1   670 167 BONE-METABOLISM-RELATED SERUM MICRORNAS TO DIAGNOSE OSTEOPOROSIS IN MIDDLE-AGED AND ELDERLY WOMEN. OBJECTIVE: POSTMENOPAUSAL OSTEOPOROSIS (PMOP), A CHRONIC SYSTEMIC METABOLIC DISEASE PREVALENT IN MIDDLE-AGED AND ELDERLY WOMEN, HEAVILY RELIES ON BONE MINERAL DENSITY (BMD) MEASUREMENT AS THE DIAGNOSTIC INDICATOR. IN THIS STUDY, WE INVESTIGATED SERUM MICRORNAS (MIRNAS) AS A POSSIBLE SCREENING TOOL FOR PMOP. METHODS: THIS INVESTIGATION RECRUITED 83 ELIGIBLE PARTICIPANTS FROM 795 COMMUNITY-DWELLING POSTMENOPAUSAL WOMEN BETWEEN JUNE 2020 AND AUGUST 2021. THE MIRNA EXPRESSION PROFILES IN THE SERUM OF PMOP PATIENTS WERE EVALUATED VIA MIRNA MICROARRAY (SIX PMOP PATIENTS AND FOUR POSTMENOPAUSAL WOMEN WITHOUT OSTEOPOROSIS (N-PMOP) AS CONTROLS). SUBSEQUENTLY, RESULTS WERE VERIFIED IN INDEPENDENT SAMPLE SETS (47 PMOP PATIENTS AND 26 N-PMOP CONTROLS) USING QUANTITATIVE REAL-TIME PCR. IN ADDITION, THE TARGET GENES AND MAIN FUNCTIONS OF THE DIFFERENTIALLY EXPRESSED MIRNAS WERE EXPLORED BY BIOINFORMATICS ANALYSIS. RESULTS: FOUR HIGHLY EXPRESSED MIRNAS IN THE SERUM OF PATIENTS (HSA-MIR-144-5P, HSA-MIR-506-3P, HSA-MIR-8068, AND HSA-MIR-6851-3P) SHOWED ACCEPTABLE DISEASE-INDEPENDENT DISCRIMINATION PERFORMANCE (AREA UNDER THE CURVE RANGE: 0.747-0.902) IN THE TRAINING SET AND VERIFICATION SET, OUTPERFORMING TRADITIONAL BONE TURNOVER MARKERS. AMONG FOUR KEY MIRNAS, HSA-MIR-144-5P IS THE ONLY ONE THAT CAN SIMULTANEOUSLY PREDICT CHANGES IN BMD IN LUMBAR SPINE 1-4, TOTAL HIP, AND FEMORAL NECK (BETA = -0.265, P = 0.022; BETA = -0.301, P = 0.005; AND BETA = -0.324, P = 0.003, RESPECTIVELY). BIOINFORMATICS ANALYSIS SUGGESTED THAT THE DIFFERENTIALLY EXPRESSED MIRNAS WERE TARGETED MAINLY TO YY1, VIM, AND YWHAE GENES, WHICH ARE EXTENSIVELY INVOLVED IN BONE METABOLISM PROCESSES. CONCLUSIONS: BONE-METABOLISM-RELATED SERUM MIRNAS, SUCH AS HSA-MIR-144-5P, HSA-MIR-506-3P, HSA-MIR-8068, AND HSA-MIR-6851-3P, CAN BE USED AS NOVEL BIOMARKERS FOR PMOP DIAGNOSIS INDEPENDENT OF RADIOLOGICAL FINDINGS AND TRADITIONAL BONE TURNOVER MARKERS. FURTHER STUDY OF THESE MIRNAS AND THEIR TARGET GENES MAY PROVIDE NEW INSIGHTS INTO THE EPIGENETIC REGULATORY MECHANISMS OF THE ONSET AND PROGRESSION OF THE DISEASE.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
2  3297  26 HIGH SODIUM INTAKE DURING POSTNATAL PHASES INDUCES AN INCREASE IN ARTERIAL BLOOD PRESSURE IN ADULT RATS. EPIGENETIC STUDIES SUGGEST THAT DISEASES THAT DEVELOP IN ADULTHOOD ARE RELATED TO CERTAIN CONDITIONS TO WHICH THE INDIVIDUAL IS EXPOSED DURING THE INITIAL STAGES OF LIFE. EXPERIMENTAL EVIDENCE HAS DEMONSTRATED THAT OFFSPRING BORN TO MOTHERS MAINTAINED ON HIGH-NA DIETS DURING PREGNANCY HAVE HIGHER MEAN ARTERIAL PRESSURE (MAP) IN ADULTHOOD. ALTHOUGH THESE STUDIES HAVE DEMONSTRATED THE IMPORTANCE OF PRENATAL PHASES TO HYPERTENSION DEVELOPMENT, NO EVIDENCE REGARDING THE ROLE OF HIGH NA INTAKE DURING POSTNATAL PHASES IN THE DEVELOPMENT OF THIS PATHOLOGY HAS BEEN REPORTED. THEREFORE, IN THE PRESENT STUDY, THE EFFECTS OF NA OVERLOAD DURING CHILDHOOD ON INDUCED WATER AND NA INTAKES AND ON CARDIOVASCULAR PARAMETERS IN ADULTHOOD WERE EVALUATED. EXPERIMENTS WERE CARRIED OUT IN TWO GROUPS OF 21-D-OLD RATS: EXPERIMENTAL GROUP, MAINTAINED ON HYPERTONIC SALINE (0.3 M-NACL) SOLUTION AND FOOD FOR 60 D, AND CONTROL GROUP, MAINTAINED ON TAP WATER AND FOOD. LATER, BOTH GROUPS WERE GIVEN WATER AND FOOD FOR 15 D (RECOVERY PERIOD). AFTER THE RECOVERY PERIOD, CHRONIC CANNULATION OF THE RIGHT FEMORAL ARTERY WAS PERFORMED IN UNANAESTHETISED RATS TO RECORD BASELINE MAP AND HEART RATE (HR). THE EXPERIMENTAL GROUP WAS FOUND TO HAVE INCREASED BASAL MAP (98.6 (SEM 2.6) V. 118.3 (SEM 2.7) MMHG, P< 0.05) AND HR (365.4 (SEM 12.2) V. 398.2 (SEM 7.5) BEATS PER MIN, P< 0.05). THERE WAS A DECREASE IN THE BAROREFLEX INDEX IN THE EXPERIMENTAL GROUP WHEN COMPARED WITH THAT IN THE CONTROL GROUP. A WATER AND NA INTAKE TEST WAS PERFORMED USING FUROSEMIDE. NA DEPLETION WAS FOUND TO INDUCE AN INCREASE IN NA INTAKE IN BOTH THE CONTROL AND EXPERIMENTAL GROUPS (12.1 (SEM 0.6) ML AND 7.8 (SEM 1.1), RESPECTIVELY, P< 0.05); HOWEVER, THIS INCREASE WAS OF LOWER MAGNITUDE IN THE EXPERIMENTAL GROUP. THESE RESULTS DEMONSTRATE THAT POSTNATAL NA OVERLOAD ALTERS BEHAVIOURAL AND CARDIOVASCULAR REGULATION IN ADULTHOOD.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
3  6516  34 TRANSCRIPTIONAL AND EPIGENETIC FACTORS ASSOCIATED WITH EARLY THROMBOSIS OF FEMORAL ARTERY INVOLVED IN ARTERIOVENOUS FISTULA. ARTERIOVENOUS FISTULAS (AVFS), CREATED FOR HEMODIALYSIS IN END-STAGE RENAL DISEASE PATIENTS, MATURE THROUGH THE OUTWARD REMODELING OF THE OUTFLOW VEIN. HOWEVER, EARLY THROMBOSIS AND CHRONIC INFLAMMATION ARE DETRIMENTAL TO THE PROCESS OF AVF MATURATION AND PRECIPITATE AVF MATURATION FAILURE. FOR THE SUCCESSFUL REMODELING OF THE OUTFLOW VEIN, BLOOD FLOW THROUGH THE FISTULA IS ESSENTIAL, BUT EARLY ARTERIAL THROMBOSIS ATTENUATES THIS BLOOD FLOW, AND THE VESSELS BECOME THROMBOSED AND STENOSED, LEADING TO AVF FAILURE. THE ALTERED EXPRESSION OF VARIOUS PROTEINS INVOLVED IN MAINTAINING VESSEL PATENCY OR THROMBOSIS IS REGULATED BY GENES OF WHICH THE EXPRESSION IS REGULATED BY TRANSCRIPTION FACTORS AND MICRORNAS. IN THIS STUDY, USING THROMBOSED AND STENOSED ARTERIES FOLLOWING AVF CREATION, WE DELINEATED TRANSCRIPTION FACTORS AND MICRORNAS ASSOCIATED WITH DIFFERENTIALLY EXPRESSED GENES IN BULK RNA SEQUENCING DATA USING UPSTREAM AND CAUSAL NETWORK ANALYSIS. WE OBSERVED CHANGES IN MANY TRANSCRIPTION FACTORS AND MICRORNAS THAT ARE INVOLVED IN ANGIOGENESIS; VASCULAR SMOOTH MUSCLE CELL PROLIFERATION, MIGRATION, AND PHENOTYPIC CHANGES; ENDOTHELIAL CELL FUNCTION; HYPOXIA; OXIDATIVE STRESS; VESSEL REMODELING; IMMUNE RESPONSES; AND INFLAMMATION. THESE FACTORS AND MICRORNAS PLAY A CRITICAL ROLE IN THE UNDERLYING MOLECULAR MECHANISMS IN AVF MATURATION. WE ALSO OBSERVED EPIGENETIC FACTORS INVOLVED IN GENE REGULATION ASSOCIATED WITH THESE MOLECULAR MECHANISMS. THE RESULTS OF THIS STUDY INDICATE THE IMPORTANCE OF INVESTIGATING THE TRANSCRIPTIONAL AND EPIGENETIC REGULATION OF AVF MATURATION AND MATURATION FAILURE AND TARGETING FACTORS PRECIPITATING EARLY THROMBOSIS AND STENOSIS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
4   223  34 ACUTE PSYCHOSOCIAL STRESS-MEDIATED CHANGES IN THE EXPRESSION AND METHYLATION OF PERFORIN IN CHRONIC FATIGUE SYNDROME. PERFORIN (PRF1) IS ESSENTIAL FOR IMMUNE SURVEILLANCE AND STUDIES REPORT DECREASED PERFORIN IN CHRONIC FATIGUE SYNDROME (CFS), AN ILLNESS POTENTIALLY ASSOCIATED WITH STRESS AND/OR INFECTION. WE HYPOTHESIZE THAT STRESS CAN INFLUENCE REGULATION OF PRF1 EXPRESSION, AND THAT THIS REGULATION WILL DIFFER BETWEEN CFS AND NON-FATIGUED (NF) CONTROLS. WE USED THE TRIER SOCIAL STRESS TEST (TSST) AS A STANDARDIZED ACUTE PSYCHOSOCIAL STRESS, AND EVALUATED ITS EFFECT ON PRF1 EXPRESSION AND METHYLATION IN CFS (N = 34) COMPARED WITH NF (N = 47) PARTICIPANTS. DURING THE TSST, NATURAL KILLER (NK) CELLS INCREASED SIGNIFICANTLY IN BOTH CFS (P = <0.0001) AND NF SUBJECTS (P = <0.0001). UNLIKE PREVIOUS REPORTS, THERE WAS NO SIGNIFICANT DIFFERENCE IN PRF1 EXPRESSION AT BASELINE OR DURING TSST BETWEEN CFS AND NF. HOWEVER, WHOLE BLOOD PRF1 EXPRESSION INCREASED 1.6 FOLD DURING THE TSST IN BOTH CFS (P = 0.0003) AND NF (P = <0.0001). FURTHER, THE PEAK RESPONSE IMMEDIATELY FOLLOWING THE TSST WAS LOWER IN CFS COMPARED WITH NF (P = 0.04). IN ADDITION, AT 1.5 HOURS POST TSST, PRF1 EXPRESSION WAS ELEVATED IN CFS COMPARED WITH NF (WHOLE BLOOD, P = 0.06; PBMC, P = 0.02). METHYLATION OF SEVEN CPG SITES IN THE METHYLATION SENSITIVE REGION OF THE PRF1 PROMOTER RANGED FROM 38%-79% WITH NO SIGNIFICANT DIFFERENCES BETWEEN CFS AND NF. ALTHOUGH, THE AVERAGE BASELINE METHYLATION OF ALL SEVEN CPG SITES DID NOT DIFFER BETWEEN CFS AND NF GROUPS, IT SHOWED A SIGNIFICANT NEGATIVE CORRELATION WITH PRF1 EXPRESSION AT ALL TSST TIME POINTS IN BOTH CFS (R = -0.56, P = <0.0001) AND NF (R = -0.38, P = <0.0001). AMONG PARTICIPANTS WITH HIGH AVERAGE METHYLATION (>/=65%), PRF1 EXPRESSION WAS SIGNIFICANTLY LOWER IN CFS THAN NF SUBJECTS IMMEDIATELY FOLLOWING TSST. THESE FINDINGS SUGGEST METHYLATION COULD BE AN IMPORTANT EPIGENETIC DETERMINANT OF INTER-INDIVIDUAL DIFFERENCES IN PRF1 EXPRESSION AND THAT THE DIFFERENCES IN PRF1 EXPRESSION AND METHYLATION BETWEEN CFS AND NF IN THE ACUTE STRESS RESPONSE REQUIRE FURTHER INVESTIGATION.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
5  4504  33 MOTHER'S PRE-PREGNANCY BMI AND PLACENTAL CANDIDATE MIRNAS: FINDINGS FROM THE ENVIRONAGE BIRTH COHORT. THERE IS INCREASING EVIDENCE THAT THE PREDISPOSITION FOR DEVELOPMENT OF CHRONIC DISEASES ARISES AT THE EARLIEST TIMES OF LIFE. IN THIS CONTEXT, MATERNAL PRE-PREGNANCY WEIGHT MIGHT MODIFY FETAL METABOLISM AND THE CHILD'S PREDISPOSITION TO DEVELOP DISEASE LATER IN LIFE. THE AIM OF THIS STUDY IS TO INVESTIGATE THE ASSOCIATION BETWEEN MATERNAL PRE-PREGNANCY BODY MASS INDEX (BMI) AND MIRNA ALTERATIONS IN PLACENTAL TISSUE AT BIRTH. IN 211 MOTHER-NEWBORN PAIRS FROM THE ENVIRONAGE BIRTH COHORT, WE ASSESSED PLACENTAL EXPRESSION OF SEVEN MIRNAS IMPORTANT IN CRUCIAL CELLULAR PROCESSES IMPLICATED IN ADIPOGENESIS AND/OR OBESITY. MULTIPLE LINEAR REGRESSION MODELS WERE USED TO ADDRESS THE ASSOCIATIONS BETWEEN PRE-PREGNANCY BMI AND PLACENTAL CANDIDATE MIRNA EXPRESSION. MATERNAL PRE-PREGNANCY BMI AVERAGED (+/-SD) 23.9 (+/-4.1) KG/M(2). IN NEWBORN GIRLS (NOT IN BOYS) PLACENTAL MIR-20A, MIR-34A AND MIR-222 EXPRESSION WAS LOWER WITH HIGHER MATERNAL PRE-PREGNANCY BMI. IN ADDITION, THE ASSOCIATION BETWEEN MATERNAL PRE-PREGNANCY BMI AND PLACENTAL EXPRESSION OF THESE MIRNAS IN GIRLS WAS MODIFIED BY GESTATIONAL WEIGHT GAIN. THE LOWER EXPRESSION OF THESE MIRNAS IN PLACENTA IN ASSOCIATION WITH PRE-PREGNANCY BMI, WAS ONLY EVIDENT IN MOTHERS WITH LOW WEIGHT GAIN (<14 KG). THE PLACENTAL EXPRESSION OF MIR-20A, MIR-34A, MIR-146A, MIR-210 AND MIR-222 MAY PROVIDE A SEX-SPECIFIC BASIS FOR EPIGENETIC EFFECTS OF PRE-PREGNANCY BMI.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
6  4350  53 MIR-181A-5P IS A POTENTIAL CANDIDATE EPIGENETIC BIOMARKER IN MULTIPLE SCLEROSIS. MULTIPLE SCLEROSIS (MS) IS A CHRONIC INFLAMMATORY DISEASE OF THE CENTRAL NERVOUS SYSTEM (CNS) CHARACTERIZED BY DEMYELINATION AND AXONAL DEGENERATION. ABNORMAL EXPRESSION OF MICRORNAS (MIRNAS) PLAYS AN IMPORTANT ROLE IN MS PATHOLOGY. IN THIS COHORT STUDY, DIFFERENTIAL EXPRESSION OF THE FOUR MIRNAS (HSA-MIR-155-5P, HSA-MIR-9-5P, HSA-MIR-181A-5P, AND HSA-MIR-125B-5P) WAS INVESTIGATED IN 69 INDIVIDUALS, INCLUDING 39 MS PATIENTS (RELAPSING-REMITTING MS (RRMS), N = 27; SECONDARY PROGRESSIVE MS (SPMS), N = 12) AND 30 HEALTHY CONTROLS. IN SILICO ANALYSES REVEALED POSSIBLE GENES AND PATHWAYS SPECIFIC TO MIRNAS. PERIPHERAL BLOOD MIRNA EXPRESSIONS WERE DETECTED BY QUANTITATIVE REAL-TIME PCR (QPCR). HSA-MIR-181A-5P WAS DOWNREGULATED AND ASSOCIATED WITH INCREASED MS RISK (P = 0.012). THE OTHER THREE MIRNAS WERE UPREGULATED AND NOT ASSOCIATED WITH MS (P < 0.05). THE AREA UNDER THE CURVE (AUC) IS 0.779. IN SILICO ANALYSES SHOWED THAT HSA-MIR-181A-5P MAY PARTICIPATE IN MS PATHOLOGY BY TARGETING MAP2K1, CREB1, ATXN1, AND ATXN3 GENES IN INFLAMMATION AND NEURODEGENERATION PATHWAYS. THE CIRCULATORY HSA-MIR-181A-5P CAN REGULATE TARGET GENES, REVERSING THE MECHANISMS INVOLVED IN MS PATHOLOGIES SUCH AS PROTEIN UPTAKE AND PROCESSING, CELL PROLIFERATION AND SURVIVAL, INFLAMMATION, AND NEURODEGENERATION. THUS, THIS MIRNA COULD BE USED AS AN EPIGENOMIC-GUIDED DIAGNOSTIC TOOL AND FOR THERAPEUTIC PURPOSE.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
7  6418  40 THE TEMPORAL EXPRESSION OF CIRCULATING MICRORNAS AFTER ACUTE EXPERIMENTAL PAIN IN HUMANS. BACKGROUND: MICRORNAS (MIRNAS) CAN MODULATE SEVERAL BIOLOGICAL SYSTEMS, INCLUDING THE PAIN SYSTEM. THIS STUDY AIMED TO EVALUATE THE TEMPORAL EXPRESSION OF CIRCULATING MIRNAS IN THE PLASMA OF HEALTHY VOLUNTEERS AS A MARKER FOR EPIGENETIC CHANGES BEFORE AND AFTER AN ACUTE, EXPERIMENTAL, PAIN PROVOCATION BY INTRAMUSCULAR HYPERTONIC SALINE INJECTION. METHODS: TWENTY VOLUNTEERS WERE RANDOMLY ALLOCATED INTO TWO GROUPS AND RECEIVED EITHER HYPERTONIC (PAIN) OR ISOTONIC (CONTROL) SALINE INJECTION IN THE FIRST DORSAL INTEROSSEOUS MUSCLE OF THEIR DOMINANT HAND. PAIN INTENSITY WAS CONTINUOUSLY RECORDED FOR 20 MINUTES AFTER INJECTION ON A VAS SCALE FROM 0 TO 100 (0 INDICATES NO PAIN AND 100 THE WORST IMAGINABLE PAIN). BLOOD SAMPLES WERE TAKEN AT BASELINE, 30 MINUTES, 3 HOURS, AND 24 HOURS POST-INJECTION, AND PLASMA WAS SEPARATED. MIRNA EXTRACTS WERE USED FOR RNA SEQUENCING WITH THE ILLUMINA NEXTSEQ PLATFORM. MIRNA TRANSCRIPTS WERE COMPARED BETWEEN THE PAIN AND THE NO-PAIN, CONTROL GROUP AT EVERY TIME POINT. SIGNIFICANT DIFFERENCES WERE CONSIDERED WHEN FOLDS WERE >2 AND THE FALSE DISCOVERY RATE WAS P < 0.05. RESULTS: AFTER 30 MINUTES, 4 MIRNAS WERE SIGNIFICANTLY ALTERED IN THE PAIN GROUP COMPARED TO CONTROLS, WHICH INCREASED TO 24 AFTER 3 HOURS AND TO 42 AFTER 24 HOURS FROM BASELINE (P < 0.0001). TWO MIRNAS WERE CONSISTENTLY UPREGULATED THROUGHOUT THE EXPERIMENT. ENRICHMENT ANALYSIS SHOWED SIGNIFICANT MIRNAS INVOLVED IN BRAIN PERCEPTION OF PAIN, BRAIN SIGNALLING AND RESPONSE TO STIMULI. CONCLUSIONS: THIS EXPLORATORY STUDY IS THE FIRST TO REPORT ON THE TEMPORAL EXPRESSION OF CIRCULATING MIRNAS AFTER AN ACUTE, HUMAN EXPERIMENTAL MUSCLE PAIN MODEL. SIGNIFICANCE: THIS EXPLORATORY STUDY EVALUATED THE TEMPORAL PROFILE OF CIRCULATING MIRNAS IN THE PLASMA OF HEALTHY SUBJECTS AFTER ACUTE EXPERIMENTAL PAIN. SEVERAL MIRNAS WERE ALTERED IN SUBJECTS AT THE TIMES OF FOLLOW-UP AFTER THE ACUTE PAIN MODEL WHEN COMPARED TO CONTROLS. MIRNAS PREVIOUSLY ASSOCIATED WITH PAIN PROCESSES WERE ALTERED IN THE PAIN GROUP. OUR RESULTS, BY SHOWING THE FAST AND PROLONGED MODIFICATIONS OF MIRNA ELICITED BY THE ACUTE EXPERIMENTAL PAIN MODEL, ADD NEW PERSPECTIVES TO THE TOPIC OF EPIGENETICS AND PAIN.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                
8  5005  40 PERIPHERAL BLOOD DNA METHYLATION-BASED MACHINE LEARNING MODELS FOR PREDICTION OF KNEE OSTEOARTHRITIS PROGRESSION: BIOLOGIC SPECIMENS AND DATA FROM THE OSTEOARTHRITIS INITIATIVE AND JOHNSTON COUNTY OSTEOARTHRITIS PROJECT. OBJECTIVE: THE LACK OF ACCURATE BIOMARKERS TO PREDICT KNEE OSTEOARTHRITIS (OA) PROGRESSION IS A KEY UNMET NEED IN OA CLINICAL RESEARCH. THE OBJECTIVE OF THIS STUDY WAS TO DEVELOP BASELINE PERIPHERAL BLOOD EPIGENETIC BIOMARKER MODELS TO PREDICT KNEE OA PROGRESSION. METHODS: GENOME-WIDE BUFFY COAT DNA METHYLATION PATTERNS FROM 554 INDIVIDUALS FROM THE OSTEOARTHRITIS BIOMARKERS CONSORTIUM (OABC) WERE DETERMINED USING ILLUMINA INFINIUM METHYLATIONEPIC 850K ARRAYS. DATA WERE DIVIDED INTO MODEL DEVELOPMENT AND VALIDATION SETS, AND MACHINE LEARNING MODELS WERE TRAINED TO CLASSIFY FUTURE OA PROGRESSION BY KNEE PAIN, RADIOGRAPHIC IMAGING, KNEE PAIN PLUS RADIOGRAPHIC IMAGING, AND ANY PROGRESSION (PAIN, RADIOGRAPHIC, OR BOTH). PARSIMONIOUS MODELS USING THE TOP 13 CPG SITES MOST FREQUENTLY SELECTED DURING DEVELOPMENT WERE TESTED ON INDEPENDENT SAMPLES FROM PARTICIPANTS IN THE JOHNSTON COUNTY OSTEOARTHRITIS (JOCO OA) PROJECT (N = 128) AND A PREVIOUSLY PUBLISHED OSTEOARTHRITIS INITIATIVE (OAI) DATA SET (N = 55). RESULTS: FULL MODELS ACCURATELY CLASSIFIED FUTURE RADIOGRAPHIC-ONLY PROGRESSION (MEAN +/- SEM ACCURACY 87 +/- 0.8%, AREA UNDER THE CURVE [AUC] 0.94 +/- 0.004), PAIN-ONLY PROGRESSION (ACCURACY 89 +/- 0.9%, AUC 0.97 +/- 0.004), PAIN PLUS RADIOGRAPHIC PROGRESSION (ACCURACY 72 +/- 0.7%, AUC 0.79 +/- 0.006), AND ANY PROGRESSION (ACCURACY 78 +/- 0.4%, AUC 0.86 +/- 0.004). PAIN-ONLY AND RADIOGRAPHIC-ONLY PROGRESSORS WERE NOT DISTINGUISHABLE (MEAN +/- SEM ACCURACY 58 +/- 1%, AUC 0.62 +/- 0.001). PARSIMONIOUS MODELS SHOWED SIMILAR PERFORMANCE AND ACCURATELY CLASSIFIED FUTURE RADIOGRAPHIC PROGRESSORS IN THE OABC COHORT AND IN BOTH VALIDATION COHORTS (MEAN +/- SEM ACCURACY 80 +/- 0.3%, AUC 0.88 +/- 0.003 [USING JOCO OA PROJECT DATA], ACCURACY 80 +/- 0.8%, AUC 0.89 +/- 0.002 [USING PREVIOUS OAI DATA]). CONCLUSION: OUR DATA SUGGEST THAT PAIN AND STRUCTURAL PROGRESSION SHARE SIMILAR EARLY SYSTEMIC IMMUNE EPIGENOTYPES. FURTHER STUDIES SHOULD FOCUS ON EVALUATING THE PATHOPHYSIOLOGIC CONSEQUENCES OF DIFFERENTIAL DNA METHYLATION AND PERIPHERAL BLOOD CELL EPIGENOTYPES IN INDIVIDUALS WITH KNEE OA.	2023	
                                                                                                                                                                                                                                                                                                                                                
9  6043  40 THE COMBINED PROGNOSTIC SIGNIFICANCE OF ALKALINE PHOSPHATASE AND INTRACRANIAL ARTERIAL CALCIFICATIONS IN HEMODIALYSIS PATIENTS. INTRODUCTION: THE PREVALENCE OF INTRACRANIAL ARTERIAL CALCIFICATION (ICAC) IN MAINTENANCE HEMODIALYSIS (MHD) PATIENTS IS ABOUT 90%, AND ITS SEVERITY IS CORRELATED WITH AGE, HEMODIALYSIS VINTAGE, AND MINERAL BONE DISEASE. ELEVATED CONCENTRATIONS OF CALCIUM AND PHOSPHORUS ARE NOT SUFFICIENT FOR MEDIAL CALCIFICATION BECAUSE OF INHIBITION BY PYROPHOSPHATE. ALKALINE PHOSPHATASE (ALP) PROMOTES CALCIFICATION BY HYDROLYZING EXTRACELLULAR PYROPHOSPHATE. EPIGENETIC MECHANISMS INVOLVING ALP INHIBITION BY APABETALONE WERE INVESTIGATED AS A POTENTIAL TARGET FOR PREVENTING VASCULAR CALCIFICATIONS (VCS). THIS STUDY ASSESSED THE COMBINED IMPACT OF VCS AND ELEVATED SERUM ALP ON MORTALITY AMONG CHRONIC HD PATIENTS. METHODS: VCS REPRESENTED BY ICAC WERE MEASURED SIMULTANEOUSLY WITH MINERAL BONE DISEASE PARAMETERS INCLUDING SERUM ALP OF MHD PATIENTS WHO UNDERWENT NONCONTRAST BRAIN COMPUTED TOMOGRAPHY FROM 2015 TO 2018 IN OUR INSTITUTION. RESULTS: THIS RETROSPECTIVE STUDY INCLUDED 150 MHD PATIENTS (MEAN AGE 71.3 +/- 12.1 YEARS, 60.1% MALE). OF THE TOTAL COHORT, 12 (7.8%) HAD NO BRAIN CALCIFICATIONS AND 69 (45.1%) HAD MULTIPLE INTRACRANIAL CALCIFICATIONS. CONSIDERING THE PATIENTS WITH NORMAL ALP AND NO CALCIFICATION AS THE REFERENCE GROUP YIELDED ADJUSTED ODDS RATIOS FOR ALL-CAUSE MORTALITY OF 4.6 (95% CI: 1.7-12.7) AMONG PATIENTS WITH BRAIN CALCIFICATIONS AND NORMAL ALP (P = 0.003) AND ODDS RATIOS FOR ALL-CAUSE MORTALITY OF 6.1 (95% CI: 2.1-17.7) AMONG PATIENTS WITH BRAIN CALCIFICATIONS AND ELEVATED ALP (P= 0.001). CONCLUSION: WE FOUND AN INDEPENDENT ASSOCIATION BETWEEN ICAC AND THE RISK OF DEATH AMONG MHD PATIENTS. THE COMBINED EFFECT OF ICAC AND ELEVATED ALP WAS ASSOCIATED WITH A HIGHER ODDS RATIO FOR ALL-CAUSE MORTALITY IN MHD PATIENTS AND MAY CONTRIBUTE TO THE RISK STRATIFICATION OF THESE PATIENTS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
10   353  45 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
11  4346  43 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
12  4349  32 MIR-155 AND MIR-122 EXPRESSION OF SPERMATOZOA IN OBESE SUBJECTS. OBESITY IS CHARACTERIZED BY MILD CHRONIC INFLAMMATION THAT IS LINKED WITH IMPAIRED IRON HOMEOSTASIS. STUDIES IN HUMAN AND MURINE SHOW THAT THERE IS A TRANSGENERATIONAL EPIGENETIC INHERITANCE VIA THE GAMETES IN OBESITY; HOWEVER, THERE IS LITTLE INFORMATION ON CHANGES IN THE EXPRESSION OF MICRORNAS RELATED TO INFLAMMATION AND IRON HOMEOSTASIS IN SPERMATOZOA FROM OBESE SUBJECTS. THE PRESENT STUDY INVESTIGATED THE EXPRESSION OF MICRORNAS RELATED TO INFLAMMATION (MIR-21 Y MIR-155) AND IRON NUTRITION (MIR-122 AND MIR-200B) IN PLASMA, PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) AND SPERMATOZOA FROM NORMOZOOSPERMIC CONTROLS (CN; N = 17; BMI: 24.6 +/- 2.0) AND OBESE (OB; N = 17; BMI: 32.6 +/- 4.4) MEN. TO DETERMINE THE INFLAMMATION LEVELS, WE MEASURED IL-6, TNF-ALPHA, AND MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP1) BY MAGNETIC LUMINEX((R)) ASSAY. MRNA EXPRESSION OF IL6, TNF-ALPHA, AND HEPCIDIN (HAMP) IN PBMC WERE EVALUATED BY RT-QPCR. THE ANALYSIS OF MICRORNAS WAS PERFORMED USING THE TAQMAN((R)) ASSAYS. THE IRON CONTENT IN PBMC, SEMINAL PLASMA, AND SPERMATOZOA WAS DETERMINED BY INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY (ICP-MS). HIGH SERUM IL6, TNF-ALPHA, AND MCP1 LEVELS WERE OBSERVED IN OB GROUP (P < 0.05). GENE EXPRESSION ANALYSIS SHOWED AN INCREASED ABUNDANCE RELATIVE OF TNF-ALPHA (P = 0.018), HAMP (P = 0.03), AND IL6 (P = 0.02) IN PBMC FROM OBESE SUBJECTS. ALSO, WE OBSERVED HIGH LEVELS OF SERUM FERRITIN (P = 0.03), IRON CONTENT IN SEMINAL PLASMA (P = 0.04), AND SPERMATOZOA (P = 0.002), BUT LOWER SERUM FE (P = 0.007) IN OBESE SUBJECTS. IN THE OB GROUP, A HIGH EXPRESSION OF MIR-155 (P = 0.02) AND MIR-21 (P = 0.03) WAS OBSERVED IN PBMC AND MIR-122 (P = 0.03) IN PLASMA. IN SPERM, BOTH MIR-155 (P = 0.004) AND MIR-122 (P = 0.028) WERE HIGH IN THE OB GROUP. OUR RESULTS SHOWED THAT OBESE SUBJECTS HAVE INCREASED EXPRESSIONS OF MIR-155 AND MIR-122, TWO MICRORNAS THAT WERE PREVIOUSLY RELATED WITH INFLAMMATION AND IRON METABOLISM, RESPECTIVELY, AT BOTH THE SYSTEMIC AND SPERM LEVELS.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
13  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	

14  2378  27 EPIGENETIC REGULATION OF VASCULAR SMOOTH MUSCLE CELL PHENOTYPE SWITCHING IN ATHEROSCLEROTIC ARTERY REMODELING: A MINI-REVIEW. ATHEROSCLEROSIS IS A CHRONIC INFLAMMATORY DISEASE CHARACTERIZED BY EXTENSIVE REMODELING OF MEDIUM AND LARGE-SIZED ARTERIES. INWARD REMODELING (=LUMEN SHRINKAGE) OF THE VASCULAR WALLS IS THE UNDERLYING CAUSE FOR ISCHEMIA IN TARGET ORGANS. THEREFORE, INWARD REMODELING CAN BE CONSIDERED THE PREDOMINANT FEATURE OF ATHEROSCLEROTIC PATHOLOGY. OUTWARD REMODELING (=LUMEN ENLARGEMENT) IS A PHYSIOLOGICAL RESPONSE COMPENSATING FOR LUMEN SHRINKAGE CAUSED BY NEOINTIMAL HYPERPLASIA, BUT AS A PATHOLOGICAL RESPONSE TO CHANGES IN BLOOD FLOW, OUTWARD REMODELING LEADS TO SUBSTANTIAL ARTERIAL WALL THINNING. THINNED VASCULAR WALLS ARE PRONE TO RUPTURE, AND SUBSEQUENT THROMBUS FORMATION ACCOUNTS FOR THE MAJORITY OF ACUTE CARDIOVASCULAR EVENTS. PATHOLOGICAL REMODELING IS DRIVEN BY INFLAMMATORY CELLS WHICH INDUCE VASCULAR SMOOTH MUSCLE CELLS TO SWITCH FROM QUIESCENT TO A PROLIFERATIVE AND MIGRATORY PHENOTYPE. AFTER DECADES OF INTENSIVE RESEARCH, THE MOLECULAR MECHANISMS OF ARTERIAL REMODELING ARE STARTING TO UNFOLD. IN THIS MINI-REVIEW, WE SUMMARIZE THE CURRENT KNOWLEDGE OF THE EPIGENETIC AND TRANSCRIPTIONAL REGULATION OF VASCULAR SMOOTH MUSCLE CELL PHENOTYPE SWITCHING FROM THE CONTRACTILE TO THE SYNTHETIC PHENOTYPE INVOLVED IN ARTERIAL REMODELING AND DISCUSS POTENTIAL THERAPEUTIC OPTIONS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
15  1030  47 CIRCULATING PLASMA MICRORNAS DYSREGULATION AND METABOLIC ENDOTOXEMIA INDUCED BY A HIGH-FAT HIGH-SATURATED DIET. HIGH-FAT DIET INCREASE TWO TO THREE TIMES THE PLASMA LIPOPOLYSACCHARIDE (LPS) LEVELS AND INDUCE SUBCLINICAL INFLAMMATION. DIET CAN MODIFY GENE EXPRESSION DUE TO EPIGENETIC PROCESSES RELATED TO MICRORNAS (MIRNAS). MICRORNAS (MIRNAS) PLAY IMPORTANT ROLE IN THE POST-TRANSCRIPTIONAL MECHANISMS INVOLVED IN REGULATION OF EXPRESSION OF GENES RELATED TO THE INFLAMMATORY RESPONSE. ALSO, DIET CAN INDIRECTLY INDUCE POST-TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION BY MIRNAS, WHICH MAY AFFECT THE RISK FOR THE DEVELOPMENT OF CHRONIC DISEASES. OBJECTIVE: THIS STUDY INVESTIGATED THE EFFECT OF HIGH-FAT HIGH-SATURATED MEAL INGESTION ON PLASMA MIRNA EXPRESSION AND LPS LEVELS DURING THE POSTPRANDIAL PERIOD IN HEALTHY WOMEN. METHODS: AN INTERVENTIONAL STUDY WAS CARRIED OUT IN WHICH A HIGH-FAT BREAKFAST (1067.45 KCAL), COMPOSED MAINLY OF SATURATED FATTY ACIDS (56 G), AND 500 ML OF WATER, WAS OFFERED. BLOOD SAMPLES WERE COLLECTED AT BASELINE AND 1, 3 AND 5 H AFTER MEAL INTAKE. THE STUDIED POPULATION CONSISTED OF HEALTHY WOMEN (N = 11), AGED BETWEEN 20 AND 40 YEARS, AND BODY MASS INDEX (BMI) BETWEEN 18.5 AND 25 KG/M(2). PLASMA LEVELS OF LIPID PROFILE, CYTOKINES, ADHESION MOLECULES, AND LPS WERE MEASURED AT THE 3 TIME POINTS. A PROFILE OF 752 HUMAN PLASMA MIRNA EXPRESSION WAS ANALYZED BY REAL-TIME PCR ASSAY. THESE ANALYZES WERE PERFORMED FOR ALL BLOOD COLLECTION TIME-POINTS. RESULTS: EXPRESSION PROFILE ANALYSIS REVEALED 33 DIFFERENTIALLY EXPRESSED PLASMA CIRCULATING MIRNAS COMPARED TO THAT OF THE CONTROL GROUP. MIR-145-5P AND MIR-200 WERE DIFFERENTIALLY MODULATED IN ALL TIME-POINTS POST MEAL CONSUMPTION. IN ADDITION, THERE WAS A SIGNIFICANT INCREASE IN PLASMA LPS, TRIGLYCERIDES, MYRISTIC AND PALMITIC SATURATED FATTY ACIDS LEVELS AT THE 3 TIME-POINTS IN COMPARISON WITH THE CONTROL BASAL LEVELS. WE ALSO OBSERVED INCREASED LEVELS OF THE PLASMA TUMOR NECROSIS FACTOR ALPHA (TNF-ALPHA) CYTOKINE AND THE VASCULAR CELL ADHESION MOLECULE 1 (VCAM-1) LEVELS AFTER 5 H POST MEAL INGESTION. CONCLUSION: INGESTION OF HIGH-FAT HIGH-SATURATED MEAL WAS ABLE TO INDUCE METABOLIC ENDOTOXEMIA AND INCREASE THE EXPRESSION OF PRO-INFLAMMATORY MOLECULES SUCH AS TNF-ALPHA AND VCAM-1, AS WELL AS MODULATING CIRCULATING MIRNAS POSSIBLY CONTROLLING INFLAMMATORY AND LIPID METABOLISM PROTEINS AT THE POSTPRANDIAL PERIOD.	2020	
                                                                                                                                                                                                                                                         
16  5734  36 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  3850  29 IS GENDER A FACTOR AFFECTING LONG-TERM HETEROTOPIC OSSIFICATION INCIDENCE AFTER SINGLE-LEVEL CERVICAL DISC ARTHROPLASTY? BACKGROUND: CERVICAL DISC DISEASES HAVE BEEN TREATED BY CERVICAL DISC ARTHROPLASTY (CDA). NEVERTHELESS, SOME PATIENTS WILL EXPERIENCE A MOBILITY FAILURE IN THEIR CERVICAL PROSTHESES OVER TIME BECAUSE OF HETEROTOPIC OSSIFICATION. THE AIM OF THIS STUDY WAS TO INVESTIGATE THE ROLE OF GENDER IN LONG-TERM OUTCOMES AFTER CDA. METHODS: A RETROSPECTIVE, SINGLE-CENTER STUDY OF PATIENTS WHO UNDERWENT SINGLE-LEVEL CDA WITH A BRYAN CERVICAL DISC PROSTHESIS WAS PERFORMED, INCLUDING A NARRATIVE REVIEW ABOUT GENDER DIFFERENCES IN BOTH STRUCTURAL AND BIOMECHANICAL FEATURES OF THE CERVICAL SPINE. RESULTS: STUDY PATIENTS (14 MEN, 30 WOMEN) HAD AN AVERAGE FOLLOW-UP OF 9.8 +/- 3.2 YEARS. SIGNIFICANT DIFFERENCES EMERGED BETWEEN GENDERS FOR SPECIFIC ITEMS IN NECK DISABILITY INDEX PREOPERATIVE EVALUATION, WITH WOMEN REPORTING WORSE PAIN SCORES (P = 0.05). AFTER STRATIFICATION BY AGE, WE FOUND A HIGHER PREOPERATIVE OVERALL NECK DISABILITY INDEX SCORE FOR FEMALE PATIENTS <36 YEARS OF AGE (P = 0.03). IN AN INTERGENDER, BODY MASS INDEX-SPECIFIC COMPARISON, WE ALSO FOUND A SIGNIFICANT DIFFERENCE IN NECK DISABILITY INDEX PREOPERATIVE SCORE WITH NORMAL-WEIGHT MALE PATIENTS FARING WORSE THAN OVERWEIGHT MALE PATIENTS (P = 0.05). AT A RADIOLOGICAL LEVEL, WE FOUND A TENDENCY TOWARD A HIGHER HETEROTOPIC OSSIFICATION INCIDENCE IN MALE PATIENTS (62% IN MEN, 17% IN WOMEN, P = 0.06). THE FEMALE CERVICAL SPINE HAS DISTINCTIVE FEATURES, INCLUDING BONE STRUCTURE, MUSCULAR ACTION, SOFT TISSUE RESPONSE, AND GENETIC AND EPIGENETIC RESPONSE TO OSTEOARTHRITIS. CONCLUSIONS: THE INCIDENCE OF MOBILITY FAILURE IN OUR SERIES OF SINGLE-LEVEL CDA WAS LOWER IN FEMALE PATIENTS. SEVERAL GENDER-SPECIFIC FACTORS BOTH IN STATIC AND IN DYNAMIC FEATURES MAY PLAY A SIGNIFICANT ROLE IN SPINAL PATHOLOGY AND CDA LONG-TERM RADIOLOGICAL OUTCOME.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
18   444  27 AORTIC AND CAROTID ARTERIAL STIFFNESS AND EPIGENETIC REGULATOR GENE EXPRESSION CHANGES PRECEDE BLOOD PRESSURE RISE IN STROKE-PRONE DAHL SALT-SENSITIVE HYPERTENSIVE RATS. MULTIPLE CLINICAL STUDIES SHOW THAT ARTERIAL STIFFNESS, MEASURED AS PULSE WAVE VELOCITY (PWV), PRECEDES HYPERTENSION AND IS AN INDEPENDENT PREDICTOR OF HYPERTENSION END ORGAN DISEASES INCLUDING STROKE, CARDIOVASCULAR DISEASE AND CHRONIC KIDNEY DISEASE. RISK FACTOR STUDIES FOR ARTERIAL STIFFNESS IMPLICATE AGE, HYPERTENSION AND SODIUM. HOWEVER, CAUSAL MECHANISMS LINKING RISK FACTOR TO ARTERIAL STIFFNESS REMAIN TO BE ELUCIDATED. HERE, WE STUDIED THE CAUSAL RELATIONSHIP OF ARTERIAL STIFFNESS AND HYPERTENSION IN THE NA-INDUCED, STROKE-PRONE DAHL SALT-SENSITIVE (S) HYPERTENSIVE RAT MODEL, AND ANALYZED PUTATIVE MOLECULAR MECHANISMS. STROKE-PRONE AND NON-STROKE-PRONE MALE AND FEMALE RATS WERE STUDIED AT 3- AND 6-WEEKS OF AGE FOR ARTERIAL STIFFNESS (PWV, STRAIN), BLOOD PRESSURE, VESSEL WALL HISTOLOGY, AND GENE EXPRESSION CHANGES. STUDIES SHOWED THAT INCREASED LEFT CAROTID AND AORTIC ARTERIAL STIFFNESS PRECEDED HYPERTENSION, PULSE PRESSURE WIDENING, AND STRUCTURAL WALL CHANGES AT THE 6-WEEK TIME-POINT. INSTEAD, DIFFERENTIAL GENE INDUCTION WAS DETECTED IMPLICATING MOLECULAR-FUNCTIONAL CHANGES IN EXTRACELLULAR MATRIX (ECM) STRUCTURAL CONSTITUENTS, MODIFIERS, CELL ADHESION, AND MATRICELLULAR PROTEINS, AS WELL AS IN ENDOTHELIAL FUNCTION, APOPTOSIS BALANCE, AND EPIGENETIC REGULATORS. IMMUNOSTAINING TESTING HISTONE MODIFIERS EP300, HDAC3, AND PRMT5 LEVELS CONFIRMED CAROTID ARTERY-UPREGULATION IN ALL THREE LAYERS: ENDOTHELIAL, SMOOTH MUSCLE AND ADVENTITIAL CELLS. OUR STUDY RECAPITULATES OBSERVATIONS IN HUMANS THAT GIVEN SALT-SENSITIVITY, INCREASED NA-INTAKE INDUCED ARTERIAL STIFFNESS BEFORE HYPERTENSION, INCREASED PULSE PRESSURE, AND STRUCTURAL VESSEL WALL CHANGES. DIFFERENTIAL GENE EXPRESSION CHANGES ASSOCIATED WITH ARTERIAL STIFFNESS SUGGEST A MOLECULAR MECHANISM LINKING SODIUM TO FULL-VESSEL WALL RESPONSE AFFECTING GENE-NETWORKS INVOLVED IN VASCULAR ECM STRUCTURE-FUNCTION, APOPTOSIS BALANCE, AND EPIGENETIC REGULATION.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
19  5236  41 PROFILING NON-CODING RNA LEVELS WITH CLINICAL CLASSIFIERS IN PEDIATRIC CROHN'S DISEASE. BACKGROUND: CROHN'S DISEASE (CD) IS A HERITABLE CHRONIC INFLAMMATORY DISORDER. NON-CODING RNAS (NCRNAS) PLAY AN IMPORTANT ROLE IN EPIGENETIC REGULATION BY AFFECTING GENE EXPRESSION, BUT CAN ALSO DIRECTLY AFFECT PROTEIN FUNCTION, THUS HAVING A SUBSTANTIAL IMPACT ON BIOLOGICAL PROCESSES. WE INVESTIGATED WHETHER NON-CODING RNAS (NCRNA) AT DIAGNOSIS ARE DYSREGULATED DURING CD AT DIFFERENT CD LOCATIONS AND FUTURE DISEASE BEHAVIORS TO DETERMINE IF NCRNA SIGNATURES CAN SERVE AS AN INDEX TO OUTCOMES. METHODS: USING SUBJECTS BELONGING TO THE RISK COHORT, WE ANALYZED NCRNA FROM THE ILEAL BIOPSIES OF 345 CD AND 71 NON-IBD CONTROLS, AND NCRNA FROM RECTAL BIOPSIES OF 329 CD AND 61 NON-IBD CONTROLS. SEQUENCE ALIGNMENT WAS DONE (STAR PACKAGE) USING HUMAN GENOME VERSION 38 (HG38) AS REFERENCE PANEL. THE DIFFERENTIAL EXPRESSION (DE) ANALYSIS WAS PERFORMED WITH EDGER PACKAGE AND DE NCRNAS WERE IDENTIFIED WITH A THRESHOLD OF FOLD CHANGE (FC) > 2 AND FDR < 0.05 AFTER MULTIPLE TEST CORRECTIONS. RESULTS: IN TOTAL, WE IDENTIFIED 130 CD SPECIFIC DE NCRNAS (89 IN ILEUM AND 41 IN RECTUM) WHEN COMPARED TO NON-IBD CONTROLS. SIMILARLY, 35 DE NCRNAS WERE IDENTIFIED BETWEEN B1 AND B2 IN ILEUM, WHEREAS NO DIFFERENCES AMONG CD DISEASE BEHAVIORS WERE NOTICED IN RECTUM. WE ALSO FOUND INFLAMMATION SPECIFIC NCRNAS BETWEEN INFLAMED AND NON-INFLAMED GROUPS IN ILEAL BIOPSIES. OVERALL, WE OBSERVED THAT EXPRESSION OF MIR1244-2, MIR1244-3, MIR1244-4, AND RN7SL2 WERE INCREASED DURING CD, REGARDLESS OF DISEASE BEHAVIOR, LOCATION, OR INFLAMMATORY STATUS. LASTLY, WE TESTED NCRNA EXPRESSION AT BASELINE AS POTENTIAL TOOL TO PREDICT THE DISEASE STATUS, DISEASE BEHAVIORS AND DISEASE INFLAMMATION AT 3-YEAR FOLLOW UP. CONCLUSIONS: WE HAVE IDENTIFIED NCRNAS THAT ARE SPECIFIC TO DISEASE LOCATION, DISEASE BEHAVIOR, AND DISEASE INFLAMMATION IN CD. BOTH ILEAL AND RECTAL SPECIFIC NCRNA ARE CHANGING OVER THE COURSE OF CD, SPECIFICALLY DURING THE DISEASE PROGRESSION IN THE INTESTINAL MUCOSA. COLLECTIVELY, OUR FINDINGS SHOW CHANGES IN NCRNA DURING CD AND MAY HAVE A CLINICAL UTILITY IN EARLY IDENTIFICATION AND CHARACTERIZATION OF DISEASE PROGRESSION.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
20   418  46 ANCESTRAL EXPOSURE TO STRESS EPIGENETICALLY PROGRAMS PRETERM BIRTH RISK AND ADVERSE MATERNAL AND NEWBORN OUTCOMES. BACKGROUND: CHRONIC STRESS IS CONSIDERED TO BE ONE OF MANY CAUSES OF HUMAN PRETERM BIRTH (PTB), BUT NO DIRECT EVIDENCE HAS YET BEEN PROVIDED. HERE WE SHOW IN RATS THAT STRESS ACROSS GENERATIONS HAS DOWNSTREAM EFFECTS ON ENDOCRINE, METABOLIC AND BEHAVIOURAL MANIFESTATIONS OF PTB POSSIBLY VIA MICRORNA (MIRNA) REGULATION. METHODS: PREGNANT DAMS OF THE PARENTAL GENERATION WERE EXPOSED TO STRESS FROM GESTATIONAL DAYS 12 TO 18. THEIR PREGNANT DAUGHTERS (F1) AND GRAND-DAUGHTERS (F2) EITHER WERE STRESSED OR REMAINED AS NON-STRESSED CONTROLS. GESTATIONAL LENGTH, MATERNAL GESTATIONAL WEIGHT GAIN, BLOOD GLUCOSE AND PLASMA CORTICOSTERONE LEVELS, LITTER SIZE AND OFFSPRING WEIGHT GAIN FROM POSTNATAL DAYS 1 TO 30 WERE RECORDED IN EACH GENERATION, INCLUDING F3. MATERNAL BEHAVIOURS WERE ANALYSED FOR THE FIRST HOUR AFTER COMPLETED PARTURITION, AND OFFSPRING SENSORIMOTOR DEVELOPMENT WAS RECORDED ON POSTNATAL DAY (P) 7. F0 THROUGH F2 MATERNAL BRAIN FRONTAL CORTEX, UTERUS AND PLACENTA MIRNA AND GENE EXPRESSION PATTERNS WERE USED TO IDENTIFY STRESS-INDUCED EPIGENETIC REGULATORY PATHWAYS OF MATERNAL BEHAVIOUR AND PREGNANCY MAINTENANCE. RESULTS: PROGRESSIVELY UP TO THE F2 GENERATION, STRESS GRADUALLY REDUCED GESTATIONAL LENGTH, MATERNAL WEIGHT GAIN AND BEHAVIOURAL ACTIVITY, AND INCREASED BLOOD GLUCOSE LEVELS. REDUCED OFFSPRING GROWTH AND DELAYED BEHAVIOURAL DEVELOPMENT IN THE STRESS COHORT WAS RECOGNIZABLE AS EARLY AS P7, WITH THE GREATEST EFFECT IN THE F3 OFFSPRING OF TRANSGENERATIONALLY STRESSED MOTHERS. FURTHERMORE, STRESS ALTERED MIRNA EXPRESSION PATTERNS IN THE BRAIN AND UTERUS OF F2 MOTHERS, INCLUDING THE MIR-200 FAMILY, WHICH REGULATES PATHWAYS RELATED TO BRAIN PLASTICITY AND PARTURITION, RESPECTIVELY. MAIN MIR-200 FAMILY TARGET GENES IN THE UTERUS, STAT5B, ZEB1 AND ZEB2, WERE DOWNREGULATED BY MULTIGENERATIONAL STRESS IN THE F1 GENERATION. ZEB2 WAS ALSO REDUCED IN THE STRESSED F2 GENERATION, SUGGESTING A CAUSAL MECHANISM FOR DISTURBED PREGNANCY MAINTENANCE. ADDITIONALLY, STRESS INCREASED PLACENTAL MIR-181A, A MARKER OF HUMAN PTB. CONCLUSIONS: THE FINDINGS INDICATE THAT A FAMILY HISTORY OF STRESS MAY PROGRAM CENTRAL AND PERIPHERAL PATHWAYS REGULATING GESTATIONAL LENGTH AND MATERNAL AND NEWBORN HEALTH OUTCOMES IN THE MATERNAL LINEAGE. THIS NEW PARADIGM MAY MODEL THE ORIGIN OF MANY HUMAN PTB CAUSES.	2014