1 4346 144 MIR-10A, MIR-15A, LET-7A, AND LET-7G EXPRESSION AS STRESS-RELEVANT BIOMARKERS TO ASSESS ACUTE OR CHRONIC PSYCHOLOGICAL STRESS AND MENTAL HEALTH IN HUMAN CAPILLARY BLOOD. BACKGROUND: PSYCHOLOGICAL STRESS, AS AN IMPORTANT COFACTOR IN THE DEVELOPMENT OF MANY ACUTE AND CHRONIC DISEASES, IS CRUCIAL FOR GENERAL HEALTH OR WELL-BEING, AND IMPROVED MARKERS ARE NEEDED TO DISTINGUISH SITUATIONS OF PROGRESSIVE PATHOLOGICAL DEVELOPMENT, SUCH AS DEPRESSION, ANXIETY, OR BURNOUT, TO BE RECOGNIZED AT AN EARLY STAGE. EPIGENETIC BIOMARKERS PLAY AN IMPORTANT ROLE IN THE EARLY DETECTION AND TREATMENT OF COMPLEX DISEASES SUCH AS CANCER, AND METABOLIC OR MENTAL DISORDERS. THEREFORE, THIS STUDY AIMED TO IDENTIFY SO-CALLED MIRNAS, WHICH WOULD BE SUITABLE AS STRESS-RELATED BIOMARKERS. METHODS AND RESULTS: IN THIS STUDY, 173 PARTICIPANTS (36.4% MALES, AND 63.6% FEMALES) WERE INTERVIEWED ABOUT STRESS, STRESS-RELATED DISEASES, LIFESTYLE, AND DIET TO ASSESS THEIR ACUTE AND CHRONIC PSYCHOLOGICAL STRESS STATUS. USING QPCR ANALYSIS, 13 DIFFERENT MIRNAS (MIR-10A-5P, MIR-15A-5P, MIR-16-5P, MIR-19B-3P, MIR-26B-5P, MIR-29C-3P, MIR-106B-5P, MIR-126-3P, MIR-142-3P, LET-7A-5P, LET-7G-5P, MIR-21-5P, AND MIR-877-5P) WERE ANALYZED IN DRIED CAPILLARY BLOOD SAMPLES. FOUR MIRNAS WERE IDENTIFIED, MIR-10A-5P, MIR-15A-5P, LET-7A-5P, AND LET-7G-5P (P < 0.05), WHICH COULD BE USED AS POSSIBLE CANDIDATES FOR MEASURING PATHOLOGICAL FORMS OF ACUTE OR CHRONIC STRESS. LET-7A-5P, LET-7G-5P, AND MIR-15A-5P (P < 0.05) WERE ALSO SIGNIFICANTLY HIGHER IN SUBJECTS WITH AT LEAST ONE STRESS-RELATED DISEASE. FURTHER, CORRELATIONS WERE IDENTIFIED BETWEEN LET-7A-5P AND MEAT CONSUMPTION (P < 0.05) AND BETWEEN MIR-15A-5P AND COFFEE CONSUMPTION (P < 0.05). CONCLUSION: THE EXAMINATION OF THESE FOUR MIRNAS AS BIOMARKERS USING A MINIMALLY INVASIVE METHOD OFFERS THE POSSIBILITY OF DETECTING HEALTH PROBLEMS AT AN EARLY STAGE AND COUNTERACTING THEM TO MAINTAIN GENERAL AND MENTAL HEALTH.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
2 4367  60 MIRNA-BASED "FITNESS SCORE" TO ASSESS THE INDIVIDUAL RESPONSE TO DIET, METABOLISM, AND EXERCISE. BACKGROUND: REGULAR, ESPECIALLY SUSTAINED EXERCISE PLAYS AN IMPORTANT ROLE IN THE PREVENTION AND TREATMENT OF MULTIPLE CHRONIC DISEASES. SOME OF THE UNDERLYING MOLECULAR AND CELLULAR MECHANISMS BEHIND THE ADAPTIVE RESPONSE TO PHYSICAL ACTIVITY ARE STILL UNCLEAR, BUT RECENT FINDINGS SUGGEST A POSSIBLE ROLE OF EPIGENETIC MECHANISMS, ESPECIALLY MIRNAS, IN THE PROGRESSION AND MANAGEMENT OF EXERCISE-RELATED CHANGES. DUE TO THE COMBINATION OF THE ANALYSIS OF EPIGENETIC BIOMARKERS (MIRNAS), THE INTAKE OF FOOD AND SUPPLEMENTS, AND GENETIC DISPOSITIONS, A "FITNESS SCORE" WAS EVALUATED TO ASSESS THE INDIVIDUAL RESPONSE TO NUTRITION, EXERCISE, AND METABOLIC INFLUENCE. METHODS: IN RESPONSE TO A 12-WEEK SPORTS INTERVENTION, WE ANALYZED GENETIC AND EPIGENETIC BIOMARKERS IN CAPILLARY BLOOD FROM 61 SEDENTARY, HEALTHY PARTICIPANTS (66.1% FEMALES, 33.9% MALES, MEAN AGE 33 YEARS), INCLUDING LINE-1 METHYLATION, THREE SNPS, AND TEN MIRNAS USING HRM AND QPCR ANALYSIS. THESE BIOMARKERS WERE ALSO ANALYZED IN A HEALTHY, AGE- AND SEX-MATCHED CONTROL GROUP (N, 20) WITHOUT INTERVENTION. FOOD FREQUENCY INTAKE, INCLUDING DIETARY SUPPLEMENT INTAKE, AND GENERAL HEALTH QUESTIONNAIRES WERE SURVEYED UNDER THE SUPERVISION OF TRAINED STAFF. RESULTS: EXERCISE TRAINING DECREASED THE EXPRESSION OF MIR-20A-5P, -22-5P, AND -505-3P (P < 0.02) AND IMPROVED THE "FITNESS SCORE," WHICH ESTIMATES EIGHT DIFFERENT LIFESTYLE FACTORS TO ASSESS, NUTRITION, INFLAMMATION, CARDIOVASCULAR FITNESS, INJURY RISK, REGENERATION, MUSCLE AND HYDRATION STATUS, AS WELL AS STRESS LEVEL. IN ADDITION, WE WERE ABLE TO DETERMINE CORRELATIONS BETWEEN INDIVIDUAL MIRNAS, MIR-20A-5P, -22-5P, AND -101-3P (P < 0.04), AND THE GENETIC PREDISPOSITION FOR ENDURANCE AND/OR STRENGTH AND OBESITY RISK (ACE, ACTN3, AND FTO), AS WELL AS BETWEEN MIRNAS AND THE BODY COMPOSITION (P < 0.05). MIR-19B-3P AND -101-3P CORRELATED WITH THE INTAKE OF B VITAMINS. FURTHER, MIR-19B-3P CORRELATED WITH MAGNESIUM AND MIR-378A-3P WITH IRON INTAKE (P < 0.05). CONCLUSIONS: IN SUMMARY, OUR RESULTS INDICATE THAT A COMBINED ANALYSIS OF SEVERAL BIOMARKERS (MIRNAS) CAN PROVIDE INFORMATION ABOUT AN INDIVIDUAL'S TRAINING ADAPTIONS/FITNESS, BODY COMPOSITION, NUTRITIONAL NEEDS, AND POSSIBLE RECOVERY. IN CONTRAST TO MOST STUDIES USING MUSCLE BIOPSIES, WE WERE ABLE TO SHOW THAT THESE BIOMARKERS CAN ALSO BE MEASURED USING A MINIMALLY INVASIVE METHOD.	2022	
                                                                                                                                                                                                
3 5638  32 SERUM METABOLOMICS REVEALS PATHWAYS AND BIOMARKERS ASSOCIATED WITH ASTHMA PATHOGENESIS. BACKGROUND: ASTHMA IS A CHRONIC INFLAMMATORY DISEASE CAUSED BY COMPLEX INTERACTIONS OF GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS. FOR THIS REASON, NEW APPROACHES ARE REQUIRED TO CLARIFY THE PATHOGENESIS OF ASTHMA BY SYSTEMIC REVIEW. OBJECTIVE: WE APPLIED A (1)H-NMR METABOLOMICS APPROACH TO INVESTIGATE THE ALTERED METABOLIC PATTERN IN SERA FROM PATIENTS WITH ASTHMA AND SOUGHT TO IDENTIFY THE MECHANISM UNDERLYING ASTHMA AND POTENTIAL BIOMARKERS. METHOD: A GLOBAL PROFILE OF SERA FROM PATIENTS WITH ASTHMA (N = 39) AND CONTROLS (N = 26) WAS GENERATED USING (1)H-NMR SPECTROSCOPY COUPLED WITH MULTIVARIATE STATISTICAL ANALYSIS. ENDOGENOUS METABOLITES IN SERUM WERE RAPIDLY MEASURED USING THE TARGET-PROFILING PROCEDURE. RESULTS: MULTIVARIATE STATISTICAL ANALYSIS SHOWED A CLEAR DISTINCTION BETWEEN PATIENTS WITH ASTHMA AND HEALTHY SUBJECTS. SERA OF ASTHMA PATIENTS WERE CHARACTERIZED BY INCREASED LEVELS OF METHIONINE, GLUTAMINE, AND HISTIDINE AND BY DECREASED LEVELS OF FORMATE, METHANOL, ACETATE, CHOLINE, O-PHOSPHOCHOLINE, ARGININE, AND GLUCOSE. THE METABOLITES DETECTED IN THE SERA OF PATIENTS WITH ASTHMA ARE INVOLVED IN HYPERMETHYLATION, RESPONSE TO HYPOXIA, AND IMMUNE REACTION. FURTHERMORE, THE LEVELS OF SERUM METABOLITES FROM PATIENTS WITH ASTHMA CORRELATED WITH ASTHMA SEVERITY; IN PARTICULAR, LIPID METABOLISM WAS ALTERED IN PATIENTS WITH LOWER FORCED EXPIRATORY VOLUME IN 1 S PERCENTAGE (FEV(1)%) PREDICTED VALUES. IN ADDITION, POTENTIAL BIOMARKERS SHOWED STRONG PREDICTIVE POWER IN ROC ANALYSIS, AND THE PRESENCE OF ASTHMA IN EXTERNAL VALIDATION MODELS WAS PREDICTED WITH HIGH ACCURACY (90.9% FOR ASTHMA AND 100% FOR CONTROL SUBJECTS). CONCLUSION & CLINICAL RELEVANCE: THESE DATA SHOWED THAT (1)H-NMR-BASED METABOLITE PROFILING OF SERUM MAY BE USEFUL FOR THE EFFECTIVE DIAGNOSIS OF ASTHMA AND A FURTHER UNDERSTANDING OF ITS PATHOGENESIS.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
4 6547  38 TRANSCRIPTOMICS OF LONG-TERM MEDITATION PRACTICE: EVIDENCE FOR PREVENTION OR REVERSAL OF STRESS EFFECTS HARMFUL TO HEALTH. BACKGROUND AND OBJECTIVES: STRESS CAN OVERLOAD ADAPTIVE MECHANISMS, LEADING TO EPIGENETIC EFFECTS HARMFUL TO HEALTH. RESEARCH ON THE REVERSAL OF THESE EFFECTS IS IN ITS INFANCY. EARLY RESULTS SUGGEST SOME MEDITATION TECHNIQUES HAVE HEALTH BENEFITS THAT GROW WITH REPEATED PRACTICE. THIS STUDY FOCUSED ON POSSIBLE TRANSCRIPTOMIC EFFECTS OF 38 YEARS OF TWICE-DAILY TRANSCENDENTAL MEDITATION((R)) (TM((R))) PRACTICE. MATERIALS AND METHODS: FIRST, USING ILLUMINA((R)) BEADCHIP MICROARRAY TECHNOLOGY, DIFFERENCES IN GLOBAL GENE EXPRESSION IN PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMCS) WERE SOUGHT BETWEEN HEALTHY PRACTITIONERS AND TIGHTLY MATCHED CONTROLS (N = 12, AGE 65). SECOND, THESE MICROARRAY RESULTS WERE VERIFIED ON A SUBSET OF GENES USING QUANTITATIVE POLYMERASE CHAIN REACTION (QPCR) AND WERE VALIDATED USING QPCR IN LARGER TM AND CONTROL GROUPS (N = 45, AGE 63). BIOINFORMATICS INVESTIGATION EMPLOYED INGENUITY((R)) PATHWAY ANALYSIS (IPA((R))), DAVID, GENOMATIX, AND R PACKAGES. RESULTS: THE 200 GENES AND LOCI FOUND TO MEET STRICT CRITERIA FOR DIFFERENTIAL EXPRESSION IN THE MICROARRAY EXPERIMENT SHOWED CONTRASTING PATTERNS OF EXPRESSION THAT DISTINGUISHED THE TWO GROUPS. DIFFERENTIAL EXPRESSION RELATING TO IMMUNE FUNCTION AND ENERGY EFFICIENCY WERE MOST APPARENT. IN THE TM GROUP, RELATIVE TO THE CONTROL, ALL 49 GENES ASSOCIATED WITH INFLAMMATION WERE DOWNREGULATED, WHILE GENES ASSOCIATED WITH ANTIVIRAL AND ANTIBODY COMPONENTS OF THE DEFENSE RESPONSE WERE UPREGULATED. THE LARGEST EXPRESSION DIFFERENCES WERE SHOWN BY SIX GENES RELATED TO ERYTHROCYTE FUNCTION THAT APPEARED TO REFLECT A CONDITION OF LOWER ENERGY EFFICIENCY IN THE CONTROL GROUP. RESULTS SUPPORTING THESE GENE EXPRESSION DIFFERENCES WERE OBTAINED WITH QPCR-MEASURED EXPRESSION BOTH IN THE WELL-MATCHED MICROARRAY GROUPS AND IN THE LARGER, LESS WELL-MATCHED GROUPS. CONCLUSIONS: THESE FINDINGS ARE CONSISTENT WITH PREDICTIONS BASED ON RESULTS FROM EARLIER RANDOMIZED TRIALS OF MEDITATION AND MAY PROVIDE EVIDENCE FOR STRESS-RELATED MOLECULAR MECHANISMS UNDERLYING REDUCTIONS IN ANXIETY, POST-TRAUMATIC STRESS DISORDER (PTSD), CARDIOVASCULAR DISEASE (CVD), AND OTHER CHRONIC DISORDERS AND DISEASES.	2021	
                                                                                                                                                                                                                                                                                                                                                                             
5 1025  31 CIRCULATING MIRNAS ARE ASSOCIATED WITH INFLAMMATION BIOMARKERS IN CHILDREN WITH OVERWEIGHT AND OBESITY: RESULTS OF THE I.FAMILY STUDY. INCREASING DATA SUGGEST THAT OVERNUTRITION-INDUCED OBESITY MAY TRIGGER AN INFLAMMATORY PROCESS IN ADIPOSE TISSUE AND UPTURN IN THE INNATE IMMUNE SYSTEM. NUMEROUS PLAYERS HAVE BEEN INVOLVED IN GOVERNING THE INFLAMMATORY RESPONSE, INCLUDING EPIGENETICS. AMONG EPIGENETIC PLAYERS, MIRNAS ARE EMERGING AS CRUCIAL REGULATORS OF IMMUNE CELL DEVELOPMENT, IMMUNE RESPONSES, AUTOIMMUNITY, AND INFLAMMATION. IN THIS STUDY, WE AIMED AT IDENTIFYING THE INVOLVEMENT OF CANDIDATE MIRNAS IN RELATION TO INFLAMMATION-ASSOCIATED BIOMARKERS IN A SUBSAMPLE OF EUROPEAN CHILDREN WITH OVERWEIGHT AND OBESITY PARTICIPATING IN THE I.FAMILY STUDY. THE STUDY SAMPLE INCLUDED INDIVIDUALS WITH INCREASED ADIPOSITY SINCE THIS CONDITION CONTRIBUTES TO THE EARLY OCCURRENCE OF CHRONIC LOW-GRADE INFLAMMATION. WE FOCUSED ON THE ACUTE-PHASE REAGENT C-REACTIVE PROTEIN (CRP) AS THE PRIMARY OUTCOME AND SELECTED CYTOKINES AS PLAUSIBLE BIOMARKERS OF INFLAMMATION. WE FOUND THAT CHRONIC LOW-GRADE CRP ELEVATION SHOWS A HIGHLY SIGNIFICANT ASSOCIATION WITH MIR-26B-3P AND HSA-MIR-576-5P IN BOYS. FURTHERMORE, THE ASSOCIATION OF CRP WITH HSA-MIR-10B-5P AND HSA-MIR-31-5P IS HIGHLY SIGNIFICANT IN GIRLS. WE ALSO OBSERVED MAJOR SEX-RELATED ASSOCIATIONS OF CANDIDATE MIRNAS WITH SELECTED CYTOKINES. EXCEPT FOR IL-6, A SIGNIFICANT ASSOCIATION OF HSA-MIR-26B-3P AND HSA-MIR-576-5P WITH TNF-ALPHA, IL1-RA, IL-8, AND IL-15 LEVELS WAS FOUND EXCLUSIVELY IN BOYS. THE FINDINGS OF THIS EXPLORATORY STUDY SUGGEST SEX DIFFERENCES IN THE ASSOCIATION OF CIRCULATING MIRNAS WITH INFLAMMATORY RESPONSE BIOMARKERS, AND INDICATE A POSSIBLE ROLE OF MIRNAS AMONG THE CANDIDATE EPIGENETIC MECHANISMS RELATED TO THE PROCESS OF LOW-GRADE INFLAMMATION IN CHILDHOOD OBESITY.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
6 1024  33 CIRCULATING MICRORNAS 34A, 122, AND 192 ARE LINKED TO OBESITY-ASSOCIATED INFLAMMATION AND METABOLIC DISEASE IN PEDIATRIC PATIENTS. BACKGROUND: OBESITY-ASSOCIATED CHRONIC LOW-GRADE INFLAMMATION LEADS TO DYSREGULATION OF CENTRAL LIPID AND GLUCOSE METABOLISM PATHWAYS LEADING TO METABOLIC DISORDERS. MICRORNAS (MIRNAS) ARE KNOWN TO CONTROL REGULATORS OF METABOLIC HOMEOSTASIS. WE AIMED TO ASSESS THE RELATIONSHIP OF CIRCULATING MIRNAS WITH INFLAMMATORY MODULATORS AND METABOLIC DISORDERS IN PEDIATRIC OBESITY. METHODS: FROM A PEDIATRIC COHORT WITH SEVERE OBESITY (N = 109), CLINICALLY THOROUGHLY CHARACTERIZED INCLUDING DIVERSE ROUTINE BLOOD PARAMETERS, ORAL GLUCOSE TOLERANCE TEST, AND LIVER MRI, A PANEL OF 16 CIRCULATING MIRNAS WAS QUANTIFIED USING QRT-PCR. ADDITIONALLY, MARKERS OF INFLAMMATION TNFALPHA, IL1 RECEPTOR ANTAGONIST, PROCALCITONIN, CRP, AND IL-6 WERE MEASURED. RESULTS: MARKERS OF OBESITY-ASSOCIATED INFLAMMATION, TNFALPHA, IL-1RA, AND PROCALCITONIN, ALL SIGNIFICANTLY CORRELATED WITH CONCENTRATIONS OF MIRNAS 122 AND 192. CONCENTRATIONS OF THESE MIRNAS NEGATIVELY CORRELATED WITH SERUM ADIPONECTIN AND WERE AMONG THOSE STRONGLY LINKED TO PARAMETERS OF DYSLIPIDEMIA AND LIVER FUNCTION. MOREOVER, MIRNA122 CONCENTRATIONS CORRELATED WITH HOMA-IR. SEVERAL MIRNA LEVELS INCLUDING MIRNAS 34A, 93, 122, AND 192 WERE STATISTICALLY SIGNIFICANTLY DIFFERING BETWEEN INDIVIDUALS WITH PREDIABETES, IMPAIRED GLUCOSE TOLERANCE, METABOLIC SYNDROME, OR NONALCOHOLIC FATTY LIVER DISEASE COMPARED TO THE RESPECTIVE CONTROLS. ADDITIONALLY, MIRNA 192 WAS SIGNIFICANTLY ELEVATED IN METABOLICALLY UNHEALTHY OBESITY. CONCLUSIONS: A MIRNA PATTERN ASSOCIATED WITH OBESITY-ASSOCIATED INFLAMMATION AND COMORBIDITIES MAY BE USED TO DISTINGUISH METABOLICALLY HEALTHY FROM UNHEALTHY PEDIATRIC PATIENTS WITH OBESITY. MOREOVER, THESE CHANGES IN EPIGENETIC REGULATION COULD POTENTIALLY BE INVOLVED IN THE ETIOLOGY OF OBESITY-LINKED METABOLIC DISEASE IN CHILDREN AND ADOLESCENTS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
7 5827  34 STRESS, BURNOUT AND DEPRESSION: A SYSTEMATIC REVIEW ON DNA METHYLATION MECHANISMS. DESPITE THAT BURNOUT PRESENTS A SERIOUS BURDEN FOR MODERN SOCIETY, THERE ARE NO DIAGNOSTIC CRITERIA. ADDITIONAL DIFFICULTY IS THE DIFFERENTIAL DIAGNOSIS WITH DEPRESSION. CONSEQUENTLY, THERE IS A NEED TO DISPOSE OF A BURNOUT BIOMARKER. EPIGENETIC STUDIES SUGGEST THAT DNA METHYLATION IS A POSSIBLE MEDIATOR LINKING INDIVIDUAL RESPONSE TO STRESS AND PSYCHOPATHOLOGY AND COULD BE CONSIDERED AS A POTENTIAL BIOMARKER OF STRESS-RELATED MENTAL DISORDERS. THUS, THE AIM OF THIS REVIEW IS TO PROVIDE AN OVERVIEW OF DNA METHYLATION MECHANISMS IN STRESS, BURNOUT AND DEPRESSION. IN ADDITION TO STATE-OF-THE-ART OVERVIEW, THE GOAL OF THIS REVIEW IS TO PROVIDE A SCIENTIFIC BASE FOR BURNOUT BIOMARKER RESEARCH. WE PERFORMED A SYSTEMATIC LITERATURE SEARCH AND IDENTIFIED 25 PERTINENT ARTICLES. AMONG THESE, 15 FOCUSED ON DEPRESSION, 7 ON CHRONIC STRESS AND ONLY 3 ON WORK STRESS/BURNOUT. THREE EPIGENOME-WIDE STUDIES WERE IDENTIFIED AND THE MAJORITY OF STUDIES USED THE CANDIDATE-GENE APPROACH, ASSESSING 12 DIFFERENT GENES. THE GLUCOCORTICOID RECEPTOR GENE (NR3C1) DISPLAYED DIFFERENT METHYLATION PATTERNS IN CHRONIC STRESS AND DEPRESSION. THE SEROTONIN TRANSPORTER GENE (SLC6A4) METHYLATION WAS SIMILARLY AFFECTED IN STRESS, DEPRESSION AND BURNOUT. WORK-RELATED STRESS AND DEPRESSIVE SYMPTOMS WERE ASSOCIATED WITH DIFFERENT METHYLATION PATTERNS OF THE BRAIN DERIVED NEUROTROPHIC FACTOR GENE (BDNF) IN THE SAME HUMAN SAMPLE. THE TYROSINE HYDROXYLASE (TH) METHYLATION WAS CORRELATED WITH WORK STRESS IN A SINGLE STUDY. ADDITIONAL, THOROUGHLY DESIGNED LONGITUDINAL STUDIES ARE NECESSARY FOR REVEALING THE CAUSE-EFFECT RELATIONSHIP OF WORK STRESS, EPIGENETICS AND BURNOUT, INCLUDING ITS OVERLAP WITH DEPRESSION.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
8  981  31 CHRONIC PESTICIDE EXPOSURE IN FARM WORKERS IS ASSOCIATED WITH THE EPIGENETIC MODULATION OF HSA-MIR-199A-5P. THE INCREASING USE OF PESTICIDES IN INTENSIVE AGRICULTURE HAS HAD A NEGATIVE IMPACT ON HUMAN HEALTH. IT WAS WIDELY DEMONSTRATED HOW PESTICIDES CAN INDUCE DIFFERENT GENETIC AND EPIGENETIC ALTERATIONS ASSOCIATED WITH THE DEVELOPMENT OF DIFFERENT DISEASES, INCLUDING TUMORS AND NEUROLOGICAL DISORDERS. THEREFORE, THE IDENTIFICATION OF EFFECTIVE INDICATORS FOR THE PREDICTION OF HARMFUL PESTICIDE EXPOSURE IS MANDATORY. IN THIS CONTEXT, THE AIM OF THE STUDY WAS TO EVALUATE THE MODIFICATION OF HSA-MIR-199A-5P EXPRESSION LEVELS IN LIQUID BIOPSY SAMPLES OBTAINED FROM HEALTHY DONORS AND FARM WORKERS WITH CHRONIC EXPOSURE TO PESTICIDES. FOR THIS PURPOSE, THE HIGH-SENSITIVE DROPLET DIGITAL PCR ASSAY (DDPCR) WAS USED TO DETECT VARIATION IN THE EXPRESSION LEVELS OF THE SELECTED MICRORNA (MIRNA). THE DDPCR ANALYSES REVEALED A SIGNIFICANT DOWN-REGULATION OF HSA-MIR-199A-5P OBSERVED IN INDIVIDUALS EXPOSED TO PESTICIDES COMPARED TO CONTROL SAMPLES HIGHLIGHTING THE GOOD PREDICTIVE VALUE OF THIS MIRNA AS DEMONSTRATED BY STATISTICAL ANALYSES. OVERALL, THE OBTAINED RESULTS ENCOURAGE THE ANALYSIS OF MIRNAS AS PREDICTIVE BIOMARKERS OF CHRONIC PESTICIDE EXPOSURE THUS IMPROVING THE CURRENT STRATEGIES FOR THE MONITORING OF HARMFUL PESTICIDE EXPOSURE.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
9 3751  41 INTAKE OF NATURAL COMPOUNDS AND CIRCULATING MICRORNA EXPRESSION LEVELS: THEIR RELATIONSHIP INVESTIGATED IN HEALTHY SUBJECTS WITH DIFFERENT DIETARY HABITS. DIET HAS A STRONG INFLUENCE ON MANY PHYSIOLOGICAL PROCESSES, WHICH IN TURN HAVE IMPORTANT IMPLICATIONS ON A VARIETY OF PATHOLOGICAL CONDITIONS. IN THIS RESPECT, MICRORNAS (MIRNAS), A CLASS OF SMALL NON-CODING RNAS PLAYING A RELEVANT EPIGENETIC ROLE IN CONTROLLING GENE EXPRESSION, MAY REPRESENT MEDIATORS BETWEEN THE DIETARY INTAKE AND THE HEALTHY STATUS. DESPITE GREAT ADVANCES IN THE FIELD OF NUTRI-EPIGENOMICS, IT REMAINS UNCLEAR HOW MIRNA EXPRESSION IS MODULATED BY THE DIET AND, SPECIFICALLY, THE INTAKE OF SPECIFIC NUTRIENTS. WE INVESTIGATED THE WHOLE CIRCULATING MIRNOME BY SMALL RNA-SEQUENCING PERFORMED ON PLASMA SAMPLES OF 120 HEALTHY VOLUNTEERS WITH DIFFERENT DIETARY HABITS (VEGANS, VEGETARIANS, AND OMNIVORES). DIETARY INTAKES OF SPECIFIC NUTRIENTS WERE ESTIMATED FOR EACH SUBJECT FROM THE INFORMATION REPORTED IN THE FOOD-FREQUENCY QUESTIONNAIRE PREVIOUSLY VALIDATED IN THE EPIC STUDY. WE FOCUSED HEREBY ON THE INTAKE OF 23 NATURAL COMPOUNDS (NCS) OF THE CLASSES OF LIPIDS, MICRO-ELEMENTS, AND VITAMINS. WE IDENTIFIED 78 SIGNIFICANT CORRELATIONS (RHO > 0.300, P-VALUE < 0.05) AMONG THE ESTIMATED DAILY INTAKE OF 13 NCS AND THE EXPRESSION LEVELS OF 58 PLASMA MIRNAS. OVERALL, VITAMIN D, SODIUM, AND VITAMIN E CORRELATED WITH THE LARGEST NUMBER OF MIRNAS. ALL THE IDENTIFIED CORRELATIONS WERE CONSISTENT AMONG THE THREE DIETARY GROUPS AND 22 OF THEM WERE CONFIRMED AS SIGNIFICANT (P-VALUE < 0.05) BY AGE-, GENDER-, AND BODY-MASS INDEX-ADJUSTED GENERALIZED LINEAR REGRESSION MODEL ANALYSIS. MIR-23A-3P EXPRESSION LEVELS WERE RELATED WITH DIFFERENT NCS INCLUDING A SIGNIFICANT POSITIVE CORRELATION WITH SODIUM (RHO = 0.377) AND SIGNIFICANT NEGATIVE CORRELATIONS WITH LIPID-RELATED NCS AND VITAMIN E. CONVERSELY, THE ESTIMATED INTAKE OF VITAMIN D WAS NEGATIVELY CORRELATED WITH THE EXPRESSION OF THE HIGHEST NUMBER OF CIRCULATING MIRNAS, PARTICULARLY MIR-1277-5P (RHO = -0.393) AND MIR-144-3P (RHO = -0.393). FUNCTIONAL ANALYSIS OF THE TARGETS OF SODIUM INTAKE-CORRELATED MIRNAS HIGHLIGHTED TERMS RELATED TO CARDIAC DEVELOPMENT. A SIMILAR APPROACH ON TARGETS OF THOSE MIRNAS CORRELATED WITH VITAMIN D INTAKE SHOWED AN ENRICHMENT IN GENES INVOLVED IN HORMONE METABOLISMS, WHILE THE RESPONSE TO CHRONIC INFLAMMATION WAS AMONG THE TOP ENRICHED PROCESSES INVOLVING TARGETS OF MIRNAS NEGATIVELY RELATED WITH VITAMIN E INTAKE. OUR FINDINGS SHOW THAT NUTRIENTS THROUGH THE HABITUAL DIET INFLUENCE CIRCULATING MIRNA PROFILES AND HIGHLIGHT THAT THIS ASPECT MUST BE CONSIDERED IN THE NUTRI-EPIGENOMIC RESEARCH.	2020	

10 3652  29 INDIVIDUAL DNA METHYLATION PATTERN SHIFTS IN NANOPARTICLES-EXPOSED WORKERS ANALYZED IN FOUR CONSECUTIVE YEARS. A DNA METHYLATION PATTERN REPRESENTS AN ORIGINAL PLAN OF THE FUNCTION SETTINGS OF INDIVIDUAL CELLS AND TISSUES. THE BASIC STRATEGIES OF ITS DEVELOPMENT AND CHANGES DURING THE HUMAN LIFETIME ARE KNOWN, BUT THE DETAILS RELATED TO ITS MODIFICATION OVER THE YEARS ON AN INDIVIDUAL BASIS HAVE NOT YET BEEN STUDIED. MOREOVER, CURRENT EVIDENCE SHOWS THAT ENVIRONMENTAL EXPOSURE COULD GENERATE CHANGES IN DNA METHYLATION SETTINGS AND, SUBSEQUENTLY, THE FUNCTION OF GENES. IN THIS STUDY, WE ANALYZED THE EFFECT OF CHRONIC EXPOSURE TO NANOPARTICLES (NP) IN OCCUPATIONALLY EXPOSED WORKERS REPEATEDLY SAMPLED IN FOUR CONSECUTIVE YEARS (2016-2019). A DETAILED METHYLATION PATTERN ANALYSIS OF 14 PERSONS (10 EXPOSED AND 4 CONTROLS) WAS PERFORMED ON AN INDIVIDUAL BASIS. A MICROARRAY-BASED APPROACH USING CHIPS, ALLOWING THE ASSESSMENT OF MORE THAN 850 K CPG LOCI, WAS USED. INDIVIDUAL DNA METHYLATION PATTERNS WERE COMPARED BY PRINCIPAL COMPONENT ANALYSIS (PCA). THE RESULTS SHOW THE SHIFT IN DNA METHYLATION PATTERNS IN INDIVIDUAL YEARS IN ALL THE EXPOSED AND CONTROL SUBJECTS. THE OVERALL RANGE OF DIFFERENCES VARIED BETWEEN THE YEARS IN INDIVIDUAL PERSONS. THE DIFFERENCES BETWEEN THE FIRST AND LAST YEAR OF EXAMINATION (A THREE-YEAR TIME PERIOD) SEEM TO BE CONSISTENTLY GREATER IN THE NP-EXPOSED SUBJECTS IN COMPARISON WITH THE CONTROLS. THE SELECTED 14 MOST DIFFERENTLY METHYLATED CG LOCI WERE RELATIVELY STABLE IN THE CHRONICALLY EXPOSED SUBJECTS. IN SUMMARY, THE SPECIFIC TYPE OF LONG-TERM EXPOSURE CAN CONTRIBUTE TO THE FIXING OF RELEVANT EPIGENETIC CHANGES RELATED TO A SPECIFIC ENVIRONMENT AS, E.G., NP INHALATION.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
11 1519  34 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
12 1345  36 DETECTION OF DIFFERENTIALLY METHYLATED REGIONS USING BAYES FACTOR FOR ORDINAL GROUP RESPONSES. RESEARCHERS IN GENOMICS ARE INCREASINGLY INTERESTED IN EPIGENETIC FACTORS SUCH AS DNA METHYLATION, BECAUSE THEY PLAY AN IMPORTANT ROLE IN REGULATING GENE EXPRESSION WITHOUT CHANGES IN THE DNA SEQUENCE. THERE HAVE BEEN SIGNIFICANT ADVANCES IN DEVELOPING STATISTICAL METHODS TO DETECT DIFFERENTIALLY METHYLATED REGIONS (DMRS) ASSOCIATED WITH BINARY DISEASE STATUS. MOST OF THESE METHODS ARE BEING DEVELOPED FOR DETECTING DIFFERENTIAL METHYLATION RATES BETWEEN CASES AND CONTROLS. WE CONSIDER MULTIPLE SEVERITY LEVELS OF DISEASE, AND DEVELOP A BAYESIAN STATISTICAL METHOD TO DETECT THE REGION WITH INCREASING (OR DECREASING) METHYLATION RATES AS THE DISEASE SEVERITY INCREASES. PATIENTS ARE CLASSIFIED INTO MORE THAN TWO GROUPS, BASED ON THE DISEASE SEVERITY (E.G., STAGES OF CANCER), AND DMRS ARE DETECTED BY USING MOVING WINDOWS ALONG THE GENOME. WITHIN EACH WINDOW, THE BAYES FACTOR IS CALCULATED TO TEST THE HYPOTHESIS OF MONOTONIC INCREASE IN METHYLATION RATES CORRESPONDING TO SEVERITY OF THE DISEASE VERSUS NO DIFFERENCE. A MIXED-EFFECT MODEL IS USED TO INCORPORATE THE CORRELATION OF METHYLATION RATES OF NEARBY CPG SITES IN THE REGION. RESULTS FROM EXTENSIVE SIMULATION INDICATE THAT OUR PROPOSED METHOD IS STATISTICALLY VALID AND REASONABLY POWERFUL. WE DEMONSTRATE OUR APPROACH ON A BISULFITE SEQUENCING DATASET FROM A CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) STUDY.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
13 1537  23 DNA METHYLATION IN ADOLESCENTS WITH ANXIETY DISORDER: A LONGITUDINAL STUDY. ANXIETY DISORDERS (AD) TYPICALLY MANIFEST IN CHILDREN AND ADOLESCENTS AND MIGHT PERSIST INTO ADULTHOOD. HOWEVER, THERE ARE STILL FEW DATA CONCERNING EPIGENETIC MECHANISMS ASSOCIATED WITH ONSET, PERSISTENCE OR REMISSION OF AD OVER TIME. WE INVESTIGATED A COHORT OF ADOLESCENTS AND YOUNG ADULTS AT BASELINE (AGE; 13.19 +/- 2.38) AND AFTER 5 YEARS AND CLASSIFIED THEM ACCORDING TO THE AD DIAGNOSIS AND THEIR LONGITUDINAL TRAJECTORIES INTO 4 GROUPS: (1) TYPICALLY DEVELOPING COMPARISONS (TDC; CONTROL GROUP, N = 14); (2) INCIDENT (AD IN THE SECOND EVALUATION ONLY, N = 11); (3) PERSISTENT (AD IN BOTH EVALUATIONS, N = 14) AND (4) REMITTENT (AD IN THE FIRST EVALUATION ONLY, N = 8). DNA METHYLATION WAS EVALUATED WITH THE INFINIUM HUMANMETHYLATION450 BEADCHIP FROM SALIVA SAMPLES COLLECTED AT BOTH EVALUATIONS. GENE SET ENRICHMENT ANALYSIS WAS APPLIED TO CONSIDER BIOLOGICAL PATHWAYS. WE FOUND DECREASED DNA METHYLATION IN TDC GROUP WHILE THE CHRONIC CASES OF AD PRESENTED HYPERMETHYLATION IN CENTRAL NERVOUS SYSTEM DEVELOPMENT PATHWAYS. MOREOVER, WE SHOWED THAT THIS PERSISTENT GROUP ALSO PRESENTED HYPERMETHYLATION WHILE THE OTHER THREE GROUPS WERE ASSOCIATED WITH HYPOMETHYLATION IN NERVOUS SYSTEM DEVELOPMENT PATHWAY. INCIDENCE AND REMISSION GROUPS WERE ASSOCIATED WITH INCREASED AND DECREASED METHYLATION IN NEURON DEVELOPMENT PATHWAYS, RESPECTIVELY. LARGER STUDIES ARE LIKELY TO DETECT SPECIFIC GENES RELEVANT TO AD.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
14 2999  36 GENETIC VARIATION, STRESS, AND PHYSIOLOGICAL STRESS RESPONSE IN ADULTS WITH FOOD ALLERGY OR CELIAC DISEASE. BACKGROUND: PERSISTENTLY HIGH CHRONIC STRESS CAN LEAD TO MALADAPTIVE PSYCHOLOGICAL, BEHAVIORAL, AND PHYSIOLOGICAL STRESS RESPONSES AND POOR MENTAL AND PHYSICAL HEALTH, HIGHLIGHTING THE IMPORTANCE OF IDENTIFYING INDIVIDUALS AT INCREASED RISK. CHRONIC HEALTH CONDITION DIAGNOSIS AND GENETICS ARE 2 CHARACTERISTICS THAT CAN INFLUENCE STRESS, STRESS RESPONSE, AND HEALTH OUTCOMES. PURPOSE: FOOD ALLERGY (FA) AND CELIAC DISEASE (CD) REQUIRE CONSTANT VIGILANCE IN DAILY LIFE AND CAN LEAD TO INCREASED STRESS. THE PURPOSE OF THIS EXPLORATORY ANALYSIS WAS TO EXAMINE THE ASSOCIATION OF VARIANTS IN SELECTED STRESS-RELATED GENES WITH STRESS EXPOSURES, STRESS, CLINICAL MEASURES OF PHYSIOLOGICAL STRESS RESPONSE, AND MENTAL HEALTH SYMPTOMS IN ADULTS WITH AND WITHOUT FA OR CD. METHODS: WE COMPARED STRESS EXPOSURES, SYMPTOMS OF PTSD, DEPRESSION, ANXIETY, AND STRESS, BMI, AND WAIST-HIP RATIO BETWEEN CASES AND CONTROLS. WE ANALYZED THE ASSOCIATION OF SNPS IN GENES WITH KNOWN OR HYPOTHESIZED ASSOCIATIONS WITH STRESS-RELATED MEASURES IN 124 CASES AND 124 MATCHED CONTROLS: CRHBP (RS7718461, RS10474485), CRHR1 (RS242940) AND OXTR (RS2268490). FOR THIS EXPLORATORY STUDY, P-VALUES </= 0.10 WERE CONSIDERED SUGGESTIVE. RESULTS: FOR CASES AND CONTROLS, RS7718461 WAS ASSOCIATED WITH STRESS SYMPTOMS, RS2268490 WITH SYMPTOMS OF STRESS AND PTSD, AND RS242940 WITH SYMPTOMS OF STRESS, PTSD, ANXIETY, AND DEPRESSION. FURTHER ANALYSES FOUND THAT STRESS-RELATED OUTCOMES IN INDIVIDUALS WITH FA OR CD MAY BE INFLUENCED BY SNP GENOTYPE. CONCLUSIONS: GIVEN THESE SUGGESTIVE FINDINGS, LARGER PROSPECTIVE STUDIES SHOULD EXAMINE SIMILAR RELATIONSHIPS IN INDIVIDUALS WITH OTHER CHRONIC HEALTH CONDITIONS, INCORPORATING FACTORS SUCH AS ENVIRONMENTAL EXPOSURES, INDIVIDUAL EXPERIENCES, AND EPIGENETIC MODIFICATIONS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
15 1729  36 DYSREGULATION OF MIR-155 EXPRESSION IN PROFESSIONAL MIXED MARTIAL ARTS (MMA) FIGHTERS. PSYCHOLOGICAL AND PHYSICAL STRESS CAN INDUCE DYSREGULATION OF GENE EXPRESSION VIA CHANGES IN DNA METHYLATION AND MICRORNA (MIRNA) EXPRESSION. SUCH EPIGENETIC MODIFICATIONS ARE YET TO BE INVESTIGATED IN PROFESSIONAL MIXED MARTIAL ARTS (MMA) FIGHTERS SUBJECT TO HIGHLY STRESSFUL TRAINING INVOLVING REPETITIVE HEAD IMPACTS. THIS STUDY EXAMINED DIFFERENCES IN DNA METHYLATION AND MIRNA EXPRESSION IN ELITE MMA FIGHTERS COMPARED TO ACTIVE CONTROLS. GLOBAL METHYLATION DIFFERENCES BETWEEN GROUPS WERE ASSESSED VIA A LINE-1 ASSAY. AT THE SAME TIME, PCR ARRAYS WERE USED TO ESTIMATE DIFFERENTIAL EXPRESSION IN SAMPLES OF 21 FIGHTERS AND 15 CONTROLS FOR 192 DIFFERENT MIRNAS ASSOCIATED WITH INFLAMMATORY DISEASES. AN INDEPENDENT-SAMPLES T-TEST FOUND NO SIGNIFICANT DIFFERENCE IN LINE-1 METHYLATION BETWEEN GROUPS. HOWEVER, AN INDEPENDENT-SAMPLES MANN-WHITNEY U TEST REVEALED A SIGNIFICANT UPREGULATION IN THE EXPRESSION OF MIR-155 IN MMA FIGHTER PLASMA. SINCE MIR-155 HAS BEEN RECOGNIZED AS AN IMPORTANT REGULATOR OF NEUROINFLAMMATION, THIS DYSREGULATION SUGGESTS A POSSIBLE EPIGENETIC MECHANISM RESPONSIBLE FOR CHRONIC INFLAMMATION ASSOCIATED WITH PROFESSIONAL-LEVEL MMA TRAINING. CONSISTENT WITH OTHER PUBLISHED WORKS, THIS STUDY HIGHLIGHTS THE POTENTIAL OF MIR-155 NOT ONLY AS A BIOMARKER FOR MONITORING LONG-TERM HEALTH RISKS LINKED TO HEAD TRAUMA BUT ALSO AS A TARGET TO REMEDIATE THE IMPACT OF CHRONIC NEUROINFLAMMATION.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
16 5734  34 SMALL NON-CODING RNAS ARE ALTERED BY SHORT-TERM SPRINT INTERVAL TRAINING IN MEN. SMALL NON-CODING RNAS (NCRNAS) ARE EMERGING AS IMPORTANT MOLECULES FOR NORMAL BIOLOGICAL PROCESSES AND ARE DEREGULATED IN DISEASE. EXERCISE TRAINING IS A POWERFUL THERAPEUTIC STRATEGY THAT PREVENTS CARDIOMETABOLIC DISEASE AND IMPROVES CARDIORESPIRATORY FITNESS AND PERFORMANCE. DESPITE THE KNOWN SYSTEMIC HEALTH BENEFITS OF EXERCISE TRAINING, THE UNDERLYING MOLECULAR MECHANISMS ARE INCOMPLETELY UNDERSTOOD. RECENT EVIDENCE SUGGESTS A ROLE FOR EPIGENETIC MECHANISMS, SUCH AS MICRORNAS, BUT WHETHER OTHER SMALL NCRNAS ARE MODULATED BY CHRONIC EXERCISE TRAINING IS UNKNOWN. HERE, WE USED SMALL RNA SEQUENCING TO EXPLORE WHETHER SPRINT INTERVAL TRAINING (SIT) CONTROLS THE ABUNDANCE OF CIRCULATING SMALL NCRNAS IN HUMAN WHOLE BLOOD SAMPLES. TEN HEALTHY MEN PERFORMED SIT THREE TIMES A WEEK FOR 6 WEEKS. AFTER TRAINING, SUBJECTS SHOWED MARKED IMPROVEMENTS IN MAXIMAL OXYGEN CONSUMPTION AND CYCLING PERFORMANCE WITH CONCURRENT CHANGES TO THE ABUNDANCE OF DIVERSE SPECIES OF CIRCULATING SMALL NCRNAS (N = 1266 SMALL NCRNAS, N = 13 MICRORNAS, Q < 0.05). TWELVE MICRORNAS ALTERED BY 6 WEEKS OF SIT WERE UBIQUITOUSLY EXPRESSED MICRORNAS AND TWO REGULATED IMPORTANT SIGNALING PATHWAYS, INCLUDING P53, THYROID HORMONE AND CELL CYCLE SIGNALING. MICRORNAS ALTERED BY 6 WEEKS OF SIT WERE UNCHANGED AFTER A SINGLE SESSION OF SIT (N = 24, ALL P > 0.05). RELATIVE TO OLDER INDIVIDUALS, YOUNGER SUBJECTS EXHIBITED AN INCREASED ACUTE SIT-INDUCED FOLD CHANGE IN MIR-1301-3P (P = 0.02) - A MICRORNA PREDICTED TO TARGET MRNAS INVOLVED IN ALTERNATIVE SPLICING, PHOSPHOPROTEIN AND CHROMOSOMAL REARRANGEMENT PROCESSES (ALL P < 0.001). OUR FINDINGS INDICATE MANY SPECIES OF CIRCULATING SMALL NCRNAS ARE MODULATED BY EXERCISE TRAINING AND THAT THEY COULD CONTROL SIGNALING PATHWAYS RESPONSIBLE FOR HEALTH BENEFITS ACHIEVED FROM EXERCISE.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
17  344  41 ALTERED BDNF METHYLATION IN PATIENTS WITH CHRONIC MUSCULOSKELETAL PAIN AND HIGH BIOPSYCHOSOCIAL COMPLEXITY. PURPOSE: THE INTERMED INSTRUMENT, WHICH WAS DEVELOPED TO MEASURE PATIENT'S BIOPSYCHOSOCIAL (BPS) COMPLEXITY, REPRESENTS A POWERFUL DIAGNOSTIC AND THERAPEUTIC TOOL. EPIGENETIC CHANGES ARE THE INTERFACE BETWEEN SIGNALS FROM THE ENVIRONMENT AND GENETIC MODIFICATIONS, AFFECTING GENE EXPRESSION, IN PARTICULAR, BY DNA METHYLATION OF CPG DINUCLEOTIDES IN PROMOTOR REGIONS OF THE CORRESPONDING GENES. THE BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) GENE PLAYS A CRUCIAL ROLE IN THE CENTRAL SENSITIZATION (CS) OF PAIN. IN THIS STUDY, WE HYPOTHESIZED THAT CHRONIC PAIN MODIFIES THE METHYLATION LEVELS OF THE BDNF GENE IN A MANNER THAT IS INTERCONNECTED WITH THE BPS STATUS. PATIENTS AND METHODS: FIFTY-EIGHT CHRONIC MUSCULOSKELETAL PAIN PATIENTS (CMSP) WERE ENROLLED IN THE STUDY. DNA WAS EXTRACTED FROM BLOOD SAMPLES, THE METHYLATION LEVELS OF 13 CPG SITES IN THE BDNF PROMOTER WERE MEASURED BY PYROSEQUENCING, AND ASSOCIATION STUDIES WITH VARIOUS PATIENT PARAMETERS AND THE INTERMED SCORES WERE PERFORMED. RESULTS: INTERESTINGLY, A NEGATIVE CORRELATION (-0.40) WAS FOUND BETWEEN THE TOTAL INTERMED SCORES AND THE AVERAGE CPG METHYLATION VALUES OF THE BDNF GENE, BUT NO CORRELATION WAS OBSERVED WITH THE SEVERITY OF PAIN, DEGREE OF ANXIETY, DEPRESSION, OR KINESIOPHOBIA AND CATASTROPHISM. MOREOVER, THE ASSOCIATION WAS INDEPENDENT OF AGE, SEX AND LEVEL OF COMORBIDITIES. CONCLUSION: THIS RESULT SHOWS THAT CMSP, IN ASSOCIATION WITH ITS BIOPSYCHOSOCIAL CONTEXT, EPIGENETICALLY DECREASES THE DEGREE OF METHYLATION OF THE BDNF PROMOTER AND SHOULD THEREFORE INCREASE THE LEVEL OF BDNF TRANSCRIPTION. IT ALSO SUGGESTS A ROLE OF THE INTERMED TOOL TO DETECT A RELATIONSHIP BETWEEN THE BPS COMPLEXITY AND THE EPIGENETIC CONTROL OF A TARGET GENE. THE POSSIBLE UPREGULATION OF BDNF EXPRESSION MIGHT BE, AT LEAST IN PART, THE SIGNAL FOR CHRONIC PAIN-INDUCED CENTRAL SENSITIZATION (CS). THIS COULD PARTLY EXPLAIN WHY PATIENTS WITH A HIGHER LEVEL OF COMPLEXITY FEEL MORE PAIN THAN THOSE WITH LOWER COMPLEXITY.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
18 6311  33 THE RELATION BETWEEN DNA METHYLATION PATTERNS AND SERUM CYTOKINE LEVELS IN COMMUNITY-DWELLING ADULTS: A PRELIMINARY STUDY. BACKGROUND: THE LEVELS OF CIRCULATING CYTOKINES FLUCTUATE WITH AGE, ACUTE ILLNESS, AND CHRONIC DISEASE, AND ARE PREDICTIVE OF MORTALITY; THIS IS ALSO TRUE FOR PATTERNS OF DNA (CPG) METHYLATION. GIVEN THAT IMMUNE CELLS ARE PARTICULARLY SENSITIVE TO CHANGES IN THE CONCENTRATION OF CYTOKINES IN THEIR MICROENVIRONMENT, WE HYPOTHESIZED THAT SERUM LEVELS OF TNF, IL-6, IL-8 AND IL-10 WOULD CORRELATE WITH GENOME-WIDE ALTERATIONS IN THE DNA METHYLATION LEVELS OF BLOOD LEUKOCYTES. TO TEST THIS, WE EVALUATED COMMUNITY-DWELLING ADULTS (N = 14; 48-78 YEARS OLD) RECRUITED TO A PILOT STUDY FOR THE CANADIAN LONGITUDINAL STUDY ON AGING (CLSA), EXAMINING DNA METHYLATION PATTERNS IN PERIPHERAL BLOOD MONONUCLEAR CELLS USING THE ILLUMINA HUMANMETHYLATION 450 K BEADCHIP. RESULTS: WE SHOW THAT, APART FROM AGE, SERUM IL-10 LEVELS EXHIBITED THE MOST SUBSTANTIAL ASSOCIATION TO DNA METHYLATION PATTERNS, FOLLOWED BY TNF, IL-6 AND IL-8. FURTHERMORE, WHILE THE LEVELS OF THESE CYTOKINES WERE HIGHER IN ELDERLY ADULTS, NO ASSOCIATIONS WITH EPIGENETIC ACCELERATED AGING, DERIVED USING THE EPIGENETIC CLOCK, WERE OBSERVED. CONCLUSIONS: AS A PRELIMINARY STUDY WITH A SMALL SAMPLE SIZE, THE CONCLUSIONS DRAWN FROM THIS WORK MUST BE VIEWED WITH CAUTION; HOWEVER, OUR OBSERVATIONS ARE ENCOURAGING AND CERTAINLY WARRANT MORE SUITABLY POWERED STUDIES OF THIS RELATIONSHIP.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
19  353  37 ALTERED LEVELS OF IMMUNE-REGULATORY MICRORNAS IN PLASMA SAMPLES OF PATIENTS WITH LUPUS NEPHRITIS. INTRODUCTION: LUPUS NEPHRITIS (LN) IS A MAJOR CAUSE OF MORTALITY AND MORBIDITY IN THE PATIENTS WITH LUPUS, A CHRONIC AUTOIMMUNE DISEASE. THE ROLE OF GENETIC AND EPIGENETIC FACTORS IS EMPHASIZED IN THE PATHOGENESIS OF LN. THE AIM OF THE PRESENT STUDY WAS TO EVALUATE THE LEVELS OF IMMUNE-REGULATORY MICRORNAS (E.G., MIR-31, MIR-125A, MIR-142-3P, MIR-146A, AND MIR-155) IN PLASMA SAMPLES OF PATIENTS WITH LN. METHODS: IN THIS STUDY, 26 PATIENTS WITH LN AND 26 HEALTHY INDIVIDUALS WERE INCLUDED. THE PLASMA LEVELS OF THE MICRORNAS WERE EVALUATED BY A QUANTITATIVE REAL-TIME PCR. MOREOVER, THE CORRELATION OF CIRCULATING PLASMA MICRORNAS WITH DISEASE ACTIVITY AND PATHOLOGICAL FINDINGS ALONG WITH THEIR ABILITY TO DISTINGUISH PATIENTS WITH LN WERE ASSESSED. RESULTS: PLASMA LEVELS OF MIR-125A (P = 0.048), MIR-146A (P = 0.005), AND MIR-155 (P< 0.001) WERE SIGNIFICANTLY HIGHER IN COMPARISON BETWEEN THE CASES AND CONTROLS. THE PLASMA LEVEL OF MIR-146A SIGNIFICANTLY CORRELATED WITH THE LEVEL OF ANTI-DOUBLE STRAND-DNA ANTIBODY AND PROTEINURIA. MOREOVER, THERE WAS A SIGNIFICANT CORRELATION BETWEEN MIR-142-3P LEVELS AND DISEASE CHRONICITY AND ACTIVITY INDEX (P <0.05). THE MULTIVARIATE ROC CURVE ANALYSIS INDICATED THE PLASMA CIRCULATING MIR-125A, MIR-142-3P, MIR-146, AND MIR-155 TOGETHER COULD DISCRIMINATE MOST OF THE PATIENTS WITH LN FROM CONTROLS WITH AREA AN UNDER CURVE (AUC) OF 0.89 [95% CI, 0.80-0.98, P<0.001], 88% SENSITIVITY, AND 78% SPECIFICITY. CONCLUSION: BASED ON THE FINDINGS OF THE PRESENT STUDY, THE STUDIED MICRORNAS MAY BE INVOLVED IN THE PATHOGENESIS AND DEVELOPMENT OF LN AND HAVE THE POTENTIAL TO BE USED AS DIAGNOSTIC AND THERAPEUTIC MARKERS IN LN.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
20 2093  30 EPIGENETIC EFFECTS FOLLOWING ACUTE AND CHRONIC EXERCISE IN CARDIOVASCULAR DISEASE: A SYSTEMATIC REVIEW. INTRODUCTION: ACUTE EXERCISE AND EXERCISE TRAINING MAY CONFER EPIGENETIC MODIFICATIONS IN HEALTHY SUBJECTS. EPIGENETIC EFFECTS AFTER EXERCISE HAVE BEEN SHOWED IN PATIENTS WITH CARDIOVASCULAR DISEASE. THE AIM OF THIS SYSTEMATIC REVIEW WAS TO SUMMARIZE THE EVIDENCE FROM AVAILABLE CLINICAL TRIALS THAT STUDY EPIGENETIC ADAPTATIONS AFTER EXERCISE IN PATIENTS WITH CARDIOVASCULAR DISEASE. METHODS: THE SEARCH STRATEGY WAS PERFORMED IN PUBMED AND CENTRAL DATABASES ON ARTICLES PUBLISHED UNTIL SEPTEMBER 2020. STUDIES WITH TITLES AND ABSTRACTS RELEVANT TO EXERCISE EPIGENETIC MODIFICATION APPLIED TO CARDIOVASCULAR PATIENTS WERE FULLY EXAMINED. INCLUSION AND EXCLUSION CRITERIA WERE UTILIZED FOR STUDIES SCREENING. QUALITY ASSESSMENT WITH PEDRO SCALE AND EVALUATION BY TWO INDEPENDENT REVIEWERS WAS PERFORMED. RESULTS: OF THE 1714 ARTICLES RETRIEVED, 88 ARTICLES WERE ASSESSED FOR ELIGIBILITY CRITERIA AND 8 ARTICLES MATCHED OUR SEARCH CRITERIA AND FINALLY INCLUDED IN THE SYSTEMATIC ANALYSIS. THE ACUTE EXERCISE EPIGENETIC (MIRNAS) EFFECTS WERE ASSESSED IN THREE STUDIES AND THE CHRONIC EXERCISE TRAINING EFFECTS (MIRNAS AND DNA METHYLATION) IN SIX STUDIES. THE RESULTS HAVE SHOWN THAT THERE IS POSSIBLY AN ACUTE SIGNIFICANT EXERCISE EFFECT ON EPIGENETIC TARGETS WHICH IS MORE EVIDENT AFTER CHRONIC EXERCISE TRAINING. CONCLUSIONS: BY THE PRESENT SYSTEMATIC REVIEW, WE PROVIDE PRELIMINARY EVIDENCE OF BENEFICIAL EPIGENETIC ADAPTATIONS FOLLOWING ACUTE AND CHRONIC EXERCISE IN PATIENTS WITH CARDIOVASCULAR DISEASE. MORE CONTROLLED STUDIES ARE NEEDED TO CONFIRM SUCH EVIDENCE.	2021