1 4295 154 MICRORNA RESPONSE OF INHALATION EXPOSURE TO HEXANAL IN LUNG TISSUES FROM FISCHER 344 RATS. IN PREVIOUS STUDIES, WE HAVE INVESTIGATED THE RELATIONSHIPS BETWEEN ENVIRONMENTAL CHEMICALS AND HEALTH RISK BASED ON OMICS ANALYSIS AND IDENTIFIED SIGNIFICANT BIOMARKERS. OUR CURRENT FINDINGS INDICATE THAT HEXANAL MAY BE AN IMPORTANT TOXICANT OF THE PULMONARY SYSTEM IN EPIGENETIC INSIGHTS. MICRORNA (MIRNA) IS AN IMPORTANT INDICATOR OF BIOMEDICAL RISK ASSESSMENT AND TARGET IDENTIFICATION. HEXANAL IS HIGHLY DETECTABLE IN THE EXHALED BREATH OF PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND CHRONIC INFLAMMATORY LUNG DISEASE. IN THIS STUDY, WE AIMED TO IDENTIFY HEXANAL-CHARACTERIZED MIRNA-MRNA CORRELATIONS INVOLVED IN LUNG TOXICITY. MICROARRAY ANALYSIS IDENTIFIED 56 MIRNAS THAT COMMONLY CHANGED THEIR EXPRESSION MORE THAN 1.3-FOLD IN THREE DOSES (600, 1000, AND 1500 PPM) WITHIN HEXANAL-EXPOSED FISCHER 344 RATS BY INHALATION, AND 226 GENES WERE PREDICTED TO BE TARGET GENES OF MIRNAS THROUGH TARGETSCAN ANALYSIS. BY INTEGRATING ANALYSES OF MIRNA AND MRNA EXPRESSION PROFILES, WE IDENTIFIED ONE ANTI-CORRELATED TARGET GENE (CHGA; CHROMOGRANIN A; PARATHYROID SECRETORY PROTEIN 1). COMPARATIVE TOXICOGENOMICS DATABASE (CTD) ANALYSIS OF THIS GENE SHOWED THAT CHGA IS INVOLVED WITH SEVERAL DISEASE CATEGORIES SUCH AS CANCER, RESPIRATORY TRACT DISEASE, NERVOUS SYSTEM DISEASE, AND CARDIOVASCULAR DISEASE. FURTHER RESEARCH IS NECESSARY TO ELUCIDATE THE MECHANISMS OF HEXANAL-RESPONSIVE TOXICOLOGIC PATHWAYS AT THE MOLECULAR LEVEL. THIS STUDY CONCLUDES THAT OUR INTEGRATED APPROACH TO MIRNA AND MRNA ENABLES US TO IDENTIFY MOLECULAR EVENTS IN DISEASE DEVELOPMENT INDUCED BY HEXANAL IN AN IN VIVO RAT MODEL. (C) 2015 WILEY PERIODICALS, INC. ENVIRON TOXICOL 31: 1909-1921, 2016. 2016 2 6350 30 THE ROLE OF EPIGENOMICS IN AQUATIC TOXICOLOGY. OVER THE PAST DECADE, THE FIELD OF MOLECULAR BIOLOGY HAS RAPIDLY INCORPORATED EPIGENETIC STUDIES TO EVALUATE ORGANISM-ENVIRONMENT INTERACTIONS THAT CAN RESULT IN CHRONIC EFFECTS. SUCH RESPONSES ARISE FROM EARLY LIFE STAGE STRESS, THE UTILIZATION OF GENETIC INFORMATION OVER AN INDIVIDUAL'S LIFE TIME, AND TRANSGENERATIONAL INHERITANCE. KNOWLEDGE OF EPIGENETIC MECHANISMS PROVIDES THE POTENTIAL FOR A COMPREHENSIVE EVALUATION OF MULTIGENERATIONAL AND HERITABLE EFFECTS FROM ENVIRONMENTAL STRESSORS, SUCH AS CONTAMINANTS. FOCUSED STUDIES HAVE PROVIDED A GREATER UNDERSTANDING OF HOW MANY RESPONSES TO ENVIRONMENTAL STRESSORS ARE DRIVEN BY EPIGENETIC MODIFIERS. WE DISCUSS THE PROMISE OF EPIGENETICS AND SUGGEST FUTURE RESEARCH DIRECTIONS WITHIN THE FIELD OF AQUATIC TOXICOLOGY, WITH A PARTICULAR FOCUS ON THE POTENTIAL FOR IDENTIFYING KEY HERITABLE MARKS WITH CONSEQUENTIAL IMPACTS AT THE ORGANISM AND POPULATION LEVELS. ENVIRON TOXICOL CHEM 2017;36:2565-2573. (C) 2017 SETAC. 2017 3 3844 38 IRREVERSIBLE DOWN-REGULATION OF MIR-375 IN THE LIVERS OF FISCHER 344 RATS AFTER CHRONIC FURAN EXPOSURE. FURAN, A RODENT LIVER CARCINOGEN, IS A CHEMICAL CONTAMINANT FOUND IN A BROAD RANGE OF COOKED FOODS. DESPITE A LACK OF CONCLUSIVE EVIDENCE REGARDING FURAN GENOTOXICITY, SEVERAL REPORTS INDICATE THAT FURAN INDUCES A BROAD RANGE OF NON-GENOTOXIC ALTERATIONS, INCLUDING ABERRANT EXPRESSION MICRORNAS (MIRNAS). IN ORDER TO CLARIFY THE ROLE OF MIRNA ALTERATIONS WITH RESPECT TO FURAN CARCINOGENICITY, WE INVESTIGATED THE EXPRESSION OF SEVERAL CANCER-RELATED MIRNAS IN THE LIVERS OF FISCHER 344 RATS TREATED CONTINUOUSLY WITH FURAN. THE RESULTS DEMONSTRATE THAT FURAN INDUCED MARKED CHANGES IN MIRNA EXPRESSION, CHARACTERIZED BY OVER-EXPRESSION OF HEPATIC MIRNAS, MIR-34A, MIR-93, MIR-200A, MIR-200B, AND MIR-224, AND DOWN-REGULATION OF MIR-375. INTERESTINGLY, A MAJORITY OF FURAN-INDUCED MIRNA CHANGES DIMINISHED AFTER THE CESSATION OF THE FURAN TREATMENT. IN CONTRAST, THE EXPRESSION OF MIR-375 STEADILY DECREASED IN A TIME-DEPENDENT MANNER FOLLOWING FURAN TREATMENT. THE REDUCED EXPRESSION OF MIR-375 WAS ACCOMPANIED BY CYTOSINE DNA HYPERMETHYLATION AND INCREASED LYSINE METHYLATION OF HISTONE H3K9 AND H3K27 AT THE MIR-375 GENE. THE SIGNIFICANCE OF MIR-375 INHIBITION WITH RESPECT TO THE PATHOGENESIS OF FURAN-INDUCED LIVER TOXICITY AND CARCINOGENICITY MAY BE ATTRIBUTED TO ITS ROLE IN THE UP-REGULATION OF YES-ASSOCIATED PROTEIN 1 (YAP1), WHICH IS ONE OF THE PRINCIPAL EVENTS IN THE LIVER CARCINOGENESIS. THE RESULTS OF THE PRESENT STUDY SUPPORT THE HYPOTHESIS OF THE NON-GENOTOXIC MODE OF ACTION OF FURAN AND EMPHASIZE THE IMPORTANCE OF EPIGENETIC ALTERATIONS IN THE MECHANISM OF FURAN HEPATOTOXICITY. 2016 4 354 47 ALTERED LONG NON-CODING RNAS EXPRESSION IN NORMAL AND DISEASED PRIMARY HUMAN AIRWAY EPITHELIAL CELLS EXPOSED TO DIESEL EXHAUST PARTICLES. BACKGROUND: EXPOSURE TO DIESEL EXHAUST PARTICLES (DEP) HAS BEEN LINKED TO A VARIETY OF ADVERSE HEALTH EFFECTS, INCLUDING INCREASED MORBIDITY AND MORTALITY FROM CARDIOVASCULAR DISEASES, CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), METABOLIC SYNDROME, AND LUNG CANCER. THE EPIGENETIC CHANGES CAUSED BY AIR POLLUTION HAVE BEEN ASSOCIATED WITH INCREASED HEALTH RISKS. HOWEVER, THE EXACT MOLECULAR MECHANISMS UNDERLYING THE LNCRNA-MEDIATED PATHOGENESIS INDUCED BY DEP EXPOSURE HAVE NOT BEEN REVEALED. METHODS: THROUGH RNA-SEQUENCING AND INTEGRATIVE ANALYSIS OF BOTH MRNA AND LNCRNA PROFILES, THIS STUDY INVESTIGATED THE ROLE OF LNCRNAS IN ALTERED GENE EXPRESSION IN HEALTHY AND DISEASED HUMAN PRIMARY EPITHELIAL CELLS (NHBE AND DHBE-COPD) EXPOSED TO DEP AT A DOSE OF 30 MUG/CM(2). RESULTS: WE IDENTIFIED 503 AND 563 DIFFERENTIALLY EXPRESSED (DE) MRNAS AND A TOTAL OF 10 AND 14 DE LNCRNAS IN NHBE AND DHBE-COPD CELLS EXPOSED TO DEP, RESPECTIVELY. IN BOTH NHBE AND DHBE-COPD CELLS, ENRICHED CANCER-RELATED PATHWAYS WERE IDENTIFIED AT MRNA LEVEL, AND 3 COMMON LNCRNAS OLMALINC, AC069234.2, AND LINC00665 WERE FOUND TO BE ASSOCIATED WITH CANCER INITIATION AND PROGRESSION. IN ADDITION, WE IDENTIFIED TWO CIS-ACTING (TMEM51-AS1 AND TTN-AS1) AND SEVERAL TRANS-ACTING LNCRNAS (E.G. LINC01278, SNHG29, AC006064.4, TMEM51-AS1) ONLY DIFFERENTIALLY EXPRESSED IN COPD CELLS, WHICH COULD POTENTIALLY PLAY A ROLE IN CARCINOGENESIS AND DETERMINE THEIR SUSCEPTIBILITY TO DEP EXPOSURE. CONCLUSIONS: OVERALL, OUR WORK HIGHLIGHTS THE POTENTIAL IMPORTANCE OF LNCRNAS IN REGULATING DEP-INDUCED GENE EXPRESSION CHANGES ASSOCIATED WITH CARCINOGENESIS, AND INDIVIDUALS SUFFERING FROM COPD ARE LIKELY TO BE MORE VULNERABLE TO THESE ENVIRONMENTAL TRIGGERS. 2023 5 5174 37 PREDICTIVE AND PROGNOSTIC BIOMARKERS OF RESPIRATORY DISEASES DUE TO PARTICULATE MATTER EXPOSURE. AIR POLLUTION IS GETTING SEVERE AND CONCERNS ABOUT ITS TOXICITY EFFECTS ON AIRWAY AND LUNG DISEASE ARE ALSO INCREASING. PARTICULATE MATTER (PM) IS MAJOR COMPONENT OF AIR POLLUTANT. IT CAUSES RESPIRATORY DISEASES, SUCH AS ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, LUNG CANCER, AND SO ON. PM PARTICLES ENTER THE AIRWAY AND LUNG BY INHALATION, CAUSING DAMAGES TO THEM. ESPECIALLY, PM(2.5) CAN PENETRATE INTO THE ALVEOLUS AND PASS TO THE SYSTEMIC CIRCULATION. IT CAN AFFECT THE CARDIOPULMONARY SYSTEM AND CAUSE CARDIOPULMONARY DISORDERS. IN THIS REVIEW, WE FOCUSED ON PM-INDUCING TOXICITY MECHANISMS IN THE FRAMEWORK OF OXIDATIVE STRESS, INFLAMMATION, AND EPIGENETIC CHANGES. WE ALSO REVIEWED ITS CORRELATION WITH RESPIRATORY DISEASES. IN ADDITION, WE REVIEWED BIOMARKERS RELATED TO PM-INDUCED RESPIRATORY DISEASES. THESE BIOMARKERS MIGHT BE USED FOR DISEASE PREDICTION AND EARLY DIAGNOSIS. WITH RECENT TREND OF USING GENOMIC ANALYSIS TOOLS IN THE FIELD OF TOXICOGENOMICS, RESPIRATORY DISEASE BIOMARKERS ASSOCIATED WITH PM WILL BE CONTINUOUSLY INVESTIGATED. EFFECTIVE BIOMARKERS DERIVED FROM EARLIER STUDIES AND FURTHER STUDIES MIGHT BE UTILIZED TO REDUCE RESPIRATORY DISEASES. 2017 6 3802 37 INTERSTITIAL LUNG DISEASE IN CONNECTIVE TISSUE DISEASE: A COMMON LESION WITH HETEROGENEOUS MECHANISMS AND TREATMENT CONSIDERATIONS. CONNECTIVE TISSUE DISEASE (CTD) RELATED INTERSTITIAL LUNG DISEASE (CTD-ILD) IS ONE OF THE LEADING CAUSES OF MORBIDITY AND MORTALITY OF CTD. CLINICALLY, CTD-ILD IS HIGHLY HETEROGENOUS AND INVOLVES RHEUMATIC IMMUNITY AND MULTIPLE MANIFESTATIONS OF RESPIRATORY COMPLICATIONS AFFECTING THE AIRWAYS, VESSELS, LUNG PARENCHYMA, PLEURA, AND RESPIRATORY MUSCLES. THE MAJOR PATHOLOGICAL FEATURES OF CTD ARE CHRONIC INFLAMMATION OF BLOOD VESSELS AND CONNECTIVE TISSUES, WHICH CAN AFFECT ANY ORGAN LEADING TO MULTI-SYSTEM DAMAGE. THE HUMAN LUNG IS PARTICULARLY VULNERABLE TO SUCH DAMAGE BECAUSE ANATOMICALLY IT IS ABUNDANT WITH COLLAGEN AND BLOOD VESSELS. THE COMPLEX ETIOLOGY OF CTD-ILD INCLUDES GENETIC RISKS, EPIGENETIC CHANGES, AND DYSREGULATED IMMUNITY, WHICH INTERACT LEADING TO DISEASE UNDER VARIOUS ILL-DEFINED ENVIRONMENTAL TRIGGERS. CTD-ILD EXHIBITS A BROAD SPECTRA OF CLINICAL MANIFESTATIONS: FROM ASYMPTOMATIC TO SEVERE DYSPNEA; FROM SINGLE-ORGAN RESPIRATORY SYSTEM INVOLVEMENT TO MULTI-ORGAN INVOLVEMENT. THE DISEASE COURSE IS ALSO FEATURED BY REMISSIONS AND RELAPSES. IT CAN RANGE FROM STABILITY OR SLOW PROGRESSION OVER SEVERAL YEARS TO RAPID DETERIORATION. IT CAN ALSO PRESENT CLINICALLY AS HIGHLY PROGRESSIVE FROM THE INITIAL ONSET OF DISEASE. CURRENTLY, THE DIAGNOSIS OF CTD-ILD IS PRIMARILY BASED ON DISTINCT PATHOLOGY SUBTYPE(S), IMAGING, AS WELL AS RELATED CTD AND AUTOANTIBODIES PROFILES. METICULOUS COMPREHENSIVE CLINICAL AND LABORATORY ASSESSMENT TO IMPROVE THE DIAGNOSTIC PROCESS AND MANAGEMENT STRATEGIES ARE MUCH NEEDED. IN THIS REVIEW, WE FOCUS ON EXAMINING THE PATHOGENESIS OF CTD-ILD WITH RESPECT TO GENETICS, ENVIRONMENTAL FACTORS, AND IMMUNOLOGICAL FACTORS. WE ALSO DISCUSS THE CURRENT STATE OF KNOWLEDGE AND ELABORATE ON THE CLINICAL CHARACTERISTICS OF CTD-ILD, DISTINCT PATHOHISTOLOGICAL SUBTYPES, IMAGING FEATURES, AND RELATED AUTOANTIBODIES. FURTHERMORE, WE COMMENT ON THE IDENTIFICATION OF HIGH-RISK PATIENTS AND ADDRESS HOW TO STRATIFY PATIENTS FOR PRECISION MEDICINE MANAGEMENT APPROACHES. 2021 7 1130 35 COMPREHENSIVE ANALYSIS OF TRANSCRIPTOME-WIDE M(6)A METHYLOME IN THE LUNG TISSUES OF MICE WITH ACUTE PARTICULATE MATTER EXPOSURE. PARTICULATE MATTER (PM) EXPOSURE IS IDENTIFIED AS A CRITICAL RISK FACTOR FOR CHRONIC AIRWAY DISEASES, BUT THE BIOLOGICAL MECHANISM OF PM-INDUCED LUNG DAMAGE WAS NOT FULLY ELUCIDATED. THE M(6)A METHYLATION, AS THE MAIN MEMBER OF EPIGENETIC MODIFICATIONS, HAS BEEN FOUND TO PLAY AN IMPORTANT ROLE IN DIFFERENT PULMONARY DISEASES, BUT ITS REGULATORY EFFECT ON PM-INDUCED LUNG DAMAGE REMAINS UNKNOWN. THIS STUDY FIRSTLY USED THE METHYLATED RNA IMMUNOPRECIPITATION SEQUENCING (MERIP-SEQ) TO REVEAL THE M(6)A METHYLOME PROFILES IN THE LUNG TISSUES OF MICE WITH ACUTE PM EXPOSURE. COMPARED WITH THE NORMAL CONTROL, A TOTAL OF 2210 DIFFERENTIALLY HYPERMETHYLATED M(6)A PEAKS WITHIN 1879 GENES AND 1278 DIFFERENTIALLY HYPOMETHYLATED M(6)A PEAKS WITHIN 1153 GENES WERE IDENTIFIED IN THE PM-EXPOSED GROUP. CONJOINT ANALYSIS OF MERIP-SEQ AND HIGH-THROUGHPUT SEQUENCING FOR RNA (RNA-SEQ) DATA PREDICATED SEVERAL POTENTIAL PATHWAYS INCLUDING MAPK SIGNALING PATHWAY, CELL SENESCENCE, AND CELL CYCLE. FOUR M(6)A-MODIFIED DIFFERENTIALLY EXPRESSED GENES (IL-1A, IL-1B, ADAM-8, AND HMOX-1) WERE SELECTED FOR VALIDATION USING MERIP-QPCR. FURTHERMORE, THE M(6)A-MODIFIED IL-1A PROMOTED PM-INDUCED INFLAMMATION VIA REGULATING MAPK SIGNALING PATHWAY. THESE RESULTS PROVIDE A NEW INSIGHT INTO THE BIOLOGICAL MECHANISM OF PM-INDUCED LUNG DAMAGE, AND HELP US TO DEVELOP NEW METHODS TO PREVENT AND TREAT PM-INDUCED ADVERSE HEALTH EFFECTS. 2022 8 3764 43 INTEGRATIVE ANALYSIS OF DNA METHYLATION AND GENE EXPRESSION DATA IDENTIFIES EPAS1 AS A KEY REGULATOR OF COPD. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A COMPLEX DISEASE. GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS ARE KNOWN TO CONTRIBUTE TO COPD RISK AND DISEASE PROGRESSION. THEREFORE WE DEVELOPED A SYSTEMATIC APPROACH TO IDENTIFY KEY REGULATORS OF COPD THAT INTEGRATES GENOME-WIDE DNA METHYLATION, GENE EXPRESSION, AND PHENOTYPE DATA IN LUNG TISSUE FROM COPD AND CONTROL SAMPLES. OUR INTEGRATIVE ANALYSIS IDENTIFIED 126 KEY REGULATORS OF COPD. WE IDENTIFIED EPAS1 AS THE ONLY KEY REGULATOR WHOSE DOWNSTREAM GENES SIGNIFICANTLY OVERLAPPED WITH MULTIPLE GENES SETS ASSOCIATED WITH COPD DISEASE SEVERITY. EPAS1 IS DISTINCT IN COMPARISON WITH OTHER KEY REGULATORS IN TERMS OF METHYLATION PROFILE AND DOWNSTREAM TARGET GENES. GENES PREDICTED TO BE REGULATED BY EPAS1 WERE ENRICHED FOR BIOLOGICAL PROCESSES INCLUDING SIGNALING, CELL COMMUNICATIONS, AND SYSTEM DEVELOPMENT. WE CONFIRMED THAT EPAS1 PROTEIN LEVELS ARE LOWER IN HUMAN COPD LUNG TISSUE COMPARED TO NON-DISEASE CONTROLS AND THAT EPAS1 GENE EXPRESSION IS REDUCED IN MICE CHRONICALLY EXPOSED TO CIGARETTE SMOKE. AS EPAS1 DOWNSTREAM GENES WERE SIGNIFICANTLY ENRICHED FOR HYPOXIA RESPONSIVE GENES IN ENDOTHELIAL CELLS, WE TESTED EPAS1 FUNCTION IN HUMAN ENDOTHELIAL CELLS. EPAS1 KNOCKDOWN BY SIRNA IN ENDOTHELIAL CELLS IMPACTED GENES THAT SIGNIFICANTLY OVERLAPPED WITH EPAS1 DOWNSTREAM GENES IN LUNG TISSUE INCLUDING HYPOXIA RESPONSIVE GENES, AND GENES ASSOCIATED WITH EMPHYSEMA SEVERITY. OUR FIRST INTEGRATIVE ANALYSIS OF GENOME-WIDE DNA METHYLATION AND GENE EXPRESSION PROFILES ILLUSTRATES THAT NOT ONLY DOES DNA METHYLATION PLAY A 'CAUSAL' ROLE IN THE MOLECULAR PATHOPHYSIOLOGY OF COPD, BUT IT CAN BE LEVERAGED TO DIRECTLY IDENTIFY NOVEL KEY MEDIATORS OF THIS PATHOPHYSIOLOGY. 2015 9 5238 30 PROFILING OF H3K27AC REVEALS THE INFLUENCE OF ASTHMA ON THE EPIGENOME OF THE AIRWAY EPITHELIUM. BACKGROUND: ASTHMA IS A CHRONIC AIRWAY DISEASE DRIVEN BY COMPLEX GENETIC-ENVIRONMENTAL INTERACTIONS. THE ROLE OF EPIGENETIC MODIFICATIONS IN BRONCHIAL EPITHELIAL CELLS (BECS) IN ASTHMA IS POORLY UNDERSTOOD. METHODS: WE PILOTED GENOME-WIDE PROFILING OF THE ENHANCER-ASSOCIATED HISTONE MODIFICATION H3K27AC IN BECS FROM PEOPLE WITH ASTHMA (N = 4) AND HEALTHY CONTROLS (N = 3). RESULTS: WE IDENTIFIED N = 4,321 (FDR < 0.05) REGIONS EXHIBITING DIFFERENTIAL H3K27AC ENRICHMENT BETWEEN ASTHMA AND HEALTH, CLUSTERING AT GENES ASSOCIATED PREDOMINATELY WITH EPITHELIAL PROCESSES (EMT). WE IDENTIFIED INITIAL EVIDENCE OF ASTHMA-ASSOCIATED SUPER-ENHANCERS ENCOMPASSING GENES ENCODING TRANSCRIPTION FACTORS (TP63) AND ENZYMES REGULATING LIPID METABOLISM (PTGS1). WE INTEGRATED PUBLISHED DATASETS TO IDENTIFY EPITHELIUM-SPECIFIC TRANSCRIPTION FACTORS ASSOCIATED WITH H3K27AC IN ASTHMA (TP73) AND IDENTIFY INITIAL RELATIONSHIPS BETWEEN ASTHMA-ASSOCIATED CHANGES IN H3K27AC AND TRANSCRIPTIONAL PROFILES. FINALLY, WE INVESTIGATED THE POTENTIAL OF CRISPR-BASED APPROACHES TO FUNCTIONALLY EVALUATE H3K27AC-ASTHMA LANDSCAPE IN VITRO BY IDENTIFYING GUIDE-RNAS CAPABLE OF TARGETING ACETYLATION TO ASTHMA DERS AND INDUCING GENE EXPRESSION (TLR3). CONCLUSION: OUR SMALL PILOT STUDY VALIDATES GENOME-WIDE APPROACHES FOR DECIPHERING EPIGENETIC MECHANISMS UNDERLYING ASTHMA PATHOGENESIS IN THE AIRWAYS. 2020 10 161 32 ABHD4-REGULATING RNA PANEL: NOVEL BIOMARKERS IN ACUTE CORONARY SYNDROME DIAGNOSIS. BACKGROUND: ACUTE CORONARY SYNDROME (ACS) IS A MAJOR CAUSE OF DEATH ALL OVER THE WORLD. STEMI REPRESENTS A TYPE OF MYOCARDIAL INFARCTION WITH ACUTE ST ELEVATION. WE AIMED TO ASSESS THE PREDICTIVE POWER OF POTENTIAL RNA PANEL EXPRESSION IN ACUTE CORONARY SYNDROME. METHOD: WE USED IN SILICO DATA ANALYSIS TO RETRIEVE RNAS RELATED TO GLYCEROPHOSPHOLIPID METABOLISM DYSREGULATION AND SPECIFIC TO ACS THAT RESULTS IN THE SELECTION OF ALPHA/BETA HYDROLASE FOLD DOMAIN4 (ABHD4) MRNA AND ITS EPIGENETIC REGULATORS (FOXF1 ADJACENT NONCODING DEVELOPMENTAL REGULATORY RNA (FENDRR) LNCRNA, MIRNA-221, AND MIRNA-197). WE ASSESSED THE EXPRESSION OF THE SERUM RNA PANEL IN 68 PATIENTS WITH ACS, 21 PATIENTS WITH CHEST PAIN DUE TO NON-CARDIAC CAUSES, AND 21 HEALTHY VOLUNTEERS BY QUANTITATIVE REAL-TIME POLYMERASE CHAIN REACTION. RESULTS: THE STUDY DATA SHOWED SIGNIFICANT DOWN REGULATION IN THE EXPRESSION OF THE SERUM LEVELS OF FENDRR LNCRNA AND MIRNA-221-3P BY 120-FOLD AND 22-FOLD IN UNSTABLE ANGINA (UA) IN COMPARISON WITH HEALTHY VOLUNTEERS, AND BY 8.6-FOLD AND 2-FOLD IN ST SEGMENT ELEVATION MYOCARDIAL INFARCTION (STEMI) PATIENTS VERSUS UA; CONCOMITANT UPREGULATION IN THE EXPRESSION OF ABHD4 MRNA AND MIRNA-197-5P BY 444-FOLD AND 10-FOLD IN UA COMPARED WITH HEALTHY VOLUNTEERS, AND BY 1.54-FOLD AND 4.5-FOLD IN STEMI VERSUS UNSTABLE ANGINA. PERFORMANCE CHARACTERISTICS ANALYSIS SHOWED THAT THE ABHD4-REGULATING RNA PANEL WERE POTENTIAL BIOMARKERS FOR PREDICTION OF ACS. MOREOVER, THERE WAS A SIGNIFICANT ASSOCIATION BETWEEN THE 2 MIRNAS AND ABHD4 MRNA AND THE REGULATING FENDRR LNCRNA. CONCLUSION: COLLECTIVELY, ABHD4 MRNA REGULATING RNA PANEL BASED ON PUTATIVE INTERACTIONS SEEMS TO BE NOVEL NON-INVASIVE BIOMARKERS THAT COULD DETECT ACS EARLY AND STRATIFY SEVERITY OF THE CONDITION THAT COULD IMPROVE HEALTH OUTCOME. 2021 11 6642 35 UNRAVELING THE PATHOGENESIS OF ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE OVERLAP: FOCUSING ON EPIGENETIC MECHANISMS. ASTHMA AND COPD OVERLAP (ACO) IS CHARACTERIZED BY PATIENTS PRESENTING WITH PERSISTENT AIRFLOW LIMITATION AND FEATURES OF BOTH ASTHMA AND COPD. IT IS ASSOCIATED WITH A HIGHER FREQUENCY AND SEVERITY OF EXACERBATIONS, A FASTER LUNG FUNCTION DECLINE, AND A HIGHER HEALTHCARE COST. SYSTEMIC INFLAMMATION IN COPD AND ASTHMA IS DRIVEN BY TYPE 1 T HELPER (TH1) AND TH2 IMMUNE RESPONSES, RESPECTIVELY, BOTH OF WHICH MAY CONTRIBUTE TO AIRWAY REMODELING IN ACO. ACO-RELATED BIOMARKERS CAN BE CLASSIFIED INTO FOUR CATEGORIES: NEUTROPHIL-MEDIATED INFLAMMATION, TH2 CELL RESPONSES, ARACHIDONIC ACID-EICOSANOIDS PATHWAY, AND METABOLITES. GENE-ENVIRONMENT INTERACTIONS ARE KEY CONTRIBUTORS TO THE COMPLEXITY OF ACO AND ARE REGULATED BY EPIGENETIC MECHANISMS, INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS, AND NON-CODING RNAS. THUS, THIS REVIEW FOCUSES ON THE LINK BETWEEN EPIGENETICS AND ACO, AND OUTLINES THE FOLLOWING: (I) INHERITING EPIGENOTYPES WITHOUT CHANGE WITH ENVIRONMENTAL STIMULI, OR EPIGENETIC CHANGES IN RESPONSE TO LONG-TERM EXPOSURE TO INHALED PARTICLES PLUS INTERMITTENT EXPOSURE TO SPECIFIC ALLERGENS; (II) EPIGENETIC MARKERS DISTINGUISHING ACO FROM COPD AND ASTHMA; (III) POTENTIAL EPIGENETIC DRUGS THAT CAN REVERSE OXIDATIVE STRESS, GLUCOCORTICOID INSENSITIVITY, AND CELL INJURY. IMPROVED UNDERSTANDING OF THE EPIGENETIC REGULATIONS HOLDS GREAT VALUE TO GIVE DEEPER INSIGHT INTO THE MECHANISMS, AND CLARIFY THEIR IMPLICATIONS FOR BIOMEDICAL RESEARCH IN ACO. 2022 12 1728 41 DYSREGULATION OF MICRORNAS IN HYPERTROPHY AND OSSIFICATION OF LIGAMENTUM FLAVUM: NEW ADVANCES, CHALLENGES, AND POTENTIAL DIRECTIONS. PATHOLOGICAL CHANGES IN THE LIGAMENTUM FLAVUM (LF) CAN BE DEFINED AS A PROCESS OF CHRONIC PROGRESSIVE ABERRATIONS IN THE NATURE AND STRUCTURE OF LIGAMENTOUS TISSUES CHARACTERIZED BY INCREASED THICKNESS, REDUCED ELASTICITY, LOCAL CALCIFICATION, OR AGGRAVATED OSSIFICATION, WHICH MAY CAUSE SEVERE MYELOPATHY, RADICULOPATHY, OR BOTH. HYPERTROPHY OF LIGAMENTUM FLAVUM (HLF) AND OSSIFICATION OF LIGAMENTUM FLAVUM (OLF) ARE CLINICALLY COMMON ENTITIES. THOUGH ACCUMULATED EVIDENCE HAS INDICATED BOTH GENETIC AND ENVIRONMENTAL FACTORS COULD CONTRIBUTE TO THE INITIATION AND PROGRESSION OF HLF/OLF, THE DEFINITE PATHOGENESIS REMAINS FULLY UNCLEAR. MICRORNAS (MIRNAS), ONE OF THE IMPORTANT EPIGENETIC MODIFICATIONS, ARE SHORT SINGLE-STRANDED RNA MOLECULES THAT REGULATE PROTEIN-CODING GENE EXPRESSION AT POSTTRANSCRIPTIONAL LEVEL, WHICH CAN DISCLOSE THE MECHANISM UNDERLYING DISEASES, IDENTIFY VALUABLE BIOMARKERS, AND EXPLORE POTENTIAL THERAPEUTIC TARGETS. CONSIDERING THAT MIRNAS PLAY A CENTRAL ROLE IN REGULATING GENE EXPRESSION, WE SUMMARIZED CURRENT STUDIES FROM THE POINT OF VIEW OF MIRNA-RELATED MOLECULAR REGULATION NETWORKS IN HLF/OLF. EXPLORATORY STUDIES REVEALED A VARIETY OF MIRNA EXPRESSION PROFILES AND IDENTIFIED A BATTERY OF UPREGULATED AND DOWNREGULATED MIRNAS IN OLF/HLF PATIENTS THROUGH MICROARRAY DATASETS OR TRANSCRIPTOME SEQUENCING. EXPERIMENTAL STUDIES VALIDATED THE ROLES OF SPECIFIC MIRNAS (E.G., MIR-132-3P, MIR-199B-5P IN OLF, MIR-155, AND MIR-21 IN HLF) IN REGULATING FIBROSIS OR OSTEOGENESIS DIFFERENTIATION OF LF CELLS AND RELATED TARGET GENES OR MOLECULAR SIGNALING PATHWAYS. FINALLY, WE DISCUSSED THE PERSPECTIVES AND CHALLENGES OF MIRNA-BASED MOLECULAR MECHANISM, DIAGNOSTIC BIOMARKERS, AND THERAPEUTIC TARGETS OF HLF/OLF. 2021 13 481 38 ARSENIC-INDUCED SUMOYLATION OF MUS81 IS INVOLVED IN REGULATING GENOMIC STABILITY. CHRONIC ENVIRONMENTAL EXPOSURE TO METAL TOXICANTS SUCH AS CHROMIUM AND ARSENIC IS CLOSELY RELATED TO THE DEVELOPMENT OF SEVERAL TYPES OF COMMON CANCERS. GENETIC AND EPIGENETIC STUDIES IN THE PAST DECADE REVEAL THAT POST-TRANSLATIONAL MODIFICATIONS OF HISTONES PLAY A ROLE IN METAL CARCINOGENESIS. HOWEVER, EXACT MOLECULAR MECHANISMS OF METAL CARCINOGENESIS REMAIN TO BE ELUCIDATED. IN THIS STUDY WE FOUND THAT AS(2)O(3), AN ENVIRONMENTAL METAL TOXICANT, UPREGULATED OVERALL MODIFICATIONS OF MANY CELLULAR PROTEINS BY SUMO2/3. SUMOYLATED PROTEINS FROM ARSENIC-TREATED CELLS CONSTITUTIVELY EXPRESSING HIS(6)-SUMO2 WERE PULLED DOWN BY NI-IDA RESIN UNDER DENATURING CONDITIONS. MASS SPECTROMETRIC ANALYSIS REVEALED OVER 100 PROTEINS THAT WERE POTENTIALLY MODIFIED BY SUMOYLATION. MUS81, A DNA ENDONUCLEASE INVOLVED IN HOMOLOGOUS RECOMBINATION REPAIR, WAS AMONG THE IDENTIFIED PROTEINS WHOSE SUMOYLATION WAS INCREASED AFTER TREATMENT WITH AS(2)O(3.) WE FURTHER SHOWED THAT K10 AND K524 WERE 2 LYSINE RESIDUES ESSENTIAL FOR MUS81 SUMOYLATION. MOREOVER, WE DEMONSTRATED THAT MUS81 SUMOYLATION IS IMPORTANT FOR NORMAL MITOTIC CHROMOSOME CONGRESSION AND THAT CELLS EXPRESSING SUMO-RESISTANT MUS81 MUTANTS DISPLAYED COMPROMISED DNA DAMAGE RESPONSES AFTER EXPOSURE TO METAL TOXINS SUCH AS CR(VI) AND ARSENIC. 2017 14 3752 30 INTEGRATED ANALYSIS OF CIRCRNAS AND MRNAS EXPRESSION PROFILE REVEALED THE INVOLVEMENT OF HSA_CIRC_0007919 IN THE PATHOGENESIS OF ULCERATIVE COLITIS. BACKGROUND: ULCERATIVE COLITIS (UC) IS CHARACTERIZED BY CHRONIC INFLAMMATION IN THE COLON AND EPIGENETIC FACTORS UNDERLYING THE OCCURRENCE. CIRCULAR RNAS (CIRCRNAS) HAVE BEEN UNDER INTENSIVE FOCUS DUE TO THE CIRCULAR CONSTRUCT AND GENE-REGULATING FUNCTIONS. HOWEVER, THE CHANGES AND ROLES OF CIRCRNAS IN UC REMAIN UNKNOWN. METHODS: MICROARRAYS WERE USED TO DETECT THE DIFFERENTIALLY EXPRESSED GENES, AND QUANTITATIVE REAL-TIME PCR WAS USED TO IDENTIFY THE CHANGES IN UC. IN SILICO ANALYSES WERE PERFORMED TO PREDICT THE FUNCTIONS OF CIRCRNAS AND MRNAS. IN VITRO, EPITHELIAL CELL LINES WERE STIMULATED BY PRO-INFLAMMATION EFFECTORS TO TEST THE ALTERATIONS IN CIRCRNAS. CIRCRNAS-MICRORNAS-MRNAS NETWORK CLARIFIED THE POTENTIAL MECHANISMS UNDERLYING CIRCRNAS IN UC. THE BINDING SITE BETWEEN HSA_CIRC_0007919 AND MIR-138 OR LET-7A WAS VERIFIED USING DUAL-LUCIFERASE ASSAY. RESULTS: A TOTAL OF 264 SIGNIFICANTLY DYSREGULATED CIRCRNAS AND 1869 DIFFERENTIALLY EXPRESSED MRNAS IN INFLAMED MUCOSA WERE COMPARED WITH THE NON-INFLAMED MUCOSA IN UC. HSA_CIRC_0004662 AND HSA_CIRC_0007919 WERE ALTERED LARGELY IN UC TISSUES. HSA_CIRC_0007919 WAS REDUCED PERSISTENTLY AFTER INFLAMMATORY TREATMENTS, AND IT WAS RELEVANT TO MAYO ENDOSCOPIC SUBSCORES AND THE EXPRESSION OF TIGHT JUNCTION MOLECULES. FINALLY, HSA_CIRC_0007919 COULD HARBOR MIR-138, AND LET-7A TO REGULATE THE TARGETED MRNAS EPC1 AND VIPR1. CONCLUSIONS: SEVERAL CIRCRNAS WERE DIFFERENTIALLY EXPRESSED IN UC. HSA_CIRC_0007919 IS RELATED TO CLINICAL CHARACTERISTICS AND EPITHELIAL INTEGRITY BY BINDING TO HSA-LET-7A, HSA-MIR-138 TO REGULATE THE TARGET GENES. CIRCRNAS, ESPECIALLY HSA_CIRC_0007919, ARE ASSOCIATED WITH THE PATHOGENESIS AND DEVELOPMENT OF UC, WITH POTENTIAL DIAGNOSTIC AND THERAPEUTIC IMPLICATIONS. 2019 15 3482 34 IDENTIFICATION OF CDC5L AS BRIDGE GENE BETWEEN CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND LUNG ADENOCARCINOMA. AIM: THIS STUDY AIMED TO EXPLORE THE GENETIC AND EPIGENETIC SIMILARITIES BETWEEN CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND LUNG ADENOCARCINOMA (LUAD). MATERIALS & METHODS: WE MAINLY USED WEIGHTED CORRELATION NETWORK ANALYSIS, PROTEIN-PROTEIN INTERACTION NETWORK AND PIVOT ANALYSIS TO IDENTIFY HUB MODULES, BRIDGE REGULATORS, BRIDGE GENES AND HUB-DRIVING GENES IN BOTH DISEASES AND CARRIED OUT VERIFYING USING EXTERNAL DATASETS. RESULTS: WE IDENTIFIED EIGHT BRIDGE REGULATORS, 19 KEY MOLECULES IN THE COPD MODEL AND TEN KEY MOLECULES IN THE LUAD MODEL. MOREOVER, WE VALIDATED THAT CDC5L COULD BE A RELIABLE BIOMARKER IN COPD AND MAY REGULATE CELL PROLIFERATION AND METASTASIS IN LUAD VIA PROMOTER METHYLATION. CONCLUSION: OUR RESULTS MIGHT FORM A THEORETICAL FOUNDATION FOR FUTURE STUDY AT AN EPIGENETIC LEVEL. 2020 16 6433 30 THE VINDICATION OF LAMARCK? EPIGENETICS AT THE INTERSECTION OF LAW AND MENTAL HEALTH. RESEARCH ON EPIGENETIC MECHANISMS IS GAINING TRACTION, YET IS POORLY UNDERSTOOD BY CRIMINOLOGISTS AND BEHAVIORAL SCIENTISTS. THE CURRENT OBJECTIVE IS TO REVIEW RELEVANT STUDIES OF INTEREST TO BEHAVIORAL SCIENTISTS WHO STUDY CRIME, AND TO TRANSLATE ADMITTEDLY CHALLENGING SCIENTIFIC INFORMATION INTO TEXT THAT IS DIGESTIBLE TO THE AVERAGE CRIMINOLOGIST. USING SYSTEMATIC SEARCH PROCEDURES THE AUTHORS IDENTIFIED AND REVIEWED 41 STUDIES OF EPIGENETIC MECHANISMS IN PSYCHIATRIC AND BEHAVIORAL PHENOTYPES AMONG HUMANS. FINDINGS REVEALED SIGNIFICANT EPIGENETIC EFFECTS IN AN ASSORTMENT OF GENES THAT ARE IMPLICATED IN THE ETIOLOGY OF DEPRESSION, SUICIDALITY, CALLOUS-UNEMOTIONAL TRAITS, AND CHRONIC AND INTERGENERATIONAL AGGRESSIVE BEHAVIOR. SEVERAL POLYMORPHISMS THAT MEDIATE THE HPA AXIS, NEUROTRANSMISSION, IMMUNE RESPONSE, BRAIN DEVELOPMENT, SEROTONIN SYNTHESIS, AND OTHER PROCESSES WERE FOUND. ALTHOUGH PRESCRIPTIVE KNOWLEDGE BASED ON EPIGENETIC FINDINGS TO DATE IS PREMATURE, EPIGENETICS IS A NEW AND EXCITING SCIENTIFIC FRONTIER NOT TOO DIFFERENT IN SPIRIT FROM LAMARCK'S OBSERVATIONS CENTURIES AGO. 2015 17 5814 25 STRESS AND FELINE HEALTH. IN THE HEALTH SCIENCES, STRESS OFTEN IS DEFINED IN TERMS OF STRESSORS; EVENTS THAT ARE PERCEIVED AS THREATS TO ONE'S PERCEPTION OF CONTROL. FROM THIS PERSPECTIVE, A STRESSOR IS ANYTHING THAT ACTIVATES THE CENTRAL THREAT RESPONSE SYSTEM (CTRS). RECENT RESEARCH SHOWS THAT THE CTRS CAN BE SENSITIZED TO ENVIRONMENTAL EVENTS THROUGH EPIGENETIC MODULATION OF GENE EXPRESSION. WHEN CTRS ACTIVATION IS CHRONIC, HEALTH AND WELFARE MAY BE HARMED. ENVIRONMENTAL MODIFICATION CAN MITIGATE THE HARMFUL EFFECTS OF CHRONIC CTRS ACTIVATION BY REDUCING THE INDIVIDUAL'S PERCEPTION OF THREAT AND INCREASING ITS PERCEPTION OF CONTROL, WHICH IMPROVES HEALTH AND WELFARE. 2020 18 254 35 ADVANCES IN ASTHMA 2015: ACROSS THE LIFESPAN. IN 2015, PROGRESS IN UNDERSTANDING ASTHMA RANGED FROM INSIGHTS TO ASTHMA INCEPTION, EXACERBATIONS, AND SEVERITY TO ADVANCEMENTS THAT WILL IMPROVE DISEASE MANAGEMENT THROUGHOUT THE LIFESPAN. 2015'S INSIGHTS TO ASTHMA INCEPTION INCLUDED HOW THE INTESTINAL MICROBIOME AFFECTS ASTHMA EXPRESSION WITH THE IDENTIFICATION OF SPECIFIC GASTROINTESTINAL BACTERIAL TAXA IN EARLY INFANCY ASSOCIATED WITH LESS ASTHMA RISK, POSSIBLY BY PROMOTING REGULATORY IMMUNE DEVELOPMENT AT A CRITICAL EARLY AGE. THE RELEVANCE OF EPIGENETIC MECHANISMS IN REGULATING ASTHMA-RELATED GENE EXPRESSION WAS STRENGTHENED. PREDICTING AND PREVENTING EXACERBATIONS THROUGHOUT LIFE MIGHT HELP TO REDUCE PROGRESSIVE LUNG FUNCTION DECREASE AND DISEASE SEVERITY IN ADULTHOOD. ALTHOUGH ALLERGY HAS LONG BEEN LINKED TO ASTHMA EXACERBATIONS, A MECHANISM THROUGH WHICH IGE IMPAIRS RHINOVIRUS IMMUNITY AND UNDERLIES ASTHMA EXACERBATIONS WAS DEMONSTRATED AND IMPROVED BY ANTI-IGE THERAPY (OMALIZUMAB). OTHER KEY MOLECULAR PATHWAYS UNDERLYING ASTHMA EXACERBATIONS, SUCH AS CADHERIN-RELATED FAMILY MEMBER 3 (CDHR3) AND OROSOMUCOID LIKE 3 (ORMDL3), WERE ELUCIDATED. NEW ANTI-IL-5 THERAPEUTICS, MEPOLIZUMAB AND RESLIZUMAB, WERE US FOOD AND DRUG ADMINISTRATION APPROVED FOR THE TREATMENT OF PATIENTS WITH SEVERE EOSINOPHILIC ASTHMA. IN A CLINICAL TRIAL THE NOVEL THERAPEUTIC INHALED GATA3 MRNA-SPECIFIC DNAZYME ATTENUATED EARLY- AND LATE-PHASE ALLERGIC RESPONSES TO INHALED ALLERGEN. THESE CURRENT FINDINGS ARE SIGNIFICANT STEPS TOWARD ADDRESSING UNMET NEEDS IN ASTHMA PREVENTION, SEVERITY MODIFICATION, DISPARITIES, AND LIFESPAN OUTCOMES. 2016 19 6815 18 [EVOLUTIONARY ONTOGENETIC ASPECTS OF PATHOGENETICS OF CHRONIC HUMAN DISEASES]. THIS ARTICLE IS A REVIEW OF SCIENTIFIC PUBLICATIONS, IN WHICH ISSUES OF PATHOGENETICS OF MULTIFACTORIAL DISEASES (MFDS) ARE CONSIDERED FROM THE VIEWPOINT OF EVOLUTION AND ONTOGENY. CONCEPTS EXPLAINING SIGNIFICANCE OF EVOLUTIONARY PROCESSES IN THE FORMATION OF GENETIC ARCHITECTURE OF HUMAN CHRONIC DISEASES ("THRIFTY" GENOMES AND PHENOTYPES, "DRIFTING GENES," DECANALIZATION) ARE ANALYZED. THE ROLES OF NATURAL SELECTION AND GENETIC DRIFT IN THE FORMATION OF HEREDITARY DIVERSITY OF GENES FOR SUSCEPTIBILITY TO MFDS ARE CONSIDERED. THE MODERN CONCEPT OF DISEASE ONTOGENY (SOMATIC MOSAICISM, LOSS OFHETEROZYGOSITY, PARADOMINANT INHERITANCE, EPIGENETIC VARIABILITY) IS DISCUSSED. IT IS DEMONSTRATED THAT THE EVOLUTIONARY AND ONTOGENETIC APPROACHES TO ANALYSIS OF GENIMUC AND OTHER "-OMIC" DATA ARE ESSENTIAL FOR UNDERSTANDING THE BIOLOGY OF DISEASES. 2011 20 1 16 ON DECEMBER 5, 2017, THE NATIONAL ACADEMIES OF SCIENCES, ENGINEERING, AND MEDICINE HOSTED A PUBLIC WORKSHOP TITLED NUTRIGENOMICS AND THE FUTURE OF NUTRITION IN WASHINGTON, DC, TO REVIEW CURRENT KNOWLEDGE IN THE FIELD OF NUTRIGENOMICS AS IT RELATES TO NUTRITION. WORKSHOP PARTICIPANTS EXPLORED THE INFLUENCE OF GENETIC AND EPIGENETIC EXPRESSION ON NUTRITIONAL STATUS AND THE POTENTIAL IMPACT OF PERSONALIZED NUTRITION ON HEALTH MAINTENANCE AND CHRONIC DISEASE PREVENTION. THIS PUBLICATION SUMMARIZES THE PRESENTATIONS AND DISCUSSIONS FROM THE WORKSHOP. 2018