1 5122 112 POSSIBLE ROLE OF FRUCTOSAMINE 3-KINASE GENOTYPING FOR THE MANAGEMENT OF DIABETIC PATIENTS. DIABETES MELLITUS IS A GLOBAL PANDEMIC AND CONTINUES TO INCREASE IN NUMBERS AND SIGNIFICANCE. SEVERAL PATHOGENIC PROCESSES ARE INVOLVED IN THE DEVELOPMENT OF SUCH DISEASE AND THESE MECHANISMS COULD BE INFLUENCED BY GENETIC, EPIGENETIC AND ENVIRONMENTAL FACTORS. NON-ENZYMATIC GLYCATION REACTIONS OF PROTEINS HAVE BEEN STRONGLY RELATED TO PATHOGENESIS OF CHRONIC DIABETIC COMPLICATIONS. THE IDENTIFICATION OF FRUCTOSAMINE 3-KINASE (FN3K), AN ENZYME INVOLVED IN PROTEIN DEGLYCATION, A NEW FORM OF PROTEIN REPAIR, IS OF GREAT INTEREST. FN3K PHOSPHORYLATES FRUCTOSAMINES ON THE THIRD CARBON OF THEIR SUGAR MOIETY, MAKING THEM UNSTABLE AND CAUSING THEM TO DETACH FROM PROTEINS, SUGGESTING A PROTECTIVE ROLE OF THIS ENZYME. MOREOVER, THE VARIABILITY IN FN3K ACTIVITY HAS BEEN ASSOCIATED WITH SOME POLYMORPHISMS IN THE FN3K GENE. HERE WE ARGUE ABOUT GENETIC STUDIES AND EVIDENCE OF FN3K INVOLVEMENT IN DIABETES, TOGETHER WITH RESULTS OF OUR ANALYSIS OF THE FN3K GENE ON A CAUCASIAN COHORT OF DIABETIC PATIENTS. PRESENT KNOWLEDGE SUGGESTS THAT FN3K COULD ACT IN CONCERT WITH OTHER MOLECULAR MECHANISMS AND MAY IMPACT ON GENE EXPRESSION AND ACTIVITY OF OTHER ENZYMES INVOLVED IN DEGLYCATION PROCESS. 2015 2 1900 34 ENERGY SENSING PATHWAYS: BRIDGING TYPE 2 DIABETES AND COLORECTAL CANCER? THE RECENTLY RAPID INCREASE OF OBESITY AND TYPE 2 DIABETES MELLITUS HAS CAUSED GREAT BURDEN TO OUR SOCIETY. A POSITIVE ASSOCIATION BETWEEN TYPE 2 DIABETES AND RISK OF COLORECTAL CANCER HAS BEEN REPORTED BY INCREASING EPIDEMIOLOGICAL STUDIES. THE MOLECULAR MECHANISM OF THIS CONNECTION REMAINS ELUSIVE. HOWEVER, TYPE 2 DIABETES MAY RESULT IN ABNORMAL CARBOHYDRATE AND LIPID METABOLISM, HIGH LEVELS OF CIRCULATING INSULIN, INSULIN GROWTH FACTOR-1, AND ADIPOCYTOKINES, AS WELL AS CHRONIC INFLAMMATION. ALL THESE FACTORS COULD LEAD TO THE ALTERATION OF ENERGY SENSING PATHWAYS SUCH AS THE AMP ACTIVATED KINASE (PRKA), MECHANISTIC (MAMMALIAN) TARGET OF RAPAMYCIN (MTOR), SIRT1, AND AUTOPHAGY SIGNALING PATHWAYS. THE RESULTED IMPAIRED SIRT1 AND AUTOPHAGY SIGNALING PATHWAY COULD INCREASE THE RISK OF GENE MUTATION AND CANCER GENESIS BY DECREASING GENETIC STABILITY AND DNA MISMATCH REPAIR. THE DYSREGULATED MTOR AND PRKA PATHWAY COULD REMODEL CELL METABOLISM DURING THE GROWTH AND METASTASIS OF CANCER IN ORDER FOR THE CANCER CELL TO SURVIVE THE UNFAVORABLE MICROENVIRONMENT SUCH AS HYPOXIA AND LOW BLOOD SUPPLY. MOREOVER, THESE PATHWAYS MAY BE COUPLING METABOLIC AND EPIGENETIC ALTERATIONS THAT ARE CENTRAL TO ONCOGENIC TRANSFORMATION. FURTHER RESEARCHES INCLUDING MOLECULAR PATHOLOGIC EPIDEMIOLOGIC STUDIES ARE WARRANTED TO BETTER ADDRESS THE PRECISE LINKS BETWEEN THESE TWO IMPORTANT DISEASES. 2017 3 2332 32 EPIGENETIC REGULATION OF INFLAMMATION IN INSULIN RESISTANCE. EPIGENETICS FOCUSES ON THE STUDY OF CHANGES IN GENE EXPRESSION BASED ON MODIFICATIONS THAT DO NOT INTERFERE WITH THE DNA SEQUENCE, SUCH AS DNA METHYLATION, POST-TRANSLATIONAL HISTONE MODIFICATION, AND NON-CODING RNA. EPIGENETIC CHANGES REGULATE THE EXPRESSION OF MANY GENES, INCLUDING INFLAMMATORY ONES. CHRONIC INFLAMMATION IS OFTEN ACCOMPANIED BY INSULIN RESISTANCE (IR), WHICH IS CHARACTERISTIC OF INTER ALIA TYPE 2 DIABETES. RECENTLY, IT HAS BEEN REPORTED THAT ALTERED EPIGENETIC SIGNATURE IN THE PROMOTER REGIONS OF INFLAMMATORY GENES MAY CONTRIBUTE TO THE DEVELOPMENT OF IR. THEREFORE, THE AIM OF THIS REVIEW IS TO PRESENT THE CURRENT STATE OF KNOWLEDGE REGARDING THE EPIGENETIC REGULATION OF INFLAMMATION IN IR. IT INCLUDES ORIGINAL PAPERS PUBLISHED FROM 2014 TO 2022. IT APPEARS THAT HYPOMETHYLATION OF THE SOCS3 GENE INCREASES THE RISK OF IR, WHILE THE ALTERATION OF H3K4ME IN THE NF-KB PROMOTER PROMOTES CHANGES IN INFLAMMATORY PHENOTYPE. FINALLY, IN HYPERGLYCEMIC STATES ASSOCIATED WITH IR, ALTERED LEVELS OF H3K4/K9M3 AND H3K9/K14AC RESULT IN INCREASED EXPRESSION OF THE INFLAMMATORY CYTOKINE IL-6. IN ADDITION, NUMEROUS MIRNAS HAVE BEEN IDENTIFIED THAT MAY BECOME A TARGET IN THE FIGHT AGAINST DISEASES RELATED TO INFLAMMATION AND IR. FUTURE STUDIES SHOULD EXAMINE THE EPIGENETIC MODIFICATIONS OF IR INFLAMMATORY MARKERS ASSOCIATED WITH ENVIRONMENTAL FACTORS. 2022 4 1505 34 DNA METHYLATION AND HISTONE MODIFICATION IN HYPERTENSION. SYSTEMIC HYPERTENSION, WHICH EVENTUALLY RESULTS IN HEART FAILURE, RENAL FAILURE OR STROKE, IS A COMMON CHRONIC HUMAN DISORDER THAT PARTICULARLY AFFECTS ELDERS. ALTHOUGH MANY SIGNALING PATHWAYS INVOLVED IN THE DEVELOPMENT OF HYPERTENSION HAVE BEEN REPORTED OVER THE PAST DECADES, WHICH HAS LED TO THE IMPLEMENTATION OF A WIDE VARIETY OF ANTI-HYPERTENSIVE THERAPIES, ONE HALF OF ALL HYPERTENSIVE PATIENTS STILL DO NOT HAVE THEIR BLOOD PRESSURE CONTROLLED. THE FRONTIER IN UNDERSTANDING THE MOLECULAR MECHANISMS UNDERLYING HYPERTENSION HAS NOW ADVANCED TO THE LEVEL OF EPIGENOMICS. PARTICULARLY, INCREASING EVIDENCE IS EMERGING THAT DNA METHYLATION AND HISTONE MODIFICATIONS PLAY AN IMPORTANT ROLE IN GENE REGULATION AND ARE INVOLVED IN ALTERATION OF THE PHENOTYPE AND FUNCTION OF VASCULAR CELLS IN RESPONSE TO ENVIRONMENTAL STRESSES. THIS REVIEW SEEKS TO HIGHLIGHT THE RECENT ADVANCES IN OUR KNOWLEDGE OF THE EPIGENETIC REGULATIONS AND MECHANISMS OF HYPERTENSION, FOCUSING ON THE ROLE OF DNA METHYLATION AND HISTONE MODIFICATION IN THE VASCULAR WALL. A BETTER UNDERSTANDING OF THE EPIGENOMIC REGULATION IN THE HYPERTENSIVE VESSEL MAY LEAD TO THE IDENTIFICATION OF NOVEL TARGET MOLECULES THAT, IN TURN, MAY LEAD TO NOVEL DRUG DISCOVERIES FOR THE TREATMENT OF HYPERTENSION. 2018 5 3801 33 INTERPLAY OF VITAMIN D AND SIRT1 IN TISSUE-SPECIFIC METABOLISM-POTENTIAL ROLES IN PREVENTION AND TREATMENT OF NON-COMMUNICABLE DISEASES INCLUDING CANCER. THE IMPORTANCE OF THE PREVENTION AND CONTROL OF NON-COMMUNICABLE DISEASES, INCLUDING OBESITY, METABOLIC SYNDROME, TYPE 2 DIABETES, CARDIOVASCULAR DISEASES, AND CANCER, IS INCREASING AS A REQUIREMENT OF THE AGING POPULATION IN DEVELOPED COUNTRIES AND THE SUSTAINABILITY OF HEALTHCARE. SIMILARLY, THE 2013-2030 ACTION PLAN OF THE WHO FOR THE PREVENTION AND CONTROL OF NON-COMMUNICABLE DISEASES SEEKS THESE ACHIEVEMENTS. ADEQUATE LIFESTYLE CHANGES, ALONE OR WITH THE NECESSARY TREATMENTS, COULD REDUCE THE RISK OF MORTALITY OR THE DETERIORATION OF QUALITY OF LIFE. IN OUR RECENT WORK, WE SUMMARIZED THE ROLE OF TWO CENTRAL FACTORS, I.E., APPROPRIATE LEVELS OF VITAMIN D AND SIRT1, WHICH ARE CONNECTED TO ADEQUATE LIFESTYLES WITH BENEFICIAL EFFECTS ON THE PREVENTION AND CONTROL OF NON-COMMUNICABLE DISEASES. BOTH OF THESE FACTORS HAVE RECEIVED INCREASED ATTENTION IN RELATION TO THE COVID-19 PANDEMIC AS THEY BOTH TAKE PART IN REGULATION OF THE MAIN METABOLIC PROCESSES, I.E., LIPID/GLUCOSE/ENERGY HOMEOSTASIS, OXIDATIVE STRESS, REDOX BALANCE, AND CELL FATE, AS WELL AS IN THE HEALTHY REGULATION OF THE IMMUNE SYSTEM. VITAMIN D AND SIRT1 HAVE DIRECT AND INDIRECT INFLUENCE OF THE REGULATION OF TRANSCRIPTION AND EPIGENETIC CHANGES AND ARE RELATED TO CYTOPLASMIC SIGNALING PATHWAYS SUCH AS PLC/DAG/IP3/PKC/MAPK, MEK/ERK, INSULIN/MTOR/CELL GROWTH, PROLIFERATION; LEPTIN/PI3K-AKT-MTORC1, AKT/NFKB/COX-2, NFKB/TNFALPHA, IL-6, IL-8, IL-1BETA, AND AMPK/PGC-1ALPHA/GLUT4, AMONG OTHERS. THROUGH THEIR PROPER REGULATION, THEY MAINTAIN NORMAL BODY WEIGHT, LIPID PROFILE, INSULIN SECRETION AND SENSITIVITY, BALANCE BETWEEN THE PRO- AND ANTI-INFLAMMATORY PROCESSES UNDER NORMAL CONDITIONS AND INFECTIONS, MAINTAIN ENDOTHELIAL HEALTH; BALANCE CELL DIFFERENTIATION, PROLIFERATION, AND FATE; AND BALANCE THE CIRCADIAN RHYTHM OF THE CELLULAR METABOLISM. THE ROLE OF THESE TWO MOLECULES IS INTERCONNECTED IN THE MOLECULAR NETWORK, AND THEY REGULATE EACH OTHER IN SEVERAL LAYERS OF THE HOMEOSTASIS OF ENERGY AND THE CELLULAR METABOLISM. BOTH HAVE A CENTRAL ROLE IN THE MAINTENANCE OF HEALTHY AND BALANCED IMMUNE REGULATION AND REDOX REACTIONS; THEREFORE, THEY COULD CONSTITUTE PROMISING TARGETS EITHER FOR PREVENTION OR AS COMPLEMENTARY THERAPIES TO ACHIEVE A BETTER QUALITY OF LIFE, AT ANY AGE, FOR HEALTHY PEOPLE AND PATIENTS UNDER CHRONIC CONDITIONS. 2023 6 4719 31 NONCODING RNA AND EPIGENETIC GENE REGULATION IN RENAL DISEASES. KIDNEYS HAVE A MAJOR ROLE IN NORMAL PHYSIOLOGY AND METABOLIC HOMEOSTASIS. LOSS OR IMPAIRMENT OF KIDNEY FUNCTION IS A COMMON OCCURRENCE IN SEVERAL METABOLIC DISORDERS, INCLUDING HYPERTENSION AND DIABETES. CHRONIC KIDNEY DISEASE (CKD) AFFECT NEARLY 10% OF THE POPULATION WORLDWIDE; RANKS 18TH IN THE LIST OF CAUSES OF DEATH; AND CONTRIBUTES TO A SIGNIFICANT PROPORTION OF HEALTHCARE COSTS. THE TISSUE REPAIR AND REGENERATIVE POTENTIAL OF KIDNEYS ARE LIMITED AND THEY DECLINE DURING AGING. RECENT STUDIES HAVE DEMONSTRATED A KEY ROLE FOR EPIGENETIC PROCESSES AND PLAYERS, SUCH AS DNA METHYLATION, HISTONE MODIFICATIONS, NONCODING (NC)RNA, AND SO ON, IN BOTH KIDNEY DEVELOPMENT AND DISEASE. IN THIS REVIEW, WE HIGHLIGHT THESE RECENT FINDINGS WITH AN EMPHASIS ON ABERRANT EPIGENETIC CHANGES THAT ACCOMPANY RENAL DISEASES, KEY TARGETS, AND THEIR THERAPEUTIC VALUE. 2017 7 6199 39 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 8 1515 31 DNA METHYLATION AND THE POTENTIAL ROLE OF DEMETHYLATING AGENTS IN PREVENTION OF PROGRESSIVE CHRONIC KIDNEY DISEASE. CHRONIC KIDNEY DISEASE (CKD) IS A GLOBAL EPIDEMIC, AND ITS MAJOR RISK FACTORS INCLUDE OBESITY AND TYPE 2 DIABETES. OBESITY NOT ONLY PROMOTES METABOLIC DYSREGULATION AND THE DEVELOPMENT OF DIABETIC KIDNEY DISEASE BUT ALSO MAY INDEPENDENTLY LEAD TO CKD BY A VARIETY OF MECHANISMS, INCLUDING ENDOCRINE AND METABOLIC DYSFUNCTION, INFLAMMATION, OXIDATIVE STRESS, ALTERED RENAL HEMODYNAMICS, AND LIPOTOXICITY. DELETERIOUS RENAL EFFECTS OF OBESITY CAN ALSO BE TRANSMITTED FROM ONE GENERATION TO THE NEXT, AND IT IS INCREASINGLY RECOGNIZED THAT OFFSPRING OF OBESE MOTHERS ARE PREDISPOSED TO CKD. EPIGENETIC MODIFICATIONS ARE CHANGES THAT REGULATE GENE EXPRESSION WITHOUT ALTERING THE DNA SEQUENCE. OF THESE, DNA METHYLATION IS THE MOST STUDIED. EPIGENETIC IMPRINTS, PARTICULARLY DNA METHYLATION, ARE LAID DOWN DURING CRITICAL PERIODS OF FETAL DEVELOPMENT, AND THEY MAY PROVIDE A MECHANISM BY WHICH MATERNAL-FETAL TRANSMISSION OF CHRONIC DISEASE OCCURS. OUR CURRENT REVIEW EXPLORES THE EVIDENCE FOR THE ROLE OF DNA METHYLATION IN THE DEVELOPMENT OF CKD, DIABETIC KIDNEY DISEASE, DIABETES, AND OBESITY. DNA METHYLATION HAS BEEN IMPLICATED IN RENAL FIBROSIS-THE FINAL PATHOPHYSIOLOGIC PATHWAY IN THE DEVELOPMENT OF END-STAGE KIDNEY DISEASE-WHICH SUPPORTS THE NOTION THAT DEMETHYLATING AGENTS MAY PLAY A POTENTIAL THERAPEUTIC ROLE IN PREVENTING DEVELOPMENT AND PROGRESSION OF CKD.-LARKIN, B. P., GLASTRAS, S. J., CHEN, H., POLLOCK, C. A., SAAD, S. DNA METHYLATION AND THE POTENTIAL ROLE OF DEMETHYLATING AGENTS IN PREVENTION OF PROGRESSIVE CHRONIC KIDNEY DISEASE. 2018 9 2059 34 EPIGENETIC CONTROL OF GENE EXPRESSION IN THE LUNG. EPIGENETICS IS TRADITIONALLY DEFINED AS THE STUDY OF HERITABLE CHANGES IN GENE EXPRESSION CAUSED BY MECHANISMS OTHER THAN CHANGES IN THE UNDERLYING DNA SEQUENCE. THERE ARE THREE MAIN CLASSES OF EPIGENETIC MARKS--DNA METHYLATION, MODIFICATIONS OF HISTONE TAILS, AND NONCODING RNAS--EACH OF WHICH MAY BE INFLUENCED BY THE ENVIRONMENT, DIET, DISEASES, AND AGEING. IMPORTANTLY, EPIGENETIC MARKS HAVE BEEN SHOWN TO INFLUENCE IMMUNE CELL MATURATION AND ARE ASSOCIATED WITH THE RISK OF DEVELOPING VARIOUS FORMS OF CANCER, INCLUDING LUNG CANCER. MOREOVER, THERE IS EMERGING EVIDENCE THAT THESE EPIGENETIC MARKS AFFECT GENE EXPRESSION IN THE LUNG AND ARE ASSOCIATED WITH BENIGN LUNG DISEASES, SUCH AS ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, AND INTERSTITIAL LUNG DISEASE. TECHNOLOGICAL ADVANCES HAVE MADE IT FEASIBLE TO STUDY EPIGENETIC MARKS IN THE LUNG, AND IT IS ANTICIPATED THAT THIS KNOWLEDGE WILL ENHANCE OUR UNDERSTANDING OF THE DYNAMIC BIOLOGY IN THE LUNG AND LEAD TO THE DEVELOPMENT OF NOVEL DIAGNOSTIC AND THERAPEUTIC APPROACHES FOR OUR PATIENTS WITH LUNG DISEASE. 2011 10 4192 30 METABOLIC MEMORY AND CHRONIC DIABETES COMPLICATIONS: POTENTIAL ROLE FOR EPIGENETIC MECHANISMS. RECENT ESTIMATES INDICATE THAT DIABETES MELLITUS CURRENTLY AFFECTS MORE THAN 10 % OF THE WORLD'S POPULATION. EVIDENCE FROM BOTH THE LABORATORY AND LARGE SCALE CLINICAL TRIALS HAS REVEALED THAT PROLONGED HYPERGLYCEMIA INDUCES CHRONIC COMPLICATIONS WHICH PERSIST AND PROGRESS UNIMPEDED EVEN WHEN GLYCEMIC CONTROL IS PHARMACEUTICALLY ACHIEVED VIA THE PHENOMENON OF METABOLIC MEMORY. THE EPIGENOME IS COMPRISED OF ALL CHROMATIN MODIFICATIONS INCLUDING POST TRANSLATIONAL HISTONE MODIFICATION, EXPRESSION CONTROL VIA MIRNAS AND THE METHYLATION OF CYTOSINE WITHIN DNA. MODIFICATIONS OF THESE EPIGENETIC MARKS NOT ONLY ALLOW CELLS AND ORGANISMS TO QUICKLY RESPOND TO CHANGING ENVIRONMENTAL STIMULI BUT ALSO CONFER THE ABILITY OF THE CELL TO "MEMORIZE" THESE ENCOUNTERS. AS SUCH, THESE PROCESSES HAVE GAINED MUCH ATTENTION AS POTENTIAL MOLECULAR MECHANISMS UNDERLYING METABOLIC MEMORY AND CHRONIC DIABETIC COMPLICATIONS. HERE WE PRESENT A REVIEW OF THE VERY RECENT LITERATURE PUBLISHED PERTAINING TO THIS SUBJECT. 2012 11 6200 30 THE INFLAMMATORY EFFECT OF EPIGENETIC FACTORS AND MODIFICATIONS IN TYPE 2 DIABETES. INFLAMMATION HAS A CENTRAL ROLE IN THE ETIOLOGY OF TYPE 2 DIABETES (T2D) AND ITS COMPLICATIONS. BOTH GENETIC AND EPIGENETIC FACTORS HAVE BEEN IMPLICATED IN THE DEVELOPMENT OF T2D-ASSOCIATED INFLAMMATION. EPIGENETIC MECHANISMS REGULATE THE FUNCTION OF SEVERAL COMPONENTS OF THE IMMUNE SYSTEM. DIABETIC CONDITIONS TRIGGER ABERRANT EPIGENETIC ALTERATIONS THAT CONTRIBUTE TO THE PROGRESSION OF INSULIN RESISTANCE AND BETA-CELL DYSFUNCTION BY INDUCTION OF INFLAMMATORY RESPONSES. THUS, TARGETING EPIGENETIC FACTORS AND MODIFICATIONS, AS ONE OF THE UNDERLYING CAUSES OF INFLAMMATION, COULD LEAD TO THE DEVELOPMENT OF NOVEL IMMUNE-BASED STRATEGIES FOR THE TREATMENT OF T2D. THE AIM OF THIS REVIEW IS TO PROVIDE AN OVERVIEW OF THE EPIGENETIC MECHANISMS INVOLVED IN THE PROPAGATION AND PERPETUATION OF CHRONIC INFLAMMATION IN T2D. WE ALSO DISCUSS THE POSSIBLE ANTI-INFLAMMATORY APPROACHES THAT TARGET EPIGENETIC FACTORS FOR THE TREATMENT OF T2D. 2020 12 2560 38 EPIGENETICS IN THE DEVELOPMENT, MODIFICATION, AND PREVENTION OF CARDIOVASCULAR DISEASE. EPIGENETICS HAS MAJOR RELEVANCE TO ALL DISEASE PROCESSES; CARDIOVASCULAR (CV) DISEASE AND ITS RELATED CONDITIONS ARE NO EXCEPTION. EPIGENETICS IS DEFINED AS THE STUDY OF HERITABLE ALTERATIONS IN GENE EXPRESSION, OR CELLULAR PHENOTYPE, AND GOES FAR BEYOND A PURE GENETIC APPROACH. A MORE PRECISE DEFINITION IS THAT EPIGENETICS REPRESENTS ALL THE MEIOTICALLY AND MITOTICALLY INHERITED CHANGES IN GENE EXPRESSION THAT ARE NOT ENCODED ON THE DEOXYRIBONUCLEIC ACID (DNA) SEQUENCE ITSELF. MAJOR EPIGENETIC MECHANISMS ARE MODIFICATIONS OF HISTONE PROTEINS IN CHROMATIN AND DNA METHYLATION (WHICH DOES NOT ALTER THE DNA SEQUENCE). THERE IS INCREASING EVIDENCE FOR THE INVOLVEMENT OF EPIGENETICS IN HUMAN DISEASE SUCH AS CANCER, INFLAMMATORY DISEASE AND CV DISEASE. OTHER CHRONIC DISEASES ARE ALSO SUSCEPTIBLE TO EPIGENETIC MODIFICATION SUCH AS METABOLIC DISEASES INCLUDING OBESITY, METABOLIC SYNDROME, AND DIABETES MELLITUS. THERE IS MUCH EVIDENCE FOR THE MODIFICATION OF EPIGENETICS BY NUTRITION AND EXERCISE. THROUGH THESE MODIFICATIONS, THERE IS INFINITE POTENTIAL FOR BENEFIT FOR THE FETUS, THE NEWBORN, AND THE INDIVIDUAL AS WELL AS POPULATION EFFECTS. ASSOCIATION WITH CV DISEASE, INCLUDING CORONARY HEART DISEASE AND PERIPHERAL VASCULAR DISEASE, IS EVIDENT THROUGH EPIGENETIC RELATIONSHIPS AND MODIFICATION BY MAJOR CV RISK FACTORS SUCH AS TOBACCO ABUSE. AGING ITSELF MAY BE ALTERED BY EPIGENETIC MODIFICATION. KNOWLEDGE OF EPIGENETICS AND ITS RELEVANCE TO THE DEVELOPMENT, MODIFICATION, AND PREVENTION OF CV DISEASE IS IN A VERY PRELIMINARY STAGE BUT HAS AN INFINITE FUTURE. 2015 13 2965 41 GENETIC AND EPIGENETIC MODIFICATIONS IN THE PATHOGENESIS OF DIABETIC RETINOPATHY: A MOLECULAR LINK TO REGULATE GENE EXPRESSION. INTENSIFICATION IN THE FREQUENCY OF DIABETES AND THE ASSOCIATED VASCULAR COMPLICATIONS HAS BEEN A ROOT CAUSE OF BLINDNESS AND VISUAL IMPAIRMENT WORLDWIDE. ONE SUCH VASCULAR COMPLICATION WHICH HAS BEEN THE PROMINENT CAUSE OF BLINDNESS; RETINAL VASCULATURE, NEURONAL AND GLIAL ABNORMALITIES IS DIABETIC RETINOPATHY (DR), A CHRONIC COMPLICATED OUTCOME OF TYPE 1 AND TYPE 2 DIABETES. IT HAS ALSO BECOME CLEAR THAT "GENETIC" VARIATIONS IN POPULATION ALONE CAN'T EXPLAIN THE DEVELOPMENT AND PROGRESSION OF DIABETES AND ITS COMPLICATIONS INCLUDING DR. DR EXPERIENCES ENGAGEMENT OF FOREMOST MEDIATORS OF DIABETES SUCH AS HYPERGLYCEMIA, OXIDANT STRESS, AND INFLAMMATORY FACTORS THAT LEAD TO THE DYSREGULATION OF "EPIGENETIC" MECHANISMS INVOLVING HISTONE ACETYLATION AND HISTONE AND DNA METHYLATION, CHROMATIN REMODELING AND EXPRESSION OF A COMPLEX SET OF STRESS-REGULATED AND DISEASE-ASSOCIATED GENES. IN ADDITION, BOTH ELEVATED GLUCOSE CONCENTRATION AND INSULIN RESISTANCE LEAVE A ROBUST EFFECT ON EPIGENETIC REPROGRAMMING OF THE ENDOTHELIAL CELLS TOO, SINCE ENDOTHELIUM ASSOCIATED WITH THE EYE AIDS IN MAINTAINING THE VASCULAR HOMEOSTASIS. FURTHERMORE, SEVERAL STUDIES CONDUCTED ON THE DISEASE SUGGEST THAT THE MODIFICATIONS OF THE EPIGENOME MIGHT BE THE FUNDAMENTAL MECHANISM(S) FOR THE PROPOSED METABOLIC MEMORY' RESULTING INTO PROLONGED GENE EXPRESSION FOR INFLAMMATION AND CELLULAR DYSFUNCTION EVEN AFTER ATTAINING THE GLYCEMIC CONTROL IN DIABETICS. HENCEFORTH, THE PRESENT REVIEW FOCUSES ON THE ASPECTS OF GENETIC AND EPIGENETIC ALTERATIONS IN GENES SUCH AS VASCULAR ENDOTHELIAL GROWTH FACTOR AND ALDOSE REDUCTASE CONSIDERED BEING ASSOCIATED WITH DR. IN ADDITION, WE DISCUSS BRIEFLY THE ROLE OF THE THIOREDOXIN-INTERACTING PROTEIN TXNIP, WHICH IS STRONGLY INDUCED BY HIGH GLUCOSE AND DIABETES, IN CELLULAR OXIDATIVE STRESS AND MITOCHONDRIAL DYSFUNCTION POTENTIALLY LEADING TO CHROMATIN REMODELING AND OCULAR COMPLICATIONS OF DIABETES. THE IDENTIFICATION OF DISEASE-ASSOCIATED GENES AND THEIR EPIGENETIC REGULATIONS WILL LEAD TO POTENTIAL NEW DRUGS AND GENE THERAPIES AS WELL AS PERSONALIZED MEDICINE TO PREVENT OR SLOW DOWN THE PROGRESSION OF DR. 2016 14 2549 38 EPIGENETICS IN OBESITY AND DIABETES MELLITUS: NEW INSIGHTS. A LONG-TERM COMPLICATION OF OBESITY IS THE DEVELOPMENT OF TYPE 2 DIABETES (T2D). PATIENTS WITH T2D HAVE BEEN DESCRIBED AS HAVING EPIGENETIC MODIFICATIONS. EPIGENETICS IS THE POST-TRANSCRIPTIONAL MODIFICATION OF DNA OR ASSOCIATED FACTORS CONTAINING GENETIC INFORMATION. THESE ENVIRONMENTALLY-INFLUENCED MODIFICATIONS, MAINTAINED DURING CELL DIVISION, CAUSE STABLE CHANGES IN GENE EXPRESSION. EPIGENETIC MODIFICATIONS OF T2D ARE DNA METHYLATION, ACETYLATION, UBIQUITYLATION, SUMOYLATION, AND PHOSPHORYLATION AT THE LYSINE RESIDUE AT THE AMINO TERMINUS OF HISTONES, AFFECTING DNA, HISTONES, AND NON-CODING RNA. DNA METHYLATION HAS BEEN SHOWN IN PANCREATIC ISLETS, ADIPOSE TISSUE, SKELETAL MUSCLE, AND THE LIVER. FURTHERMORE, EPIGENETIC CHANGES HAVE BEEN OBSERVED IN CHRONIC COMPLICATIONS OF T2D, SUCH AS DIABETIC NEPHROPATHY, DIABETIC RETINOPATHY, AND DIABETIC NEUROPATHY. RECENTLY, A NEW DRUG HAS BEEN DEVELOPED WHICH ACTS ON BROMODOMAINS AND EXTRATERMINAL (BET) DOMAIN PROTEINS, WHICH OPERATE LIKE EPIGENETIC READERS AND COMMUNICATE WITH CHROMATIN TO MAKE DNA ACCESSIBLE FOR TRANSCRIPTION BY INHIBITING THEM. THIS DRUG (APABETALONE) IS BEING STUDIED TO PREVENT MAJOR ADVERSE CARDIOVASCULAR EVENTS IN PEOPLE WITH T2D, LOW HDL CHOLESTEROL, CHRONIC KIDNEY FAILURE, AND RECENT CORONARY EVENTS. THIS REVIEW AIMS TO DESCRIBE THE RELATIONSHIP BETWEEN OBESITY, LONG-TERM COMPLICATIONS SUCH AS T2D, AND EPIGENETIC MODIFICATIONS AND THEIR POSSIBLE TREATMENTS. 2023 15 2163 38 EPIGENETIC MECHANISMS IN DIABETIC VASCULAR COMPLICATIONS. THERE HAS BEEN A RAPID INCREASE IN THE INCIDENCE OF DIABETES AS WELL THE ASSOCIATED VASCULAR COMPLICATIONS. BOTH GENETIC AND ENVIRONMENTAL FACTORS HAVE BEEN IMPLICATED IN THESE PATHOLOGIES. INCREASING EVIDENCE SUGGESTS THAT EPIGENETIC FACTORS PLAY A KEY ROLE IN THE COMPLEX INTERPLAY BETWEEN GENES AND THE ENVIRONMENT. ACTIONS OF MAJOR PATHOLOGICAL MEDIATORS OF DIABETES AND ITS COMPLICATIONS SUCH AS HYPERGLYCAEMIA, OXIDANT STRESS, AND INFLAMMATORY FACTORS CAN LEAD TO DYSREGULATED EPIGENETIC MECHANISMS THAT AFFECT CHROMATIN STRUCTURE AND GENE EXPRESSION. FURTHERMORE, PERSISTENCE OF THIS ALTERED STATE OF THE EPIGENOME MAY BE THE UNDERLYING MECHANISM CONTRIBUTING TO A 'METABOLIC MEMORY' THAT RESULTS IN CHRONIC INFLAMMATION AND VASCULAR DYSFUNCTION IN DIABETES EVEN AFTER ACHIEVING GLYCAEMIC CONTROL. FURTHER EXAMINATION OF EPIGENETIC MECHANISMS BY ALSO TAKING ADVANTAGE OF RECENTLY DEVELOPED NEXT-GENERATION SEQUENCING TECHNOLOGIES CAN PROVIDE NOVEL INSIGHTS INTO THE PATHOLOGY OF DIABETES AND ITS COMPLICATIONS AND LEAD TO THE DISCOVERY OF MUCH NEEDED NEW DRUG TARGETS FOR THESE DISEASES. IN THIS REVIEW, WE HIGHLIGHT THE ROLE OF EPIGENETICS IN DIABETES AND ITS VASCULAR COMPLICATIONS, AND RECENT TECHNOLOGICAL ADVANCES THAT HAVE SIGNIFICANTLY ACCELERATED THE FIELD. 2011 16 125 34 A SYSTEMS BIOLOGY OVERVIEW ON HUMAN DIABETIC NEPHROPATHY: FROM GENETIC SUSCEPTIBILITY TO POST-TRANSCRIPTIONAL AND POST-TRANSLATIONAL MODIFICATIONS. DIABETIC NEPHROPATHY (DN), A MICROVASCULAR COMPLICATION OCCURRING IN APPROXIMATELY 20-40% OF PATIENTS WITH TYPE 2 DIABETES MELLITUS (T2DM), IS CHARACTERIZED BY THE PROGRESSIVE IMPAIRMENT OF GLOMERULAR FILTRATION AND THE DEVELOPMENT OF KIMMELSTIEL-WILSON LESIONS LEADING TO END-STAGE RENAL FAILURE (ESRD). THE CAUSES AND MOLECULAR MECHANISMS MEDIATING THE ONSET OF T2DM CHRONIC COMPLICATIONS ARE YET SKETCHY AND IT IS NOT CLEAR WHY DISEASE PROGRESSION OCCURS ONLY IN SOME PATIENTS. WE PERFORMED A SYSTEMATIC ANALYSIS OF THE MOST RELEVANT STUDIES INVESTIGATING GENETIC SUSCEPTIBILITY AND SPECIFIC TRANSCRIPTOMIC, EPIGENETIC, PROTEOMIC, AND METABOLOMIC PATTERNS IN ORDER TO SUMMARIZE THE MOST SIGNIFICANT TRAITS ASSOCIATED WITH THE DISEASE ONSET AND PROGRESSION. THE PICTURE THAT EMERGES IS COMPLEX AND FASCINATING AS IT INCLUDES THE REGULATION/DYSREGULATION OF NUMEROUS BIOLOGICAL PROCESSES, CONVERGING TOWARD THE ACTIVATION OF INFLAMMATORY PROCESSES, OXIDATIVE STRESS, REMODELING OF CELLULAR FUNCTION AND MORPHOLOGY, AND DISTURBANCE OF METABOLIC PATHWAYS. THE GROWING INTEREST IN THE CHARACTERIZATION OF PROTEIN POST-TRANSLATIONAL MODIFICATIONS AND THE IMPORTANCE OF HANDLING LARGE DATASETS USING A SYSTEMS BIOLOGY APPROACH ARE ALSO DISCUSSED. 2016 17 4204 29 METABOLISM, EPIGENETICS, AND CAUSAL INFERENCE IN HEART FAILURE. EUKARYOTES MUST BALANCE THE METABOLIC AND CELL DEATH ACTIONS OF MITOCHONDRIA VIA CONTROL OF GENE EXPRESSION AND CELL FATE BY CHROMATIN, THEREBY FUNCTIONALLY BINDING THE METABOLOME AND EPIGENOME. THIS INTERACTION HAS FAR-REACHING IMPLICATIONS FOR CHRONIC DISEASES IN HUMANS, THE MOST COMMON OF WHICH ARE THOSE OF THE CARDIOVASCULAR SYSTEM. THE MOST DEVASTATING CONSEQUENCE OF CARDIOVASCULAR DISEASE, HEART FAILURE, IS NOT A SINGLE DISEASE, DIAGNOSIS, OR ENDPOINT. HUMAN AND ANIMAL STUDIES HAVE REVEALED THAT, REGARDLESS OF ETIOLOGY AND SYMPTOMS, HEART FAILURE IS UNIVERSALLY ASSOCIATED WITH ABNORMAL METABOLISM AND GENE EXPRESSION - TO FRAME THIS AS CAUSE OR CONSEQUENCE, HOWEVER, MAY BE TO WRONGFOOT THE QUESTION. THIS ESSAY AIMS TO CHALLENGE CURRENT THINKING ON METABOLIC-EPIGENETIC CROSSTALK IN HEART FAILURE, PRESENTING HYPOTHESES FOR HOW CHRONIC DISEASES ARISE, TAKE HOLD, AND PERSIST. WE UNPACK ASSUMPTIONS ABOUT THE ORDER OF OPERATIONS FOR GENE EXPRESSION AND METABOLISM, EXPLORING RECENT FINDINGS IN NONCARDIAC SYSTEMS THAT LINK METABOLIC INTERMEDIATES DIRECTLY TO CHROMATIN REMODELING. LASTLY, WE DISCUSS POTENTIAL MECHANISMS BY WHICH CHROMATIN MAY SERVE AS A SUBSTRATE FOR METABOLIC MEMORY, AND HOW CHANGES IN CELLULAR TRANSCRIPTOMES (AND HENCE IN CELLULAR BEHAVIOR) IN RESPONSE TO STRESS CORRESPOND TO GLOBAL CHANGES IN CHROMATIN ACCESSIBILITY AND STRUCTURE. 2020 18 3593 28 IMPLICATION OF THE MEDITERRANEAN DIET ON THE HUMAN EPIGENOME. EPIGENETICS, DEFINED AS "HEREDITARY CHANGES IN GENE EXPRESSION THAT OCCUR WITHOUT ANY CHANGE IN THE DNA SEQUENCE", CONSISTS OF VARIOUS EPIGENETIC MARKS, INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS, AND NON-CODING RNAS. THE EPIGENOME, WHICH HAS A DYNAMIC STRUCTURE IN RESPONSE TO INTRACELLULAR AND EXTRACELLULAR STIMULI, HAS A KEY ROLE IN THE CONTROL OF GENE ACTIVITY, SINCE IT IS LOCATED AT THE INTERSECTION OF CELLULAR INFORMATION ENCODED IN THE GENOME AND MOLECULAR/CHEMICAL INFORMATION OF EXTRACELLULAR ORIGIN. THE FOCUS SHIFT OF STUDIES TO EPIGENETIC REPROGRAMMING HAS LED TO THE FORMATION AND PROGRESSIVE IMPORTANCE OF A CONCEPT CALLED "NUTRIEPIGENETICS", WHOSE AIM IS TO PREVENT DISEASES BY INTERVENING ON NUTRITION STYLE. AMONG THE DIET TYPES ADOPTED IN THE WORLD, THE RENOWNED MEDITERRANEAN DIET (MD), BEING RICH IN UNSATURATED FATTY ACIDS AND CONTAINING HIGH LEVELS OF WHOLE GRAIN FOODS AND LARGE QUANTITIES OF FRUITS, VEGETABLES, AND LEGUMES, HAS SHOWN NUMEROUS ADVANTAGES IN EXCLUDING CHRONIC DISEASES. ADDITIONALLY, THE FACT THAT THIS DIET IS RICH IN POLYPHENOLS WITH HIGH ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES HAS AN UNDENIABLE EFFECT IN TURNING SOME CELLULAR PATHWAYS AGAINST THE DISEASE. IT IS ALSO APPARENT THAT THE EFFECTS OF POLYPHENOLS ON THE EPIGENOME CAUSE CHANGES IN MECHANISMS SUCH AS DNA METHYLATION AND HISTONE ACETYLATION/DEACETYLATION, WHICH HAVE A REGULATORY EFFECT ON GENE REGULATION. THIS REVIEW PRESENTS THE EFFECTS OF LONG-TERM CONSUMPTION OF NUTRIENTS FROM THE MD ON THE EPIGENOME AND DISCUSSES THE BENEFITS OF THIS DIET IN THE TREATMENT AND EVEN PREVENTION OF CHRONIC DISEASES. 2022 19 2609 31 EPIGENETICS: A POTENTIAL KEY MECHANISM INVOLVED IN THE PATHOGENESIS OF CARDIORENAL SYNDROMES. EPIGENETICS IS DEFINED AS THE HERITABLE CHANGES IN GENE EXPRESSION PATTERNS WHICH ARE NOT DIRECTLY ENCODED BY MODIFICATIONS IN THE NUCLEOTIDE DNA SEQUENCE OF THE GENOME, INCLUDING HIGHER ORDER CHROMATIN ORGANIZATION, DNA METHYLATION, CYTOSINE MODIFICATIONS, COVALENT HISTONE TAIL MODIFICATIONS, AND SHORT NON-CODING RNA MOLECULES. RECENTLY, MUCH ATTENTION HAS BEEN PAID TO THE ROLE AND THE FUNCTION OF EPIGENETICS AND EPIMUTATIONS IN THE CELLULAR AND SUBCELLULAR PATHWAYS AND IN THE REGULATION OF GENES IN THE SETTING OF BOTH KIDNEY AND CARDIOVASCULAR DISEASE. INDEED, DEREGULATION OF HISTONE ALTERATIONS HAS BEEN HIGHLIGHTED IN A LARGE SPECTRUM OF RENAL AND CARDIAC DISEASE, INCLUDING CHRONIC AND ACUTE RENAL INJURY, RENAL AND CARDIAC FIBROSIS, CARDIAC HYPERTROPHY AND FAILURE, KIDNEY CONGENITAL ANOMALIES, RENAL HYPOXIA, AND DIABETIC RENAL COMPLICATIONS. NEVERTHELESS, THE ROLE OF EPIGENETICS IN THE PATHOGENESIS AND PATHOPHYSIOLOGY OF CARDIORENAL SYNDROMES IS CURRENTLY UNDEREXPLORED. GIVEN THE SIGNIFICANT CLINICAL RELEVANCE OF HEART-KIDNEY CROSSTALK, EFFORTS IN THE RESEARCH FOR NEW ACTION MECHANISMS CONCURRENTLY OPERATING IN BOTH PATHOLOGIES ARE THUS OF MAXIMUM INTEREST. THIS REVIEW FOCUSES ON EPIGENETIC MECHANISMS INVOLVED IN HEART AND KIDNEY DISEASE, AND THEIR POSSIBLE ROLE IN THE SETTING OF CARDIORENAL SYNDROMES. 2018 20 2136 39 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