1 2932 95 GENES AND EPIGENETIC PROCESSES AS PROSPECTIVE PAIN TARGETS. CHRONIC PAIN AFFECTS APPROXIMATELY ONE IN FIVE ADULTS, RESULTING IN A GREATLY REDUCED QUALITY OF LIFE AND A HIGHER RISK OF DEVELOPING CO-MORBIDITIES SUCH AS DEPRESSION. AVAILABLE TREATMENTS OFTEN PROVIDE INADEQUATE PAIN RELIEF, BUT IT IS HOPED THAT THROUGH DEEPER UNDERSTANDING OF THE MOLECULAR MECHANISMS UNDERLYING CHRONIC PAIN STATES WE CAN DISCOVER NEW AND IMPROVED THERAPIES. ALTHOUGH GENETIC RESEARCH HAS FLOURISHED OVER THE PAST DECADE AND HAS IDENTIFIED MANY KEY GENES IN PAIN PROCESSING, THE BUDDING FIELD OF EPIGENETICS PROMISES TO PROVIDE NEW INSIGHTS AND A MORE DYNAMIC VIEW OF PAIN REGULATION. THIS REVIEW GIVES AN OVERVIEW OF BASIC MECHANISMS AND CURRENT THERAPIES TO TREAT PAIN, AND DISCUSSES THE CLINICAL AND PRECLINICAL EVIDENCE FOR THE CONTRIBUTION OF GENETIC AND EPIGENETIC FACTORS, WITH A FOCUS ON HOW THIS KNOWLEDGE CAN AFFECT DRUG DEVELOPMENT. 2013 2 3399 31 HOW CAN GENETICS AND EPIGENETICS HELP THE NEPHROLOGIST IMPROVE THE DIAGNOSIS AND TREATMENT OF CHRONIC KIDNEY DISEASE PATIENTS? DISCOVERY OF NOVEL IMPROVED TOOLS FOR DIAGNOSIS, PREVENTION AND THERAPY OF CHRONIC KIDNEY DISEASE (CKD) IS AN IMPORTANT TASK FOR THE NEPHROLOGY COMMUNITY AND IT IS LIKELY THAT SCIENTIFIC BREAKTHROUGHS, TO A LARGE EXTENT, WILL BE BASED ON GENOMICS. THE RAPID GROWTH OF THE NUMBER OF GENOME-WIDE ASSOCIATION STUDIES, MAJOR ADVANCES IN DNA SEQUENCING AND OMICS PROFILING, AND ACCELERATING BIOMEDICAL RESEARCH EFFORTS IN THIS AREA HAVE GREATLY EXPANDED THE KNOWLEDGE BASE NEEDED FOR APPLIED GENOMICS. HOWEVER, TRANSLATING AND IMPLEMENTING GENOTYPE-PHENOTYPE DATA INTO GENE-BASED MEDICINE IN CKD POPULATIONS IS STILL IN AN EARLY PHASE AND WILL REQUIRE CONTINUOUS RESEARCH EFFORTS WITH INTEGRATED APPROACHES AND INTENSIFIED INVESTIGATIONS THAT FOCUS ON THE BIOLOGICAL PATHWAYS, WHICH CAUSATIVELY LINK A GENETIC VARIANT WITH THE DISEASE PHENOTYPE. IN THIS ARTICLE, WE REVIEW SOME CURRENT STRATEGIES TO UNRAVEL THESE TRANSLATIONAL GAPS AS WELL AS PROSPECTS FOR THE IMPLEMENTATION OF GENETIC AND EPIGENETIC METHODS INTO NOVEL CLINICAL PRACTICE. 2014 3 3769 18 INTEGRATIVE MEDICINE TO TACKLE THE PROBLEM OF CHRONIC DISEASES. THIS ARTICLE SUMMARIZES IMPORTANT WAYS THAT INTEGRATIVE MEDICINE CAN CONTRIBUTE TO RESOLVING THE GLOBAL HEALTH CRISIS WITH SPECIAL REFERENCE TO THE US. RESEARCH USING MODERN METHODS OF ANALYSIS OF CELLULAR CHANGES AT THE EPIGENETIC LEVEL HAS SHOWN THAT DIET AND LIFESTYLE INTERVENTIONS GREATLY IMPROVE THE STATE OF PATIENTS' HEALTH. ESTIMATES HAVE BEEN GIVEN THAT UP TO 75% OF ALL US HEALTH COSTS CAN BE SAVED BY THESE METHODS, PARTICULARLY IF APPLIED PREVENTATIVELY. IT IS THUS VITAL THAT ACTIVE STEPS ARE TAKEN TO IMPLEMENT SUCH PROGRAMS, TO REDUCE COSTS TO CITIZENS AND SOCIETY ALIKE, AS WELL AS TO GOVERNMENT. 2010 4 2062 32 EPIGENETIC CONTROL OF HYPERTENSION BY DNA METHYLATION: A REAL POSSIBILITY. HYPERTENSION IS A COMMON CHRONIC DISEASE THAT PARTICULARLY AFFECTS THE ELDERLY AND CAN TRIGGER SEVERAL CARDIOVASCULAR CONDITIONS. ALTHOUGH THE TREATMENT OF HYPERTENSION HAS EVOLVED IN RECENT DECADES, MANY HYPERTENSIVE PATIENTS STILL DO NOT HAVE PROPERLY CONTROLLED BLOOD PRESSURE. ACCUMULATING EVIDENCE SUPPORTS THE HYPOTHESIS THAT DNA METHYLATION PLAYS AN IMPORTANT ROLE IN REGULATING GENE EXPRESSION, ALTERING THE PHENOTYPE AND FUNCTION OF THE CARDIOVASCULAR SYSTEM. THE PRESENT REVIEW HIGHLIGHTS RECENT ADVANCES IN RESEARCH ON DNA METHYLATION IN THE DEVELOPMENT OF HYPERTENSION. SEVERAL PRECLINICAL AND CLINICAL EVIDENCE SHOW THAT METHYLATION OF DIFFERENT TARGETS APPEARS TO BE INVOLVED IN HYPERTENSION. STUDIES OF THE INVOLVEMENT OF DNA METHYLATION HAVE GREATLY IMPROVED OUR UNDERSTANDING OF HYPERTENSION, BUT ITS USE AS A VALID THERAPEUTIC TARGET IS STILL UNKNOWN. FURTHER STUDIES COULD HELP TO BRING TO LIGHT THE TRUTH ABOUT GENE THERAPY IN HYPERTENSION. 2021 5 3035 27 GENETICS/GENOMICS IN CHRONIC KIDNEY DISEASE--TOWARDS PERSONALIZED MEDICINE? THE PROGRESSION RATE OF CHRONIC KIDNEY DISEASE (CKD) TO ITS TERMINAL STAGE, END-STAGE RENAL DISEASE (ESRD), AND THE DEVELOPMENT AND SEVERITY OF VARIOUS COMPLICATIONS, ARE AT LEAST INDIRECTLY INFLUENCED BY GENETIC--AND EPIGENETIC--FACTORS. FOR YEARS, SCIENTISTS HAVE HELD OUT HOPE THAT THE RAPIDLY EVOLVING FIELD OF GENETICS COULD TRANSFORM MEDICAL DIAGNOSIS AND TREATMENT, MOVING BEYOND A TRIAL-AND-ERROR APPROACH TOWARDS "PERSONALIZED MEDICINE." INDEED, THERE ARE NOW SIGNS THAT THE ROLE OF GENETICS AND THE PURSUIT OF "PERSONALIZED MEDICINE" IN MEDICAL CARE WILL BE A PRIORITY FOR GOVERNMENTS DURING YEARS TO COME. BUT THE VISION OF INDIVIDUALIZED TREATMENT BASED ON A PATIENT'S GENETIC MAKEUP AND OTHER BIOLOGICAL MARKERS HAS YET TO MATERIALIZE IN THE FIELD OF CKD AND ESRD. AS THE TOXIC UREMIC ENVIRONMENT MAY RENDER CKD PATIENTS MORE SENSITIVE TO THE EFFECTS OF GENETIC VARIANTS, IT IS LIKELY THAT GENETIC FACTORS COULD BE OF SPECIAL IMPORTANCE IN THIS HIGH-RISK POPULATION. THEREFORE, OUTCOME IN THE CKD POPULATION MAY BE IMPROVED BY ESTABLISHING INDIVIDUAL GENETIC/EPIGENETIC PROFILES, THUS ENABLING PHYSICIANS TO DESIGN AN INDIVIDUALIZED THERAPEUTIC STRATEGY. PERSONALIZED MEDICINE BASED ON A MORE INDIVIDUALIZED THERAPY COULD BE APPLIED IN, FOR EXAMPLE, PHARMACOTHERAPY (CYP GENES), DIALYSIS THERAPY, AND NUTRITIONAL AND LIFESTYLE MODIFICATIONS. 2009 6 3105 33 GENOMICS AND PROTEOMICS IN LIVER FIBROSIS AND CIRRHOSIS. GENOMICS AND PROTEOMICS HAVE BECOME INCREASINGLY IMPORTANT IN BIOMEDICAL SCIENCE IN THE PAST DECADE, AS THEY PROVIDE AN OPPORTUNITY FOR HYPOTHESIS-FREE EXPERIMENTS THAT CAN YIELD MAJOR INSIGHTS NOT PREVIOUSLY FORESEEN WHEN SCIENTIFIC AND CLINICAL QUESTIONS ARE BASED ONLY ON HYPOTHESIS-DRIVEN APPROACHES. USE OF THESE TOOLS, THEREFORE, OPENS NEW AVENUES FOR UNCOVERING PHYSIOLOGICAL AND PATHOLOGICAL PATHWAYS. LIVER FIBROSIS IS A COMPLEX DISEASE PROVOKED BY A RANGE OF CHRONIC INJURIES TO THE LIVER, AMONG WHICH ARE VIRAL HEPATITIS, (NON-) ALCOHOLIC STEATOHEPATITIS AND AUTOIMMUNE DISORDERS. SOME CHRONIC LIVER PATIENTS WILL NEVER DEVELOP FIBROSIS OR CIRRHOSIS, WHEREAS OTHERS RAPIDLY PROGRESS TOWARDS CIRRHOSIS IN A FEW YEARS. THIS VARIETY CAN BE CAUSED BY DISEASE-RELATED FACTORS (FOR EXAMPLE, VIRAL GENOTYPE) OR HOST-FACTORS (GENETIC/EPIGENETIC). IT IS VITAL TO ESTABLISH ACCURATE TOOLS TO IDENTIFY THOSE PATIENTS AT HIGHEST RISK FOR DISEASE SEVERITY OR PROGRESSION IN ORDER TO DETERMINE WHO ARE IN NEED OF IMMEDIATE THERAPIES. MOREOVER, THERE IS AN URGENT IMPERATIVE TO IDENTIFY NON-INVASIVE MARKERS THAT CAN ACCURATELY DISTINGUISH MILD AND INTERMEDIATE STAGES OF FIBROSIS. IDEALLY, BIOMARKERS CAN BE USED TO PREDICT DISEASE PROGRESSION AND TREATMENT RESPONSE, BUT THESE STUDIES WILL TAKE MANY YEARS DUE TO THE REQUIREMENT FOR LENGTHY FOLLOW-UP PERIODS TO ASSESS OUTCOMES. CURRENT GENOMIC AND PROTEOMIC RESEARCH PROVIDES MANY CANDIDATE BIOMARKERS, BUT INDEPENDENT VALIDATION OF THESE BIOMARKERS IS LACKING, AND REPRODUCIBILITY IS STILL A KEY CONCERN. THUS, GREAT OPPORTUNITIES AND CHALLENGES LIE AHEAD IN THE FIELD OF GENOMICS AND PROTEOMICS, WHICH, IF SUCCESSFUL, COULD TRANSFORM THE DIAGNOSIS AND TREATMENT OF CHRONIC FIBROSING LIVER DISEASES. 2012 7 4716 42 NON-GENETIC RATS MODELS FOR ATHEROSCLEROSIS RESEARCH: FROM PAST TO PRESENT. ATHEROSCLEROSIS IS AN INFLAMMATORY, PROGRESSIVE, AND CHRONIC ILLNESS THAT INVOLVES SEVERAL MOLECULAR AND EPIGENETIC FACTORS. DESPITE TREATMENT LIMITATIONS, CLINICAL AND THERAPEUTIC APPROACHES HAVE UNDENIABLY CHANGED RADICALLY IN RECENT DECADES THROUGH BETTER KNOWLEDGE OF THE PATHOPHYSIOLOGICAL BASIS OF THE DISEASE, WHICH HAS CONSIDERABLY IMPROVED PATIENTS' SURVIVAL AND QUALITY OF LIFE. SOME OF THESE ADVANCES ARE ATTRIBUTABLE TO BASIC BIOMEDICAL RESEARCH THAT PROVIDES INSIGHTS INTO A BETTER UNDERSTANDING AND IDENTIFICATION OF NEW MOLECULAR AND CELLULAR TARGETS FOR ATHEROSCLEROSIS TREATMENT. ALTHOUGH RODENT MODELS HAVE CONTRIBUTED SUBSTANTIALLY TO A BETTER UNDERSTANDING OF THE DEVELOPMENT OF ATHEROSCLEROSIS, THE ACCURACY OF THESE MODELS REMAINS CONTROVERSIAL. RESEARCH THAT UTILIZES GENETIC RODENT MODELS IS WELL ESTABLISHED, BUT THE USE OF SPECIFIC DIETS THAT ARE ASSOCIATED WITH OTHER RISK FACTORS (E.G., HYPERTENSION, HORMONE DEPRIVATION, AND PHARMACOLOGICAL TOOLS) IS STILL DEBATABLE. THE PRESENT REVIEW PROVIDES AN UPDATE ON NON-GENETIC RAT MODELS OF ATHEROSCLEROSIS AND AN OVERVIEW OF THE MAIN METHODOLOGIES THAT ARE CURRENTLY AVAILABLE. 2019 8 5161 32 PRECISION AND PERSONALIZED MEDICINE: HOW GENOMIC APPROACH IMPROVES THE MANAGEMENT OF CARDIOVASCULAR AND NEURODEGENERATIVE DISEASE. LIFE EXPECTANCY HAS GRADUALLY GROWN OVER THE LAST CENTURY. THIS HAS DEEPLY AFFECTED HEALTHCARE COSTS, SINCE THE GROWTH OF AN AGING POPULATION IS CORRELATED TO THE INCREASING BURDEN OF CHRONIC DISEASES. THIS REPRESENTS THE INTERESTING CHALLENGE OF HOW TO MANAGE PATIENTS WITH CHRONIC DISEASES IN ORDER TO IMPROVE HEALTH CARE BUDGETS. EFFECTIVE PRIMARY PREVENTION COULD REPRESENT A PROMISING ROUTE. TO THIS END, PRECISION, TOGETHER WITH PERSONALIZED MEDICINE, ARE USEFUL INSTRUMENTS IN ORDER TO INVESTIGATE PATHOLOGICAL PROCESSES BEFORE THE APPEARANCE OF CLINICAL SYMPTOMS AND TO GUIDE PHYSICIANS TO CHOOSE A TARGETED THERAPY TO MANAGE THE PATIENT. CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES REPRESENT SUITABLE MODELS FOR TAKING FULL ADVANTAGE OF PRECISION MEDICINE TECHNOLOGIES APPLIED TO ALL STAGES OF DISEASE DEVELOPMENT. THE AVAILABILITY OF HIGH TECHNOLOGY INCORPORATING ARTIFICIAL INTELLIGENCE AND ADVANCEMENT PROGRESS MADE IN THE FIELD OF BIOMEDICAL RESEARCH HAVE BEEN SUBSTANTIAL TO UNDERSTAND HOW GENES, EPIGENETIC MODIFICATIONS, AGING, NUTRITION, DRUGS, MICROBIOME AND OTHER ENVIRONMENTAL FACTORS CAN IMPACT HEALTH AND CHRONIC DISORDERS. THE AIM OF THE PRESENT REVIEW IS TO ADDRESS HOW PRECISION AND PERSONALIZED MEDICINE CAN BRING GREATER CLARITY TO THE CLINICAL AND BIOLOGICAL COMPLEXITY OF THESE TYPES OF DISORDERS ASSOCIATED WITH HIGH MORTALITY, INVOLVING TREMENDOUS HEALTH CARE COSTS, BY DESCRIBING IN DETAIL THE METHODS THAT CAN BE APPLIED. THIS MIGHT OFFER PRECIOUS TOOLS FOR PREVENTIVE STRATEGIES AND POSSIBLE CLUES ON THE EVOLUTION OF THE DISEASE AND COULD HELP IN PREDICTING MORBIDITY, MORTALITY AND DETECTING CHRONIC DISEASE INDICATORS MUCH EARLIER IN THE DISEASE COURSE. THIS, OF COURSE, WILL HAVE A MAJOR EFFECT ON BOTH IMPROVING THE QUALITY OF CARE AND QUALITY OF LIFE OF THE PATIENTS AND REDUCING TIME EFFORTS AND HEALTHCARE COSTS. 2020 9 3169 30 GUIDE FOR CURRENT NUTRIGENETIC, NUTRIGENOMIC, AND NUTRIEPIGENETIC APPROACHES FOR PRECISION NUTRITION INVOLVING THE PREVENTION AND MANAGEMENT OF CHRONIC DISEASES ASSOCIATED WITH OBESITY. CHRONIC DISEASES, INCLUDING OBESITY, ARE MAJOR CAUSES OF MORBIDITY AND MORTALITY IN MOST COUNTRIES. THE ADVERSE IMPACTS OF OBESITY AND ASSOCIATED COMORBIDITIES ON HEALTH REMAIN A MAJOR CONCERN DUE TO THE LACK OF EFFECTIVE INTERVENTIONS FOR PREVENTION AND MANAGEMENT. PRECISION NUTRITION IS AN EMERGING THERAPEUTIC APPROACH THAT TAKES INTO ACCOUNT AN INDIVIDUAL'S GENETIC AND EPIGENETIC INFORMATION, AS WELL AS AGE, GENDER, OR PARTICULAR PHYSIOPATHOLOGICAL STATUS. ADVANCES IN GENOMIC SCIENCES ARE CONTRIBUTING TO A BETTER UNDERSTANDING OF THE ROLE OF GENETIC VARIANTS AND EPIGENETIC SIGNATURES AS WELL AS GENE EXPRESSION PATTERNS IN THE DEVELOPMENT OF DIVERSE CHRONIC CONDITIONS, AND HOW THEY MAY MODIFY THERAPEUTIC RESPONSES. THIS KNOWLEDGE HAS LED TO THE SEARCH FOR GENETIC AND EPIGENETIC BIOMARKERS TO PREDICT THE RISK OF DEVELOPING CHRONIC DISEASES AND PERSONALIZING THEIR PREVENTION AND TREATMENT. ADDITIONALLY, ORIGINAL NUTRITIONAL INTERVENTIONS BASED ON NUTRIENTS AND BIOACTIVE DIETARY COMPOUNDS THAT CAN MODIFY EPIGENETIC MARKS AND GENE EXPRESSION HAVE BEEN IMPLEMENTED. ALTHOUGH CAUTION MUST BE EXERCISED, THESE SCIENTIFIC INSIGHTS ARE PAVING THE WAY FOR THE DESIGN OF INNOVATIVE STRATEGIES FOR THE CONTROL OF CHRONIC DISEASES ACCOMPANYING OBESITY. THIS DOCUMENT PROVIDES A NUMBER OF EXAMPLES OF THE HUGE POTENTIAL OF UNDERSTANDING NUTRIGENETIC, NUTRIGENOMIC, AND NUTRIEPIGENETIC ROLES IN PRECISION NUTRITION. 2017 10 4325 33 MICRORNAS IN THE EVALUATION AND POTENTIAL TREATMENT OF LIVER DISEASES. ACUTE AND CHRONIC LIVER DISEASE CONTINUE TO RESULT IN SIGNIFICANT MORBIDITY AND MORTALITY OF PATIENTS, ALONG WITH INCREASING BURDEN ON THEIR FAMILIES, SOCIETY AND THE HEALTH CARE SYSTEM. THIS IN PART IS DUE TO INCREASED INCIDENCE OF LIVER DISEASE ASSOCIATED FACTORS SUCH AS METABOLIC SYNDROME; IMPROVED SURVIVAL OF PATIENTS WITH CHRONIC PREDISPOSING CONDITIONS SUCH AS HIV; AS WELL AS ADVANCES IN THE FIELD OF TRANSPLANTATION AND ASSOCIATED CARE LEADING TO IMPROVED SURVIVAL. THE FACT THAT ONE DISEASE CAN RESULT IN DIFFERENT MANIFESTATIONS AND OUTCOMES HIGHLIGHTS THE NEED FOR IMPROVED UNDERSTANDING OF NOT JUST GENETIC PHENOMENON PREDISPOSING TO A CONDITION, BUT ADDITIONALLY THE ROLE OF EPIGENETIC AND ENVIRONMENTAL FACTORS LEADING TO THE PHENOTYPE OF THE DISEASE. IT IS NOT SURPRISING THAT PROVIDERS CONTINUE TO FACE DAILY CHALLENGES PERTAINING TO DIAGNOSTIC ACCURACY, PROGNOSTICATION OF DISEASE SEVERITY, PROGRESSION, AND RESPONSE TO THERAPIES. A NUMBER OF THESE CHALLENGES CAN BE ADDRESSED BY INCORPORATING A PERSONALIZED APPROACH OF MANAGEMENT TO THE CURRENT PARADIGM OF CARE. RECENT ADVANCES IN THE FIELDS OF MOLECULAR BIOLOGY AND GENETICS HAVE PAVED THE WAY TO MORE ACCURATE, INDIVIDUALIZED AND PRECISE APPROACH TO CARING FOR LIVER DISEASE. THE STUDY OF MICRORNAS AND THEIR ROLE IN BOTH HEALTHY AND DISEASED LIVERS IS ONE EXAMPLE OF SUCH ADVANCES. AS THESE SMALL, NON-CODING RNAS WORK ON FINE-TUNING OF CELLULAR ACTIVITIES AND ORGAN FUNCTION IN A DYNAMIC AND PRECISE FASHION, THEY PROVIDE US A GOLDEN OPPORTUNITY TO ADVANCE THE FIELD OF HEPATOLOGY. THE STUDY OF MICRORNAS IN LIVER DISEASE PROMISES TREMENDOUS IMPROVEMENT IN HEPATOLOGY AND IS LIKELY TO LAY THE FOUNDATION TOWARDS A PERSONALIZED APPROACH IN LIVER DISEASE. 2016 11 3110 35 GENOTYPE- OR PHENOTYPE-TARGETING ANTICANCER THERAPIES? LESSONS FROM TUMOR EVOLUTIONARY BIOLOGY. DESPITE THE EFFICACY OF MOST CANCER THERAPIES, DRUG RESISTANCE REMAINS A MAJOR PROBLEM IN THE CLINIC. THE ERADICATION OF THE ENTIRE TUMOR AND THE CURE OF THE PATIENT BY CHEMOTHERAPY ALONE ARE RARE, IN PARTICULAR FOR ADVANCED DISEASE. FROM AN EVOLUTIONARY PERSPECTIVE, THE SELECTIVE PRESSURE EXERTED BY CHEMOTHERAPY LEADS TO THE EMERGENCE OF RESISTANT CLONES WHERE RESISTANCE CAN BE ASSOCIATED WITH MANY DIFFERENT FUNCTIONAL MECHANISMS AT THE SINGLE CELL LEVEL OR CAN INVOLVE CHANGES IN THE TUMOR MICRO-ENVIRONMENT. IN THE LAST DECADE, TUMOR GENOMICS HAS CONTRIBUTED TO THE IMPROVEMENT OF OUR UNDERSTANDING OF TUMORIGENESIS AND HAS LED TO THE IDENTIFICATION OF NUMEROUS CELLULAR TARGETS FOR THE DEVELOPMENT OF NOVEL THERAPIES. HOWEVER, SINCE TUMORS ARE BY NATURE EXTREMELY HETEROGENEOUS, THE DRUG EFFICACY AND ECONOMICAL SUSTAINABILITY OF THIS APPROACH IS NOW DEBATABLE. IMPORTANTLY, TUMOR CELL HETEROGENEITY DEPENDS NOT ONLY ON GENETIC MODIFICATIONS BUT ALSO ON NON-GENETIC PROCESSES INVOLVING EITHER STOCHASTIC EVENTS OR EPIGENETIC MODIFICATIONS MAKING GENETIC BIOMARKERS OF UNCERTAIN UTILITY. IN THIS REVIEW, WE WISH TO HIGHLIGHT HOW EVOLUTIONARY BIOLOGY CAN IMPACT OUR UNDERSTANDING OF CARCINOGENESIS AND RESISTANCE TO THERAPIES. WE WILL DISCUSS NEW APPROACHES BASED ON APPLIED ECOLOGY AND EVOLUTION DYNAMICS THAT CAN BE USED TO CONVERT THE CANCER INTO A CHRONIC DISEASE WHERE THE DRUGS WOULD CONTROL TUMOR GROWTH. FINALLY, WE WILL DISCUSS THE WAY METABOLIC DYSFUNCTION OR PHENOTYPIC CHANGES CAN HELP DEVELOPING NEW DELIVERY SYSTEMS OR PHENOTYPETARGETED DRUGS AND HOW EXPLORING NEW SOURCES OF ACTIVE COMPOUNDS CAN CONDUCT TO THE DEVELOPMENT OF DRUGS WITH ORIGINAL MECHANISMS OF ACTION. 2016 12 4832 30 OMICS BIOMARKERS IN OBESITY: NOVEL ETIOLOGICAL INSIGHTS AND TARGETS FOR PRECISION PREVENTION. PURPOSE OF REVIEW: OMICS-BASED TECHNOLOGIES WERE SUGGESTED TO PROVIDE AN ADVANCED UNDERSTANDING OF OBESITY ETIOLOGY AND ITS METABOLIC CONSEQUENCES. THIS REVIEW HIGHLIGHTS THE RECENT DEVELOPMENTS IN "OMICS"-BASED RESEARCH AIMED TO IDENTIFY OBESITY-RELATED BIOMARKERS. RECENT FINDINGS: RECENT ADVANCES IN OBESITY AND METABOLISM RESEARCH INCREASINGLY RELY ON NEW TECHNOLOGIES TO IDENTIFY MECHANISMS IN THE DEVELOPMENT OF OBESITY USING VARIOUS "OMICS" PLATFORMS. GENETIC AND EPIGENETIC BIOMARKERS THAT TRANSLATE INTO CHANGES IN TRANSCRIPTOME, PROTEOME, AND METABOLOME COULD SERVE AS TARGETS FOR OBESITY PREVENTION. DESPITE A NUMBER OF PROMISING CANDIDATE BIOMARKERS, THERE IS AN INCREASED DEMAND FOR LARGER PROSPECTIVE COHORT STUDIES TO VALIDATE FINDINGS AND DETERMINE BIOMARKER REPRODUCIBILITY BEFORE THEY CAN FIND APPLICATIONS IN PRIMARY CARE AND PUBLIC HEALTH. "OMICS" BIOMARKERS HAVE ADVANCED OUR KNOWLEDGE ON THE ETIOLOGY OF OBESITY AND ITS LINKS WITH CHRONIC DISEASES. THEY BRING SUBSTANTIAL PROMISE IN IDENTIFYING EFFECTIVE PUBLIC HEALTH STRATEGIES THAT PAVE THE WAY TOWARDS PATIENT STRATIFICATION AND PRECISION PREVENTION. 2020 13 3022 31 GENETICS AND EPIGENETICS PURPOSE IN NONALCOHOLIC FATTY LIVER DISEASE. INTRODUCTION: NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) COMPRISES A BROAD SPECTRUM OF DISEASES, WHICH CAN PROGRESS FROM BENIGN STEATOSIS TO NONALCOHOLIC STEATOHEPATITIS, LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA. NAFLD IS THE MOST COMMON CHRONIC LIVER DISEASE IN DEVELOPED COUNTRIES, AFFECTING APPROXIMATELY 25% OF THE GENERAL POPULATION. INSULIN RESISTANCE, ADIPOSE TISSUE DYSFUNCTION, MITOCHONDRIAL AND ENDOPLASMIC RETICULUM STRESS, CHRONIC INFLAMMATION, GENETIC AND EPIGENETIC FACTORS ARE NAFLD TRIGGERS THAT CONTROL THE DISEASE SUSCEPTIBILITY AND PROGRESSION. AREAS COVERED: IN RECENT YEARS A LARGE NUMBER OF INVESTIGATIONS HAVE BEEN CARRIED OUT TO ELUCIDATE GENETIC AND EPIGENETIC FACTORS IN THE DISEASE PATHOGENESIS, AS WELL AS THE SEARCH FOR DIAGNOSTIC MARKERS AND THERAPEUTIC TARGETS. THIS PAPER OBJECTIVE IS TO REPORT THE MOST STUDIED GENETIC AND EPIGENETIC VARIANTS AROUND NAFLD. EXPERT OPINION: NAFLD LEAD TO VARIOUS COMORBIDITIES, WHICH HAVE A CONSIDERABLE IMPACT ON THE PATIENT WELLNESS AND LIFE QUALITY, AS WELL AS ON THE COSTS THEY GENERATE FOR THE COUNTRY'S HEALTH SERVICES. IT IS ESSENTIAL TO CONTINUE WITH MOLECULAR RESEARCH, SINCE IT COULD BE USED AS A CLINICAL TOOL FOR PROGNOSIS AND DISEASE SEVERITY. SPECIFICALLY, IN THE FIELD OF HEPATOLOGY, PLASMA MIRNAS COULD PROVIDE A NOVEL TOOL IN LIVER DISEASES DIAGNOSIS AND MONITORING, REPRESENTING AN ALTERNATIVE TO INVASIVE DIAGNOSTIC PROCEDURES. 2020 14 264 29 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 15 2496 30 EPIGENETICS AND EARLY LIFE ORIGINS OF CHRONIC NONCOMMUNICABLE DISEASES. IN LIGHT OF THE INCREASING THREATS OF CHRONIC NONCOMMUNICABLE DISEASES IN DEVELOPING COUNTRIES, THE GROWING RECOGNITION OF THE EARLY LIFE ORIGINS OF CHRONIC DISEASE, AND INNOVATIVE BREAKTHROUGHS IN BIOMEDICAL RESEARCH AND TECHNOLOGY, IT IS IMPERATIVE THAT WE HARNESS CUTTING-EDGE DATA TO IMPROVE HEALTH PROMOTION AND MAINTENANCE. IT IS WELL RECOGNIZED THAT CHRONIC DISEASES ARE COMPLEX TRAITS AFFECTED BY A WIDE RANGE OF ENVIRONMENTAL AND GENETIC FACTORS; HOWEVER, THE ROLE OF EPIGENETIC FACTORS, PARTICULARLY WITH REGARD TO EARLY LIFE ORIGINS, REMAINS LARGELY UNEXPLORED. GIVEN THE UNIQUE PROPERTIES OF THE EPIGENOME-FUNCTIONALITY DURING CRITICAL TIME WINDOWS, SUCH AS THE INTRAUTERINE PERIOD, HERITABILITY, AND REVERSIBILITY-ENHANCING OUR UNDERSTANDING OF EPIGENETIC MECHANISMS MAY OFFER NEW OPPORTUNITIES FOR THE DEVELOPMENT OF NOVEL EARLY PREDICTION AND PREVENTION PARADIGMS. THIS MAY PRESENT AN UNPARALLELED OPPORTUNITY TO OFFER MATERNAL AND CHILD HEALTH PROFESSIONALS IMPORTANT TOOLS WITH THE TRANSLATIONAL VALUE TO PREDICT, DETECT, AND PREVENT DISEASE AT AN EARLY AGE, LONG BEFORE ITS CLINICAL OCCURRENCE, AND AS SUCH, BREAK LIFELONG AND TRANSGENERATIONAL CYCLES OF DISEASE. IN DOING SO, MODERN TECHNOLOGY CAN BE LEVERAGED TO MAKE GREAT CONTRIBUTIONS TO POPULATION HEALTH, QUALITY OF LIFE, AND REDUCING THE BURDENSOME ECONOMIC COSTS OF NONCOMMUNICABLE DISEASES IN DEVELOPING COUNTRIES. 2013 16 6204 34 THE INFLUENCE OF EPIGENETICS AND INFLAMMATION ON CARDIOMETABOLIC RISKS. CARDIOMETABOLIC DISEASES INCLUDE METABOLIC SYNDROME, OBESITY, TYPE 2 DIABETES MELLITUS, AND HYPERTENSION. EPIGENETIC MODIFICATIONS PARTICIPATE IN CARDIOMETABOLIC DISEASES THROUGH SEVERAL PATHWAYS, INCLUDING INFLAMMATION, VASCULAR DYSFUNCTION, AND INSULIN RESISTANCE. EPIGENETIC MODIFICATIONS, WHICH ENCOMPASS ALTERATIONS TO GENE EXPRESSION WITHOUT MUTATING THE DNA SEQUENCE, HAVE GAINED MUCH ATTENTION IN RECENT YEARS, SINCE THEY HAVE BEEN CORRELATED WITH CARDIOMETABOLIC DISEASES AND MAY BE TARGETED FOR THERAPEUTIC INTERVENTIONS. EPIGENETIC MODIFICATIONS ARE GREATLY INFLUENCED BY ENVIRONMENTAL FACTORS, SUCH AS DIET, PHYSICAL ACTIVITY, CIGARETTE SMOKING, AND POLLUTION. SOME MODIFICATIONS ARE HERITABLE, INDICATING THAT THE BIOLOGICAL EXPRESSION OF EPIGENETIC ALTERATIONS MAY BE OBSERVED ACROSS GENERATIONS. MOREOVER, MANY PATIENTS WITH CARDIOMETABOLIC DISEASES PRESENT WITH CHRONIC INFLAMMATION, WHICH CAN BE INFLUENCED BY ENVIRONMENTAL AND GENETIC FACTORS. THE INFLAMMATORY ENVIRONMENT WORSENS THE PROGNOSIS OF CARDIOMETABOLIC DISEASES AND FURTHER INDUCES EPIGENETIC MODIFICATIONS, PREDISPOSING PATIENTS TO THE DEVELOPMENT OF OTHER METABOLISM-ASSOCIATED DISEASES AND COMPLICATIONS. A DEEPER UNDERSTANDING OF INFLAMMATORY PROCESSES AND EPIGENETIC MODIFICATIONS IN CARDIOMETABOLIC DISEASES IS NECESSARY TO IMPROVE OUR DIAGNOSTIC CAPABILITIES, PERSONALIZED MEDICINE APPROACHES, AND THE DEVELOPMENT OF TARGETED THERAPEUTIC INTERVENTIONS. FURTHER UNDERSTANDING MAY ALSO ASSIST IN PREDICTING DISEASE OUTCOMES, ESPECIALLY IN CHILDREN AND YOUNG ADULTS. THIS REVIEW DESCRIBES EPIGENETIC MODIFICATIONS AND INFLAMMATORY PROCESSES UNDERLYING CARDIOMETABOLIC DISEASES, AND FURTHER DISCUSSES ADVANCES IN THE RESEARCH FIELD WITH A FOCUS ON SPECIFIC POINTS FOR INTERVENTIONAL THERAPY. 2023 17 3513 31 IDIOPATHIC PULMONARY FIBROSIS: PATHOGENESIS AND MANAGEMENT. BACKGROUND: IDIOPATHIC PULMONARY FIBROSIS (IPF) IS A CHRONIC, PROGRESSIVE DISEASE CHARACTERIZED BY THE ABERRANT ACCUMULATION OF FIBROTIC TISSUE IN THE LUNGS PARENCHYMA, ASSOCIATED WITH SIGNIFICANT MORBIDITY AND POOR PROGNOSIS. THIS REVIEW WILL PRESENT THE SUBSTANTIAL ADVANCES ACHIEVED IN THE UNDERSTANDING OF IPF PATHOGENESIS AND IN THE THERAPEUTIC OPTIONS THAT CAN BE OFFERED TO PATIENTS, AND WILL ADDRESS THE ISSUES REGARDING DIAGNOSIS AND MANAGEMENT THAT ARE STILL OPEN. MAIN BODY: OVER THE LAST TWO DECADES MUCH HAS BEEN CLARIFIED ABOUT THE PATHOGENIC PATHWAYS UNDERLYING THE DEVELOPMENT AND PROGRESSION OF THE LUNG SCARRING IN IPF. SUSTAINED ALVEOLAR EPITHELIAL MICRO-INJURY AND ACTIVATION HAS BEEN RECOGNISED AS THE TRIGGER OF SEVERAL BIOLOGICAL EVENTS OF DISORDERED REPAIR OCCURRING IN GENETICALLY SUSCEPTIBLE AGEING INDIVIDUALS. DESPITE MULTIDISCIPLINARY TEAM DISCUSSION HAS DEMONSTRATED TO INCREASE DIAGNOSTIC ACCURACY, PATIENTS CAN STILL REMAIN UNCLASSIFIED WHEN THE CURRENT DIAGNOSTIC CRITERIA ARE STRICTLY APPLIED, REQUIRING THE IDENTIFICATION OF A USUAL INTERSTITIAL PATTERN EITHER ON HIGH-RESOLUTION COMPUTED TOMOGRAPHY SCAN OR LUNG BIOPSY. OUTSTANDING ACHIEVEMENTS HAVE BEEN MADE IN THE MANAGEMENT OF THESE PATIENTS, AS NINTEDANIB AND PIRFENIDONE CONSISTENTLY PROVED TO REDUCE THE RATE OF PROGRESSION OF THE FIBROTIC PROCESS. HOWEVER, MANY UNCERTAINTIES STILL LIE IN THE CORRECT USE OF THESE DRUGS, RANGING FROM THE INITIAL CHOICE OF THE DRUG, THE APPROPRIATE TIMING FOR TREATMENT AND THE BENEFIT-RISK RATIO OF A COMBINED TREATMENT REGIMEN. SEVERAL NOVEL COMPOUNDS ARE BEING DEVELOPED IN THE PERSPECTIVE OF A MORE TARGETED THERAPEUTIC APPROACH; IN THE MEANTIME, THE SUPPORTIVE CARE OF THESE PATIENTS AND THEIR CARERS SHOULD BE APPROPRIATELY PRIORITIZED, AND GREATER EFFORTS SHOULD BE MADE TOWARD THE PROMPT IDENTIFICATION AND MANAGEMENT OF RELEVANT COMORBIDITIES. CONCLUSIONS: BUILDING ON THE ADVANCES IN THE UNDERSTANDING OF IPF PATHOBIOLOGY, THE FURTHER INVESTIGATION OF THE ROLE OF GENE VARIANTS, EPIGENETIC ALTERATIONS AND OTHER MOLECULAR BIOMARKERS REFLECTING DISEASE ACTIVITY AND BEHAVIOUR WILL HOPEFULLY ENABLE EARLIER AND MORE CONFIDENT DIAGNOSIS, IMPROVE DISEASE PHENOTYPING AND SUPPORT THE DEVELOPMENT OF NOVEL AGENTS FOR PERSONALIZED TREATMENT OF IPF. 2018 18 5025 29 PERSONALIZED MANAGEMENT OF CARDIOVASCULAR DISORDERS. PERSONALIZED MANAGEMENT OF CARDIOVASCULAR DISORDERS (CVD), ALSO REFERRED TO AS PERSONALIZED OR PRECISION CARDIOLOGY IN ACCORDANCE WITH GENERAL PRINCIPLES OF PERSONALIZED MEDICINE, IS SELECTION OF THE BEST TREATMENT FOR AN INDIVIDUAL PATIENT. IT INVOLVES THE INTEGRATION OF VARIOUS "OMICS" TECHNOLOGIES SUCH AS GENOMICS AND PROTEOMICS AS WELL AS OTHER NEW TECHNOLOGIES SUCH AS NANOBIOTECHNOLOGY. MOLECULAR DIAGNOSTICS AND BIOMARKERS ARE IMPORTANT FOR LINKING DIAGNOSIS WITH THERAPY AND MONITORING THERAPY. BECAUSE CVD INVOLVE PERTURBATIONS OF LARGE COMPLEX BIOLOGICAL NETWORKS, A SYSTEMS BIOLOGY APPROACH TO CVD RISK STRATIFICATION MAY BE USED FOR IMPROVING RISK-ESTIMATING ALGORITHMS, AND MODELING OF PERSONALIZED BENEFIT OF TREATMENT MAY BE HELPFUL FOR GUIDING THE CHOICE OF INTERVENTION. BIOINFORMATICS TOOLS ARE HELPFUL IN ANALYZING AND INTEGRATING LARGE AMOUNTS OF DATA FROM VARIOUS SOURCES. PERSONALIZED THERAPY IS CONSIDERED DURING DRUG DEVELOPMENT, INCLUDING METHODS OF TARGETED DRUG DELIVERY AND CLINICAL TRIALS. INDIVIDUALIZED RECOMMENDATIONS CONSIDER MULTIPLE FACTORS - GENETIC AS WELL AS EPIGENETIC - FOR PATIENTS' RISK OF HEART DISEASE. EXAMPLES OF PERSONALIZED TREATMENT ARE THOSE OF CHRONIC MYOCARDIAL ISCHEMIA, HEART FAILURE, AND HYPERTENSION. SIMILAR APPROACHES CAN BE USED FOR THE MANAGEMENT OF ATRIAL FIBRILLATION AND HYPERCHOLESTEROLEMIA, AS WELL AS THE USE OF ANTICOAGULANTS. PERSONALIZED MANAGEMENT INCLUDES PHARMACOTHERAPY, SURGERY, LIFESTYLE MODIFICATIONS, AND COMBINATIONS THEREOF. FURTHER PROGRESS IN UNDERSTANDING THE PATHOMECHANISM OF COMPLEX CARDIOVASCULAR DISEASES AND IDENTIFICATION OF CAUSATIVE FACTORS AT THE INDIVIDUAL PATIENT LEVEL WILL PROVIDE OPPORTUNITIES FOR THE DEVELOPMENT OF PERSONALIZED CARDIOLOGY. APPLICATION OF PRINCIPLES OF PERSONALIZED MEDICINE WILL IMPROVE THE CARE OF THE PATIENTS WITH CVD. 2017 19 2497 18 EPIGENETICS AND ENVIRONMENTAL LUNG DISEASE. GENE-ENVIRONMENT INTERACTIONS ARE THE INDISPUTABLE CAUSE OF MOST RESPIRATORY DISEASES. HOWEVER, WE STILL HAVE VERY LIMITED UNDERSTANDING OF THE MECHANISMS THAT GUIDE THESE INTERACTIONS. ALTHOUGH THE CONCEPTUAL APPROACHES TO ENVIRONMENTAL GENOMICS WERE ESTABLISHED SEVERAL DECADES AGO, THE TOOLS ARE ONLY NOW AVAILABLE TO BETTER DEFINE THE MECHANISMS THAT UNDERLIE THE INTERACTION BETWEEN THESE IMPORTANT ETIOLOGIC FEATURES OF LUNG DISEASE. EPIGENETIC MECHANISMS CAN MEDIATE THE EFFECT OF THE ENVIRONMENT ON THE HUMAN GENOME BY CONTROLLING THE TRANSCRIPTIONAL ACTIVITY OF SPECIFIC GENES, AT SPECIFIC POINTS IN TIME, IN SPECIFIC ORGANS. IN THIS ARTICLE, WE DEMONSTRATE THE POTENTIAL IMPORTANCE OF EPIGENETIC MECHANISMS IN THE DEVELOPMENT AND PROGRESSION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND ASTHMA. 2010 20 1291 28 DECODING THE ROLE OF EPIGENETICS AND GENOMICS IN PAIN MANAGEMENT. PERSISTENT PAIN IS A COSTLY EPIDEMIC, AFFECTING >50 MILLION AMERICANS WITH ESTIMATED EXPENDITURES OF >$200 BILLION ANNUALLY FOR DIRECT CARE AND LOST PRODUCTIVITY. RECENT ADVANCES IN EPIGENETIC/GENOMIC UNDERSTANDING OF PAIN AND ANALGESIC RESPONSE MAY LEAD TO IMPROVEMENTS IN PAIN MANAGEMENT AND HELP CURTAIL COSTS BY PROVIDING MORE PRECISE DETECTION OF THE PAIN MECHANISMS INVOLVED AND THEREBY MORE PERSONALIZED AND EFFECTIVE TREATMENTS. HOWEVER, THE TRANSLATION OF EPIGENETIC AND GENOMIC STRATEGIES FOR PAIN MANAGEMENT INTO CLINICAL PRACTICE WILL DEPEND ON UNDERSTANDING THEIR POTENTIAL APPLICATIONS. THE PURPOSE OF THIS ARTICLE IS TO EXAMINE CURRENT KNOWLEDGE ABOUT EPIGENETIC AND GENOMIC MECHANISMS OF PERSISTENT PAIN AND POTENTIAL OPPORTUNITIES FOR IMPROVING PAIN MANAGEMENT. THE INITIAL DISCUSSION FOCUSES ON PRESENT UNDERSTANDING OF NOCICEPTIVE PATHWAYS AND ALTERATIONS THAT LEAD TO PATHOLOGIC PAIN. THE DISCUSSION THEN MOVES TO A REVIEW OF EPIGENETIC MECHANISMS THAT HAVE BEEN IDENTIFIED IN THE TRANSITION TO AND MAINTENANCE OF PERSISTENT PAIN AS WELL AS IN THE INDIVIDUAL'S RESPONSE TO ANALGESICS. POTENTIAL APPLICATIONS OF EPIGENETICS/GENOMICS TO IDENTIFY PEOPLE AT RISK AND POSSIBLY PREVENT PERSISTENT PAIN AND GUIDE DIAGNOSIS AND THE SELECTION OF THERAPEUTIC MODALITIES ARE PRESENTED. 2013