1 3432 171 HYDROGEN SULFIDE BIOSYNTHESIS IS IMPAIRED IN THE OSTEOARTHRITIC JOINT. OSTEOARTHRITIS (OA) IS THE MOST COMMON FORM OF ARTHRITIS AND IT IS A LEADING CAUSE OF DISABILITY IN THE ELDERLY. ITS COMPLETE ETIOLOGY IS NOT KNOWN ALTHOUGH THERE ARE SEVERAL METABOLIC, GENETIC, EPIGENETIC, AND LOCAL CONTRIBUTING FACTORS INVOLVED. AT THE MOMENT, THERE IS NO CURE FOR THIS PATHOLOGY AND TREATMENT ALTERNATIVES TO RETARD OR STOP ITS PROGRESSION ARE INTENSIVELY BEING SOUGHT. HYDROGEN SULFIDE (H(2)S) IS A SMALL GASEOUS MOLECULE AND IS PRESENT IN SULFUROUS MINERAL WATERS AS ITS ACTIVE COMPONENT. DATA FROM RECENT CLINICAL TRIALS SHOWS THAT BALNEOTHERAPY (IMMERSION IN MINERAL AND/OR THERMAL WATERS FROM NATURAL SPRINGS) IN SULFUROUS WATERS CAN IMPROVE OA SYMPTOMS, IN PARTICULAR, PAIN AND FUNCTION. YET, THE UNDERLYING MECHANISMS ARE POORLY KNOWN. HYDROGEN SULFIDE IS ALSO CONSIDERED, WITH NO AND CO, AN ENDOGENOUS SIGNALING GASOTRANSMITTER. IT IS SYNTHESIZED ENDOGENOUSLY WITH THE HELP OF THREE ENZYMES, CYSTATHIONINE GAMMA-LYASE (CTH), CYSTATHIONINE BETA-SYNTHASE (CBS), AND 3-MERCAPTOPYRUVATE SULFURTRANSFERASE (3-MPST). HERE, THE EXPRESSION OF THESE THREE ENZYMES WAS DEMONSTRATED BY QUANTITATIVE REAL-TIME POLYMERASE CHAIN REACTION (QRT-PCR) AND THEIR PROTEIN ABUNDANCE [BY IMMUNOHISTOCHEMISTRY AND WESTERN BLOT (WB)] IN HUMAN ARTICULAR CARTILAGE. NO SIGNIFICANT DIFFERENCES WERE FOUND IN CBS OR CTH EXPRESSION OR ABUNDANCE, BUT MRNA AND PROTEIN LEVELS OF 3-MPST WERE SIGNIFICANTLY REDUCED IN CARTILAGE FORM OA DONORS. ALSO, THE BIOSYNTHESIS OF H(2)S FROM OA CARTILAGE, MEASURED WITH A SPECIFIC MICROELECTRODE, WAS SIGNIFICANTLY LOWER THAN IN OA-FREE TISSUE. YET, NO DIFFERENCES WERE FOUND IN H(2)S CONCENTRATION IN SERUM FROM OA PATIENTS AND OA-FREE DONORS. THE CURRENT RESULTS SUGGEST THAT REDUCED LEVELS OF THE MITOCHONDRIAL ENZYME 3-MPST IN OA CARTILAGE MIGHT BE, AT LEAST IN PART, RESPONSIBLE FOR A REDUCTION IN H(2)S BIOSYNTHESIS IN THIS TISSUE AND THAT IMPAIRED H(2)S BIOSYNTHESIS IN THE JOINT MIGHT BE A CONTRIBUTING FACTOR TO OA. THIS COULD CONTRIBUTE TO EXPLAIN WHY EXOGENOUS SUPPLEMENTATION OF H(2)S, FOR INSTANCE WITH SULFUROUS THERMAL WATER, HAS POSITIVE EFFECTS IN OA PATIENTS. 2020 2 4147 38 MECHANISMS UNDERLYING BIOLOGICAL EFFECTS OF CRUCIFEROUS GLUCOSINOLATE-DERIVED ISOTHIOCYANATES/INDOLES: A FOCUS ON METABOLIC SYNDROME. AN INVERSE CORRELATION BETWEEN VEGETABLE CONSUMPTION AND THE INCIDENCE OF CANCER HAS LONG BEEN DESCRIBED. THIS PROTECTIVE EFFECT IS STRONGER WHEN CRUCIFEROUS VEGETABLES ARE SPECIFICALLY CONSUMED. THE BENEFICIAL PROPERTIES OF VEGETABLES ARE ATTRIBUTED TO THEIR BIOACTIVE COMPONENTS LIKE FIBER, ANTIOXIDANTS VITAMINS, ANTIOXIDANTS, MINERALS, AND PHENOLIC COMPOUNDS. CRUCIFEROUS VEGETABLES CONTAIN ALL THESE MOLECULES; HOWEVER, WHAT MAKES THEM DIFFERENT ARE THEIR SULFUROUS COMPONENTS, CALLED GLUCOSINOLATES, RESPONSIBLE FOR THEIR SPECIAL SMELL AND TASTE. GLUCOSINOLATES ARE INACTIVE BIOLOGICALLY IN THE ORGANISM BUT ARE HYDROLYZED BY THE ENZYME MYROSINASE RELEASED AS A RESULT OF CHEWING, LEADING TO THE FORMATION OF ACTIVE DERIVATIVES SUCH AS ISOTHIOCYANATES AND INDOLES. A CONSIDERABLE NUMBER OF IN VITRO AND IN VIVO STUDIES HAVE REPORTED THAT ISOTHIOCYANATES AND INDOLES ELICIT CHEMOPREVENTIVE POTENCY THROUGH MULTIPLE MECHANISMS THAT INCLUDE MODULATION OF PHASES I AND II DETOXIFICATION PATHWAY ENZYMES, REGULATION OF CELL CYCLE ARREST, AND CONTROL OF CELL GROWTH, INDUCTION OF APOPTOSIS, ANTIOXIDANT ACTIVITY, ANTI-ANGIOGENIC EFFECTS, AND EPIGENETIC REGULATION. NUCLEAR ERYTHROID 2-RELATED FACTOR 2 (NRF2) AND NUCLEAR FACTOR-KAPPAB (NF-KAPPAB) ARE KEY AND CENTRAL REGULATORS IN ALL THESE PROCESSES WITH A MAIN ROLE IN OXIDATIVE STRESS AND INFLAMMATION CONTROL. IT HAS BEEN DESCRIBED THAT ISOTHIOCYANATES AND INDOLES REGULATE THEIR ACTIVITY DIRECTLY AND INDIRECTLY. TODAY, THE METABOLIC SYNDROME (CENTRAL OBESITY, INSULIN RESISTANCE, HYPERLIPIDEMIA, AND HYPERTENSION) IS RESPONSIBLE FOR A MAJORITY OF DEATHS WORLDWIDE. ALL COMPONENTS OF METABOLIC SYNDROME ARE CHARACTERIZED BY CHRONIC INFLAMMATION WITH DEREGULATION OF THE PI3K/AKT/MTOR, MAPK/EKR/JNK, NRF2, AND NF-KAPPAB SIGNALING PATHWAYS. THE EFFECTS OF GLSS DERIVATIVES CONTROLLING THESE PATHWAYS HAVE BEEN WIDELY DESCRIBED IN RELATION TO CANCER. CHANGES IN FOOD CONSUMPTION PATTERNS OBSERVED IN THE LAST DECADES TO HIGHER CONSUMPTION OF ULTRA-PROCESSED FOODS, WITH ELEVATION IN SIMPLE SUGAR AND SATURATED FAT CONTENTS AND LOWER CONSUMPTION OF VEGETABLES AND FRUITS HAVE BEEN DIRECTLY CORRELATED WITH METABOLIC SYNDROME PREVALENCE. IN THIS REVIEW, IT IS SUMMARIZED THE KNOWLEDGE REGARDING THE MECHANISMS BY WHICH CRUCIFEROUS GLUCOSINOLATE DERIVATIVES (ISOTHIOCYANATES AND INDOLES) DIRECTLY AND INDIRECTLY REGULATE THESE PATHWAYS. HOWEVER, THE REVIEW PLACES A SPECIAL FOCUS ON THE KNOWLEDGE OF THE EFFECTS OF GLUCOSINOLATES DERIVATIVES IN METABOLIC SYNDROME, SINCE THIS HAS NOT BEEN REVIEWED BEFORE. 2020 3 1066 56 CLINICAL USE OF AMINO ACIDS AS DIETARY SUPPLEMENT: PROS AND CONS. NITROGEN SUPPLY IS PIVOTAL FOR THE MAINTENANCE OF LIFE. AMINO ACIDS CAN BE UTILIZED TO SYNTHESIZE BOTH GLUCOSE AND LIPIDS. THE OPPOSITE, I.E., PRODUCTION OF AMINO ACIDS FROM EITHER ONE OF THEM, IS NOT POSSIBLE IN THE ABSENCE OF OTHER AMINO ACIDS AS DONORS OF NITROGEN. THE QUALITY OF AMINO ACID CONTENT IN PROTEIN HAS BEEN RE-EVALUATED RECENTLY, AND THE RELEVANCE OF ESSENTIAL AMINO ACIDS HAS BEEN REPEATEDLY UNDERLINED. ESSENTIAL AMINO ACID REQUIREMENTS IN DIFFERENT MAMMALS ARE NOT IDENTICAL, AND RATIOS AMONG THEM SHOULD BE TAKEN INTO ACCOUNT WHEN PROJECTING AN EFFICIENT FORMULATION. RECENT RESEARCH HAS DEMONSTRATED THAT GENES RESPOND TO DIFFERENT QUALITIES AND QUANTITIES OF NUTRITIONAL SUPPLY, AND INCREASED PROVISION OF ESSENTIAL AMINO ACIDS INCREASES LIFESPAN IN ANIMAL EXPERIMENTS THROUGH MITOCHONDRIOGENESIS AND MAINTENANCE OF ELEVATED RATES OF SYNTHESIS OF ANTI-OXIDANT MOLECULES. MOREOVER, GENETIC EXPRESSION OF KEY CONTROLLERS OF SYNTHESIS, LIKE MTOR, MAY BE PARTICULARLY IMPORTANT FOR UNDERSTANDING SKELETAL MUSCLE MAINTENANCE. LOSSES OF MUSCLE MASS AND IMPAIRED IMMUNE FUNCTION ARE RELATED TO REDUCED PROTEIN SUPPLY, AND THERE IS INCREASING EVIDENCE THAT REGULAR ESSENTIAL AMINO ACID INTAKE AS PART OF AN ORAL DIET IS EFFECTIVE IN REVERSING MUSCLE CATABOLISM, PROMOTING MUSCLE ANABOLISM, AND RESTORING IMMUNOLOGICAL FUNCTION. THEREFORE, THE USE OF AMINO ACIDS AS SUPPLEMENTS TO DIET WOULD BE EXPANDING IN THE NEAR FUTURE. IS THIS SAFE? FEW DATA ARE AVAILABLE ON AMINO ACID TOXICITY, AND ONLY ONE ESSENTIAL AMINO ACID MAY BE CONSIDERED TO HAVE CLINICALLY RELEVANT TOXICITY: METHIONINE, BECAUSE IT IS TRANSFORMED INTO A TOXIC INTERMEDIATE, HOMOCYSTEINE, WHEN CYSTEINE SYNTHESIS IS REQUIRED BY METABOLIC NEEDS. MATCHING OF STOICHIOMETRIC RATIOS BETWEEN METHIONINE AND CYSTEINE MAY SOLVE THE PROBLEM OF SUPPLYING SUFFICIENT AMOUNTS OF SULFUR TO THE BODY. ARGININE AND GLUTAMINE ARE TWO NON-ESSENTIAL AMINO ACIDS THAN CAN BECOME "CONDITIONALLY ESSENTIAL" BECAUSE OF ELEVATED NEEDS DURING PATHOLOGICAL CONDITIONS, AND METABOLISM MAY NOT BE ABLE TO MAINTAIN THEIR CONCENTRATIONS AT SUFFICIENT LEVELS TO MATCH METABOLIC REQUIREMENTS. CHRONIC EXOGENOUS ARGININE SUPPLEMENTATION HAS NOT PROVEN TO EXERT POSITIVE CLINICAL EFFECTS IN DIFFERENT TRIALS, AND SEQUENTIAL ARTICULATION OF THE KNOWLEDGE OF INTRODUCTION OF ARGININE-DRIVEN TRANSCRIPTIONAL, TRANSLATIONAL, AND EPIGENETIC ADAPTATIONS MAY GIVE US A KEY FOR INTERPRETING THOSE PUZZLING RESULTS. 2011 4 3212 30 HEALTH PROMOTING EFFECTS OF BRASSICA-DERIVED PHYTOCHEMICALS: FROM CHEMOPREVENTIVE AND ANTI-INFLAMMATORY ACTIVITIES TO EPIGENETIC REGULATION. A HIGH INTAKE OF BRASSICA VEGETABLES MAY BE ASSOCIATED WITH A DECREASED CHRONIC DISEASE RISK. HEALTH PROMOTING EFFECTS OF BRASSICACEAE HAVE BEEN PARTLY ATTRIBUTED TO GLUCOSINOLATES AND IN PARTICULAR TO THEIR HYDROLYZATION PRODUCTS INCLUDING ISOTHIOCYANATES. IN VITRO AND IN VIVO STUDIES SUGGEST A CHEMOPREVENTIVE ACTIVITY OF ISOTHIOCYANATES THROUGH THE REDOX-SENSITIVE TRANSCRIPTION FACTOR NRF2. FURTHERMORE, STUDIES IN CULTURED CELLS, IN LABORATORY RODENTS, AND ALSO IN HUMANS SUPPORT AN ANTI-INFLAMMATORY EFFECT OF BRASSICA-DERIVED PHYTOCHEMICALS. HOWEVER, THE UNDERLYING MECHANISMS OF HOW THESE COMPOUNDS MEDIATE THEIR HEALTH PROMOTING EFFECTS ARE YET NOT FULLY UNDERSTOOD. RECENT FINDINGS SUGGEST THAT BRASSICA-DERIVED COMPOUNDS ARE REGULATORS OF EPIGENETIC MECHANISMS. IT HAS BEEN SHOWN THAT ISOTHIOCYANATES MAY INHIBIT HISTONE DEACETYLASE TRANSFERASES AND DNA-METHYLTRANSFERASES IN CULTURED CELLS. ONLY A FEW PAPERS HAVE DEALT WITH THE EFFECT OF BRASSICA-DERIVED COMPOUNDS ON EPIGENETIC MECHANISMS IN LABORATORY ANIMALS, WHEREAS DATA IN HUMANS ARE CURRENTLY LACKING. THE PRESENT REVIEW AIMS TO SUMMARIZE THE CURRENT KNOWLEDGE REGARDING THE BIOLOGICAL ACTIVITIES OF BRASSICA-DERIVED PHYTOCHEMICALS REGARDING CHEMOPREVENTIVE, ANTI-INFLAMMATORY, AND EPIGENETIC PATHWAYS. 2013 5 5010 37 PEROXIDATION OF LINOLEIC, ARACHIDONIC AND OLEIC ACID IN RELATION TO THE INDUCTION OF OXIDATIVE DNA DAMAGE AND CYTOGENETIC EFFECTS. IN THE PRESENT STUDY, THE POSSIBLE ROLE OF THE POLYUNSATURATED FATTY ACIDS LINOLEIC AND ARACHIDONIC ACID IN THE CHEMICAL INDUCTION OF CARCINOGENESIS HAS BEEN INVESTIGATED. ANALYSIS OF 7,8-DIHYDRO-8-OXO-2'-DEOXYGUANOSINE (8-OXODG) LEVELS IN 2'-DEOXYGUANOSINE (DG) AND ISOLATED DNA HAS DEMONSTRATED THAT LINOLEIC AND ARACHIDONIC ACID ARE CAPABLE OF INDUCING THIS SPECIFIC GENOTOXIC DAMAGE. THIS EFFECT APPEARS TO BE RELATED TO THE DEGREE OF FATTY ACID UNSATURATION, SINCE IT WAS NOT INDUCED BY MONOUNSATURATED OLEIC ACID. ENZYMATIC PEROXIDATION OF LINOLEIC AND ARACHIDONIC ACID RESULTED IN A SIGNIFICANT INCREASE IN OXIDATIVE DNA DAMAGE. STUDIES ON THE INTERFERENCE OF RADICAL SCAVENGERS WITH THE INDUCTION OF 8-OXODG IN COMBINATION WITH ELECTRON SPIN RESONANCE SPECTROSCOPY DEMONSTRATED THAT THE SUPEROXIDE ANION WAS GENERATED DURING PEROXIDATION OF THESE FATTY ACIDS AND THAT SINGLET OXYGEN IS MOST LIKELY INVOLVED IN THE FORMATION OF OXIDATIVE DNA DAMAGE. THE LEVEL OF OXIDATIVE DAMAGE IN DG AND SINGLE-STRANDED DNA WAS HIGHER AS COMPARED TO THAT IN NATIVE DNA AFTER EQUIMOLAR TREATMENT. EXPOSURE OF HUMAN LYMPHOCYTES TO LINOLEIC OR ARACHIDONIC ACID DID NOT RESULT IN A SIGNIFICANT INCREASE IN LEVELS OF 8-OXODG. THIS MAY INDICATE THAT THE RATE OF INTRACELLULAR PEROXIDATION IS RELATIVELY LOW AND/OR THAT NUCLEAR DNA IN INTACT CELLS IS EFFECTIVELY PROTECTED AGAINST GENETIC DAMAGE INDUCED BY REACTIVE OXYGEN SPECIES. IT IS THEREFORE CONCLUDED THAT RELATIVELY SHORT PERIODS OF LINOLEIC OR ARACHIDONIC ACID ADMINISTRATION ARE NOT LIKELY TO IMPOSE A DIRECT GENOTOXIC RISK. IT CAN, HOWEVER, NOT BE EXCLUDED THAT CHRONIC EXPOSURE TO POLYUNSATURATED FATTY ACIDS INDUCES OXIDATIVE DNA DAMAGE OR IS RELATED TO CANCER RISK BY EPIGENETIC MECHANISMS, AS IS ALSO INDICATED BY THE OBSERVED CYTOTOXIC EFFECTS OF LINOLEIC AND ARACHIDONIC ACID. 1994 6 6290 30 THE POTENTIAL ROLE OF NUTRITIONAL GENOMICS TOOLS IN VALIDATING HIGH HEALTH FOODS FOR CANCER CONTROL: BROCCOLI AS EXAMPLE. NUTRITIONAL GENOMICS REFLECTS GENE/NUTRIENT INTERACTIONS, UTILISING HIGH-THROUGHPUT GENOMIC TOOLS IN NUTRITION RESEARCH. THE FIELD ALSO CONSIDERS THE CONTRIBUTION OF INDIVIDUAL GENOTYPES TO WELLNESS AND THE RISK OF CHRONIC DISEASE (NUTRIGENETICS), AND HOW SUCH GENETIC PREDISPOSITION MAY BE MODIFIED BY APPROPRIATE DIETS. FOR EXAMPLE, HIGH CONSUMPTION OF BRASSICACEOUS VEGETABLES, INCLUDING BROCCOLI, HAS REGULARLY ASSOCIATED WITH LOW CANCER RISK. BIOACTIVE CHEMICALS IN BROCCOLI INCLUDE GLUCOSINOLATES, PLANT PIGMENTS INCLUDING KAEMPFEROL, QUERCETIN, LUTEIN AND CAROTENOIDS, VARIOUS VITAMINS, MINERALS AND AMINO ACIDS. CANCER PREVENTION IS HYPOTHESISED TO ACT THROUGH VARIOUS MECHANISMS INCLUDING MODULATION OF XENOBIOTIC METABOLISING ENZYMES, NF-E2 P45-RELATED FACTOR-2 (NRF2)-MEDIATED STRESS-RESPONSE MECHANISMS, AND PROTECTION AGAINST GENOMIC INSTABILITY. BROCCOLI AND BROCCOLI EXTRACTS ALSO REGULATE THE PROGRESSION OF CANCER THROUGH ANTI-INFLAMMATORY EFFECTS, EFFECTS ON SIGNAL TRANSDUCTION, EPIGENETIC EFFECTS AND MODULATION OF THE COLONIC MICROFLORA. HUMAN INTERVENTION STUDIES WITH BROCCOLI AND RELATED FOODS, USING STANDARD BIOMARKER METHODOLOGIES, REVEAL PART OF A COMPLEX PICTURE. NUTRIGENOMIC APPROACHES, ESPECIALLY TRANSCRIPTOMICS, ENABLE SIMULTANEOUS STUDY OF VARIOUS SIGNALLING PATHWAYS AND NETWORKS. PHENOTYPIC, GENETIC AND/OR METABOLIC STRATIFICATION MAY IDENTIFY INDIVIDUALS MOST LIKELY TO RESPOND POSITIVELY TO FOODS OR DIETS. JOINTLY, THESE TECHNOLOGIES CAN PROVIDE PROOF OF HUMAN EFFICACY, AND MAY BE ESSENTIAL TO ENSURE EFFECTIVE MARKET TRANSFER AND UPTAKE OF BROCCOLI AND RELATED FOODS. 2012 7 6166 35 THE GLUTATHIONE SYSTEM: A NEW DRUG TARGET IN NEUROIMMUNE DISORDERS. GLUTATHIONE (GSH) HAS A CRUCIAL ROLE IN CELLULAR SIGNALING AND ANTIOXIDANT DEFENSES EITHER BY REACTING DIRECTLY WITH REACTIVE OXYGEN OR NITROGEN SPECIES OR BY ACTING AS AN ESSENTIAL COFACTOR FOR GSH S-TRANSFERASES AND GLUTATHIONE PEROXIDASES. GSH ACTING IN CONCERT WITH ITS DEPENDENT ENZYMES, KNOWN AS THE GLUTATHIONE SYSTEM, IS RESPONSIBLE FOR THE DETOXIFICATION OF REACTIVE OXYGEN AND NITROGEN SPECIES (ROS/RNS) AND ELECTROPHILES PRODUCED BY XENOBIOTICS. ADEQUATE LEVELS OF GSH ARE ESSENTIAL FOR THE OPTIMAL FUNCTIONING OF THE IMMUNE SYSTEM IN GENERAL AND T CELL ACTIVATION AND DIFFERENTIATION IN PARTICULAR. GSH IS A UBIQUITOUS REGULATOR OF THE CELL CYCLE PER SE. GSH ALSO HAS CRUCIAL FUNCTIONS IN THE BRAIN AS AN ANTIOXIDANT, NEUROMODULATOR, NEUROTRANSMITTER, AND ENABLER OF NEURON SURVIVAL. DEPLETION OF GSH LEADS TO EXACERBATION OF DAMAGE BY OXIDATIVE AND NITROSATIVE STRESS; HYPERNITROSYLATION; INCREASED LEVELS OF PROINFLAMMATORY MEDIATORS AND INFLAMMATORY POTENTIAL; DYSFUNCTIONS OF INTRACELLULAR SIGNALING NETWORKS, E.G., P53, NUCLEAR FACTOR-KAPPAB, AND JANUS KINASES; DECREASED CELL PROLIFERATION AND DNA SYNTHESIS; INACTIVATION OF COMPLEX I OF THE ELECTRON TRANSPORT CHAIN; ACTIVATION OF CYTOCHROME C AND THE APOPTOTIC MACHINERY; BLOCKADE OF THE METHIONINE CYCLE; AND COMPROMISED EPIGENETIC REGULATION OF GENE EXPRESSION. AS SUCH, GSH DEPLETION HAS MARKED CONSEQUENCES FOR THE HOMEOSTATIC CONTROL OF THE IMMUNE SYSTEM, OXIDATIVE AND NITROSATIVE STRESS (O&NS) PATHWAYS, REGULATION OF ENERGY PRODUCTION, AND MITOCHONDRIAL SURVIVAL AS WELL. GSH DEPLETION AND CONCOMITANT INCREASE IN O&NS AND MITOCHONDRIAL DYSFUNCTIONS PLAY A ROLE IN THE PATHOPHYSIOLOGY OF DIVERSE NEUROIMMUNE DISORDERS, INCLUDING DEPRESSION, MYALGIC ENCEPHALOMYELITIS/CHRONIC FATIGUE SYNDROME AND PARKINSON'S DISEASE, SUGGESTING THAT DEPLETED GSH IS AN INTEGRAL PART OF THESE DISEASES. THERAPEUTICAL INTERVENTIONS THAT AIM TO INCREASE GSH CONCENTRATIONS IN VIVO INCLUDE N-ACETYL CYSTEINE; NRF-2 ACTIVATION VIA HYPERBARIC OXYGEN THERAPY; DIMETHYL FUMARATE; PHYTOCHEMICALS, INCLUDING CURCUMIN, RESVERATROL, AND CINNAMON; AND FOLATE SUPPLEMENTATION. 2014 8 4796 33 NUTRITIONAL INTERVENTION AS AN ESSENTIAL PART OF MULTIPLE SCLEROSIS TREATMENT? MULTIPLE SCLEROSIS (MS) IS A CHRONIC INFLAMMATORY AND DEMYELINATING DISEASE OF THE CENTRAL NERVOUS SYSTEM. IN ADDITION TO THE GENETIC, EPIGENETIC AND IMMUNOLOGICAL COMPONENTS, VARIOUS OTHER FACTORS, E.G. UNHEALTHY DIETARY HABITS, PLAY A ROLE IN THE MS PATHOGENESIS. DIETARY INTERVENTION IS A HIGHLY APPEALING APPROACH, AS IT PRESENTS A SIMPLE AND RELATIVELY LOW RISK METHOD TO POTENTIALLY IMPROVE OUTCOMES IN PATIENTS WITH BRAIN DISORDERS IN ORDER TO ACHIEVE REMISSION AND IMPROVEMENT OF CLINICAL STATUS, WELL-BEING AND LIFE EXPECTANCY OF PATIENTS WITH MS. THE IMPORTANCE OF SATURATED FAT INTAKE RESTRICTION FOR THE CLINICAL STATUS IMPROVEMENT OF MS PATIENTS WAS POINTED FOR THE FIRST TIME IN 1950S. RECENTLY, DECREASED RISK OF FIRST CLINICAL DIAGNOSIS OF CNS DEMYELINATION ASSOCIATED WITH HIGHER INTAKE OF OMEGA-3 POLYUNSATURATED FATTY ACIDS PARTICULARLY ORIGINATING FROM FISH WAS REPORTED. ONLY FEW CLINICAL TRIALS HAVE BEEN PERFORMED TO ADDRESS THE QUESTION OF THE ROLE OF DIETARY INTERVENTION, SUCH IS E.G. LOW SATURATED FAT DIET IN MS TREATMENT. THIS REVIEW SUMMARIZES CURRENT KNOWLEDGE ABOUT THE EFFECT OF DIFFERENT DIETARY APPROACHES (DIETS LOW IN SATURATED FAT AND DIETARY SUPPLEMENTS SUCH AS FISH OIL, LIPOIC ACID, OMEGA-3 POLYUNSATURATED FATTY ACIDS, SEEDS OILS, HIGH FIBER DIET, VITAMIN D, ETC.) ON NEUROLOGICAL SIGNS, PATIENT'S WELL-BEING, PHYSICAL AND INFLAMMATORY STATUS. SO FAR THE RESULTS ARE NOT CONCLUSIVE, THEREFORE MUCH MORE RESEARCH IS NEEDED TO CONFIRM AND TO UNDERSTAND THE EFFECTIVENESS OF THESE DIETARY INTERVENTIONS IN THE LONG TERM AND WELL DEFINED STUDIES. 2018 9 361 38 AMBIENT AIR POLLUTION AND THROMBOSIS. AIR POLLUTION IS A GROWING PUBLIC HEALTH CONCERN OF GLOBAL SIGNIFICANCE. ACUTE AND CHRONIC EXPOSURE IS KNOWN TO IMPAIR CARDIOVASCULAR FUNCTION, EXACERBATE DISEASE AND INCREASE CARDIOVASCULAR MORTALITY. SEVERAL PLAUSIBLE BIOLOGICAL MECHANISMS HAVE BEEN PROPOSED FOR THESE ASSOCIATIONS, HOWEVER, AT PRESENT, THE PATHWAYS ARE INCOMPLETE. A SEMINAL REVIEW BY THE AMERICAN HEART ASSOCIATION (2010) CONCLUDED THAT THE THROMBOTIC EFFECTS OF PARTICULATE AIR POLLUTION LIKELY CONTRIBUTED TO THEIR EFFECTS ON CARDIOVASCULAR MORTALITY AND MORBIDITY. THE AIM OF THE CURRENT REVIEW IS TO APPRAISE THE NEWLY ACCUMULATED SCIENTIFIC EVIDENCE (2009-2016) ON CONTRIBUTION OF HAEMOSTASIS AND THROMBOSIS TOWARDS CARDIOVASCULAR DISEASE INDUCED BY EXPOSURE TO BOTH PARTICULATE AND GASEOUS POLLUTANTS.SEVENTY FOUR PUBLICATIONS WERE REVIEWED IN-DEPTH. THE WEIGHT OF EVIDENCE SUGGESTS THAT ACUTE EXPOSURE TO FINE PARTICULATE MATTER (PM(2.5)) INDUCES A SHIFT IN THE HAEMOSTATIC BALANCE TOWARDS A PRO-THROMBOTIC/PRO-COAGULATIVE STATE. INSUFFICIENT DATA WAS AVAILABLE TO ASCERTAIN IF A SIMILAR RELATIONSHIP EXISTS FOR GASEOUS POLLUTANTS, AND VERY FEW STUDIES HAVE ADDRESSED LONG-TERM EXPOSURE TO AMBIENT AIR POLLUTION. PLATELET ACTIVATION, OXIDATIVE STRESS, INTERPLAY BETWEEN INTERLEUKIN-6 AND TISSUE FACTOR, ALL APPEAR TO BE POTENTIALLY IMPORTANT MECHANISMS IN POLLUTION-MEDIATED THROMBOSIS, TOGETHER WITH AN EMERGING ROLE FOR CIRCULATING MICROVESICLES AND EPIGENETIC CHANGES.OVERALL, THE RECENT LITERATURE SUPPORTS, AND ARGUABLY STRENGTHENS, THE CONTENTION THAT AIR POLLUTION CONTRIBUTES TO CARDIOVASCULAR MORBIDITY BY PROMOTING HAEMOSTASIS. THE VOLUME AND DIVERSITY OF THE EVIDENCE HIGHLIGHTS THE COMPLEXITY OF THE PATHOPHYSIOLOGIC MECHANISMS BY WHICH AIR POLLUTION PROMOTES THROMBOSIS; MULTIPLE PATHWAYS ARE PLAUSIBLE AND IT IS MOST LIKELY THEY ACT IN CONCERT. FUTURE RESEARCH SHOULD ADDRESS THE ROLE GASEOUS POLLUTANTS PLAY IN THE CARDIOVASCULAR EFFECTS OF AIR POLLUTION MIXTURE AND DIRECT COMPARISON OF POTENTIALLY SUSCEPTIBLE GROUPS TO HEALTHY INDIVIDUALS. 2018 10 4652 25 NEUROPROTECTION WITH NATURAL ANTIOXIDANTS AND NUTRACEUTICALS IN THE CONTEXT OF BRAIN CELL DEGENERATION: THE EPIGENETIC CONNECTION. BIOACTIVE ANTIOXIDANT AGENTS PRESENT IN SELECTED PLANTS ARE KNOWN TO PROVIDE THE FIRST LINE OF BIOLOGICAL DEFENSE AGAINST OXIDATIVE STRESS. IN PARTICULAR, SOLUBLE VITAMIN C, E, CAROTENOIDS AND PHENOLIC COMPOUNDS HAVE DEMONSTRATED CRUCIAL BIOLOGICAL EFFECTS IN CELLS AGAINST OXIDATIVE DAMAGE, PREVENTING PREVALENT CHRONIC DISEASES, SUCH AS DIABETES, CANCER AND CARDIOVASCULAR DISEASE. THE REPORTED WIDE RANGE OF EFFECTS THAT INCLUDED ANTI-AGING, ANTI-ATHEROSCLEROSIS, ANTI-INFLAMMATORY AND ANTICANCER ACTIVITY WERE STUDIED AGAINST DEGENERATIVE PATHOLOGIES OF THE BRAIN. VITAMINS AND DIFFERENT PHYTOCHEMICALS ARE IMPORTANT EPIGENETIC MODIFIERS THAT PREVENT NEURODEGENERATION. IN ORDER TO EXPLORE THE POTENTIAL ANTIOXIDANT SOURCES IN FUNCTIONAL FOODS AND NUTRACEUTICALS AGAINST NEURODEGENERATION, THE PRESENT PAPER AIMS TO SHOW A COMPREHENSIVE ASSESSMENT OF ANTIOXIDANT ACTIVITY AT CHEMICAL AND CELLULAR LEVELS. THE EFFECTS OF THE DIFFERENT BIOACTIVE COMPOUNDS AVAILABLE AND THEIR ANTIOXIDANT ACTIVITY THROUGH AN EPIGENETIC POINT OF VIEW ARE ALSO DISCUSSED. 2019 11 6742 47 WHITHER THE ETIOPATHOGENESIS (AND SCOLIOGENY) OF ADOLESCENT IDIOPATHIC SCOLIOSIS? ALTHOUGH CONSIDERABLE PROGRESS HAD BEEN MADE IN THE PAST TWO DECADES IN UNDERSTANDING THE ETIOPATHOGENESIS OF ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS), IT STILL LACKS AN AGREED THEORY OF ETIOPATHOGENESIS. ONE PROBLEM MAY BE THAT AIS RESULTS NOT FROM ONE CAUSE, BUT SEVERAL THAT INTERACT WITH VARIOUS GENETIC PREDISPOSING FACTORS. THERE IS A VIEW THERE ARE TWO OTHER PATHOGENIC PROCESSES FOR IDIOPATHIC SCOLIOSIS NAMELY, INITIATING (OR INDUCING), AND THOSE THAT CAUSE CURVE PROGRESSION. TWIN STUDIES AND OBSERVATIONS OF FAMILY AGGREGATION HAVE REVEALED SIGNIFICANT GENETIC CONTRIBUTIONS TO IDIOPATHIC SCOLIOSIS, THAT PLACE AIS AMONG OTHER COMMON DISEASE OR COMPLEX TRAITS WITH A HIGH HERITABILITY INTERPRETED BY THE GENETIC VARIANT HYPOTHESIS OF DISEASE. WE SUMMARIZE ETIOPATHOGENETIC KNOWLEDGE OF AIS AS THEORIES OF PATHOGENESIS INCLUDING RECENT MULTIPLE CONCEPTS, AND BLOOD TESTS FOR AIS BASED ON PREDICTIVE BIOMARKERS AND GENETIC VARIANTS THAT SIGNIFY DISEASE RISK. THERE IS INCREASING EVIDENCE FOR THE POSSIBILITY OF AN UNDERLYING NEUROLOGICAL DISORDER FOR AIS, RESEARCH WHICH HOLDS PROMISE. LIKE BRAIN RESEARCH, MOST AIS WORKERS FOCUS ON THEIR OWN CORNER AND THERE IS A NEED FOR GREATER INTEGRATION OF RESEARCH EFFORT. EPIGENETICS, A RELATIVELY RECENT FIELD, EVALUATES FACTORS CONCERNED WITH GENE EXPRESSION IN RELATION TO ENVIRONMENT, DISEASE, NORMAL DEVELOPMENT AND AGING, WITH A COMPLEX REGULATION ACROSS THE GENOME DURING THE FIRST DECADE OF LIFE. RESEARCH ON THE ROLE OF ENVIRONMENTAL FACTORS, EPIGENETICS AND CHRONIC NON-COMMUNICABLE DISEASES (NCDS) INCLUDING ADIPOSITY, AFTER A SLOW START, HAS EXPLODED IN THE LAST DECADE. NOT SO FOR AIS RESEARCH AND THE ENVIRONMENT WHERE, EXCEPT FOR MONOZYGOTIC TWIN STUDIES, THERE ARE ONLY SPORADIC REPORTS TO SUGGEST THAT ENVIRONMENTAL FACTORS ARE AT WORK IN ETIOLOGY. HERE, WE EXAMINE EPIGENETIC CONCEPTS AS THEY MAY RELATE TO HUMAN DEVELOPMENT, NORMAL LIFE HISTORY PHASES AND AIS PATHOGENESIS. ALTHOUGH AIS IS NOT REGARDED AS AN NCD, LIKE THEM, IT IS ASSOCIATED WITH WHOLE ORGANISM METABOLIC PHENOMENA, INCLUDING LOWER BODY MASS INDEX, LOWER CIRCULATING LEPTIN LEVELS AND OTHER SYSTEMIC DISORDERS. SOME EPIGENETIC RESEARCH APPLIED TO SILVER-RUSSELL SYNDROME AND ADIPOSITY IS EXAMINED, FROM WHICH SUGGESTIONS ARE MADE FOR CONSIDERATION OF AIS EPIGENETIC RESEARCH, CROSS-SECTIONAL AND LONGITUDINAL. THE WORD SCOLIOGENY IS SUGGESTED TO INCLUDE ETIOLOGY, PATHOGENESIS AND PATHOMECHANISM. 2012 12 4044 26 MACROPHAGES IN OXIDATIVE STRESS AND MODELS TO EVALUATE THE ANTIOXIDANT FUNCTION OF DIETARY NATURAL COMPOUNDS. ANTIOXIDANT TESTING OF NATURAL PRODUCTS HAS ATTRACTED INCREASING INTEREST IN RECENT YEARS, MAINLY DUE TO THE FACT THAT AN ANTIOXIDANT-RICH DIET MIGHT PROVIDE HEALTH BENEFITS. ACTIVATED MACROPHAGES ARE A MAJOR SOURCE OF REACTIVE OXYGEN SPECIES, REACTIVE NITROGEN SPECIES, AND PEROXYNITRITE GENERATED THROUGH THE SO-CALLED RESPIRATORY BURST. CONSTITUTIVELY RELEASED PROINFLAMMATORY CYTOKINE, ESPECIALLY TUMOR NECROSIS FACTOR-ALPHA, TRIGGERS NUCLEAR FACTOR-KAPPAB, AND ACTIVATOR PROTEIN-1 TRANSLOCATION LEADING TO THE OVER PRODUCTION OF REACTIVE OXYGEN SPECIES AND REACTIVE NITROGEN SPECIES IN MACROPHAGES. ACTIVATION OF TRANSCRIPTION FACTORS IN THE LONG-LIVED TISSUE-RESIDENT MACROPHAGES AND/OR MONOCYTE-DERIVED MACROPHAGES, TRIGGER EPIGENETIC MODIFICATIONS LEADING TO THE PATHOGENESIS OF CHRONIC DISEASES. NUTRACEUTICALS INCLUDING LIPID RAFT STRUCTURE DISRUPTION AGENT, CHOLESTEROL DEPLETION AGENT, FARNESYLTRANSFERASE INHIBITOR, NUCLEAR FACTOR-KAPPAB BLOCKER (ALPHA,BETA-UNSATURATED CARBONYL COMPOUNDS), GLUCOCORTICOID RECEPTOR AGONIST, AND PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA AGONIST HAVE LONG BEEN USED TO INACTIVE MACROPHAGE. THE INHIBITION EFFECTS ON THE FORMATION OF NITRIC OXIDE, SUPEROXIDE, AND NITRITE PEROXIDE MAY BE RESPONSIBLE FOR THE ANTI-INFLAMMATORY FUNCTIONALITIES. ACTIVATED MACROPHAGE MODELS COULD BE USED TO IDENTIFY THE ACTIVE COMPONENTS FOR FUNCTIONAL DIETS DEVELOPMENT THROUGH A MULTIPLE TARGETS STRATEGY. 2017 13 6436 29 THERAPEUTIC ACTIONS OF TEA PHENOLIC COMPOUNDS AGAINST OXIDATIVE STRESS AND INFLAMMATION AS CENTRAL MEDIATORS IN THE DEVELOPMENT AND PROGRESSION OF HEALTH PROBLEMS: A REVIEW FOCUSING ON MICRORNA REGULATION. MANY HEALTH PROBLEMS INCLUDING CHRONIC DISEASES ARE CLOSELY ASSOCIATED WITH OXIDATIVE STRESS AND INFLAMMATION. TEA HAS ABUNDANT PHENOLIC COMPOUNDS WITH VARIOUS HEALTH BENEFITS INCLUDING ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES. THIS REVIEW FOCUSES ON THE PRESENT UNDERSTANDING OF THE IMPACT OF TEA PHENOLIC COMPOUNDS ON THE EXPRESSION OF MIRNAS, AND ELUCIDATES THE BIOCHEMICAL AND MOLECULAR MECHANISMS UNDERLYING THE TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL PROTECTIVE ACTIONS OF TEA PHENOLIC COMPOUNDS AGAINST OXIDATIVE STRESS- AND/OR INFLAMMATION-MEDIATED DISEASES. CLINICAL STUDIES SHOWED THAT DRINKING TEA OR TAKING CATECHIN SUPPLEMENT ON A DAILY BASIS PROMOTED THE ENDOGENOUS ANTIOXIDANT DEFENSE SYSTEM OF THE BODY WHILE INHIBITING INFLAMMATORY FACTORS. THE REGULATION OF CHRONIC DISEASES BASED ON EPIGENETIC MECHANISMS, AND THE EPIGENETIC-BASED THERAPIES INVOLVING DIFFERENT TEA PHENOLIC COMPOUNDS, HAVE BEEN INSUFFICIENTLY STUDIED. THE MOLECULAR MECHANISMS AND APPLICATION STRATEGIES OF MIR-27 AND MIR-34 INVOLVED IN OXIDATIVE STRESS RESPONSE AND MIR-126 AND MIR-146 INVOLVED IN INFLAMMATION PROCESS WERE PRELIMINARILY INVESTIGATED. SOME EMERGING EVIDENCE SUGGESTS THAT TEA PHENOLIC COMPOUNDS MAY PROMOTE EPIGENETIC CHANGES, INVOLVING NON-CODING RNA REGULATION, DNA METHYLATION, HISTONE MODIFICATION, UBIQUITIN AND SUMO MODIFICATIONS. HOWEVER, EPIGENETIC MECHANISMS AND EPIGENETIC-BASED DISEASE THERAPIES INVOLVING PHENOLIC COMPOUNDS FROM DIFFERENT TEAS, AND THE POTENTIAL CROSS-TALKS AMONG THE EPIGENETIC EVENTS, REMAIN UNDERSTUDIED. 2023 14 5145 33 POTENTIAL ROLE OF NUTRACEUTICALS VIA TARGETING A WNT/BETA-CATENIN AND NF-KAPPAB PATHWAY IN TREATMENT OF OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS A DISEASE DUE TO THE AGING OF THE ARTICULAR CARTILAGE, A POST-MITOTIC TISSUE THAT STAYS FUNCTIONING UNTIL PRIMARY HOMEOSTATIC PROCESSES FAIL. BECAUSE OF PAIN AND DISABILITY, OA SIGNIFICANTLY INFLUENCES NATIONAL HEALTHCARE EXPENSES AND PATIENT QUALITY OF LIFE. IT IS A WHOLE-JOINT ILLNESS CHARACTERIZED BY INFLAMMATORY AND OXIDATIVE SIGNALING PATHWAYS AND SIGNIFICANT EPIGENETIC ALTERATIONS THAT CAUSE CARTILAGE EXTRACELLULAR MATRIX DEGRADATION. THE CANONICAL WNT PATHWAY (WNT/BETA-CATENIN PATHWAY) AND NUCLEAR FACTOR KAPPA B (NF-KAPPAB) SIGNALING PATHWAYS MAY FUNCTION IN JOINT TISSUES BY MODULATING THE ACTIVITY OF SYNOVIAL CELLS, OSTEOBLASTS, AND CHONDROCYTES. HOWEVER, FINDING INNOVATIVE WAYS TO TREAT OSTEOARTHRITIS AND GET THE JOINT BACK TO AVERAGE BALANCE IS STILL A STRUGGLE. NUTRACEUTICALS ARE DIETARY SUPPLEMENTS THAT PROMOTE JOINT HEALTH BY BALANCING ANABOLIC AND CATABOLIC SIGNALS. NEW THERAPEUTIC METHODS FOR OA TREATMENT HAVE BEEN DEVELOPED BASED ON MANY RESEARCH FINDINGS THAT SHOW NUTRACEUTICALS HAVE STRONG ANTI-INFLAMMATION, ANTIOXIDANT, ANTI-BONE RESORPTION, AND ANABOLIC PROPERTIES. FOR THE TREATMENT OF OSTEOARTHRITIS, WE EXPLORE THE POSSIBLE INVOLVEMENT OF NUTRACEUTICALS THAT TARGET THE WNT/BETA-CATENIN AND NF-KAPPAB PATHWAYS. PRACTICAL APPLICATIONS: IN KEEPING WITH THE AGING POPULATION, OSTEOARTHRITIS IS BECOMING MORE WIDESPREAD. IN THIS EXTENSIVE RESEARCH, WE STUDIED THE ROLE OF THE WNT/BETA-CATENIN AND NF-KAPPAB PATHWAY IN OA FORMATION AND PROGRESSION. NUTRACEUTICALS THAT TARGET THESE OA-RELATED SIGNALING PATHWAYS ARE A VIABLE THERAPY OPTION. WNT/BETA-CATENIN AND NF-KAPPAB SIGNALING PATHWAY ARE INHIBITED BY POLYPHENOLS, FLAVONOIDS, ALKALOIDS, AND VITAMINS FROM THE NUTRACEUTICAL CATEGORY, MAKING THEM POSSIBLE THERAPEUTIC DRUGS FOR OA THERAPY. 2022 15 6743 52 WHITHER THE ETIOPATHOGENESIS (AND SCOLIOGENY) OF ADOLESCENT IDIOPATHIC SCOLIOSIS? INCORPORATING PRESENTATIONS ON SCOLIOGENY AT THE 2012 IRSSD AND SRS MEETINGS. THIS PAPER AIMS TO INTEGRATE INTO CURRENT UNDERSTANDING OF AIS CAUSATION, ETIOPATHOGENETIC INFORMATION PRESENTED AT TWO MEETINGS DURING 2012 NAMELY, THE INTERNATIONAL RESEARCH SOCIETY OF SPINAL DEFORMITIES (IRSSD) AND THE SCOLIOSIS RESEARCH SOCIETY (SRS). THE ULTIMATE HOPE IS TO PREVENT THE OCCURRENCE OR PROGRESSION OF THE SPINAL DEFORMITY OF AIS WITH NON-INVASIVE TREATMENT, POSSIBLY MEDICAL. THIS MIGHT BE ATTAINED BY PERSONALISED POLYMECHANISTIC PREVENTIVE THERAPY TARGETING THE APPROPRIATE ETIOLOGY AND/OR ETIOPATHOGENETIC PATHWAYS, TO AVOID FUSION AND MAINTAIN SPINAL MOBILITY. ALTHOUGH CONSIDERABLE PROGRESS HAD BEEN MADE IN THE PAST TWO DECADES IN UNDERSTANDING THE ETIOPATHOGENESIS OF ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS), IT STILL LACKS AN AGREED THEORY OF ETIOPATHOGENESIS. ONE PROBLEM MAY BE THAT AIS RESULTS NOT FROM ONE CAUSE, BUT SEVERAL THAT INTERACT WITH VARIOUS GENETIC PREDISPOSING FACTORS. THERE IS A VIEW THERE ARE TWO OTHER PATHOGENIC PROCESSES FOR IDIOPATHIC SCOLIOSIS NAMELY, INITIATING (OR INDUCING), AND THOSE THAT CAUSE CURVE PROGRESSION. TWIN STUDIES AND OBSERVATIONS OF FAMILY AGGREGATION HAVE REVEALED SIGNIFICANT GENETIC CONTRIBUTIONS TO IDIOPATHIC SCOLIOSIS, THAT PLACE AIS AMONG OTHER COMMON DISEASE OR COMPLEX TRAITS WITH A HIGH HERITABILITY INTERPRETED BY THE GENETIC VARIANT HYPOTHESIS OF DISEASE. WE SUMMARIZE ETIOPATHOGENETIC KNOWLEDGE OF AIS AS THEORIES OF PATHOGENESIS INCLUDING RECENT MULTIPLE CONCEPTS, AND BLOOD TESTS FOR AIS BASED ON PREDICTIVE BIOMARKERS AND GENETIC VARIANTS THAT SIGNIFY DISEASE RISK. THERE IS INCREASING EVIDENCE FOR THE POSSIBILITY OF AN UNDERLYING NEUROLOGICAL DISORDER FOR AIS, RESEARCH WHICH HOLDS PROMISE. LIKE BRAIN RESEARCH, MOST AIS WORKERS FOCUS ON THEIR OWN CORNER AND THERE IS A NEED FOR GREATER INTEGRATION OF RESEARCH EFFORT. EPIGENETICS, A RELATIVELY RECENT FIELD, EVALUATES FACTORS CONCERNED WITH GENE EXPRESSION IN RELATION TO ENVIRONMENT, DISEASE, NORMAL DEVELOPMENT AND AGING, WITH A COMPLEX REGULATION ACROSS THE GENOME DURING THE FIRST DECADE OF LIFE. RESEARCH ON THE ROLE OF ENVIRONMENTAL FACTORS, EPIGENETICS AND CHRONIC NON-COMMUNICABLE DISEASES (NCDS) INCLUDING ADIPOSITY, AFTER A SLOW START, HAS EXPLODED IN THE LAST DECADE. NOT SO FOR AIS RESEARCH AND THE ENVIRONMENT WHERE, EXCEPT FOR MONOZYGOTIC TWIN STUDIES, THERE ARE ONLY SPORADIC REPORTS TO SUGGEST THAT ENVIRONMENTAL FACTORS ARE AT WORK IN ETIOLOGY. HERE, WE EXAMINE EPIGENETIC CONCEPTS AS THEY MAY RELATE TO HUMAN DEVELOPMENT, NORMAL LIFE HISTORY PHASES AND AIS PATHOGENESIS. ALTHOUGH AIS IS NOT REGARDED AS AN NCD, LIKE THEM, IT IS ASSOCIATED WITH WHOLE ORGANISM METABOLIC PHENOMENA, INCLUDING LOWER BODY MASS INDEX, LOWER CIRCULATING LEPTIN LEVELS AND OTHER SYSTEMIC DISORDERS. SOME EPIGENETIC RESEARCH APPLIED TO SILVER-RUSSELL SYNDROME AND ADIPOSITY IS EXAMINED, FROM WHICH SUGGESTIONS ARE MADE FOR CONSIDERATION OF AIS EPIGENETIC RESEARCH, CROSS-SECTIONAL AND LONGITUDINAL. THE WORD SCOLIOGENY IS SUGGESTED TO INCLUDE ETIOLOGY, PATHOGENESIS AND PATHOMECHANISM. 2013 16 6038 39 THE CHEMICAL DEFENSIVE SYSTEM IN THE PATHOBIOLOGY OF IDIOPATHIC ENVIRONMENT-ASSOCIATED DISEASES. CHEMICAL DEFENSIVE SYSTEM CONSISTING OF BIO-SENSORING, TRANSMITTING, AND RESPONSIVE ELEMENTS HAS BEEN EVOLVED TO PROTECT MULTI-CELLULAR ORGANISMS AGAINST ENVIRONMENTAL CHEMICAL INSULTS (XENOBIOTICS) AND TO MAINTAIN HOMEOSTASIS OF ENDOGENOUS LOW MOLECULAR WEIGHT METABOLITES (ENDOBIOTICS). BOTH GENETIC AND EPIGENETIC DEFECTS OF THE SYSTEM IN ASSOCIATION WITH CARCINOGENESIS AND INDIVIDUAL SENSITIVITY TO ANTI-TUMOR THERAPIES HAVE BEEN INTENSELY STUDIED. RECENTLY, SEVERAL NON-TUMOR HUMAN PATHOLOGIES WITH EVIDENT ENVIRONMENTAL COMPONENTS SUCH AS RATHER RARE FUNCTIONAL SYNDROMES (MULTIPLE CHEMICAL SENSITIVITY, CHRONIC FATIGUE, PERSIAN GULF, AND FIBROMYALGIA NOW COLLECTIVELY LABELED AS IDIOPATHIC ENVIRONMENTAL INTOLERANCES) AND COMMON DISEASES (VITILIGO AND SYSTEMIC LUPUS ERYTHEMATOSUS) HAVE BECOME SUBJECTS OF THE RESEARCH ON THE IMPAIRED METABOLISM AND DETOXIFICATION OF XENOBIOTICS AND ENDOGENOUS TOXINS. HERE, WE COLLECTED AND CRITICALLY REVIEWED EPIDEMIOLOGICAL, GENETIC, AND BIOCHEMICAL DATA ON THE INVOLVEMENT AND POSSIBLE ROLE OF CYTOCHROME P450 SUPER FAMILY ENZYMES, GLUTATHIONE-S-TRANSFERASE ISOZYMES, CATECHOL-O-METHYL-TRANSFERASE, UDP-GLUCURONOSYL TRANSFERASES, AND PROTEINS DETOXIFYING INORGANIC AND ORGANIC PEROXIDES (CATALASE, GLUTATHIONE PEROXIDASE, AND PEROXIREDOXIN) IN THE ABOVE PATHOLOGIES. GENETIC PREDISPOSITION ASSESSED MAINLY BY SINGLE NUCLEOTIDE POLYMORPHISM AND GENE EXPRESSION ANALYSES REVEALED CORRELATIONS BETWEEN DEFECTS IN GENES ENCODING XENOBIOTIC-METABOLIZING AND/OR DETOXIFYING ENZYMES AND RISK/SEVERITY OF THESE SYNDROMES/DISEASES. PROTEOME ANALYSIS IDENTIFIED ABNORMAL EXPRESSION OF THE ENZYMES. THEIR FUNCTIONS WERE AFFECTED EPIGENETICALLY LEADING TO METABOLIC IMPAIRMENT AND, AS A CONSEQUENCE, TO THE NEGATIVE HEALTH OUTCOMES SHARED BY SOME OF THESE PATHOLOGIES. DATA OBTAINED SO FAR SUGGEST THAT DISTINCT COMPONENTS OF THE CHEMICAL DEFENSIVE SYSTEM COULD BE SUITABLE MOLECULAR TARGETS FOR FUTURE PATHOGENIC THERAPIES. 2009 17 4786 32 NUTRITION AND HEALTH DURING MID-LIFE: SEARCHING FOR SOLUTIONS AND MEETING CHALLENGES FOR THE AGING POPULATION. INTERACTIONS BETWEEN GENETIC (GENOME) AND ENVIRONMENTAL FACTORS (EPIGENOME) OPERATE DURING A PERSON'S ENTIRE LIFESPAN. THE AGING PROCESS IS ASSOCIATED WITH SEVERAL CELLULAR AND ORGANIC FUNCTIONAL ALTERATIONS THAT, AT THE END, CAUSE MULTI-ORGANIC CELL FAILURE. EPIGENETIC MECHANISMS OF AGING ARE MODIFIABLE BY APPROPRIATE PREVENTIVE ACTIONS MEDIATED BY SIRTUINS, CALORIC INPUT, DIET COMPONENTS, ADIPOSE TISSUE-RELATED INFLAMMATORY REACTIONS, AND PHYSICAL ACTIVITY. THE MEDITERRANEAN LIFESTYLE HAS BEEN FOR MANY MILLENNIA A DAILY HABIT FOR PEOPLE IN WESTERN CIVILIZATIONS LIVING AROUND THE MEDITERRANEAN SEA WHO WORKED INTENSIVELY AND SURVIVED WITH VERY FEW SEASONAL FOODS. A HIGH ADHERENCE TO THE TRADITIONAL MEDITERRANEAN DIET IS ASSOCIATED WITH LOW MORTALITY (HIGHER LONGEVITY) AND REDUCED RISK OF DEVELOPING CHRONIC DISEASES, INCLUDING CANCER, THE METABOLIC SYNDROME, DEPRESSION AND CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES. REPORTS INDICATE THAT SOME DIETARY COMPONENTS, SUCH AS OLIVE OIL, ANTIOXIDANTS, OMEGA-3 AND -6 POLYUNSATURATED ACIDS, POLYPHENOLS AND FLAVONOIDS, MEDIATE BENEFICIAL ANTI-AGING EFFECTS (ANTI-CHRONIC DISEASES AND INCREASED LONGEVITY). EQUALLY, PHYSICAL ACTIVITY DISPLAYS A POSITIVE EFFECT, PRODUCING CALORIC CONSUMPTION AND REGULATION OF ADIPOSE AND PANCREATIC FUNCTION. THE PREDICTIVE STRENGTH OF SOME FOOD PATTERNS MAY BE A WAY OF DEVELOPING RECOMMENDATIONS FOR FOOD AND HEALTH POLICIES. THIS PAPER WILL DISCUSS SEVERAL WAYS OF IMPROVING HEALTH DURING MID-LIFE, FOCUSING ON CERTAIN GROUPS OF FUNCTIONAL FOODS AND HEALTHY HABITS WHICH MAY REDUCE OR PREVENT AGE-RELATED CHRONIC DISEASES. 2013 18 4269 26 MICROBIAL DYSBIOSIS AND LACK OF SCFA PRODUCTION IN A SPANISH COHORT OF PATIENTS WITH MULTIPLE SCLEROSIS. BACKGROUND: MULTIPLE SCLEROSIS (MS) IS A CHRONIC, DEMYELINATING, AND IMMUNE-MEDIATED DISEASE OF THE CENTRAL NERVOUS SYSTEM CAUSED BY A COMBINATION OF GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS. THE INCIDENCE OF MS HAS INCREASED IN THE PAST SEVERAL DECADES, SUGGESTING CHANGES IN THE ENVIRONMENTAL RISK FACTORS. MUCH EFFORT HAS BEEN MADE IN THE DESCRIPTION OF THE GUT MICROBIOTA IN MS; HOWEVER, LITTLE IS KNOWN ABOUT THE DYSBIOSIS ON ITS FUNCTION. THE MICROBIOTA PRODUCES THOUSANDS OF BIOLOGICALLY ACTIVE SUBSTANCES AMONG WHICH ARE NOTABLE THE SHORT-CHAIN FATTY ACID (SCFA) EXCRETION. OBJECTIVES: ANALYZE THE INTERACTION BETWEEN MICROBIOTA, SCFAS, DIET, AND MS. METHODS: 16S, NUTRITIONAL QUESTIONNAIRES, AND SCFAS QUANTIFICATION HAVE BEEN RECOVERED FROM MS PATIENTS AND CONTROLS. RESULTS: OUR RESULTS REVEALED AN INCREMENT IN THE PHYLUM PROTEOBACTERIA, ESPECIALLY THE FAMILY ENTEROBACTERIACEAE, A LACK IN TOTAL SCFA EXCRETION, AND AN ALTERED PROFILE OF SCFAS IN A SPANISH COHORT OF MS PATIENTS. THESE ALTERATIONS ARE MORE EVIDENT IN PATIENTS WITH HIGHER DISABILITY. CONCLUSIONS: THE ABUNDANCE OF PROTEOBACTERIA AND ACETATE AND THE LOW EXCRETION OF TOTAL SCFAS, ESPECIALLY BUTYRATE, ARE COMMON CHARACTERISTICS OF MS PATIENTS, AND BESIDES, BOTH ARE ASSOCIATED WITH A WORSE PROGNOSIS OF THE DISEASE. 2022 19 1417 33 DIETARY TRENDS AND THE DECLINE IN MALE REPRODUCTIVE HEALTH. OVER THE TWENTIETH CENTURY, MALE REPRODUCTIVE HEALTH HAS SUFFERED A SUBSTANTIAL DECLINE, AS EVIDENCED BY DECREASES IN SPERM COUNTS AND TESTOSTERONE LEVELS AND INCREASES IN REPRODUCTIVE PATHOLOGIES. AT THE SAME TIME, THE PREVALENCE OF CHRONIC DISEASES SUCH AS OBESITY, DIABETES, AND METABOLIC SYNDROME HAS RISEN DRAMATICALLY. METABOLIC AND REPRODUCTIVE HEALTH ARE HIGHLY INTERCONNECTED, SUGGESTING THAT THEIR RESPECTIVE TRENDS ARE INTERTWINED AND, GIVEN THE TIMEFRAME OF SUCH TRENDS, ENVIRONMENTAL AND NOT GENETIC FACTORS ARE MOST LIKELY TO BE THE PRIMARY CAUSES. INDUSTRIALIZATION, WHICH BEGAN IN EUROPE IN THE MID-EIGHTEENTH CENTURY, HAS RESULTED IN PROFOUND CHANGES TO OUR DIET, LIFESTYLE, AND ENVIRONMENT, MANY OF WHICH ARE CAUSAL FACTORS IN THE RISE IN CHRONIC DISEASES. INDUSTRIALIZATION RESULTS IN A NUTRITION TRANSITION FROM AN AGRICULTURAL UNPROCESSED TO A MODERN PROCESSED DIET, INCORPORATING INCREASES IN SUGAR, VEGETABLE OILS, ULTRA-PROCESSED FOODS, LINOLEIC ACID, TRANS-FATS, AND TOTAL ENERGY. THIS DIETARY SHIFT HAS INCURRED NUMEROUS ADVERSE EFFECTS ON METABOLIC AND REPRODUCTIVE HEALTH, CHARACTERIZED BY CHRONIC INFLAMMATION, OXIDATIVE STRESS, AND INSULIN RESISTANCE. MOREOVER, THESE EFFECTS APPEAR TO MULTIPLY ACROSS SUBSEQUENT GENERATIONS VIA EPIGENETIC INHERITANCE. MEN'S FERTILITY IS MARKEDLY AFFECTED BY OBESITY AND DIABETES, WITH AN INCREASE IN TOTAL ENERGY VIA PROCESSED FOOD INTAKE ARGUABLY BEING THE KEY FACTOR DRIVING THE DIABESITY PANDEMIC. IN CONTRAST, WHOLEFOODS RICH IN MICRONUTRIENTS AND PHYTONUTRIENTS SUPPORT MALE FERTILITY AND A HEALTHY BODY WEIGHT. THEREFORE, MEN WANTING TO MAXIMIZE THEIR FERTILITY SHOULD CONSIDER MAKING POSITIVE DIETARY CHANGES, SUCH AS REPLACING PROCESSED FOODS WITH UNPROCESSED FOODS THAT SUPPORT METABOLIC AND REPRODUCTIVE HEALTH. 2023 20 4778 38 NUTRACEUTICALS AND THE NETWORK OF OBESITY MODULATORS. OBESITY IS CONSIDERED AN INCREASINGLY WIDESPREAD DISEASE IN THE WORLD POPULATION, REGARDLESS OF AGE AND GENDER. GENETIC BUT ALSO LIFESTYLE-DEPENDENT CAUSES HAVE BEEN IDENTIFIED. NUTRITION AND PHYSICAL EXERCISE PLAY AN IMPORTANT ROLE, ESPECIALLY IN NON-GENETIC OBESITY. IN A THREE-COMPARTMENT MODEL, THE BODY IS DIVIDED INTO FAT MASS, FAT-FREE MASS AND WATER, AND OBESITY CAN BE CONSIDERED A CONDITION IN WHICH THE PERCENTAGE OF TOTAL FAT MASS IS IN EXCESS. PEOPLE WITH A HIGH BMI INDEX OR OVERWEIGHT USE SELF-MEDICATIONS, SUCH AS FOOD SUPPLEMENTS OR TEAS, WITH THE AIM TO PREVENT OR TREAT THEIR PROBLEM. UNFORTUNATELY, THERE ARE SEVERAL OBESITY MODULATORS THAT ACT BOTH ON THE PATHWAYS THAT PROMOTE ADIPOGENESIS AND THOSE THAT INHIBIT LIPOLYSIS. MOREOVER, THESE PATHWAYS INVOLVE DIFFERENT TISSUES AND ORGANS, SO IT IS VERY DIFFICULT TO IDENTIFY ANTI-OBESITY SUBSTANCES. A NETWORK OF FACTORS AND CELLS CONTRIBUTES TO THE ACCUMULATION OF FAT IN COMPLETELY DIFFERENT BODY DISTRICTS. THE IDENTIFICATION OF NATURAL ANTI-OBESITY AGENTS SHOULD CONSIDER THIS NETWORK, WHICH WE WOULD LIKE TO CALL "OBESOSOME". THE NUTRIGENOMIC, NUTRIGENETIC AND EPIGENETIC CONTRIBUTE TO MAKING THE IDENTIFICATION OF ACTIVE COMPOUNDS VERY DIFFICULT. THIS NARRATIVE REVIEW AIMS TO HIGHLIGHT NUTRACEUTICALS THAT, IN VITRO OR IN VIVO, SHOWED AN ANTI-OBESITY ACTIVITY OR WERE FOUND TO BE USEFUL IN THE CONTROL OF DYSFUNCTIONS WHICH ARE SECONDARY TO OBESITY. THE RESULTS SUGGEST THAT IT IS NOT POSSIBLE TO USE A SINGLE COMPOUND TO TREAT OBESITY, BUT THAT THE STUDIES HAVE TO BE ADDRESSED TOWARDS THE IDENTIFICATION OF MIXTURES OF NUTRACEUTICALS. 2022