAS PERFORMED INDEPENDENTLY BY AUTHORS. RESULTS: WE IDENTIFIED 2,944 PUBLICATIONS IN OUR SYSTEMATIC SEARCH. AMONG THEM, 65 RESEARCH ARTICLES WERE RELATED TO OS A-ASSOCIATED DIFFERENTIAL GENE EXPRESSION, GENETIC VARIATION, AND EPIGENETIC MODIFICATIONS. ALTHOUGH THESE 65 ARTICLES WERE CONSIDERED FOR FULL MANUSCRIPT REVIEW, ONLY 12 ARTICLES MET THE CRITERIA OF OSA-ASSOCIATED EPIGENETIC MODIFICATIONS IN HUMAN AND ANIMAL MODELS. HUMAN PATIENTS WITH OSA HAD UNIQUE EPIGENETIC CHANGES COMPARED TO HEALTHY CONTROL PATIENTS AND, INTERESTINGLY, EPIGENETIC SIGNATURES WERE COMMONLY IDENTIFIED IN GENES ASSOCIATED WITH METABOLIC AND INFLAMMATORY PATHWAYS. CONCLUSIONS: ALTHOUGH THE AVAILABLE STUDIES ARE LIMITED, THIS RESEARCH PROVIDES NOVEL INSIGHTS FOR THE DEVELOPMENT OF EPIGENETIC MARKERS FOR THE DIAGNOSIS AND TREATMENT OF OSA. THOROUGH GENOME-WIDE INVESTIGATIONS WILL BE REQUIRED TO DEVELOP COST-EFFECTIVE, ROBUST BIOMARKERS FOR THE IDENTIFICATION OF OSA AMONG CHILDREN AND ADULTS. HERE, WE OFFER A STUDY DESIGN FOR SUCH EFFORTS. CITATION: LEADER BA, KORITALA BSC, MOORE CA, DEAN EG, KOTTYAN LC, SMITH DF. EPIGENETICS OF OBSTRUCTIVE SLEEP APNEA SYNDROME: A SYSTEMATIC REVIEW. J CLIN SLEEP MED. 2021;17(12):2533-2541. 2021 4 6141 34 THE ETIOLOGY OF PEYRONIE'S DISEASE: PATHOGENESIS AND GENETIC CONTRIBUTIONS. INTRODUCTION: PEYRONIE'S DISEASE (PD) IS A CHRONIC FIBROSING CONDITION THAT CONTRIBUTES TO PENILE DEFORMITY, CURVATURE, AND PAIN. INITIAL FAMILIAL STUDIES DEMONSTRATED POTENTIAL GENETIC LINKS TO PD. SINCE THAT TIME, VERY FEW INVESTIGATIONS HAVE SIGNIFICANTLY ADVANCED THE SCIENCE IN THIS AREA. HENCE, THERE IS A LARGE OPPORTUNITY AND SIGNIFICANT NEED TO BETTER STUDY THE UNDERLYING GENOMICS AND PATHOGENESIS OF PD. AIM: TO SUMMARIZE THE CURRENT GENOMIC LITERATURE RELEVANT TO PD. METHODS: A REVIEW WAS PERFORMED OF ALL PUBMED-INDEXED LITERATURE FROM 1970-2018 RELATING TO THE PATHOPHYSIOLOGY AND GENETICS OF PD. KEY FINDINGS WERE CATEGORICALLY SUMMARIZED TO INCLUDE EPIDEMIOLOGY, RISK FACTORS, INHERITANCE PATTERNS, CHROMOSOMAL INSTABILITY, GENETIC ASSOCIATIONS, EPIGENETICS, DIFFERENTIAL GENE EXPRESSION, AND PRECLINICAL MODELS OF PD. MAIN OUTCOME MEASURES: SUMMARY OF THE CURRENT LITERATURE ON THE GENETICS OF PD. RESULTS: PD IS A COMMON CONDITION AND HAS SEVERAL KNOWN RISK FACTORS AND COMORBID DISEASE ASSOCIATIONS. ALTHOUGH MEN WITH PD ARE BELIEVED TO BE GENETICALLY PREDISPOSED, THERE ARE LIKELY SEVERAL SUBTYPES OF THE CONDITION, EACH WITH VARIED PATHOPHYSIOLOGICAL DISORDERS AND CONTRIBUTING FACTORS. AVAILABLE DATA SUGGEST THAT PD IS ASSOCIATED WITH UNDERLYING GENETIC INSTABILITY, INCLUDING DYSREGULATION OF GENES RELATING TO FIBROSIS AND CELLULAR DEGRADATION, THUS, RESULTING IN ABNORMAL PLAQUE DEVELOPMENT AND PENILE DEFORMITY. PRECLINICAL MODELS, INCLUDING CELL CULTURES AND RAT MODELS, DEMONSTRATE SEVERAL CONSISTENCIES WITH PD CLINICAL AND HISTOPATHOLOGIC CHARACTERISTICS; HOWEVER, AN IDEAL MODEL WITH SPONTANEOUS DEVELOPMENT OF PD IS LACKING. CONCLUSION: BASED ON LIMITED DATA, PD LIKELY REPRESENTS A HETEROGENEOUS CONDITION, WITH BOTH HERITABLE AND ENVIRONMENTALLY-DRIVEN EPIGENETIC FACTORS CONTRIBUTING TO ITS DEVELOPMENT AND PROGRESSION. HOWEVER, THERE REMAINS A SIGNIFICANT GAP IN THE LITERATURE ON THE UNDERLYING CAUSE AND PATHOPHYSIOLOGY OF THE CONDITION, SUGGESTING A SUBSTANTIAL NEED FOR FURTHER INVESTIGATION AND STUDY. SHARMA KL, ALOM M, TROST L. THE ETIOLOGY OF PEYRONIE'S DISEASE: PATHOGENESIS AND GENETIC CONTRIBUTIONS. SEX MED REV 2020;8:314-323. 2020 5 6137 27 THE EPIGENETICS OF PSYCHOSIS: A STRUCTURED REVIEW WITH REPRESENTATIVE LOCI. THE EVIDENCE FOR AN ENVIRONMENTAL COMPONENT IN CHRONIC PSYCHOTIC DISORDERS IS STRONG AND RESEARCH ON THE EPIGENETIC MANIFESTATIONS OF THESE ENVIRONMENTAL IMPACTS HAS COMMENCED IN EARNEST. IN REVIEWING THIS RESEARCH, THE FOCUS IS ON THREE GENES AS MODELS FOR DIFFERENTIAL METHYLATION, MCHR1, AKT1 AND TDO2, EACH OF WHICH HAVE BEEN INVESTIGATED FOR GENETIC ASSOCIATION WITH PSYCHOTIC DISORDERS. ENVIRONMENTAL FACTORS ASSOCIATED WITH PSYCHOTIC DISORDERS, AND WHICH INTERACT WITH THESE MODEL GENES, ARE EXPLORED IN DEPTH. THE LOCATION OF TRANSCRIPTION FACTOR MOTIFS RELATIVE TO KEY METHYLATION SITES IS EVALUATED FOR PREDICTED GENE EXPRESSION RESULTS, AND FOR OTHER SITES, EVIDENCE IS PRESENTED FOR METHYLATION DIRECTING ALTERNATIVE SPLICING. EXPERIMENTAL RESULTS FROM KEY STUDIES SHOW DIFFERENTIAL METHYLATION: FOR MCHR1, IN PSYCHOSIS CASES VERSUS CONTROLS; FOR AKT1, AS A PRE-EXISTING METHYLATION PATTERN INFLUENCING BRAIN ACTIVATION FOLLOWING ACUTE ADMINISTRATION OF A PSYCHOSIS-ELICITING ENVIRONMENTAL STIMULUS; AND FOR TDO2, IN A PATTERN ASSOCIATED WITH A DEVELOPMENTAL FACTOR OF RISK FOR PSYCHOSIS, IN ALL CASES THE PREDICTED EXPRESSION IMPACT BEING HIGHLY DEPENDENT ON LOCATION. METHYLATION INDUCED BY SMOKING, A CONFOUNDING VARIABLE, EXHIBITS AN INTRIGUING PATTERN FOR ALL THREE GENES. FINALLY, HOW DIFFERENTIAL METHYLATION MESHES WITH DARWINIAN PRINCIPLES IS EXAMINED, IN PARTICULAR AS IT RELATES TO THE "FLEXIBLE STEM" THEORY OF EVOLUTION. 2022 6 6678 42 USING GENETIC BURDEN SCORES FOR GENE-BY-METHYLATION INTERACTION ANALYSIS ON METABOLIC SYNDROME IN AFRICAN AMERICANS. WITH THE RAPID ADVANCEMENT OF OMICS-BASED RESEARCH, PARTICULARLY BIG DATA SUCH AS GENOME- AND EPIGENOME-WIDE ASSOCIATION STUDIES THAT INCLUDE EXTENSIVE ENVIRONMENTAL AND CLINICAL VARIABLES, DATA ANALYTICS HAVE BECOME INCREASINGLY COMPLEX. RESEARCHERS FACE SIGNIFICANT CHALLENGES REGARDING HOW TO ANALYZE MULTIFACTORIAL DATA AND MAKE USE OF THE FINDINGS FOR CLINICAL TRANSLATION. THE PURPOSE OF THIS ARTICLE IS TO PROVIDE A SCIENTIFIC EXEMPLAR FOR USE OF GENETIC BURDEN SCORES AS A DATA ANALYSIS METHOD FOR STUDIES WITH BOTH GENOTYPE AND DNA METHYLATION DATA IN WHICH THE GOAL IS TO EVALUATE ASSOCIATIONS WITH CHRONIC CONDITIONS SUCH AS METABOLIC SYNDROME (METS). THIS STUDY INCLUDED 739 AFRICAN AMERICAN MEN AND WOMEN FROM THE GENETIC EPIDEMIOLOGY NETWORK OF ARTERIOPATHY STUDY WHO MET DIAGNOSTIC CRITERIA FOR METS AND HAD AVAILABLE GENETIC AND EPIGENETIC DATA. GENETIC BURDEN SCORES FOR EVALUATED GENES WERE NOT SIGNIFICANT AFTER MULTIPLE TESTING CORRECTIONS, BUT DNA METHYLATION AT 2 CPG SITES (DIHYDROOROTATE DEHYDROGENASE CG22381196 PFDR = .014; CTNNA3 CG00132141 PFDR = .043) WAS SIGNIFICANTLY ASSOCIATED WITH METS AFTER CONTROLLING FOR MULTIPLE COMPARISONS. INTERACTIONS BETWEEN THE MARGINALLY SIGNIFICANT CPG SITES AND BURDEN SCORES, HOWEVER, WERE NOT SIGNIFICANT. MORE WORK IS REQUIRED IN THIS AREA TO IDENTIFY INTERMEDIATE BIOLOGICAL PATHWAYS INFLUENCED BY ENVIRONMENTAL, GENETIC, AND EPIGENETIC VARIATION THAT MAY EXPLAIN THE HIGH PREVALENCE OF METS AMONG AFRICAN AMERICANS. THIS STUDY DOES SERVE, HOWEVER, AS AN EXAMPLE OF THE USE OF THE GENETIC BURDEN SCORE AS AN ALTERNATIVE DATA ANALYSIS APPROACH FOR COMPLEX STUDIES INVOLVING THE ANALYSIS OF GENETIC AND EPIGENETIC DATA SIMULTANEOUSLY. 2019 7 4926 40 PARKINSON'S DISEASE AND SARS-COV-2 INFECTION: PARTICULARITIES OF MOLECULAR AND CELLULAR MECHANISMS REGARDING PATHOGENESIS AND TREATMENT. ACCUMULATING DATA SUGGEST THAT CHRONIC NEUROINFLAMMATION-MEDIATED NEURODEGENERATION IS A SIGNIFICANT CONTRIBUTING FACTOR FOR PROGRESSIVE NEURONAL AND GLIAL CELL DEATH IN AGE-RELATED NEURODEGENERATIVE PATHOLOGY. FURTHERMORE, IT COULD BE ENCOUNTERED AS LONG-TERM CONSEQUENCES IN SOME VIRAL INFECTIONS, INCLUDING POST-COVID-19 PARKINSONISM-RELATED CHRONIC SEQUELAE. THE CURRENT SYSTEMATIC REVIEW IS FOCUSED ON A RECENT QUESTION AROUSED DURING THE PANDEMIC'S SUCCESSIVE WAVES: ARE THERE POST-SARS-COV-2 IMMUNE-MEDIATED REACTIONS RESPONSIBLE FOR PROMOTING NEURODEGENERATION? DOES THE HOST'S DYSREGULATED IMMUNE COUNTER-OFFENSIVE CONTRIBUTE TO THE PATHOGENESIS OF NEURODEGENERATIVE DISEASES, EMERGING AS PARKINSON'S DISEASE, IN A COMPLEX INTERRELATION BETWEEN GENETIC AND EPIGENETIC RISK FACTORS? A SYNTHETIC AND SYSTEMATIC LITERATURE REVIEW WAS ACCOMPLISHED BASED ON THE "PREFERRED REPORTING ITEMS FOR SYSTEMATIC PRINCIPLES REVIEWS AND META-ANALYSES" (PRISMA) METHODOLOGY, INCLUDING REGISTRATION ON THE SPECIFIC ONLINE PLATFORM: INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS-PROSPERO, NO. 312183. INITIALLY, 1894 ARTICLES WERE DETECTED. AFTER FULFILLING THE FIVE STEPS OF THE SELECTION METHODOLOGY, 104 PAPERS WERE SELECTED FOR THIS SYNTHETIC REVIEW. DOCUMENTATION WAS ENHANCED WITH A SUPPLEMENTARY 47 BIBLIOGRAPHIC RESOURCES IDENTIFIED IN THE LITERATURE WITHIN A NON-STANDARDIZED SEARCH CONNECTED TO THE SUBJECT. AS A FINAL STEP OF THE PRISMA METHOD, WE HAVE FULFILLED A POPULATION-INTERVENTION-COMPARISON-OUTCOME-TIME (PICOT)/POPULATION-INTERVENTION-COMPARISON-OUTCOME-STUDY TYPE (PICOS)-BASED METANALYSIS OF CLINICAL TRIALS IDENTIFIED AS CONNECTED TO OUR SEARCH, TARGETING THE OUTCOMES OF REHABILITATIVE KINESITHERAPEUTIC INTERVENTIONS COMPARED TO CLINICAL APPROACHES LACKING SUCH KIND OF TREATMENT. ACCORDINGLY, WE IDENTIFIED 10 CLINICAL TRIALS RELATED TO OUR ARTICLE. THE MULTI/INTERDISCIPLINARY CONVENTIONAL THERAPY OF PARKINSON'S DISEASE AND NON-CONVENTIONAL MULTITARGET APPROACH TO AN INTEGRATIVE TREATMENT WAS BRIEFLY ANALYZED. THIS ARTICLE SYNTHESIZES THE CURRENT FINDINGS ON THE PATHOGENIC INTERFERENCE BETWEEN THE DYSREGULATED COMPLEX MECHANISMS INVOLVED IN AGING, NEUROINFLAMMATION, AND NEURODEGENERATION, FOCUSING ON PARKINSON'S DISEASE AND THE ACUTE AND CHRONIC REPERCUSSIONS OF COVID-19. TIME WILL TELL WHETHER COVID-19 NEUROINFLAMMATORY EVENTS COULD TRIGGER LONG-TERM NEURODEGENERATIVE EFFECTS AND CONTRIBUTE TO THE WORSENING AND/OR EXPLOSION OF NEW CASES OF PD. THE EXTENT OF THE INTERRELATED NEUROPATHOGENIC PHENOMENON REMAINS OBSCURE, SO FURTHER CLINICAL OBSERVATIONS AND PROSPECTIVE LONGITUDINAL COHORT STUDIES ARE NEEDED. 2022 8 6720 29 VITAMIN D METABOLISM GENES ARE DIFFERENTIALLY METHYLATED IN INDIVIDUALS WITH CHRONIC KNEE PAIN. CONTEXT: RECENT EVIDENCE SUGGESTS THAT VITAMIN D MAY INTERACT WITH THE EPIGENOME AND PLAY A ROLE IN THE PAIN EXPERIENCE. IN ORDER FOR PROPER FUNCTIONING TO OCCUR, THERE MUST BE AN ADEQUATE LEVEL OF VITAMIN D PRESENT, MADE POSSIBLE BY ENZYMATIC REACTIONS THAT ALLOW VITAMIN D TO BE BIOLOGICALLY ACTIVE. THE PURPOSE OF THIS STUDY WAS TO EXPLORE THE EPIGENETIC LANDSCAPE OF GENES INVOLVED IN VITAMIN D METABOLISM IN INDIVIDUALS WITH AND WITHOUT CHRONIC KNEE PAIN. PROCEDURES: COMMUNITY-DWELLING INDIVIDUALS RECRUITED AS PART OF A LARGER STUDY FOCUSED ON KNEE PAIN PROVIDED DEMOGRAPHIC, CLINICAL AND PAIN-RELATED INFORMATION, AS WELL AS AN INTRAVENOUS BLOOD SAMPLE TO DETERMINE DNA METHYLATION LEVELS AT CPG SITES. MAIN FINDINGS: THERE WERE DIFFERENCES IN DNA METHYLATION BETWEEN THOSE WITH AND WITHOUT PAIN IN GENES THAT CODE FOR ENZYMES RELATED TO VITAMIN D METABOLISM: CYP24A1 (24-HYDROXYLASE) AND CYP27B1 (1-?-HYDROXYLASE). THERE WAS ALSO HYPERMETHYLATION ON THE GENE THAT CODES FOR THE VITAMIN D RECEPTOR (VDR). PRINCIPAL CONCLUSIONS: THE PRESENCE OF CHRONIC PAIN IS ASSOCIATED WITH EPIGENETIC MODIFICATIONS IN GENES RESPONSIBLE FOR THE EXPRESSION OF ENZYMES INVOLVED IN VITAMIN D METABOLISM AND CELLULAR FUNCTION. THESE RESULTS LAY GROUNDWORK IN UNDERSTANDING THE MECHANISM UNDERLYING THE ASSOCIATION BETWEEN VITAMIN D AND CHRONIC PAIN. 2023 9 4869 39 OSTEOARTHRITIS YEAR IN REVIEW: GENETICS, GENOMICS, EPIGENETICS. OBJECTIVE: IN THIS REVIEW, WE HAVE HIGHLIGHTED ADVANCES IN GENETICS, GENOMICS AND EPIGENETICS IN THE FIELD OF OSTEOARTHRITIS (OA) OVER THE PAST YEAR. METHODS: A LITERATURE SEARCH WAS PERFORMED USING PUBMED AND THE CRITERIA: "OSTEOARTHRITIS" AND ONE OF THE FOLLOWING TERMS "GENETIC(S), GENOMIC(S), EPIGENETIC(S), EPIGENOMIC(S), NONCODING RNA, MICRORNA, LONG NONCODING RNA, LNCRNA, CIRCULAR RNA, RNA SEQUENCING, SINGLE CELL SEQUENCING, OR DNA METHYLATION BETWEEN APRIL 1, 2019 AND APRIL 30, 2020. RESULTS: WE IDENTIFIED 653 UNIQUE PUBLICATIONS, MANY STUDIES SPANNED MULTIPLE SEARCH TERMS. WE SUMMARIZED ADVANCES RELATING TO EVOLUTIONARY GENETICS, PAIN, ETHNICITY SPECIFIC RISK FACTORS, FUNCTIONAL STUDIES OF GENE VARIANTS, AND INTERACTIONS BETWEEN CODING AND NON-CODING RNAS IN OA PATHOGENESIS. CONCLUSIONS: STUDIES HAVE IDENTIFIED VARIANTS CONTRIBUTING TO OA SUSCEPTIBILITY, CANDIDATE BIOMARKERS FOR DIAGNOSIS AND PROGNOSIS, AS WELL AS PROMISING THERAPEUTIC CANDIDATES. VALIDATION IN MULTIPLE COHORTS, MULTI-OMICS STRATEGIES, AND MACHINE LEARNING AIDED COMPUTATIONAL ANALYSES HAVE ALL CONTRIBUTED TO THE STRENGTH OF PUBLISHED LITERATURE. OPEN ACCESS DATA-SETS, GREATER SAMPLE SIZES TO CAPTURE BROADER POPULATIONS AND UNDERSTANDING DISEASE MECHANISMS BY INVESTIGATING THE INTERACTIONS BETWEEN MULTIPLE TISSUE TYPES WILL FURTHER AID IN PROGRESS TOWARDS UNDERSTANDING AND CURING OA. 2021 10 2815 31 FIBROMYALGIA: GENETICS AND EPIGENETICS INSIGHTS MAY PROVIDE THE BASIS FOR THE DEVELOPMENT OF DIAGNOSTIC BIOMARKERS. FIBROMYALGIA IS A DISEASE CHARACTERIZED BY CHRONIC WIDESPREAD PAIN WITH ADDITIONAL SYMPTOMS, SUCH AS JOINT STIFFNESS, FATIGUE, SLEEP DISTURBANCE, COGNITIVE DYSFUNCTION, AND DEPRESSION. CURRENTLY, FIBROMYALGIA DIAGNOSIS IS BASED EXCLUSIVELY ON A COMPREHENSIVE CLINICAL ASSESSMENT, ACCORDING TO 2016 ACR CRITERIA, BUT VALIDATED BIOLOGICAL BIOMARKERS ASSOCIATED WITH FIBROMYALGIA HAVE NOT YET BEEN IDENTIFIED. GENOME-WIDE ASSOCIATION STUDIES INVESTIGATED GENES POTENTIALLY INVOLVED IN FIBROMYALGIA PATHOGENESIS HIGHLIGHTING THAT GENETIC FACTORS ARE POSSIBLY RESPONSIBLE FOR UP TO 50% OF THE DISEASE SUSCEPTIBILITY. POTENTIAL CANDIDATE GENES FOUND ASSOCIATED TO FIBROMYALGIA ARE SLC64A4, TRPV2, MYT1L, AND NRXN3. FURTHERMORE, A GENE-ENVIRONMENTAL INTERACTION HAS BEEN PROPOSED AS TRIGGERING MECHANISM, THROUGH EPIGENETIC ALTERATIONS: IN PARTICULAR, FIBROMYALGIA APPEARS TO BE CHARACTERIZED BY A HYPOMETHYLATED DNA PATTERN, IN GENES IMPLICATED IN STRESS RESPONSE, DNA REPAIR, AUTONOMIC SYSTEM RESPONSE, AND SUBCORTICAL NEURONAL ABNORMALITIES. DIFFERENCES IN THE GENOME-WIDE EXPRESSION PROFILE OF MICRORNAS WERE FOUND AMONG MULTIPLE TISSUES, INDICATING THE INVOLVEMENT OF DISTINCT PROCESSES IN FIBROMYALGIA PATHOGENESIS. FURTHER STUDIES SHOULD BE DEDICATED TO STRENGTH THESE PRELIMINARY FINDINGS, IN LARGER MULTICENTER COHORTS, TO IDENTIFY RELIABLE DIRECTIONS FOR BIOMARKER RESEARCH AND CLINICAL PRACTICE. 2019 11 4209 31 METALLOTHIONEIN 2A GENE POLYMORPHISMS IN RELATION TO DISEASES AND TRACE ELEMENT LEVELS IN HUMANS. HUMAN METALLOTHIONEINS ARE A SUPERFAMILY OF LOW MOLECULAR WEIGHT INTRACELLULAR PROTEINS, WHOSE SYNTHESIS CAN BE INDUCED BY ESSENTIAL ELEMENTS (PRIMARILY ZN AND CU), TOXIC ELEMENTS AND CHEMICAL AGENTS, AND STRESS-PRODUCING CONDITIONS. OF THE FOUR KNOWN ISOFORMS IN THE HUMAN BODY MT2 IS THE MOST COMMON. THE EXPRESSION OF METALLOTHIONEINS IS ENCODED BY A MULTIGENE FAMILY OF LINKED GENES AND CAN BE INFLUENCED BY SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) IN THESE GENES. TO DATE, 24 SNPS IN THE MT2A GENE HAVE BEEN IDENTIFIED WITH THE INCIDENCE OF ABOUT 1 % IN VARIOUS POPULATION GROUPS, AND THREE OF THEM WERE SHOWN TO AFFECT PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL PROCESSES. THIS REVIEW SUMMARISES CURRENT KNOWLEDGE ABOUT THESE THREE SNPS IN THE MT2A GENE AND THEIR ASSOCIATIONS WITH ELEMENT CONCENTRATIONS IN THE BODY OF HEALTHY AND DISEASED PERSONS. THE MOST INVESTIGATED SNP IS RS28366003 (MT2A -5 A/G). REPORTS ASSOCIATE IT WITH LONGEVITY, CANCER (BREAST, PROSTATE, LARYNGEAL, AND IN PARANASAL SINUSES), AND CHRONIC RENAL DISEASE. THE SECOND MOST INVESTIGATED SNP, RS10636 (MT2A +838G/C), IS ASSOCIATED WITH BREAST CANCER, CARDIOVASCULAR DISEASE, AND TYPE 2 DIABETES. BOTH ARE ALSO ASSOCIATED WITH SEVERAL METAL/METALLOID CONCENTRATIONS IN THE ORGANISM. THE THIRD SNP, RS1610216 (MT2A -209A/G), HAS BEEN STUDIED FOR ASSOCIATION WITH TYPE 2 DIABETES, CARDIOMYOPATHY, HYPERGLYCAEMIA, AND ZN CONCENTRATIONS. METALLOTHIONEIN CONCENTRATIONS AND MT2A POLYMORPHISMS HAVE A POTENTIAL TO BE USED AS BIOMARKERS OF METAL EXPOSURE AND CLINICAL MARKERS OF A NUMBER OF CHRONIC DISEASES. THIS POTENTIAL NEEDS TO BE STUDIED AND VERIFIED IN A LARGE NUMBER OF WELL-DEFINED GROUPS OF PARTICIPANTS (SEVERAL HUNDREDS AND THOUSANDS) WITH A FOCUS ON PARTICULAR PHYSIOLOGICAL OR PATHOLOGICAL CONDITION AND TAKING INTO CONSIDERATION OTHER CONTRIBUTING FACTORS, SUCH AS ENVIRONMENTAL EXPOSURE AND INDIVIDUAL GENETIC AND EPIGENETIC MAKEUP. 2020 12 3076 31 GENOME-WIDE EPIGENOMIC ANALYSES IN PATIENTS WITH NOCICEPTIVE AND NEUROPATHIC CHRONIC PAIN SUBTYPES REVEALS ALTERATIONS IN METHYLATION OF GENES INVOLVED IN THE NEURO-MUSCULOSKELETAL SYSTEM. NOCICEPTIVE PAIN INVOLVES THE ACTIVATION OF NOCICEPTORS WITHOUT DAMAGE TO THE NERVOUS SYSTEM, WHEREAS NEUROPATHIC PAIN IS RELATED TO AN ALTERATION IN THE CENTRAL OR PERIPHERAL NERVOUS SYSTEM. CHRONIC PAIN ITSELF AND THE TRANSITION FROM ACUTE TO CHRONIC PAIN MAY BE EPIGENETICALLY CONTROLLED. IN THIS CROSS-SECTIONAL STUDY, A GENOME-WIDE DNA METHYLATION ANALYSIS WAS PERFORMED USING THE BLOOD DNA REDUCED REPRESENTATION BISULFITE SEQUENCING (RRBS) TECHNIQUE. THREE PROSPECTIVE COHORTS INCLUDING 20 HEALTHY CONTROLS (CTL), 18 PATIENTS WITH CHRONIC NOCICEPTIVE PAIN (NOCI), AND 19 PATIENTS WITH CHRONIC NEUROPATHIC PAIN (NEURO) WERE COMPARED AT BOTH THE SINGLE CPG AND DIFFERENTIALLY METHYLATED REGION (DMR) LEVELS. GENES WITH DMRS WERE SEEN IN THE NOCI AND NEURO GROUPS BELONGED TO THE NEURO-MUSCULOSKELETAL SYSTEM AND DIFFERED BETWEEN NOCI AND NEURO PATIENTS. OUR RESULTS DEMONSTRATE THAT THE EPIGENETIC DISTURBANCES ACCOMPANYING NOCICEPTIVE PAIN ARE VERY DIFFERENT FROM THOSE ACCOMPANYING NEUROPATHIC PAIN. IN THE FORMER, AMONG OTHERS, THE EPIGENETIC DISTURBANCE OBSERVED WOULD AFFECT THE FUNCTION OF THE OPIOID ANALGESIC SYSTEM, WHEREAS IN THE LATTER IT WOULD AFFECT THAT OF THE GABAERGIC REWARD SYSTEM. THIS STUDY PRESENTS BIOLOGICAL FINDINGS THAT HELP TO CHARACTERIZE NOCI- AND NEURO-AFFECTED PATHWAYS AND OPENS THE POSSIBILITY OF DEVELOPING EPIGENETIC DIAGNOSTIC ASSAYS. PERSPECTIVE: OUR RESULTS HELP TO EXPLAIN THE VARIOUS BIOLOGICAL PATHWAYS MODIFICATIONS UNDERLYING THE DIFFERENT CLINICAL MANIFESTATIONS OF NOCICEPTIVE AND NEUROPATHIC PAINS. FURTHERMORE, THE NEW TARGETS IDENTIFIED IN OUR STUDY MIGHT HELP TO DISCOVER MORE SPECIFIC TREATMENTS FOR NOCICEPTIVE OR NEUROPATHIC PAINS. 2022 13 276 28 AGE-RELATED DIFFERENCES IN MONOCYTE DNA METHYLATION AND IMMUNE FUNCTION IN HEALTHY KENYAN ADULTS AND CHILDREN. BACKGROUND: AGE-RELATED CHANGES IN ADAPTIVE AND INNATE IMMUNE CELLS HAVE BEEN ASSOCIATED WITH A DECLINE IN EFFECTIVE IMMUNITY AND CHRONIC, LOW-GRADE INFLAMMATION. EPIGENETIC, TRANSCRIPTIONAL, AND FUNCTIONAL CHANGES IN MONOCYTES OCCUR WITH AGING, THOUGH MOST STUDIES TO DATE HAVE FOCUSED ON DIFFERENCES BETWEEN YOUNG ADULTS AND THE ELDERLY IN POPULATIONS WITH EUROPEAN ANCESTRY; FEW DATA EXIST REGARDING CHANGES THAT OCCUR IN CIRCULATING MONOCYTES DURING THE FIRST FEW DECADES OF LIFE OR IN AFRICAN POPULATIONS. WE ANALYZED DNA METHYLATION PROFILES, CYTOKINE PRODUCTION, AND INFLAMMATORY GENE EXPRESSION PROFILES IN MONOCYTES FROM YOUNG ADULTS AND CHILDREN FROM WESTERN KENYA. RESULTS: WE IDENTIFIED SEVERAL HYPO- AND HYPER-METHYLATED CPG SITES IN MONOCYTES FROM KENYAN YOUNG ADULTS VS. CHILDREN THAT REPLICATED FINDINGS IN THE CURRENT LITERATURE OF DIFFERENTIAL DNA METHYLATION IN MONOCYTES FROM ELDERLY PERSONS VS. YOUNG ADULTS ACROSS DIVERSE POPULATIONS. DIFFERENTIALLY METHYLATED CPG SITES WERE ALSO NOTED IN GENE REGIONS IMPORTANT TO INFLAMMATION AND INNATE IMMUNE RESPONSES. MONOCYTES FROM KENYAN YOUNG ADULTS VS. CHILDREN DISPLAYED INCREASED PRODUCTION OF IL-8, IL-10, AND IL-12P70 IN RESPONSE TO TLR4 AND TLR2/1 STIMULATION AS WELL AS DISTINCT INFLAMMATORY GENE EXPRESSION PROFILES. CONCLUSIONS: THESE FINDINGS COMPLEMENT PREVIOUS REPORTS OF AGE-RELATED METHYLATION CHANGES IN ISOLATED MONOCYTES AND PROVIDE NOVEL INSIGHTS INTO THE ROLE OF AGE-ASSOCIATED CHANGES IN INNATE IMMUNE FUNCTIONS. 2021 14 1519 32 DNA METHYLATION AT ATP11A CG11702988 IS A BIOMARKER OF LUNG DISEASE SEVERITY IN CYSTIC FIBROSIS: A LONGITUDINAL STUDY. CYSTIC FIBROSIS (CF) IS A CHRONIC GENETIC DISEASE THAT MAINLY AFFECTS THE RESPIRATORY AND GASTROINTESTINAL SYSTEMS. NO CURATIVE TREATMENTS ARE AVAILABLE, BUT THE FOLLOW-UP IN SPECIALIZED CENTERS HAS GREATLY IMPROVED THE PATIENT LIFE EXPECTANCY. ROBUST BIOMARKERS ARE REQUIRED TO MONITOR THE DISEASE, GUIDE TREATMENTS, STRATIFY PATIENTS, AND PROVIDE OUTCOME MEASURES IN CLINICAL TRIALS. IN THE PRESENT STUDY, WE OUTLINE A STRATEGY TO SELECT PUTATIVE DNA METHYLATION BIOMARKERS OF LUNG DISEASE SEVERITY IN CYSTIC FIBROSIS PATIENTS. IN THE DISCOVERY STEP, WE SELECTED SEVEN POTENTIAL BIOMARKERS USING A GENOME-WIDE DNA METHYLATION DATASET THAT WE GENERATED IN NASAL EPITHELIAL SAMPLES FROM THE METHYLCF COHORT. IN THE REPLICATION STEP, WE ASSESSED THE SAME BIOMARKERS USING SPUTUM CELL SAMPLES FROM THE METHYLBIOMARK COHORT. OF INTEREST, DNA METHYLATION AT THE CG11702988 SITE (ATP11A GENE) POSITIVELY CORRELATED WITH LUNG FUNCTION AND BMI, AND NEGATIVELY CORRELATED WITH LUNG DISEASE SEVERITY, P. AERUGINOSA CHRONIC INFECTION, AND THE NUMBER OF EXACERBATIONS. THESE RESULTS WERE REPLICATED IN PROSPECTIVE SPUTUM SAMPLES COLLECTED AT FOUR TIME POINTS WITHIN AN 18-MONTH PERIOD AND LONGITUDINALLY. TO CONCLUDE, (I) WE IDENTIFIED A DNA METHYLATION BIOMARKER THAT CORRELATES WITH CF SEVERITY, (II) WE PROVIDED A METHOD TO EASILY ASSESS THIS BIOMARKER, AND (III) WE CARRIED OUT THE FIRST LONGITUDINAL ANALYSIS OF DNA METHYLATION IN CF PATIENTS. THIS NEW EPIGENETIC BIOMARKER COULD BE USED TO STRATIFY CF PATIENTS IN CLINICAL TRIALS. 2021 15 1979 38 EPIGENETIC ALTERATIONS IN CHRONIC DISEASE FOCUSING ON BEHCET'S DISEASE: REVIEW. OBJECTIVE: 'EPIGENETICS' IS SPECIFIED AS THE INHERITABLE CHANGES IN GENE EXPRESSION WITH NO ALTERATIONS IN DNA SEQUENCES. EPIGENETICS IS A RAPIDLY OVERSPREADING SCIENTIFIC FIELD, AND THE STUDY OF EPIGENETIC REGULATION IN CHRONIC DISEASE IS EMERGING. THIS STUDY AIMS TO EVALUATE EPIGENETIC CHANGES INCLUDING DNA METHYLATION, HISTONE MODIFICATION, AND NON-CODING RNAS (NCRNAS) IN INFLAMMATORY DISEASE, WITH FOCUS ON BEHCET'S DISEASE. IN THIS REVIEW, FIRST WE DESCRIBE THE HISTORY AND CLASSIFICATION OF EPIGENETIC CHANGES, AND THEN THE ROLE OF EPIGENETIC ALTERATIONS IN CHRONIC DISEASES IS EXPLAINED. METHODS: SYSTEMATIC SEARCH OF MEDLINE, EMBASE, AND COCHRANE LIBRARY WAS CONDUCTED FOR ALL COMPARATIVE STUDIES SINCE 2000 TO 2015 WITH THE LIMITATIONS OF THE ENGLISH LANGUAGE. RESULTS: FOR A NOTABLE PERIOD OF TIME, RESEARCHERS HAVE MAINLY FOCUSED ON THE EPIGENETIC PATHWAYS THAT ARE INVOLVED IN THE MODULATION OF INFLAMMATORY AND ANTI-INFLAMMATORY GENES. RECENT STUDIES HAVE PROPOSED A CENTRAL ROLE FOR CHRONIC INFLAMMATION IN THE PATHOGENESIS OF CHRONIC DISEASE, INCLUDING BEHCET'S DISEASE. CONCLUSION: STUDIES HAVE BEEN REPORTED ON THE EPIGENETIC OF BD SHOWED THE ROLE OF ALTERATIONS IN THE METHYLATION LEVEL OF IRS ELEMENTS; HISTONE MODIFICATIONS SUCH AS H3K4ME27 AND H3K4ME3; UP REGULATION OF MIR-182 AND MIR-3591-3P; DOWN REGULATION OF MIR-155, MIR-638 AND MIR-4488 IN THE PATHOGENESIS OF THE DISEASE. 2017 16 4198 24 METABOLIC PROFILING DISTINGUISHES THREE SUBTYPES OF ALZHEIMER'S DISEASE. THE CAUSE OF ALZHEIMER'S DISEASE IS INCOMPLETELY DEFINED, AND NO TRULY EFFECTIVE THERAPY EXISTS. HOWEVER, MULTIPLE STUDIES HAVE IMPLICATED METABOLIC ABNORMALITIES SUCH AS INSULIN RESISTANCE, HORMONAL DEFICIENCIES, AND HYPERHOMOCYSTEINEMIA. OPTIMIZING METABOLIC PARAMETERS IN A COMPREHENSIVE WAY HAS YIELDED COGNITIVE IMPROVEMENT, BOTH IN SYMPTOMATIC AND ASYMPTOMATIC INDIVIDUALS. THEREFORE, EXPANDING THE STANDARD LABORATORY EVALUATION IN PATIENTS WITH DEMENTIA MAY BE REVEALING. HERE I REPORT THAT METABOLIC PROFILING REVEALS THREE ALZHEIMER'S DISEASE SUBTYPES. THE FIRST IS INFLAMMATORY, IN WHICH MARKERS SUCH AS HS-CRP AND GLOBULIN:ALBUMIN RATIO ARE INCREASED. THE SECOND TYPE IS NON-INFLAMMATORY, IN WHICH THESE MARKERS ARE NOT INCREASED, BUT OTHER METABOLIC ABNORMALITIES ARE PRESENT. THE THIRD TYPE IS A VERY DISTINCTIVE CLINICAL ENTITY THAT AFFECTS RELATIVELY YOUNG INDIVIDUALS, EXTENDS BEYOND THE TYPICAL ALZHEIMER'S DISEASE INITIAL DISTRIBUTION TO AFFECT THE CORTEX WIDELY, IS CHARACTERIZED BY EARLY NON-AMNESTIC FEATURES SUCH AS DYSCALCULIA AND APHASIA, IS OFTEN MISDIAGNOSED OR LABELED ATYPICAL ALZHEIMER'S DISEASE, TYPICALLY AFFECTS APOE4-NEGATIVE INDIVIDUALS, AND IS ASSOCIATED WITH STRIKING ZINC DEFICIENCY. GIVEN THE INVOLVEMENT OF ZINC IN MULTIPLE ALZHEIMER'S-RELATED METABOLIC PROCESSES, SUCH AS INSULIN RESISTANCE, CHRONIC INFLAMMATION, ADAM10 PROTEOLYTIC ACTIVITY, AND HORMONAL SIGNALING, THIS SYNDROME OF ALZHEIMER'S-PLUS WITH LOW ZINC (APLZ) WARRANTS FURTHER METABOLIC, GENETIC, AND EPIGENETIC CHARACTERIZATION. 2015 17 2510 39 EPIGENETICS AND POSTSURGICAL PAIN: A SCOPING REVIEW. OBJECTIVE: MULTIPLE FACTORS ARE INVOLVED IN THE PHYSIOLOGY AND VARIABILITY OF POSTSURGICAL PAIN, A GREAT PART OF WHICH CAN BE EXPLAINED BY GENETIC AND ENVIRONMENTAL FACTORS AND THEIR INTERACTION. EPIGENETICS REFERS TO THE MECHANISM BY WHICH THE ENVIRONMENT ALTERS THE STABILITY AND EXPRESSION OF GENES. WE CONDUCTED A SCOPING REVIEW TO EXAMINE THE AVAILABLE EVIDENCE IN BOTH ANIMAL MODELS AND CLINICAL STUDIES ON EPIGENETIC MECHANISMS INVOLVED IN THE REGULATION OF POSTSURGICAL AND CHRONIC POSTSURGICAL PAIN. METHODS: THE ARKSEY AND O'MALLEY FRAMEWORK AND THE PRISMA-SCR (PREFERRED REPORTING ITEMS FOR SYSTEMATIC REVIEW AND META-ANALYSIS, SCOPING REVIEWS EXTENSION) GUIDELINES WERE USED. THE PUBMED, WEB OF SCIENCE, AND GOOGLE SCHOLAR DATABASES WERE SEARCHED, AND THE ORIGINAL ARTICLES CITED IN REVIEWS LOCATED THROUGH THE SEARCH WERE ALSO REVIEWED. ENGLISH-LANGUAGE ARTICLES WITHOUT TIME LIMITS WERE RETRIEVED. ARTICLES WERE SELECTED IF THE ABSTRACT ADDRESSED INFORMATION ON THE EPIGENETIC OR EPIGENOMIC MECHANISMS, HISTONE, OR DNA METHYLATION AND MICRORIBONUCLEIC ACIDS INVOLVED IN POSTSURGICAL AND CHRONIC POSTSURGICAL PAIN IN ANIMAL MODELS AND CLINICAL STUDIES. RESULTS: THE INITIAL SEARCH PROVIDED 174 ARTICLES, AND 95 WERE USED. THE AVAILABLE STUDIES TO DATE, MOSTLY IN ANIMAL MODELS, HAVE SHOWN THAT EPIGENETICS CONTRIBUTES TO THE REGULATION OF GENE EXPRESSION IN THE PATHWAYS INVOLVED IN POSTSURGICAL PAIN AND IN MAINTAINING LONG-TERM PAIN. CONCLUSION: RESEARCH ON POSSIBLE EPIGENETIC MECHANISMS INVOLVED IN POSTSURGICAL PAIN AND CHRONIC POSTSURGICAL PAIN IN HUMANS IS SCARCE. IN VIEW OF THE EVIDENCE AVAILABLE IN ANIMAL MODELS, THERE IS A NEED TO EVALUATE EPIGENETIC PAIN MECHANISMS IN THE CONTEXT OF HUMAN AND CLINICAL STUDIES. 2022 18 5737 35 SMOKING AND HEALTH: ASSOCIATION BETWEEN TELOMERE LENGTH AND FACTORS IMPACTING ON HUMAN DISEASE, QUALITY OF LIFE AND LIFE SPAN IN A LARGE POPULATION-BASED COHORT UNDER THE EFFECT OF SMOKING DURATION. REACTIVE OXYGEN SPECIES (ROS) ARE OF PRIMARY IMPORTANCE AS THEY CAUSE DAMAGE TO LIPIDS, PROTEINS, AND DNA EITHER ENDOGENOUSLY BY CELLULAR MECHANISM, OR THROUGH EXOGENOUS EXPOSURE TO ENVIRONMENTAL INJURY FACTORS, INCLUDING OXIDATION INSULT FACTORS, SUCH AS TOBACCO SMOKE. CURRENTLY 46.3 MILLION ADULTS (25.7 PERCENT OF THE POPULATION) ARE SMOKERS. THIS INCLUDES 24 MILLION MEN (28.1 PERCENT OF THE TOTAL) AND MORE THAN 22 MILLION WOMEN (23.5 PERCENT). THE PREVALENCE IS HIGHEST AMONG PERSONS 25-44 YEARS OF AGE. CIGARETTE SMOKERS HAVE A HIGHER RISK OF DEVELOPING SEVERAL CHRONIC DISORDERS. THESE INCLUDE FATTY BUILDUPS IN ARTERIES, SEVERAL TYPES OF CANCER AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (LUNG PROBLEMS). AS PERIPHERAL LEUKOCYTES HAVE BEEN THE MAIN TARGET OF HUMAN TELOMERE RESEARCH, MOST OF WHAT IS KNOWN ABOUT HUMAN TELOMERE DYNAMICS IN VIVO IS BASED ON THESE CELLS. LEUKOCYTE TELOMERE LENGTH (TL) IS A COMPLEX TRAIT THAT IS SHAPED BY GENETIC, EPIGENETIC, AND ENVIRONMENTAL DETERMINANTS. IN THIS ARTICLE, WE CONSIDER THAT SMOKING MODIFIES LEUKOCYTE TL IN HUMANS AND CONTRIBUTES TO ITS VARIABILITY AMONG INDIVIDUALS, ALTHOUGH THE SMOKING EFFECT ON TL AND ITS RELATION WITH OTHER METABOLIC INDICES MAY ACCELERATE BIOLOGICAL AGING AND DEVELOPMENT OF SMOKING-INDUCED CHRONIC DISEASES IN A LARGE HUMAN POPULATION-BASED COHORTS WITH SMOKING BEHAVIOR. RECENT STUDIES CONFIRMED THAT INDIVIDUALS WITH SHORTER TELOMERES PRESENT A HIGHER PREVALENCE OF ARTERIAL LESIONS AND HIGHER RISK OF CARDIOVASCULAR DISEASE MORTALITY. THIS STUDY ORIGINALLY SUGGESTS THAT EFFICIENT THERAPEUTIC PROTECTION OF TL AND STRUCTURE IN RESPONSE TO STRESSES THAT ARE KNOWN TO REDUCE TL, SUCH AS OXIDATIVE DAMAGE OR INFLAMMATION ASSOCIATED WITH TOBACCO SMOKING, WOULD LEAD TO BETTER TELOMERE MAINTENANCE. RECENTLY, WE HAVE DISCOVERED THE POTENTIAL USE OF TELOMERE-RESTORATIVE IMIDAZOLE-CONTAINING DIPEPTIDE (NON-HYDROLIZED CARNOSINE, CARCININE) BASED THERAPY FOR BETTER SURVIVAL OF SMOKERS. WE CONCLUDE THAT A BETTER THERAPEUTIC OR NUTRITIONAL MAINTENANCE OF TL MAY CONFER HEALTHY AGING IN SMOKERS AND EXCEPTIONAL LONGEVITY IN REGULARLY ROS-EXPOSED HUMAN SURVIVORS. 2011 19 2533 34 EPIGENETICS IN AUTOIMMUNE CONNECTIVE TISSUE DISEASES. BACKGROUND. AUTOIMMUNE CONNECTIVE TISSUE DISEASES (ACTDS) ENCOMPASS A HETEROGENEOUS GROUP OF CHRONIC IMMUNE-MEDIATED INFLAMMATORY DISORDERS, PRIMARILY AFFECTING CONNECTIVE TISSUES AND CLINICALLY CHARACTERIZED BY VARIABLE MULTISYSTEM MANIFESTATIONS, FREQUENTLY OVERLAPPING. ENVIRONMENTAL FACTORS ARE THOUGHT TO PROMOTE ACTD DEVELOPMENT IN GENETIC PREDISPOSING/ENDOCRINE PERMISSIVE BACKGROUND THROUGH THE INDUCTION OF EPIGENETIC MODIFICATIONS, CONSISTING OF STABLE, HERITABLE, BUT POTENTIALLY REVERSIBLE CHANGES IN GENE EXPRESSION, OCCURRING WITHOUT ALTERATIONS OF THE DNA SEQUENCE. ACTUALLY, EPIGENETIC MECHANISMS (SUCH AS HISTONE MODIFICATIONS, DNA METHYLATION, NUCLEOSOME POSITIONING, AND RNA INTERFERENCE) LINK GENOTYPE UPSTREAM AND PHENOTYPE DOWNSTREAM, AND, IF PERSISTENTLY ABERRANT, MAY CAUSE A VARIETY OF HUMAN DISEASES, INCLUDING ACTDS. WE AIMED TO REVIEW THE RECENT ADVANCES IN THE KNOWLEDGE OF THE ACTD EPIGENETIC ALTERATIONS. METHODS: A DETAILED SEARCH OF THE AVAILABLE LITERATURE WAS PERFORMED IN THE PUBMED (U.S. NATIONAL LIBRARY OF MEDICINE) DATABASE. RESULTS: GROWING EVIDENCE UNDERLINES THE RELEVANT ROLE OF EPIGENETIC DEFECTS IN THE ACTD PATHOGENESIS, AND SPECIFIC EPIGENETIC PATTERNS CAN REPRESENT DISEASE BIOMARKERS. IN PATIENTS WITH RHEUMATOID ARTHRITIS (RA), EPIGENETIC VARIATIONS INTERACT DETERMINING THE TYPICAL "AGGRESSIVE" PHENOTYPE DISPLAYED BY RA SYNOVIAL FIBROBLASTS. EPIGENETIC MODIFICATIONS ARE INVOLVED IN THE PROFIBROTIC PROCESS THAT CHARACTERIZES SYSTEMIC SCLEROSIS. IN SYSTEMIC LUPUS ERYTHEMATOSUS AND SJOGREN'S SYNDROME, COMPLEX EPIGENETIC CHANGES ALTERING GENE EXPRESSION HAVE BEEN DEMONSTRATED. CONCLUSIONS: COMPREHENSIVE STUDIES WILL CONTRIBUTE TO FURTHER DEFINE THE ABERRANT EPIGENETIC MECHANISMS INVOLVED IN THE ACTDS ETIOPATHOGENESIS. MOREOVER, BEING EPIGENETIC CHANGES POTENTIALLY REVERSIBLE, THE IDENTIFICATION OF ACTDS EPIGENETIC BIOMARKERS WILL ALLOW THE DEVELOPMENT OF THERAPEUTIC STRATEGIES ADDRESSED TO TARGET DYSREGULATED GENES AND CORRECT ABERRANT EPIGENOMIC ALTERATIONS. 2014 20 6334 22 THE ROLE OF DNA METHYLATION AND HYDROXYMETHYLATION IN IMMUNOSENESCENCE. A HEALTHY FUNCTIONING IMMUNE SYSTEM IS CRITICAL TO STAVE OFF INFECTIOUS DISEASES, BUT AS HUMANS AND OTHER ORGANISMS AGE, THEIR IMMUNE SYSTEMS DECLINE. AS A RESULT, DISEASES THAT WERE READILY THWARTED IN EARLY LIFE POSE NONTRIVIAL HARM AND CAN EVEN BE DEADLY IN LATE LIFE. IMMUNOSENESCENCE IS DEFINED AS THE GENERAL DETERIORATION OF THE IMMUNE SYSTEM WITH AGE, AND IT IS CHARACTERIZED BY FUNCTIONAL CHANGES IN HEMATOPOIETIC STEM CELLS (HSCS) AND SPECIFIC BLOOD CELL TYPES AS WELL AS CHANGES IN LEVELS OF NUMEROUS FACTORS, PARTICULARLY THOSE INVOLVED IN INFLAMMATION. POTENTIAL MECHANISMS UNDERLYING IMMUNOSENESCENCE INCLUDE EPIGENETIC CHANGES SUCH AS CHANGES IN DNA METHYLATION (DNAM) AND DNA HYDROXYMETHYLATION (DNAHM) THAT OCCUR WITH AGE. THE PURPOSE OF THIS REVIEW IS TO DESCRIBE WHAT IS CURRENTLY KNOWN ABOUT THE RELATIONSHIP BETWEEN IMMUNOSENESCENCE AND THE AGE-RELATED CHANGES TO DNAM AND DNAHM, AND TO DISCUSS EXPERIMENTAL APPROACHES BEST SUITED TO FILL GAPS IN OUR UNDERSTANDING. 2019