1 30 180 A BRIEF LOOK AT HASHIMOTO'S DISEASE, ADRENAL INCIDENTALOMAS, OBESITY AND INSULIN RESISTANCE-COULD ENDOCRINE DISRUPTORS BE THE OTHER SIDE OF THE SAME COIN? HASHIMOTO'S DISEASE (HD) IS THE MOST COMMON CAUSE OF HYPOTHYROIDISM IN DEVELOPED COUNTRIES. THE EXACT PATHOMECHANISM BEHIND IT HAS NOT BEEN CLEARLY ESTABLISHED; HOWEVER, AN INTERPLAY OF GENETIC SUSCEPTIBILITY, ENVIRONMENTAL TRIGGERS (INCLUDING DIET) AND EPIGENETIC FACTORS SEEMS TO BE INVOLVED. AMONG THE LATTER, INCREASINGLY MORE ATTENTION HAS BEEN PAID TO SOME HORMONALLY ACTIVE SUBSTANCES, KNOWN AS ENDOCRINE DISRUPTORS, WHICH ARE COMMONLY USED WORLDWIDE. HD HAS BECOME A CONDITION WIDELY REPORTED IN THE MEDIA, ACTING AS A CULPRIT FOR INEXPLICABLE WEIGHT GAIN, CHRONIC FATIGUE OR WEAKNESS. NEVERTHELESS, THE RECOGNITION OF HD IS UNDENIABLY INCREASING AND REPRESENTS A MAJOR PUBLIC HEALTH BURDEN. AT THE SAME TIME, IMPROVING ACCESS TO IMAGING TESTS HAS INCREASED THE NUMBER OF INCIDENTALLY DIAGNOSED ADRENAL TUMORS. ABOVE ALL, THE WIDESPREAD USE OF CHEST COMPUTED TOMOGRAPHY (CT) DUE TO THE COVID-19 PANDEMIC HAS CONTRIBUTED TO FREQUENT INCIDENTAL DETECTION OF ADRENAL LESIONS. FORTUNATELY, A VAST MAJORITY OF THESE FINDINGS ARE ASYMPTOMATIC BENIGN TUMORS WITH NO EXCESSIVE HORMONAL ACTIVITY, AND THEREFORE, THEY ARE DEFINED AS ADRENAL INCIDENTALOMAS (AIS). INTERESTINGLY, RECENT STUDIES HAVE INDICATED THAT PATIENTS WITH AIS ARE MORE PRONE TO OBESITY AND INSULIN RESISTANCE. ALTHOUGH MUTUAL RELATIONSHIPS BETWEEN THE THYROID AND THE ADRENAL GLANDS HAVE BEEN STUDIED WIDELY, STILL, LITTLE IS KNOWN ABOUT THE POSSIBLE PATHOPHYSIOLOGICAL ASSOCIATIONS BETWEEN THYROID AUTOIMMUNITY AND THE OCCURRENCE OF ADRENAL INCIDENTALOMAS. THIS ARTICLE PRESENTS A BRIEF REVIEW OF THE COMMON ENDOCRINE DISORDERS WITH A SPECIAL FOCUS ON THE FREQUENTLY COEXISTING INSULIN RESISTANCE AND/OR OBESITY. FURTHERMORE, IN RESPONSE TO THE RECENT GROWING INTEREST IN ENDOCRINE DISRUPTORS, WITH THEIR TRANSGENERATIONAL EPIGENETIC EFFECTS THAT INFLUENCE HORMONAL SYSTEM FUNCTION, A CONCISE OVERVIEW OF THE TOPIC HAS ALSO BEEN INCLUDED. 2023 2 6667 34 URATE-INDUCED IMMUNE PROGRAMMING: CONSEQUENCES FOR GOUTY ARTHRITIS AND HYPERURICEMIA. TRAINED IMMUNITY IS A PROCESS IN WHICH INNATE IMMUNE CELLS UNDERGO FUNCTIONAL REPROGRAMMING IN RESPONSE TO PATHOGENS OR DAMAGE-ASSOCIATED MOLECULES LEADING TO AN ENHANCED NON-SPECIFIC IMMUNE RESPONSE TO SUBSEQUENT STIMULATION. WHILE THIS CAPACITY TO RESPOND MORE STRONGLY TO STIMULI IS BENEFICIAL FOR HOST DEFENSE, IN SOME CIRCUMSTANCES IT CAN LEAD TO MALADAPTIVE PROGRAMMING AND CHRONIC INFLAMMATION. GOUT IS CHARACTERIZED BY PERSISTENT LOW-GRADE INFLAMMATION AND IS ASSOCIATED WITH AN INCREASED NUMBER OF COMORBIDITIES. HYPERURICEMIA IS THE MAIN RISK FACTOR FOR GOUT AND IS LINKED TO THE DEVELOPMENT OF COMORBIDITIES. SEVERAL EXPERIMENTAL STUDIES HAVE SHOWN THAT URATE CAN MECHANISTICALLY ALTER THE INFLAMMATORY CAPACITY OF MYELOID CELLS, WHILE OBSERVATIONAL STUDIES HAVE INDICATED AN ASSOCIATION OF HYPERURICEMIA TO A WIDE SPECTRUM OF COMMON ADULT INFLAMMATORY DISEASES. IN THIS REVIEW, WE ARGUE THAT HYPERURICEMIA IS A MAIN CULPRIT IN THE DEVELOPMENT OF THE LONG-TERM SYSTEMIC INFLAMMATION SEEN IN GOUT. WE REVISIT EXISTING EVIDENCE FOR URATE-INDUCED TRANSCRIPTIONAL AND EPIGENETIC REPROGRAMMING THAT COULD LEAD TO AN ALTERED FUNCTIONAL STATE OF CIRCULATING MONOCYTES CONSISTING IN ENHANCED RESPONSIVENESS AND MALADAPTIVE IMMUNE RESPONSES. BY DISCUSSING SPECIFIC FUNCTIONAL ADAPTATIONS OF MONOCYTES AND MACROPHAGES INDUCED BY SOLUBLE URATE OR MONOSODIUM URATE CRYSTALS AND THEIR CONTRIBUTION TO INFLAMMATION IN VITRO AND IN VIVO, WE FURTHER ENFORCE THAT URATE IS A METABOLITE THAT CAN INDUCE INNATE IMMUNE MEMORY AND WE DISCUSS FUTURE RESEARCH AND POSSIBLE NEW THERAPEUTIC APPROACHES FOR GOUT AND ITS COMORBIDITIES. 2020 3 2737 40 EXPOSING A DEADLY ALLIANCE: NOVEL INSIGHTS INTO THE BIOLOGICAL LINKS BETWEEN COPD AND LUNG CANCER. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AFFECTS MORE THAN 200 MILLION PEOPLE WORLDWIDE AND IS EXPECTED TO BECOME THE THIRD LEADING CAUSE OF DEATH IN 2020. COPD IS CHARACTERIZED BY PROGRESSIVE AIRFLOW LIMITATION, DUE TO A COMBINATION OF CHRONIC INFLAMMATION AND REMODELING OF THE SMALL AIRWAYS (BRONCHIOLITIS) AND LOSS OF ELASTIC RECOIL CAUSED BY DESTRUCTION OF THE ALVEOLAR WALLS (EMPHYSEMA). LUNG CANCER IS THE MOST IMPORTANT CAUSE OF CANCER-RELATED DEATH IN THE WORLD. (CIGARETTE) SMOKING IS THE PRINCIPAL CULPRIT CAUSING BOTH COPD AND LUNG CANCER; IN ADDITION, EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE, BIOMASS FUEL SMOKE, COAL SMOKE AND OUTDOOR AIR POLLUTION HAVE ALSO BEEN ASSOCIATED WITH AN INCREASED INCIDENCE OF BOTH DISEASES. IMPORTANTLY, SMOKERS WITH COPD--DEFINED AS EITHER NOT FULLY REVERSIBLE AIRFLOW LIMITATION OR EMPHYSEMA--HAVE A TWO- TO FOUR-FOLD INCREASED RISK TO DEVELOP LUNG CANCER. IN THIS REVIEW, WE HIGHLIGHT SEVERAL OF THE GENETIC, EPIGENETIC AND INFLAMMATORY MECHANISMS, WHICH LINK COPD AND CARCINOGENESIS IN THE LUNGS. ELUCIDATING THE BIOLOGICAL PATHWAYS AND NETWORKS, WHICH UNDERLIE THE INCREASED SUSCEPTIBILITY OF LUNG CANCER IN PATIENTS WITH COPD, HAS IMPORTANT IMPLICATIONS FOR SCREENING, PREVENTION, DIAGNOSIS AND TREATMENT OF THESE TWO DEVASTATING PULMONARY DISEASES. 2013 4 3438 43 HYPERHOMOCYSTEINEMIA IN UREMIA--A RED FLAG IN A DISRUPTED CIRCUIT. HYPERHOMOCYSTEINEMIA IS AN INDEPENDENT CARDIOVASCULAR RISK FACTOR, ACCORDING TO MOST OBSERVATIONAL STUDIES AND TO STUDIES USING THE MENDELIAN RANDOMIZATION APPROACH, UTILIZING THE COMMON POLYMORPHISM C677T OF METHYLENE TETRAHYDROFOLATE REDUCTASE. IN CONTRAST, THE MOST RECENT SECONDARY PREVENTIVE INTERVENTION STUDIES, IN THE GENERAL POPULATION AND IN CHRONIC KIDNEY DISEASE (CKD) AND UREMIA, WHICH ARE ALL NEGATIVE (WITH THE POSSIBLE NOTABLE EXCEPTION OF STROKE), POINT TO OTHER DIRECTIONS. HOWEVER, ALL TRIALS USE FOLIC ACID IN VARIOUS DOSAGES AS A MEANS TO REDUCE HOMOCYSTEINE LEVELS, WITH THE ADDITION OF VITAMINS B6 AND B12. IT IS POSSIBLE THAT FOLIC ACID HAS NEGATIVE EFFECTS, WHICH OFFSET THE BENEFITS; ALTERNATIVELY, HOMOCYSTEINE COULD BE AN INNOCENT BY-STANDER, OR A SURROGATE OF THE REAL CULPRIT. THE LATTER POSSIBILITY LEADS US TO THE SEARCH FOR POTENTIAL CANDIDATES. FIRST, THE ACCUMULATION OF HOMOCYSTEINE IN BLOOD LEADS TO AN INTRACELLULAR INCREASE OF S-ADENOSYLHOMOCYSTEINE (ADOHCY), A POWERFUL COMPETITIVE METHYLTRANSFERASE INHIBITOR, WHICH BY ITSELF IS CONSIDERED A PREDICTOR OF CARDIOVASCULAR EVENTS. DNA METHYLTRANSFERASES ARE AMONG THE PRINCIPAL TARGETS OF HYPERHOMOCYSTEINEMIA, AS STUDIES IN SEVERAL CELL CULTURE AND ANIMAL MODELS, AS WELL AS IN HUMANS, SHOW. IN CKD AND IN UREMIA, HYPERHOMOCYSTEINEMIA AND HIGH INTRACELLULAR ADOHCY ARE PRESENT AND ARE ASSOCIATED WITH ABNORMAL ALLELIC EXPRESSION OF GENES REGULATED THROUGH METHYLATION, SUCH AS IMPRINTED GENES, AND PSEUDOAUTOSOMAL GENES, THUS POINTING TO EPIGENETIC DYSREGULATION. THESE ALTERATIONS ARE SUSCEPTIBLE TO REVERSAL UPON HOMOCYSTEINE-LOWERING THERAPY OBTAINED THROUGH FOLATE ADMINISTRATION. SECOND, IT HAS TO BE KEPT IN MIND THAT HOMOCYSTEINE IS MAINLY PROTEIN-BOUND, AND ITS EFFECTS COULD BE LINKED THEREFORE TO PROTEIN HOMOCYSTEINYLATION. IN THIS RESPECT, INCREASED PROTEIN HOMOCYSTEINYLATION HAS BEEN FOUND IN UREMIA, LEADING TO ALTERATIONS IN PROTEIN FUNCTION. 2009 5 537 38 ASYMPTOMATIC HYPERURICEMIA: IS IT REALLY ASYMPTOMATIC? PURPOSE OF REVIEW: HYPERURICEMIA IS HIGHLY PREVALENT, AFFECTING APPROXIMATELY 38 MILLION INDIVIDUALS IN THE UNITED STATES. HOWEVER, THE SIGNIFICANCE OF ASYMPTOMATIC HYPERURICEMIA - HYPERURICEMIA IN THE ABSENCE OF GOUT - CONTINUES TO BE DEBATED. RECENT FINDINGS: ASYMPTOMATIC HYPERURICEMIA RESULTS IN MONOSODIUM URATE CRYSTAL DEPOSITION IN TISSUES, WHICH MAY PROMOTE CHRONIC INFLAMMATION. INTRACELLULARLY, HYPERURICEMIA INHIBITS THE MASTER REGULATOR ADENOSINE MONOPHOSPHATE (AMP)-ASSOCIATED PROTEIN KINASE AND MAY CONDITION INNATE IMMUNE RESPONSES THROUGH DURABLE EPIGENETIC MODIFICATIONS. AT THE POPULATION LEVEL, ASYMPTOMATIC HYPERURICEMIA IS ASSOCIATED WITH MULTIPLE COMORBIDITIES, INCLUDING HYPERTENSION, CHRONIC KIDNEY DISEASE, CORONARY ARTERY DISEASE, AND DIABETES; LIMITATIONS OF THESE STUDIES INCLUDE THAT MOST ARE RETROSPECTIVE AND SOME DO NOT RIGOROUSLY DISTINGUISH BETWEEN ASYMPTOMATIC HYPERURICEMIA AND GOUT. TREATMENT STUDIES SUGGEST THAT URATE LOWERING MAY REDUCE THE RISK OF INCIDENCE OR PROGRESSION OF SOME OF THESE COMORBIDITIES; UNFORTUNATELY, MANY OF THESE TREATMENT STUDIES ARE SMALL OR FLAWED, AND NOT ALL STUDY RESULTS ARE CONSISTENT. SUMMARY: ACCUMULATING EVIDENCE SUGGESTS THAT ASYMPTOMATIC HYPERURICEMIA CONTRIBUTES TO THE COMORBIDITIES WITH WHICH IT ASSOCIATES AND THAT PROPER ASYMPTOMATIC HYPERURICEMIA TREATMENT MAY REDUCE FUTURE RISK. ADDITIONAL PROSPECTIVE TRIALS ARE NEEDED TO DEFINITELY ESTABLISH CAUSALITY AND SUPPORT DECISION-MAKING AS TO WHETHER, AND WHICH PATIENTS WITH ASYMPTOMATIC HYPERURICEMIA WOULD WARRANT URATE-LOWERING TREATMENT. 2020 6 4675 30 NEW INSIGHTS INTO UNDERSTANDING THE MECHANISMS, PATHOGENESIS, AND MANAGEMENT OF MALIGNANT MESOTHELIOMAS. MALIGNANT MESOTHELIOMA (MM) IS A RELATIVELY RARE BUT DEVASTATING TUMOR THAT IS INCREASING WORLDWIDE. YET, BECAUSE OF DIFFICULTIES IN EARLY DIAGNOSIS AND RESISTANCE TO CONVENTIONAL THERAPIES, MM REMAINS A CHALLENGE FOR PATHOLOGISTS AND CLINICIANS TO TREAT. IN RECENT YEARS, MUCH HAS BEEN REVEALED REGARDING THE MECHANISMS OF INTERACTIONS OF PATHOGENIC FIBERS WITH MESOTHELIAL CELLS, CRUCIAL SIGNALING PATHWAYS, AND GENETIC AND EPIGENETIC EVENTS THAT MAY OCCUR DURING THE PATHOGENESIS OF THESE UNUSUAL, PLEIOMORPHIC TUMORS. THESE OBSERVATIONS SUPPORT A SCENARIO WHEREBY MESOTHELIAL CELLS UNDERGO A SERIES OF CHRONIC INJURY, INFLAMMATION, AND PROLIFERATION IN THE LONG LATENCY PERIOD OF MM DEVELOPMENT THAT MAY BE PERPETUATED BY DURABLE FIBERS, THE TUMOR MICROENVIRONMENT, AND INFLAMMATORY STIMULI. ONE CULPRIT IN SUSTAINED INFLAMMATION IS THE ACTIVATED INFLAMMASOME, A COMPONENT OF MACROPHAGES OR MESOTHELIAL CELLS THAT LEADS TO PRODUCTION OF CHEMOTACTIC, GROWTH-PROMOTING, AND ANGIOGENIC CYTOKINES. THIS INFORMATION HAS BEEN VITAL TO DESIGNING NOVEL THERAPEUTIC APPROACHES FOR PATIENTS WITH MM THAT FOCUS ON IMMUNOTHERAPY, TARGETING GROWTH FACTOR RECEPTORS AND PATHWAYS, OVERCOMING RESISTANCE TO APOPTOSIS, AND MODIFYING EPIGENETIC CHANGES. 2013 7 1398 53 DIET, GUT MICROBIOME AND EPIGENETICS: EMERGING LINKS WITH INFLAMMATORY BOWEL DISEASES AND PROSPECTS FOR MANAGEMENT AND PREVENTION. INFLAMMATORY BOWEL DISEASES (IBD) REPRESENT A GROWING PUBLIC HEALTH CONCERN DUE TO INCREASING INCIDENCE WORLDWIDE. THE CURRENT NOTION ON THE PATHOGENESIS OF IBD IS THAT GENETICALLY SUSCEPTIBLE INDIVIDUALS DEVELOP INTOLERANCE TO DYSREGULATED GUT MICROFLORA (DYSBIOSIS) AND CHRONIC INFLAMMATION DEVELOPS AS A RESULT OF ENVIRONMENTAL TRIGGERS. AMONG THE ENVIRONMENTAL FACTORS ASSOCIATED WITH IBD, DIET PLAYS AN IMPORTANT ROLE IN MODULATING THE GUT MICROBIOME, INFLUENCING EPIGENETIC CHANGES, AND, THEREFORE, COULD BE APPLIED AS A THERAPEUTIC TOOL TO IMPROVE THE DISEASE COURSE. NEVERTHELESS, THE CURRENT DIETARY RECOMMENDATIONS FOR DISEASE PREVENTION AND MANAGEMENT ARE SCARCE AND HAVE WEAK EVIDENCE. THIS REVIEW SUMMARISES THE CURRENT KNOWLEDGE ON THE COMPLEX INTERACTIONS BETWEEN DIET, MICROBIOME AND EPIGENETICS IN IBD. WHEREAS AN OVERABUNDANCE OF CALORIES AND SOME MACRONUTRIENTS INCREASE GUT INFLAMMATION, SEVERAL MICRONUTRIENTS HAVE THE POTENTIAL TO MODULATE IT. IMMUNONUTRITION HAS EMERGED AS A NEW CONCEPT PUTTING FORWARD THE IMPORTANCE OF VITAMINS SUCH AS VITAMINS A, C, E, AND D, FOLIC ACID, BETA CAROTENE AND TRACE ELEMENTS SUCH AS ZINC, SELENIUM, MANGANESE AND IRON. HOWEVER, WHEN ASSESSED IN CLINICAL TRIALS, SPECIFIC MICRONUTRIENTS EXERTED A LIMITED BENEFIT. BEYOND NUTRIENTS, AN ANTI-INFLAMMATORY DIETARY PATTERN AS A COMPLEX INTERVENTION APPROACH HAS BECOME POPULAR IN RECENT YEARS. HENCE, EXCLUSIVE ENTERAL NUTRITION IN PAEDIATRIC CROHN'S DISEASE IS THE ONLY NUTRITIONAL INTERVENTION CURRENTLY RECOMMENDED AS A FIRST-LINE THERAPY. OTHER NUTRITIONAL INTERVENTIONS OR SPECIFIC DIETS INCLUDING THE SPECIFIC CARBOHYDRATE DIET (SCD), THE LOW FERMENTABLE OLIGOSACCHARIDES, DISACCHARIDES, MONOSACCHARIDES, AND POLYOL (FODMAP) DIET AND, MOST RECENTLY, THE MEDITERRANEAN DIET HAVE SHOWN STRONG ANTI-INFLAMMATORY PROPERTIES AND SHOW PROMISE FOR IMPROVING DISEASE SYMPTOMS. MORE WORK IS REQUIRED TO EVALUATE THE ROLE OF INDIVIDUAL FOOD COMPOUNDS AND COMPLEX NUTRITIONAL INTERVENTIONS WITH THE POTENTIAL TO DECREASE INFLAMMATION AS A MEANS OF PREVENTION AND MANAGEMENT OF IBD. 2017 8 4274 47 MICROBIOTA IN INFLAMMATORY BOWEL DISEASE PATHOGENESIS AND THERAPY: IS IT ALL ABOUT DIET? INFLAMMATORY BOWEL DISEASE (IBD), INCLUDING ULCERATIVE COLITIS, CROHN'S DISEASE, AND UNCLASSIFIED IBD, CONTINUES TO CAUSE SIGNIFICANT MORBIDITY. WHILE ITS INCIDENCE IS INCREASING, NO CLEAR ETIOLOGY AND NO CURE HAVE YET BEEN DISCOVERED. RECENT FINDINGS SUGGEST THAT IBD MAY HAVE A MULTIFACTORIAL ETIOLOGY, WHERE COMPLEX INTERACTIONS BETWEEN GENETICS, EPIGENETICS, ENVIRONMENTAL FACTORS (INCLUDING DIET BUT ALSO INFECTIONS, ANTIBIOTICS, AND SANITATION), AND HOST IMMUNE SYSTEM LEAD TO ABNORMAL IMMUNE RESPONSES AND CHRONIC INFLAMMATION. OVER THE PAST YEARS, THE ROLE OF ALTERED GUT MICROBIOTA (IN BOTH COMPOSITION AND FUNCTION) IN IBD PATHOGENESIS HAS EMERGED AS AN OUTSTANDING AREA OF INTEREST. ACCORDING TO NEW FINDINGS, GUT DYSBIOSIS MAY APPEAR AS A KEY ELEMENT IN INITIATION OF INFLAMMATION IN IBD AND ITS COMPLICATIONS. MOREOVER, COMPLEX METAGENOMIC STUDIES PROVIDE POSSIBILITIES TO DISTINGUISH BETWEEN IBD TYPES AND APPRECIATE SEVERITY AND PROGNOSIS OF THE DISEASE, AS WELL AS RESPONSE TO THERAPY. THIS REVIEW PROVIDES AN UPDATED KNOWLEDGE OF RECENT FINDINGS LINKING ALTERED BACTERIAL COMPOSITION AND FUNCTIONS, VIRUSES, AND FUNGI TO IBD PATHOGENESIS. IT ALSO HIGHLIGHTS THE COMPLEX GENETIC, EPIGENETIC, IMMUNE, AND MICROBIAL INTERACTIONS IN RELATION TO ENVIRONMENTAL FACTORS (INCLUDING DIET). WE OVERVIEW THE ACTUAL OPTIONS TO MANIPULATE THE ALTERED MICROBIOTA, SUCH AS MODIFIED DIET, PROBIOTICS, PREBIOTICS, SYNBIOTICS, ANTIBIOTICS, AND FECAL TRANSPLANTATION. FUTURE POSSIBLE THERAPIES ARE ALSO INCLUDED. TARGETING ALTERED MICROBIOTA COULD BE THE NEXT THERAPEUTIC PERSONALIZED APPROACH, BUT MORE RESEARCH AND WELL-DESIGNED COMPARATIVE PROSPECTIVE STUDIES ARE REQUIRED TO FORMULATE ADEQUATE DIRECTIONS FOR PREVENTION AND THERAPY. 2015 9 6114 43 THE EPIGENETIC CONTRIBUTION TO THE PATHOGENESIS OF PSORIASIS: RECENT ADVANCES. PSORIASIS IS DEFINED AS A CHRONIC AUTOIMMUNE DISORDER OF THE SKIN IN WHICH ABNORMAL PROLIFERATION AND DIFFERENTIATION OF KERATINOCYTES ARE BLAMED AS THE CENTRAL CULPRIT OF DISEASE ETIOPATHOGENESIS. A COMPLEX INTERPLAY BETWEEN ENVIRONMENTAL FACTORS AND GENETIC RISK FACTORS HAS BEEN SUGGESTED TO TRIGGER THE DISEASE. HOWEVER, EPIGENETIC REGULATION APPEARS TO CONNECT EXTERNAL STIMULI AND GENETIC ABNORMALITIES IN THE DEVELOPMENT OF PSORIASIS. THE DISCORDANCE IN THE PREVALENCE OF PSORIASIS BETWEEN MONOZYGOTIC TWINS AND ENVIRONMENTAL FACTORS THAT CONTRIBUTE TO ITS ONSET HAVE CAUSED A PARADIGM SHIFT REGARDING THE MECHANISMS UNDERLYING THE PATHOGENESIS OF THIS DISEASE. EPIGENETIC DYSREGULATION MAY BE INVOLVED IN ABERRANCIES OF KERATINOCYTE DIFFERENTIATION, T-CELL ACTIVATION, AND OTHER PLAUSIBLE CELLS, LEADING TO THE INITIATION AND PERPETUATION OF PSORIASIS. EPIGENETICS IS CHARACTERIZED BY HERITABLE ALTERATIONS IN THE TRANSCRIPTION OF GENES WITHOUT NUCLEOTIDE CHANGE AND IS COMMONLY CONSIDERED AT THREE LEVELS, I.E., DNA METHYLATION, HISTONE MODIFICATIONS, AND MICRORNAS. TO DATE, SCIENTIFIC EVIDENCE HAS INDICATED ABNORMAL DNA METHYLATION, HISTONE MODIFICATIONS, AND NON-CODING RNA TRANSCRIPTION IN PSORIATIC PATIENTS. IN ORDER TO REVERSE ABERRANT EPIGENETIC CHANGES IN PSORIASIS PATIENTS, SEVERAL COMPOUNDS AND DRUGS (EPI-DRUGS) HAVE BEEN DEVELOPED TO AFFECT THE MAJOR ENZYMES INVOLVED IN THE METHYLATION OF DNA, OR THE ACETYLATION OF HISTONES, WHICH AIM TO CORRECT THE ABERRANT METHYLATION AND ACETYLATION PATTERNS. A NUMBER OF CLINICAL TRIALS HAVE SUGGESTED THE THERAPEUTIC POTENTIAL OF SUCH DRUGS IN THE TREATMENT OF PSORIASIS. IN THE PRESENT REVIEW, WE ATTEMPT TO CLARIFY RECENT FINDINGS WITH RESPECT TO EPIGENETIC IRREGULARITIES IN PSORIASIS AND DISCUSS FUTURE CHALLENGES. 2023 10 6737 33 WHAT MAKES GOUTY INFLAMMATION SO VARIABLE? ACUTE GOUT ARTHRITIS FLARES CONTRIBUTE DOMINANTLY TO GOUT-SPECIFIC IMPAIRED HEALTH-RELATED QUALITY OF LIFE, REPRESENTING A PROGRESSIVELY INCREASING PUBLIC HEALTH PROBLEM. FLARES CAN BE COMPLEX AND EXPENSIVE TO TREAT, PARTLY DUE TO THE FREQUENT COMORBIDITIES. UNMET NEEDS IN GOUT MANAGEMENT ARE MORE PRESSING GIVEN THE MARKEDLY INCREASING GOUT FLARE HOSPITAL ADMISSION RATES. IN ADDITION, CHRONIC GOUTY ARTHRITIS CAN CAUSE JOINT DAMAGE AND FUNCTIONAL IMPAIRMENT. THIS REVIEW ADDRESSES NEW KNOWLEDGE ON THE BASIS FOR THE MARKED, INHERENT VARIABILITY OF RESPONSES TO DEPOSITED URATE CRYSTALS, INCLUDING THE UNPREDICTABLE AND SELF-LIMITED ASPECTS OF MANY GOUT FLARES. SPECIFIC TOPICS REVIEWED INCLUDE HOW INNATE IMMUNITY AND TWO-SIGNAL INFLAMMASOME ACTIVATION INTERSECT WITH DIET, METABOLISM, NUTRITIONAL BIOSENSING, THE MICROBIOME, AND THE PHAGOCYTE CYTOSKELETON AND CELL FATE. THE PAPER DISCUSSES THE ROLES OF ENDOGENOUS CONSTITUTIVE REGULATORS OF INFLAMMATION, INCLUDING CERTAIN NUTRITIONAL BIOSENSORS, AND EMERGING GENETIC AND EPIGENETIC FACTORS. RECENT ADVANCES IN THE BASIS OF VARIABILITY IN RESPONSES TO URATE CRYSTALS IN GOUT PROVIDE INFORMATION ABOUT INFLAMMATORY ARTHRITIS, AND HAVE IDENTIFIED POTENTIAL NEW TARGETS AND STRATEGIES FOR ANTI-INFLAMMATORY PREVENTION AND TREATMENT OF GOUTY ARTHRITIS. 2017 11 2731 29 EXPLORING THE COMPLEX RELATIONSHIP BETWEEN MICROBIOTA AND SYSTEMIC LUPUS ERYTHEMATOSUS. PURPOSE OF REVIEW: SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC AUTOIMMUNE DISEASE CHARACTERIZED BY VARIOUS AUTOANTIBODIES AND MULTI-ORGAN. MICROBIOTA DYSBIOSIS IN THE GUT, SKIN, ORAL, AND OTHER SURFACES HAS A SIGNIFICANT IMPACT ON SLE DEVELOPMENT. THIS ARTICLE SUMMARIZES RELEVANT RESEARCH AND PROVIDES NEW MICROBIOME-RELATED STRATEGIES FOR EXPLORING THE MECHANISMS AND TREATING PATIENTS WITH SLE. RECENT FINDINGS: SLE PATIENTS HAVE DISRUPTIONS IN MULTIPLE MICROBIOMES, WITH THE GUT MICROBIOTA (BACTERIA, VIRUSES, AND FUNGI) AND THEIR METABOLITES BEING THE MOST THOROUGHLY RESEARCHED. THIS DYSBIOSIS CAN PROMOTE SLE PROGRESSION THROUGH MECHANISMS SUCH AS THE LEAKY GUT, MOLECULAR MIMICRY, AND EPIGENETIC REGULATION. NOTWITHSTANDING STUDY CONSTRAINTS ON THE RELATIONSHIP BETWEEN MICROBIOTA AND SLE, SPECIFIC INTERVENTIONS TARGETING THE GUT MICROBIOTA, SUCH AS PROBIOTICS, DIETARY MANAGEMENT, AND FECAL MICROBIOTA TRANSPLANTATION, HAVE EMERGED AS PROMISING SLE THERAPEUTICS. 2023 12 3701 31 INFLAMMATORY RESPONSE TO REGULATED CELL DEATH IN GOUT AND ITS FUNCTIONAL IMPLICATIONS. GOUT, A CHRONIC INFLAMMATORY ARTHRITIS DISEASE, IS CHARACTERIZED BY HYPERURICEMIA AND CAUSED BY INTERACTIONS BETWEEN GENETIC, EPIGENETIC, AND METABOLIC FACTORS. ACUTE GOUT SYMPTOMS ARE TRIGGERED BY THE INFLAMMATORY RESPONSE TO MONOSODIUM URATE CRYSTALS, WHICH IS MEDIATED BY THE INNATE IMMUNE SYSTEM AND IMMUNE CELLS (E.G., MACROPHAGES AND NEUTROPHILS), THE NACHT, LRR, AND PYD DOMAINS-CONTAINING PROTEIN 3 (NLRP3) INFLAMMASOME ACTIVATION, AND PRO-INFLAMMATORY CYTOKINE (E.G., IL-1BETA) RELEASE. RECENT STUDIES HAVE INDICATED THAT THE MULTIPLE PROGRAMMED CELL DEATH PATHWAYS INVOLVED IN THE INFLAMMATORY RESPONSE INCLUDE PYROPTOSIS, NETOSIS, NECROPTOSIS, AND APOPTOSIS, WHICH INITIATE INFLAMMATORY REACTIONS. IN THIS REVIEW, WE EXPLORE THE CORRELATION AND INTERACTIONS AMONG THESE FACTORS AND THEIR ROLES IN THE PATHOGENESIS OF GOUT TO PROVIDE FUTURE RESEARCH DIRECTIONS AND POSSIBILITIES FOR IDENTIFYING POTENTIAL NOVEL THERAPEUTIC TARGETS AND ENHANCING OUR UNDERSTANDING OF GOUT PATHOGENESIS. 2022 13 1183 34 CONVERGING RELATIONSHIPS OF OBESITY AND HYPERURICEMIA WITH SPECIAL REFERENCE TO METABOLIC DISORDERS AND PLAUSIBLE THERAPEUTIC IMPLICATIONS. BACKGROUND: OBESITY AND HYPERURICEMIA MUTUALLY INFLUENCE METABOLIC SYNDROME. THIS STUDY DISCUSSES THE METABOLIC RELATIONSHIPS BETWEEN OBESITY AND HYPERURICEMIA IN TERMS OF PATHOPHYSIOLOGY, COMPLICATIONS, AND TREATMENTS. METHODS: WE SEARCHED FOR PRECLINICAL OR CLINICAL STUDIES ON THE PATHOPHYSIOLOGY, COMPLICATIONS, AND THERAPY OF OBESITY AND HYPERURICEMIA ON THE PUBMED DATABASE. RESULTS: IN THIS SYSTEMIC REVIEW, WE SUMMARIZED OUR SEARCHING RESULTS ON TOPICS OF PATHOPHYSIOLOGY, COMPLICATIONS AND THERAPEUTIC STRATEGY. IN PATHOPHYSIOLOGY, WE FIRSTLY INTRODUCE GENETIC VARIATIONS FOR OBESITY, HYPERURICEMIA AND THEIR RELATIONSHIPS BY GENETIC STUDIES. SECONDLY, WE TALK ABOUT THE EPIGENETIC INFLUENCES ON OBESITY AND HYPERURICEMIA. THIRDLY, WE DESCRIBE THE CENTRAL METABOLIC REGULATION AND THE ROLE OF HYPERURICEMIA. THEN, WE REFER TO THE CHARACTER OF ADIPOSE TISSUE INFLAMMATION AND OXIDATIVE STRESS IN THE OBESITY AND HYPERURICEMIA. IN THE LAST PART OF THIS TOPIC, WE REVIEWED THE CRITICAL LINKS OF GUT MICROBIOTA IN THE OBESITY AND HYPERURICEMIA. IN THE FOLLOWING PART, WE REVIEW THE PATHOPHYSIOLOGY OF MAJOR COMPLICATIONS IN OBESITY AND HYPERURICEMIA INCLUDING INSULIN RESISTANCE AND TYPE 2 DIABETES MELLITUS, CHRONIC KIDNEY DISEASE, CARDIOVASCULAR DISEASES, AND CANCERS. FINALLY, WE RECAPITULATE THE THERAPEUTIC STRATEGIES ESPECIALLY THE NOVEL PHARMACEUTIC INTERVENTIONS FOR OBESITY AND HYPERURICEMIA, WHICH CONCURRENTLY SHOW THE MUTUAL METABOLIC INFLUENCES BETWEEN TWO DISEASES. CONCLUSION: THE DATA REVIEWED HERE DELINEATE THE METABOLIC RELATIONSHIPS BETWEEN OBESITY AND HYPERURICEMIA, AND PROVIDE A COMPREHENSIVE OVERVIEW OF THE THERAPEUTIC TARGETS FOR THE MANAGEMENT OF METABOLIC SYNDROMES. 2020 14 1395 42 DIET AND MICROBIOME IN THE BEGINNING OF THE SEQUENCE OF GUT INFLAMMATION. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC INFLAMMATORY CONDITION OF THE GASTROINTESTINAL TRACT DUE, AT LEAST PARTIALLY, TO AN ABERRANT AND EXCESSIVE MUCOSAL IMMUNE RESPONSE TO GUT BACTERIA IN GENETICALLY-PREDISPOSED INDIVIDUALS UNDER CERTAIN ENVIRONMENTAL FACTORS. THE INCIDENCE OF IBD IS RISING IN WESTERN AND NEWLY INDUSTRIALIZED COUNTRIES, PARALLELING THE INCREASE OF WESTERNIZED DIETARY PATTERNS, THROUGH NEW ANTIGENS, EPITHELIAL FUNCTION AND PERMEABILITY, EPIGENETIC MECHANISMS (E.G., DNA METHYLATION), AND ALTERATION OF THE GUT MICROBIOME. ALTERATION IN THE COMPOSITION AND FUNCTIONALITY OF THE GUT MICROBIOME (INCLUDING BACTERIA, VIRUSES AND FUNGI) SEEMS TO BE A NUCLEAR PATHOGENIC FACTOR. THE MICROBIOME ITSELF IS DYNAMIC, AND THE CHANGES IN FOOD QUALITY, DIETARY HABITS, LIVING CONDITIONS AND HYGIENE OF THESE WESTERN SOCIETIES, COULD INTERACT IN A COMPLEX MANNER AS MODULATORS OF DYSBIOSIS, THEREBY INFLUENCING THE ACTIVATION OF IMMUNE CELLS' PROMOTING INFLAMMATION. THE MICROBIOME PRODUCES DIVERSE SMALL MOLECULES VIA SEVERAL METABOLIC WAYS, WITH THE FIBER-DERIVED SHORT-CHAIN FATTY ACIDS (I.E., BUTYRATE) AS MAIN ELEMENTS AND HAVING ANTI-INFLAMMATORY EFFECTS. THESE METABOLITES AND SOME MICRONUTRIENTS OF THE DIET (I.E., VITAMINS, FOLIC ACID, BETA CAROTENE AND TRACE ELEMENTS) ARE REGULATORS OF INNATE AND ADAPTIVE INTESTINAL IMMUNE HOMEOSTASIS. AN EXCESSIVE AND UNHEALTHY CONSUMPTION OF SUGAR, ANIMAL FAT AND A LOW-VEGETABLE AND -FIBER DIET ARE RISK FACTORS FOR IBD APPEARANCE. FURTHERMORE, METABOLISM OF NUTRIENTS IN INTESTINAL EPITHELIUM AND IN GUT MICROBIOTA IS ALTERED BY INFLAMMATION, CHANGING THE DEMAND FOR NUTRIENTS NEEDED FOR HOMEOSTASIS. THIS ROLE OF FOOD AND A REDUCED GUT MICROBIAL DIVERSITY IN CAUSING IBD MIGHT ALSO HAVE A PROPHYLACTIC OR THERAPEUTIC ROLE FOR IBD. THE RELATIONSHIP BETWEEN DIETARY INTAKE, SYMPTOMS, AND BOWEL INFLAMMATION COULD LEAD TO DIETARY AND LIFESTYLE RECOMMENDATIONS, INCLUDING DIETS WITH ABUNDANT FRUITS, VEGETABLES, OLIVE OIL AND OILY FISH, WHICH HAVE ANTI-INFLAMMATORY EFFECTS AND COULD PREVENT DYSBIOSIS AND IBD. DIETARY MODULATION AND APPROPRIATE EXCLUSION DIETS MIGHT BE A NEW COMPLEMENTARY MANAGEMENT FOR TREATMENT AT DISEASE FLARES AND IN REFRACTORY PATIENTS, EVEN REDUCING COMPLICATIONS, HOSPITALIZATIONS AND SURGERY, THROUGH MODIFYING THE LUMINAL INTESTINAL ENVIRONMENT. 2021 15 465 36 ARE TARGETED THERAPIES FOR DIABETIC CARDIOMYOPATHY ON THE HORIZON? DIABETES INCREASES THE RISK OF HEART FAILURE APPROXIMATELY 2.5-FOLD, INDEPENDENT OF CORONARY ARTERY DISEASE AND OTHER COMORBIDITIES. THIS PROCESS, TERMED DIABETIC CARDIOMYOPATHY, IS CHARACTERIZED BY INITIAL IMPAIRMENT OF LEFT VENTRICULAR (LV) RELAXATION FOLLOWED BY LV CONTRACTILE DYSFUNCTION. POST-MORTEM EXAMINATION REVEALS THAT HUMAN DIASTOLIC DYSFUNCTION IS CLOSELY ASSOCIATED WITH LV DAMAGE, INCLUDING CARDIOMYOCYTE HYPERTROPHY, APOPTOSIS AND FIBROSIS, WITH IMPAIRED CORONARY MICROVASCULAR PERFUSION. THE PATHOPHYSIOLOGICAL MECHANISMS UNDERPINNING THE CHARACTERISTIC FEATURES OF DIABETIC CARDIOMYOPATHY REMAIN POORLY UNDERSTOOD, ALTHOUGH MULTIPLE FACTORS INCLUDING ALTERED LIPID METABOLISM, MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, ENDOPLASMIC RETICULUM (ER) STRESS, INFLAMMATION, AS WELL AS EPIGENETIC CHANGES, ARE IMPLICATED. DESPITE A RECENT RISE IN RESEARCH INTERROGATING THESE MECHANISMS AND AN INCREASED UNDERSTANDING OF THE CLINICAL IMPORTANCE OF DIABETIC CARDIOMYOPATHY, THERE REMAINS A LACK OF SPECIFIC TREATMENT STRATEGIES. HOW THE CHRONIC METABOLIC DISTURBANCES OBSERVED IN DIABETES LEAD TO STRUCTURAL AND FUNCTIONAL CHANGES REMAINS A PERTINENT QUESTION, AND IT IS HOPED THAT RECENT ADVANCES, PARTICULARLY IN THE AREA OF EPIGENETICS, AMONG OTHERS, MAY PROVIDE SOME ANSWERS. THIS REVIEW HENCE EXPLORES THE TEMPORAL ONSET OF THE PATHOLOGICAL FEATURES OF DIABETIC CARDIOMYOPATHY, AND THEIR RELATIVE CONTRIBUTION TO THE RESULTANT DISEASE PHENOTYPE, AS WELL AS BOTH CURRENT AND POTENTIAL THERAPEUTIC OPTIONS. THE EMERGENCE OF GLUCOSE-OPTIMIZING AGENTS, NAMELY GLUCAGON-LIKE PEPTIDE-1 (GLP-1) AGONISTS AND SODIUM/GLUCOSE CO-TRANSPORTER (SGLT)2 INHIBITORS THAT CONFER BENEFITS ON CARDIOVASCULAR OUTCOMES, TOGETHER WITH NOVEL EXPERIMENTAL APPROACHES, HIGHLIGHT A NEW AND EXCITING ERA IN DIABETES RESEARCH, WHICH IS LIKELY TO RESULT IN MAJOR CLINICAL IMPACT. 2017 16 1397 32 DIET PHYTOCHEMICALS AND CUTANEOUS CARCINOMA CHEMOPREVENTION: A REVIEW. CUTANEOUS CARCINOMA, WHICH HAS OCCUPIED A PECULIAR PLACE AMONG WORLDWIDE POPULATIONS, IS COMMONLY RESPONSIBLE FOR THE CONSIDERABLY INCREASING MORBIDITY AND MORTALITY RATES. CURRENTLY AVAILABLE MEDICAL PROCEDURES FAIL TO COMPLETELY AVOID CUTANEOUS CARCINOMA DEVELOPMENT OR TO PREVENT MORTALITY. CANCER CHEMOPREVENTION, AS AN ALTERNATIVE STRATEGY, IS BEING CONSIDERED TO REDUCE THE INCIDENCE AND BURDEN OF CANCERS THROUGH CHEMICAL AGENTS. DERIVED FROM DIETARY FOODS, PHYTOCHEMICALS HAVE BECOME SAFE AND RELIABLE COMPOUNDS FOR THE CHEMOPREVENTION OF CUTANEOUS CARCINOMA BY RELIEVING MULTIPLE PATHOLOGICAL PROCESSES, INCLUDING OXIDATIVE DAMAGE, EPIGENETIC ALTERATION, CHRONIC INFLAMMATION, ANGIOGENESIS, ETC. IN THIS REVIEW, WE PRESENTED COMPREHENSIVE KNOWLEDGES, MAIN MOLECULAR MECHANISMS FOR THE INITIATION AND DEVELOPMENT OF CUTANEOUS CARCINOMA AS WELL AS EFFECTS OF VARIOUS DIET PHYTOCHEMICALS ON CHEMOPREVENTION. 2017 17 246 50 ADULT STEM CELL THERAPY FOR CARDIAC REPAIR IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION LEADING TO ISCHEMIC HEART FAILURE: AN OVERVIEW OF EVIDENCE FROM THE RECENT CLINICAL TRIALS. BACKGROUND: CARDIOVASCULAR DISEASES (CVD) STILL REPRESENT THE LEADING CAUSE OF MORTALITY WORLDWIDE, DESPITE THE REMARKABLE ADVANCES IN INTERVENTIONAL CARDIOLOGY, CARDIAC SURGERY, AND MODERN PHARMACOTHERAPY, PARTICULARLY IN THE SETTING OF ACUTE MYOCARDIAL INFARCTION (AMI), CHRONIC ISCHEMIC HEART FAILURE (HF), CARDIOMYOPATHY (CM), AND THE ASSOCIATED LEFT VENTRICULAR (LV) DYSFUNCTION. A SIGNIFICANT LOSS OF CARDIOMYOCYTES THAT UNDERLIES ALL OF THESE CONDITIONS WAS PREVIOUSLY CONSIDERED IRREVERSIBLE. HOWEVER, CURRENT EVIDENCE INDICATES THAT THE HUMAN HEART HAS SOME POTENTIAL FOR REPAIR, AND OVER THE PAST DECADE, MANY RESEARCH STUDIES HAVE BEEN EXPLORING THE USE OF STEM CELLS (SCS) TO FACILITATE RESTORATION OF MYOCARDIUM. CONSEQUENTLY, THE SAFETY, FEASIBILITY, AND EFFECTIVENESS OF SC THERAPY HAVE BEEN REPORTED IN MANY RANDOMIZED CLINICAL TRIALS (RCTS), USING DIFFERENT LINEAGES OF ADULT SCS. NEVERTHELESS, THE CLINICAL BENEFITS OF SC THERAPY ARE NOT YET WELL ESTABLISHED. IN THE NEAR FUTURE, UNDERSTANDING OF THE COMPLEX INTERRELATIONS BETWEEN SCS, PARACRINE FACTORS, GENETIC OR EPIGENETIC PREDISPOSITIONS, AND MYOCARDIAL MICROENVIRONMENT, IN THE CONTEXT OF AN INDIVIDUAL PATIENT, WILL BE CRUCIAL FOR TRANSLATION OF THIS KNOWLEDGE INTO PRACTICAL DEVELOPMENT OF SUCCESSFUL, LONG-TERM REGENERATIVE SC THERAPEUTIC APPLICATIONS, IN A GROWING POPULATION OF PATIENTS SUFFERING FROM PREVIOUS MYOCARDIAL INFARCTION (MI) LEADING TO CHRONIC ISCHEMIC CARDIOMYOPATHY. CONCLUSION: THIS OVERVIEW HIGHLIGHTS THE THERAPEUTIC POTENTIAL OF ADULT SCS IN TERMS OF THEIR POSSIBLE REGENERATIVE CAPACITY, SAFETY, AND CLINICAL OUTCOMES, IN PATIENTS WITH AMI, AND/OR SUBSEQUENT HF (DUE TO CHRONIC ISCHEMIC CARDIOMYOPATHY). THIS REVIEW WAS BASED UPON PUBMED DATABASE SEARCH FOR TRIALS ON SC THERAPY, IN PATIENTS WITH AMI AND HF, AND THE MAIN TIMEFRAME WAS SET FROM 2006 TO 2016. 2017 18 264 34 ADVANCING ASTHMA CARE: THE GLASS IS ONLY HALF FULL! OVER THE PAST 20 YEARS, THERE HAS BEEN A CONCERTED EFFORT IN THE UNITED STATES TO REDUCE MORBIDITY RELATED TO CHRONIC DISEASE, INCLUDING ASTHMA. ATTENTION WAS INITIALLY DIRECTED TOWARD ASTHMA IN RESPONSE TO THE RECOGNITION THAT ASTHMA MORTALITY WAS INCREASING AND THAT THE BURDEN OF DISEASE WAS SIGNIFICANT. THESE EFFORTS TO ADDRESS ASTHMA MORTALITY LED TO MANY NEW INITIATIVES TO DEVELOP CLINICAL PRACTICE GUIDELINES, IMPLEMENT THE ASTHMA GUIDELINES INTO CLINICAL PRACTICE, CONDUCT RESEARCH TO FILL THE GAPS IN THE GUIDELINES, AND CONTINUOUSLY REVISE THE ASTHMA GUIDELINES AS MORE INFORMATION BECAME AVAILABLE. AN ASSESSMENT OF OUR PROGRESS SHOWS SIGNIFICANT ACCOMPLISHMENTS IN RELATION TO REDUCING ASTHMA MORTALITY AND HOSPITALIZATIONS. CONSEQUENTLY, WE ARE NOW AT A CROSSROADS IN ASTHMA CARE. ALTHOUGH WE HAVE RECOGNIZED SOME REMARKABLE ACCOMPLISHMENTS IN REDUCING ASTHMA MORTALITY AND MORBIDITY, THE AVAILABILITY OF NEW TOOLS TO MONITOR DISEASE ACTIVITY, INCLUDING BIOMARKERS AND EPIGENETIC MARKERS, ALONG WITH INFORMATION TECHNOLOGY SYSTEMS TO MONITOR ASTHMA CONTROL HOLD SOME PROMISE IN IDENTIFYING GAPS IN DISEASE MANAGEMENT. THESE ADVANCES SHOULD PROMPT THE EVOLUTION OF NEW STRATEGIES AND NEW TREATMENTS TO FURTHER REDUCE DISEASE BURDEN. IT NOW BECOMES IMPERATIVE TO CONTINUE A FOCUS ON WAYS TO FURTHER REDUCE THE BURDEN OF ASTHMA AND PREVENT ITS ONSET. 2011 19 4663 34 NEW HORIZONS: NOVEL APPROACHES TO ENHANCE HEALTHSPAN THROUGH TARGETING CELLULAR SENESCENCE AND RELATED AGING MECHANISMS. THE ELDERLY POPULATION IS INCREASING FASTER THAN OTHER SEGMENTS OF THE POPULATION THROUGHOUT THE WORLD. AGE IS THE LEADING PREDICTOR FOR MOST CHRONIC DISEASES AND DISORDERS, MULTIMORBIDITY, GERIATRIC SYNDROMES, AND IMPAIRED ABILITY TO RECOVER FROM ACCIDENTS OR ILLNESSES. ENHANCING THE DURATION OF HEALTH AND INDEPENDENCE, TERMED HEALTHSPAN, WOULD BE MORE DESIRABLE THAN EXTENDING LIFESPAN MERELY BY PROLONGING THE PERIOD OF MORBIDITY TOWARD THE END OF LIFE. THE GEROSCIENCE HYPOTHESIS POSITS THAT HEALTHSPAN CAN BE EXTENDED BY TARGETING FUNDAMENTAL AGING MECHANISMS, RATHER THAN ATTEMPTING TO ADDRESS EACH AGE-RELATED DISEASE ONE AT A TIME, ONLY SO THE AFFLICTED INDIVIDUAL SURVIVES DISABLED AND DIES SHORTLY AFTERWARD OF ANOTHER AGE-RELATED DISEASE. THESE FUNDAMENTAL AGING MECHANISMS INCLUDE, AMONG OTHERS, CHRONIC INFLAMMATION, FIBROSIS, STEM CELL/ PROGENITOR DYSFUNCTION, DNA DAMAGE, EPIGENETIC CHANGES, METABOLIC SHIFTS, DESTRUCTIVE METABOLITE GENERATION, MITOCHONDRIAL DYSFUNCTION, MISFOLDED OR AGGREGATED PROTEIN ACCUMULATION, AND CELLULAR SENESCENCE. THESE PROCESSES APPEAR TO BE TIGHTLY INTERLINKED, AS TARGETING ANY ONE APPEARS TO AFFECT MANY OF THE REST, UNDERLYING OUR UNITARY THEORY OF FUNDAMENTAL AGING MECHANISMS. INTERVENTIONS TARGETING MANY FUNDAMENTAL AGING PROCESSES ARE BEING DEVELOPED, INCLUDING DIETARY MANIPULATIONS, METFORMIN, MTOR (MECHANISTIC TARGET OF RAPAMYCIN) INHIBITORS, AND SENOLYTICS, WHICH ARE IN EARLY HUMAN TRIALS. THESE INTERVENTIONS COULD LEAD TO GREATER HEALTHSPAN BENEFITS THAN TREATING AGE-RELATED DISEASES ONE AT A TIME. TO ILLUSTRATE THESE POINTS, WE FOCUS ON CELLULAR SENESCENCE AND THERAPIES IN DEVELOPMENT TO TARGET SENESCENT CELLS. COMBINING INTERVENTIONS TARGETING AGING MECHANISMS WITH DISEASE-SPECIFIC DRUGS COULD RESULT IN MORE THAN ADDITIVE BENEFITS FOR CURRENTLY DIFFICULT-TO-TREAT OR INTRACTABLE DISEASES. MORE RESEARCH ATTENTION NEEDS TO BE DEVOTED TO TARGETING FUNDAMENTAL AGING PROCESSES. 2021 20 2859 43 FROM SMOKING TO COPD--CURRENT APPROACHES. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) REMAINS A LEADING CAUSE OF DEATH ALL OVER THE WORLD. EVEN THOUGH IT IS THE MOST INTENSELY STUDIED DISEASE INDUCED BY CIGARETTE SMOKING THERE ARE STILL INCOMPLETE RESEARCHES CONCERNING ITS PATHOPHYSIOLOGY AND TREATMENT. SO FAR IT HAS BEEN DETERMINED THE DELETERIOUS EFFECTS OF THE SECRETED MOLECULES DIVERSITY AND SOME FEASIBLE THERAPIES FOR THEIR DIMINUTION. ACCORDING TO CURRENT STUDIES MORE RELEVANCE GAINS THE POSSIBLE AUTOIMMUNE ORIGIN OF COPD AND THE EPIGENETIC MODIFICATIONS. THE IDEA OF AUTOIMMUNITY IN SMOKING INDUCED COPD BEGAN TO BE SPECULATED WITH THE DISCOVERY OF AUTOANTIBODIES IN PATIENT'S SERUM, BUT THERE ARE SOME STUDIES WHO CONSIDER ANTIBODY COMPLEXES THAT RESIDE IN THE LUNG TISSUE AS MORE RELEVANT FOR FUTURE RESEARCH. BY DEVELOPING THE AUTOIMMUNE ASPECT OF COPD IT WILL BECOME POSSIBLE TO SELECT MORE PRECISE TREATMENT STRATEGIES. THE IMPORTANCE OF EPIGENETIC CHANGES IN THIS FIELD MIGHT BE APPRECIATED STARTING WITH THE FACT OF AN EXISTING CONNECTION BETWEEN EPIGENETIC MODIFICATIONS INDUCED BY MATERNAL SMOKING AND LATTER COPD DEVELOPMENT. THIS EXPLAINS THE TENDENCY TOWARD DIFFERENT DRUGS CAPABLE OF RESTORING THESE TRANSFORMATIONS SUCH AS DEACETYLATION AGENTS EXPECTED ALSO TO PREVENT STEROID RESISTANCE. NEVERTHELESS SMOKING CESSATION REMAINS AS THE INDISPENSABLE APPROACH FOR COPD TREATMENT AND PREVENTION. 2016