1 298 161 AIR POLLUTION AND AIRWAY DISEASE. EPIDEMIOLOGICAL AND TOXICOLOGICAL RESEARCH CONTINUES TO SUPPORT A LINK BETWEEN URBAN AIR POLLUTION AND AN INCREASED INCIDENCE AND/OR SEVERITY OF AIRWAY DISEASE. DETRIMENTAL EFFECTS OF OZONE (O(3)), NITROGEN DIOXIDE (NO(2)) AND PARTICULATE MATTER (PM), AS WELL AS TRAFFIC-RELATED POLLUTION AS A WHOLE, ON RESPIRATORY SYMPTOMS AND FUNCTION ARE WELL DOCUMENTED. NOT ONLY DO WE HAVE STRONG EPIDEMIOLOGICAL EVIDENCE OF A RELATIONSHIP BETWEEN AIR POLLUTION AND EXACERBATION OF ASTHMA AND RESPIRATORY MORBIDITY AND MORTALITY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), BUT RECENT STUDIES, PARTICULARLY IN URBAN AREAS, HAVE SUGGESTED A ROLE FOR POLLUTANTS IN THE DEVELOPMENT OF BOTH ASTHMA AND COPD. SIMILARLY, WHILE PREVALENCE AND SEVERITY OF ATOPIC CONDITIONS APPEAR TO BE MORE COMMON IN URBAN COMPARED WITH RURAL COMMUNITIES, EVIDENCE IS EMERGING THAT TRAFFIC-RELATED POLLUTANTS MAY CONTRIBUTE TO THE DEVELOPMENT OF ALLERGY. FURTHERMORE, NUMEROUS EPIDEMIOLOGICAL AND EXPERIMENTAL STUDIES SUGGEST AN ASSOCIATION BETWEEN EXPOSURE TO NO(2) , O(3) , PM AND COMBUSTION PRODUCTS OF BIOMASS FUELS AND AN INCREASED SUSCEPTIBILITY TO AND MORBIDITY FROM RESPIRATORY INFECTION. GIVEN THE CONSIDERABLE CONTRIBUTION THAT TRAFFIC EMISSIONS MAKE TO URBAN AIR POLLUTION RESEARCHERS HAVE SOUGHT TO CHARACTERIZE THE RELATIVE TOXICITY OF TRAFFIC-RELATED PM POLLUTANTS. RECENT ADVANCES IN MECHANISMS IMPLICATED IN THE ASSOCIATION OF AIR POLLUTANTS AND AIRWAY DISEASE INCLUDE EPIGENETIC ALTERATION OF GENES BY COMBUSTION-RELATED POLLUTANTS AND HOW POLYMORPHISMS IN GENES INVOLVED IN ANTIOXIDANT PATHWAYS AND AIRWAY INFLAMMATION CAN MODIFY RESPONSES TO AIR POLLUTION EXPOSURES. OTHER INTERESTING EPIDEMIOLOGICAL OBSERVATIONS RELATED TO INCREASED HOST SUSCEPTIBILITY INCLUDE A POSSIBLE LINK BETWEEN CHRONIC PM EXPOSURE DURING CHILDHOOD AND VULNERABILITY TO COPD IN ADULTHOOD, AND THAT INFANTS SUBJECTED TO HIGHER PRENATAL LEVELS OF AIR POLLUTION MAY BE AT GREATER RISK OF DEVELOPING RESPIRATORY CONDITIONS. WHILE THE CHARACTERIZATION OF POLLUTANT COMPONENTS AND SOURCES PROMISE TO GUIDE POLLUTION CONTROL STRATEGIES, THE IDENTIFICATION OF SUSCEPTIBLE SUBPOPULATIONS WILL BE NECESSARY IF TARGETED THERAPY/PREVENTION OF POLLUTION-INDUCED RESPIRATORY DISEASES IS TO BE DEVELOPED. 2011 2 2950 28 GENETIC AND EPIGENETIC DAMAGE INDUCED BY REACTIVE NITROGEN SPECIES: IMPLICATIONS IN CARCINOGENESIS. CHRONIC INFECTION AND INFLAMMATION ARE RECOGNIZED RISK FACTORS FOR HUMAN CANCER AT VARIOUS SITES. INFECTION AND INFLAMMATION CAN ACTIVATE AND INDUCE A VARIETY OF OXIDANT-GENERATING ENZYMES, INCLUDING NADPH OXIDASE AND INDUCIBLE NITRIC OXIDE SYNTHASE. REACTIVE OXYGEN AND NITROGEN SPECIES PRODUCED BY SUCH ENZYMES REACT WITH EACH OTHER TO GENERATE NEW AND MORE POTENT REACTIVE SPECIES. THESE OXIDANTS NOT ONLY CAN DAMAGE DNA AND INDUCE MUTATIONS, BUT ALSO CAN ACTIVATE ONCOGENE PRODUCTS AND/OR INACTIVATE TUMOR-SUPPRESSOR PROTEINS, THUS CONTRIBUTING TO MOST PROCESSES OF CARCINOGENESIS. APPROPRIATE TREATMENT OF INFLAMMATION SHOULD BE FURTHER EXPLORED FOR CHEMOPREVENTION OF HUMAN CANCERS, ESPECIALLY THOSE ASSOCIATED WITH CHRONIC INFLAMMATION. 2003 3 4044 31 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 4 3712 43 INHALED POLLUTANTS: THE MOLECULAR SCENE BEHIND RESPIRATORY AND SYSTEMIC DISEASES ASSOCIATED WITH ULTRAFINE PARTICULATE MATTER. AIR POLLUTION OF ANTHROPOGENIC ORIGIN IS LARGELY FROM THE COMBUSTION OF BIOMASS (E.G., WOOD), FOSSIL FUELS (E.G., CARS AND TRUCKS), INCINERATORS, LANDFILLS, AGRICULTURAL ACTIVITIES AND TOBACCO SMOKE. AIR POLLUTION IS A COMPLEX MIXTURE THAT VARIES IN SPACE AND TIME, AND CONTAINS HUNDREDS OF COMPOUNDS INCLUDING VOLATILE ORGANIC COMPOUNDS (E.G., BENZENE), METALS, SULPHUR AND NITROGEN OXIDES, OZONE AND PARTICULATE MATTER (PM). PM(0.1) (ULTRAFINE PARTICLES (UFP)), THOSE PARTICLES WITH A DIAMETER LESS THAN 100 NM (INCLUDES NANOPARTICLES (NP)) ARE CONSIDERED ESPECIALLY DANGEROUS TO HUMAN HEALTH AND MAY CONTRIBUTE SIGNIFICANTLY TO THE DEVELOPMENT OF NUMEROUS RESPIRATORY AND CARDIOVASCULAR DISEASES SUCH AS CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND ATHEROSCLEROSIS. SOME OF THE PATHOGENIC MECHANISMS THROUGH WHICH PM(0.1) MAY CONTRIBUTE TO CHRONIC DISEASE IS THEIR ABILITY TO INDUCE INFLAMMATION, OXIDATIVE STRESS AND CELL DEATH BY MOLECULAR MECHANISMS THAT INCLUDE TRANSCRIPTION FACTORS SUCH AS NUCLEAR FACTOR KAPPAB (NF-KAPPAB) AND NUCLEAR FACTOR (ERYTHROID-DERIVED 2)-LIKE 2 (NRF2). EPIGENETIC MECHANISMS INCLUDING NON-CODING RNA (NCRNA) MAY ALSO CONTRIBUTE TOWARDS THE DEVELOPMENT OF CHRONIC DISEASE ASSOCIATED WITH EXPOSURE TO PM(0.1). THIS PAPER HIGHLIGHTS EMERGING MOLECULAR CONCEPTS ASSOCIATED WITH INHALATIONAL EXPOSURE TO PM(0.1) AND THEIR ABILITY TO CONTRIBUTE TO CHRONIC RESPIRATORY AND SYSTEMIC DISEASE. 2017 5 6166 34 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 6 363 52 AMBIENT AIR POLLUTION: HEALTH HAZARDS TO CHILDREN. AMBIENT AIR POLLUTION IS PRODUCED BY SOURCES INCLUDING VEHICULAR TRAFFIC, COAL-FIRED POWER PLANTS, HYDRAULIC FRACTURING, AGRICULTURAL PRODUCTION, AND FOREST FIRES. IT CONSISTS OF PRIMARY POLLUTANTS GENERATED BY COMBUSTION AND SECONDARY POLLUTANTS FORMED IN THE ATMOSPHERE FROM PRECURSOR GASES. AIR POLLUTION CAUSES AND EXACERBATES CLIMATE CHANGE, AND CLIMATE CHANGE WORSENS HEALTH EFFECTS OF AIR POLLUTION. INFANTS AND CHILDREN ARE UNIQUELY SENSITIVE TO AIR POLLUTION, BECAUSE THEIR ORGANS ARE DEVELOPING AND THEY HAVE HIGHER AIR PER BODY WEIGHT INTAKE. HEALTH EFFECTS LINKED TO AIR POLLUTION INCLUDE NOT ONLY EXACERBATIONS OF RESPIRATORY DISEASES BUT ALSO REDUCED LUNG FUNCTION DEVELOPMENT AND INCREASED ASTHMA INCIDENCE. ADDITIONAL OUTCOMES OF CONCERN INCLUDE PRETERM BIRTH, LOW BIRTH WEIGHT, NEURODEVELOPMENTAL DISORDERS, IQ LOSS, PEDIATRIC CANCERS, AND INCREASED RISKS FOR ADULT CHRONIC DISEASES. THESE EFFECTS ARE MEDIATED BY OXIDATIVE STRESS, CHRONIC INFLAMMATION, ENDOCRINE DISRUPTION, AND GENETIC AND EPIGENETIC MECHANISMS ACROSS THE LIFE SPAN. NATURAL EXPERIMENTS DEMONSTRATE THAT WITH INITIATIVES SUCH AS INCREASED USE OF PUBLIC TRANSPORTATION, BOTH AIR QUALITY AND COMMUNITY HEALTH IMPROVE. SIMILARLY, THE CLEAN AIR ACT HAS IMPROVED AIR QUALITY, ALTHOUGH EXPOSURE INEQUITIES PERSIST. OTHER EFFECTIVE STRATEGIES FOR REDUCING AIR POLLUTION INCLUDE ENDING RELIANCE ON COAL, OIL, AND GAS; REGULATING INDUSTRIAL EMISSIONS; REDUCING EXPOSURE WITH ATTENTION TO PROXIMITY OF RESIDENCES, SCHOOLS, AND CHILD CARE FACILITIES TO TRAFFIC; AND A GREATER AWARENESS OF THE AIR QUALITY INDEX. THIS POLICY REVIEWS BOTH SHORT- AND LONG-TERM HEALTH CONSEQUENCES OF AMBIENT AIR POLLUTION, ESPECIALLY IN RELATION TO DEVELOPMENTAL EXPOSURES. IT EXAMINES INDIVIDUAL, COMMUNITY, AND LEGISLATIVE STRATEGIES TO MITIGATE AIR POLLUTION. 2021 7 299 52 AIR POLLUTION AND DNA METHYLATION: EFFECTS OF EXPOSURE IN HUMANS. AIR POLLUTION EXPOSURE IS ESTIMATED TO CONTRIBUTE TO APPROXIMATELY SEVEN MILLION EARLY DEATHS EVERY YEAR WORLDWIDE AND MORE THAN 3% OF DISABILITY-ADJUSTED LIFE YEARS LOST. AIR POLLUTION HAS NUMEROUS HARMFUL EFFECTS ON HEALTH AND CONTRIBUTES TO THE DEVELOPMENT AND MORBIDITY OF CARDIOVASCULAR DISEASE, METABOLIC DISORDERS, AND A NUMBER OF LUNG PATHOLOGIES, INCLUDING ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). EMERGING DATA INDICATE THAT AIR POLLUTION EXPOSURE MODULATES THE EPIGENETIC MARK, DNA METHYLATION (DNAM), AND THAT THESE CHANGES MIGHT IN TURN INFLUENCE INFLAMMATION, DISEASE DEVELOPMENT, AND EXACERBATION RISK. SEVERAL TRAFFIC-RELATED AIR POLLUTION (TRAP) COMPONENTS, INCLUDING PARTICULATE MATTER (PM), BLACK CARBON (BC), OZONE (O(3)), NITROGEN OXIDES (NO(X)), AND POLYAROMATIC HYDROCARBONS (PAHS), HAVE BEEN ASSOCIATED WITH CHANGES IN DNAM; TYPICALLY LOWERING DNAM AFTER EXPOSURE. EFFECTS OF AIR POLLUTION ON DNAM HAVE BEEN OBSERVED ACROSS THE HUMAN LIFESPAN, BUT IT IS NOT YET CLEAR WHETHER EARLY LIFE DEVELOPMENTAL SENSITIVITY OR THE ACCUMULATION OF EXPOSURES HAVE THE MOST SIGNIFICANT EFFECTS ON HEALTH. AIR POLLUTION EXPOSURE-ASSOCIATED DNAM PATTERNS ARE OFTEN CORRELATED WITH LONG-TERM NEGATIVE RESPIRATORY HEALTH OUTCOMES, INCLUDING THE DEVELOPMENT OF LUNG DISEASES, A FOCUS IN THIS REVIEW. RECENTLY, INTERVENTIONS SUCH AS EXERCISE AND B VITAMINS HAVE BEEN PROPOSED TO REDUCE THE IMPACT OF AIR POLLUTION ON DNAM AND HEALTH. ULTIMATELY, IMPROVED KNOWLEDGE OF HOW EXPOSURE-INDUCED CHANGE IN DNAM IMPACTS HEALTH, BOTH ACUTELY AND CHRONICALLY, MAY ENABLE PREVENTATIVE AND REMEDIAL STRATEGIES TO REDUCE MORBIDITY IN POLLUTED ENVIRONMENTS. 2019 8 5391 35 REDOX-RELATED BIOMARKERS IN HUMAN CARDIOVASCULAR DISEASE - CLASSICAL FOOTPRINTS AND BEYOND. GLOBAL EPIDEMIOLOGICAL STUDIES SHOW THAT CHRONIC NON-COMMUNICABLE DISEASES SUCH AS ATHEROSCLEROSIS AND METABOLIC DISORDERS REPRESENT THE LEADING CAUSE OF PREMATURE MORTALITY AND MORBIDITY. CARDIOVASCULAR DISEASE SUCH AS ISCHEMIC HEART DISEASE IS A MAJOR CONTRIBUTOR TO THE GLOBAL BURDEN OF DISEASE AND THE SOCIOECONOMIC HEALTH COSTS. CLINICAL AND EPIDEMIOLOGICAL DATA SHOW AN ASSOCIATION OF TYPICAL OXIDATIVE STRESS MARKERS SUCH AS LIPID PEROXIDATION PRODUCTS, 3-NITROTYROSINE OR OXIDIZED DNA/RNA BASES WITH ALL MAJOR CARDIOVASCULAR DISEASES. THIS SUPPORTS THE CONCEPT THAT THE FORMATION OF REACTIVE OXYGEN AND NITROGEN SPECIES BY VARIOUS SOURCES (NADPH OXIDASES, XANTHINE OXIDASE AND MITOCHONDRIAL RESPIRATORY CHAIN) REPRESENTS A HALLMARK OF THE LEADING CARDIOVASCULAR COMORBIDITIES SUCH AS HYPERLIPIDEMIA, HYPERTENSION AND DIABETES. THESE REACTIVE OXYGEN AND NITROGEN SPECIES CAN LEAD TO OXIDATIVE DAMAGE BUT ALSO ADVERSE REDOX SIGNALING AT THE LEVEL OF KINASES, CALCIUM HANDLING, INFLAMMATION, EPIGENETIC CONTROL, CIRCADIAN CLOCK AND PROTEASOMAL SYSTEM. THE IN VIVO FOOTPRINTS OF THESE ADVERSE PROCESSES (REDOX BIOMARKERS) ARE DISCUSSED IN THE PRESENT REVIEW WITH FOCUS ON THEIR CLINICAL RELEVANCE, WHEREAS THE DETAILS OF THEIR MECHANISMS OF FORMATION AND TECHNICAL ASPECTS OF THEIR DETECTION ARE ONLY BRIEFLY MENTIONED. THE MAJOR CATEGORIES OF REDOX BIOMARKERS ARE SUMMARIZED AND EXPLAINED ON THE BASIS OF SUITABLE EXAMPLES. ALSO THE POTENTIAL PROGNOSTIC VALUE OF REDOX BIOMARKERS IS CRITICALLY DISCUSSED TO UNDERSTAND WHAT KIND OF INFORMATION THEY CAN PROVIDE BUT ALSO WHAT THEY CANNOT ACHIEVE. 2021 9 6865 35 [OXIDATIVE STRESS IN PROSTATE HYPERTROPHY AND CARCINOGENESIS]. AGING, SIGNIFICANT IMPAIRMENT OF THE OXIDATION/REDUCTION BALANCE, INFECTION, AND INFLAMMATION ARE RECOGNIZED RISK FACTORS OF BENIGN HYPERPLASIA AND PROSTATE CANCER. CHRONIC SYMPTOMATIC AND ASYMPTOMATIC PROSTATE INFLAMMATORY PROCESSES GENERATE SIGNIFICANTLY ELEVATED LEVELS OF REACTIVE OXYGEN AND NITROGEN SPECIES, AND HALOGENATED COMPOUNDS. PROSTATE CANCER PATIENTS SHOWED SIGNIFICANTLY HIGHER LIPID PEROXIDATION AND LOWER ANTIOXIDANT LEVELS IN PERIPHERAL BLOOD THAN HEALTHY CONTROLS, WHEREAS PATIENTS WITH PROSTATE HYPERPLASIA DID NOT SHOW SUCH SYMPTOMS. OXIDATIVE/NITROSATIVE/HALOGENATIVE STRESS CAUSES DNA MODIFICATIONS LEADING TO GENOME INSTABILITY THAT MAY INITIATE CARCINOGENESIS; HOWEVER, IT WAS SHOWN THAT OXIDATIVE DAMAGE ALONE IS NOT SUFFICIENT TO INITIATE THIS PROCESS. PEROXIDATION PRODUCTS INDUCED BY REACTIVE OXYGEN AND NITROGEN SPECIES SEEM TO TAKE PART IN EPIGENETIC MECHANISMS REGULATING GENOME ACTIVITY. ONE OF THE MOST COMMON CHANGES OCCURRING IN MORE THAN 90% OF ALL ANALYZED PROSTATE CANCERS IS THE SILENCING OF GSTP1 GENE ACTIVITY. THE GENE ENCODES GLUTATHIONE TRANSFERASE, AN ENZYME PARTICIPATING IN DETOXIFICATION PROCESSES. PROSTATE HYPERPLASIA IS OFTEN ACCOMPANIED BY CHRONIC INFLAMMATION AND SUCH A RELATIONSHIP WAS NOT OBSERVED IN PROSTATE CANCER. THE PARTICIPATION OF INFECTION AND INFLAMMATION IN THE DEVELOPMENT OF HYPERPLASIA IS UNQUESTIONABLE AND THESE FACTORS PROBABLY ALSO TAKE PART IN INITIATING THE EARLY STAGES OF PROSTATE CARCINOGENESIS. THUS IT SEEMS THAT THERAPEUTIC STRATEGIES THAT PREVENT GENOME OXIDATIVE DAMAGE IN SITUATIONS INVOLVING OXIDATIVE/NITROSATIVE/HALOGENATIVE STRESS, I.E. USE OF ANTIOXIDANTS, PLANT STEROIDS, ANTIBIOTICS, AND NON-STEROIDAL ANTI-INFLAMMATORY DRUGS, COULD HELP PREVENT CARCINOGENESIS. 2009 10 361 48 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 11 4652 24 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 12 360 34 AMBIENT AIR POLLUTION AND BIOMARKERS OF HEALTH EFFECT. RECENTLY, THE AIR POLLUTION SITUATION OF OUR COUNTRY IS VERY SERIOUS ALONG WITH THE DEVELOPMENT OF URBANIZATION AND INDUSTRIALIZATION. STUDIES INDICATE THAT THE EXPOSURE OF AIR POLLUTION CAN CAUSE A RISE OF INCIDENCE AND MORTALITY OF MANY DISEASES, SUCH AS CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), ASTHMA, MYOCARDIAL INFARCTION, AND SO ON. HOWEVER, THERE IS NOW GROWING EVIDENCE SHOWING THAT SIGNIFICANT AIR POLLUTION EXPOSURES ARE ASSOCIATED WITH EARLY BIOMARKERS IN VARIOUS SYSTEMS OF THE BODY. IN ORDER TO BETTER PREVENT AND CONTROL THE DAMAGE EFFECT OF AIR POLLUTION, THIS ARTICLE SUMMARIZES COMPREHENSIVELY EPIDEMIOLOGICAL STUDIES ABOUT THE BAD EFFECTS ON THE BIOMARKERS OF RESPIRATORY SYSTEM, CARDIOVASCULAR SYSTEM, AND GENETIC AND EPIGENETIC SYSTEM EXPOSURE TO AMBIENT AIR POLLUTION. 2017 13 6909 39 [TOXIC COMPONENTS OF PM(2.5) AND THEIR TOXICITY MECHANISMS-ON THE TOXICITY OF SULFATE AND CARBON COMPONENTS]. RECENTLY, THE MAIN AIR POLLUTANT HAS BEEN FINE PARTICULATE MATTER (PM(2.5)), WHICH IS TAKEN UP BY THE WHOLE BODY WITH SEVERE ADVERSE HEALTH EFFECTS. THE MAIN CHEMICAL COMPONENTS OF PM(2.5) ARE SALTS OF SULFATE (AND NITRATE) AND CARBONS. HOWEVER, IT REMAINS UNKNOWN WHICH COMPONENTS ARE TOXIC. HERE, THE AUTHOR REVIEWED THE LITERATURES TO DETERMINE WHICH COMPONENTS ARE TOXIC AND THE MAIN MECHANISMS UNDERLYING THEIR TOXICITY. MANY EPIDEMIOLOGICAL STUDIES HAVE SHOWN THAT SULFATE CONCENTRATION IS STRONGLY RELATED TO MORTALITY. HOWEVER, THERE IS NO EXPERIMENTAL EVIDENCE SHOWING THAT SULFATE AT ENVIRONMENTAL CONCENTRATIONS OF PM(2.5) CAUSES CARDIOVASCULAR DISEASE OR OTHER DISEASE. ON THE OTHER HAND, CARBON COMPONENTS SUCH AS ELEMENTARY CARBON (EC) PRODUCES HIGH CONCENTRATIONS OF REACTIVE OXYGEN SPECIES (ROS) VIA ITS PHAGOCYTOSIS BY MACROPHAGES, AND ORGANIC CARBON (OC) ALSO PRODUCES HIGH CONCENTRATIONS OF ROS DURING ITS METABOLIC PROCESSES, AND THE ROS CAUSE ACUTE AND CHRONIC INFLAMMATION. THEY CAUSE MANY DISEASES INCLUDING CARDIOVASCULAR DISEASE, ASTHMA AND CANCER. FURTHERMORE, THERE ARE MANY LINES OF EVIDENCE SHOWING THAT EPIGENETIC CHANGES SUCH AS DNA METHYLATION OR MICRORNA EXPRESSION INDUCED BY PARTICULATE MATTERS ALSO INDUCE THE DEVELOPMENT OF MANY DISEASES SUCH AS THOSE MENTIONED ABOVE. IT HAS BEEN REPORTED THAT CARBON COMPONENTS ARE INCORPORATED INTO THE BRAIN AND PRODUCE ROS, AND THAT THE ROS CAUSE DAMAGE TO BRAIN CELLS AND ALZHEIMER'S DISEASE AND COGNITIVE DISORDERS IN THE ELDERLY.FROM THESE LINES OF EVIDENCE, THE AUTHOR WOULD LIKE TO EMPHASIZE THAT THE MAIN TOXICITY OF PM(2.5) IS DUE TO CARBON COMPONENTS, AND IT IS IMPORTANT TO TAKE COUNTERMEASURES TO DECREASE THE CONCENTRATION OF CARBON COMPONENTS IN AMBIENT AIR. 2019 14 300 44 AIR POLLUTION AND INDOOR SETTINGS. INDOOR ENVIRONMENTS CONTRIBUTE SIGNIFICANTLY TO TOTAL HUMAN EXPOSURE TO AIR POLLUTANTS, AS PEOPLE SPEND MOST OF THEIR TIME INDOORS. HOUSEHOLD AIR POLLUTION (HAP) RESULTING FROM COOKING WITH POLLUTING ("DIRTY") FUELS, WHICH INCLUDE COAL, KEROSENE, AND BIOMASS (WOOD, CHARCOAL, CROP RESIDUES, AND ANIMAL MANURE) IS A GLOBAL ENVIRONMENTAL HEALTH PROBLEM. INDOOR POLLUTANTS ARE GASES, PARTICULATES, TOXINS, AND MICROORGANISMS AMONG OTHERS, THAT CAN HAVE AN IMPACT ESPECIALLY ON THE HEALTH OF CHILDREN AND ADULTS THROUGH A COMBINATION OF DIFFERENT MECHANISMS ON OXIDATIVE STRESS AND GENE ACTIVATION, EPIGENETIC, CELLULAR, AND IMMUNOLOGICAL SYSTEMS. AIR POLLUTION IS A MAJOR RISK FACTOR AND CONTRIBUTOR TO MORBIDITY AND MORTALITY FROM MAJOR CHRONIC DISEASES. CHILDREN ARE SIGNIFICANTLY AFFECTED BY THE IMPACT OF THE ENVIRONMENT DUE TO BIOLOGICAL IMMATURITY, PRENATAL AND POSTNATAL LUNG DEVELOPMENT. POOR AIR QUALITY HAS BEEN RELATED TO AN INCREASED PREVALENCE OF CLINICAL MANIFESTATIONS OF ALLERGIC ASTHMA AND RHINITIS. HEALTH PROFESSIONALS SHOULD INCREASE THEIR ROLE IN MANAGING THE EXPOSURE OF CHILDREN AND ADULTS TO AIR POLLUTION WITH BETTER METHODS OF CARE, PREVENTION, AND COLLECTIVE ACTION. INTERVENTIONS TO REDUCE HOUSEHOLD POLLUTANTS MAY PROMOTE HEALTH AND CAN BE ACHIEVED WITH EDUCATION, COMMUNITY, AND HEALTH PROFESSIONAL INVOLVEMENT. 2021 15 935 52 CHRONIC LOW-DOSE EXPOSURE TO XENOESTROGEN AMBIENT AIR POLLUTANTS AND BREAST CANCER RISK: XENAIR PROTOCOL FOR A CASE-CONTROL STUDY NESTED WITHIN THE FRENCH E3N COHORT. BACKGROUND: BREAST CANCER IS THE MOST FREQUENT CANCER IN WOMEN IN INDUSTRIALIZED COUNTRIES. LIFESTYLE AND ENVIRONMENTAL FACTORS, PARTICULARLY ENDOCRINE-DISRUPTING POLLUTANTS, HAVE BEEN SUGGESTED TO PLAY A ROLE IN BREAST CANCER RISK. CURRENT EPIDEMIOLOGICAL STUDIES, ALTHOUGH NOT FULLY CONSISTENT, SUGGEST A POSITIVE ASSOCIATION OF BREAST CANCER RISK WITH EXPOSURE TO SEVERAL INTERNATIONAL AGENCY FOR RESEARCH ON CANCER GROUP 1 AIR-POLLUTANT CARCINOGENS, SUCH AS PARTICULATE MATTER, POLYCHLORINATED BIPHENYLS (PCB), DIOXINS, BENZO[A]PYRENE (BAP), AND CADMIUM. HOWEVER, EPIDEMIOLOGICAL STUDIES REMAIN SCARCE AND INCONSISTENT. IT HAS BEEN PROPOSED THAT THE MENOPAUSAL STATUS COULD MODIFY THE RELATIONSHIP BETWEEN POLLUTANTS AND BREAST CANCER AND THAT THE ASSOCIATION VARIES WITH HORMONE RECEPTOR STATUS. OBJECTIVE: THE XENAIR PROJECT WILL INVESTIGATE THE ASSOCIATION OF BREAST CANCER RISK (OVERALL AND BY HORMONE RECEPTOR STATUS) WITH CHRONIC EXPOSURE TO SELECTED AIR POLLUTANTS, INCLUDING PARTICULATE MATTER, NITROGEN DIOXIDE (NO2), OZONE (O3), BAP, DIOXINS, PCB-153, AND CADMIUM. METHODS: OUR RESEARCH IS BASED ON A CASE-CONTROL STUDY NESTED WITHIN THE FRENCH NATIONAL E3N COHORT OF 5222 INVASIVE BREAST CANCER CASES IDENTIFIED DURING FOLLOW-UP FROM 1990 TO 2011, AND 5222 MATCHED CONTROLS. A QUESTIONNAIRE WAS SENT TO ALL PARTICIPANTS TO COLLECT THEIR LIFETIME RESIDENTIAL ADDRESSES AND INFORMATION ON INDOOR POLLUTION. WE WILL ASSESS THESE EXPOSURES USING COMPLEMENTARY MODELS OF LAND-USE REGRESSION, ATMOSPHERIC DISPERSION, AND REGIONAL CHEMISTRY-TRANSPORT (CHIMERE) MODELS, VIA A GEOGRAPHIC INFORMATION SYSTEM. ASSOCIATIONS WITH BREAST CANCER RISK WILL BE MODELED USING CONDITIONAL LOGISTIC REGRESSION MODELS. WE WILL ALSO STUDY THE IMPACT OF EXPOSURE ON DNA METHYLATION AND INTERACTIONS WITH GENETIC POLYMORPHISMS. APPROPRIATE STATISTICAL METHODS, INCLUDING BAYESIAN MODELING, PRINCIPAL COMPONENT ANALYSIS, AND CLUSTER ANALYSIS, WILL BE USED TO ASSESS THE IMPACT OF MULTIPOLLUTANT EXPOSURE. THE FRACTION OF BREAST CANCER CASES ATTRIBUTABLE TO AIR POLLUTION WILL BE ESTIMATED. RESULTS: THE XENAIR PROJECT WILL CONTRIBUTE TO CURRENT KNOWLEDGE ON THE HEALTH EFFECTS OF AIR POLLUTION AND IDENTIFY AND UNDERSTAND ENVIRONMENTAL MODIFIABLE RISK FACTORS RELATED TO BREAST CANCER RISK. CONCLUSIONS: THE RESULTS WILL PROVIDE RELEVANT EVIDENCE TO GOVERNMENTS AND POLICY-MAKERS TO IMPROVE EFFECTIVE PUBLIC HEALTH PREVENTION STRATEGIES ON AIR POLLUTION. THE XENAIR DATASET CAN BE USED IN FUTURE EFFORTS TO STUDY THE EFFECTS OF EXPOSURE TO AIR POLLUTION ASSOCIATED WITH OTHER CHRONIC CONDITIONS. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15167. 2020 16 6876 51 [PROLONGED EXPOSURE TO ATMOSPHERIC AIR POLLUTION AND MORTALITY FROM RESPIRATORY CAUSES]. DIFFERENT DESIGNS CAN BE USED TO ANALYZE THE RELATIONSHIPS BETWEEN RESPIRATORY MORTALITY AND LONG TERM EXPOSURE TO ATMOSPHERIC POLLUTION: EPIDEMIOLOGICAL STUDIES (COHORT, PREVALENCE STUDY) DEMONSTRATE THE REALITY OF THE RELATIONSHIP AND TOXICOLOGICAL STUDIES EXPLAIN IT. COHORT STUDIES HAVE THE ADVANTAGE OF BEING ABLE TO TAKE INTO ACCOUNT MANY CONFOUNDING FACTORS AND THUS AVOID BIASES (WHICH IS NOT THE CASE WITH PREVALENCE STUDIES), BUT REQUIRE SIGNIFICANT HUMAN AND FINANCIAL RESOURCES. THEY WERE FIRST ADOPTED IN THE US, BUT ARE NOW MORE OFTEN APPLIED IN EUROPE. THE RESULTS ARE RELATIVELY CONSISTENT, AS THEY ALL SHOW A STATISTICALLY SIGNIFICANT ASSOCIATION BETWEEN AN INCREASE IN PARTICULATE POLLUTION AND CARDIOPULMONARY MORTALITY. MORTALITY FROM LUNG CANCER IS ALSO ASSOCIATED WITH LONG TERM EXPOSITION TO PARTICLES AND SOMETIMES TO OZONE OR NITROGEN OXIDES. CEREBROVASCULAR DISEASES AND SUDDEN DEATH OF YOUNG CHILDREN HAVE ALSO BEEN ASSOCIATED WITH PARTICULATE POLLUTION. THE RELATIONSHIPS ARE MORE POWERFUL FOR LONG TERM THAN SHORT TERM EXPOSURE BUT ARE ALSO LINEAR AND WITHOUT THRESHOLD. IN ORDER TO EXPLAIN THESE EFFECTS (TODAY THE CAUSALITY OF THE RELATIONSHIP IS CERTAIN) THERE ARE MANY POSSIBLE FACTORS, PARTICULARLY REGARDING PARTICULATE EXPOSURES: AN INCREASE IN CARDIOVASCULAR RISK BIOMARKERS (FIBRINOGEN, WHITE BLOOD CELLS, AND PLATELETS), ATHEROSCLEROSIS, CHRONIC INFLAMMATION OF LUNG TISSUES INCREASED BY ACUTE EXPOSURE, ETC. MORE AND MORE STUDIES ADDRESS THE INTERACTION BETWEEN GENE AND ENVIRONMENT AND EVEN EPIGENETIC PHENOMENA WHICH COULD BE RESPONSIBLE OF THESE EFFECTS. PUBLIC HEALTH IMPACT COULD BE QUANTIFIED. THE EUROPEAN E&H SURVEILLANCE PROGRAM APHEIS, FOR EXAMPLE, ESTIMATED THAT IF PM2.5 LEVELS REMAINED BELOW 15 MICROG/M(3), A 30 YEAR OLD PERSON COULD SEE HIS LIFE EXPECTANCY INCREASED BY 1 MONTH TO 2 YEARS, DEPENDING ON THE STUDIED CITY. FINALLY, MORTALITY IS NOT THE ONLY RELEVANT INDICATOR FOR HEALTH EFFECTS OF AIR POLLUTION. ISAAC STUDIES ADDRESS ASTHMA, ALLERGIC RHINITIS AND ECZEMA AMONG CHILDREN. 2009 17 4453 28 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 18 4984 33 PATHWAYS OF GASTRIC CARCINOGENESIS, HELICOBACTER PYLORI VIRULENCE AND INTERACTIONS WITH ANTIOXIDANT SYSTEMS, VITAMIN C AND PHYTOCHEMICALS. HELICOBACTER PYLORI IS A CLASS ONE CARCINOGEN WHICH CAUSES CHRONIC ATROPHIC GASTRITIS, GASTRIC INTESTINAL METAPLASIA, DYSPLASIA AND ADENOCARCINOMA. THE MECHANISMS BY WHICH H. PYLORI INTERACTS WITH OTHER RISK AND PROTECTIVE FACTORS, PARTICULARLY VITAMIN C IN GASTRIC CARCINOGENESIS ARE COMPLEX. GASTRIC CARCINOGENESIS INCLUDES METABOLIC, ENVIRONMENTAL, EPIGENETIC, GENOMIC, INFECTIVE, INFLAMMATORY AND ONCOGENIC PATHWAYS. THE MOLECULAR CLASSIFICATION OF GASTRIC CANCER SUBTYPES HAS REVOLUTIONIZED THE UNDERSTANDING OF GASTRIC CARCINOGENESIS. THIS INCLUDES THE TUMOUR MICROENVIRONMENT, GERMLINE MUTATIONS, AND THE ROLE OF HELICOBACTER PYLORI BACTERIA, EPSTEIN BARR VIRUS AND EPIGENETICS IN SOMATIC MUTATIONS. THERE IS EVIDENCE THAT ASCORBIC ACID, PHYTOCHEMICALS AND ENDOGENOUS ANTIOXIDANT SYSTEMS CAN MODIFY THE RISK OF GASTRIC CANCER. GASTRIC JUICE ASCORBATE LEVELS DEPEND ON DIETARY INTAKE OF ASCORBIC ACID BUT CAN ALSO BE DECREASED BY H. PYLORI INFECTION, H. PYLORI CAGA SECRETION, TOBACCO SMOKING, ACHLORHYDRIA AND CHRONIC ATROPHIC GASTRITIS. ASCORBIC ACID MAY BE PROTECTIVE AGAINST GASTRIC CANCER BY ITS ANTIOXIDANT EFFECT IN GASTRIC CYTOPROTECTION, REGENERATING ACTIVE VITAMIN E AND GLUTATHIONE, INHIBITING ENDOGENOUS N-NITROSATION, REDUCING TOXIC EFFECTS OF INGESTED NITROSODIMETHYLAMINES AND HETEROCYCLIC AMINES, AND PREVENTING H. PYLORI INFECTION. THE EFFECTIVENESS OF SUCH CYTOPROTECTION IS RELATED TO H. PYLORI STRAIN VIRULENCE, PARTICULARLY CAGA EXPRESSION. THE ROLE OF VITAMIN C IN EPIGENETIC REPROGRAMMING IN GASTRIC CANCER IS STILL EVOLVING. OTHER FACTORS IN CONJUNCTION WITH VITAMIN C ALSO PLAY A ROLE IN GASTRIC CARCINOGENESIS. ERADICATION OF H. PYLORI MAY LEAD TO RECOVERY OF VITAMIN C SECRETION BY GASTRIC EPITHELIUM AND ENABLE REGRESSION OF PREMALIGNANT GASTRIC LESIONS, THEREBY INTERRUPTING THE CORREA CASCADE OF GASTRIC CARCINOGENESIS. 2020 19 4893 35 OXIDATIVE STRESS BIOMARKERS IN THE RELATIONSHIP BETWEEN TYPE 2 DIABETES AND AIR POLLUTION. THE INCIDENCE AND PREVALENCE OF TYPE 2 DIABETES HAVE INCREASED IN THE LAST DECADES AND ARE EXPECTED TO FURTHER GROW IN THE COMING YEARS. CHRONIC HYPERGLYCEMIA TRIGGERS FREE RADICAL GENERATION AND CAUSES INCREASED OXIDATIVE STRESS, AFFECTING A NUMBER OF MOLECULAR MECHANISMS AND CELLULAR PATHWAYS, INCLUDING THE GENERATION OF ADVANCED GLYCATION END PRODUCTS, PROINFLAMMATORY AND PROCOAGULANT EFFECTS, INDUCTION OF APOPTOSIS, VASCULAR SMOOTH-MUSCLE CELL PROLIFERATION, ENDOTHELIAL AND MITOCHONDRIAL DYSFUNCTION, REDUCTION OF NITRIC OXIDE RELEASE, AND ACTIVATION OF PROTEIN KINASE C. AMONG TYPE 2 DIABETES DETERMINANTS, MANY DATA HAVE DOCUMENTED THE ADVERSE EFFECTS OF ENVIRONMENTAL FACTORS (E.G., AIR POLLUTANTS) THROUGH MULTIPLE EXPOSURE-INDUCED MECHANISMS (E.G., SYSTEMIC INFLAMMATION AND OXIDATIVE STRESS, HYPERCOAGULABILITY, AND ENDOTHELIAL AND IMMUNE RESPONSES). THEREFORE, HERE WE DISCUSS THE ROLE OF AIR POLLUTION IN OXIDATIVE STRESS-RELATED DAMAGE TO GLYCEMIC METABOLISM HOMEOSTASIS, WITH A PARTICULAR FOCUS ON ITS IMPACT ON HEALTH. IN THIS CONTEXT, THE IMPROVEMENT OF NEW ADVANCED TOOLS (E.G., OMIC TECHNIQUES AND THE STUDY OF EPIGENETIC CHANGES) MAY PROVIDE A SUBSTANTIAL CONTRIBUTION, HELPING IN THE EVALUATION OF THE INDIVIDUAL IN HIS BIOLOGICAL TOTALITY, AND OFFER A COMPREHENSIVE ASSESSMENT OF THE MOLECULAR, CLINICAL, ENVIRONMENTAL, AND EPIDEMIOLOGICAL ASPECTS. 2021 20 4805 35 OBESITY AND METABOLIC COMORBIDITIES: ENVIRONMENTAL DISEASES? OBESITY AND METABOLIC COMORBIDITIES REPRESENT INCREASING HEALTH PROBLEMS. ENDOCRINE DISRUPTING COMPOUNDS (EDCS) ARE EXOGENOUS AGENTS THAT CHANGE ENDOCRINE FUNCTION AND CAUSE ADVERSE HEALTH EFFECTS. MOST EDCS ARE SYNTHETIC CHEMICALS; SOME ARE NATURAL FOOD COMPONENTS AS PHYTOESTROGENS. PEOPLE ARE EXPOSED TO COMPLEX MIXTURES OF CHEMICALS THROUGHOUT THEIR LIVES. EDCS IMPACT HORMONE-DEPENDENT METABOLIC SYSTEMS AND BRAIN FUNCTION. LABORATORY AND HUMAN STUDIES PROVIDE COMPELLING EVIDENCE THAT HUMAN CHEMICAL CONTAMINATION CAN PLAY A ROLE IN OBESITY EPIDEMIC. CHEMICAL EXPOSURES MAY INCREASE THE RISK OF OBESITY BY ALTERING THE DIFFERENTIATION OF ADIPOCYTES. EDCS CAN ALTER METHYLATION PATTERNS AND NORMAL EPIGENETIC PROGRAMMING IN CELLS. OXIDATIVE STRESS MAY BE INDUCED BY MANY OF THESE CHEMICALS, AND ACCUMULATING EVIDENCE INDICATES THAT IT PLAYS IMPORTANT ROLES IN THE ETIOLOGY OF CHRONIC DISEASES. THE INDIVIDUAL SENSITIVITY TO CHEMICALS IS VARIABLE, DEPENDING ON ENVIRONMENT AND ABILITY TO METABOLIZE HAZARDOUS CHEMICALS. A NUMBER OF GENES, ESPECIALLY THOSE REPRESENTING ANTIOXIDANT AND DETOXIFICATION PATHWAYS, HAVE POTENTIAL APPLICATION AS BIOMARKERS OF RISK ASSESSMENT. THE POTENTIAL HEALTH EFFECTS OF COMBINED EXPOSURES MAKE THE RISK ASSESSMENT PROCESS MORE COMPLEX COMPARED TO THE ASSESSMENT OF SINGLE CHEMICALS. TECHNIQUES AND METHODS NEED TO BE FURTHER DEVELOPED TO FILL DATA GAPS AND INCREASE THE KNOWLEDGE ON HARMFUL EXPOSURE COMBINATIONS. 2013