1  426 115 ANTI-DIABETIC FUNCTIONS OF SOY ISOFLAVONE GENISTEIN: MECHANISMS UNDERLYING ITS EFFECTS ON PANCREATIC BETA-CELL FUNCTION. TYPE 2 DIABETES IS A RESULT OF CHRONIC INSULIN RESISTANCE AND LOSS OF FUNCTIONAL PANCREATIC BETA-CELL MASS. STRATEGIES TO PRESERVE BETA-CELL MASS AND A GREATER UNDERSTANDING OF THE MECHANISMS UNDERLYING BETA-CELL TURNOVER ARE NEEDED TO PREVENT AND TREAT THIS DEVASTATING DISEASE. GENISTEIN, A NATURALLY OCCURRING SOY ISOFLAVONE, IS REPORTED TO HAVE NUMEROUS HEALTH BENEFITS ATTRIBUTED TO MULTIPLE BIOLOGICAL FUNCTIONS. OVER THE PAST 10 YEARS, NUMEROUS STUDIES HAVE DEMONSTRATED THAT GENISTEIN HAS ANTI-DIABETIC EFFECTS, IN PARTICULAR, DIRECT EFFECTS ON BETA-CELL PROLIFERATION, GLUCOSE-STIMULATED INSULIN SECRETION AND PROTECTION AGAINST APOPTOSIS, INDEPENDENT OF ITS FUNCTIONS AS AN ESTROGEN RECEPTOR AGONIST, ANTIOXIDANT, OR TYROSINE KINASE INHIBITOR. EFFECTS ARE STRUCTURE-SPECIFIC AND NOT COMMON TO ALL FLAVONOIDS. WHILE THERE ARE LIMITED DATA ON THE EFFECTS OF GENISTEIN CONSUMPTION IN HUMANS WITH DIABETES, THERE ARE A PLETHORA OF ANIMAL AND CELL-CULTURE STUDIES THAT DEMONSTRATE A DIRECT EFFECT OF GENISTEIN ON BETA-CELLS AT PHYSIOLOGICALLY RELEVANT CONCENTRATIONS (<10 MUM). THE EFFECTS APPEAR TO INVOLVE CAMP/PKA SIGNALING AND THERE ARE SOME STUDIES THAT SUGGEST AN EFFECT ON EPIGENETIC REGULATION OF GENE EXPRESSION. THIS REVIEW FOCUSES ON THE ANTI-DIABETIC EFFECTS OF GENISTEIN IN BOTH IN VITRO AND IN VIVO MODELS AND POTENTIAL MECHANISMS UNDERLYING ITS DIRECT EFFECTS ON BETA-CELLS.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
2 6205  36 THE INFLUENCE OF PLANT EXTRACTS AND PHYTOCONSTITUENTS ON ANTIOXIDANT ENZYMES ACTIVITY AND GENE EXPRESSION IN THE PREVENTION AND TREATMENT OF IMPAIRED GLUCOSE HOMEOSTASIS AND DIABETES COMPLICATIONS. DIABETES IS A COMPLEX METABOLIC DISORDER RESULTING EITHER FROM INSULIN RESISTANCE OR AN IMPAIRED INSULIN SECRETION. PROLONGED ELEVATED BLOOD GLUCOSE CONCENTRATION, THE KEY CLINICAL SIGN OF DIABETES, INITIATES AN ENHANCEMENT OF REACTIVE OXYGEN SPECIES DERIVED FROM GLUCOSE AUTOXIDATION AND GLYCOSYLATION OF PROTEINS. CONSEQUENTLY, CHRONIC OXIDATIVE STRESS OVERWHELMS CELLULAR ENDOGENOUS ANTIOXIDANT DEFENSES AND LEADS TO THE ACUTE AND LONG-STANDING STRUCTURAL AND FUNCTIONAL CHANGES OF MACROMOLECULES RESULTING IN IMPAIRED CELLULAR FUNCTIONING, CELL DEATH AND ORGAN DYSFUNCTION. THE OXIDATIVE STRESS PROVOKED CHAIN OF PATHOLOGICAL EVENTS OVER TIME CAUSE DIABETIC COMPLICATIONS SUCH AS NEPHROPATHY, PERIPHERAL NEUROPATHY, CARDIOMYOPATHY, RETINOPATHY, HYPERTENSION, AND LIVER DISEASE. UNDER DIABETIC CONDITIONS, ACCOMPANYING GENOME/EPIGENOME AND METABOLITE MARKERS ALTERATIONS MAY ALSO AFFECT GLUCOSE HOMEOSTASIS, PANCREATIC BETA-CELLS, MUSCLE, LIVER, AND ADIPOSE TISSUE. BY PROVIDING DEEPER GENETIC/EPIGENETIC INSIGHT OF DIRECT OR INDIRECT DIETARY EFFECTS, NUTRIGENOMICS OFFERS A PROMISING OPPORTUNITY TO IMPROVE THE QUALITY OF LIFE OF DIABETIC PATIENTS. NATURAL PLANT EXTRACTS, OR THEIR NATURALLY OCCURRING COMPOUNDS, WERE SHOWN TO BE VERY PROFICIENT IN THE PREVENTION AND TREATMENT OF DIFFERENT PATHOLOGIES ASSOCIATED WITH OXIDATIVE STRESS INCLUDING DIABETES AND ITS COMPLICATIONS. CONSIDERING THAT FOOD INTAKE IS ONE OF THE CRUCIAL COMPONENTS IN DIABETES' PREVALENCE, PROGRESSION AND COMPLICATIONS, THIS REVIEW SUMMARIZES THE EFFECT OF THE MAJOR PLANT SECONDARY METABOLITE AND PHYTOCONSTITUENTS ON THE ANTIOXIDANT ENZYMES ACTIVITY AND GENE EXPRESSION UNDER DIABETIC CONDITIONS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
3 2964  28 GENETIC AND EPIGENETIC MECHANISMS UNDERLYING ARSENIC-ASSOCIATED DIABETES MELLITUS: A PERSPECTIVE OF THE CURRENT EVIDENCE. CHRONIC EXPOSURE TO ARSENIC HAS BEEN ASSOCIATED WITH THE DEVELOPMENT OF DIABETES MELLITUS (DM), A DISEASE CHARACTERIZED BY HYPERGLYCEMIA RESULTING FROM DYSREGULATION OF GLUCOSE HOMEOSTASIS. THIS REVIEW SUMMARIZES FOUR MAJOR MECHANISMS BY WHICH ARSENIC INDUCES DIABETES, NAMELY INHIBITION OF INSULIN-DEPENDENT GLUCOSE UPTAKE, PANCREATIC BETA-CELL DAMAGE, PANCREATIC BETA-CELL DYSFUNCTION AND STIMULATION OF LIVER GLUCONEOGENESIS THAT ARE SUPPORTED BY BOTH IN VIVO AND IN VITRO STUDIES. ADDITIONALLY, THE ROLE OF POLYMORPHIC VARIANTS ASSOCIATED WITH ARSENIC TOXICITY AND DISEASE SUSCEPTIBILITY, AS WELL AS EPIGENETIC MODIFICATIONS ASSOCIATED WITH ARSENIC EXPOSURE, ARE CONSIDERED IN THE CONTEXT OF ARSENIC-ASSOCIATED DM. TAKEN TOGETHER, IN VITRO, IN VIVO AND HUMAN GENETIC/EPIGENETIC STUDIES SUPPORT THAT ARSENIC HAS THE POTENTIAL TO INDUCE DM PHENOTYPES AND IMPAIR KEY PATHWAYS INVOLVED IN THE REGULATION OF GLUCOSE HOMEOSTASIS.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
4 4185  34 METABOLIC ADAPTIONS/REPROGRAMMING IN ISLET BETA-CELLS IN RESPONSE TO PHYSIOLOGICAL STIMULATORS-WHAT ARE THE CONSEQUENCES. IRREVERSIBLE PANCREATIC BETA-CELL DAMAGE MAY BE A RESULT OF CHRONIC EXPOSURE TO SUPRAPHYSIOLOGICAL GLUCOSE OR LIPID CONCENTRATIONS OR CHRONIC EXPOSURE TO THERAPEUTIC ANTI-DIABETIC DRUGS. THE BETA-CELLS ARE ABLE TO RESPOND TO BLOOD GLUCOSE IN A NARROW CONCENTRATION RANGE AND RELEASE INSULIN IN RESPONSE, FOLLOWING ACTIVATION OF METABOLIC PATHWAYS SUCH AS GLYCOLYSIS AND THE TCA CYCLE. THE BETA-CELL CANNOT PROTECT ITSELF FROM GLUCOSE TOXICITY BY BLOCKING GLUCOSE UPTAKE, BUT INDEED RELIES ON ALTERNATIVE METABOLIC PROTECTION MECHANISMS TO AVOID DYSFUNCTION AND DEATH. ALTERATION OF NORMAL METABOLIC PATHWAY FUNCTION OCCURS AS A COUNTER REGULATORY RESPONSE TO HIGH NUTRIENT, INFLAMMATORY FACTOR, HORMONE OR THERAPEUTIC DRUG CONCENTRATIONS. METABOLIC REPROGRAMMING IS A TERM WIDELY USED TO DESCRIBE A CHANGE IN REGULATION OF VARIOUS METABOLIC ENZYMES AND TRANSPORTERS, USUALLY ASSOCIATED WITH CELL GROWTH AND PROLIFERATION AND MAY INVOLVE RESHAPING EPIGENETIC RESPONSES, IN PARTICULAR THE ACETYLATION AND METHYLATION OF HISTONE PROTEINS AND DNA. OTHER METABOLIC MODIFICATIONS SUCH AS MALONYLATION, SUCCINYLATION, HYDROXYBUTYRYLATION, ADP-RIBOSYLATION, AND LACTYLATION, MAY IMPACT REGULATORY PROCESSES, MANY OF WHICH NEED TO BE INVESTIGATED IN DETAIL TO CONTRIBUTE TO CURRENT ADVANCES IN METABOLISM. BY DESCRIBING MULTIPLE MECHANISMS OF METABOLIC ADAPTION THAT ARE AVAILABLE TO THE BETA-CELL ACROSS ITS LIFESPAN, WE HOPE TO IDENTIFY SITES FOR METABOLIC REPROGRAMMING MECHANISMS, MOST OF WHICH ARE INCOMPLETELY DESCRIBED OR UNDERSTOOD. MANY OF THESE MECHANISMS ARE RELATED TO PROMINENT ANTIOXIDANT RESPONSES. HERE, WE HAVE ATTEMPTED TO DESCRIBE THE KEY BETA-CELL METABOLIC ADAPTIONS AND CHANGES WHICH ARE REQUIRED FOR SURVIVAL AND FUNCTION IN VARIOUS PHYSIOLOGICAL, PATHOLOGICAL AND PHARMACOLOGICAL CONDITIONS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
5 4974  27 PATHOPHYSIOLOGICAL MECHANISMS LEADING TO MUSCLE LOSS IN CHRONIC KIDNEY DISEASE. LOSS OF MUSCLE PROTEINS IS A DELETERIOUS CONSEQUENCE OF CHRONIC KIDNEY DISEASE (CKD) THAT CAUSES A DECREASE IN MUSCLE STRENGTH AND FUNCTION, AND CAN LEAD TO A REDUCTION IN QUALITY OF LIFE AND INCREASED RISK OF MORBIDITY AND MORTALITY. THE EFFECTIVENESS OF CURRENT TREATMENT STRATEGIES IN PREVENTING OR REVERSING MUSCLE PROTEIN LOSSES IS LIMITED. THE LIMITATIONS LARGELY STEM FROM THE SYSTEMIC NATURE OF DISEASES SUCH AS CKD, WHICH STIMULATE SKELETAL MUSCLE PROTEIN DEGRADATION PATHWAYS WHILE SIMULTANEOUSLY ACTIVATING MECHANISMS THAT IMPAIR MUSCLE PROTEIN SYNTHESIS AND REPAIR. STIMULI THAT INITIATE MUSCLE PROTEIN LOSS INCLUDE METABOLIC ACIDOSIS, INSULIN AND IGF1 RESISTANCE, CHANGES IN HORMONES, CYTOKINES, INFLAMMATORY PROCESSES AND DECREASED APPETITE. A GROWING BODY OF EVIDENCE SUGGESTS THAT SIGNALLING MOLECULES SECRETED FROM MUSCLE CAN ENTER THE CIRCULATION AND SUBSEQUENTLY INTERACT WITH RECIPIENT ORGANS, INCLUDING THE KIDNEYS, WHILE CONVERSELY, PATHOLOGICAL EVENTS IN THE KIDNEY CAN ADVERSELY INFLUENCE PROTEIN METABOLISM IN SKELETAL MUSCLE, DEMONSTRATING THE EXISTENCE OF CROSSTALK BETWEEN KIDNEY AND MUSCLE. TOGETHER, THESE SIGNALS, WHETHER DIRECT OR INDIRECT, INDUCE CHANGES IN THE LEVELS OF REGULATORY AND EFFECTOR PROTEINS VIA ALTERATIONS IN MRNAS, MICRORNAS AND CHROMATIN EPIGENETIC RESPONSES. ADVANCES IN OUR UNDERSTANDING OF THE SIGNALS AND PROCESSES THAT MEDIATE MUSCLE LOSS IN CKD AND OTHER MUSCLE WASTING CONDITIONS WILL SUPPORT THE FUTURE DEVELOPMENT OF THERAPEUTIC STRATEGIES TO REDUCE MUSCLE LOSS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
6 3748  36 INSIGHTS INTO THE ROLE OF DNA METHYLATION AND PROTEIN MISFOLDING IN DIABETES MELLITUS. BACKGROUND: DIABETES MELLITUS IS A METABOLIC DISORDER THAT IS CHARACTERIZED BY IMPAIRED GLUCOSE TOLERANCE RESULTING FROM DEFECTS IN INSULIN SECRETION, INSULIN ACTION, OR BOTH. EPIGENETIC MODIFICATIONS, WHICH ARE DEFINED AS INHERITED CHANGES IN GENE EXPRESSION THAT OCCUR WITHOUT CHANGES IN GENE SEQUENCE, ARE INVOLVED IN THE ETIOLOGY OF DIABETES. METHODS: IN THIS REVIEW, WE FOCUSED ON THE ROLE OF DNA METHYLATION AND PROTEIN MISFOLDING AND THEIR CONTRIBUTION TO THE DEVELOPMENT OF BOTH TYPE 1 AND TYPE 2 DIABETES MELLITUS. RESULTS: CHANGES IN DNA METHYLATION IN PARTICULAR ARE HIGHLY ASSOCIATED WITH THE DEVELOPMENT OF DIABETES. PROTEIN FUNCTION IS DEPENDENT ON THEIR PROPER FOLDING IN THE ENDOPLASMIC RETICULUM. DEFECTIVE PROTEIN FOLDING AND CONSEQUENTLY THEIR FUNCTIONS HAVE ALSO BEEN REPORTED TO PLAY A ROLE. EARLY TREATMENT OF DIABETES HAS PROVEN TO BE OF GREAT BENEFIT, AS EVEN TRANSIENT HYPERGLYCEMIA MAY LEAD TO PATHOLOGICAL EFFECTS AND COMPLICATIONS LATER ON. THIS HAS BEEN EXPLAINED BY THE THEORY OF THE DEVELOPMENT OF A METABOLIC MEMORY IN DIABETES. THE BASIS FOR THIS METABOLIC MEMORY WAS ATTRIBUTED TO OXIDATIVE STRESS, CHRONIC INFLAMMATION, NON-ENZYMATIC GLYCATION OF PROTEINS AND IMPORTANTLY, EPIGENETIC CHANGES. THIS HIGHLIGHTS THE IMPORTANCE OF LINKING NEW THERAPEUTICS TARGETING EPIGENETIC MECHANISMS WITH TRADITIONAL ANTIDIABETIC DRUGS. CONCLUSION: ALTHOUGH NEW DATA IS EVOLVING ON THE RELATION BETWEEN DNA METHYLATION, PROTEIN MISFOLDING, AND THE ETIOLOGY OF DIABETES, MORE STUDIES ARE REQUIRED FOR DEVELOPING NEW RELEVANT DIAGNOSTICS AND THERAPEUTICS.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
7 6259  29 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
8 1974  29 EPIGENETIC ALTERATIONS CAUSED BY NUTRITIONAL STRESS DURING FETAL PROGRAMMING OF THE ENDOCRINE PANCREAS. NUTRITION DURING CRITICAL PERIODS OF DEVELOPMENT IS ONE OF THE PIVOTAL FACTORS IN ESTABLISHING A LIFELONG HEALTHY METABOLISM. DIFFERENT NUTRITIONAL DEFICIENCIES SUCH AS A LOW AVAILABILITY OF PROTEINS IN THE MATERNAL DIET PRODUCE ALTERATIONS IN OFFSPRING THAT INCLUDE CHANGES IN INSULIN AND GLUCOSE METABOLISM, A DECREASE IN THE SIZE AND NUMBER OF CELLS OF PANCREATIC ISLETS OF LANGERHANS, AND PREMATURE AGEING OF THE SECRETORY FUNCTION OF PANCREATIC BETA CELLS. MOREOVER, IT HAS BEEN REPORTED THAT CHRONIC NUTRITIONAL STRESS IS ASSOCIATED WITH EPIGENETIC ALTERATIONS IN MECHANISMS OF GENE REGULATION DURING PANCREATIC DEVELOPMENT AND FUNCTION. THESE ALTERATIONS CAN LEAD TO DYSFUNCTIONAL STATES IN PANCREATIC BETA CELLS, WHICH IN THE LONG RUN ARE RESPONSIBLE FOR THE ONSET OF METABOLIC DISEASES LIKE TYPE 2 DIABETES. THE PRESENT REVIEW SUMMARIZES THE MOST IMPORTANT EVIDENCE IN RELATION TO THE PARTICIPATION OF EPIGENETIC MECHANISMS IN THE REGULATION OF GENE EXPRESSION DURING THE INTRAUTERINE PROGRAMMING OF THE ENDOCRINE PANCREAS IN ANIMAL MODELS. SUCH MECHANISMS INCLUDE DNA METHYLATION AS WELL AS MODIFICATIONS OF HISTONES AND MICRORNAS (MIRNAS).	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
9 6715  32 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
10 4891  29 OXIDATIVE STRESS AND INFLAMMATORY MARKERS IN PREDIABETES AND DIABETES. PREDIABETES IS A STATE OF ELEVATED PLASMA GLUCOSE IN WHICH THE THRESHOLD FOR DIABETES HAS NOT YET BEEN REACHED AND CAN PREDISPOSE TO THE DEVELOPMENT OF TYPE 2 DIABETES AND CARDIOVASCULAR DISEASES. INSULIN RESISTANCE AND IMPAIRED BETA-CELL FUNCTION ARE OFTEN ALREADY PRESENT IN PREDIABETES. HYPERGLYCEMIA CAN UPREGULATE MARKERS OF CHRONIC INFLAMMATION AND CONTRIBUTE TO INCREASED REACTIVE OXYGEN SPECIES (ROS) GENERATION, WHICH ULTIMATELY CAUSE VASCULAR DYSFUNCTION. CONVERSELY, INCREASED OXIDATIVE STRESS AND INFLAMMATION CAN LEAD TO INSULIN RESISTANCE AND IMPAIRED INSULIN SECRETION. PROPER TREATMENT OF HYPERGLYCEMIA AND INHIBITION OF ROS OVERPRODUCTION IS CRUCIAL FOR DELAYING ONSET OF DIABETES AND FOR PREVENTION OF CARDIOVASCULAR COMPLICATIONS. THUS, IT IS IMPERATIVE TO DETERMINE THE MECHANISMS INVOLVED IN THE PROGRESSION FROM PREDIABETES TO DIABETES INCLUDING A CLARIFICATION OF HOW OLD AND NEW MEDICATIONS AFFECT OXIDATIVE AND IMMUNE MECHANISMS OF DIABETES. IN THIS REVIEW, WE DISCUSS THE RELATIONSHIP BETWEEN OXIDATIVE STRESS AND HYPERGLYCEMIA ALONG WITH LINKS BETWEEN INFLAMMATION AND PREDIABETES. ADDITIONALLY, THE EFFECTS OF HYPERGLYCEMIC MEMORY, MICROVESICLES, MICRO-RNA, AND EPIGENETIC REGULATION ON INFLAMMATION, OXIDATIVE STATE, AND GLYCEMIC CONTROL ARE HIGHLIGHTED. ADIPOSE TISSUE AND THEIR INFLUENCE ON CHRONIC INFLAMMATION ARE ALSO BRIEFLY REVIEWED. FINALLY, THE ROLE OF IMMUNE-TARGETED THERAPIES AND ANTI-DIABETIC MEDICATION ON GLYCEMIC CONTROL AND OXIDATIVE STRESS ARE DISCUSSED.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
11 5373  32 RECENT ADVANCES IN UNDERSTANDING THE ROLE OF DIET AND OBESITY IN THE DEVELOPMENT OF COLORECTAL CANCER. COLORECTAL CANCER (CRC) IS A MAJOR CAUSE OF PREMATURE DEATH IN THE UK AND MANY DEVELOPED COUNTRIES. HOWEVER, THE RISK OF DEVELOPING CRC IS WELL RECOGNISED TO BE ASSOCIATED NOT ONLY WITH DIET BUT ALSO WITH OBESITY AND LACK OF EXERCISE. WHILE EPIDEMIOLOGICAL EVIDENCE SHOWS AN ASSOCIATION WITH FACTORS SUCH AS HIGH RED MEAT INTAKE AND LOW INTAKE OF VEGETABLES, FIBRE AND FISH, THE MECHANISMS UNDERLYING THESE EFFECTS ARE ONLY NOW BEING ELUCIDATED. CRC DEVELOPS OVER MANY YEARS AND IS TYPICALLY CHARACTERISED BY AN ACCUMULATION OF MUTATIONS, WHICH MAY ARISE AS A CONSEQUENCE OF INHERITED POLYMORPHISMS IN KEY GENES, BUT MORE COMMONLY AS A RESULT OF SPONTANEOUSLY ARISING MUTATIONS AFFECTING GENES CONTROLLING CELL PROLIFERATION, DIFFERENTIATION, APOPTOSIS AND DNA REPAIR. EPIGENETIC CHANGES ARE OBSERVED THROUGHOUT THE PROGRESS FROM NORMAL MORPHOLOGY THROUGH FORMATION OF ADENOMA, AND THE SUBSEQUENT DEVELOPMENT OF CARCINOMA. THE REASONS WHY THIS ACCUMULATION OF LOSS OF HOMOEOSTATIC CONTROLS ARISES ARE UNCLEAR BUT CHRONIC INFLAMMATION HAS BEEN PROPOSED TO PLAY A CENTRAL ROLE. OBESITY IS ASSOCIATED WITH INCREASED PLASMA LEVELS OF CHEMOKINES AND ADIPOKINES CHARACTERISTIC OF CHRONIC SYSTEMIC INFLAMMATION, AND DIETARY FACTORS SUCH AS FISH OILS AND PHYTOCHEMICALS HAVE BEEN SHOWN TO HAVE ANTI-INFLAMMATORY PROPERTIES AS WELL AS MODULATING ESTABLISHED RISK FACTORS SUCH AS APOPTOSIS AND CELL PROLIFERATION. THERE IS ALSO SOME EVIDENCE THAT DIET CAN MODIFY EPIGENETIC CHANGES. THIS PAPER BRIEFLY REVIEWS THE CURRENT STATE OF KNOWLEDGE IN RELATION TO CRC DEVELOPMENT AND CONSIDERS EVIDENCE FOR POTENTIAL MECHANISMS BY WHICH DIET MAY MODIFY RISK.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
12  599  36 BETA-CELL DIFFERENTIATION STATUS IN TYPE 2 DIABETES. TYPE 2 DIABETES (T2D) AFFECTS 415 MILLION PEOPLE WORLDWIDE AND IS CHARACTERIZED BY CHRONIC HYPERGLYCAEMIA AND INSULIN RESISTANCE, PROGRESSING TO INSUFFICIENT INSULIN PRODUCTION, AS A RESULT OF BETA-CELL FAILURE. OVER TIME, CHRONIC HYPERGLYCAEMIA CAN ULTIMATELY LEAD TO LOSS OF BETA-CELL FUNCTION, LEAVING PATIENTS INSULIN-DEPENDENT. UNTIL RECENTLY THE LOSS OF BETA-CELL MASS SEEN IN T2D WAS CONSIDERED TO BE THE RESULT OF INCREASED RATES OF APOPTOSIS; HOWEVER, IT HAS BEEN PROPOSED THAT APOPTOSIS ALONE CANNOT ACCOUNT FOR THE EXTENT OF BETA-CELL MASS LOSS SEEN IN THE DISEASE, AND THAT A LOSS OF FUNCTION MAY ALSO OCCUR AS A RESULT OF CHANGES IN BETA-CELL DIFFERENTIATION STATUS. IN THE PRESENT REVIEW, WE CONSIDER CURRENT KNOWLEDGE OF DETERMINANTS OF BETA-CELL FATE IN THE CONTEXT OF UNDERSTANDING ITS RELEVANCE TO DISEASE PROCESS IN T2D, AND ALSO THE IMPACT OF A DIABETOGENIC ENVIRONMENT (HYPERGLYCAEMIA, HYPOXIA, INFLAMMATION AND DYSLIPIDAEMIA) ON THE EXPRESSION OF GENES INVOLVED IN MAINTENANCE OF BETA-CELL IDENTITY. WE DESCRIBE CURRENT KNOWLEDGE OF THE IMPACT OF THE DIABETIC MICROENVIRONMENT ON GENE REGULATORY PROCESSES SUCH ALTERNATIVE SPLICING, THE EXPRESSION OF DISALLOWED GENES AND EPIGENETIC MODIFICATIONS. ELUCIDATING THE MOLECULAR MECHANISMS THAT UNDERPIN CHANGES TO BETA-CELL DIFFERENTIATION STATUS AND THE CONCOMITANT BETA-CELL FAILURE OFFERS POTENTIAL TREATMENT TARGETS FOR THE FUTURE MANAGEMENT OF PATIENTS WITH T2D.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
13 2704  25 EXERCISE AND COLORECTAL CANCER: PREVENTION AND MOLECULAR MECHANISMS. EXERCISE AND PHYSICAL ACTIVITY HAVE BEEN SHOWN TO BE STRONGLY ASSOCIATED WITH A DECREASED INCIDENCE RATE OF VARIOUS CHRONIC DISEASES ESPECIALLY NUMEROUS HUMAN MALIGNANCIES. A HUGE NUMBER OF CLINICAL TRIALS AND META-ANALYSIS HAVE DEMONSTRATED THAT EXERCISE IS SIGNIFICANTLY EFFECTIVE IN LOWERING THE RISK OF COLORECTAL CANCER. IN ADDITION, IT IS SUGGESTED AS AN EFFECTIVE THERAPEUTIC MODALITY AGAINST THIS CANCER TYPE. THEREFORE, IN THIS REVIEW, WE WILL REVIEW COMPREHENSIBLY THE EFFECTS OF EXERCISE IN PREVENTING, TREATING, AND ALLEVIATING THE ADVERSE EFFECTS OF CONVENTIONAL THERAPEUTIC OPTIONS IN COLORECTAL CANCER. MOREOVER, THE POSSIBLE MECHANISMS UNDERLYING THE POSITIVE EFFECTS OF EXERCISE AND PHYSICAL ACTIVITY IN COLORECTAL CANCER, INCLUDING REGULATION OF INFLAMMATION, APOPTOSIS, GROWTH FACTOR AXIS, IMMUNITY, EPIGENETIC, ETC. WILL BE ALSO DISCUSSED.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
14 6067  35 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	
                                                                                                                                                                                                                                                                                                                                                                                                             
15 3576  34 IMPACT OF NUTRITION ON POLLUTANT TOXICITY: AN UPDATE WITH NEW INSIGHTS INTO EPIGENETIC REGULATION. EXPOSURE TO ENVIRONMENTAL POLLUTANTS IS A GLOBAL HEALTH PROBLEM AND IS ASSOCIATED WITH THE DEVELOPMENT OF MANY CHRONIC DISEASES, INCLUDING CARDIOVASCULAR DISEASE, DIABETES AND METABOLIC SYNDROME. THERE IS A GROWING BODY OF EVIDENCE THAT NUTRITION CAN BOTH POSITIVELY AND NEGATIVELY MODULATE THE TOXIC EFFECTS OF POLLUTANT EXPOSURE. DIETS HIGH IN PROINFLAMMATORY FATS, SUCH AS LINOLEIC ACID, CAN EXACERBATE POLLUTANT TOXICITY, WHEREAS DIETS RICH IN BIOACTIVE AND ANTI-INFLAMMATORY FOOD COMPONENTS, INCLUDING OMEGA-3 FATTY ACIDS AND POLYPHENOLS, CAN ATTENUATE TOXICANT-ASSOCIATED INFLAMMATION. PREVIOUSLY, RESEARCHERS HAVE ELUCIDATED DIRECT MECHANISMS OF NUTRITIONAL MODULATION, INCLUDING ALTERATION OF NUCLEAR FACTOR KAPPA-LIGHT-CHAIN-ENHANCER OF ACTIVATED B CELLS (NF-KAPPAB) SIGNALING, BUT RECENTLY, INCREASED FOCUS HAS BEEN GIVEN TO THE WAYS IN WHICH NUTRITION AND POLLUTANTS AFFECT EPIGENETICS. NUTRITION HAS BEEN DEMONSTRATED TO MODULATE EPIGENETIC MARKERS THAT HAVE BEEN LINKED EITHER TO INCREASED DISEASE RISKS OR TO PROTECTION AGAINST DISEASES. OVERNUTRITION (I.E. OBESITY) AND UNDERNUTRITION (I.E. FAMINE) HAVE BEEN OBSERVED TO ALTER PRENATAL EPIGENETIC TAGS THAT MAY INCREASE THE RISK OF OFFSPRING DEVELOPING DISEASE LATER IN LIFE. CONVERSELY, BIOACTIVE FOOD COMPONENTS, INCLUDING CURCUMIN, HAVE BEEN SHOWN TO ALTER EPIGENETIC MARKERS THAT SUPPRESS THE ACTIVATION OF NF-KAPPAB, THUS REDUCING INFLAMMATORY RESPONSES. EXPOSURE TO POLLUTANTS ALSO ALTERS EPIGENETIC MARKERS AND MAY CONTRIBUTE TO INFLAMMATION AND DISEASE. IT HAS BEEN DEMONSTRATED THAT POLLUTANTS, VIA EPIGENETIC MODULATIONS, CAN INCREASE THE ACTIVATION OF NF-KAPPAB AND UPREGULATE MICRORNAS ASSOCIATED WITH INFLAMMATION, CARDIAC INJURY AND OXIDATIVE DAMAGE. IMPORTANTLY, RECENT EVIDENCE SUGGESTS THAT NUTRITIONAL COMPONENTS, INCLUDING EPIGALLOCATECHIN GALLATE (EGCG), CAN PROTECT AGAINST POLLUTANT-INDUCED INFLAMMATION THROUGH EPIGENETIC REGULATION OF PROINFLAMMATORY TARGET GENES OF NF-KAPPAB. FURTHER RESEARCH IS NEEDED TO BETTER UNDERSTAND HOW NUTRITION CAN MODULATE POLLUTANT TOXICITY THROUGH EPIGENETIC REGULATION. THEREFORE, THE OBJECTIVE OF THIS REVIEW IS TO ELUCIDATE THE CURRENT EVIDENCE LINKING EPIGENETIC CHANGES TO POLLUTANT-INDUCED DISEASES AND HOW THIS REGULATION MAY BE MODULATED BY NUTRIENTS ALLOWING FOR THE DEVELOPMENT OF FUTURE PERSONALIZED LIFESTYLE INTERVENTIONS.	2017	

16 3547  29 IMMUNOMODULATORY ROLE OF NUTRIENTS: HOW CAN PULMONARY DYSFUNCTIONS IMPROVE? NUTRITION IS AN IMPORTANT TOOL THAT CAN BE USED TO MODULATE THE IMMUNE RESPONSE DURING INFECTIOUS DISEASES. IN ADDITION, THROUGH DIET, IMPORTANT SUBSTRATES ARE ACQUIRED FOR THE BIOSYNTHESIS OF REGULATORY MOLECULES IN THE IMMUNE RESPONSE, INFLUENCING THE PROGRESSION AND TREATMENT OF CHRONIC LUNG DISEASES, SUCH AS ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). IN THIS WAY, NUTRITION CAN PROMOTE LUNG HEALTH STATUS. A RANGE OF NUTRIENTS, SUCH AS VITAMINS (A, C, D, AND E), MINERALS (ZINC, SELENIUM, IRON, AND MAGNESIUM), FLAVONOIDS AND FATTY ACIDS, PLAY IMPORTANT ROLES IN REDUCING THE RISK OF PULMONARY CHRONIC DISEASES AND VIRAL INFECTIONS. THROUGH THEIR ANTIOXIDANT AND ANTI-INFLAMMATORY EFFECTS, NUTRIENTS ARE ASSOCIATED WITH BETTER LUNG FUNCTION AND A LOWER RISK OF COMPLICATIONS SINCE THEY CAN DECREASE THE HARMFUL EFFECTS FROM THE IMMUNE SYSTEM DURING THE INFLAMMATORY RESPONSE. IN ADDITION, BIOACTIVE COMPOUNDS CAN EVEN CONTRIBUTE TO EPIGENETIC CHANGES, INCLUDING HISTONE DEACETYLASE (HDAC) MODIFICATIONS THAT INHIBIT THE TRANSCRIPTION OF PROINFLAMMATORY CYTOKINES, WHICH CAN CONTRIBUTE TO THE MAINTENANCE OF HOMEOSTASIS IN THE CONTEXT OF INFECTIONS AND CHRONIC INFLAMMATORY DISEASES. THESE NUTRIENTS ALSO PLAY AN IMPORTANT ROLE IN ACTIVATING IMMUNE RESPONSES AGAINST PATHOGENS, WHICH CAN HELP THE IMMUNE SYSTEM DURING INFECTIONS. HERE, WE PROVIDE AN UPDATED OVERVIEW OF THE ROLES PLAYED BY DIETARY FACTORS AND HOW THEY CAN AFFECT RESPIRATORY HEALTH. THEREFORE, WE WILL SHOW THE ANTI-INFLAMMATORY ROLE OF FLAVONOIDS, FATTY ACIDS, VITAMINS AND MICROBIOTA, IMPORTANT FOR THE CONTROL OF CHRONIC INFLAMMATORY DISEASES AND ALLERGIES, IN ADDITION TO THE ANTIVIRAL ROLE OF VITAMINS, FLAVONOIDS, AND MINERALS DURING PULMONARY VIRAL INFECTIONS, ADDRESSING THE MECHANISMS INVOLVED IN EACH FUNCTION. THESE MECHANISMS ARE INTERESTING IN THE DISCUSSION OF PERSPECTIVES ASSOCIATED WITH SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) INFECTION AND ITS PULMONARY COMPLICATIONS SINCE PATIENTS WITH SEVERE DISEASE HAVE VITAMINS DEFICIENCY, ESPECIALLY VITAMIN D. IN ADDITION, RESEARCHES WITH THE USE OF FLAVONOIDS HAVE BEEN SHOWN TO DECREASE VIRAL REPLICATION IN VITRO. THIS WAY, A FULL UNDERSTANDING OF DIETARY INFLUENCES CAN IMPROVE THE LUNG HEALTH OF PATIENTS.	2021	
                                                                                                       
17 2613  27 EPIGENETICS: DECIPHERING ITS ROLE IN DIABETES AND ITS CHRONIC COMPLICATIONS. 1. INCREASING EVIDENCE SUGGESTS THAT EPIGENETIC FACTORS MIGHT REGULATE THE COMPLEX INTERPLAY BETWEEN GENES AND THE ENVIRONMENT, AND AFFECT HUMAN DISEASES, SUCH AS DIABETES AND ITS COMPLICATIONS. 2. CLINICAL TRIALS HAVE UNDERSCORED THE LONG LASTING BENEFICIAL EFFECTS OF STRICT GLYCAEMIC CONTROL FOR REDUCING THE PROGRESSION OF DIABETIC COMPLICATIONS. THEY HAVE ALSO SHOWN THAT DIABETIC COMPLICATIONS, SUCH AS DIABETIC NEPHROPATHY, A CHRONIC KIDNEY DISORDER, CAN CONTINUE EVEN AFTER BLOOD GLUCOSE NORMALIZATION, SUGGESTING A METABOLIC MEMORY OF THE PRIOR GLYCAEMIC STATE. 3. DYSREGULATION OF EPIGENETIC POST-TRANSCRIPTIONAL MODIFICATIONS OF HISTONES IN CHROMATIN, INCLUDING HISTONE LYSINE METHYLATION, HAS BEEN IMPLICATED IN ABERRANT GENE REGULATION ASSOCIATED WITH THE PATHOLOGY OF DIABETES AND ITS COMPLICATIONS. GENOME-WIDE STUDIES HAVE SHOWN CELL-TYPE SPECIFIC CHANGES IN HISTONE METHYLATION PATTERNS UNDER DIABETIC CONDITIONS. IN ADDITION, STUDIES IN VASCULAR CELLS HAVE SHOWN LONG LASTING CHANGES IN EPIGENETIC MODIFICATIONS AT KEY INFLAMMATORY GENE PROMOTERS AFTER PRIOR EXPOSURE TO DIABETIC CONDITIONS, SUGGESTING A POSSIBLE MECHANISM FOR METABOLIC MEMORY. 4. RECENT STUDIES HAVE SHOWN ROLES FOR HISTONE METHYLATION, DNA METHYLATION, AS WELL AS MICRORNA IN DIABETIC NEPHROPATHY. WHETHER THESE EPIGENETIC FACTORS PLAY A ROLE IN METABOLIC MEMORY OF DIABETIC KIDNEY DISEASE IS LESS WELL UNDERSTOOD. 5. THE INCIDENCE OF DIABETES IS GROWING RAPIDLY, AS ALSO THE COST OF TREATING THE RESULTING COMPLICATIONS. A BETTER UNDERSTANDING OF METABOLIC MEMORY AND THE POTENTIAL INVOLVEMENT OF EPIGENETIC MECHANISMS IN THIS PHENOMENON COULD ENABLE THE DEVELOPMENT OF NEW THERAPEUTIC TARGETS FOR THE TREATMENT AND/OR PREVENTION OF SUSTAINED DIABETIC COMPLICATIONS.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
18 4453  29 MOLECULAR MECHANISMS AND PATHWAYS AS TARGETS FOR CANCER PREVENTION AND PROGRESSION WITH DIETARY COMPOUNDS. A UNIQUE FEATURE OF BIOACTIVE FOOD INGREDIENTS IS THEIR BROAD ANTIOXIDANT FUNCTION. ANTIOXIDANTS HAVING A WIDE SPECTRUM OF CHEMICAL STRUCTURE AND ACTIVITY BEYOND BASIC NUTRITION; DISPLAY DIFFERENT HEALTH BENEFITS BY THE PREVENTION AND PROGRESSION OF CHRONIC DISEASES. FUNCTIONAL FOOD COMPONENTS ARE CAPABLE OF ENHANCING THE NATURAL ANTIOXIDANT DEFENSE SYSTEM BY SCAVENGING REACTIVE OXYGEN AND NITROGEN SPECIES, PROTECTING AND REPAIRING DNA DAMAGE, AS WELL AS MODULATING THE SIGNAL TRANSDUCTION PATHWAYS AND GENE EXPRESSION. MAJOR PATHWAYS AFFECTED BY BIOACTIVE FOOD INGREDIENTS INCLUDE THE PRO-INFLAMMATORY PATHWAYS REGULATED BY NUCLEAR FACTOR KAPPA B (NF-KAPPAB), AS WELL AS THOSE ASSOCIATED WITH CYTOKINES AND CHEMOKINES. THE PRESENT REVIEW SUMMARIZES THE IMPORTANCE OF PLANT BIOACTIVES AND THEIR ROLES IN THE REGULATION OF INFLAMMATORY PATHWAYS. BIOACTIVES INFLUENCE SEVERAL PHYSIOLOGICAL PROCESSES SUCH AS GENE EXPRESSION, CELL CYCLE REGULATION, CELL PROLIFERATION, CELL MIGRATION, ETC., RESULTING IN CANCER PREVENTION. CANCER INITIATION IS ASSOCIATED WITH CHANGES IN METABOLIC PATHWAYS SUCH AS GLUCOSE METABOLISM, AND THE EFFECT OF BIOACTIVES IN NORMALIZING THIS PROCESS HAS BEEN PROVIDED. INITIATION AND PROGRESSION OF INFLAMMATORY BOWEL DISEASES (IBD) WHICH INCREASE THE CHANCES OF DEVELOPING OF COLORECTAL CANCERS CAN BE DOWNREGULATED BY PLANT BIOACTIVES. SEVERAL ASPECTS OF THE POTENTIAL ROLES OF MICRORNAS AND EPIGENETIC MODIFICATIONS IN THE DEVELOPMENT OF CANCERS HAVE ALSO BEEN PRESENTED.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
19 2360  22 EPIGENETIC REGULATION OF SKELETAL MUSCLE METABOLISM. NORMAL SKELETAL MUSCLE METABOLISM IS ESSENTIAL FOR WHOLE BODY METABOLIC HOMOEOSTASIS AND DISRUPTIONS IN MUSCLE METABOLISM ARE ASSOCIATED WITH A NUMBER OF CHRONIC DISEASES. TRANSCRIPTIONAL CONTROL OF METABOLIC ENZYME EXPRESSION IS A MAJOR REGULATORY MECHANISM FOR MUSCLE METABOLIC PROCESSES. SUBSTANTIAL EVIDENCE IS EMERGING THAT HIGHLIGHTS THE IMPORTANCE OF EPIGENETIC MECHANISMS IN THIS PROCESS. THIS REVIEW WILL EXAMINE THE IMPORTANCE OF EPIGENETICS IN THE REGULATION OF MUSCLE METABOLISM, WITH A PARTICULAR EMPHASIS ON DNA METHYLATION AND HISTONE ACETYLATION AS EPIGENETIC CONTROL POINTS. THE EMERGING CROSS-TALK BETWEEN METABOLISM AND EPIGENETICS IN THE CONTEXT OF HEALTH AND DISEASE WILL ALSO BE EXAMINED. THE CONCEPT OF INHERITANCE OF SKELETAL MUSCLE METABOLIC PHENOTYPES WILL BE DISCUSSED, IN ADDITION TO EMERGING EPIGENETIC THERAPIES THAT COULD BE USED TO ALTER MUSCLE METABOLISM IN CHRONIC DISEASE STATES.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
20 1451  28 DISALLOWED AND ALLOWED GENE EXPRESSION: TWO FACES OF MATURE ISLET BETA CELLS. GLUCOSE HOMEOSTASIS GREATLY DEPENDS ON THE MATCH BETWEEN FLUCTUATING INSULIN DEMANDS AND ADJUSTED RATES OF INSULIN SECRETION, WHICH IS THE FUNCTION OF PANCREATIC BETA CELLS. EMERGING EVIDENCE SUGGESTS THAT WHEN NEONATAL BETA CELLS MATURE, THEY ACQUIRE TWO FACES OF DIFFERENTIATED FUNCTION: AN EXPECTED "VISIBLE FACE" THAT DEPENDS ON SPECIFIC BETA CELL PROTEINS NEEDED FOR REGULATED INSULIN RELEASE, BUT ALSO A "HIDDEN FACE" THAT REPRESSES UBIQUITOUS PROTEINS TO PREVENT INAPPROPRIATE BETA CELL FUNCTION SUCH AS ELEVATED BASAL HORMONE SECRETION OR INSULIN RELEASE TRIGGERED BY EXERCISE. THIS REVIEW HIGHLIGHTS THIS NOVEL CONCEPT, AND WE FIRST PROPOSE THAT HIDDEN FACES MAY ALSO BE RELEVANT FOR OTHER SPECIALIZED TISSUE FUNCTIONS, SUCH AS KETOGENESIS IN THE LIVER. NEXT, WE DISCUSS THREE SCENARIOS IN WHICH ABERRANT GENE EXPRESSION CAUSES ABNORMAL GLUCOSE-INDUCED INSULIN RELEASE AND THE EPIGENETIC REGULATION OF THE HIDDEN FACE IN BETA CELLS. WE CONCLUDE WITH PERSPECTIVES FOR NEW RESEARCH, INCLUDING BETA CELL REPLACEMENT TO CURE DIABETES.	2016