1 6407 108 THE SEVERITY OF SARS-COV-2 INFECTION IS DICTATED BY HOST FACTORS? EPIGENETIC PERSPECTIVES. THE EMERGENCE OF COVID-19, CAUSED BY SARS-COV-2 POSES A SIGNIFICANT THREAT TO HUMANS AS IT IS HIGHLY CONTAGIOUS WITH INCREASING MORTALITY. THERE EXISTS A HIGH DEGREE OF HETEROGENEITY IN THE MORTALITY RATES OF COVID-19 ACROSS THE GLOBE. THERE ARE MULTIPLE SPECULATIONS ON THE VARYING DEGREE OF MORTALITY. STILL, ALL THE CLINICAL REPORTS HAVE INDICATED THAT PREEXISTING CHRONIC DISEASES LIKE HYPERTENSION, DIABETES, CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), KIDNEY DISORDERS, AND CARDIOVASCULAR DISEASES ARE ASSOCIATED WITH THE INCREASED RISK FOR HIGH MORTALITY IN SARS-COV-2 INFECTED PATIENTS. IT IS WORTH NOTING THAT HOST FACTORS, MAINLY EPIGENETIC FACTORS COULD PLAY A SIGNIFICANT ROLE IN DECIDING THE OUTCOME OF COVID-19 DISEASES. OVER THE RECENT YEARS, IT IS EVIDENT THAT CHRONIC DISEASES ARE DEVELOPED DUE TO ALTERED EPIGENOME THAT INCLUDES A SELECTIVE LOSS/GAIN OF DNA AND HISTONE METHYLATION ON THE CHROMATIN OF THE CELLS. SINCE, THERE IS A HIGH POSITIVE CORRELATION BETWEEN CHRONIC DISEASES AND ELEVATED MORTALITY DUE TO SARS-COV-2, IN THIS REVIEW; WE DISCUSS THE OVERALL PICTURE OF THE ABERRANT EPIGENOME MAP IN VARYING CHRONIC AILMENTS AND ITS IMPLICATIONS IN COVID-19 DISEASE SEVERITY AND HIGH MORTALITY. 2021 2 5618 33 SARS-COV-2 INTERACTION WITH HUMAN DNA METHYL TRANSFERASE 1: A POTENTIAL RISK FOR INCREASING THE INCIDENCE OF LATER CHRONIC DISEASES IN THE SURVIVED PATIENTS. CURRENTLY, THE COVID-19 PANDEMIC IS THE MOST DISCUSSED SUBJECT IN MEDICAL RESEARCHES WORLDWIDE. AS THE KNOWLEDGE IS EXPANDED ABOUT THE DISEASE, MORE HYPOTHESES BECOME CREATED. A RECENT STUDY ON THE VIRAL PROTEIN INTERACTION MAP REVEALED THAT SARS-COV-2 OPEN READING FRAME 8 (ORF8) INTERACTS WITH HUMAN DNA METHYL TRANSFERASE1 (DNMT1), AN ACTIVE EPIGENETIC AGENT IN DNA METHYLATION. MOREOVER, DNMT1 IS A CONTRIBUTOR TO A VARIETY OF CHRONIC DISEASES WHICH COULD CAUSE SOME EPIGENETIC DYSREGULATION IN INFECTED CELLS, ESPECIALLY LEUKOCYTES, PANCREATIC BETA, AND ENDOTHELIAL CELLS. REGARDING THE FACT THAT EPIGENETIC ALTERATIONS HAVE A PARTIAL, BUT NOT COMPLETELY REVERSIBLE PHENOMENA, IT RAISES THE QUESTION THAT IF THIS INTERACTION MAY CAUSE LONG-TERM COMPLICATIONS SUCH AS DIABETES, ATHEROSCLEROSIS, CANCER, AND AUTOIMMUNE DISEASES. ACCORDINGLY, LONG FOLLOW-UP STUDIES ON THE RECOVERED PATIENTS FROM COVID-19 ARE RECOMMENDED. 2022 3 1207 37 COVID-19 AND CROSSTALK WITH THE HALLMARKS OF AGING. WITHIN THE PAST SEVERAL DECADES, THE EMERGENCE OF NEW VIRAL DISEASES WITH SEVERE HEALTH COMPLICATIONS AND MORTALITY IS EVIDENCE OF AN AGE-DEPENDENT, COMPROMISED BODILY RESPONSE TO ABRUPT STRESS WITH CONCOMITANTLY REDUCED IMMUNITY. THE NEW SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2, SARS-COV-2, CAUSES CORONAVIRUS DISEASE 2019 (COVID-19). IT HAS INCREASED MORBIDITY AND MORTALITY IN PERSONS WITH UNDERLYING CHRONIC DISEASES AND THOSE WITH A COMPROMISED IMMUNE SYSTEM REGARDLESS OF AGE AND IN OLDER ADULTS WHO ARE MORE LIKELY TO HAVE THESE CONDITIONS. WHILE SARS-COV-2 IS HIGHLY VIRULENT, THERE IS VARIABILITY IN THE SEVERITY OF THE DISEASE AND ITS COMPLICATIONS IN HUMANS. SEVERE PNEUMONIA, ACUTE RESPIRATORY DISTRESS SYNDROME, LUNG FIBROSIS, CARDIOVASCULAR EVENTS, ACUTE KIDNEY INJURY, STROKE, HOSPITALIZATION, AND MORTALITY HAVE BEEN REPORTED THAT RESULT FROM PATHOGEN-HOST INTERACTIONS. HALLMARKS OF AGING, INTERACTING WITH ONE ANOTHER, HAVE BEEN PROPOSED TO INFLUENCE HEALTH SPAN IN OLDER ADULTS, POSSIBLY VIA MECHANISMS REGULATING THE IMMUNE SYSTEM. HERE, WE REVIEW THE POTENTIAL ROLES OF THE HALLMARKS OF AGING, COUPLED WITH HOST-CORONAVIRUS INTERACTIONS. OF THESE HALLMARKS, WE FOCUSED ON THOSE THAT DIRECTLY OR INDIRECTLY INTERACT WITH VIRAL INFECTIONS, INCLUDING IMMUNOSENESCENCE, INFLAMMATION AND INFLAMMASOMES, ADAPTIVE IMMUNOSENESCENCE, GENOMIC INSTABILITY, MITOCHONDRIAL DYSFUNCTION, EPIGENETIC ALTERATIONS, TELOMERE ATTRITION, AND IMPAIRED AUTOPHAGY. THESE HALLMARKS LIKELY CONTRIBUTE TO THE INCREASED PATHOPHYSIOLOGICAL RESPONSES TO SARS-COV-2 AMONG OLDER ADULTS AND MAY PLAY ROLES AS AN ADDITIVE RISK OF ACCELERATED BIOLOGICAL AGING EVEN AFTER RECOVERY. WE ALSO BRIEFLY DISCUSS THE ROLE OF ANTIAGING DRUG CANDIDATES THAT REQUIRE PARAMOUNT ATTENTION IN COVID-19 RESEARCH. 2020 4 5135 30 POTENTIAL MECHANISMS FOR LUNG FIBROSIS ASSOCIATED WITH COVID-19 INFECTION. PULMONARY FIBROSIS IS A SEQUELAE OF SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) INFECTION THAT CURRENTLY LACKS EFFECTIVE PREVENTATIVE OR THERAPEUTIC MEASURES. POST-VIRAL LUNG FIBROSIS DUE TO SARS-COV-2 HAS BEEN SHOWN TO BE PROGRESSIVE ON SELECTED PATIENTS USING IMAGING STUDIES. PERSISTENT INFILTRATION OF MACROPHAGES AND MONOCYTES, A MAIN FEATURE OF SARS-COV-2 PULMONARY FIBROSIS, AND LONG-LIVED CIRCULATING INFLAMMATORY MONOCYTES MIGHT BE DRIVING FACTORS PROMOTING THE PROFIBROTIC MILIEU IN THE LUNG. THE UPSTREAM SIGNAL(S) THAT REGULATES THE PRESENCE OF THESE IMMUNE CELLS (DESPITE COMPLETE VIRAL CLEARANCE) REMAINS TO BE EXPLORED. CURRENT DATA INDICATE THAT MUCH OF THE STIMULATING SIGNALS ARE LOCALIZED IN THE LUNGS. HOWEVER, AN ONGOING LOW-GRADE SYSTEMIC INFLAMMATION IN LONG CORONAVIRUS DISEASE 2019 (COVID-19) SYMPTOMS SUGGESTS THAT CERTAIN NON-PULMONARY REGULATORS SUCH AS EPIGENETIC CHANGES IN HEMATOPOIETIC STEM CELLS MIGHT BE CRITICAL TO THE CHRONIC INFLAMMATORY RESPONSE. SINCE NEARLY ONE-THIRD OF THE WORLD POPULATION HAVE BEEN INFECTED, A TIMELY UNDERSTANDING OF THE UNDERLYING PATHOGENESIS LEADING TO TISSUE REMODELING IS REQUIRED. HEREIN, WE REVIEW THE POTENTIAL PATHOGENIC MECHANISMS DRIVING LUNG FIBROSIS FOLLOWING SARS-COV-2 INFECTION BASED UPON AVAILABLE STUDIES AND OUR PRELIMINARY FINDINGS (GRAPHICAL ABSTRACT). 2023 5 727 33 CAN VITAMINS, AS EPIGENETIC MODIFIERS, ENHANCE IMMUNITY IN COVID-19 PATIENTS WITH NON-COMMUNICABLE DISEASE? PURPOSE OF REVIEW: THE HIGHLY INFECTIOUS TRANSMISSIBLE DISEASE, THE NOVEL SARS-COV-2, CAUSING THE CORONAVIRUS DISEASE (COVID-19), HAS A MEDIAN INCUBATION TIME OF 5 TO 15 DAYS. THE SYMPTOMS VARY FROM PERSON TO PERSON AND MANY ARE "HIDDEN CARRIERS." FEW PEOPLE EXPERIENCE IMMEDIATE REACTION AND EVEN DEATH WITHIN 48 H OF INFECTION. HOWEVER, MANY SHOW MILD TO CHRONIC SYMPTOMS AND RECOVER. NEVERTHELESS, THE DEATH RATE DUE TO COVID-19 TRANSMISSION IS HIGH ESPECIALLY AMONG PATIENTS WITH NON-COMMUNICABLE DISEASES. THE PURPOSE OF THIS REVIEW IS TO PROVIDE EVIDENCE TO CONSIDER VITAMINS AS EPIGENETIC MODIFIERS TO ENHANCE IMMUNITY AND REDUCE INFLAMMATORY RESPONSE IN COVID-19 PATIENTS WITH NON-COMMUNICABLE DISEASES. RECENT FINDINGS: CLINICAL EVIDENCE HAS SUGGESTED THE RISK OF GETTING INFECTED IS HIGH AMONG INDIVIDUALS WITH NON-COMMUNICABLE DISEASES SUCH AS CARDIOVASCULAR DISEASE, TYPE-2 DIABETES, CANCER, ACUTE RESPIRATORY DISTRESS SYNDROME, AND RENAL DISEASE, AS WELL AS THE ELDERLY WITH HIGH MORTALITY RATE AMONG THE COHORT. THE IMPACT IS DUE TO AN ALREADY COMPROMISED IMMUNE SYSTEM OF PATIENTS. EVERY PATIENT HAS A DIFFERENT RESPONSE TO COVID-19, WHICH SHOWS THAT THE ABILITY TO COMBAT THE DEADLY VIRUS VARIES INDIVIDUALLY. THUS, TREATMENT CAN BE PERSONALIZED AND ADJUSTED TO HELP PROTECT AND COMBAT COVID-19 INFECTIONS, ESPECIALLY IN INDIVIDUALS WITH NON-COMMUNICABLE DISEASES. BASED ON CURRENT PUBLISHED SCIENTIFIC AND MEDICAL EVIDENCE, THE SUGGESTIONS MADE IN THIS ARTICLE FOR COMBINATION OF VITAMIN THERAPY AS EPIGENETIC MODIFIERS TO CONTROL THE UNREGULATED INFLAMMATORY AND CYTOKINE MARKER EXPRESSIONS, FURTHER NEEDS TO BE CLINICALLY PROVEN. FUTURE RESEARCH AND CLINICAL TRIALS CAN APPLY THE SUGGESTIONS GIVEN IN THIS ARTICLE TO SUPPORT METABOLIC ACTIVITIES IN PATIENTS AND ENHANCE THE IMMUNE RESPONSE. 2020 6 2474 36 EPIGENETIC UNDERPINNINGS OF INFLAMMATION: CONNECTING THE DOTS BETWEEN PULMONARY DISEASES, LUNG CANCER AND COVID-19. INFLAMMATION IS AN ESSENTIAL COMPONENT OF SEVERAL RESPIRATORY DISEASES, SUCH AS CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), ASTHMA AND ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS). IT IS CENTRAL TO LUNG CANCER, THE LEADING CANCER IN TERMS OF ASSOCIATED MORTALITY THAT HAS AFFECTED MILLIONS OF INDIVIDUALS WORLDWIDE. INFLAMMATION AND PULMONARY MANIFESTATIONS ARE ALSO THE MAJOR CAUSES OF COVID-19 RELATED DEATHS. ACUTE HYPERINFLAMMATION PLAYS AN IMPORTANT ROLE IN THE COVID-19 DISEASE PROGRESSION AND SEVERITY, AND DEVELOPMENT OF PROTECTIVE IMMUNITY AGAINST THE VIRUS IS GREATLY SOUGHT. FURTHER, THE SEVERITY OF COVID-19 IS GREATLY ENHANCED IN LUNG CANCER PATIENTS, PROBABLY DUE TO THE GENES SUCH AS ACE2, TMPRSS2, PAI-1 AND FURIN THAT ARE COMMONLY INVOLVED IN CANCER PROGRESSION AS WELL AS SAR-COV-2 INFECTION. THE IMPORTANCE OF INFLAMMATION IN PULMONARY MANIFESTATIONS, CANCER AND COVID-19 CALLS FOR A CLOSER LOOK AT THE UNDERLYING PROCESSES, PARTICULARLY THE ASSOCIATED INCREASE IN IL-6 AND OTHER CYTOKINES, THE DYSREGULATION OF IMMUNE CELLS AND THE COAGULATION PATHWAY. TOWARDS THIS END, SEVERAL REPORTS HAVE IDENTIFIED EPIGENETIC REGULATION OF INFLAMMATION AT DIFFERENT LEVELS. EXPRESSION OF SEVERAL KEY INFLAMMATION-RELATED CYTOKINES, CHEMOKINES AND OTHER GENES IS AFFECTED BY METHYLATION AND ACETYLATION WHILE NON-CODING RNAS, INCLUDING MICRORNAS AS WELL AS LONG NON-CODING RNAS, ALSO AFFECT THE OVERALL INFLAMMATORY RESPONSES. SELECT MIRNAS CAN REGULATE INFLAMMATION IN COVID-19 INFECTION, LUNG CANCER AS WELL AS OTHER INFLAMMATORY LUNG DISEASES, AND CAN SERVE AS EPIGENETIC LINKS THAT CAN BE THERAPEUTICALLY TARGETED. FURTHERMORE, EPIGENETIC CHANGES ALSO MEDIATE THE ENVIRONMENTAL FACTORS-INDUCED INFLAMMATION. THEREFORE, A BETTER UNDERSTANDING OF EPIGENETIC REGULATION OF INFLAMMATION CAN POTENTIALLY HELP DEVELOP NOVEL STRATEGIES TO PREVENT, DIAGNOSE AND TREAT CHRONIC PULMONARY DISEASES, LUNG CANCER AND COVID-19. 2022 7 3676 34 INFLAMMATION AND NEUTROPHIL IMMUNOSENESCENCE IN HEALTH AND DISEASE: TARGETED TREATMENTS TO IMPROVE CLINICAL OUTCOMES IN THE ELDERLY. DESPITE INCREASING LONGEVITY, MANY OLD PEOPLE ARE NOT IN GOOD HEALTH. THERE HAS BEEN AN INCREASE IN THE PREVALENCE OF AGE-ASSOCIATED MULTI-MORBIDITY (TWO OR MORE CHRONIC CONDITIONS IN THE SAME PERSON). ALSO, SEVERE INFECTIONS, SUCH AS PNEUMONIA, REMAIN SIGNIFICANT CAUSES OF MORTALITY AND MORBIDITY IN THIS AGING GROUP. MANY CHRONIC HEALTH CONDITIONS SHARE RISK FACTORS SUCH AS INCREASING AGE, SMOKING, A SEDENTARY LIFE STYLE AND BEING PART OF A LOWER SOCIOECONOMIC GROUP. HOWEVER, DESPITE THIS, MULTI-MORBIDITIES OFTEN CO-OCCUR MORE COMMONLY THAN WOULD BE PREDICTED. THIS HAS LED TO THE HYPOTHESIS THAT THEY SHARE COMMON UNDERLYING MECHANISMS. THIS IS AN IMPORTANT CONCEPT, FOR IF IT WERE TRUE, TREATMENTS COULD BE DEVISED WHICH TARGET THESE COMMON PATHWAYS AND IMPROVE A NUMBER OF AGE-ASSOCIATED HEALTH CONDITIONS. MANY CHRONIC ILLNESSES ASSOCIATED WITH MULTI-MORBIDITY AND SEVERE INFECTIONS ARE CHARACTERIZED BY AN ABNORMAL AND SUSTAINED INFLAMMATORY RESPONSE, WITH NEUTROPHILS BEING KEY EFFECTOR CELLS IN THE PATHOLOGICAL PROCESS. STUDIES HAVE DESCRIBED ABERRANT NEUTROPHIL FUNCTIONS ACROSS THESE CONDITIONS, AND SOME HAVE HIGHLIGHTED POTENTIAL MECHANISMS FOR ALTERED CELL BEHAVIOURS WHICH APPEAR SHARED ACROSS DISEASE STATES. IT HAS BEEN SUGGESTED THAT ALTERED FUNCTIONS MAY REPRESENT NEUTROPHIL "SENESCENCE". THIS REVIEW CONSIDERS HOW AND WHY NEUTROPHIL FUNCTIONS CHANGE AS THE CELL AGES, AND HOW AND WHY NEUTROPHIL FUNCTIONS CHANGE AS THE HOST AGES IN HEALTH AND DISEASE AND DISCUSSES WHETHER NEUTROPHIL FUNCTIONS COULD BE TARGETED TO IMPROVE HEALTH OUTCOMES IN OLDER ADULTS. 2018 8 2570 26 EPIGENETICS OF CHRONIC INFLAMMATORY DISEASES. CHRONIC, NONCOMMUNICABLE, AND INFLAMMATION-ASSOCIATED DISEASES REMAIN THE LARGEST CAUSE OF MORBIDITY AND MORTALITY GLOBALLY AND WITHIN THE UNITED STATES. THIS IS MAINLY DUE TO OUR LIMITED UNDERSTANDING OF THE MOLECULAR MECHANISMS THAT UNDERLIE THESE COMPLEX PATHOLOGIES. THE AVAILABLE EVIDENCE INDICATES THAT STUDIES OF EPIGENETICS (TRADITIONALLY DEFINED AS THE HERITABLE CHANGES TO GENE EXPRESSION THAT ARE INDEPENDENT OF CHANGES TO DNA) ARE SIGNIFICANTLY ADVANCING OUR KNOWLEDGE OF THESE INFLAMMATORY CONDITIONS. THIS REVIEW WILL FOCUS ON EPIGENETIC STUDIES OF THREE DISEASES, THAT ARE AMONG THE MOST BURDENSOME GLOBALLY: CARDIOVASCULAR DISEASE, THE NUMBER ONE CAUSE OF DEATHS WORLDWIDE, TYPE 2 DIABETES AND, ALZHEIMER'S DISEASE. THE CURRENT STATUS OF EPIGENETIC RESEARCH, INCLUDING THE ABILITY TO PREDICT DISEASE RISK, AND KEY PATHOPHYSIOLOGICAL DEFECTS ARE DISCUSSED. THE SIGNIFICANCE OF DEFINING THE CONTRIBUTION OF EPIGENETIC DEFECTS TO NONRESOLVING INFLAMMATION AND AGING, EACH ASSOCIATED WITH THESE DISEASES, IS HIGHLIGHTED, AS THESE ARE LIKELY TO PROVIDE NEW INSIGHTS INTO INFLAMMATORY DISEASE PATHOGENESIS. 2019 9 6204 33 THE INFLUENCE OF EPIGENETICS AND INFLAMMATION ON CARDIOMETABOLIC RISKS. CARDIOMETABOLIC DISEASES INCLUDE METABOLIC SYNDROME, OBESITY, TYPE 2 DIABETES MELLITUS, AND HYPERTENSION. EPIGENETIC MODIFICATIONS PARTICIPATE IN CARDIOMETABOLIC DISEASES THROUGH SEVERAL PATHWAYS, INCLUDING INFLAMMATION, VASCULAR DYSFUNCTION, AND INSULIN RESISTANCE. EPIGENETIC MODIFICATIONS, WHICH ENCOMPASS ALTERATIONS TO GENE EXPRESSION WITHOUT MUTATING THE DNA SEQUENCE, HAVE GAINED MUCH ATTENTION IN RECENT YEARS, SINCE THEY HAVE BEEN CORRELATED WITH CARDIOMETABOLIC DISEASES AND MAY BE TARGETED FOR THERAPEUTIC INTERVENTIONS. EPIGENETIC MODIFICATIONS ARE GREATLY INFLUENCED BY ENVIRONMENTAL FACTORS, SUCH AS DIET, PHYSICAL ACTIVITY, CIGARETTE SMOKING, AND POLLUTION. SOME MODIFICATIONS ARE HERITABLE, INDICATING THAT THE BIOLOGICAL EXPRESSION OF EPIGENETIC ALTERATIONS MAY BE OBSERVED ACROSS GENERATIONS. MOREOVER, MANY PATIENTS WITH CARDIOMETABOLIC DISEASES PRESENT WITH CHRONIC INFLAMMATION, WHICH CAN BE INFLUENCED BY ENVIRONMENTAL AND GENETIC FACTORS. THE INFLAMMATORY ENVIRONMENT WORSENS THE PROGNOSIS OF CARDIOMETABOLIC DISEASES AND FURTHER INDUCES EPIGENETIC MODIFICATIONS, PREDISPOSING PATIENTS TO THE DEVELOPMENT OF OTHER METABOLISM-ASSOCIATED DISEASES AND COMPLICATIONS. A DEEPER UNDERSTANDING OF INFLAMMATORY PROCESSES AND EPIGENETIC MODIFICATIONS IN CARDIOMETABOLIC DISEASES IS NECESSARY TO IMPROVE OUR DIAGNOSTIC CAPABILITIES, PERSONALIZED MEDICINE APPROACHES, AND THE DEVELOPMENT OF TARGETED THERAPEUTIC INTERVENTIONS. FURTHER UNDERSTANDING MAY ALSO ASSIST IN PREDICTING DISEASE OUTCOMES, ESPECIALLY IN CHILDREN AND YOUNG ADULTS. THIS REVIEW DESCRIBES EPIGENETIC MODIFICATIONS AND INFLAMMATORY PROCESSES UNDERLYING CARDIOMETABOLIC DISEASES, AND FURTHER DISCUSSES ADVANCES IN THE RESEARCH FIELD WITH A FOCUS ON SPECIFIC POINTS FOR INTERVENTIONAL THERAPY. 2023 10 6199 31 THE IMPORTANCE OF EPIGENETICS IN THE DEVELOPMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. IT IS GENERALLY ACCEPTED THAT GENETIC PREDISPOSITION PLAYS A ROLE IN COPD DEVELOPMENT IN SUSCEPTIBLE INDIVIDUALS. THEREFORE, MANY CANDIDATE GENES THAT COULD BE LINKED TO THE DEVELOPMENT OF DISEASE HAVE BEEN EXAMINED IN COPD. HOWEVER, INCONSISTENT RESULTS IN DIFFERENT STUDY POPULATIONS OFTEN LIMIT THIS APPROACH, SUGGESTING THAT NOT ONLY GENETICS, BUT ALSO OTHER FACTORS, MAY BE CONTRIBUTED TO THE SUSCEPTIBILITY TO COPD. EPIGENETIC MECHANISMS CAN AFFECT THE TRANSCRIPTIONAL ACTIVITY OF SPECIFIC GENES, AT DIFFERENT POINTS IN TIME, AND IN DIFFERENT ORGANS. MOREOVER, THESE MECHANISMS CAN HAVE AN EFFECT ON PEOPLE'S HEALTH. RECENTLY, THERE IS EMERGING EVIDENCE SUPPORTING A ROLE OF EPIGENETICS FOR THE REGULATION OF INFLAMMATORY GENES IN DISEASES SUCH AS ASTHMA AND COPD. MOREOVER, RECENT STUDIES SUGGEST THAT THE CURRENTLY USED TREATMENTS INCLUDING CORTICOSTEROIDS MAY WORK THROUGH EPIGENETIC MECHANISMS. EPIGENETIC REGULATION CAN BE REPROGRAMMED, POTENTIALLY AFFECTING THE RISK, AETIOLOGY AND TREATMENT OF VARIOUS DISEASE STATES. THE EPIGENETICALLY INFLUENCED PHENOTYPE COULD BE REVERSED WITH DEMETHYLATING OR DEACETYLATING AGENTS, CONSISTENT WITH EPIGENETIC PLASTICITY. THE POSTNATAL REVERSIBILITY OF THESE METHYLATION OR ACETYLATION EVENTS MAY THEREFORE PROVIDE GOOD OPPORTUNITIES FOR INTERVENTION. THE RECOGNITION OF THE ROLE OF GENETIC AND EPIGENETIC MECHANISMS IN THE DEVELOPMENT OF COPD MAY IDENTIFY NOVEL TARGETS THAT HATCH NEW THERAPIES FOR PATIENTS WITH COPD. 2011 11 6120 35 THE EPIGENETIC IMPLICATION IN CORONAVIRUS INFECTION AND THERAPY. EPIGENETICS IS A RELATIVELY NEW FIELD OF SCIENCE THAT STUDIES THE GENETIC AND NON-GENETIC ASPECTS RELATED TO HERITABLE PHENOTYPIC CHANGES, FREQUENTLY CAUSED BY ENVIRONMENTAL AND METABOLIC FACTORS. IN THE HOST, THE EPIGENETIC MACHINERY CAN REGULATE GENE EXPRESSION THROUGH A SERIES OF REVERSIBLE EPIGENETIC MODIFICATIONS, SUCH AS HISTONE METHYLATION AND ACETYLATION, DNA/RNA METHYLATION, CHROMATIN REMODELING, AND NON-CODING RNAS. THE CORONAVIRUS DISEASE 19 (COVID-19) IS A HIGHLY TRANSMITTABLE AND PATHOGENIC VIRAL INFECTION. THE SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2), WHICH EMERGED IN WUHAN, CHINA, AND SPREAD WORLDWIDE, CAUSES IT. COVID-19 SEVERITY AND CONSEQUENCES LARGELY DEPEND ON PATIENT AGE AND HEALTH STATUS. IN THIS REVIEW, WE WILL SUMMARIZE AND COMPARATIVELY ANALYZE HOW VIRUSES REGULATE THE HOST EPIGENOME. MAINLY, WE WILL BE FOCUSING ON HIGHLY PATHOGENIC RESPIRATORY RNA VIRUS INFECTIONS SUCH AS CORONAVIRUSES. IN THIS CONTEXT, EPIGENETIC ALTERATIONS MIGHT PLAY AN ESSENTIAL ROLE IN THE ONSET OF CORONAVIRUS DISEASE COMPLICATIONS. ALTHOUGH MANY THERAPEUTIC APPROACHES ARE UNDER STUDY, MORE RESEARCH IS URGENTLY NEEDED TO IDENTIFY EFFECTIVE VACCINE OR SAFER CHEMOTHERAPEUTIC DRUGS, INCLUDING EPIGENETIC DRUGS, TO COPE WITH THIS VIRAL OUTBREAK AND TO DEVELOP PRE- AND POST-EXPOSURE PROPHYLAXIS AGAINST COVID-19. 2020 12 2984 33 GENETIC DETERMINANTS OF POOR RESPONSE TO TREATMENT IN SEVERE ASTHMA. SEVERE ASTHMA IS A MULTIFACTORIAL DISORDER WITH MARKED PHENOTYPIC HETEROGENEITY AND COMPLEX INTERACTIONS BETWEEN GENETICS AND ENVIRONMENTAL RISK FACTORS, WHICH COULD, AT LEAST IN PART, EXPLAIN WHY DURING STANDARD PHARMACOLOGIC TREATMENT, MANY PATIENTS REMAIN POORLY CONTROLLED AND AT AN INCREASED RISK OF AIRWAY REMODELING AND DISEASE PROGRESSION. THE CONCEPT OF "PRECISION MEDICINE" TO BETTER SUIT INDIVIDUAL UNIQUE NEEDS IS AN EMERGING TREND IN THE MANAGEMENT OF CHRONIC RESPIRATORY DISEASES. OVER THE PAST FEW YEARS, GENOME-WIDE ASSOCIATION STUDIES (GWAS) HAVE REVEALED NOVEL PHARMACOGENETIC VARIANTS RELATED TO RESPONSES TO INHALED CORTICOSTEROIDS AND THE CLINICAL EFFICACY OF BRONCHODILATORS. OPTIMAL CLINICAL RESPONSE TO TREATMENT MAY VARY BETWEEN RACIAL/ETHNIC GROUPS OR INDIVIDUALS DUE TO GENETIC DIFFERENCES. IT IS ALSO PLAUSIBLE TO ASSUME THAT EPIGENETIC FACTORS PLAY A KEY ROLE IN THE MODULATION OF GENE EXPRESSION PATTERNS AND INFLAMMATORY CYTOKINES. REMARKABLY, SPECIFIC GENETIC VARIANTS RELATED TO TREATMENT EFFECTIVENESS MAY INDICATE PROMISING PATHWAYS FOR NOVEL THERAPIES IN SEVERE ASTHMA. IN THIS REVIEW, WE PROVIDE A CONCISE UPDATE OF GENETIC DETERMINANTS OF POOR RESPONSE TO TREATMENT IN SEVERE ASTHMA AND FUTURE DIRECTIONS IN THE FIELD. 2021 13 2507 33 EPIGENETICS AND OBESITY: THE DEVIL IS IN THE DETAILS. OBESITY IS A COMPLEX DISEASE WITH MULTIPLE WELL-DEFINED RISK FACTORS. NEVERTHELESS, SUSCEPTIBILITY TO OBESITY AND ITS SEQUELAE WITHIN OBESOGENIC ENVIRONMENTS VARIES GREATLY FROM ONE PERSON TO THE NEXT, SUGGESTING A ROLE FOR GENE X ENVIRONMENT INTERACTIONS IN THE ETIOLOGY OF THE DISORDER. EPIGENETIC REGULATION OF THE HUMAN GENOME PROVIDES A PUTATIVE MECHANISM BY WHICH SPECIFIC ENVIRONMENTAL EXPOSURES CONVEY RISK FOR OBESITY AND OTHER HUMAN DISEASES AND IS ONE POSSIBLE MECHANISM THAT UNDERLIES THE GENE X ENVIRONMENT/TREATMENT INTERACTIONS OBSERVED IN EPIDEMIOLOGICAL STUDIES AND CLINICAL TRIALS. A STUDY PUBLISHED IN BMC MEDICINE THIS MONTH BY WANG ET AL. REPORTS ON AN EXAMINATION OF DNA METHYLATION IN PERIPHERAL BLOOD LEUKOCYTES OF LEAN AND OBESE ADOLESCENTS, COMPARING METHYLATION PATTERNS BETWEEN THE TWO GROUPS. THE AUTHORS IDENTIFIED TWO GENES THAT WERE DIFFERENTIALLY METHYLATED, BOTH OF WHICH HAVE ROLES IN IMMUNE FUNCTION. HERE WE OVERVIEW THE FINDINGS FROM THIS STUDY IN THE CONTEXT OF THOSE EMERGING FROM OTHER RECENT GENETIC AND EPIGENETIC STUDIES, DISCUSS THE STRENGTHS AND WEAKNESSES OF THE STUDY AND SPECULATE ON THE FUTURE OF EPIGENETICS IN CHRONIC DISEASE RESEARCH. 2010 14 3028 28 GENETICS OF COMPLEX AIRWAY DISEASE. THE PAST 3 YEARS HAVE SEEN HIGHLY SIGNIFICANT GENETIC EFFECTS IDENTIFIED FOR A WIDE VARIETY OF COMMON COMPLEX DISEASES, INCLUDING THE AIRWAY DISORDERS OF ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. IT APPEARS THAT ONLY A PORTION OF THE GENETICALLY MEDIATED SUSCEPTIBILITY TO COMPLEX DISEASES HAS BEEN IDENTIFIED, AND THERE IS MUCH LEFT TO BE DISCOVERED. THIS REVIEW BRIEFLY DESCRIBES THE RESULTS OF THE GENOME-WIDE ASSOCIATION STUDIES OF ASTHMA AND GIVES AN OVERVIEW OF THE PARALLEL AND INCREASINGLY LARGE-SCALE STUDIES THAT ARE TAKING PLACE WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE. THE FUTURE IMPACT IS DISCUSSED OF TECHNOLOGICAL ADVANCES THAT ALLOW INCREASINGLY LARGE-SCALE GENE EXPRESSION STUDIES, NEXT-GENERATION SEQUENCING, AND GENOME-WIDE TESTING FOR EPIGENETIC EFFECTS. THE USE OF GENETIC TECHNOLOGY TO EXAMINE THE AIRWAY MICROBIOTA THAT INTERACT WITH THE MUCOSA IN HEALTH AND DISEASE IS DESCRIBED. 2011 15 1208 31 COVID-19 INFECTION AND RESPONSE TO VACCINATION IN CHRONIC KIDNEY DISEASE AND RENAL TRANSPLANTATION: A BRIEF PRESENTATION. CHRONIC KIDNEY DISEASE (CKD) IS ASSOCIATED WITH PHENOTYPIC AND FUNCTIONAL CHANGES IN THE IMMUNE SYSTEM, FOLLOWED BY DETRIMENTAL CLINICAL CONSEQUENCES, SUCH AS SEVERE INFECTIONS AND DEFECTIVE RESPONSE TO VACCINATION. TWO YEARS OF THE PANDEMIC, DUE TO SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2), HAVE UNDOUBTEDLY CHANGED THE WORLD; HOWEVER, ALL EFFORTS TO CONFRONT INFECTION AND PROVIDE NEW GENERATION VACCINES TREMENDOUSLY IMPROVED OUR UNDERSTANDING OF THE MECHANISMS OF THE IMMUNE RESPONSE AGAINST INFECTIONS AND AFTER VACCINATION. HUMORAL AND CELLULAR RESPONSES TO VACCINES, INCLUDING MRNA VACCINES, ARE APPARENTLY AFFECTED IN CKD PATIENTS, AS ELIMINATION OF RECENT THYMIC EMIGRANT AND NAIVE LYMPHOCYTES AND REGULATORY T-CELLS, TOGETHER WITH CONTRACTION OF T-CELL REPERTOIRE AND HOMEOSTATIC PROLIFERATION RATE, WHICH CHARACTERIZED CKD PATIENTS ARE RESPONSIBLE FOR IMPAIRED IMMUNE ACTIVATION. SUCCESSFUL RENAL TRANSPLANTATION WILL RESTORE SOME OF THESE CHANGES, ALTHOUGH SEVERAL EPIGENETIC CHANGES ARE IRREVERSIBLE AND EVEN ACCELERATED BY THE INDUCTION OF IMMUNOSUPPRESSION. RESPONSE TO VACCINATION IS DEFINITELY IMPAIRED AMONG BOTH CKD AND RT PATIENTS. IN THE PRESENT REVIEW, WE ANALYZED THE DIFFERENCES IN IMMUNE RESPONSE AFTER VACCINATION BETWEEN THESE PATIENTS AND HEALTHY INDIVIDUALS AND DEPICTED SPECIFIC PARAMETERS, SUCH AS ALTERATIONS IN THE IMMUNE SYSTEM, PREDISPOSING TO THIS DEFICIENT RESPONSE. 2022 16 2651 33 EPIGENOMICS AND TRANSCRIPTOMICS IN THE PREDICTION AND DIAGNOSIS OF CHILDHOOD ASTHMA: ARE WE THERE YET? ASTHMA IS THE MOST COMMON NON-COMMUNICABLE CHRONIC DISEASE OF CHILDHOOD. DESPITE ITS HIGH PREVALENCE, TO DATE WE LACK METHODS THAT ARE BOTH EFFICIENT AND ACCURATE IN DIAGNOSING ASTHMA. MOST TRADITIONAL APPROACHES HAVE BEEN BASED ON GARNERING CLINICAL EVIDENCE, SUCH AS RISK FACTORS AND EXPOSURES. GIVEN THE HIGH HERITABILITY OF ASTHMA, MORE RECENT APPROACHES HAVE LOOKED AT GENETIC POLYMORPHISMS AS POTENTIAL "RISK FACTORS." HOWEVER, GENETIC VARIANTS EXPLAIN ONLY A SMALL PROPORTION OF ASTHMA RISK, AND HAVE BEEN LESS THAN OPTIMAL AT PREDICTING RISK FOR INDIVIDUAL SUBJECTS. EPIGENOMIC STUDIES OFFER SIGNIFICANT ADVANTAGES OVER PREVIOUS APPROACHES. EPIGENETIC REGULATION IS HIGHLY TISSUE-SPECIFIC, AND CAN INDUCE BOTH SHORT- AND LONG-TERM CHANGES IN GENE EXPRESSION. SUCH CHANGES CAN START IN UTERO, CAN VARY THROUGHOUT THE LIFE SPAN, AND IN SOME INSTANCES CAN BE PASSED ON FROM ONE GENERATION TO ANOTHER. MOST IMPORTANTLY, THE EPIGENOME CAN BE MODIFIED BY ENVIRONMENTAL FACTORS AND EXPOSURES, AND THUS EPIGENETIC AND TRANSCRIPTOMIC PROFILING MAY YIELD THE MOST ACCURATE RISK ESTIMATES FOR A GIVEN PATIENT BY INCORPORATING ENVIRONMENTAL (AND TREATMENT) EFFECTS THROUGHOUT THE LIFESPAN. HERE WE WILL REVIEW THE MOST RECENT ADVANCES IN THE USE OF EPIGENETIC AND TRANSCRIPTOMIC ANALYSIS FOR THE EARLY DIAGNOSIS OF ASTHMA AND ATOPY, AS WELL AS CHALLENGES AND FUTURE DIRECTIONS IN THE FIELD AS IT MOVES FORWARD. WE WILL PARTICULARLY FOCUS ON DNA METHYLATION, THE MOST STUDIED MECHANISM OF EPIGENETIC REGULATION. 2019 17 396 35 AN UPDATE ON EPIGENETICS AND CHILDHOOD RESPIRATORY DISEASES. EPIGENETIC MECHANISMS, DEFINED AS CHANGES IN PHENOTYPE OR GENE EXPRESSION CAUSED BY MECHANISMS OTHER THAN CHANGES IN THE UNDERLYING DNA SEQUENCE, HAVE BEEN PROPOSED TO CONSTITUTE A LINK BETWEEN GENETIC AND ENVIRONMENTAL FACTORS THAT AFFECT COMPLEX DISEASES. RECENT STUDIES SHOW THAT DNA METHYLATION, ONE OF THE KEY EPIGENETIC MECHANISMS, IS ALTERED IN CHILDREN EXPOSED TO AIR POLLUTANTS AND ENVIRONMENTAL TOBACCO SMOKE EARLY IN LIFE. SEVERAL CANDIDATE GENE STUDIES ON EPIGENETICS HAVE BEEN PUBLISHED TO DATE, BUT IT IS ONLY RECENTLY THAT GLOBAL METHYLATION ANALYSES HAVE BEEN PERFORMED FOR RESPIRATORY DISORDERS SUCH AS ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. HOWEVER, LARGE-SCALE STUDIES WITH ADEQUATE POWER ARE YET TO BE PRESENTED IN CHILDREN, AND IMPLICATIONS FOR CLINICAL USE REMAIN TO BE EVALUATED. IN THIS REVIEW, WE SUMMARIZE THE RECENT ADVANCES IN EPIGENETICS AND RESPIRATORY DISORDERS IN CHILDREN, WITH A MAIN FOCUS ON METHODOLOGICAL CHALLENGES AND ANALYSES RELATED TO PHENOTYPE AND EXPOSURE USING GLOBAL METHYLATION APPROACHES. 2014 18 931 28 CHRONIC KIDNEY DISEASE IN CHILDREN AND THE ROLE OF EPIGENETICS: FUTURE THERAPEUTIC TRAJECTORIES. GLOBAL DIFFERENCES IN THE OBSERVED CAUSES OF CHRONIC KIDNEY DISEASE (CKD) IN CHILDREN ARE WELL DOCUMENTED AND ARE ATTRIBUTED TO DISSIMILARITIES IN CLIME, RACE, HEREDITARY, AND ANCESTRY. THUS, FAMILIAL CLUSTERING AND DISPARITIES IN CKD PREVALENCE RATES ACROSS ETHNIC AND RACIAL GROUPS INDICATE THAT THE PROGRESSION OF RENAL DISEASE HAS A STRONG GENETIC COMPONENT. MAMMALIAN STUDIES HAVE DEMONSTRATED A FEASIBLE NEXUS BETWEEN NUTRITION AND NON-GENETIC EXPOSURE (AROUND THE TIME OF CONCEPTION AND IN EPIGENETIC CHANGES) IN THE EXPRESSION OF MAJOR GENES IDENTIFIED IN RENAL ORGANOGENESIS. THE MAJOR CONSEQUENCE IS A REDUCTION IN THE NUMBER OF NEPHRONS, WITH SUBSEQUENT PREDISPOSITION TO HYPERTENSION AND CKD. IDENTIFYING THESE EPIGENETIC CHANGES IS CRUCIAL (DUE TO THEIR POTENTIALLY REVERSIBLE NATURE), AS THEY MAY SERVE AS FUTURE THERAPEUTIC TARGETS TO PREVENT KIDNEY FIBROSIS AND CKD. DESPITE PROGRESS IN THE FIELD OF EPIGENETICS IN ONCOLOGY, RESEARCH IN OTHER SUBSPECIALTIES OF MEDICINE IS LARGELY EXPERIMENTAL WITH FEW EXISTING STUDIES REGARDING THE CLINICAL IMPLICATION OF EPIGENETICS IN RENAL DISEASE. THERAPEUTIC TRAJECTORIES FOR CKD IN CHILDREN BASED ON THE INFLUENCE OF EPIGENETICS MAY EVENTUALLY REVOLUTIONIZE THE MANAGEMENT OF THIS DISEASE. THE AIM OF THE CURRENT NARRATIVE REVIEW IS TO APPRAISE THE ROLE OF EPIGENETICS IN CKD, AND HIGHLIGHT THE POTENTIAL FUTURE THERAPEUTIC PATHWAYS. 2016 19 3020 29 GENETICS AND EPIGENETICS OF OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS A COMMON AGE-RELATED DISEASE THAT AFFECTS THE TISSUES OF THE SYNOVIAL JOINT, LEADING TO LOSS OF FUNCTION AND PAIN. IT IMPACTS ON BOTH PATIENT MORBIDITY AND MORTALITY. IT IS A COMPLEX, POLYGENIC DISEASE THAT LACKS ANY LARGE-EFFECT SUSCEPTIBILITY LOCI. INSTEAD, OA SUSCEPTIBILITY ALLELES INDIVIDUALLY CONTRIBUTE ONLY MODESTLY TO THE OVERALL DISEASE RISK, MAKING THEIR IDENTIFICATION CHALLENGING. DESPITE THIS, BREAKTHROUGHS HAVE OCCURRED WITH COMPELLING ASSOCIATIONS SO FAR REPORTED TO POLYMORPHISMS WITHIN THE GENES GDF5 AND MCF2L AND TO THE GENOMIC REGION 7Q22. THE LATTER TWO HAVE EMERGED FROM GENOME-WIDE ASSOCIATION SCANS, WHICH ARE LIKELY TO YIELD MORE HITS IN THE NEAR FUTURE. AS FOR MANY COMPLEX DISEASES, IT IS NOW APPARENT THAT EPIGENETIC EFFECTS ARE ALSO IMPORTANT MEDIATORS OF DISEASE BIOLOGY, WITH DNA METHYLATION, HISTONE MODIFICATIONS AND NON-CODING RNAS ALL HAVING A ROLE. AT PRESENT, MUCH OF THE EPIGENETIC FOCUS HAS BEEN ON CARTILAGE, THE TISSUE AT THE CENTER OF THE OA DISEASE PROCESS. IF WE ARE TO GET CLOSE TO A QUALITATIVE AND QUANTITATIVE UNDERSTANDING OF THE IMPACT OF EPIGENETICS ON OA, THEN IN FUTURE THE OTHER TISSUES OF THE JOINT WILL ALSO NEED TO BE INVESTIGATED. ONE OF THE MORE EXCITING INSIGHTS TO HAVE EMERGED RECENTLY IS THE FACT THAT EPIGENETIC EFFECTS CAN IMPACT ON OA GENETIC EFFECTS AND THIS MAY BE A PARTICULARLY FRUITFUL AVENUE FOR INTEGRATING BOTH AS WE MOVE TOWARD A CLEARER UNDERSTANDING OF THE PATHOPHYSIOLOGY OF THIS INTRIGUING DISEASE. 2012 20 2136 35 EPIGENETIC INFLUENCES IN THE OBESITY/COLORECTAL CANCER AXIS: A NOVEL THERAGNOSTIC AVENUE. THE WORLD HEALTH ORGANIZATION (WHO) CONSIDERS THAT OBESITY HAS REACHED PROPORTIONS OF PANDEMIC. EXPERTS ALSO INSIST ON THE IMPORTANCE OF CONSIDERING OBESITY AS A CHRONIC DISEASE AND ONE OF THE MAIN CONTRIBUTORS TO THE WORLDWIDE BURDEN OF OTHER NONTRANSMISSIBLE CHRONIC DISEASES, WHICH HAVE A GREAT IMPACT ON HEALTH, LIFESTYLE, AND ECONOMIC COST. ONE OF THE MOST CURRENT CHALLENGES OF BIOMEDICAL SCIENCE FACES IS TO UNDERSTAND THE ORIGIN OF THE CHRONIC NONTRANSMISSIBLE DISEASES, SUCH AS OBESITY AND CANCER. THERE IS A LARGE EVIDENCE, BOTH IN EPIDEMIOLOGICAL STUDIES IN HUMANS AND IN ANIMAL MODELS, OF THE ASSOCIATION BETWEEN OBESITY AND AN INCREASED RISK OF CANCER INCIDENCE. IN THE LAST YEARS, THE INITIAL DISCOVERY OF EPIGENETIC MECHANISMS REPRESENTS THE MOST RELEVANT FINDING TO EXPLAIN HOW THE GENOME INTERACTS WITH ENVIRONMENTAL FACTORS AND THE RIPPLE EFFECTS ON DISEASE PATHOGENESES. SINCE THEN, ALL EPIGENETIC PROCESS HAS BEEN INVESTIGATED BY THE SCIENTIFIC COMMUNITIES FOR NEARLY TWO DECADES TO DETERMINE WHICH COMPONENTS ARE INVOLVED IN THIS PROCESS. DNA/RNA METHYLATION AND MIRNA ARE CLASSIFIED AS TWO OF THE MOST IMPORTANT REPRESENTATIVE CLASSES OF SUCH EPIGENETIC MECHANISMS AND DYSREGULATED ACTIVITY OF SUCH MECHANISM CAN CERTAINLY CONTRIBUTE TO DISEASE PATHOGENESIS AND/OR PROGRESSION ESPECIALLY IN TUMORS. THIS REVIEW ARTICLE SERVES TO HIGHLIGHT THE IMPACT OF DNA/RNA METHYLATION AND MIRNA-BASED EPIGENETIC MECHANISM ACTIVITIES IN THE INTERPLAY BETWEEN OBESITY AND THE DEVELOPMENT AND CLINICAL SIGNIFICANCE OF COLORECTAL CANCER. 2019