1 3029 102 GENETICS OF INFLAMMATORY BOWEL DISEASES: A COMPARISON BETWEEN WESTERN AND EASTERN PERSPECTIVES. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC RELAPSING INTESTINAL INFLAMMATORY DISORDER WITH UNIDENTIFIED CAUSES. CURRENTLY, STUDIES INDICATE THAT IBD RESULTS FROM A COMPLEX INTERPLAY BETWEEN VARIOUS GENETIC AND ENVIRONMENTAL FACTORS THAT PRODUCE INTESTINAL INFLAMMATION. HOWEVER, THESE FACTORS MAY DIFFER FOR ASIANS AND CAUCASIANS. THUS, DIFFERENCES IN EPIDEMIOLOGY, GENETIC VARIANTS, AND CLINICAL PHENOTYPES OF IBD HAVE BEEN OBSERVED BETWEEN THE TWO POPULATIONS. UNDERSTANDING THE DISCREPANCIES BETWEEN DATA FROM POPULATIONS WITH DIFFERENT GENETIC BACKGROUNDS AND ENVIRONMENTAL FACTORS MAY REVEAL FUNDAMENTAL ASPECTS OF IBD PATHOGENESIS. ACCORDINGLY, THIS REVIEW WILL SUMMARIZE THE CURRENT KNOWLEDGE OF IBD GENETICS STUDIED IN ASIAN COUNTRIES AND COMPARE IT WITH THAT FROM WESTERN COUNTRIES, WITH SPECIAL FOCUS ON INNATE BACTERIAL SENSING, AUTOPHAGY, AND THE INTERLEUKIN-23 RECEPTOR-T HELPER CELL 17 PATHWAY. THE EPIGENETIC NATURE OF IBD PATHOGENESIS AS WELL AS THE PHARMACOGENETICS RELATED TO THE USE OF IMMUNOMODULATORS WILL ALSO BE BRIEFLY COVERED.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
2 3541  32 IMMUNOEPIGENETIC REGULATION OF INFLAMMATORY BOWEL DISEASE: CURRENT INSIGHTS INTO NOVEL EPIGENETIC MODULATIONS OF THE SYSTEMIC IMMUNE RESPONSE. THE IMMUNE SYSTEM AND ENVIRONMENTAL FACTORS ARE INVOLVED IN VARIOUS DISEASES, SUCH AS INFLAMMATORY BOWEL DISEASE (IBD), THROUGH THEIR EFFECT ON GENETICS, WHICH MODULATES IMMUNE CELLS. IBD ENCOMPASSES TWO MAIN PHENOTYPES, CROHN'S DISEASE, AND ULCERATIVE COLITIS, WHICH ARE MANIFESTED AS CHRONIC AND SYSTEMIC RELAPSE-REMITTING GASTROINTESTINAL TRACT DISORDERS WITH RISING GLOBAL INCIDENCE AND PREVALENCE. THE PATHOPHYSIOLOGY OF IBD IS COMPLEX AND NOT FULLY UNDERSTOOD. EPIGENETIC RESEARCH HAS RESULTED IN VALUABLE INFORMATION FOR UNRAVELING THE ETIOLOGY OF THIS IMMUNE-MEDIATED DISEASE. THUS, THE MAIN OBJECTIVE OF THE PRESENT REVIEW IS TO SUMMARIZE THE CURRENT FINDINGS ON THE ROLE OF EPIGENETIC MECHANISMS IN IBD TO SHED LIGHT ON THEIR POTENTIAL CLINICAL RELEVANCE. THIS REVIEW FOCUSES ON THE LATEST EVIDENCE REGARDING PERIPHERAL BLOOD MONONUCLEAR CELLS AND EPIGENETIC CHANGES IN HISTONE MODIFICATION, DNA METHYLATION, AND TELOMERE SHORTENING IN IBD. THE VARIOUS IDENTIFIED EPIGENETIC DNA PROFILES WITH CLINICAL VALUE IN IBD COULD BE USED AS BIOMARKERS FOR MORE ACCURATELY PREDICTING DISEASE DEVELOPMENT, TREATMENT RESPONSE, AND THERAPY-RELATED ADVERSE EVENTS. ULTIMATELY, THE INFORMATION PRESENTED HERE COULD BE OF POTENTIAL RELEVANCE FOR FUTURE CLINICAL PRACTICE IN DEVELOPING MORE EFFICIENT AND PRECISE MEDICINE TO IMPROVE THE QUALITY OF LIFE FOR PATIENTS WITH IBD.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
3 3690  37 INFLAMMATORY BOWEL DISEASE: GENETICS, EPIGENETICS, AND PATHOGENESIS. INFLAMMATORY BOWEL DISEASES (IBDS) ARE COMPLEX, MULTIFACTORIAL DISORDERS CHARACTERIZED BY CHRONIC RELAPSING INTESTINAL INFLAMMATION. ALTHOUGH ETIOLOGY REMAINS LARGELY UNKNOWN, RECENT RESEARCH HAS SUGGESTED THAT GENETIC FACTORS, ENVIRONMENT, MICROBIOTA, AND IMMUNE RESPONSE ARE INVOLVED IN THE PATHOGENESIS. EPIDEMIOLOGICAL EVIDENCE FOR A GENETIC CONTRIBUTION IS DEFINED: 15% OF PATIENTS WITH CROHN'S DISEASE (CD) HAVE AN AFFECTED FAMILY MEMBER WITH IBD, AND TWIN STUDIES FOR CD HAVE SHOWN 50% CONCORDANCE IN MONOZYGOTIC TWINS COMPARED TO <10% IN DIZYGOTICS. THE MOST RECENT AND LARGEST GENETIC ASSOCIATION STUDIES, WHICH EMPLOYED GENOME-WIDE ASSOCIATION DATA FOR OVER 75,000 PATIENTS AND CONTROLS, IDENTIFIED 163 SUSCEPTIBILITY LOCI FOR IBD. MORE RECENTLY, A TRANS-ETHNIC ANALYSIS, INCLUDING OVER 20,000 INDIVIDUALS, IDENTIFIED AN ADDITIONAL 38 NEW IBD LOCI. ALTHOUGH MOST CASES ARE CORRELATED WITH POLYGENIC CONTRIBUTION TOWARD GENETIC SUSCEPTIBILITY, THERE IS A SPECTRUM OF RARE GENETIC DISORDERS THAT CAN CONTRIBUTE TO EARLY-ONSET IBD (BEFORE 5 YEARS) OR VERY EARLY ONSET IBD (BEFORE 2 YEARS). GENETIC VARIANTS THAT CAUSE THESE DISORDERS HAVE A WIDE EFFECT ON GENE FUNCTION. THESE VARIANTS ARE SO RARE IN ALLELE FREQUENCY THAT THE GENETIC SIGNALS ARE NOT DETECTED IN GENOME-WIDE ASSOCIATION STUDIES OF PATIENTS WITH IBD. WITH RECENT ADVANCES IN SEQUENCING TECHNIQUES, ~50 GENETIC DISORDERS HAVE BEEN IDENTIFIED AND ASSOCIATED WITH IBD-LIKE IMMUNOPATHOLOGY. MONOGENIC DEFECTS HAVE BEEN FOUND TO ALTER INTESTINAL IMMUNE HOMEOSTASIS THROUGH MANY MECHANISMS. CANDIDATE GENE RESEQUENCING SHOULD BE CARRIED OUT IN EARLY-ONSET PATIENTS IN CLINICAL PRACTICE. THE EVIDENCE THAT GENETIC FACTORS CONTRIBUTE IN SMALL PART TO DISEASE PATHOGENESIS CONFIRMS THE IMPORTANT ROLE OF MICROBIAL AND ENVIRONMENTAL FACTORS. EPIGENETIC FACTORS CAN MEDIATE INTERACTIONS BETWEEN ENVIRONMENT AND GENOME. EPIGENETIC MECHANISMS COULD AFFECT DEVELOPMENT AND PROGRESSION OF IBD. EPIGENOMICS IS AN EMERGING FIELD, AND FUTURE STUDIES COULD PROVIDE NEW INSIGHT INTO THE PATHOGENESIS OF IBD.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
4 3017  31 GENETICS AND EPIGENETICS OF INFLAMMATORY BOWEL DISEASE. THE RELEVANCE OF GENETIC AND EPIGENETIC ALTERATIONS IN THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE (IBD) IS STILL POORLY UNDERSTOOD. SO FAR, 240 RISK GENE LOCI HAVE BEEN ASSOCIATED WITH IBD. THEY ARE MAINLY INVOLVED IN REGULATING INNATE AND ADAPTIVE IMMUNITY, AS WELL AS MAINTAINING INTESTINAL EPITHELIAL BARRIER FUNCTION. HOWEVER, THE FUNCTIONAL CONSEQUENCES OF THE IDENTIFIED GENETIC POLYMORPHISMS FOR IBD PATHOGENESIS IN VIVO ARE OFTEN UNKNOWN. EVEN LESS IS KNOWN ABOUT THE ROLE FOR EPIGENETIC MODIFICATIONS IN IBD PATHOGENESIS. THOUGH A NUMBER OF EPIGENETIC EVENTS SEEM TO BE CAUSATIVELY INVOLVED IBD PATHOGENESIS, OUR KNOWLEDGE ABOUT THE FUNCTIONAL RELEVANCE OF THOSE EPIGENETIC MODIFICATIONS IS SCANTY. THIS OPENS UP A BROAD RESEARCH FIELD THAT GENERATES NOVEL INSIGHTS INTO THE PATHOPHYSIOLOGY OF INTESTINAL AND CHRONIC INFLAMMATORY DISEASE. PATTERNS OF DNA METHYLATION AND HISTONE MODIFICATIONS MIGHT SERVE NOT ONLY AS BIOMARKERS OF DISEASE ACTIVITY OR DISEASE COURSE, BUT ALSO AS NEW TARGETS IN THERAPEUTIC INTERVENTIONS IN IBD PATIENTS.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
5 4692  47 NEWS FROM THE "5TH INTERNATIONAL MEETING ON INFLAMMATORY BOWEL DISEASES" CAPRI 2010. AT THE "5TH INTERNATIONAL MEETING ON INFLAMMATORY BOWEL DISEASES SELECTED TOPICS OF INFLAMMATORY BOWEL DISEASE (IBD), INCLUDING THE ENVIRONMENT, GENETICS, THE GUT FLORA, THE CELL RESPONSE AND IMMUNOMODULATION WERE DISCUSSED IN ORDER TO BETTER UNDERSTAND SPECIFIC CLINICAL AND THERAPEUTIC ASPECTS. THE INCIDENCE OF IBD CONTINUES TO RISE, BOTH IN LOW AND IN HIGH-INCIDENCE AREAS. IT IS BELIEVED THAT FACTORS ASSOCIATED WITH 'WESTERNIZATION' MAY BE CONDITIONING THE EXPRESSION OF THESE DISORDERS. THE INCREASED INCIDENCE OF IBD AMONG MIGRANTS FROM LOW-INCIDENCE TO HIGH-INCIDENCE AREAS WITHIN THE SAME GENERATION SUGGESTS A STRONG ENVIRONMENTAL INFLUENCE. THE DEVELOPMENT OF GENOME-WIDE ASSOCIATION SCANNING (GWAS) TECHNOLOGIES HAS LEAD TO THE DISCOVERY OF MORE THAN 100 IBD LOCI. SOME, AS THE TH 17 PATHWAY GENES, ARE SHARED BETWEEN CROHN'S DISEASE (CD) AND ULCERATIVE COLITIS (UC), WHILE OTHER ARE IBD SUBTYPE-SPECIFIC (AUTOPHAGY GENES, EPITHELIAL BARRIER GENES). DISEASE-SPECIFIC THERAPIES TARGETING THESE PATHWAYS SHOULD BE DEVELOPED. EPIGENETIC REGULATION OF THE INFLAMMATORY RESPONSE ALSO APPEARS TO PLAY AN IMPORTANT ROLE IN THE PATHOGENESIS OF IBD. THE IMPORTANCE OF GUT FLORA IN INTESTINAL HOMEOSTASIS AND INFLAMMATION WAS REINFORCED, THE CONCEPTS OF EUBIOSIS AND DYSBIOSIS WERE INTRODUCED, AND SOME STRATEGIES FOR REVERTING DYSBIOSIS TO A HOMEOSTATIC STATE OF EUBIOSIS WERE PROPOSED. THE CURRENT STATUS OF STUDIES ON THE HUMAN GUT MICROBIOTA METAGENOME, METAPROTOME, AND METABOLOME WAS ALSO PRESENTED. THE CELL RESPONSE IN INFLAMMATION, INCLUDING ENDOPLASMIC RETICULUM (ER) STRESS RESPONSES, AUTOPHAGY AND INFLAMMASOME-DEPENDENT EVENTS WERE RELATED TO IBD PATHOGENESIS. IT WAS SUGGESTED THAT INFLAMMATION-ASSOCIATED ER STRESS RESPONSES MAY BE A COMMON TRAIT IN THE PATHOGENESIS OF VARIOUS CHRONIC IMMUNE AND METABOLIC DISEASES. HOW INNATE AND ADAPTIVE IMMUNITY SIGNALING EVENTS CAN PERPETUATE CHRONIC INFLAMMATION WAS DISCUSSED EXTENSIVELY. SIGNAL TRANSDUCTION PATHWAYS PROVIDE INTRACELLULAR MECHANISMS BY WHICH CELLS RESPOND AND ADAPT TO MULTIPLE ENVIRONMENTAL STRESSES. THE IDENTIFICATION OF THESE SIGNALS HAS LED TO A GREATER MECHANISTIC UNDERSTANDING OF IBD PATHOGENESIS AND POINTED TO POTENTIALLY NEW THERAPEUTIC TARGETS. A CRITICAL ANALYSIS OF CLINICAL TRIALS AND OF RISK-BENEFIT OF BIOLOGICAL THERAPY WAS PRESENTED. THE PROBLEM OF EPSTEIN-BARR VIRUS (EBV) AND LYMPHOMA IN IBD WAS EXTENSIVELY DISCUSSED. LYMPHOMAS CAN DEVELOP IN INTESTINAL SEGMENTS AFFECTED BY IBD AND ARE IN MOST CASES ASSOCIATED WITH EBV. THE REASONS OF TREATMENT FAILURE WERE ALSO ANALYZED BOTH FROM BASIC AND CLINICAL POINTS OF VIEW. TWO VERY INTERESTING PRESENTATIONS ON THE INTEGRATION OF RESEARCH AND CLINICAL CARE IN THE NEAR FUTURE CLOSED THE MEETING. THESE PRESENTATIONS WERE FOCUSED ON MACROTRENDS AFFECTING HEALTHCARE DELIVERY AND RESEARCH, AND THE NEED TO INNOVATE TRADITIONAL INFRASTRUCTURES TO DEAL WITH THESE CHANGING TRENDS AS WELL AS NEW OPPORTUNITIES TO ACCELERATE SCIENTIFIC KNOWLEDGE.	2010	

6 3681  33 INFLAMMATION, DNA METHYLATION AND COLITIS-ASSOCIATED CANCER. INFLAMMATION CAN RESULT FROM A RANGE OF SOURCES INCLUDING MICROBIAL INFECTIONS, EXPOSURE TO ALLERGENS AND TOXIC CHEMICALS, AUTOIMMUNE DISEASE AND OBESITY. A WELL-BALANCED IMMUNE RESPONSE CAN BE ANTI-TUMORIGENIC; HOWEVER, A SUSTAINED OR CHRONIC INFLAMMATORY RESPONSE IS GENERALLY HARMFUL AS THE IMMUNE RESPONSE BECOMES DISTORTED. A CAUSAL LINK BETWEEN CHRONIC INFLAMMATION AND CANCER IS NOW WELL ACCEPTED AND MANY CHRONICALLY INFLAMED ORGANS OF THE GASTROINTESTINAL TRACT SHOW THIS ASSOCIATION. FOR EXAMPLE, PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD), INCLUDING BOTH ULCERATIVE COLITIS AND CROHN'S DISEASE, HAVE A 2- TO 3-FOLD GREATER LIFETIME RISK OF DEVELOPING COLORECTAL CANCER COMPARED WITH THE GENERAL POPULATION. THE DEVELOPMENT OF COLITIS-ASSOCIATED CANCER (CAC) IS THOUGHT TO BE MULTIFACETED AND IS PROBABLY DUE TO A COMBINATION OF GENETIC FACTORS, EPIGENETIC FACTORS AND THE DURATION, EXTENT AND SEVERITY OF DISEASE. RECENTLY, EPIGENETIC ALTERATIONS, IN PARTICULAR ALTERATIONS IN DNA METHYLATION, HAVE BEEN OBSERVED DURING INFLAMMATION AND INFLAMMATION-ASSOCIATED CARCINOGENESIS. THE MEDIATORS OF THIS, THE SIGNIFICANCE OF THESE CHANGES IN DNA METHYLATION AND THE EFFECT THIS HAS ON GENE EXPRESSION AND THE MALIGNANT TRANSFORMATION OF THE EPITHELIAL CELLS DURING IBD AND CAC ARE DISCUSSED IN THIS REVIEW. THE RECENT ADVANCES IN TECHNOLOGIES TO STUDY GENOME-WIDE DNA METHYLATION AND THE THERAPEUTIC POTENTIAL OF UNDERSTANDING THESE MOLECULAR MECHANISMS ARE ALSO HIGHLIGHTED.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
7 2675  28 ETIOPATHOGENESIS OF INFLAMMATORY BOWEL DISEASE: TODAY AND TOMORROW. PURPOSE OF REVIEW: CROHN'S DISEASE AND ULCERATIVE COLITIS, THE TWO MAJOR FORMS OF INFLAMMATORY BOWEL DISEASE (IBD), REPRESENT CHRONIC DISEASES OF UNKNOWN CAUSE, AND THEY ARE REGARDED AS PROTOTYPICAL COMPLEX DISEASES. DESPITE ALL THE RECENT ADVANCES, A COMPLETE APPRECIATION OF THE PATHOGENESIS OF IBD IS STILL LIMITED. IN THIS REVIEW, WE PRESENT RECENT INFORMATION CONTRIBUTING TO A BETTER UNDERSTANDING OF MECHANISMS UNDERLYING IBD. RECENT FINDINGS: HERE, WE ATTEMPT TO HIGHLIGHT NOVEL ENVIRONMENTAL TRIGGERS, DATA ON THE GUT MICROBIOTA, ITS INTERACTION WITH THE HOST, AND THE POTENTIAL INFLUENCE OF DIET AND FOOD COMPONENTS. WE DISCUSS RECENT FINDINGS ON DEFECTIVE SIGNALING PATHWAYS AND THE POTENTIAL EFFECTS ON THE IMMUNE RESPONSE, AND WE PRESENT NEW DATA ON EPIGENETIC CHANGES, INFLAMMASOME, AND DAMAGE-ASSOCIATED MOLECULAR PATTERNS ASSOCIATED WITH IBD. SUMMARY: THE CONTINUING IDENTIFICATION OF SEVERAL EPIGENETIC, TRANSCRIPTOMIC, PROTEOMIC, AND METABOLOMIC ALTERATIONS IN PATIENTS WITH IBD REFLECTS THE COMPLEX NATURE OF THE DISEASE AND SUGGESTS THE NEED FOR INNOVATIVE APPROACHES SUCH AS SYSTEMS BIOLOGY FOR IDENTIFYING NOVEL RELEVANT TARGETS IN IBD.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
8 3016  34 GENETICS AND EPIGENETICS OF IBD. INFLAMMATORY BOWEL DISEASES (IBD) ARE CHRONIC INTERMITTENT INFLAMMATORY DISORDERS OF THE GASTROINTESTINAL TRACT OF UNKNOWN ETIOLOGY BUT A CLEAR GENETIC PREDISPOSITION. PROMPTED BY THE FIRST INVESTIGATIONS ON IBD FAMILIES AND TWINS, THE GENETIC AND EPIGENETIC STUDIES HAVE PRODUCED AN UNPRECEDENTED AMOUNT OF INFORMATION IN COMPARISON WITH OTHER IMMUNE-MEDIATED OR COMPLEX DISEASES. NEW INFLAMMATORY PATHWAYS AND POSSIBLE MECHANISMS OF ACTION HAVE BEEN DISCLOSED, POTENTIALLY LEADING TO NEW-TARGETED THERAPY. HOWEVER, THE IDENTIFICATION OF GENETIC MARKERS DUE TO THE GREAT DISEASE HETEROGENEITY AND THE OVERWHELMING CONTRIBUTION OF ENVIRONMENTAL RISK FACTORS HAS NOT MODIFIED YET THE DISEASE MANAGEMENT. THE POSSIBILITY FOR THE FUTURE OF A BETTER PREDICTION OF DISEASE COURSE, RESPONSE TO THERAPY AND THERAPY-RELATED ADVERSE EVENTS MAY ALLOW A MORE EFFICIENT AND PERSONALIZED STRATEGY. THIS REVIEW WILL FOCUS ON MORE RECENT DISCOVERIES THAT MAY POTENTIALLY BE OF RELEVANCE IN DAILY CLINICAL PRACTICE.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
9 2952  23 GENETIC AND EPIGENETIC ETIOLOGY OF INFLAMMATORY BOWEL DISEASE: AN UPDATE. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC DISEASE WITH PERIODS OF EXACERBATION AND REMISSION OF THE DISEASE. THE ETIOLOGY OF IBD IS NOT FULLY UNDERSTOOD. MANY STUDIES POINT TO THE PRESENCE OF GENETIC, IMMUNOLOGICAL, ENVIRONMENTAL, AND MICROBIOLOGICAL FACTORS AND THE INTERACTIONS BETWEEN THEM IN THE OCCURRENCE OF IBD. THE REVIEW LOOKS AT GENETIC FACTORS IN THE CONTEXT OF BOTH IBD PREDISPOSITION AND PHARMACOGENETICS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
10 2027  37 EPIGENETIC CHANGES IN CHRONIC INFLAMMATORY DISEASES. THE NUMBER OF PEOPLE DIAGNOSED WITH CHRONIC INFLAMMATORY DISEASES HAS INCREASED NOTEWORTHY IN THE LAST 40 YEARS. SPONDYLOARTHRITIS (SPA), INFLAMMATORY BOWEL DISEASES (IBD), AND PSORIASIS ARE THE MOST FREQUENT CHRONIC INFLAMMATORY DISEASES, RESULTING FROM A COMBINATION OF GENETIC PREDISPOSITION AND ENVIRONMENTAL FACTORS. EPIGENETIC MODIFICATIONS INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS, AND SMALL AND LONG NONCODING RNAS. THEY ARE INFLUENCED BY ENVIRONMENTAL EXPOSURE, LIFE-STYLE, AND AGING AND HAVE RECENTLY BEEN SHOWN TO BE ALTERED IN MANY COMPLEX DISEASES INCLUDING INFLAMMATORY DISEASES. WHILE EPIGENETIC MODIFICATIONS HAVE BEEN WELL CHARACTERIZED IN OTHER DISEASES SUCH AS CANCER AND AUTOIMMUNE DISEASES, KNOWLEDGE ON CHANGES IN INFLAMMATORY DISEASES IS LAGGING BEHIND WITH SOME DISEASE-SPECIFIC DIFFERENCES. WHILE THE DNA METHYLATION PROFILE OF DIFFERENT CELL TYPES IN PATIENTS WITH IBD HAS BEEN RELATIVELY WELL DESCRIBED, LESS IS KNOWN ON CHANGES IMPLICATED IN PSORIASIS, AND NO SYSTEMATIC GENOME-WIDE STUDIES HAVE SO FAR BEEN PERFORMED IN SPA. IN THIS CHAPTER, WE REVIEW IN DETAIL THE REPORTED CHANGES IN PATTERNS OF DNA METHYLATION AND POSTTRANSLATIONAL HISTONE MODIFICATIONS IN CHRONIC INFLAMMATORY DISEASES HIGHLIGHTING POTENTIAL CONNECTIONS BETWEEN DISEASE-ASSOCIATED PATHOPHYSIOLOGICAL CHANGES SUCH AS THE DYSBIOSIS OF THE MICROBIOME OR GENETIC VARIATIONS ASSOCIATED WITH DISEASE SUSCEPTIBILITY AND THE EPIGENOME. WE ALSO DISCUSS IMPORTANT PARAMETERS OF MEANINGFUL EPIGENETIC STUDIES SUCH AS THE USE OF WELL DEFINED, DISEASE-RELEVANT CELL POPULATIONS, AND ELUDE ON THE POTENTIAL FUTURE OF ENGINEERING OF THE EPIGENOME IN INFLAMMATORY DISEASES.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
11  566  41 BASES FOR THE ADEQUATE DEVELOPMENT OF NUTRITIONAL RECOMMENDATIONS FOR PATIENTS WITH INFLAMMATORY BOWEL DISEASE. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC AND RELAPSING INFLAMMATORY CONDITION OF THE GASTROINTESTINAL TRACT; IT IS A HETEROGENEOUS AND MULTIFACTORIAL DISORDER RESULTING FROM A COMPLEX INTERPLAY BETWEEN GENETIC VARIATION, INTESTINAL MICROBIOTA, THE HOST IMMUNE SYSTEM AND ENVIRONMENTAL FACTORS SUCH AS DIET, DRUGS, BREASTFEEDING AND SMOKING. THE INTERACTIONS BETWEEN DIETARY NUTRIENTS AND INTESTINAL IMMUNITY ARE COMPLEX. THERE IS A COMPELLING ARGUMENT FOR ENVIRONMENTAL FACTORS SUCH AS DIET PLAYING A ROLE IN THE CAUSE AND COURSE OF IBD, GIVEN THAT THREE IMPORTANT FACTORS IN THE PATHOGENESIS OF IBD CAN BE MODULATED AND CONTROLLED BY DIET: INTESTINAL MICROBIOTA, THE IMMUNE SYSTEM AND EPITHELIAL BARRIER FUNCTION. THE AIM OF THIS REVIEW IS TO SUMMARIZE THE EPIDEMIOLOGICAL FINDINGS REGARDING DIET AND TO FOCUS ON THE EFFECTS THAT NUTRIENTS EXERT ON THE INTESTINAL MUCOSA-MICROBIOTA-PERMEABILITY INTERACTION. THE NATURE OF THESE INTERACTIONS IN IBD IS INFLUENCED BY ALTERATIONS IN THE NUTRITIONAL METABOLISM OF THE GUT MICROBIOTA AND HOST CELLS THAT CAN INFLUENCE THE OUTCOME OF NUTRITIONAL INTERVENTION. A BETTER UNDERSTANDING OF DIET-HOST-MICROBIOTA INTERACTIONS IS ESSENTIAL FOR UNRAVELLING THE COMPLEX MOLECULAR BASIS OF EPIGENETIC, GENETIC AND ENVIRONMENTAL INTERACTIONS UNDERLYING IBD PATHOGENESIS AS WELL AS FOR OFFERING NEW THERAPEUTIC APPROACHES FOR THE TREATMENT OF IBD.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
12 1404  30 DIETARY COMPOSITION AND EFFECTS IN INFLAMMATORY BOWEL DISEASE. DRAMATIC CHANGES IN THE ENVIRONMENT AND HUMAN LIFESTYLE HAVE BEEN ASSOCIATED WITH THE RISE OF VARIOUS CHRONIC COMPLEX DISEASES, SUCH AS INFLAMMATORY BOWEL DISEASE (IBD). A DYSBIOTIC GUT MICROBIOTA HAS BEEN PROPOSED AS A CRUCIAL PATHOGENIC ELEMENT, CONTRIBUTING TO IMMUNE IMBALANCES AND FOSTERING A PROINFLAMMATORY MILIEU, WHICH MAY BE ASSOCIATED WITH DISEASE RELAPSES OR EVEN THE INITIATION OF IBD. IN ADDITION TO REPRESENTING IMPORTANT REGULATORS OF THE MUCOSAL IMMUNITY AND THE COMPOSITION OF THE GUT MICROBIOTA, FOOD COMPONENTS HAVE BEEN SHOWN TO BE POTENTIAL ENVIRONMENTAL TRIGGERS OF EPIGENETIC MODIFICATIONS. IN THE CONTEXT OF CHRONIC INTESTINAL INFLAMMATION, DIETARY HABITS AND SPECIFIC FOOD COMPONENTS HAVE BEEN IMPLICATED AS IMPORTANT MODULATORS OF EPIGENETIC MECHANISMS, INCLUDING DNA METHYLATION, WHICH MAY PREDISPOSE A PERSON TO THE INCREASED RISK OF THE INITIATION AND EVOLUTION OF IBD. THIS REVIEW PROVIDES NOVEL INSIGHTS ABOUT HOW DIETARY FACTORS MAY INTERACT WITH THE INTESTINAL MUCOSA AND MODULATE IMMUNE HOMEOSTASIS BY SHAPING THE INTESTINAL ECOSYSTEM, AS WELL AS THE POTENTIAL INFLUENCE OF DIET IN THE ETIOPATHOGENESIS AND MANAGEMENT OF IBD.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
13 2945  30 GENETIC AND EPIGENETIC BASIS OF PSORIASIS PATHOGENESIS. PSORIASIS IS A CHRONIC INFLAMMATORY SKIN DISEASE WHOSE PREVALENCE VARIES AMONG DIFFERENT POPULATIONS WORLDWIDE. IT IS A COMPLEX MULTI-FACTORIAL DISEASE AND THE EXACT ETIOLOGY IS LARGELY UNKNOWN. FAMILY BASED STUDIES HAVE INDICATED A GENETIC PREDISPOSITION; HOWEVER THEY CANNOT FULLY EXPLAIN THE DISEASE PATHOGENESIS. IN ADDITION TO GENETIC SUSCEPTIBILITY, ENVIRONMENTAL AS WELL AS GENDER AND AGE RELATED FACTORS WERE ALSO BEEN FOUND TO BE ASSOCIATED. RECENTLY, IMBALANCES IN EPIGENETIC NETWORKS ARE INDICATED TO BE CAUSATIVE ELEMENTS IN PSORIASIS. THE PRESENT KNOWLEDGE OF EPIGENETIC INVOLVEMENT, MAINLY THE DNA METHYLATION, CHROMATIN MODIFICATIONS AND MIRNA DEREGULATION IS SURVEYED HERE. AN INTEGRATED APPROACH CONSIDERING GENETIC AND EPIGENETIC ANOMALIES IN THE LIGHT OF IMMUNOLOGICAL NETWORK MAY EXPLORE THE PATHOGENESIS OF PSORIASIS.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
14 2601  37 EPIGENETICS, DNA ORGANIZATION, AND INFLAMMATORY BOWEL DISEASE. INFLAMMATORY BOWEL DISEASES (IBDS) ARE CHRONIC INFLAMMATORY DISORDERS AFFECTING THE GASTROINTESTINAL TRACT. THE INCIDENCE OF IBD IS INCREASING, WITH MORE CASES OCCURRING IN DEVELOPED COUNTRIES. MULTIPLE FACTORS SUCH AS GENETICS, ENVIRONMENTAL CHANGES, GUT MICROBIOTA, AND IMMUNE ABNORMALITIES HAVE BEEN ASSOCIATED WITH DEVELOPMENT OF IBD. IN RECENT YEARS, IT HAS BECOME INCREASINGLY APPARENT THAT EPIGENETIC MODIFICATIONS OF CHROMATIN AND THE MANNER IN WHICH CHROMATIN IS ORGANIZED IN THE NUCLEUS ARE ADDITIONALLY IMPORTANT ELEMENTS THAT CAN INFLUENCE RESPONSES INDUCED BY THE FACTORS DESCRIBED ABOVE, AND MAY THEREFORE CONTRIBUTE TO THE ONSET AND PATHOGENESIS OF IBD. EPIGENETICS AND CHROMATIN ORGANIZATION REGULATE DIVERSE FUNCTIONS THAT INCLUDE MAINTENANCE OF HOMEOSTASIS IN THE INTESTINAL EPITHELIUM, THE DEVELOPMENT AND DIFFERENTIATION OF IMMUNE CELLS, AND MODULATION OF RESPONSES GENERATED BY THE IMMUNE SYSTEM TO DEFEND AGAINST POTENTIAL PATHOGENS. FURTHERMORE, CHANGES IN EPIGENETIC CHROMATIN MARKS AND IN CHROMATIN ORGANIZATION HAVE NOW BEEN LINKED TO DIFFERENTIAL GENE EXPRESSION IN IBD PATIENT CELLS. ALTHOUGH DIRECT EVIDENCE FOR A ROLE OF HISTONE MODIFICATIONS IN IBD IS CURRENTLY VERY LIMITED, IN THIS REVIEW, WE SUMMARIZE THE LINKS BETWEEN VARIOUS EPIGENETIC MODIFICATIONS, THE PROTEINS THAT CATALYZE OR RECOGNIZE THESE MODIFICATIONS, AND THE DEVELOPMENT OR PROGRESSION OF IBD IN HUMAN AND EXPERIMENTAL IBD. WE ALSO DISCUSS HOW EPIGENETICS INFLUENCE THE ORGANIZATION OF DNA CONTACTS TO REGULATE GENE EXPRESSION AND THE IMPLICATIONS THIS MAY HAVE FOR DIAGNOSING AND TREATING IBD.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
15 5528  29 RNA MODIFICATION IN INFLAMMATORY BOWEL DISEASES. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC INFLAMMATORY DISORDER CHARACTERIZED BY DAMAGE TO THE INTESTINAL MUCOSA, WHICH IS CAUSED BY A COMBINATION OF FACTORS. THESE INCLUDE GENETIC AND EPIGENETIC ALTERATIONS, ENVIRONMENTAL INFLUENCE, MICROORGANISM INTERACTIONS, AND IMMUNE CONDITIONS. SOME POPULATIONS WITH IBD SHOW A CANCER-PRONE PHENOTYPE. RECENT STUDIES HAVE PROVIDED INSIGHT INTO THE INVOLVEMENT OF RNA MODIFICATIONS IN THE SPECIFIC PATHOGENESIS OF IBD THROUGH REGULATION OF RNA BIOLOGY IN EPITHELIAL AND IMMUNE CELLS. STUDIES OF SEVERAL RNA MODIFICATION-TARGETING REAGENTS HAVE SHOWN PREFERABLE OUTCOMES IN PATIENTS WITH COLITIS. HERE, WE NOTE A NEW AWARENESS OF RNA MODIFICATION IN THE TARGETING OF IBD AND RELATED DISEASES, WHICH WILL CONTRIBUTE TO EARLY DIAGNOSIS, DISEASE MONITORING, AND POSSIBLE CONTROL BY INNOVATIVE THERAPEUTIC APPROACHES.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
16 1522  34 DNA METHYLATION CHANGE PROFILING OF COLORECTAL DISEASE: SCREENING TOWARDS CLINICAL USE. COLON CANCER REMAINS ONE OF THE LEADING CAUSES OF CANCER-RELATED DEATHS WORLDWIDE. TRANSFORMATION OF COLON EPITHELIAL CELLS INTO INVASIVE ADENOCARCINOMAS HAS BEEN WELL KNOWN TO BE DUE TO THE ACCUMULATION OF MULTIPLE GENETIC AND EPIGENETIC CHANGES. IN THE PAST DECADE, THE ETIOLOGY OF INFLAMMATORY BOWEL DISEASE (IBD) WHICH IS CHARACTERIZED BY CHRONIC INFLAMMATION OF THE INTESTINAL MUCOSA, WAS ONLY PARTIALLY EXPLAINED BY GENETIC STUDIES PROVIDING SUSCEPTIBILITY LOCI, BUT RECENTLY EPIGENETIC STUDIES HAVE PROVIDED CRITICAL EVIDENCES AFFECTING IBD PATHOGENESIS. OVER THE PAST DECADE, A DEEP UNDERSTANDING OF EPIGENETICS ALONG WITH TECHNOLOGICAL ADVANCES HAVE LED TO IDENTIFYING NUMEROUS GENES THAT ARE REGULATED BY PROMOTER DNA HYPERMETHYLATION IN COLORECTAL DISEASES. RECENT ADVANCES IN OUR UNDERSTANDING OF THE ROLE OF DNA METHYLATION IN COLORECTAL DISEASES COULD IMPROVE A MULTITUDE OF POWERFUL DNA METHYLATION-BASED BIOMARKERS, PARTICULARLY FOR USE AS DIAGNOSIS, PROGNOSIS, AND PREDICTION FOR THERAPEUTIC APPROACHES. THIS REVIEW FOCUSES ON THE EMERGING POTENTIAL FOR TRANSLATIONAL RESEARCH OF EPIGENETIC ALTERATIONS INTO CLINICAL UTILITY AS MOLECULAR BIOMARKERS. MOREOVER, THIS REVIEW DISCUSSES RECENT PROGRESS REGARDING THE IDENTIFICATION OF UNKNOWN HYPERMETHYLATED GENES IN COLON CANCERS AND IBD, AS WELL AS THEIR POSSIBLE ROLE IN CLINICAL PRACTICE, WHICH WILL HAVE IMPORTANT CLINICAL SIGNIFICANCE, PARTICULARLY IN THE ERA OF THE PERSONALIZED MEDICINE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
17 4670  24 NEW INSIGHTS INTO THE EPIGENETIC REGULATION OF INFLAMMATORY BOWEL DISEASE. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC INFLAMMATORY DISEASE OF THE COLONIC MUCOSA. ENVIRONMENTAL FACTORS, GENETICS, INTESTINAL MICROBIOTA, AND THE IMMUNE SYSTEM ARE ALL INVOLVED IN THE PATHOPHYSIOLOGY OF IBD. LATELY, ACCUMULATING EVIDENCE HAS SHOWN THAT ABNORMAL EPIGENETIC CHANGES IN DNA METHYLATION, HISTONE MARKERS, AND NON-CODING RNA EXPRESSION GREATLY CONTRIBUTE TO THE DEVELOPMENT OF THE ENTIRE DISEASE. EPIGENETICS REGULATES MANY FUNCTIONS, SUCH AS MAINTAINING THE HOMEOSTASIS OF THE INTESTINAL EPITHELIUM AND REGULATING THE IMMUNE SYSTEM OF THE IMMUNE CELLS. IN THE PRESENT STUDY, WE SYSTEMATICALLY SUMMARIZED THE LATEST ADVANCES IN EPIGENETIC MODIFICATION OF IBD AND HOW EPIGENETICS REVEALS NEW MECHANISMS OF IBD. OUR PRESENT REVIEW PROVIDED NEW INSIGHTS INTO THE PATHOPHYSIOLOGY OF IBD. MOREOVER, EXPLORING THE PATTERNS OF DNA METHYLATION AND HISTONE MODIFICATION THROUGH EPIGENETICS CAN NOT ONLY BE USED AS BIOMARKERS OF IBD BUT ALSO AS A NEW TARGET FOR THERAPEUTIC INTERVENTION IN IBD PATIENTS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
18 3585  29 IMPACT OF THE EXPOSOME ON THE EPIGENOME IN INFLAMMATORY BOWEL DISEASE PATIENTS AND ANIMAL MODELS. INFLAMMATORY BOWEL DISEASES (IBD) ARE CHRONIC INFLAMMATORY DISORDERS OF THE GASTROINTESTINAL TRACT THAT ENCOMPASS TWO MAIN PHENOTYPES, NAMELY CROHN'S DISEASE AND ULCERATIVE COLITIS. THESE CONDITIONS OCCUR IN GENETICALLY PREDISPOSED INDIVIDUALS IN RESPONSE TO ENVIRONMENTAL FACTORS. EPIGENETICS, ACTING BY DNA METHYLATION, POST-TRANSLATIONAL HISTONES MODIFICATIONS OR BY NON-CODING RNAS, COULD EXPLAIN HOW THE EXPOSOME (OR ALL ENVIRONMENTAL INFLUENCES OVER THE LIFE COURSE, FROM CONCEPTION TO DEATH) COULD INFLUENCE THE GENE EXPRESSION TO CONTRIBUTE TO INTESTINAL INFLAMMATION. WE PERFORMED A SCOPING SEARCH USING MEDLINE TO IDENTIFY ALL THE ELEMENTS OF THE EXPOSOME THAT MAY PLAY A ROLE IN INTESTINAL INFLAMMATION THROUGH EPIGENETIC MODIFICATIONS, AS WELL AS THE UNDERLYING MECHANISMS. THE ENVIRONMENTAL FACTORS EPIGENETICALLY INFLUENCING THE OCCURRENCE OF INTESTINAL INFLAMMATION ARE THE MATERNAL LIFESTYLE (MAINLY DIET, THE OCCURRENCE OF INFECTION DURING PREGNANCY AND SMOKING); BREASTFEEDING; MICROBIOTA; DIET (INCLUDING A LOW-FIBER DIET, HIGH-FAT DIET AND DEFICIENCY IN MICRONUTRIENTS); SMOKING HABITS, VITAMIN D AND DRUGS (E.G., IBD TREATMENTS, ANTIBIOTICS AND PROBIOTICS). INFLUENCED BY BOTH MICROBIOTA AND DIET, SHORT-CHAIN FATTY ACIDS ARE GUT MICROBIOTA-DERIVED METABOLITES RESULTING FROM THE ANAEROBIC FERMENTATION OF NON-DIGESTIBLE DIETARY FIBERS, PLAYING AN EPIGENETICALLY MEDIATED ROLE IN THE INTEGRITY OF THE EPITHELIAL BARRIER AND IN THE DEFENSE AGAINST INVADING MICROORGANISMS. ALTHOUGH THE IMPACT OF SOME ENVIRONMENTAL FACTORS HAS BEEN IDENTIFIED, THE EXPOSOME-INDUCED EPIMUTATIONS IN IBD REMAIN A LARGELY UNDEREXPLORED FIELD. HOW THESE ENVIRONMENTAL EXPOSURES INDUCE EPIGENETIC MODIFICATIONS (IN TERMS OF DURATION, FREQUENCY AND THE TIMING AT WHICH THEY OCCUR) AND HOW OTHER ENVIRONMENTAL FACTORS ASSOCIATED WITH IBD MODULATE EPIGENETICS DESERVE TO BE FURTHER INVESTIGATED.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
19 1168  33 CONTRIBUTION OF EPITHELIAL AND GUT MICROBIOME INFLAMMATORY BIOMARKERS TO THE IMPROVEMENT OF COLORECTAL CANCER PATIENTS' STRATIFICATION. IN ORDER TO ENSURE THAT PRIMARY ENDPOINTS OF CLINICAL STUDIES ARE ATTAINED, THE PATIENTS' STRATIFICATION IS AN IMPORTANT ASPECT. SELECTION CRITERIA INCLUDE AGE, GENDER, AND ALSO SPECIFIC BIOMARKERS, SUCH AS INFLAMMATION SCORES. THESE CRITERIA ARE NOT SUFFICIENT TO ACHIEVE A STRAIGHTFORWARD SELECTION, HOWEVER, IN CASE OF MULTIFACTORIAL DISEASES, WITH UNKNOWN OR PARTIALLY IDENTIFIED MECHANISMS, OCCASIONALLY INCLUDING HOST FACTORS, AND THE MICROBIOME. IN THESE CASES, THE EFFICACY OF INTERVENTIONS IS DIFFICULT TO PREDICT, AND AS A RESULT, THE SELECTION OF SUBJECTS IS OFTEN RANDOM. COLORECTAL CANCER (CRC) IS A HIGHLY HETEROGENEOUS DISEASE, WITH VARIABLE CLINICAL FEATURES, OUTCOMES, AND RESPONSE TO THERAPY; THE CRC ONSET AND PROGRESS INVOLVES MULTIPLE SEQUENTIAL STEPS WITH ACCUMULATION OF GENETIC ALTERATIONS, NAMELY, MUTATIONS, GENE AMPLIFICATION, AND EPIGENETIC CHANGES. THE GUT MICROBES, EITHER EUBIOTIC OR DYSBIOTIC, COULD INFLUENCE THE CRC EVOLUTION THROUGH A COMPLEX AND VERSATILE CROSSTALK WITH THE INTESTINAL AND IMMUNE CELLS, PERMANENTLY CHANGING THE TUMOR MICROENVIRONMENT. THERE HAVE BEEN SIGNIFICANT ADVANCES IN THE DEVELOPMENT OF PERSONALIZED APPROACHES FOR CRC SCREENING, TREATMENT, AND POTENTIAL PREVENTION. ADVANCES IN MOLECULAR TECHNIQUES BRING NEW CRITERIA FOR PATIENTS' STRATIFICATION-MUTATIONAL ANALYSIS AT THE TIME OF DIAGNOSIS TO GUIDE TREATMENT, FOR EXAMPLE. GUT MICROBIOME HAS EMERGED AS THE MAIN TRIGGER OF GUT MUCOSAL HOMEOSTASIS. THIS MAY IMPACT CANCER SUSCEPTIBILITY THROUGH MAINTENANCE OF THE EPITHELIAL/MUCUS BARRIER AND PRODUCTION OF PROTECTIVE METABOLITES, SUCH AS SHORT-CHAIN FATTY ACIDS (SCFAS) VIA INTERACTIONS WITH THE HOSTS' DIET AND METABOLISM. MICROBIOME DYSBIOSIS LEADS TO THE ENRICHMENT OF CANCER-PROMOTING BACTERIAL POPULATIONS, LOSS OF PROTECTIVE POPULATIONS OR MAINTAINING AN INFLAMMATORY CHRONIC STATE, ALL OF WHICH CONTRIBUTE TO THE DEVELOPMENT AND PROGRESSION OF CRC. MEANWHILE, VARIATIONS IN PATIENT RESPONSES TO ANTI-CANCER IMMUNO- AND CHEMOTHERAPIES WERE ALSO LINKED TO INTER-INDIVIDUAL DIFFERENCES IN INTESTINE MICROBIOMES. THE AUTHORS AIM TO HIGHLIGHT THE CONTRIBUTION OF EPITHELIAL AND GUT MICROBIOME INFLAMMATORY BIOMARKERS IN THE IMPROVEMENT OF CRC PATIENTS' STRATIFICATION TOWARDS A PERSONALIZED APPROACH OF EARLY DIAGNOSIS AND TREATMENT.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
20 6288  40 THE POTENTIAL ROLE OF EPIGENETIC MODIFICATIONS ON DIFFERENT FACETS IN THE PERIODONTAL PATHOGENESIS. PERIODONTITIS IS A CHRONIC INFLAMMATORY DISEASE THAT AFFECTS THE SUPPORTING STRUCTURES OF TEETH. IN THE LITERATURE, THE ASSOCIATION BETWEEN THE PATHOGENICITY OF BACTERIA AND ENVIRONMENTAL FACTORS IN THIS REGARD HAVE BEEN EXTENSIVELY EXAMINED. IN THE PRESENT STUDY, WE WILL SHED LIGHT ON THE POTENTIAL ROLE THAT EPIGENETIC CHANGE CAN PLAY ON DIFFERENT FACETS OF ITS PROCESS, MORE PARTICULARLY THE MODIFICATIONS CONCERNING THE GENES INVOLVED IN INFLAMMATION, DEFENSE, AND IMMUNE SYSTEMS. SINCE THE 1960S, THE ROLE OF GENETIC VARIANTS IN THE ONSET AND SEVERITY OF PERIODONTAL DISEASE HAS BEEN WIDELY DEMONSTRATED. THESE MAKE SOME PEOPLE MORE SUSCEPTIBLE TO DEVELOPING IT THAN OTHERS. IT HAS BEEN DOCUMENTED THAT THE WIDE VARIATION IN ITS FREQUENCY FOR VARIOUS RACIAL AND ETHNIC POPULATIONS IS DUE PRIMARILY TO THE COMPLEX INTERPLAY AMONG GENETIC FACTORS WITH THOSE AFFECTING THE ENVIRONMENT AND THE DEMOGRAPHY. IN MOLECULAR BIOLOGY, EPIGENETIC MODIFICATIONS ARE DEFINED AS ANY CHANGE IN THE PROMOTER FOR THE CPG ISLANDS, IN THE STRUCTURE OF THE HISTONE PROTEIN, AS WELL AS POST-TRANSLATIONAL REGULATION BY MICRORNAS (MIRNAS), BEING KNOWN TO CONTRIBUTE TO THE ALTERATION IN GENE EXPRESSION FOR COMPLEX MULTIFACTORIAL DISEASES SUCH AS PERIODONTITIS. THE KEY ROLE OF EPIGENETIC MODIFICATION IS TO UNDERSTAND THE MECHANISM INVOLVED IN THE GENE-ENVIRONMENT INTERACTION, AND THE DEVELOPMENT OF PERIODONTITIS IS NOW THE SUBJECT OF MORE AND MORE STUDIES THAT ATTEMPT TO IDENTIFY WHICH FACTORS ARE STIMULATING IT, BUT ALSO AFFECT THE REDUCED RESPONSE TO THERAPY.	2023