1 6725 141 VITAMIN D: NOT JUST BONE METABOLISM BUT A KEY PLAYER IN CARDIOVASCULAR DISEASES. VITAMIN D IS THE FIRST ITEM OF DRUG EXPENDITURE FOR THE TREATMENT OF OSTEOPOROSIS. ITS DEFICIENCY IS A CONDITION THAT AFFECTS NOT ONLY OLDER INDIVIDUALS BUT ALSO YOUNG PEOPLE. RECENTLY, THE SCIENTIFIC COMMUNITY HAS FOCUSED ITS ATTENTION ON THE POSSIBLE ROLE OF VITAMIN D IN THE DEVELOPMENT OF SEVERAL CHRONIC DISEASES SUCH AS CARDIOVASCULAR AND METABOLIC DISEASES. THIS REVIEW AIMS TO HIGHLIGHT THE POSSIBLE ROLE OF VITAMIN D IN CARDIOVASCULAR AND METABOLIC DISEASES. IN PARTICULAR, HERE WE EXAMINE (1) THE ROLE OF VITAMIN D IN DIABETES MELLITUS, METABOLIC SYNDROME, AND OBESITY, AND ITS INFLUENCE ON INSULIN SECRETION; (2) ITS ROLE IN ATHEROSCLEROSIS, IN WHICH CHRONIC VITAMIN D DEFICIENCY, LOWER THAN 20 NG/ML (50 NMOL/L), HAS EMERGED AMONG THE NEW RISK FACTORS; (3) THE ROLE OF VITAMIN D IN ESSENTIAL HYPERTENSION, IN WHICH LOW PLASMA LEVELS OF VITAMIN D HAVE BEEN ASSOCIATED WITH BOTH AN INCREASE IN THE PREVALENCE OF HYPERTENSION AND DIASTOLIC HYPERTENSION; (4) THE ROLE OF VITAMIN D IN PERIPHERAL ARTERIOPATHIES AND ANEURYSMAL PATHOLOGY, REPORTING THAT PATIENTS WITH PERIPHERAL ARTERY DISEASES HAD LOWER VITAMIN D VALUES THAN NON-SUFFERING PAD CONTROLS; (5) THE GENETIC AND EPIGENETIC ROLE OF VITAMIN D, HIGHLIGHTING ITS TRANSCRIPTIONAL REGULATION CAPACITY; AND (6) THE ROLE OF VITAMIN D IN CARDIAC REMODELING AND DISEASE. DESPITE THE MANY OBSERVATIONAL STUDIES AND META-ANALYSES SUPPORTING THE CRITICAL ROLE OF VITAMIN D IN CARDIOVASCULAR PHYSIOPATHOLOGY, CLINICAL TRIALS DESIGNED TO EVALUATE THE SPECIFIC ROLE OF VITAMIN D IN CARDIOVASCULAR DISEASE ARE SCARCE. THE CHARACTERIZATION OF THE IMPORTANCE OF VITAMIN D AS A MARKER OF PATHOLOGY SHOULD REPRESENT A FUTURE RESEARCH CHALLENGE. 2021 2 6259 37 THE MOLECULAR MECHANISMS BY WHICH VITAMIN D PREVENTS INSULIN RESISTANCE AND ASSOCIATED DISORDERS. NUMEROUS STUDIES HAVE SHOWN THAT VITAMIN D DEFICIENCY IS VERY COMMON IN MODERN SOCIETIES AND IS PERCEIVED AS AN IMPORTANT RISK FACTOR IN THE DEVELOPMENT OF INSULIN RESISTANCE AND RELATED DISEASES SUCH AS OBESITY AND TYPE 2 DIABETES (T2DM). WHILE IT IS GENERALLY ACCEPTED THAT VITAMIN D IS A REGULATOR OF BONE HOMEOSTASIS, ITS ABILITY TO COUNTERACT INSULIN RESISTANCE IS SUBJECT TO DEBATE. THE GOAL OF THIS COMMUNICATION IS TO REVIEW THE MOLECULAR MECHANISM BY WHICH VITAMIN D REDUCES INSULIN RESISTANCE AND RELATED COMPLICATIONS. THE UNIVERSITY LIBRARY, PUBMED, AND GOOGLE SCHOLAR WERE SEARCHED TO FIND RELEVANT STUDIES TO BE SUMMARIZED IN THIS REVIEW ARTICLE. INSULIN RESISTANCE IS ACCOMPANIED BY CHRONIC HYPERGLYCAEMIA AND INFLAMMATION. RECENT STUDIES HAVE SHOWN THAT VITAMIN D EXHIBITS INDIRECT ANTIOXIDATIVE PROPERTIES AND PARTICIPATES IN THE MAINTENANCE OF NORMAL RESTING ROS LEVEL. APPEALINGLY, VITAMIN D REDUCES INFLAMMATION AND REGULATES CA(2+) LEVEL IN MANY CELL TYPES. THEREFORE, THE BENEFICIAL ACTIONS OF VITAMIN D INCLUDE DIMINISHED INSULIN RESISTANCE WHICH IS OBSERVED AS AN IMPROVEMENT OF GLUCOSE AND LIPID METABOLISM IN INSULIN-SENSITIVE TISSUES. 2020 3 6718 39 VITAMIN D AND CARDIOVASCULAR DISEASES: CAUSALITY. VITAMIN D REGULATES BLOOD PRESSURE, CARDIAC FUNCTIONS, AND ENDOTHELIAL AND SMOOTH MUSCLE CELL FUNCTIONS, THUS, PLAYING AN IMPORTANT ROLE IN CARDIOVASCULAR HEALTH. OBSERVATIONAL STUDIES REPORT ASSOCIATIONS BETWEEN VITAMIN D DEFICIENCY WITH HYPERTENSION AND CARDIOVASCULAR-RELATED DEATHS. PEER-REVIEWED PAPERS WERE EXAMINED IN SEVERAL RESEARCH DATABASES AS PER THE GUIDELINES OF THE PREFERRED REPORTING ITEMS FOR SYSTEMATIC REVIEWS, USING KEY WORDS THAT ADDRESS THE RELATIONSHIP BETWEEN VITAMIN D AND CARDIOVASCULAR DISEASE. CORRELATIONS AND INTERPRETATIONS WERE MADE CONSIDERING THE RISKS-BENEFITS, BROADER EVIDENCE, AND IMPLICATIONS. THIS REVIEW ANALYZED CURRENT KNOWLEDGE REGARDING THE EFFECTS OF VITAMIN D ON THE CARDIOVASCULAR SYSTEM. 1,25(OH)(2)D AND RELATED EPIGENETIC MODIFICATIONS SUBDUE CELLULAR INFLAMMATION, IMPROVE OVERALL ENDOTHELIAL FUNCTIONS, REDUCE AGE-RELATED SYSTOLIC HYPERTENSION AND VASCULAR RIGIDITY, AND ATTENUATE THE ACTIONS OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM. MOST OBSERVATIONAL AND ECOLOGICAL STUDIES SUPPORT 25(OH)VITAMIN D HAVING PROTECTIVE EFFECTS ON THE CARDIOVASCULAR SYSTEM. HOWEVER, THE ASSOCIATION OF VITAMIN D DEFICIENCY WITH CARDIOVASCULAR DISEASES IS BASED PRIMARILY ON OBSERVATIONAL AND ECOLOGICAL STUDIES AND THUS, IS A MATTER OF CONTROVERSY. ADEQUATELY POWERED, RANDOMIZED CONTROLLED CLINICAL TRIAL DATA ARE NOT AVAILABLE TO CONFIRM THESE ASSOCIATIONS. THUS, TO TEST THE HYPOTHESIS THAT CORRECTION OF VITAMIN D DEFICIENCY PROTECTS THE CARDIOVASCULAR SYSTEM, WELL-DESIGNED, STATISTICALLY POWERED, LONGER-TERM CLINICAL TRIALS ARE NEEDED IN PERSONS WITH VITAMIN D DEFICIENCY. NEVERTHELESS, THE AVAILABLE DATA SUPPORT THAT ADEQUATE VITAMIN D SUPPLEMENTATION AND/OR SENSIBLE SUNLIGHT EXPOSURE TO ACHIEVE OPTIMAL VITAMIN D STATUS ARE IMPORTANT IN THE PREVENTION OF CARDIOVASCULAR DISEASE AND OTHER CHRONIC DISEASES. 2018 4 3915 40 LINE-1 IN OBESITY AND CARDIOMETABOLIC DISEASES: A SYSTEMATIC REVIEW. EPIGENETIC MECHANISMS MAY PLAY AN IMPORTANT ROLE IN THE ETIOLOGY OF OBESITY AND CARDIOMETABOLIC DISEASES, BY ACTIVATING OR SILENCING THE RELATED-GENES. SCIENTIFIC EVIDENCE HAS SUGGESTED THAT LINE-1 METHYLATION IS ASSOCIATED WITH BODY COMPOSITION AND OBESITY-RELATED DISEASES, INCLUDING INSULIN RESISTANCE, TYPE 2 DIABETES MELLITUS, AND CARDIOVASCULAR DISEASE (CVD). IT ALSO HAS BEEN EVALUATED AS PREDICTOR OF WEIGHT LOSS. THE STUDIES' RESULTS ARE STILL CONFLICTING, AND POSITIVE AND NEGATIVE ASSOCIATIONS HAVE BEEN FOUND TO LINE-1 METHYLATION REGARDING ADIPOSITY AND CARDIOMETABOLIC MARKERS. OVERALL, THIS REVIEW PRESENTS OBSERVATIONAL (CROSS-SECTIONAL AND LONGITUDINAL) STUDIES AND INTERVENTIONS (DIET, EXERCISES, AND BARIATRIC SURGERY) THAT EVALUATED THE RELATIONSHIP OF THE LINE-1 METHYLATION WITH OBESITY, WEIGHT LOSS, DYSLIPIDEMIAS, HYPERTENSION, INSULIN RESISTANCE, CVD, AND METABOLIC SYNDROME. TEACHING POINTS EPIGENETIC MECHANISMS MAY PLAY AN IMPORTANT ROLE IN THE ETIOLOGY OF OBESITY AND CARDIOMETABOLIC DISEASES. MANY STUDIES HAVE RELATED METHYLATION OF LINE-1 WITH CARDIOMETABOLIC DISEASES; HOWEVER, THE RESULTS ARE STILL CONTROVERSIAL. THE RELATIONSHIP BETWEEN THE ETIOLOGY OF CHRONIC DISEASES AND THE METHYLATION OF LINE-1 IS NOT FULLY ELUCIDATED. WITH ADVANCES IN EPIGENETIC STUDIES, RELATED MECHANISMS MAY BE EARLY BIOMARKERS IN WEIGHT CHANGE AND CARDIOMETABOLIC RISK. 2019 5 3801 46 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 1710 39 DYSFUNCTIONAL IMMUNOMETABOLIC EFFECTS OF VITAMIN D DEFICIENCY, INCREASED CARDIOMETABOLIC RISK. POTENTIAL EPIDEMIOLOGICAL ALERT IN AMERICA? VITAMIN D DEFICIENCY IS A SERIOUS PUBLIC HEALTH PROBLEM WORLDWIDE THAT AFFECTS NOT ONLY SKELETAL HEALTH, BUT ALSO A WIDE RANGE OF ACUTE AND CHRONIC DISEASES. HOWEVER, THERE IS STILL SKEPTICISM BECAUSE OF THE LACK OF RANDOMIZED, CONTROLLED TRIALS TO SUPPORT ASSOCIATION STUDIES ON THE BENEFITS OF VITAMIN D FOR NON-SKELETAL HEALTH. THIS REVIEW WAS BASED ON ARTICLES PUBLISHED DURING THE 1980-2015 OBTAINED FROM THE COCHRANE CENTRAL REGISTER OF CONTROLLED TRIALS, MEDLINE AND PUBMED, AND FOCUSES ON RECENT CHALLENGES WITH REGARD TO THE DEFINITION OF VITAMIN D DEFICIENCY AND HOW TO ACHIEVE OPTIMAL SERUM 25-HYDROXYVITAMIN D LEVELS FROM DIETARY SOURCES, SUPPLEMENTS, AND SUN EXPOSURE. THE EFFECT OF VITAMIN D ON EPIGENETIC FETAL PROGRAMMING AND REGULATION OF GENES THAT MAY POTENTIALLY EXPLAIN WHY VITAMIN D COULD HAVE SUCH LIFELONG COMPREHENSIVE HEALTH BENEFITS IS REVIEWED. OPTIMIZATION OF VITAMIN D LEVELS IN CHILDREN AND ADULTS AROUND THE WORLD HAS POTENTIAL BENEFITS TO IMPROVE SKELETAL HEALTH AND TO REDUCE THE RISK OF CHRONIC DISEASES, INCLUDING SOME TYPES OF CANCER, AUTOIMMUNE DISEASES, INFECTIOUS DISEASES, TYPE 2 DIABETES MELLITUS, AND SEVERE CARDIOVASCULAR DISORDERS SUCH AS ATHEROTHROMBOSIS, NEUROCOGNITIVE DISORDERS, AND MORTALITY. 2017 7 4662 39 NEW DEVELOPMENTS IN THE PATHOGENESIS OF OBESITY-INDUCED HYPERTENSION. OBESITY IS A DISORDER THAT DEVELOPS FROM THE INTERACTION BETWEEN GENOTYPE AND ENVIRONMENT INVOLVING SOCIAL, BEHAVIORAL, CULTURAL, AND PHYSIOLOGICAL FACTORS. OBESITY INCREASES THE RISK FOR TYPE 2 DIABETES MELLITUS, HYPERTENSION, CARDIOVASCULAR DISEASE, CANCER, MUSCULOSKELETAL DISORDERS, CHRONIC KIDNEY AND PULMONARY DISEASE. ALTHOUGH OBESITY IS CLEARLY ASSOCIATED WITH AN INCREASED PREVALENCE OF HYPERTENSION, MANY OBESE INDIVIDUALS MAY NOT DEVELOP HYPERTENSION. PROTECTING FACTORS MAY EXIST AND IT IS IMPORTANT TO UNDERSTAND WHY OBESITY IS NOT ALWAYS RELATED TO HYPERTENSION. THE AIM OF THIS REVIEW IS TO HIGHLIGHT THE KNOWLEDGE GAP FOR THE ASSOCIATION BETWEEN OBESITY, HYPERTENSION, AND POTENTIAL GENETIC AND RACIAL DIFFERENCES OR ENVIRONMENTAL FACTORS THAT MAY PROTECT OBESE PATIENTS AGAINST THE DEVELOPMENT OF HYPERTENSION AND OTHER CO-MORBIDITIES. SPECIFIC MUTATIONS IN THE LEPTIN AND THE MELANINOCORTIN RECEPTOR GENES IN ANIMAL MODELS OF OBESITY WITHOUT HYPERTENSION, THE ACTIONS OF ALPHA-MELANOCYTE STIMULATING HORMONE, AND SNS ACTIVITY IN OBESITY-RELATED HYPERTENSION MAY PROMOTE RECOGNITION OF PROTECTIVE AND PROMOTING FACTORS FOR HYPERTENSION IN OBESITY. FURTHERMORE, GENE-ENVIRONMENT INTERACTIONS MAY HAVE THE POTENTIAL TO MODIFY GENE EXPRESSION AND EPIGENETIC MECHANISMS COULD ALSO CONTRIBUTE TO THE HERITABILITY OF OBESITY-INDUCED HYPERTENSION. FINALLY, DIFFERENCES IN NUTRITION, GUT MICROBIOTA, EXPOSURE TO SUN LIGHT AND EXERCISE MAY PLAY AN IMPORTANT ROLE IN THE PRESENCE OR ABSENCE OF HYPERTENSION IN OBESITY. 2015 8 6399 39 THE ROLES AND MECHANISMS OF ACTIONS OF VITAMIN C IN BONE: NEW DEVELOPMENTS. VITAMIN C IS AN IMPORTANT ANTIOXIDANT AND COFACTOR THAT IS INVOLVED IN THE REGULATION OF DEVELOPMENT, FUNCTION, AND MAINTENANCE OF SEVERAL CELL TYPES IN THE BODY. DEFICIENCIES IN VITAMIN C CAN LEAD TO CONDITIONS SUCH AS SCURVY, WHICH, AMONG OTHER AILMENTS, CAUSES GINGIVIA, BONE PAIN, AND IMPAIRED WOUND HEALING. THIS REVIEW EXAMINES THE FUNCTIONAL IMPORTANCE OF VITAMIN C AS IT RELATES TO THE DEVELOPMENT AND MAINTENANCE OF BONE TISSUES. ANALYSIS OF SEVERAL EPIDEMIOLOGICAL STUDIES AND GENETIC MOUSE MODELS REGARDING THE EFFECT OF VITAMIN C SHOWS A POSITIVE EFFECT ON BONE HEALTH. OVERALL, VITAMIN C EXERTS A POSITIVE EFFECT ON TRABECULAR BONE FORMATION BY INFLUENCING EXPRESSION OF BONE MATRIX GENES IN OSTEOBLASTS. RECENT STUDIES ON THE MOLECULAR PATHWAY FOR VITAMIN C ACTIONS THAT INCLUDE DIRECT EFFECTS OF VITAMIN C ON TRANSCRIPTIONAL REGULATION OF TARGET GENES BY INFLUENCING THE ACTIVITY OF TRANSCRIPTION FACTORS AND BY EPIGENETIC MODIFICATION OF KEY GENES INVOLVED IN SKELETAL DEVELOPMENT AND MAINTENANCE ARE DISCUSSED. WITH AN UNDERSTANDING OF MECHANISMS INVOLVED IN THE UPTAKE AND METABOLISM OF VITAMIN C AND KNOWLEDGE OF PRECISE MOLECULAR PATHWAYS FOR VITAMIN C ACTIONS IN BONE CELLS, IT IS POSSIBLE THAT NOVEL THERAPEUTIC STRATEGIES CAN BE DEVELOPED OR EXISTING THERAPIES CAN BE MODIFIED FOR THE TREATMENT OF OSTEOPOROTIC FRACTURES. 2015 9 5821 39 STRESS IN OBESITY AND ASSOCIATED METABOLIC AND CARDIOVASCULAR DISORDERS. OBESITY HAS SIGNIFICANT IMPLICATIONS FOR HEALTHCARE, SINCE IT IS A MAJOR RISK FACTOR FOR BOTH TYPE 2 DIABETES AND THE METABOLIC SYNDROME. THIS SYNDROME IS A COMMON AND COMPLEX DISORDER COMBINING OBESITY, DYSLIPIDEMIA, HYPERTENSION, AND INSULIN RESISTANCE. IT IS ASSOCIATED WITH HIGH ATHEROSCLEROTIC CARDIOVASCULAR RISK, WHICH CAN ONLY PARTIALLY BE EXPLAINED BY ITS COMPONENTS. THEREFORE, TO EXPLAIN HOW OBESITY CONTRIBUTES TO THE DEVELOPMENT OF METABOLIC AND CARDIOVASCULAR DISORDERS, MORE AND BETTER INSIGHT IS REQUIRED INTO THE EFFECTS OF PERSONAL AND ENVIRONMENTAL STRESS ON DISEASE PROCESSES. IN THIS PAPER, WE SHOW THAT OBESITY IS A CHRONIC INFLAMMATORY DISEASE, WHICH HAS MANY MOLECULAR MECHANISMS IN COMMON WITH ATHEROSCLEROSIS. FURTHERMORE, WE FOCUS ON THE ROLE OF OXIDATIVE STRESS ASSOCIATED WITH OBESITY IN THE DEVELOPMENT OF THE METABOLIC SYNDROME. WE DISCUSS HOW SEVERAL STRESS CONDITIONS ARE RELATED TO INFLAMMATION AND OXIDATIVE STRESS IN ASSOCIATION WITH OBESITY AND ITS COMPLICATIONS. WE ALSO EMPHASIZE THE RELATION BETWEEN STRESS CONDITIONS AND THE DEREGULATION OF EPIGENETIC CONTROL MECHANISMS BY MEANS OF MICRORNAS AND SHOW HOW THIS IMPAIRMENT FURTHER CONTRIBUTES TO THE DEVELOPMENT OF OBESITY, CLOSING THE VICIOUS CIRCLE. FINALLY, WE DISCUSS THE LIMITATIONS OF CURRENT ANTI-INFLAMMATION AND ANTIOXIDANT THERAPY TO TREAT OBESITY. 2012 10 6716 34 VITAMIN A: TOO GOOD TO BE BAD? VITAMIN A IS A MICRONUTRIENT IMPORTANT FOR VISION, CELL GROWTH, REPRODUCTION AND IMMUNITY. BOTH DEFICIENCY AND EXCESS CONSUMING OF VITAMIN A CAUSE SEVERE HEALTH CONSEQUENCES. ALTHOUGH DISCOVERED AS THE FIRST LIPOPHILIC VITAMIN ALREADY MORE THAN A CENTURY AGO AND THE DEFINITION OF PRECISE BIOLOGICAL ROLES OF VITAMIN A IN THE SETTING OF HEALTH AND DISEASE, THERE ARE STILL MANY UNRESOLVED ISSUES RELATED TO THAT VITAMIN. PROTOTYPICALLY, THE LIVER THAT PLAYS A KEY ROLE IN THE STORAGE, METABOLISM AND HOMEOSTASIS OF VITAMIN A CRITICALLY RESPONDS TO THE VITAMIN A STATUS. ACUTE AND CHRONIC EXCESS VITAMIN A IS ASSOCIATED WITH LIVER DAMAGE AND FIBROSIS, WHILE ALSO HYPOVITAMINOSIS A IS ASSOCIATED WITH ALTERATIONS IN LIVER MORPHOLOGY AND FUNCTION. HEPATIC STELLATE CELLS ARE THE MAIN STORAGE SITE OF VITAMIN A. THESE CELLS HAVE MULTIPLE PHYSIOLOGICAL ROLES FROM BALANCING RETINOL CONTENT OF THE BODY TO MEDIATING INFLAMMATORY RESPONSES IN THE LIVER. STRIKINGLY, DIFFERENT ANIMAL DISEASE MODELS ALSO RESPOND TO VITAMIN A STATUSES DIFFERENTLY OR EVEN OPPOSING. IN THIS REVIEW, WE DISCUSS SOME OF THESE CONTROVERSIAL ISSUES IN UNDERSTANDING VITAMIN A BIOLOGY. MORE STUDIES OF THE INTERACTIONS OF VITAMIN A WITH ANIMAL GENOMES AND EPIGENETIC SETTINGS ARE ANTICIPATED IN THE FUTURE. 2023 11 4801 31 OBESITY AND INSULIN RESISTANCE: ASSOCIATIONS WITH CHRONIC INFLAMMATION, GENETIC AND EPIGENETIC FACTORS. BACKGROUND: OBESITY IS KNOWN TO BE A MULTIFACTORIAL DISEASE. IN ITS PATHOGENESIS, DIFFERENT FACTORS SUCH AS CHRONIC INFLAMMATION, OXIDATIVE STRESS, INSULIN RESISTANCE, GENETIC FACTORS, ENVIRONMENTAL EFFECTS, VEGETATIVE DISTURBANCE, AND UNBALANCED NUTRITION PLAY A SIGNIFICANT ROLE. METHODOLOGY: THIS STUDY DESCRIBES THE ASSOCIATION OF OBESITY AND INSULIN RESISTANCE WITH CHRONIC INFLAMMATION, GENETIC, AND EPIGENETIC FACTORS. PREVIOUS LITERATURE HAS BEEN REVIEWED TO EXPLAIN THE RELATION OF OBESITY WITH THOSE FACTORS INVOLVED IN CHRONIC LOW-GRADE INFLAMMATION AND INSULIN. RESULTS: OBESITY IS ASSOCIATED WITH A DECREASE IN GHRELIN SECRETION, ELEVATED PLASMA LEPTIN LEVELS, OXIDATIVE STRESS, INCREASED MACROPHAGE PHAGOCYTIC ACTIVITY, AND THE INDUCTION OF PROINFLAMMATORY SYNTHESIS OF CYTOKINES AND INTERFERON-GAMMA. OBESITY IS LINKED TO DECREASED LEVELS OF CYTOCHROME P450 (CYP) ENZYMES AND IMPAIRED DETOXIFICATION PROCESSES. DEFICIENCY OF VITAMINS AND MINERALS CAN ALSO PLAY A SIGNIFICANT ROLE IN THE DEVELOPMENT OF OXIDATIVE STRESS AND CHRONIC INFLAMMATION IN OBESITY. THERE IS EVIDENCE OF ASSOCIATIONS BETWEEN A GENETIC PREDISPOSITION TO OBESITY IN CHILDREN WITH ELEVATED LEVELS OF CERTAIN MIRNAS. CONCLUSION: THE PURPOSE OF THE PRESENT REVIEW IS AN ANALYSIS OF THE MULTIPLE FACTORS ASSOCIATED WITH OBESITY. 2021 12 6067 46 THE DIABETES MELLITUS-ATHEROSCLEROSIS CONNECTION: THE ROLE OF LIPID AND GLUCOSE METABOLISM AND CHRONIC INFLAMMATION. DIABETES MELLITUS COMPRISES A GROUP OF CARBOHYDRATE METABOLISM DISORDERS THAT SHARE A COMMON MAIN FEATURE OF CHRONIC HYPERGLYCEMIA THAT RESULTS FROM DEFECTS OF INSULIN SECRETION, INSULIN ACTION, OR BOTH. INSULIN IS AN IMPORTANT ANABOLIC HORMONE, AND ITS DEFICIENCY LEADS TO VARIOUS METABOLIC ABNORMALITIES IN PROTEINS, LIPIDS, AND CARBOHYDRATES. ATHEROSCLEROSIS DEVELOPS AS A RESULT OF A MULTISTEP PROCESS ULTIMATELY LEADING TO CARDIOVASCULAR DISEASE ASSOCIATED WITH HIGH MORBIDITY AND MORTALITY. ALTERATION OF LIPID METABOLISM IS A RISK FACTOR AND CHARACTERISTIC FEATURE OF ATHEROSCLEROSIS. POSSIBLE LINKS BETWEEN THE TWO CHRONIC DISORDERS DEPENDING ON ALTERED METABOLIC PATHWAYS HAVE BEEN INVESTIGATED IN NUMEROUS STUDIES. IT WAS SHOWN THAT BOTH TYPES OF DIABETES MELLITUS CAN ACTUALLY INDUCE ATHEROSCLEROSIS DEVELOPMENT OR FURTHER ACCELERATE ITS PROGRESSION. ELEVATED GLUCOSE LEVEL, DYSLIPIDEMIA, AND OTHER METABOLIC ALTERATIONS THAT ACCOMPANY THE DISEASE DEVELOPMENT ARE TIGHTLY INVOLVED IN THE PATHOGENESIS OF ATHEROSCLEROSIS AT ALMOST EVERY STEP OF THE ATHEROGENIC PROCESS. CHRONIC INFLAMMATION IS CURRENTLY CONSIDERED AS ONE OF THE KEY FACTORS IN ATHEROSCLEROSIS DEVELOPMENT AND IS PRESENT STARTING FROM THE EARLIEST STAGES OF THE PATHOLOGY INITIATION. IT MAY ALSO BE REGARDED AS ONE OF THE POSSIBLE LINKS BETWEEN ATHEROSCLEROSIS AND DIABETES MELLITUS. HOWEVER, THE DATA AVAILABLE SO FAR DO NOT ALLOW FOR DEVELOPING EFFECTIVE ANTI-INFLAMMATORY THERAPEUTIC STRATEGIES THAT WOULD STOP ATHEROSCLEROTIC LESION PROGRESSION OR INDUCE LESION REDUCTION. IN THIS REVIEW, WE SUMMARIZE THE MAIN ASPECTS OF DIABETES MELLITUS THAT POSSIBLY AFFECT THE ATHEROGENIC PROCESS AND ITS RELATIONSHIP WITH CHRONIC INFLAMMATION. WE ALSO DISCUSS THE ESTABLISHED PATHOPHYSIOLOGICAL FEATURES THAT LINK ATHEROSCLEROSIS AND DIABETES MELLITUS, SUCH AS OXIDATIVE STRESS, ALTERED PROTEIN KINASE SIGNALING, AND THE ROLE OF CERTAIN MIRNA AND EPIGENETIC MODIFICATIONS. 2020 13 4855 39 OPTIMIZE DIETARY INTAKE OF VITAMIN D: AN EPIGENETIC PERSPECTIVE. PURPOSE OF REVIEW: VITAMIN D HAS RECEIVED GLOBAL ATTENTION BECAUSE OF ITS MANY HEALTH BENEFITS. ALTHOUGH THERE IS GENERAL AGREEMENT ABOUT THE IMPORTANCE OF VITAMIN D FOR BONE HEALTH, THERE REMAINS SKEPTICISM ABOUT THE NONSKELETAL HEALTH BENEFITS OF VITAMIN D. THIS REVIEW WILL NOT ONLY FOCUS ON THE VITAMIN D DEFICIENCY PANDEMIC AND WAYS TO TREAT AND PREVENT VITAMIN D DEFICIENCY BUT WILL ALSO EXPLORE THE EPIGENETIC MECHANISMS OF VITAMIN D THAT COULD HELP EXPLAIN MANY OF THE NONSKELETAL BENEFITS OF ENHANCING VITAMIN D STATUS. RECENT FINDINGS: THE INSTITUTE OF MEDICINE AND THE ENDOCRINE SOCIETY HAVE MADE NEW RECOMMENDATIONS FOR VITAMIN D INTAKE TO PREVENT VITAMIN D DEFICIENCY. VITAMIN D DEFICIENCY IS DEFINED AS A 25-HYDROXYVITAMIN D LEVEL BELOW 20 NG/ML AND VITAMIN D INSUFFICIENCY IS DEFINED AS 21-29 NG/ML. RECENT OBSERVATIONS HAVE SUGGESTED THAT VITAMIN D CAN INFLUENCE EPIGENETICS WHICH MAY HELP EXPLAIN THE NONSKELETAL HEALTH BENEFITS THAT HAVE BEEN REPORTED FOR VITAMIN D. SUMMARY: THERE IS GENERAL AGREEMENT THAT VITAMIN D DEFICIENCY IS A WORLDWIDE HEALTH PROBLEM. THIS IS DUE IN PART TO THE LACK OF APPRECIATION THAT SUNLIGHT IS AN IMPORTANT SOURCE OF VITAMIN D. THERE IS NO DOWNSIDE TO INCREASING VITAMIN D INTAKE AND RECENT OBSERVATIONS SUGGESTING THAT VITAMIN D INFLUENCES EPIGENETICS PROVIDE A NEW INSIGHT FOR THE IMPORTANCE OF VITAMIN D IN UTERO IN REDUCING RISK OF CHRONIC DISEASES LATER IN LIFE. 2012 14 6204 46 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 15 6342 43 THE ROLE OF EPIGENETIC REGULATOR SIRT1 IN BALANCING THE HOMEOSTASIS AND PREVENTING THE FORMATION OF SPECIFIC "SOIL" OF METABOLIC DISORDERS AND RELATED CANCERS. SIRT1 WAS DISCOVERED IN 1979 BUT GROWING INTEREST IN THIS PROTEIN OCCURRED ONLY 20 YEARS LATER WHEN ITS OVEREXPRESSION WAS REPORTED TO PROLONG THE LIFESPAN OF YEAST. SINCE THEN, SEVERAL STUDIES HAVE SHOWN THE BENEFITS OF ITS INCREASED EXPRESSION IN PREVENTING OR DELAYING OF MANY DISEASES. SIRT1, AS A HISTONE DEACETYLASE, IS AN EPIGENETIC REGULATOR BUT IT HAS WIDE RANGE OF NON-HISTONE TARGETS WHICH ARE INVOLVED IN METABOLISM, ENERGY SENSING PATHWAYS, CIRCADIAN MACHINERY AND IN INFLAMMATORY REGULATION. DISTURBANCES IN THESE INTERCONNECTED PROCESSES CAUSE DIFFERENT DISEASES, HOWEVER IT SEEMS THEY HAVE COMMON ROOTS IN UNBALANCED INFLAMMATORY PROCESSES AND LOWER LEVEL OR INACTIVATION OF SIRT1. SIRT1 INACTIVATION WAS IMPLICATED IN CORONAVIRUS DISEASE (COVID-19) SEVERITY AS WELL AND ITS LOW LEVEL COUNTED AS A PREDICTOR OF UNCONTROLLED COVID-19. SEVERAL OTHER DISEASES SUCH AS METABOLIC DISEASE, OBESITY, DIABETES, ALZHEIMER'S DISEASE, CARDIOVASCULAR DISEASE OR DEPRESSION ARE RELATED TO CHRONIC INFLAMMATION AND SIMILARLY SHOW DECREASED SIRT1 LEVEL. IT HAS RECENTLY BEEN KNOWN THAT SIRT1 IS INDUCIBLE BY CALORIE RESTRICTION/PROPER DIET, PHYSICAL ACTIVITY AND APPROPRIATE EMOTIONAL STATE. INDEED, A HEALTHIER METABOLIC STATE BELONGS TO HIGHER LEVEL OF SIRT1 EXPRESSION. THESE SUGGEST THAT APPROPRIATE LIFESTYLE AS NON-PHARMACOLOGICAL TREATMENT MAY BE A BENEFICIAL TOOL IN THE PREVENTION OF INFLAMMATION OR METABOLIC DISTURBANCE-RELATED DISEASES AS WELL AS COULD BE A PART OF THE COMPLEMENTARY THERAPY IN MEDICAL PRACTICE TO REACH BETTER THERAPEUTIC RESPONSE AND QUALITY OF LIFE. WE AIMED IN THIS REVIEW TO LINK THE BENEFICIAL EFFECT OF SIRT1 WITH THOSE DISEASES, WHERE ITS LEVEL DECREASED. MOREOVER, WE AIMED TO COLLECT EVIDENCES OF INTERVENTIONS OR TREATMENTS, WHICH INCREASE SIRT1 EXPRESSION AND THUS, OPEN THE POSSIBILITY TO USE THEM AS PREVENTIVE OR COMPLEMENTARY THERAPIES IN MEDICAL PRACTICE. 2022 16 2507 38 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 17 6133 43 THE EPIGENETIC ROLE OF VITAMIN C IN NEURODEVELOPMENT. THE MATERNAL DIET DURING PREGNANCY IS A KEY DETERMINANT OF OFFSPRING HEALTH. EARLY STUDIES HAVE LINKED POOR MATERNAL NUTRITION DURING GESTATION WITH A PROPENSITY FOR THE DEVELOPMENT OF CHRONIC CONDITIONS IN OFFSPRING. THESE CONDITIONS INCLUDE CARDIOVASCULAR DISEASE, TYPE 2 DIABETES AND EVEN COMPROMISED MENTAL HEALTH. WHILE MULTIPLE FACTORS MAY CONTRIBUTE TO THESE OUTCOMES, DISTURBED EPIGENETIC PROGRAMMING DURING EARLY DEVELOPMENT IS ONE POTENTIAL BIOLOGICAL MECHANISM. THE EPIGENOME IS PROGRAMMED PRIMARILY IN UTERO, AND DURING THIS TIME, THE DEVELOPING FETUS IS HIGHLY SUSCEPTIBLE TO ENVIRONMENTAL FACTORS SUCH AS NUTRITIONAL INSULTS. DURING NEURODEVELOPMENT, EPIGENETIC PROGRAMMING COORDINATES THE FORMATION OF PRIMITIVE CENTRAL NERVOUS SYSTEM STRUCTURES, NEUROGENESIS, AND NEUROPLASTICITY. DYSREGULATED EPIGENETIC PROGRAMMING HAS BEEN IMPLICATED IN THE AETIOLOGY OF SEVERAL NEURODEVELOPMENTAL DISORDERS SUCH AS TATTON-BROWN-RAHMAN SYNDROME. ACCORDINGLY, THERE IS GREAT INTEREST IN DETERMINING HOW MATERNAL NUTRIENT AVAILABILITY IN PREGNANCY MIGHT AFFECT THE EPIGENETIC STATUS OF OFFSPRING, AND HOW SUCH INFLUENCES MAY PRESENT PHENOTYPICALLY. IN RECENT YEARS, A NUMBER OF EPIGENETIC ENZYMES THAT ARE ACTIVE DURING EMBRYONIC DEVELOPMENT HAVE BEEN FOUND TO REQUIRE VITAMIN C AS A COFACTOR. THESE ENZYMES INCLUDE THE TEN-ELEVEN TRANSLOCATION METHYLCYTOSINE DIOXYGENASES (TETS) AND THE JUMONJI C DOMAIN-CONTAINING HISTONE LYSINE DEMETHYLASES THAT CATALYSE THE OXIDATIVE REMOVAL OF METHYL GROUPS ON CYTOSINES AND HISTONE LYSINE RESIDUES, RESPECTIVELY. THESE ENZYMES ARE INTEGRAL TO EPIGENETIC REGULATION AND HAVE FUNDAMENTAL ROLES IN CELLULAR DIFFERENTIATION, THE MAINTENANCE OF PLURIPOTENCY AND DEVELOPMENT. THE DEPENDENCE OF THESE ENZYMES ON VITAMIN C FOR OPTIMAL CATALYTIC ACTIVITY ILLUSTRATES A POTENTIALLY CRITICAL CONTRIBUTION OF THE NUTRIENT DURING MAMMALIAN DEVELOPMENT. THESE INSIGHTS ALSO HIGHLIGHT A POTENTIAL RISK ASSOCIATED WITH VITAMIN C INSUFFICIENCY DURING PREGNANCY. THE LINK BETWEEN VITAMIN C INSUFFICIENCY AND DEVELOPMENT IS PARTICULARLY APPARENT IN THE CONTEXT OF NEURODEVELOPMENT AND HIGH VITAMIN C CONCENTRATIONS IN THE BRAIN ARE INDICATIVE OF IMPORTANT FUNCTIONAL REQUIREMENTS IN THIS ORGAN. ACCORDINGLY, THIS REVIEW CONSIDERS THE EVIDENCE FOR THE POTENTIAL IMPACT OF MATERNAL VITAMIN C STATUS ON NEURODEVELOPMENTAL EPIGENETICS. 2022 18 6715 34 VITAMIN A AND THE EPIGENOME. THE EPIGENETIC PHENOMENA REFER TO HERITABLE CHANGES IN GENE EXPRESSION OTHER THAN THOSE IN THE DNA SEQUENCE, SUCH AS DNA METHYLATION AND HISTONE MODIFICATIONS. MAJOR RESEARCH PROGRESS IN THE LAST FEW YEARS HAS PROVIDED FURTHER PROOF THAT ENVIRONMENTAL FACTORS, INCLUDING DIET AND NUTRITION, CAN INFLUENCE PHYSIOLOGIC AND PATHOLOGIC PROCESSES THROUGH EPIGENETIC ALTERATIONS, WHICH IN TURN INFLUENCE GENE EXPRESSION. THIS INFLUENCE IS TERMED NUTRITIONAL EPIGENETICS, AND ONE PROMINENT EXAMPLE IS THE REGULATION OF GENE TRANSCRIPTION BY VITAMIN A THROUGH INTERACTION TO ITS NUCLEAR RECEPTOR. VITAMIN A IS CRITICAL THROUGHOUT LIFE. TOGETHER WITH ITS DERIVATIVES, IT REGULATES DIVERSE PROCESSES INCLUDING REPRODUCTION, EMBRYOGENESIS, VISION, GROWTH, CELLULAR DIFFERENTIATION AND PROLIFERATION, MAINTENANCE OF EPITHELIAL CELLULAR INTEGRITY AND IMMUNE FUNCTION. HERE WE REVIEW THE EPIGENETIC ROLE OF VITAMIN A IN CANCER, STEM CELLS DIFFERENTIATION, PROLIFERATION, AND IMMUNITY. THE DATA PRESENTED HERE SHOW THAT RETINOIC ACID IS A POTENT AGENT CAPABLE OF INDUCING ALTERATIONS IN EPIGENETIC MODIFICATIONS THAT PRODUCE VARIOUS EFFECTS ON THE PHENOTYPE. MEDICAL BENEFITS OF VITAMIN A AS AN EPIGENETIC MODULATOR, ESPECIALLY WITH RESPECT TO ITS CHRONIC USE AS NUTRITIONAL SUPPLEMENT, SHOULD RELY ON OUR FURTHER UNDERSTANDING OF ITS EPIGENETIC EFFECTS DURING HEALTH AND DISEASE, AS WELL AS THROUGH DIFFERENT GENERATIONS. 2017 19 1388 27 DIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE: NON-INVASIVE ASSESSMENT OF CARDIOVASCULAR RISK. THE PREVALENCE AND BURDEN OF DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE ON GLOBAL HEALTH AND SOCIOECONOMIC DEVELOPMENT IS ALREADY HEAVY AND STILL RISING. DIABETES MELLITUS BY ITSELF IS LINKED TO ADVERSE CARDIOVASCULAR EVENTS, AND THE PRESENCE OF CONCOMITANT CHRONIC KIDNEY DISEASE FURTHER AMPLIFIES CARDIOVASCULAR RISK. THE CULMINATION OF TRADITIONAL (MALE GENDER, SMOKING, ADVANCED AGE, OBESITY, ARTERIAL HYPERTENSION AND DYSLIPIDEMIA) AND NON-TRADITIONAL RISK FACTORS (ANEMIA, INFLAMMATION, PROTEINURIA, VOLUME OVERLOAD, MINERAL METABOLISM ABNORMALITIES, OXIDATIVE STRESS, ETC.) CONTRIBUTES TO ADVANCED ATHEROSCLEROSIS AND INCREASED CARDIOVASCULAR RISK. TO DECREASE THE MORBIDITY AND MORTALITY OF THESE PATIENTS DUE TO CARDIOVASCULAR CAUSES, TIMELY AND EFFICIENT CARDIOVASCULAR RISK ASSESSMENT IS OF HUGE IMPORTANCE. CARDIOVASCULAR RISK ASSESSMENT CAN BE BASED ON LABORATORY PARAMETERS, IMAGING TECHNIQUES, ARTERIAL STIFFNESS PARAMETERS, ANKLE-BRACHIAL INDEX AND 24 H BLOOD PRESSURE MEASUREMENTS. NEWER METHODS INCLUDE EPIGENETIC MARKERS, SOLUBLE ADHESION MOLECULES, CYTOKINES AND MARKERS OF OXIDATIVE STRESS. IN THIS REVIEW, THE AUTHORS PRESENT SEVERAL NON-INVASIVE METHODS OF CARDIOVASCULAR RISK ASSESSMENT IN PATIENTS WITH DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE. 2021 20 6380 37 THE ROLE OF OBESITY AND DIABETES IN DEMENTIA. CHRONIC CONDITIONS SUCH AS OBESITY, DIABETES, AND DEMENTIA ARE INCREASING IN THE UNITED STATES (US) POPULATION. KNOWLEDGE OF THESE CHRONIC CONDITIONS, PREVENTATIVE MEASURES, AND PROPER MANAGEMENT TACTICS IS IMPORTANT AND CRITICAL TO PREVENTING DISEASE. THE OVERLAP BETWEEN OBESITY, DIABETES, AND DEMENTIA IS BECOMING FURTHER ELUCIDATED. THESE CONDITIONS SHARE A SIMILAR ORIGIN THROUGH THE COMPONENTS OF INCREASING AGE, GENDER, GENETIC AND EPIGENETIC PREDISPOSITIONS, DEPRESSION, AND A HIGH-FAT WESTERN DIET (WD) THAT ALL CONTRIBUTE TO THE INFLAMMATORY STATE ASSOCIATED WITH THE DEVELOPMENT OF OBESITY, DIABETES, AND DEMENTIA. THIS INFLAMMATORY STATE LEADS TO THE DYSREGULATION OF FOOD INTAKE AND INSULIN RESISTANCE. OBESITY IS OFTEN THE CORNERSTONE THAT LEADS TO THE DEVELOPMENT OF DIABETES AND, SUBSEQUENTLY, IN THE CASE OF TYPE 2 DIABETES MELLITUS (T2DM), PROGRESSION TO "TYPE 3 DIABETES MELLITUS (T3DM)". OBESITY AND DEPRESSION ARE CLOSELY ASSOCIATED WITH DIABETES. HOWEVER, DEMENTIA CAN BE AVOIDED WITH LIFESTYLE MODIFICATIONS, BY SWITCHING TO A PLANT-BASED DIET (E.G., A MEDITERRANEAN DIET (MD)), AND INCREASING PHYSICAL ACTIVITY. DIET AND EXERCISE ARE NOT THE ONLY TREATMENT OPTIONS. THERE ARE SEVERAL SURGICAL AND PHARMACOLOGICAL INTERVENTIONS AVAILABLE FOR PREVENTION. CURRENT AND FUTURE RESEARCH WITHIN EACH OF THESE FIELDS IS WARRANTED AND OFFERS THE CHANCE FOR NEW TREATMENT OPTIONS AND A BETTER UNDERSTANDING OF THE PATHOGENESIS OF EACH CONDITION. 2022