1  1692 146 DURATION OF EXPOSURE TO EPIDURAL ANESTHESIA AT DELIVERY, DNA METHYLATION IN UMBILICAL CORD BLOOD AND THEIR ASSOCIATION WITH OFFSPRING ASTHMA IN NON-HISPANIC BLACK WOMEN. EPIDURAL ANESTHESIA IS AN EFFECTIVE PAIN RELIEF MODALITY, WIDELY USED FOR LABOR ANALGESIA. CHILDHOOD ASTHMA IS ONE OF THE COMMONEST CHRONIC MEDICAL ILLNESSES IN THE USA WHICH PLACES A SIGNIFICANT BURDEN ON THE HEALTH-CARE SYSTEM. WE RECENTLY DEMONSTRATED A NEGATIVE ASSOCIATION BETWEEN THE DURATION OF EPIDURAL ANESTHESIA AND THE DEVELOPMENT OF CHILDHOOD ASTHMA; HOWEVER, THE UNDERLYING MOLECULAR MECHANISMS STILL REMAIN UNCLEAR. IN THIS STUDY OF 127 MOTHER-CHILD PAIRS COMPRISED OF 75 NON-HISPANIC BLACK (NHB) AND 52 NON-HISPANIC WHITE (NHW) FROM THE NEWBORN EPIGENETIC STUDY, WE TESTED THE HYPOTHESIS THAT UMBILICAL CORD BLOOD DNA METHYLATION MEDIATES THE ASSOCIATION BETWEEN THE DURATION OF EXPOSURE TO EPIDURAL ANESTHESIA AT DELIVERY AND THE DEVELOPMENT OF CHILDHOOD ASTHMA AND WHETHER THIS DIFFERED BY RACE/ETHNICITY. IN THE MOTHER-CHILD PAIRS OF NHB ANCESTRY, THE DURATION OF EXPOSURE TO EPIDURAL ANESTHESIA WAS ASSOCIATED WITH A MARGINALLY LOWER RISK OF ASTHMA (ODDS RATIO = 0.88, 95% CONFIDENCE INTERVAL = 0.76-1.01) FOR EACH 1-H INCREASE IN EXPOSURE TO EPIDURAL ANESTHESIA. OF THE 20 CPGS IN THE NHB POPULATION SHOWING THE STRONGEST MEDIATION EFFECT, 50% DEMONSTRATED AN AVERAGE MEDIATION PROPORTION OF 52%, WITH DIRECTIONAL CONSISTENCY OF DIRECT AND INDIRECT EFFECTS. THESE TOP 20 CPGS MAPPED TO 21 GENES ENRICHED FOR PATHWAYS ENGAGED IN ANTIGEN PROCESSING, ANTIGEN PRESENTATION, PROTEIN UBIQUITINATION AND REGULATORY NETWORKS RELATED TO THE MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS I COMPLEX AND NUCLEAR FACTOR KAPPA-B (NFKB) COMPLEX. OUR FINDINGS SUGGEST THAT DNA METHYLATION IN IMMUNE-RELATED PATHWAYS CONTRIBUTES TO THE EFFECTS OF THE DURATION OF EXPOSURE TO EPIDURAL ANESTHESIA ON CHILDHOOD ASTHMA RISK IN NHB OFFSPRING.	2023	
                                                                                                                                                                                               
2  5409  29 REGULATION OF ACETYLATION STATES BY NUTRIENTS IN THE INHIBITION OF VASCULAR INFLAMMATION AND ATHEROSCLEROSIS. ATHEROSCLEROSIS (AS) IS A CHRONIC METABOLIC DISORDER AND PRIMARY CAUSE OF CARDIOVASCULAR DISEASES, RESULTING IN SUBSTANTIAL MORBIDITY AND MORTALITY WORLDWIDE. INITIATED BY ENDOTHELIAL CELL STIMULATION, AS IS CHARACTERIZED BY ARTERIAL INFLAMMATION, LIPID DEPOSITION, FOAM CELL FORMATION, AND PLAQUE DEVELOPMENT. NUTRIENTS SUCH AS CAROTENOIDS, POLYPHENOLS, AND VITAMINS CAN PREVENT THE ATHEROSCLEROTIC PROCESS BY MODULATING INFLAMMATION AND METABOLIC DISORDERS THROUGH THE REGULATION OF GENE ACETYLATION STATES MEDIATED WITH HISTONE DEACETYLASES (HDACS). NUTRIENTS CAN REGULATE AS-RELATED EPIGENETIC STATES VIA SIRTUINS (SIRTS) ACTIVATION, SPECIFICALLY SIRT1 AND SIRT3. NUTRIENT-DRIVEN ALTERATIONS IN THE REDOX STATE AND GENE MODULATION IN AS PROGRESSION ARE LINKED TO THEIR PROTEIN DEACETYLATING, ANTI-INFLAMMATORY, AND ANTIOXIDANT PROPERTIES. NUTRIENTS CAN ALSO INHIBIT ADVANCED OXIDATION PROTEIN PRODUCT FORMATION, REDUCING ARTERIAL INTIMA-MEDIA THICKNESS EPIGENETICALLY. NONETHELESS, KNOWLEDGE GAPS REMAIN WHEN IT COMES TO UNDERSTANDING EFFECTIVE AS PREVENTION THROUGH EPIGENETIC REGULATION BY NUTRIENTS. THIS WORK REVIEWS AND CONFIRMS THE UNDERLYING MECHANISMS BY WHICH NUTRIENTS PREVENT ARTERIAL INFLAMMATION AND AS, FOCUSING ON THE EPIGENETIC PATHWAYS THAT MODIFY HISTONES AND NON-HISTONE PROTEINS BY REGULATING REDOX AND ACETYLATION STATES THROUGH HDACS SUCH AS SIRTS. THESE FINDINGS MAY SERVE AS A FOUNDATION FOR DEVELOPING POTENTIAL THERAPEUTIC AGENTS TO PREVENT AS AND CARDIOVASCULAR DISEASES BY EMPLOYING NUTRIENTS BASED ON EPIGENETIC REGULATION.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                  
3  3333  22 HISTONE DEACETYLASE INHIBITORS AND DIABETIC KIDNEY DISEASE. DESPITE RECENT CLINICAL TRIAL ADVANCES AND IMPROVEMENTS IN CLINICAL CARE, KIDNEY DISEASE DUE TO DIABETES REMAINS THE MOST COMMON CAUSE OF CHRONIC KIDNEY FAILURE WORLDWIDE. IN THE SEARCH FOR NEW TREATMENTS, RECENT ATTENTIONS HAVE TURNED TO DRUG REPURPOSING OPPORTUNITIES, INCLUDING STUDY OF THE HISTONE DEACETYLASE (HDAC) INHIBITOR CLASS OF AGENTS. HDACS ARE A GROUP OF ENZYMES THAT REMOVE FUNCTIONAL ACETYL GROUPS FROM HISTONE AND NON-HISTONE PROTEINS AND THEY CAN AFFECT CELLULAR FUNCTION THROUGH BOTH EPIGENETIC AND NON-EPIGENETIC MEANS. OVER THE PAST DECADE, SEVERAL HDAC INHIBITORS HAVE BEEN ADOPTED INTO CLINICAL PRACTICE, PRIMARILY FOR THE TREATMENT OF HEMATOLOGICAL MALIGNANCY, WHEREAS OTHER EXISTING THERAPIES (FOR INSTANCE VALPROATE) HAVE BEEN FOUND TO HAVE HDAC INHIBITORY EFFECTS. HERE WE REVIEW THE CURRENT HDAC INHIBITORS IN THE CLINIC AND UNDER DEVELOPMENT; THE LITERATURE EVIDENCE SUPPORTING THE RENOPROTECTIVE EFFECTS OF HDAC INHIBITORS IN EXPERIMENTAL DIABETIC KIDNEY DISEASE; AND THE ADVERSE EFFECT PROFILES THAT MAY PREVENT EXISTING THERAPIES FROM ENTERING THE CLINIC FOR THIS INDICATION. WHEREAS RECENT RESEARCH EFFORTS HAVE SHED LIGHT ON THE FUNDAMENTAL ACTIONS OF HDACS IN THE DIABETIC KIDNEY, WHETHER THESE EFFORTS WILL TRANSLATE INTO NOVEL THERAPIES FOR PATIENTS WILL REQUIRE MORE SPECIFIC AND BETTER-TOLERATED THERAPIES.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
4  4463  26 MOLECULAR MECHANISMS OF HISTONE DEACETYLASES AND INHIBITORS IN RENAL FIBROSIS PROGRESSION. RENAL FIBROSIS IS A COMMON PROGRESSIVE MANIFESTATION OF CHRONIC KIDNEY DISEASE. THIS PHENOMENON OF SELF-REPAIR IN RESPONSE TO KIDNEY DAMAGE SERIOUSLY AFFECTS THE NORMAL FILTRATION FUNCTION OF THE KIDNEY. YET, THERE ARE NO SPECIFIC TREATMENTS FOR THE CONDITION, WHICH MARKS FIBROSIS AS AN IRREVERSIBLE PATHOLOGICAL SEQUELA. AS SUCH, THERE IS A PRESSING NEED TO IMPROVE OUR UNDERSTANDING OF HOW FIBROSIS DEVELOPS AT THE CELLULAR AND MOLECULAR LEVELS AND EXPLORE SPECIFIC TARGETED THERAPIES FOR THESE PATHOGENIC MECHANISMS. IT IS NOW GENERALLY ACCEPTED THAT RENAL FIBROSIS IS A PATHOLOGICAL TRANSITION MEDIATED BY EXTRACELLULAR MATRIX (ECM) DEPOSITION, ABNORMAL ACTIVATION OF MYOFIBROBLASTS, AND EPITHELIAL-MESENCHYMAL TRANSITION (EMT) OF RENAL TUBULAR EPITHELIAL CELLS UNDER THE REGULATION OF TGF-BETA. HISTONE DEACETYLASES (HDACS) APPEAR TO PLAY AN ESSENTIAL ROLE IN PROMOTING RENAL FIBROSIS THROUGH NON-HISTONE EPIGENETIC MODIFICATIONS. IN THIS REVIEW, WE SUMMARIZE THE MECHANISMS OF RENAL FIBROSIS AND THE SIGNALING PATHWAYS THAT MIGHT BE INVOLVED IN HDACS IN RENAL FIBROSIS, AND THE SPECIFIC MECHANISMS OF ACTION OF VARIOUS HDAC INHIBITORS (HDACI) IN THE ANTI-FIBROTIC PROCESS TO ELUCIDATE HDACI AS A NOVEL THERAPEUTIC TOOL TO SLOW DOWN THE PROGRESSION OF RENAL FIBROSIS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
5  6321  14 THE ROLE AND MECHANISM OF LYSINE METHYLTRANSFERASE AND ARGININE METHYLTRANSFERASE IN KIDNEY DISEASES. METHYLATION CAN OCCUR IN BOTH HISTONES AND NON-HISTONES. KEY LYSINE AND ARGININE METHYLTRANSFERASES UNDER INVESTIGATION FOR RENAL DISEASE TREATMENT INCLUDE ENHANCER OF ZESTE HOMOLOG 2 (EZH2), G9A, DISRUPTOR OF TELOMERIC SILENCING 1-LIKE PROTEIN (DOT1L), AND PROTEIN ARGININE METHYLTRANSFERASES (PRMT) 1 AND 5. RECENT STUDIES HAVE SHOWN THAT METHYLTRANSFERASES EXPRESSION AND ACTIVITY ARE ALSO INCREASED IN SEVERAL ANIMAL MODELS OF KIDNEY INJURY, SUCH AS ACUTE KIDNEY INJURY(AKI), OBSTRUCTIVE NEPHROPATHY, DIABETIC NEPHROPATHY AND LUPUS NEPHRITIS. THE INHIBITION OF MOST METHYLTRANSFERASES CAN ATTENUATE KIDNEY INJURY, WHILE THE ROLE OF METHYLTRANSFERASE IN DIFFERENT ANIMAL MODELS REMAINS CONTROVERSIAL. IN THIS ARTICLE, WE SUMMARIZE THE ROLE AND MECHANISM OF LYSINE METHYLTRANSFERASE AND ARGININE METHYLTRANSFERASE IN VARIOUS KIDNEY DISEASES AND HIGHLIGHT METHYLTRANSFERASE AS A POTENTIAL THERAPEUTIC TARGET FOR KIDNEY DISEASES.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
6  5300  30 PROTEIN METHYLATION IN DIABETIC KIDNEY DISEASE. CHRONIC KIDNEY DISEASE (CKD) IS DEFINED BY PERSISTENT URINE ABERRATIONS, STRUCTURAL ABNORMALITIES, OR IMPAIRED EXCRETORY RENAL FUNCTION. DIABETES IS THE LEADING CAUSE OF CKD. THEIR COMMON PATHOLOGICAL MANIFESTATION IS RENAL FIBROSIS. APPROXIMATELY HALF OF ALL PATIENTS WITH TYPE 2 DIABETES AND ONE-THIRD WITH TYPE 1 DIABETES WILL DEVELOP CKD. HOWEVER, RENAL FIBROSIS MECHANISMS ARE STILL POORLY UNDERSTOOD, ESPECIALLY POST-TRANSCRIPTIONAL AND EPIGENETIC REGULATION. AND AN UNMET NEED REMAINS FOR INNOVATIVE TREATMENT STRATEGIES FOR PREVENTING, ARRESTING, TREATING, AND REVERSING DIABETIC KIDNEY DISEASE (DKD). PEOPLE BELIEVE THAT PROTEIN METHYLATION, INCLUDING HISTONE AND NON-HISTONE, IS AN ESSENTIAL TYPE OF POST-TRANSLATIONAL MODIFICATION (PTM). HOWEVER, PREVALENT REVIEWS MAINLY FOCUS ON THE CAUSES SUCH AS DNA METHYLATION. THIS REVIEW WILL TAKE INSIGHTS INTO THE PROTEIN PART. FURTHERMORE, BY EMPHASIZING THE CLOSE RELATIONSHIP BETWEEN PROTEIN METHYLATION AND DKD, WE WILL SUMMARIZE THE CLINICAL RESEARCH STATUS AND FORESEE THE APPLICATION PROSPECT OF PROTEIN METHYLTRANSFERASE (PMT) INHIBITORS IN DKD TREATMENT. IN A NUTSHELL, OUR REVIEW WILL CONTRIBUTE TO A MORE PROFOUND UNDERSTANDING OF DKD'S MOLECULAR MECHANISM AND INSPIRE PEOPLE TO DIG INTO THIS FIELD.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
7  1954  31 EPIGENETIC AGE ACCELERATION MEDIATES THE RELATIONSHIP BETWEEN NEIGHBORHOOD DEPRIVATION AND PAIN SEVERITY IN ADULTS WITH OR AT RISK FOR KNEE OSTEOARTHRITIS PAIN. AN ESTIMATED 250 MILLION PEOPLE WORLDWIDE SUFFER FROM KNEE OSTEOARTHRITIS (KOA), WITH OLDER ADULTS HAVING GREATER RISK. LIKE OTHER AGE-RELATED DISEASES, RESIDENTS OF HIGH-DEPRIVATION NEIGHBORHOODS EXPERIENCE WORSE KOA PAIN OUTCOMES COMPARED TO THEIR MORE AFFLUENT NEIGHBORS. THE PURPOSE OF THIS STUDY WAS TO EXAMINE THE RELATIONSHIP BETWEEN NEIGHBORHOOD DEPRIVATION AND PAIN SEVERITY IN KOA AND THE INFLUENCE OF EPIGENETIC AGE ACCELERATION (EPAA) ON THAT RELATIONSHIP. THE SAMPLE OF 128 PARTICIPANTS WAS MOSTLY FEMALE (60.9%), APPROXIMATELY HALF NON-HISPANIC BLACK (49.2%), AND HAD A MEAN AGE OF 58 YEARS. SPEARMAN BIVARIATE CORRELATIONS REVEALED THAT PAIN SEVERITY POSITIVELY CORRELATED WITH EPAA (RHO = 0.47, P </= 0.001) AND NEIGHBORHOOD DEPRIVATION (RHO = 0.25, P = 0.004). WE FOUND A POSITIVE SIGNIFICANT RELATIONSHIP BETWEEN NEIGHBORHOOD DEPRIVATION AND EPAA (RHO = 0.47, P </= 0.001). RESULTS INDICATE A MEDIATING RELATIONSHIP BETWEEN NEIGHBORHOOD DEPRIVATION (PREDICTOR), EPAA (MEDIATOR), AND PAIN SEVERITY (OUTCOME VARIABLE). THERE WAS A SIGNIFICANT INDIRECT EFFECT OF NEIGHBORHOOD DEPRIVATION ON PAIN SEVERITY THROUGH EPAA, AS THE MEDIATOR ACCOUNTED FOR A MODERATE PORTION OF THE TOTAL EFFECT, PM = 0.44. EPIGENETIC AGE ACCELERATION MAY ACT AS A MECHANISM THROUGH WHICH NEIGHBORHOOD DEPRIVATION LEADS TO WORSE KOA PAIN OUTCOMES AND MAY PLAY A ROLE IN THE WELL-DOCUMENTED RELATIONSHIP BETWEEN THE NEIGHBORHOOD OF RESIDENCE AND AGE-RELATED DISEASES.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
8  5208  31 PRENATAL STRESS, PREMATURITY, AND ASTHMA. ASTHMA IS THE MOST COMMON CHRONIC DISEASE OF CHILDHOOD, AFFECTING MILLIONS OF CHILDREN IN THE UNITED STATES AND WORLDWIDE. PREMATURITY IS A RISK FACTOR FOR ASTHMA, AND CERTAIN ETHNIC OR RACIAL MINORITIES SUCH AS PUERTO RICANS AND NON-HISPANIC BLACKS ARE DISPROPORTIONATELY AFFECTED BY BOTH PREMATURITY AND ASTHMA. IN THIS REVIEW, WE EXAMINE CURRENT EVIDENCE TO SUPPORT MATERNAL PSYCHOSOCIAL STRESS AS A PUTATIVE LINK BETWEEN PREMATURITY AND ASTHMA, WHILE ALSO FOCUSING ON DISRUPTION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS AND IMMUNE RESPONSES AS POTENTIAL UNDERLYING MECHANISMS FOR STRESS-INDUCED "PREMATURE ASTHMA." PRENATAL STRESS MAY CAUSE NOT ONLY ABNORMALITIES IN THE HPA AXIS BUT ALSO EPIGENETIC CHANGES IN THE FETAL GLUCOCORTICOID RECEPTOR GENE (NR3C1), LEADING TO IMPAIRED GLUCOCORTICOID METABOLISM. MOREOVER, MATERNAL STRESS CAN ALTER FETAL CYTOKINE BALANCE, FAVORING TH2 (ALLERGIC) IMMUNE RESPONSES CHARACTERISTIC OF ATOPIC ASTHMA: INTERLEUKIN 6 (IL-6), WHICH HAS BEEN ASSOCIATED WITH PREMATURE LABOR, CAN PROMOTE TH2 RESPONSES BY STIMULATING PRODUCTION OF IL-4 AND IL-13. GIVEN A LINK AMONG STRESS, PREMATURITY, AND ASTHMA, FUTURE RESEARCH SHOULD INCLUDE BIRTH COHORTS AIMED AT CONFIRMING AND BETTER CHARACTERIZING "PREMATURE ASTHMA." IF CONFIRMED, CLINICAL TRIALS OF PRENATAL MATERNAL STRESS REDUCTION WOULD BE WARRANTED TO REDUCE THE BURDEN OF THESE COMMON COMORBIDITIES. WHILE AWAITING THE RESULTS OF SUCH STUDIES, SOUND POLICIES TO PREVENT DOMESTIC AND COMMUNITY VIOLENCE (EG, FROM FIREARMS) ARE JUSTIFIED, NOT ONLY BY PUBLIC SAFETY BUT ALSO BY GROWING EVIDENCE OF DETRIMENTAL EFFECTS OF VIOLENCE-INDUCED STRESS ON PSYCHIATRIC AND SOMATIC HEALTH.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                   
9  3207  24 HDACI: CELLULAR EFFECTS, OPPORTUNITIES FOR RESTORATIVE DENTISTRY. ACETYLATION OF HISTONE AND NON-HISTONE PROTEINS ALTERS GENE EXPRESSION AND INDUCES A HOST OF CELLULAR EFFECTS. THE ACETYLATION PROCESS IS HOMEOSTATICALLY BALANCED BY TWO GROUPS OF CELLULAR ENZYMES, HISTONE ACETYLTRANSFERASES (HATS) AND HISTONE DEACETYLASES (HDACS). HAT ACTIVITY RELAXES THE STRUCTURE OF THE HUMAN CHROMATIN, RENDERING IT TRANSCRIPTIONALLY ACTIVE, THEREBY INCREASING GENE EXPRESSION. IN CONTRAST, HDAC ACTIVITY LEADS TO GENE SILENCING. THE ENZYMATIC BALANCE CAN BE 'TIPPED' BY HISTONE DEACETYLASE INHIBITORS (HDACI), LEADING TO AN ACCUMULATION OF ACETYLATED PROTEINS, WHICH SUBSEQUENTLY MODIFY CELLULAR PROCESSES INCLUDING STEM CELL DIFFERENTIATION, CELL CYCLE, APOPTOSIS, GENE EXPRESSION, AND ANGIOGENESIS. THERE IS A VARIETY OF NATURAL AND SYNTHETIC HDACI AVAILABLE, AND THEIR PLEIOTROPIC EFFECTS HAVE CONTRIBUTED TO DIVERSE CLINICAL APPLICATIONS, NOT ONLY IN CANCER BUT ALSO IN NON-CANCER AREAS, SUCH AS CHRONIC INFLAMMATORY DISEASE, BONE ENGINEERING, AND NEURODEGENERATIVE DISEASE. INDEED, IT APPEARS THAT HDACI-MODULATED EFFECTS MAY DIFFER BETWEEN 'NORMAL' AND TRANSFORMED CELLS, PARTICULARLY WITH REGARD TO REACTIVE OXYGEN SPECIES ACCUMULATION, APOPTOSIS, PROLIFERATION, AND CELL CYCLE ARREST. THE POTENTIAL BENEFICIAL EFFECTS OF HDACI FOR HEALTH, RESULTING FROM THEIR ABILITY TO REGULATE GLOBAL GENE EXPRESSION BY EPIGENETIC MODIFICATION OF DNA-ASSOCIATED PROTEINS, ALSO OFFER POTENTIAL FOR APPLICATION WITHIN RESTORATIVE DENTISTRY, WHERE THEY MAY PROMOTE DENTAL TISSUE REGENERATION FOLLOWING PULPAL DAMAGE.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
10  6194  32 THE IMPACT OF PROTEIN ACETYLATION/DEACETYLATION ON SYSTEMIC LUPUS ERYTHEMATOSUS. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE IN WHICH THE BODY'S IMMUNE SYSTEM MISTAKENLY ATTACKS HEALTHY CELLS. ALTHOUGH THE EXACT CAUSE OF SLE HAS NOT BEEN IDENTIFIED, IT IS CLEAR THAT BOTH GENETICS AND ENVIRONMENTAL FACTORS TRIGGER THE DISEASE. IDENTICAL TWINS HAVE A 24% CHANCE OF GETTING LUPUS DISEASE IF THE OTHER ONE IS AFFECTED. INTERNAL FACTORS SUCH AS FEMALE GENDER AND SEX HORMONES, THE MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) LOCUS AND OTHER GENETIC POLYMORPHISMS HAVE BEEN SHOWN TO AFFECT SLE, AS WELL AS EXTERNAL, ENVIRONMENTAL INFLUENCES SUCH AS SUNLIGHT EXPOSURE, SMOKING, VITAMIN D DEFICIENCY, AND CERTAIN INFECTIONS. SEVERAL STUDIES HAVE REPORTED AND PROPOSED MULTIPLE ASSOCIATIONS BETWEEN THE ALTERATION OF THE EPIGENOME AND THE PATHOGENESIS OF AUTOIMMUNE DISEASE. EPIGENETIC FACTORS CONTRIBUTING TO SLE INCLUDE MICRORNAS, DNA METHYLATION STATUS, AND THE ACETYLATION/DEACETYLATION OF HISTONE PROTEINS. ADDITIONALLY, THE ACETYLATION OF NON-HISTONE PROTEINS CAN ALSO INFLUENCE CELLULAR FUNCTION. A BETTER UNDERSTANDING OF NON-GENOMIC FACTORS THAT REGULATE SLE WILL PROVIDE INSIGHT INTO THE MECHANISMS THAT INITIATE AND FACILITATE DISEASE AND ALSO CONTRIBUTE TO THE DEVELOPMENT OF NOVEL THERAPEUTICS THAT CAN SPECIFICALLY TARGET PATHOGENIC MOLECULAR PATHWAYS.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
11  4770  30 NUCLEAR RECEPTORS AND EPIGENETIC REGULATION: OPPORTUNITIES FOR NUTRITIONAL TARGETING AND DISEASE PREVENTION. POSTTRANSLATIONAL MODIFICATIONS OF HISTONES, ALTERATIONS IN THE RECRUITMENT AND FUNCTIONS OF NON-HISTONE PROTEINS, DNA METHYLATION, AND CHANGES IN EXPRESSION OF NONCODING RNAS CONTRIBUTE TO CURRENT MODELS OF EPIGENETIC REGULATION. NUCLEAR RECEPTORS (NRS) ARE A GROUP OF TRANSCRIPTION FACTORS THAT, THROUGH LIGAND-BINDING, ACT AS SENSORS TO CHANGES IN NUTRITIONAL, ENVIRONMENTAL, DEVELOPMENTAL, PATHOPHYSIOLOGIC, AND ENDOCRINE CONDITIONS AND DRIVE ADAPTIVE RESPONSES VIA GENE REGULATION. ONE MECHANISM THROUGH WHICH NRS DIRECT GENE EXPRESSION IS THE ASSEMBLY OF TRANSCRIPTION COMPLEXES WITH COFACTORS AND COREGULATORS THAT POSSESS CHROMATIN-MODIFYING PROPERTIES. CHROMATIN MODIFICATIONS CAN BE TRANSIENT OR BECOME PART OF THE CELLULAR "MEMORY" AND CONTRIBUTE TO GENOMIC IMPRINTING. BECAUSE MANY FOOD COMPONENTS BIND TO NRS, THEY CAN ULTIMATELY INFLUENCE TRANSCRIPTION OF GENES ASSOCIATED WITH BIOLOGIC PROCESSES, SUCH AS INFLAMMATION, PROLIFERATION, APOPTOSIS, AND HORMONAL RESPONSE, AND ALTER THE SUSCEPTIBILITY TO CHRONIC DISEASES (E.G., CANCER, DIABETES, OBESITY). THE OBJECTIVE OF THIS REVIEW IS TO HIGHLIGHT HOW NRS INFLUENCE EPIGENETIC REGULATION AND THE RELEVANCE OF DIETARY COMPOUND-NR INTERACTIONS IN HUMAN NUTRITION AND FOR DISEASE PREVENTION AND TREATMENT. IDENTIFYING GENE TARGETS OF UNLIGANDED AND BOUND NRS MAY ASSIST IN THE DEVELOPMENT OF EPIGENETIC MAPS FOR FOOD COMPONENTS AND DIETARY PATTERNS. PROGRESS IN THESE AREAS MAY LEAD TO THE FORMULATION OF DISEASE-PREVENTION MODELS BASED ON EPIGENETIC CONTROL BY INDIVIDUAL OR ASSOCIATIONS OF FOOD LIGANDS OF NRS.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                 
12  3197  22 HDAC INHIBITORS: TARGETS FOR TUMOR THERAPY, IMMUNE MODULATION AND LUNG DISEASES. HISTONE DEACETYLASES (HDACS) ARE ENZYMES THAT PLAY A KEY ROLE IN THE EPIGENETIC REGULATION OF GENE EXPRESSION BY REMODELING CHROMATIN. INHIBITION OF HDACS IS A PROSPECTIVE THERAPEUTIC APPROACH FOR REVERSING EPIGENETIC ALTERATION IN SEVERAL DISEASES. IN PRECLINICAL RESEARCH, NUMEROUS TYPES OF HDAC INHIBITORS WERE DISCOVERED TO EXHIBIT POWERFUL AND SELECTIVE ANTICANCER PROPERTIES. HOWEVER, SUCH RESEARCH HAS REVEALED THAT THE EFFECTS OF HDAC INHIBITORS MAY BE FAR BROADER AND MORE INTRICATE THAN PREVIOUSLY THOUGHT. THIS REVIEW WILL PROVIDE INSIGHT INTO THE HDAC INHIBITORS AND THEIR MECHANISM OF ACTION WITH SPECIAL EMPHASIS ON THE SIGNIFICANCE OF HDAC INHIBITORS IN THE TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND LUNG CANCER. NANOCARRIER-MEDIATED HDAC INHIBITOR DELIVERY AND NEW APPROACHES FOR TARGETING HDACS ARE ALSO DISCUSSED.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
13  2454  19 EPIGENETIC TARGETING OF HISTONE DEACETYLASES IN DIAGNOSTICS AND TREATMENT OF DEPRESSION. DEPRESSION IS A HIGHLY PREVALENT, DISABLING, AND OFTEN CHRONIC ILLNESS THAT PLACES SUBSTANTIAL BURDENS ON PATIENTS, FAMILIES, HEALTHCARE SYSTEMS, AND THE ECONOMY. A SUBSTANTIAL MINORITY OF PATIENTS ARE UNRESPONSIVE TO CURRENT THERAPIES, SO THERE IS AN URGENT NEED TO DEVELOP MORE BROADLY EFFECTIVE, ACCESSIBLE, AND TOLERABLE THERAPIES. PHARMACOLOGICAL REGULATION OF HISTONE ACETYLATION LEVEL HAS BEEN INVESTIGATED AS ONE POTENTIAL CLINICAL STRATEGY. HISTONE ACETYLATION STATUS IS CONSIDERED A POTENTIAL DIAGNOSTIC BIOMARKER FOR DEPRESSION, WHILE INHIBITORS OF HISTONE DEACETYLASES (HDACS) HAVE GARNERED INTEREST AS NOVEL THERAPEUTICS. THIS REVIEW DESCRIBES RECENT ADVANCES IN OUR KNOWLEDGE OF HISTONE ACETYLATION STATUS IN DEPRESSION AND THE THERAPEUTIC POTENTIAL OF HDAC INHIBITORS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
14  2550  23 EPIGENETICS IN OSTEOARTHRITIS: POTENTIAL OF HDAC INHIBITORS AS THERAPEUTICS. OSTEOARTHRITIS (OA) IS THE MOST COMMON JOINT DISEASE AND THE LEADING CAUSE OF CHRONIC DISABILITY IN MIDDLE-AGED AND OLDER POPULATIONS WORLDWIDE. THE DEVELOPMENT OF DISEASE MODIFYING THERAPY FOR OA IS IN ITS INFANCY LARGELY BECAUSE THE REGULATORY MECHANISMS FOR THE MOLECULAR EFFECTORS OF OA PATHOGENESIS ARE POORLY UNDERSTOOD. RECENT STUDIES IDENTIFIED EPIGENETIC EVENTS AS A CRITICAL REGULATOR OF MOLECULAR PLAYERS INVOLVED IN THE INDUCTION AND DEVELOPMENT OF OA. EPIGENETIC MECHANISMS INCLUDE DNA METHYLATION, NON-CODING RNA AND HISTONE MODIFICATIONS. THE AIM OF THIS REVIEW IS TO BRIEFLY HIGHLIGHT THE RECENT ADVANCES IN THE EPIGENETICS OF CARTILAGE AND POTENTIAL OF HDACS (HISTONE DEACETYLASES) INHIBITORS IN THE THERAPEUTIC MANAGEMENT OF OA. WE SUMMARIZE THE RECENT STUDIES UTILIZING HDAC INHIBITORS AS POTENTIAL THERAPEUTICS FOR INHIBITING DISEASE PROGRESSION AND PREVENTING THE CARTILAGE DESTRUCTION IN OA. HDACS CONTROL NORMAL CARTILAGE DEVELOPMENT AND HOMEOSTASIS AND UNDERSTANDING THE IMPACT OF HDACS INHIBITORS ON THE DISEASE PATHOGENESIS IS OF INTEREST BECAUSE OF ITS IMPORTANCE IN AFFECTING OVERALL CARTILAGE HEALTH AND HOMEOSTASIS. THESE FINDINGS ALSO SHED NEW LIGHT ON CARTILAGE DISEASE PATHOPHYSIOLOGY AND PROVIDE SUBSTANTIAL EVIDENCE THAT HDACS MAY BE POTENTIAL NOVEL THERAPEUTIC TARGETS IN OA.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
15  1868  32 EMERGING NEUROTOXIC MECHANISMS IN ENVIRONMENTAL FACTORS-INDUCED NEURODEGENERATION. EXPOSURE TO ENVIRONMENTAL NEUROTOXIC METALS, PESTICIDES AND OTHER CHEMICALS IS INCREASINGLY RECOGNIZED AS A KEY RISK FACTOR IN THE PATHOGENESIS OF CHRONIC NEURODEGENERATIVE DISORDERS SUCH AS PARKINSON'S AND ALZHEIMER'S DISEASES. OXIDATIVE STRESS AND APOPTOSIS HAVE BEEN ACTIVELY INVESTIGATED AS NEUROTOXIC MECHANISMS OVER THE PAST TWO DECADES, RESULTING IN A GREATER UNDERSTANDING OF NEUROTOXIC PROCESSES. NEVERTHELESS, EMERGING EVIDENCE INDICATES THAT EPIGENETIC CHANGES, PROTEIN AGGREGATION AND AUTOPHAGY ARE IMPORTANT CELLULAR AND MOLECULAR CORRELATES OF NEURODEGENERATIVE DISEASES RESULTING FROM CHRONIC NEUROTOXIC CHEMICAL EXPOSURE. DURING THE JOINT CONFERENCE OF THE 13TH INTERNATIONAL NEUROTOXICOLOGY ASSOCIATION AND THE 11TH INTERNATIONAL SYMPOSIUM ON NEUROBEHAVIORAL METHODS AND EFFECTS IN OCCUPATIONAL AND ENVIRONMENTAL HEALTH, THE RECENT PROGRESS MADE TOWARD UNDERSTANDING EPIGENETIC MECHANISMS, PROTEIN AGGREGATION, AUTOPHAGY, AND DEREGULATED KINASE ACTIVATION FOLLOWING NEUROTOXIC CHEMICAL EXPOSURE AND THE RELEVANCE TO NEURODEGENERATIVE CONDITIONS WERE ONE OF THE THEMES OF THE SYMPOSIUM. DR. ANUMANTHA G. KANTHASAMY DESCRIBED THE ROLE OF ACETYLATION OF HISTONES AND NON-HISTONE PROTEINS IN NEUROTOXICANT-INDUCED NEURODEGENERATIVE PROCESSES IN THE NIGRAL DOPAMINERGIC NEURONAL SYSTEM. DR. ARTHI KANTHASAMY ILLUSTRATED THE ROLE OF AUTOPHAGY AS A KEY DETERMINANT IN CELL DEATH EVENTS DURING NEUROTOXIC INSULTS. DR. AJAY RANA PROVIDED EVIDENCE FOR POSTTRANSLATIONAL MODIFICATION OF ALPHA-SYNUCLEIN PROTEIN BY THE MIXED LINAGE KINASE (MLK) GROUP OF KINASES TO INITIATE PROTEIN AGGREGATION IN CELL CULTURE AND ANIMAL MODELS OF PARKINSON'S DISEASE. THESE PRESENTATIONS OUTLINED EMERGING CUTTING EDGE MECHANISMS THAT MIGHT SET THE STAGE FOR FUTURE MECHANISTIC INVESTIGATIONS INTO NEW FRONTIERS OF MOLECULAR NEUROTOXICOLOGY. THIS REPORT SUMMARIZES THE VIEWS OF SYMPOSIUM PARTICIPANTS, WITH EMPHASIS ON FUTURE DIRECTIONS FOR STUDY OF ENVIRONMENTALLY AND OCCUPATIONALLY LINKED CHRONIC NEURODEGENERATIVE DISEASES.	2012	

16  3335  20 HISTONE DEACETYLASE INHIBITORS FOR CARDIOVASCULAR CONDITIONS AND HEALTHY LONGEVITY. HISTONE DEACETYLASE INHIBITORS (HDACI) REGULATE GENE EXPRESSION VIA EPIGENETIC MECHANISMS. ACCUMULATING EVIDENCE SUGGESTS THAT HDACI EXERT ANTIPROLIFERATIVE, ANTIOXIDANT, ANTINEOPLASTIC, AND PROAPOPTOTIC EFFECTS THROUGH EPIGENETIC MECHANISMS. FURTHERMORE, HDACI ALSO EXERT ANTITHROMBOTIC AND ANTIFIBROTIC EFFECTS THROUGH REGULATION OF THROMBOTIC AND FIBROTIC TRANSDUCTION MECHANISMS. ONE OF THE OLDEST HDACI IS VALPROIC ACID, WHICH WAS FIRST SYNTHESISED IN 1882. AFTER THE DISCOVERY OF ITS ANTICONVULSANT PROPERTIES FOR THE TREATMENT OF EPILEPSY, THE USE OF VALPROIC ACID WAS EXTENDED TO OTHER CONDITIONS, SUCH AS BIPOLAR DISORDER AND MIGRAINE. GIVEN THE ACCUMULATING EVIDENCE SUPPORTING THE ROLE OF HDACI IN THE TREATMENT OF MULTIPLE MEDICAL CONDITIONS BEYOND EPILEPSY, THE INTEREST IN NOVEL POTENTIAL INDICATIONS FOR HDACI HAS BEEN RENEWED. CONSIDERING THE PLEOTROPIC EPIGENETIC EFFECTS OF HDACI, FUTURE STUDIES COULD ASSESS THEIR EFFICACY AND SAFETY FOR CARDIOVASCULAR DISEASE PREVENTION AND TREATMENT; TREATMENT OF VENOUS THROMBOSIS, ALZHEIMER'S DISEASE, AUTOIMMUNE AND PROINFLAMMATORY CONDITIONS, CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION, AND PULMONARY ARTERIAL HYPERTENSION; AND AS A COADJUVANT THERAPY FOR CANCER. ADEQUATELY DESIGNED AND POWERED CLINICAL TRIALS ARE REQUIRED TO ASSESS THE EFFICACY AND SAFETY OF HDACI BEFORE THEIR CLINICAL REPURPOSING.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
17  5721  19 SIRTUINS-NOVEL REGULATORS OF EPIGENETIC ALTERATIONS IN AIRWAY INFLAMMATION. HISTONE MODIFICATION IS AN IMPORTANT EPIGENETIC ALTERATION, AND HISTONE DEACETYLASES ARE INVOLVED IN THE OCCURRENCE AND DEVELOPMENT OF VARIOUS RESPIRATORY DISEASES. SIRTUINS (SIRTS) HAVE BEEN DEMONSTRATED TO PLAY AN IMPORTANT ROLE IN THE FORMATION AND PROGRESSION OF CHRONIC INFLAMMATORY DISEASES OF THE RESPIRATORY TRACT. SIRTS PARTICIPATE IN THE REGULATION OF OXIDATIVE STRESS AND INFLAMMATION AND ARE RELATED TO CELL STRUCTURE AND CELLULAR LOCALIZATION. THIS PAPER SUMMARIZES THE ROLES AND MECHANISMS OF SIRTS IN AIRWAY INFLAMMATION AND DESCRIBES THE LATEST RESEARCH ON SIRT MODULATORS, AIMING TO PROVIDE A THEORETICAL BASIS FOR THE STUDY OF POTENTIAL EPIGENETIC ALTERATION-INDUCING DRUG TARGETS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
18  5476  24 RESTORING T CELL TOLERANCE, EXPLORING THE POTENTIAL OF HISTONE DEACETYLASE INHIBITORS FOR THE TREATMENT OF JUVENILE IDIOPATHIC ARTHRITIS. JUVENILE IDIOPATHIC ARTHRITIS (JIA) IS CHARACTERIZED BY A LOSS OF IMMUNE TOLERANCE. HERE, THE BALANCE BETWEEN THE ACTIVITY OF EFFECTOR T (TEFF) CELLS AND REGULATORY T (TREG) CELLS IS DISTURBED RESULTING IN CHRONIC INFLAMMATION IN THE JOINTS. PRESENTLY, THERAPEUTIC STRATEGIES ARE PREDOMINANTLY AIMED AT SUPPRESSING IMMUNE ACTIVATION AND PRO-INFLAMMATORY EFFECTOR MECHANISMS, IGNORING THE OPPORTUNITY TO ALSO PROMOTE TOLERANCE BY BOOSTING THE REGULATORY SIDE OF THE IMMUNE BALANCE. HISTONE DEACETYLASES (HDACS) CAN DEACETYLATE BOTH HISTONE AND NON-HISTONE PROTEINS AND HAVE BEEN DEMONSTRATED TO MODULATE EPIGENETIC REGULATION AS WELL AS CELLULAR SIGNALING IN VARIOUS CELL TYPES. IMPORTANTLY, HDACS ARE POTENT REGULATORS OF BOTH TEFF CELL AND TREG CELL FUNCTION AND CAN THUS BE REGARDED AS ATTRACTIVE THERAPEUTIC TARGETS IN CHRONIC INFLAMMATORY ARTHRITIS. HDAC INHIBITORS (HDACI) HAVE PROVEN THERAPEUTIC POTENTIAL IN THE CANCER FIELD, AND ARE PRESENTLY BEING EXPLORED FOR THEIR POTENTIAL IN THE TREATMENT OF AUTOIMMUNE DISEASES. SPECIFIC HDACI HAVE ALREADY BEEN DEMONSTRATED TO REDUCE THE SECRETION OF PRO-INFLAMMATORY CYTOKINES BY TEFF CELLS, AND PROMOTE TREG NUMBERS AND SUPPRESSIVE CAPACITY IN VITRO AND IN VIVO. IN THIS REVIEW, WE OUTLINE THE ROLE OF THE DIFFERENT CLASSES OF HDACS IN BOTH TEFF CELL AND TREG CELL FUNCTION. FURTHERMORE, WE WILL REVIEW THE EFFECT OF DIFFERENT HDACI ON T CELL TOLERANCE AND EXPLORE THEIR POTENTIAL AS A THERAPEUTIC STRATEGY FOR THE TREATMENT OF OLIGOARTICULAR AND POLYARTICULAR JIA.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                             
19  6103  28 THE EMERGING ROLE OF HDACS: PATHOLOGY AND THERAPEUTIC TARGETS IN DIABETES MELLITUS. DIABETES MELLITUS (DM) IS ONE OF THE PRINCIPAL MANIFESTATIONS OF METABOLIC SYNDROME AND ITS PREVALENCE WITH MODERN LIFESTYLE IS INCREASING INCESSANTLY. CHRONIC HYPERGLYCEMIA CAN INDUCE SEVERAL VASCULAR COMPLICATIONS THAT WERE REFERRED TO BE THE MAJOR CAUSE OF MORBIDITY AND MORTALITY IN DM. ALTHOUGH SEVERAL THERAPEUTIC TARGETS HAVE BEEN IDENTIFIED AND ACCESSED CLINICALLY, THE IMMINENT RISK OF DM AND ITS PREVALENCE ARE STILL ASCENDING. SUBSTANTIAL PIECES OF EVIDENCE REVEALED THAT HISTONE DEACETYLASE (HDAC) ISOFORMS CAN REGULATE VARIOUS MOLECULAR ACTIVITIES IN DM VIA EPIGENETIC AND POST-TRANSLATIONAL REGULATION OF SEVERAL TRANSCRIPTION FACTORS. TO DATE, 18 HDAC ISOFORMS HAVE BEEN IDENTIFIED IN MAMMALS THAT WERE CATEGORIZED INTO FOUR DIFFERENT CLASSES. CLASSES I, II, AND IV ARE REGARDED AS CLASSICAL HDACS, WHICH OPERATE THROUGH A ZN-BASED MECHANISM. IN CONTRAST, CLASS III HDACS OR SIRTUINS DEPEND ON NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD(+)) FOR THEIR MOLECULAR ACTIVITY. FUNCTIONALLY, MOST OF THE HDAC ISOFORMS CAN REGULATE BETA CELL FATE, INSULIN RELEASE, INSULIN EXPRESSION AND SIGNALING, AND GLUCOSE METABOLISM. MOREOVER, THE ROLES OF HDAC MEMBERS HAVE BEEN IMPLICATED IN THE REGULATION OF OXIDATIVE STRESS, INFLAMMATION, APOPTOSIS, FIBROSIS, AND OTHER PATHOLOGICAL EVENTS, WHICH SUBSTANTIALLY CONTRIBUTE TO DIABETES-RELATED VASCULAR DYSFUNCTIONS. THEREFORE, HDACS COULD SERVE AS THE POTENTIAL THERAPEUTIC TARGET IN DM TOWARDS DEVELOPING NOVEL INTERVENTION STRATEGIES. THIS REVIEW SHEDS LIGHT ON THE EMERGING ROLE OF HDACS/ISOFORMS IN DIABETIC PATHOPHYSIOLOGY AND EMPHASIZED THE SCOPE OF THEIR TARGETING IN DM FOR CONSTITUTING NOVEL INTERVENTIONAL STRATEGIES FOR METABOLIC DISORDERS/COMPLICATIONS.	2021	
                                                                                                                                                                                                                                                                                                                
20  1640  21 DOES EPIGENETICS PLAY A ROLE IN HUMAN ASTHMA? ASTHMA AND OTHER ALLERGIC DISEASES ARE AMONG THE MOST PREVALENT CHRONIC NON-COMMUNICABLE DISEASES OF CHILDHOOD. ACCORDING TO THE WORLD HEALTH ORGANIZATION, ASTHMA AFFECTS >7.0 MILLION CHILDREN UNDER 18 IN THE UNITED STATES, WITH AN ECONOMIC BURDEN THAT IS ESTIMATED TO EXCEED THAT OF TUBERCULOSIS AND HIV/AIDS COMBINED. DESPITE MUCH RESEARCH, THE NATURAL HISTORY OF ASTHMA AND ITS PATHOGENESIS ARE STILL IN MANY WAYS ELUSIVE. THIS REVIEW DISCUSSES OUR CURRENT UNDERSTANDING OF THE ROLE EPIGENETIC PROCESSES PLAY IN ASTHMA PATHOGENESIS, FOCUSING ON GENOME-WIDE, POPULATION-BASED STUDIES.	2016