1  3589 124 IMPACTS OF ECCENTRIC RESISTANCE EXERCISE ON DNA METHYLATION OF CANDIDATE GENES FOR INFLAMMATORY CYTOKINES IN SKELETAL MUSCLE AND LEUKOCYTES OF HEALTHY MALES. PHYSICAL INACTIVITY AND A POOR DIET INCREASE SYSTEMIC INFLAMMATION, WHILE CHRONIC INFLAMMATION CAN BE REDUCED THROUGH EXERCISE AND NUTRITIONAL INTERVENTIONS. THE MECHANISMS UNDERLYING THE IMPACTS OF LIFESTYLE INTERVENTIONS ON INFLAMMATION REMAIN TO BE FULLY EXPLAINED; HOWEVER, EPIGENETIC MODIFICATIONS MAY BE CRITICAL. THE PURPOSE OF OUR STUDY WAS TO INVESTIGATE THE IMPACTS OF ECCENTRIC RESISTANCE EXERCISE AND FATTY ACID SUPPLEMENTATION ON DNA METHYLATION AND MRNA EXPRESSION OF TNF AND IL6 IN SKELETAL MUSCLE AND LEUKOCYTES. EIGHT NON-RESISTANCE EXERCISE-TRAINED MALES COMPLETED THREE BOUTS OF ISOKINETIC ECCENTRIC CONTRACTIONS OF THE KNEE EXTENSORS. THE FIRST BOUT OCCURRED AT BASELINE, THE SECOND OCCURRED FOLLOWING A THREE-WEEK SUPPLEMENTATION OF EITHER OMEGA-3 POLYUNSATURATED FATTY ACID OR EXTRA VIRGIN OLIVE OIL AND THE FINAL BOUT OCCURRED AFTER EIGHT-WEEKS OF ECCENTRIC RESISTANCE TRAINING AND SUPPLEMENTATION. ACUTE EXERCISE DECREASED SKELETAL MUSCLE TNF DNA METHYLATION BY 5% (P = 0.031), WHEREAS IL6 DNA METHYLATION INCREASED BY 3% (P = 0.01). LEUKOCYTE DNA METHYLATION WAS UNCHANGED FOLLOWING EXERCISE (P > 0.05); HOWEVER, THREE HOURS POST-EXERCISE THE TNF DNA METHYLATION DECREASED BY 2% (P = 0.004). IN SKELETAL MUSCLE, INCREASED TNF AND IL6 MRNA EXPRESSION LEVELS WERE IDENTIFIED IMMEDIATELY POST-EXERCISE (P < 0.027); HOWEVER, THE LEUKOCYTE MRNA EXPRESSION WAS UNCHANGED. ASSOCIATIONS BETWEEN DNA METHYLATION AND MARKERS OF EXERCISE PERFORMANCE, INFLAMMATION AND MUSCLE DAMAGE WERE IDENTIFIED (P < 0.05). ACUTE ECCENTRIC RESISTANCE EXERCISE IS SUFFICIENT TO INDUCE TISSUE-SPECIFIC DNA METHYLATION MODIFICATIONS TO TNF AND IL6; HOWEVER, NEITHER ECCENTRIC TRAINING NOR SUPPLEMENTATION WAS SUFFICIENT TO FURTHER MODIFY THE DNA METHYLATION.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
2   224  35 ACUTE SKELETAL MUSCLE CONTRACTIONS ORCHESTRATE SIGNALING MECHANISMS TO TRIGGER NUCLEAR NFATC1 SHUTTLING AND EPIGENETIC HISTONE MODIFICATIONS. BACKGROUND/AIMS: CALCIUM (CA(2)(+)) COORDINATES SKELETAL MUSCLE FUNCTIONS BY CONTROLLING CONTRACTIONS AS WELL AS SIGNALING PATHWAYS AND TRANSCRIPTIONAL PROPERTIES. THE RYANODINE RECEPTOR 1 (RYR1), ITS PHOSPHORYLATION SITE (PRYR1SER(2)(8)(4)(0)) AND ITS STABILIZERS NAVIGATE CA(2)(+) OSCILLATIONS TO COMMAND MUSCLE SIGNALING CASCADES AND TRANSCRIPTIONAL ACTIVITIES. WHILE CHRONIC EXERCISE INCREASES PRYR1SER(2)(8)(4)(0), INVESTIGATIONS ON ACUTE EXERCISE'S EFFECTS ON RYR1 AND CA(2)(+)-DEPENDENT MODIFICATIONS OF SKELETAL MUSCLE ARE RARE. THE AIM OF THIS STUDY WAS TO EXAMINE MOLECULAR EVENTS LEADING TO RYR1 PHOSPHORYLATION IN A PHYSIOLOGICAL MODEL OF ACUTE EXERCISE. WE HYPOTHESIZED THAT EXERCISE-INDUCED RYR1 PHOSPHORYLATION IS ASSOCIATED WITH ALTERED CA(2)(+)-DEPENDENT PHYSIOLOGICAL PHENOTYPES. METHODS: WE ANALYZED PRYR1SER(2)(8)(4)(0), ITS STABILIZERS, INVOLVED SIGNALING PATHWAYS, AND CA(2)(+)-SENSITIVE MUSCLE-DETERMINING FACTORS (I.E. NFATC1 AND EPIGENETIC HISTONE H3 MODIFICATIONS) IN RAT MUSCLES UPON ONE SINGLE RUNNING BOUT OF EITHER CONCENTRIC OR ECCENTRIC CONTRACTIONS. RESULTS: BOTH ACUTE EXERCISES SIGNIFICANTLY INCREASED PRYRSER(2)(8)(4)(0) LEVELS IN MUSCLES, WHICH WAS ACCOMPANIED BY DISSOCIATIONS OF STABILIZERS FROM RYR1. ADDITIONALLY, RYR1 PHOSPHORYLATION-INDUCING SIGNALING CASCADES PTEN/CAMKII/ PKA WERE SIGNIFICANTLY ACTIVATED UPON EXERCISE. FURTHER, RYR1 PHOSPHORYLATIONS WERE ASSOCIATED WITH INCREASED CA(2)(+)-DEPENDENT NFATC1 NUCLEAR ABUNDANCES AS WELL AS INCREASED CA(2)(+)-DEPENDENT EPIGENETIC H3 ACETYLATIONS POINTING TO A PRYR1SER(2)(8)(4)(0)-DEPENDENT RAPID AND NOVEL CA(2)(+) EQUILIBRIUM UPON EXERCISE. CONCLUSION: OUR DATA REPORT SYNERGISTIC ACTIONS OF SEVERAL DISTINCT PATHWAYS TO MODIFY RYR1 FUNCTION TO GOVERN PHYSIOLOGICAL PHENOTYPES, HERE EXPRESSED AS INCREASED NUCLEAR NFATC1 ABUNDANCES AND EPIGENETIC H3 MODIFICATIONS.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                          
3   897  26 CHRONIC EXERCISE TRAINING ACTIVATES HISTONE TURNOVER IN MOUSE SKELETAL MUSCLE FIBERS. EPIGENETIC REGULATION OF SKELETAL MUSCLE ADAPTATION TO EXERCISE IS A RECENT TOPIC FOR WHICH THERE IS LIMITED INFORMATION. THIS STUDY INVESTIGATED WHETHER EXERCISE TRAINING ACTIVATES HISTONE TURNOVER IN THE SKELETAL MUSCLE FIBERS OF MICE. EXPERIMENTS USING A TETRACYCLINE-INDUCIBLE H2B-GFP EXPRESSION MODEL DEMONSTRATED THAT 4 WEEKS OF RUNNING TRAINING, BUT NOT 2 WEEKS OF TRAINING, SIGNIFICANTLY PROMOTED THE INCORPORATION OF H2B-GFP INTO NUCLEOSOMES AND THE DISSOCIATION OF HISTONE H3.3 AT BOTH TRANSCRIPTIONALLY UPREGULATED AND NONRESPONSIVE LOCI. MUSCLE-SPECIFIC PGC-1ALPHA-B-OVEREXPRESSING MICE CROSSED WITH H2B-GFP MICE SHOWED A SLIGHT INCREASE IN H2B-GFP INCORPORATION AT TRANSCRIPTIONALLY ACTIVE LOCI, BUT NOT IN THE DISSOCIATION OF H3.3 FROM NUCLEOSOMES. GENE EXPRESSION RESPONSES TO A SINGLE BOUT OF RUNNING WERE SIGNIFICANTLY ENHANCED IN 4-WEEK TRAINED MICE WHEN COMPARED WITH THOSE IN 2-WEEK TRAINED MICE. THE MOST DRASTIC INCREASE IN THE GENE RESPONSE WAS FOUND IN THE EXPRESSION OF HSPA1A AND HSPA1B, IN WHICH THE MAGNITUDE OF UPREGULATION IN RESPONSE TO RUNNING WAS SIGNIFICANTLY ENHANCED FROM 8-FOLD IN 2 WEEK TRAINED MICE TO 97- AND 121-FOLD IN 4 WEEK TRAINED MICE, RESPECTIVELY. IT WAS ALSO FOUND THAT THE HSP70 LEVEL INCREASED DURING THE TRAINING PERIOD. IN A MYONUCLEAR IMMUNOHISTOCHEMICAL ANALYSIS OF CHROMATIN REMODELERS, WE FURTHER FOUND THAT THE LEVEL OF SPT16, AN H2A-H2B-SPECIFIC CHAPERONE, WAS UPREGULATED AFTER RUNNING TRAINING. THESE RESULTS REVEALED THAT 4 WEEKS OF RUNNING TRAINING ACTIVATED HISTONE TURNOVER IN SKELETAL MUSCLE FIBERS. THEY ALSO SUGGESTED THAT HISTONE TURNOVER LED TO LOOSENING OF THE NUCLEOSOMES AND ENHANCED GENE RESPONSES TO EXERCISE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
4  6816  29 [EXPRESSION, GENETIC AND EPIGENETIC ALTERATIONS OF LTF GENE IN NASOPHARYNGEAL CARCINOMA CELL LINES]. OBJECTIVE: TO INVESTIGATE THE EXPRESSION OF LTF MRNA IN SEVERAL NASOPHARYNGEAL CANCER (NPC) CELL LINES, AND ANALYZE THE RELATIONSHIP BETWEEN THE GENETIC AND EPIGENETIC CHANGES AND EXPRESSION OF LTF GENE. METHODS: THE EXPRESSION LEVEL OF LTF WAS DETECTED IN NPC CELL LINES HNE1, HNE2, HNE3, CNE1, CNE2, 5-8F, 6-10B CELLS AND TISSUES OF 15 CASES OF CHRONIC NASOPHARYNGITIS BY RT-PCR. THE LTF PROTEIN LEVEL WAS ANALYZED BY WESTERN BLOTTING IN 6-10B CELLS. THEN LOH, MUTATION AND METHYLATION STATUS OF LTF WAS EXAMINED BY MICROSATELLITES ANALYSIS, PCR-SSCP, MSP AND BISULFITE GENOMIC SEQUENCING, RESPECTIVELY. RESULTS: 15 CHRONIC NASOPHARYNGITIS TISSUES SHOWED STABLE LTF EXPRESSION, WHILE THERE WERE WEAK EXPRESSION IN 6-10B CELLS AND ABSENT EXPRESSION IN REMAINING DETECTED NPC CELL LINES. THERE WAS A SIGNIFICANTLY LOWER LTF EXPRESSION IN CHRONIC NASOPHARYNGITIS TISSUES (Z = -3.738, P = 0.000). NO LTF PROTEIN EXPRESSION WAS OBSERVED IN 6-10B CELLS. LOH ANALYSIS DEMONSTRATED THAT ALLELE LOSS OF LTF WASN'T FOUND IN NPC CELL LINES. LTF MUTATION WAS NOTED IN 14.3% (1/7) OF NPC CELL LINES. DNA SEQUENCING CONFIRMED THE MUTATION POINT IN THE PROMOTER REGION (-305 BP TO -50 BP) WAS AT -218 BP (DEL T) OF LTF GENE IN THE HNE1 CELL LINE. METHYLATION OF LTF GENE WAS NOT FOUND IN CHRONIC NASOPHARYNGITIS. HOWEVER, METHYLATION OF LTF PROMOTER WAS DETECTED IN ALL NPC CELL LINES. LTF MRNA EXPRESSION WAS INCREASED IN 5-8F AND 6-10B CELL LINES AFTER TREATMENT WITH 5-AZA-2-DEOXYCYTIDINE. CONCLUSION: THERE IS AN INACTIVATION OF EXPRESSION OF LTF GENE IN THE NPC CELL LINES. ITS MOLECULAR MECHANISM MAY BE RELATED WITH METHYLATION OF PROMOTER REGION AND DELETION MUTATION.	2010	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
5  1786  29 EFFECT OF ARSENIC EXPOSURE ON NRF2-KEAP1 PATHWAY AND EPIGENETIC MODIFICATION. ARSENIC (AS) IS A KNOWN TOXIC ELEMENT AND CARCINOGEN. TRANSCRIPTION FACTOR NUCLEAR FACTOR-ERYTHROID 2-RELATED FACTOR 2 (NRF2) CONTROLS CELLULAR ADAPTATION TO OXIDANTS AND ELECTROPHILES BY INDUCING ANTIOXIDANT GENES IN RESPONSE TO REDOX STRESS. TO EXPLORE ASSOCIATIONS BETWEEN AS LEVEL AND NRF2-REGULATED CYTOPROTECTIVE GENES EXPRESSION, AN OBSERVATIONAL STUDY WAS CONDUCTED IN A POPULATION OF 61 OCCUPATIONALLY EXPOSED MEN WITH MEDIAN (ME) AGE 50 YEARS (INTERQUARTILE RANGE (IQR) 42-54) AND IN A CONTROL GROUP OF 52 MEN AGED 40 (IQR 31-51.5) WITHOUT OCCUPATIONAL EXPOSURE. NRF2, KEAP1, GSTP1, HMOX1, NQO1, PRDX1, AND TXNRD1 TRANSCRIPT LEVELS WERE DETERMINED BY MEANS OF QUANTITATIVE REAL-TIME PCR ALONG WITH THE GENE EXPRESSION, METHYLATION OF NRF2 AND KEAP1, AS WELL AS GLOBAL DNA METHYLATION WERE ASSESSED. THE MEDIAN URINE AS (TOT.) LEVEL IN THE EXPOSED AND CONTROL GROUP WAS FOUND TO BE 21.8 MUG/G CREAT. (IQR 15.5-39.8 MUG/G CREAT.) AND 3.8 MUG/G CREAT. (IQR 2.5-9.3) (P < 0.001). GLOBAL DNA METHYLATION WAS SIGNIFICANTLY HIGHER IN OCCUPATIONALLY EXPOSED WORKERS THAN IN CONTROLS (ME 14.1 (IQR 9.5-18.1) VS ME 8.5 (IQR 5.9-12.6) P < 0.0001). NRF2 MRNA LEVEL WAS POSITIVELY CORRELATED WITH EXPRESSION OF ALL INVESTIGATED NRF2-TARGET GENES IN BOTH GROUPS (0.37 > R < 0.76, ALL P VALUES < 0.0001). THE MULTIVARIATE LINEAR REGRESSION ADJUSTING FOR GLOBAL METHYLATION SHOWED THAT AS(III) LEVEL WAS SIGNIFICANTLY ASSOCIATED WITH EXPRESSION OF TXNRD1, GSTP1, HMOX1, AND PRDX1. THE RESULTS OF THIS STUDY INDICATE THAT ARSENIC OCCUPATIONAL EXPOSURE IS POSITIVELY ASSOCIATED WITH GLOBAL DNA METHYLATION. THE FINDINGS PROVIDE EVIDENCE FOR RATHER INACTIVATION OF NRF2-KEAP1 PATHWAY IN RESPONSE TO CHRONIC ARSENIC EXPOSURE.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
6   659  25 BLOOD GLOBAL DNA METHYLATION IS DECREASED IN NON-SEVERE CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) PATIENTS. BACKGROUND: ALTERATIONS IN GLOBAL DNA METHYLATION HAVE BEEN ASSOCIATED WITH OXIDATIVE STRESS (OS). SINCE CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS CHARACTERIZED BY INCREASED OXIDATIVE STRESS WE AIMED TO EVALUATE THE LEVELS OF GLOBAL DNA METHYLATION IN THIS PATIENT GROUP. METHODS: WE ASSESSED METHYLCYTOSINE (MCYT) LEVELS IN DNA FROM BLOOD COLLECTED IN 43 COPD PATIENTS (29 WITH MILD AND 14 WITH MODERATE DISEASE) AND 43 AGE- AND SEX-MATCHED HEALTHY CONTROLS. RESULTS: DNA METHYLATION WAS SIGNIFICANTLY LOWER IN COPD PATIENTS VS. CONTROLS (4.20 +/- 0.18% MCYT VS. 4.29 +/- 0.18% MCYT, P = 0.02). FURTHERMORE, DNA METHYLATION IN COPD PATIENTS WITH MODERATE DISEASE WAS SIGNIFICANTLY LOWER THAN THAT IN PATIENTS WITH MILD DISEASE (4.14 +/- 0.15% MCYT VS. 4.23 +/- 0.19% MCYT, P < 0.05). UNIVARIATE LOGISTIC REGRESSION ANALYSIS SHOWED THAT LOWER DNA METHYLATION LEVELS WERE ASSOCIATED WITH PRESENCE OF COPD (CRUDE OR = 0.06, 95% CI 0.00 TO 0.67, P = 0.023). THIS RELATIONSHIP REMAINED SIGNIFICANT AFTER ADJUSTING FOR SEVERAL CONFOUNDERS (OR 0.03, 95% CI 0.00 TO 0.67; P = 0.028). RECEIVER OPERATING CHARACTERISTICS (ROC) CURVE ANALYSIS DEMONSTRATED THE AREA UNDER THE CURVE OF MCYT WAS 0.646, WITH 46.6% SENSITIVITY AND 79.1% SPECIFICITY FOR PRESENCE OF COPD. CONCLUSIONS: THERE WERE NO SIGNIFICANT CORRELATIONS BETWEEN METHYLATION AND OS INDICES. THE PRESENCE AND SEVERITY OF COPD IS ASSOCIATED WITH PROGRESSIVELY LOWER DNA METHYLATION IN BLOOD. HOWEVER, THIS EPIGENETIC ALTERATION SEEMS INDEPENDENT OF OXIDATIVE STRESS.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
7  4248  31 METHYLATION STATUS, MRNA AND PROTEIN EXPRESSION OF THE SMAD4 GENE IN PATIENTS WITH NON-MELANOCYTIC SKIN CANCERS. BACKGROUND: SMAD4 IS A POTENT TUMOR SUPPRESSOR. SMAD4 LOSS INCREASES GENOMIC INSTABILITY AND PLAYS A CRITICAL ROLE IN THE DNA DAMAGE RESPONSE THAT LEADS TO SKIN CANCER DEVELOPMENT. WE AIMED TO INVESTIGATE SMAD4 METHYLATION EFFECTS ON MRNA AND PROTEIN EXPRESSION OF SMAD4 IN CANCER AND HEALTHY TISSUES FROM PATIENTS WITH BASAL CELL CARCINOMA (BCC), CUTANEOUS SQUAMOUS CELL CARCINOMA (CSCC), AND BASOSQUAMOUS SKIN CANCER (BSC). METHODS AND RESULTS: THE STUDY INCLUDED 17 BCC, 24 CSCC AND NINE BSC PATIENTS. DNA AND RNA WERE ISOLATED FROM CANCEROUS AND HEALTHY TISSUES FOLLOWING PUNCH BIOPSY. METHYLATION-SPECIFIC POLYMERASE CHAIN REACTION (PCR) AND REAL-TIME QUANTITATIVE PCR METHODS WERE USED TO EXAMINE SMAD4 PROMOTER METHYLATION AND SMAD4 MRNA LEVELS, RESPECTIVELY. THE PERCENTAGE AND INTENSITY OF STAINING OF THE SMAD4 PROTEIN WERE DETERMINED BY IMMUNOHISTOCHEMISTRY. THE PERCENTAGE OF SMAD4 METHYLATION WAS INCREASED IN THE PATIENTS WITH BCC (P = 0.007), CSCC (P = 0.004), AND BSC (P = 0.018) COMPARED TO THE HEALTHY TISSUE. SMAD4 MRNA EXPRESSION WAS DECREASED IN THE PATIENTS WITH BCC (P<0.001), CSCC (P<0.001), AND BSC (P = 0.008). THE STAINING CHARACTERISTIC OF SMAD4 PROTEIN WAS NEGATIVE IN THE CANCER TISSUES OF THE PATIENTS WITH CSCC (P = 0.00). LOWER SMAD4 MRNA LEVELS WERE OBSERVED IN THE POORLY DIFFERENTIATED CSCC PATIENTS (P = 0.001). THE STAINING CHARACTERISTICS OF THE SMAD4 PROTEIN WERE RELATED TO AGE AND CHRONIC SUN EXPOSURE. CONCLUSIONS: HYPERMETHYLATION OF SMAD4 AND REDUCED SMAD4 MRNA EXPRESSION WERE FOUND TO PLAY A ROLE IN THE PATHOGENESIS OF BCC, CSCC, AND BSC. A DECREASE IN SMAD4 PROTEIN EXPRESSION LEVEL WAS OBSERVED ONLY IN CSCC PATIENTS. THIS SUGGESTS THAT EPIGENETIC ALTERATIONS TO THE SMAD4 GENE ARE ASSOCIATED WITH CSCC. TRIAL REGISTRATION: THE NAME OF THE TRIAL REGISTER: SMAD4 METHYLATION AND EXPRESSION LEVELS IN NON-MELANOCYTIC SKIN CANCERS; SMAD4 PROTEIN POSITIVITY. THE REGISTRATION NUMBER: NCT04759261 ( HTTPS://CLINICALTRIALS.GOV/CT2/RESULTS?TERM=NCT04759261 ).	2023	
                                                                                                                                                                                                                                                                                                                        
8  3574  23 IMPACT OF METHIONINE SYNTHASE REDUCTASE POLYMORPHISMS IN CHRONIC MYELOID LEUKEMIA PATIENTS. INTRODUCTION: METABOLISM METHIONINE AND OF FOLATE PLAY A VITAL FUNCTION IN CELLULAR METHYLATION REACTIONS, DNA SYNTHESIS AND EPIGENETIC PROCESS.HOWEVER, POLYMORPHISMS OF METHIONINE HAVE RECEIVED MUCH ATTENTION IN RECENT MEDICAL GENETICS RESEARCH. OBJECTIVES: TO ASCERTAIN WHETHER THE COMMON POLYMORPHISMS OF THE MTRR (METHIONINE SYNTHASE REDUCTASE) A66G GENE COULD PLAY A ROLE IN AFFECTING SUSCEPTIBILITY TO CHRONIC MYELOID LEUKEMIA (CML) IN SUDANESE INDIVIDUALS. METHODS: IN A CASE-CONTROLLED STUDY, WE EXTRACTED AND ANALYZED DNA FROM 200 CML PATIENTS AND 100 HEALTHY CONTROL SUBJECTS BY THE PCR-RFLP METHOD. RESULTS: WE FOUND NO SIGNIFICANT DIFFERENCE IN AGE ORGENDER BETWEEN THE PATIENT GROUP AND CONTROLS. THE MTRR A66G GENOTYPES WERE DISTRIBUTED BASED ON THE HARDY-WEINBERG EQUILIBRIUM (P > 0.05). THE VARIATION OF MTRR A66G WAS LESS SIGNIFICANTLY FREQUENT IN CASES WITH CML (68.35%) THAN IN CONTROLS (87%) (OR = 0.146, 95% CI = 0.162-0.662, P < 0.002). ADDITIONALLY, AG AND GG GENOTYPES AND G ALLELE WERE REDUCING THE CML RISK (ODDS RATIO [OR] = 0.365; 95% CI [0.179-0.746]; P = 0.006; OR = 0.292; 95% CI [0.145-0.590]; P = 0.001 AND OR = 0.146; 95% CI [0.162-0.662]; P = 0.002 AND OR = 2.0; 95% CI [1.3853-2.817]; RESPECTIVELY, (P = 0.000)). CONCLUSIONS: OUR DATA DEMONSTRATED THAT HETEROZYGOUS AND HOMOZYGOUS MUTANT GENOTYPES OF MTRR POLYMORPHISMS WERE ASSOCIATED WITH DECREASED RISK OF DEVELOPING CML IN THE SUDANESE POPULATION.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
9  3291  26 HIGH DIETARY SALT INTAKE IS ASSOCIATED WITH HISTONE METHYLATION IN SALT-SENSITIVE INDIVIDUALS. BACKGROUND: HIGH SALT DIET IS ONE OF THE IMPORTANT RISK FACTORS OF HYPERTENSION AND CARDIOVASCULAR DISEASES. INCREASINGLY STRONG EVIDENCE SUPPORTS EPIGENETIC MECHANISMS' SIGNIFICANT ROLE IN HYPERTENSION. WE AIMED TO EXPLORE ASSOCIATIONS OF EPIGENETICS WITH HIGH SALT DIET, SALT SENSITIVITY (SS), AND SS HYPERTENSION. METHODS: WE CONDUCTED A DIETARY INTERVENTION STUDY OF CHRONIC SALT LOADING IN 339 SUBJECTS FROM NORTHERN CHINA IN 2004 AND DIVIDED THE SUBJECTS INTO DIFFERENT SALT SENSITIVITY PHENOTYPES. A TOTAL OF 152 PARTICIPANTS WERE RANDOMLY SELECTED FROM THE SAME COHORT FOR FOLLOW-UP IN 2018 TO EXPLORE THE EFFECT OF A HIGH-SALT DIET ON SERUM MONOMETHYLATION OF H3K4 (H3K4ME1), HISTONE METHYLTRANSFERASE SET7, AND LYSINE-SPECIFIC DEMETHYLASE 1 (LSD-1). RESULTS: AMONG SS INDIVIDUALS, THE BLOOD PRESSURE (SBP: 140.8 VS. 132.9 MMHG; MAP: 104.2 VS. 98.7 MMHG) AND PREVALENCE OF HYPERTENSION (58.8 VS. 32.8%) WERE SIGNIFICANTLY HIGHER IN HIGH SALT (HS) DIET GROUP THAN IN NORMAL SALT (NS) DIET GROUP, BUT NOT IN THE SALT-RESISTANT (SR) INDIVIDUALS (P > 0.05). SERUM H3K4ME1 LEVEL (287.3 VS. 179.7 PG/ML, P < 0.05) SIGNIFICANTLY INCREASED IN HS GROUP OF SS INDIVIDUALS, BUT NOT IN SR INDIVIDUALS. WE FOUND DAILY SALT INTAKE IN SS INDIVIDUALS WAS POSITIVELY CORRELATED WITH SERUM H3K4ME1 (R = 0.322, P = 0.005) AND SET7 (R = 0.340, P = 0.005) LEVELS AFTER ADJUSTING FOR AGE AND GENDER, BUT NOT WITH LSD-1 (R = -0.137, P = 0.251). IN ADDITION, POSITIVE CORRELATION BETWEEN THE SERUM H3K4ME1 LEVEL AND SET7 LEVEL (R = 0.326, P = 0.007) WAS ALSO FOUND IN SS INDIVIDUALS. THESE CORRELATIONS WERE NOT EVIDENT IN SR INDIVIDUALS. CONCLUSION: OUR STUDY INDICATES THAT HIGH SALT DIET INCREASES THE SERUM H3K4ME1 AND SET7 LEVELS IN SS INDIVIDUALS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
10  4913  28 PAIN MODULATION IN WAG/RIJ EPILEPTIC RATS (A GENETIC MODEL OF ABSENCE EPILEPSY): EFFECTS OF BIOLOGICAL AND PHARMACOLOGICAL HISTONE DEACETYLASE INHIBITORS. EPIGENETIC MECHANISMS ARE INVOLVED IN EPILEPSY AND CHRONIC PAIN DEVELOPMENT. ABOUT THAT, WE STUDIED THE EFFECTS OF THE NATURAL HISTONE DEACETYLASE (HDAC) INHIBITOR SODIUM BUTYRATE (BUT) IN COMPARISON WITH VALPROIC ACID (VPA) IN A VALIDATED GENETIC MODEL OF GENERALIZED ABSENCE EPILEPSY AND EPILEPTOGENESIS. WAG/RIJ RATS WERE TREATED WITH BUT (30 MG/KG), VPA (300 MG/KG), AND THEIR COMBINATION (BUT + VPA) DAILY PER OS FOR 6 MONTHS. RATS WERE SUBJECTED AT RANDALL-SELITTO, VON FREY, HOT PLATE, AND TAIL FLICK TESTS AFTER 1, 3, AND 6 MONTHS OF TREATMENT TO EVALUATE HYPERSENSITIVITY TO NOXIOUS AND NON-NOXIUOUS STIMULI. MOREOVER, PPAR-GAMMA (G3335 1 MG/KG), GABA-B (CGP35348 80 MG/KG), AND OPIOID (NALOXONE 1 MG/KG) RECEPTOR ANTAGONISTS WERE ADMINISTRATED TO INVESTIGATE THE POSSIBLE MECHANISMS INVOLVED IN ANALGESIC ACTIVITY. THE EXPRESSION OF NFKB, GLUTATHIONE REDUCTASE, AND PROTEIN OXIDATION (CARBONYLATION) WAS ALSO EVALUATED BY WESTERN BLOT ANALYSIS. WAG/RIJ RATS SHOWED AN ALTERED PAIN THRESHOLD THROUGHOUT THE STUDY (P < 0.001). BUT AND BUT + VPA TREATMENT REDUCED HYPERSENSITIVITY (P < 0.01). VPA WAS SIGNIFICANTLY EFFECTIVE ONLY AFTER 1 MONTH (P < 0.01). ALL THE THREE RECEPTORS ARE INVOLVED IN BUT + VPA EFFECTS (P < 0.001). BUT AND BUT + VPA DECREASED THE EXPRESSION OF NFKB AND ENHANCED GLUTATHIONE REDUCTASE (P < 0.01); PROTEIN OXIDATION (CARBONYLATION) WAS REDUCED (P < 0.01). NO EFFECT WAS REPORTED WITH VPA. IN CONCLUSION BUT, ALONE OR IN COADMINISTRATION WITH VPA, IS A VALUABLE CANDIDATE FOR MANAGING THE EPILEPSY-RELATED PERSISTENT PAIN.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
11  2746  32 EXPRESSION ANALYSIS OF LONG NON-CODING RNAS AND THEIR TARGET GENES IN MULTIPLE SCLEROSIS PATIENTS. MULTIPLE SCLEROSIS (MS) IS A PROGRESSIVE CHRONIC AUTOIMMUNE-MEDIATED DISEASE. RECENTLY, LONG NON-CODING RNAS (LNCRNAS) ARE CHARACTERIZED TO PARTICIPATE IN THE ADJUSTMENT OF IMMUNE RESPONSES. HERE, WE EVALUATED THE EXPRESSION LEVELS OF GSTT1-AS1 AND IFNG-AS1 LNCRNAS AND THEIR TARGETS (TNF AND IFNG, RESPECTIVELY) IN IRANIAN MS PATIENTS.IN THIS CASE-CONTROL STUDY, 50 RELAPSING-REMITTING MS PATIENTS AND 50 HEALTHY SUBJECTS WERE RECRUITED. EXPRESSIONS OF GSTT1-AS1 AND IFNG-AS1 LNCRNAS, AS WELL AS TNF AND IFNG GENES, WERE ASSESSED IN THEIR PERIPHERAL BLOOD SAMPLES BY SYBR GREEN-BASED REAL-TIME QUANTITATIVE PCR.EXPRESSION LEVELS OF GSTT1-AS1 AND IFNG-AS1 LNCRNAS WERE BOTH SIGNIFICANTLY DOWNREGULATED (P VALUES 0.032 AND 0.013, RESPECTIVELY). ON THE OTHER HAND, THE EXPRESSION OF TNF AND IFNG SHOWED INCREASED LEVELS, HOWEVER, DID NOT REACH STATISTICAL SIGNIFICANCE AFTER OUR ANALYSIS (P > 0.05). SPEARMAN CORRELATION ANALYSIS SHOWED THAT GSTT1-AS1 HAD A SIGNIFICANT POSITIVE MODERATE CORRELATION WITH IFNG-AS1 (R = 0.541, P < 0.0001), IFNG (R = 0.329, P = 0.001), AND TNF (R = 0.204, P = 0.041). ALSO, IFNG-AS1 REVEALED THE SAME CORRELATION WITH IFNG (R = 0.475, P < 0.0001) AS WELL AS TNF (R = 0.399, P < 0.0001). FURTHERMORE, GSTT1-AS1 (R = 0.313, P = 0.027) AND (IFNG R = 0.478, P < 0.0001) DEMONSTRATED A SIGNIFICANT POSITIVE CORRELATION WITH AGE AT ONSET.BRIEFLY, THE CURRENT STUDY PROVIDED FOR THE FIRST TIME DYSREGULATION OF GSTT1-AS1 AND IFNG-AS LNCRNAS NETWORK IN MS, WHICH HIGHLIGHTS THE SIGNIFICANT ROLE OF EPIGENETIC PATHWAYS IN THIS AUTOIMMUNE DISORDER. LARGER SAMPLE SIZE AND FURTHER INVESTIGATION ASSAYS COULD SHED LIGHT ON THE UNDERLYING MECHANISMS IN THIS AREA OF SCIENCE.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
12   525  21 ASSOCIATIONS OF BODY COMPOSITION AND PHYSICAL ACTIVITY LEVEL WITH MULTIPLE MEASURES OF EPIGENETIC AGE ACCELERATION. EPIGENETIC CLOCKS USE DNA METHYLATION TO ESTIMATE BIOLOGICAL AGE. WHETHER BODY COMPOSITION AND PHYSICAL ACTIVITY ARE ASSOCIATED WITH THESE CLOCKS IS NOT WELL UNDERSTOOD. USING BLOOD SAMPLES COLLECTED AT ENROLLMENT (2003-2009) FROM 2,758 WOMEN IN THE US NATIONWIDE SISTER STUDY, WE CALCULATED 6 EPIGENETIC AGE ACCELERATION METRICS USING 4 EPIGENETIC CLOCKS (HANNUM, HORVATH, PHENOAGE, GRIMAGE). RECREATIONAL PHYSICAL ACTIVITY WAS SELF-REPORTED, AND ADIPOSITY MEASURES WERE ASSESSED BY TRAINED MEDICAL EXAMINERS (BODY MASS INDEX (BMI), WAIST-TO-HIP RATIO (WTH), WAIST CIRCUMFERENCE). IN CROSS-SECTIONAL ANALYSES, ALL ADIPOSITY MEASURES WERE ASSOCIATED WITH EPIGENETIC AGE ACCELERATION. THE STRONGEST ASSOCIATION WAS FOR BMI AND PHENOAGE, A MEASURE OF BIOLOGICAL AGE THAT CORRELATES WITH CHRONIC DISEASE (BMI OF >/=35.0 VS. 18.5-24.9, BETA = 3.15 YEARS, 95% CONFIDENCE INTERVAL (CI): 2.41, 3.90; P FOR TREND < 0.001). IN A MUTUAL-ADJUSTMENT MODEL, BOTH WERE ASSOCIATED WITH PHENOAGE AGE ACCELERATION (BMI OF >/=35.0 VS. 18.5-24.9, BETA = 2.69 YEARS, 95% CI: 1.90, 3.48; P FOR TREND < 0.001; QUARTILE 4 VS.1 WTH, BETA = 1.00 YEARS, 95% CI: 0.34, 1.65; P FOR TREND < 0.008). AFTER ADJUSTMENT, PHYSICAL ACTIVITY WAS ASSOCIATED ONLY WITH GRIMAGE (QUARTILE 4 VS. 1, BETA = -0.42 YEARS, 95% CI: -0.70, -0.14; P FOR TREND = 0.001). PHYSICAL ACTIVITY ATTENUATED THE WAIST CIRCUMFERENCE ASSOCIATIONS WITH PHENOAGE AND GRIMAGE. EXCESS ADIPOSITY WAS ASSOCIATED WITH EPIGENETIC AGE ACCELERATION; PHYSICAL ACTIVITY MIGHT ATTENUATE ASSOCIATIONS WITH WAIST CIRCUMFERENCE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
13  4244  28 METHYLATION STATUS OF COX-2 IN BLOOD LEUKOCYTE DNA AND RISK OF GASTRIC CANCER IN A HIGH-RISK CHINESE POPULATION. BACKGROUND: METHYLATION IS A COMMON EPIGENETIC MODIFICATION WHICH MAY PLAY A CRUCIAL ROLE IN CANCER DEVELOPMENT. TO INVESTIGATE THE ASSOCIATION BETWEEN METHYLATION OF COX-2 IN BLOOD LEUKOCYTE DNA AND RISK OF GASTRIC CANCER (GC), A NESTED CASE-CONTROL STUDY WAS CONDUCTED IN LINQU COUNTY, SHANDONG PROVINCE, A HIGH RISK AREA OF GC IN CHINA. METHODS: ASSOCIATION BETWEEN BLOOD LEUKOCYTE DNA METHYLATION OF COX-2 AND RISK OF GC WAS INVESTIGATED IN 133 GCS AND 285 SUPERFICIAL GASTRITIS (SG)/ CHRONIC ATROPHIC GASTRITIS (CAG). THE TEMPORAL TREND OF COX-2 METHYLATION LEVEL DURING GC DEVELOPMENT WAS FURTHER EXPLORED IN 74 PRE-GC AND 95 POST-GC SAMPLES (INCLUDING 31 CASES WITH BOTH PRE- AND POST-GC SAMPLES). IN ADDITION, THE ASSOCIATION OF DNA METHYLATION AND RISK OF PROGRESSION TO GC WAS EVALUATED IN 74 PRE-GC SAMPLES AND THEIR RELEVANT INTESTINAL METAPLASIA (IM)/DYSPLASIA (DYS) CONTROLS. METHYLATION LEVEL WAS DETERMINED BY QUANTITATIVE METHYLATION-SPECIFIC PCR (QMSP). ODDS RATIOS (ORS) AND 95% CONFIDENCE INTERVALS (CIS) WERE CALCULATED BY UNCONDITIONAL LOGISTIC REGRESSION ANALYSIS. RESULTS: THE MEDIANS OF COX-2 METHYLATION LEVELS WERE 2.3% AND 2.2% IN GC CASES AND CONTROLS, RESPECTIVELY. NO SIGNIFICANT ASSOCIATION WAS FOUND BETWEEN COX-2 METHYLATION AND RISK OF GC (OR, 1.15; 95% CI: 0.70-1.88). HOWEVER, THE TEMPORAL TREND ANALYSIS SHOWED THAT COX-2 METHYLATION LEVELS WERE ELEVATED AT 1-4 YEARS AHEAD OF CLINICAL GC DIAGNOSIS COMPARED WITH THE YEAR OF GC DIAGNOSIS (3.0% VS. 2.2%, P=0.01). FURTHER VALIDATION IN 31 GCS WITH BOTH PRE- AND POST-GC SAMPLES INDICATED THAT COX-2 METHYLATION LEVELS WERE SIGNIFICANTLY DECREASED AT THE YEAR OF GC DIAGNOSIS COMPARED WITH PRE-GC SAMPLES (1.5% VS. 2.5%, P=0.02). NO SIGNIFICANT ASSOCIATION BETWEEN COX-2 METHYLATION AND RISK OF PROGRESSION TO GC WAS FOUND IN SUBJECTS WITH IM (OR, 0.50; 95% CI: 0.18-1.42) OR DYS (OR, 0.70; 95% CI: 0.23-2.18). ADDITIONALLY, WE FOUND THAT ELDER PEOPLE HAD INCREASED RISK OF COX-2 HYPERMETHYLATION (OR, 1.55; 95% CI: 1.02-2.36) AND SUBJECTS WHO EVER INFECTED WITH H. PYLORI HAD DECREASED RISK OF COX-2 HYPERMETHYLATION (OR, 0.54; 95% CI: 0.34-0.88). CONCLUSIONS: COX-2 METHYLATION EXISTS IN BLOOD LEUKOCYTE DNA BUT AT A LOW LEVEL. COX-2 METHYLATION LEVELS IN BLOOD LEUKOCYTE DNA MAY CHANGE DURING GC DEVELOPMENT.	2015	
                
14  6832  21 [HYPOMETHYLATION OF TNF-ALPHA GENE PROMOTER IN THE PATIENTS WITH ACUTE-ON-CHRONIC HEPATITIS B LIVER FAILURE]. OBJECTIVE: THE PRESENT STUDY WAS DESIGNED TO INVESTIGATE THE POSSIBLE EPIGENETIC ALTERATION IN THE PROMOTER OF TNF-ALPHA IN THE PATIENTS WITH ACUTE-ON-CHRONIC HEPATITIS B LIVER FAILURE (ACHBLF). METHODS: THE METHYLATION OF TNF-ALPHA PROMOTER IN PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMCS) WAS MEASURED BY METHYLATION SPECIFIC PCR (MSP). THE LEVEL OF SERUM TNF-ALPHA WAS DETERMINED BY ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA). MODEL FOR END-STAGE LIVER DISEASE (MELD) WAS PERFORMED FOR THE EVALUATION OF LIVER FAILURE. RESULTS: THE SERUM LEVEL OF TNF-ALPHA IN PATIENTS WITH ACHBLF(44.9260 +/- 26.48523) WAS HIGHER THAN THAT IN CHB (18.92505 +/- 9.04461) AND HEALTHY CONTROLS (11.9172 +/- 5.04612) (P < 0.05). MOREOVER, THE SERUM TNF-ALPHA LEVEL WAS SIGNIFICANTLY DECREASED IN METHYLATION GROUP AS COMPARED TO UNMETHYLAITON GROUP IN PATIENTS WITH ACHBLF (P < 0.05). MELD WAS NOT SIGNIFICANTLY DIFFERENT BETWEEN METHYLATED AND UNMETHYLATED GROUP OF ACHBLF PATIENTS (P > 0.05). IN ADDITION, THE SERUM LEVEL OF TNF-ALPHA WAS FOUND TO BE POSITIVELY CORRELATED WITH SERUM TOTAL BILIRUBIN (R = 0.891, P < 0.01) AND MELD SCORE (R = 0.792, P < 0.01), BUT TO BE NEGATIVELY CORRELATED WITH PROTHROMBIN ACTIVITY (R = - 0.511, P < 0.05) IN PATIENTS WITH ACHBLF. CONCLUSION: THE TNF-ALPHA METHYLATION PATTEN IS STABLE FOR THE LIVER FAILURE, SUGGESTING THE EFFECT OF ENVIRONMENT ON METHYLATION.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
15  1492  24 DNA HYDROXYMETHYLATION BY TEN-ELEVEN TRANSLOCATION METHYLCYTOSINE DIOXYGENASE 1 AND 3 REGULATES NOCICEPTIVE SENSITIZATION IN A CHRONIC INFLAMMATORY PAIN MODEL. BACKGROUND: TEN-ELEVEN TRANSLOCATION METHYLCYTOSINE DIOXYGENASE CONVERTS 5-METHYLCYTOSINE IN DNA TO 5-HYDROXYMETHYLCYTOSINE, WHICH PLAYS AN IMPORTANT ROLE IN GENE TRANSCRIPTION. ALTHOUGH 5-HYDROXYMETHYLCYTOSINE IS ENRICHED IN MAMMALIAN NEURONS, ITS REGULATORY FUNCTION IN NOCICEPTIVE INFORMATION PROCESSING IS UNKNOWN. METHODS: THE GLOBAL LEVELS OF 5-HYDROXYMETHYLCYTOSINE AND TEN-ELEVEN TRANSLOCATION METHYLCYTOSINE DIOXYGENASE WERE MEASURED IN SPINAL CORDS IN MICE TREATED WITH COMPLETE FREUND'S ADJUVANT. IMMUNOBLOTTING, IMMUNOHISTOCHEMISTRY, AND BEHAVIORAL TESTS WERE USED TO EXPLORE THE DOWNSTREAM TEN-ELEVEN TRANSLOCATION METHYLCYTOSINE DIOXYGENASE-DEPENDENT SIGNALING PATHWAY. RESULTS: COMPLETE FREUND'S ADJUVANT-INDUCED NOCICEPTION INCREASED THE MEAN LEVELS (+/- SD) OF SPINAL 5-HYDROXYMETHYLCYTOSINE (178 +/- 34 VS. 100 +/- 21; P = 0.0019), TEN-ELEVEN TRANSLOCATION METHYLCYTOSINE DIOXYGENASE-1 (0.52 +/- 0.11 VS. 0.36 +/- 0.064; P = 0.0088), AND TEN-ELEVEN TRANSLOCATION METHYLCYTOSINE DIOXYGENASE-3 (0.61 +/- 0.13 VS. 0.39 +/- 0.08; P = 0.0083) COMPARED WITH LEVELS IN CONTROL MICE (N = 6/GROUP). THE KNOCKDOWN OF TEN-ELEVEN TRANSLOCATION METHYLCYTOSINE DIOXYGENASE-1 OR TEN-ELEVEN TRANSLOCATION METHYLCYTOSINE DIOXYGENASE-3 ALLEVIATED THERMAL HYPERALGESIA AND MECHANICAL ALLODYNIA, WHEREAS OVEREXPRESSION CYTOSINETHEM IN NAIVE MICE (N = 6/GROUP). DOWN-REGULATION OF SPINAL TEN-ELEVEN TRANSLOCATION METHYLCYTOSINE DIOXYGENASE-1 AND TEN-ELEVEN TRANSLOCATION METHYLCYTOSINE DIOXYGENASE-3 ALSO REVERSED THE INCREASES IN FOS EXPRESSION (123 +/- 26 VS. 294 +/- 6; P = 0.0031; AND 140 +/- 21 VS. 294 +/- 60; P = 0.0043, RESPECTIVELY; N = 6/GROUP), 5-HYDROXYMETHYLCYTOSINE LEVELS IN THE STAT3 PROMOTER (75 +/- 16.1 VS. 156 +/- 28.9; P = 0.0043; AND 91 +/- 19.1 VS. 156 +/- 28.9; P = 0.0066, RESPECTIVELY; N = 5/GROUP), AND CONSEQUENT STAT3 EXPRESSION (93 +/- 19.6 VS. 137 +/- 27.5; P = 0.035; AND 72 +/- 15.2 VS. 137 +/- 27.5; P = 0.0028, RESPECTIVELY; N = 5/GROUP) IN COMPLETE FREUND'S ADJUVANT-TREATED MICE. CONCLUSIONS: THIS STUDY REVEALS A NOVEL EPIGENETIC MECHANISM FOR TEN-ELEVEN TRANSLOCATION METHYLCYTOSINE DIOXYGENASE-1 AND TEN-ELEVEN TRANSLOCATION METHYLCYTOSINE DIOXYGENASE-3 IN THE MODULATION OF SPINAL NOCICEPTIVE INFORMATION VIA TARGETING OF STAT3.	2017	

16  4253  35 METHYLOME OF HUMAN SKELETAL MUSCLE AFTER ACUTE & CHRONIC RESISTANCE EXERCISE TRAINING, DETRAINING & RETRAINING. DNA METHYLATION IS AN IMPORTANT EPIGENETIC MODIFICATION THAT CAN REGULATE GENE EXPRESSION FOLLOWING ENVIRONMENTAL ENCOUNTERS WITHOUT CHANGES TO THE GENETIC CODE. USING INFINIUM METHYLATIONEPIC BEADCHIP ARRAYS (850,000 CPG SITES) WE ANALYSED FOR THE FIRST TIME, DNA ISOLATED FROM UNTRAINED HUMAN SKELETAL MUSCLE BIOPSIES (VASTUS LATERALIS) AT BASELINE (REST) AND IMMEDIATELY FOLLOWING AN ACUTE (SINGLE) BOUT OF RESISTANCE EXERCISE. IN THE SAME PARTICIPANTS, WE ALSO ANALYSED THE METHYLOME FOLLOWING A PERIOD OF MUSCLE GROWTH (HYPERTROPHY) EVOKED VIA CHRONIC (REPEATED BOUTS-3 SESSIONS/WK) RESISTANCE EXERCISE (RE) (TRAINING) OVER 7-WEEKS, FOLLOWED BY COMPLETE EXERCISE CESSATION FOR 7-WEEKS RETURNING MUSCLE BACK TO BASELINE LEVELS (DETRAINING), AND FINALLY FOLLOWED BY A SUBSEQUENT 7-WEEK PERIOD OF RE-INDUCED HYPERTROPHY (RETRAINING). THESE VALUABLE METHYLOME DATA SETS DESCRIBED IN THE PRESENT MANUSCRIPT AND DEPOSITED IN AN OPEN-ACCESS REPOSITORY CAN NOW BE SHARED AND RE-USED TO ENABLE THE IDENTIFICATION OF EPIGENETICALLY REGULATED GENES/NETWORKS THAT ARE MODIFIED AFTER ACUTE ANABOLIC STIMULI AND HYPERTROPHY, AND FURTHER INVESTIGATE THE PHENOMENON OF EPIGENETIC MEMORY IN SKELETAL MUSCLE.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
17  2893  23 GAS5 RS2067079 AND MIR-137 RS1625579 FUNCTIONAL SNPS AND RISK OF CHRONIC HEPATITIS B VIRUS INFECTION AMONG EGYPTIAN PATIENTS. HEPATITIS B VIRUS (HBV) INFECTION IS A SIGNIFICANT HEALTH ISSUE WORLDWIDE.. WE ATTEMPTED TO FULFILL THE MOLECULAR MECHANISMS OF EPIGENETIC AND GENETIC FACTORS ASSOCIATED WITH CHRONIC HBV (CHBV). EXPRESSION LEVELS OF THE LNCRNA GROWTH ARREST-SPECIFIC 5 (GAS5) AND MIR-137 AND THEIR CORRESPONDING SNPS, RS2067079 (C/T) AND RS1625579 (G/T) WERE ANALYZED IN 117 CHBV PATIENTS AND 120 CONTROLS TO INVESTIGATE THE PROBABLE ASSOCIATION BETWEEN THESE BIOMARKERS AND CHBV PATHOGENESIS IN THE EGYPTIAN POPULATION. SERUM EXPRESSION LEVELS OF GAS5 AND MIR-137 WERE SIGNIFICANTLY DOWN-REGULATED IN CASES VS CONTROLS. REGARDING GAS5 (RS2067079), THE MUTANT TT GENOTYPE SHOWED AN INCREASED RISK OF CHBV (P < 0.001), WHILE THE DOMINANT CC WAS A PROTECTIVE FACTOR (P = 0.004). REGARDING MIR-137 RS1625579, THE MUTANT GENOTYPE TT WAS REPORTED AS A RISK FACTOR FOR CHBV (P < 0.001) AND THE NORMAL GG GENOTYPE WAS A PROTECTIVE FACTOR, P < 0.001. THE SERUM GAS5 WAS SIGNIFICANTLY HIGHER IN THE MUTANT TT GENOTYPE OF GAS5 SNP AS COMPARED TO THE OTHER GENOTYPES (P = 0.007). CONCERNING MIR-137 RS1625579, THE MUTANT TT GENOTYPE WAS SIGNIFICANTLY ASSOCIATED WITH A LOWER SERUM EXPRESSION LEVEL OF MIR-137 (P = 0.018). WE REVEALED THE DYSREGULATED EXPRESSION LEVELS OF GAS5 AND MIR-137 LINKED TO THEIR FUNCTIONING SNPS WERE ASSOCIATED WITH CHBV RISK AND MIGHT ACT AS POTENTIAL THERAPEUTIC TARGETS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
18  1635  30 DOES A SINGLE BOUT OF EXERCISE IMPACTS BDNF, OXIDATIVE STRESS AND EPIGENETIC MARKERS IN SPINAL CORD INJURY PATIENTS? OUR AIM WAS TO EVALUATE THE IMPACT OF A SINGLE BOUT OF EXERCISE, CONSISTING OF A GAIT TRAINING SESSION WITH BODY WEIGHT SUPPORT (BWS), ON HISTONE ACETYLATION STATUS (GLOBAL HISTONE H4 AND H3 ACETYLATION LEVELS), BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) LEVELS, AND OXIDATIVE STRESS MARKERS IN PERIPHERAL BLOOD OF INDIVIDUALS WITH CHRONIC SPINAL CORD INJURY (SCI). WE ALSO SET OUT TO COMPARE THESE RESPONSES WITH THOSE RECORDED AFTER GAIT TRAINING PERFORMED USING A WALKER AND WITH NO BWS. THE SUBJECTS (NEARLY ALL WITH AN INCOMPLETE SPINAL CORD LESION) WERE EACH SUBMITTED TO TWO 60-MINUTE EXPERIMENTAL SESSIONS ON SEPARATE DAYS WITH A 1- WEEK WASH-OUT PERIOD BETWEEN THE INTERVENTIONS. THE ORDER OF THE SESSIONS WAS RANDOMIZED. BLOOD SAMPLES WERE COLLECTED BEFORE AND AFTER EACH EXPERIMENTAL TRIAL FOR MEASUREMENT OF BIOMARKERS. THE HISTONE ACETYLATION STATUS AND BDNF LEVELS REMAINED UNCHANGED AFTER BOTH INTERVENTIONS. AFTER THE TREADMILL TRAINING, THE PARTICIPANTS SHOWED A STRONG INCREASE IN LEVELS OF OXIDATIVE STRESS MARKERS [PLASMA ADVANCED OXIDATION PROTEIN PRODUCTS (AOPPS), NITRITE AND THIOBARBITURIC ACID-REACTIVE SUBSTANCES] WITHOUT CHANGES IN ANTIOXIDANT MEDIATORS. INSTEAD, ELEVATIONS IN AOPP AND NITRITE CONCENTRATIONS, IN ADDITION TO INCREASED LEVELS OF GLUTATHIONE AND CATALASE ACTIVITY, WERE FOUND AFTER THE WALKER TRAINING. A SINGLE BOUT OF GAIT TRAINING, BE IT CONDUCTED ON A TREADMILL WITH BWS OR USING A WALKER WITHOUT BWS, IS NOT ABLE TO ALTER BDNF LEVELS AND HISTONE ACETYLATION STATUS IN SCI PATIENTS. HOWEVER, THESE TRIALS CAN MODULATE OXIDATIVE STRESS PARAMETERS, SEEMINGLY IN A PROTOCOL-DEPENDENT MANNER.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
19  3627  30 INACTIVATION OF LARS2, LOCATED AT THE COMMONLY DELETED REGION 3P21.3, BY BOTH EPIGENETIC AND GENETIC MECHANISMS IN NASOPHARYNGEAL CARCINOMA. ALLELIC LOSS OF CHROMOSOME 3P, INCLUDING THE 3P21.3 REGION, IS FOUND IN 95-100% OF PRIMARY NASOPHARYNGEAL CARCINOMA (NPC) BIOPSIES, SUGGESTING THAT THIS REGION SHOULD HARBOR SOME TUMOR SUPPRESSOR GENES (TSGS) CLOSELY RELATED TO NPC DEVELOPMENT. SEVERAL TSGS LOCATED AT 3P21.3, SUCH AS RASSF1A, LTF AND BLU, HAVE BEEN DEMONSTRATED TO BE INVOLVED IN NPC DEVELOPMENT. LARS2 (LEUCYL-TRNA SYNTHETASE 2, MITOCHONDRIAL) IS ANOTHER GENE LOCATED IN THE CHROMOSOME 3 COMMON ELIMINATED REGION-1 (C3CER1) AT 3P21.3. IN THIS STUDY, WE FOCUSSED ON THE EPIGENETIC AND GENETIC ALTERATIONS OF LARS2 IN NPC. THE MRNA EXPRESSION OF LARS2 WAS DETECTED IN 36 NPC AND 8 CHRONIC NASOPHARYNGITIS (NP) TISSUES BY SEMI-QUANTITATIVE REVERSE TRANSCRIPTION-POLYMERASE CHAIN REACTION (RT-PCR) AND REAL-TIME RT-PCR. SUBSEQUENTLY, THE MUTATION, ALLELIC LOSS, AND METHYLATION STATUS OF LARS2 WERE ANALYSED BY POLYMERASE CHAIN REACTION-SINGLE-STRAND CONFORMATION POLYMORPHISM (PCR-SSCP), HOMOZYGOUS DELETION (HD) ANALYSIS AND METHYLATION-SPECIFIC POLYMERASE CHAIN REACTION IN PRIMARY NPC TISSUES. NO EXPRESSION OR DOWNREGULATION OF LARS2 WAS OBSERVED IN 78% OF PRIMARY NPC TISSUES. NO MUTATIONS, ASSESSED BY PCR-SSCP AND DNA SEQUENCING, WERE FOUND IN THE PROMOTER REGION AND EXON 1 OF LARS2 IN NPC TISSUES, WHEREAS HD WAS DETECTED IN 28% OF NPC SPECIMENS AT THE LARS2 LOCUS. IN ADDITION, HYPERMETHYLATION OF LARS2 WAS FOUND IN 64% OF NPC SAMPLES BUT ONLY IN 12.5% OF NP BIOPSIES. OUR DATA INDICATE THAT INACTIVATION OF LARS2 BY BOTH GENETIC AND EPIGENETIC MECHANISMS MAY BE A COMMON AND IMPORTANT EVENT IN THE CARCINOGENESIS OF NPC.	2009	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
20  4924  25 PARENTAL HYPOXIC EXPOSURE CONFERS OFFSPRING HYPOXIA RESISTANCE IN ZEBRAFISH (DANIO RERIO). PARENTAL INFLUENCES ARE A POTENTIALLY IMPORTANT COMPONENT OF TRANSGENERATIONAL TRANSFER OF PHENOTYPE IN VERTEBRATES. THIS STUDY EXAMINED HOW CHRONIC HYPOXIC EXPOSURE ON ADULT ZEBRAFISH (DANIO RERIO) AFFECTED THE PHENOTYPE OF THEIR OFFSPRING. SEPARATE ADULT POPULATIONS WERE EXPOSED TO HYPOXIA (13.1 KPA O(2)) OR NORMOXIA (21.1 KPA O(2)) FOR PERIODS RANGING FROM 1 TO 12 WEEKS. ADULTS WERE THEN RETURNED TO NORMOXIA AND BRED WITHIN EXPERIMENTAL GROUPS. ADULT FECUNDITY AND EGG CHARACTERISTICS (VOLUME OF EGG, YOLK AND PERIVITELLINE FLUID) WERE ASSESSED. SUBSEQUENTLY, LARVAL BODY LENGTH, TIME TO LOSS OF EQUILIBRIUM IN SEVERE HYPOXIA (~4 KPA O(2)), AND CRITICAL THERMAL MINIMA (CT(MIN)) AND MAXIMA (CT(MAX)) WERE MEASURED AT 6, 9, 12, 15, 18, 21 AND 60 DAYS POST-FERTILIZATION (D.P.F.). ADULT FECUNDITY WAS DEPRESSED BY HYPOXIC EXPOSURE. EGG COMPONENT VOLUMES WERE ALSO DEPRESSED IN ADULTS EXPOSED TO 1-2 WEEKS OF HYPOXIA, BUT RETURNED TO CONTROL LEVELS FOLLOWING LONGER HYPOXIC EXPOSURE. ADULT HYPOXIC EXPOSURES OF >1 WEEK RESULTED IN LONGER BODY LENGTHS IN THEIR LARVAL OFFSPRING. TIME TO LOSS OF EQUILIBRIUM IN SEVERE HYPOXIA (I.E. HYPOXIC RESISTANCE) IN CONTROL LARVAE DECREASED FROM 6 TO 12 D.P.F., REMAINING CONSTANT THEREAFTER. NOTABLY, HYPOXIC RESISTANCE FROM 6 TO 18 D.P.F. WAS ~15% LOWER IN LARVAE WHOSE PARENTS WERE EXPOSED TO JUST 1 WEEK OF CHRONIC HYPOXIA, BUT RESISTANCE WAS SIGNIFICANTLY INCREASED BY ~24-30% IN 6-18 D.P.F. LARVAE FROM ADULTS EXPOSED TO 2, 3 OR 4 WEEKS OF HYPOXIA. CT(MIN) (~10-12 DEGREES C) AND CT(MAX) (~39.5 DEGREES C) WERE UNCHANGED BY PARENTAL HYPOXIC EXPOSURE. THIS STUDY DEMONSTRATES THAT PARENTAL HYPOXIC EXPOSURE IN ADULT ZEBRAFISH HAS PROFOUND EPIGENETIC EFFECTS ON THE MORPHOLOGICAL AND PHYSIOLOGICAL PHENOTYPE OF THEIR OFFSPRING.	2012