1 2824 83 FLAVONOIDS IN BONE EROSIVE DISEASES: PERSPECTIVES IN OSTEOPOROSIS TREATMENT. IMBALANCE OF BONE HOMEOSTASIS, WITH EXCESSIVE BONE RESORPTION COMPARED WITH BONE FORMATION, LEADS TO THE DEVELOPMENT OF PROGRESSIVE OSTEOPENIA LEADING TO LOWER BONE RESISTANCE TO LOAD, WITH CONSEQUENT PAIN AND FUNCTIONAL LIMITATIONS. PHYTOCHEMICALS WITH THERAPEUTIC AND PREVENTIVE EFFECTS AGAINST BONE RESORPTION HAVE RECENTLY RECEIVED INCREASING ATTENTION SINCE THEY ARE POTENTIALLY MORE SUITABLE FOR LONG-TERM USE THAN TRADITIONAL THERAPEUTIC CHEMICAL COMPOUNDS. IN THIS SYSTEMATIC REVIEW OF THE LITERATURE OF THE PAST 5 YEARS, COMPREHENSIVE INFORMATION IS PROVIDED ON FLAVONOIDS WITH POTENTIAL ANTIRESORPTION AND PRO-OSTEOGENIC EFFECTS. IT AIMS TO HIGHLIGHT THE MOLECULAR MECHANISMS OF THESE MOLECULES, OFTEN EPIGENETIC, AND THEIR POSSIBLE PHARMACOLOGICAL USE, WHICH IS OF GREAT IMPORTANCE FOR THE PREVENTION AND TREATMENT OF OSTEOPOROSIS (OP). 2021 2 5968 61 TERPENOID TREATMENT IN OSTEOPOROSIS: THIS IS WHERE WE HAVE COME IN RESEARCH. LOWER BONE RESISTANCE TO LOAD IS DUE TO THE IMBALANCE OF BONE HOMEOSTASIS, WHERE EXCESSIVE BONE RESORPTION, COMPARED WITH BONE FORMATION, DETERMINES A PROGRESSIVE OSTEOPENIA, LEADING TO A HIGH RISK OF FRACTURES AND CONSEQUENT PAIN AND FUNCTIONAL LIMITATIONS. TERPENOIDS, WITH THEIR ACTIVITIES AGAINST BONE RESORPTION, HAVE RECENTLY RECEIVED INCREASED ATTENTION FROM RESEARCHERS. THEY ARE POTENTIALLY MORE SUITABLE FOR LONG-TERM USE COMPARED WITH TRADITIONAL THERAPEUTICS. IN THIS REVIEW OF THE LITERATURE OF THE PAST 5 YEARS, WE PROVIDE COMPREHENSIVE INFORMATION ON TERPENOIDS, WITH THEIR ANTI-OSTEOPOROTIC EFFECTS, HIGHLIGHTING MOLECULAR MECHANISMS THAT ARE OFTEN IN EPIGENETIC KEY AND A POSSIBLE PHARMACOLOGICAL USE IN OSTEOPOROSIS PREVENTION AND TREATMENT. 2021 3 2309 27 EPIGENETIC REGULATION OF CHONDROCYTES AND SUBCHONDRAL BONE IN OSTEOARTHRITIS. THE AIM OF THIS REVIEW IS TO PROVIDE AN UPDATED REVIEW OF THE EPIGENETIC FACTORS INVOLVED IN THE ONSET AND DEVELOPMENT OF OSTEOARTHRITIS (OA). OA IS A PREVALENT DEGENERATIVE JOINT DISEASE CHARACTERIZED BY CHRONIC INFLAMMATION, ECTOPIC BONE FORMATION WITHIN THE JOINT, AND PHYSICAL AND PROTEOLYTIC CARTILAGE DEGRADATION WHICH RESULT IN CHRONIC PAIN AND LOSS OF MOBILITY. AT PRESENT, NO DISEASE-MODIFYING THERAPEUTICS EXIST FOR THE PREVENTION OR TREATMENT OF THE DISEASE. RESEARCH HAS IDENTIFIED SEVERAL OA RISK FACTORS INCLUDING MECHANICAL STRESSORS, PHYSICAL ACTIVITY, OBESITY, TRAUMATIC JOINT INJURY, GENETIC PREDISPOSITION, AND AGE. RECENTLY, THERE HAS BEEN INCREASED INTEREST IN IDENTIFYING EPIGENETIC FACTORS INVOLVED IN THE PATHOGENESIS OF OA. IN THIS REVIEW, WE DETAIL SEVERAL OF THESE EPIGENETIC MODIFICATIONS WITH KNOWN FUNCTIONS IN THE ONSET AND PROGRESSION OF THE DISEASE. WE ALSO REVIEW CURRENT THERAPEUTICS TARGETING ABERRANT EPIGENETIC REGULATION AS POTENTIAL OPTIONS FOR PREVENTIVE OR THERAPEUTIC TREATMENT. 2022 4 1254 27 CURRENT PROGRESS ON THE MECHANISMS OF HYPERHOMOCYSTEINEMIA-INDUCED VASCULAR INJURY AND USE OF NATURAL POLYPHENOL COMPOUNDS. CARDIOVASCULAR DISEASE IS ONE OF THE MOST COMMON DISEASES IN THE ELDERLY POPULATION, AND ITS INCIDENCE HAS RAPIDLY INCREASED WITH THE PROLONGATION OF LIFE EXPECTANCY. HYPERHOMOCYSTEINEMIA IS AN INDEPENDENT RISK FACTOR FOR VARIOUS CARDIOVASCULAR DISEASES, INCLUDING ATHEROSCLEROSIS, AND DAMAGE TO VASCULAR FUNCTION PLAYS AN INITIAL ROLE IN ITS PATHOGENESIS. THIS REVIEW PRESENTS THE LATEST KNOWLEDGE ON THE MECHANISMS OF VASCULAR INJURY CAUSED BY HYPERHOMOCYSTEINEMIA, INCLUDING OXIDATIVE STRESS, ENDOPLASMIC RETICULUM STRESS, PROTEIN N-HOMOCYSTEINIZATION, AND EPIGENETIC MODIFICATION, AND DISCUSSES THE THERAPEUTIC TARGETS OF NATURAL POLYPHENOLS. STUDIES HAVE SHOWN THAT NATURAL POLYPHENOLS IN PLANTS CAN REDUCE HOMOCYSTEINE LEVELS AND REGULATE DNA METHYLATION BY ACTING ON OXIDATIVE STRESS AND ENDOPLASMIC RETICULUM STRESS-RELATED SIGNALING PATHWAYS, THUS IMPROVING HYPERHOMOCYSTEINEMIA-INDUCED VASCULAR INJURY. NATURAL POLYPHENOLS OBTAINED VIA DAILY DIET ARE SAFER AND HAVE MORE PRACTICAL SIGNIFICANCE IN THE PREVENTION AND TREATMENT OF CHRONIC DISEASES THAN TRADITIONAL DRUGS. 2021 5 2704 21 EXERCISE AND COLORECTAL CANCER: PREVENTION AND MOLECULAR MECHANISMS. EXERCISE AND PHYSICAL ACTIVITY HAVE BEEN SHOWN TO BE STRONGLY ASSOCIATED WITH A DECREASED INCIDENCE RATE OF VARIOUS CHRONIC DISEASES ESPECIALLY NUMEROUS HUMAN MALIGNANCIES. A HUGE NUMBER OF CLINICAL TRIALS AND META-ANALYSIS HAVE DEMONSTRATED THAT EXERCISE IS SIGNIFICANTLY EFFECTIVE IN LOWERING THE RISK OF COLORECTAL CANCER. IN ADDITION, IT IS SUGGESTED AS AN EFFECTIVE THERAPEUTIC MODALITY AGAINST THIS CANCER TYPE. THEREFORE, IN THIS REVIEW, WE WILL REVIEW COMPREHENSIBLY THE EFFECTS OF EXERCISE IN PREVENTING, TREATING, AND ALLEVIATING THE ADVERSE EFFECTS OF CONVENTIONAL THERAPEUTIC OPTIONS IN COLORECTAL CANCER. MOREOVER, THE POSSIBLE MECHANISMS UNDERLYING THE POSITIVE EFFECTS OF EXERCISE AND PHYSICAL ACTIVITY IN COLORECTAL CANCER, INCLUDING REGULATION OF INFLAMMATION, APOPTOSIS, GROWTH FACTOR AXIS, IMMUNITY, EPIGENETIC, ETC. WILL BE ALSO DISCUSSED. 2022 6 3958 28 LONG NON-CODING RNAS IN BONE METASTASIS: PROGRESSES AND PERSPECTIVES AS POTENTIAL DIAGNOSTIC AND PROGNOSTIC BIOMARKERS. IN A PRECISION MEDICINE PERSPECTIVE, AMONG THE BIOMARKERS POTENTIALLY USEFUL FOR EARLY DIAGNOSIS OF CANCERS, AS WELL AS TO DEFINE THEIR PROGNOSIS AND EVENTUALLY TO IDENTIFY NOVEL AND MORE EFFECTIVE THERAPEUTIC TARGETS, THERE ARE THE LONG NON-CODING RNAS (LNCRNAS). THE TERM LNCRNA IDENTIFIES A CLASS OF NON-CODING RNA MOLECULES INVOLVED IN THE REGULATION OF GENE EXPRESSION THAT INTERVENE AT THE TRANSCRIPTIONAL, POST-TRANSCRIPTIONAL, AND EPIGENETIC LEVEL. METASTASIS IS A NATURAL EVOLUTION OF SOME MALIGNANT TUMOURS, FREQUENTLY ENCOUNTERED IN PATIENTS WITH ADVANCED CANCERS. ONSET AND DEVELOPMENT OF METASTASIS REPRESENTS A DETRIMENTAL EVENT THAT WORSEN THE PATIENT'S PROGNOSIS BY PROFOUNDLY INFLUENCING THE QUALITY OF LIFE AND IS RESPONSIBLE FOR THE OMINOUS PROGRESSION OF THE DISEASE. DUE TO THE PECULIAR ENVIRONMENT AND THE BIOMECHANICAL PROPERTIES, BONE IS A PREFERENTIAL SITE FOR THE SECONDARY GROWTH OF BREAST, PROSTATE AND LUNG CANCERS. UNFORTUNATELY, ONLY PALLIATIVE AND PAIN THERAPIES ARE CURRENTLY AVAILABLE FOR PATIENTS WITH BONE METASTASES, WHILE NO EFFECTIVE AND DEFINITIVE TREATMENTS ARE AVAILABLE. THE UNDERSTANDING OF PATHOPHYSIOLOGICAL BASIS OF BONE METASTASIS FORMATION AND PROGRESSION, AS WELL AS THE IMPROVEMENT IN THE CLINICAL MANAGEMENT OF THE PATIENT, ARE CENTRAL BUT CHALLENGING TOPICS IN BASIC RESEARCH AND CLINICAL PRACTICE. THE IDENTIFICATION OF NEW MOLECULAR SPECIES THAT MAY HAVE A ROLE AS EARLY HALLMARKS OF THE METASTATIC PROCESS COULD OPEN THE DOOR TO THE DEFINITION OF NEW, AND MORE EFFECTIVE, THERAPEUTIC AND DIAGNOSTIC APPROACHES. NON-CODING RNAS SPECIES AND, PARTICULARLY, LNCRNAS ARE PROMISING COMPOUNDS IN THIS SETTING, AND THEIR STUDY MAY BRING TO THE IDENTIFICATION OF RELEVANT PROCESSES. IN THIS REVIEW, WE HIGHLIGHT THE ROLE OF LNCRNAS AS EMERGING MOLECULES IN MEDIATING THE FORMATION AND DEVELOPMENT OF BONE METASTASES, AS POSSIBLE BIOMARKERS FOR CANCER DIAGNOSIS AND PROGNOSIS, AND AS THERAPEUTIC TARGETS TO COUNTERACT CANCER SPREAD. 2023 7 2586 19 EPIGENETICS OF PAIN MEDIATORS. PURPOSE OF REVIEW: THE FIELD OF EPIGENETICS CONTINUES ITS INFLUENTIAL RISE AS A MEANS TO BETTER UNDERSTAND AN ORGANISM'S UNIQUE DEVELOPMENTAL IDENTITY OVER A LIFESPAN. WHEREAS A GENOME IS CONSTANT AND UNCHANGING, AN EPIGENOME IS DYNAMIC AND ALTERABLE. EPIGENETIC CHANGES ARE IN RESPONSE TO INNUMERABLE INTERNAL AND EXTERNAL INFLUENCES INCLUDING ENVIRONMENTAL CHANGES SUCH AS DIET, EXERCISE, DISEASE, TOXINS, AND STRESS. EPIGENETICS IS OF PARTICULAR INTEREST IN THE MEDICAL RESEARCH COMMUNITY BOTH FOR THE POTENTIAL TO CAUSE DISEASE AND AS A TARGET FOR THERAPEUTIC INTERVENTIONS. THIS ARTICLE PROVIDES A SUCCINCT EXPLANATION OF THE POTENTIAL FOR EPIGENETICS TO INFLUENCE THE UNDERSTANDING OF PAIN AS WELL AS A REVIEW OF RELEVANT RESEARCH ON THE TOPIC. RECENT FINDINGS: STUDIES ON EPIGENETICS AND PAIN REMAIN LARGELY PRECLINICAL AND INVESTIGATE THE THEORETICAL ABILITY OF EPIGENETICS TO ALTER THE NOCICEPTIVE PATHWAYS BOTH IN THE PERIPHERY AND CENTRALLY. SIGNIFICANT EVIDENCE NOW EXISTS FOR THE ABILITY OF EPIGENETICS TO MODIFY BROADLY CATEGORIZED PAIN TYPES, INCLUDING INFLAMMATORY, NEUROPATHIC, VISCERAL, AND CANCER RELATED. SUMMARY: BOTH PATIENTS AND PROVIDERS RECOGNIZE THAT NOVEL MEDICATIONS FOR THE TREATMENT OF BOTH ACUTE AND CHRONIC PAIN CONDITIONS ARE SORELY NEEDED. THE UNDERSTANDING OF EPIGENETICS AND ITS INFLUENCE ON NOCICEPTION REMAINS IN RELATIVE INFANCY BUT EARLY EVIDENCE IS STRONG FOR POTENTIAL THERAPEUTIC BENEFITS TO TREAT THESE CONDITIONS. 2018 8 6399 28 THE ROLES AND MECHANISMS OF ACTIONS OF VITAMIN C IN BONE: NEW DEVELOPMENTS. VITAMIN C IS AN IMPORTANT ANTIOXIDANT AND COFACTOR THAT IS INVOLVED IN THE REGULATION OF DEVELOPMENT, FUNCTION, AND MAINTENANCE OF SEVERAL CELL TYPES IN THE BODY. DEFICIENCIES IN VITAMIN C CAN LEAD TO CONDITIONS SUCH AS SCURVY, WHICH, AMONG OTHER AILMENTS, CAUSES GINGIVIA, BONE PAIN, AND IMPAIRED WOUND HEALING. THIS REVIEW EXAMINES THE FUNCTIONAL IMPORTANCE OF VITAMIN C AS IT RELATES TO THE DEVELOPMENT AND MAINTENANCE OF BONE TISSUES. ANALYSIS OF SEVERAL EPIDEMIOLOGICAL STUDIES AND GENETIC MOUSE MODELS REGARDING THE EFFECT OF VITAMIN C SHOWS A POSITIVE EFFECT ON BONE HEALTH. OVERALL, VITAMIN C EXERTS A POSITIVE EFFECT ON TRABECULAR BONE FORMATION BY INFLUENCING EXPRESSION OF BONE MATRIX GENES IN OSTEOBLASTS. RECENT STUDIES ON THE MOLECULAR PATHWAY FOR VITAMIN C ACTIONS THAT INCLUDE DIRECT EFFECTS OF VITAMIN C ON TRANSCRIPTIONAL REGULATION OF TARGET GENES BY INFLUENCING THE ACTIVITY OF TRANSCRIPTION FACTORS AND BY EPIGENETIC MODIFICATION OF KEY GENES INVOLVED IN SKELETAL DEVELOPMENT AND MAINTENANCE ARE DISCUSSED. WITH AN UNDERSTANDING OF MECHANISMS INVOLVED IN THE UPTAKE AND METABOLISM OF VITAMIN C AND KNOWLEDGE OF PRECISE MOLECULAR PATHWAYS FOR VITAMIN C ACTIONS IN BONE CELLS, IT IS POSSIBLE THAT NOVEL THERAPEUTIC STRATEGIES CAN BE DEVELOPED OR EXISTING THERAPIES CAN BE MODIFIED FOR THE TREATMENT OF OSTEOPOROTIC FRACTURES. 2015 9 6807 21 [EPIGENETICS AND PAIN]. CHRONIC PAIN AFFECTS APPROXIMATELY 20 % OF ADULTS WORLDWIDE AND IS OFTEN ASSOCIATED WITH A DECREASE IN THE QUALITY OF LIFE AND VARIOUS COMORBIDITIES. CONVENTIONAL ANALGESIC THERAPIES ARE FREQUENTLY INSUFFICIENT AND SOMETIMES LEAD TO SEVERE SIDE EFFECTS. THEREFORE, GREAT EFFORTS ARE STILL BEING MADE TO ELUCIDATE THE SIGNALLING PATHWAYS IN PAIN AND TO DEVELOP NEW, SAFE AND EFFECTIVE THERAPIES. EPIGENETIC MECHANISMS WHICH INTERFERE WITH THE REGULATION OF GENE EXPRESSION ARE INVOLVED IN THE PATHOGENESIS OF SEVERAL DISEASES AND ARE GAINING INCREASING IMPETUS IN MEDICAL RESEARCH. AS THEY ARE ALSO INVOLVED IN PAIN PROCESSING, A MODULATION OF THESE MECHANISMS MIGHT REPRESENT A NOVEL OPTION FOR THE THERAPY OF PAIN PATIENTS. 2014 10 3801 28 INTERPLAY OF VITAMIN D AND SIRT1 IN TISSUE-SPECIFIC METABOLISM-POTENTIAL ROLES IN PREVENTION AND TREATMENT OF NON-COMMUNICABLE DISEASES INCLUDING CANCER. THE IMPORTANCE OF THE PREVENTION AND CONTROL OF NON-COMMUNICABLE DISEASES, INCLUDING OBESITY, METABOLIC SYNDROME, TYPE 2 DIABETES, CARDIOVASCULAR DISEASES, AND CANCER, IS INCREASING AS A REQUIREMENT OF THE AGING POPULATION IN DEVELOPED COUNTRIES AND THE SUSTAINABILITY OF HEALTHCARE. SIMILARLY, THE 2013-2030 ACTION PLAN OF THE WHO FOR THE PREVENTION AND CONTROL OF NON-COMMUNICABLE DISEASES SEEKS THESE ACHIEVEMENTS. ADEQUATE LIFESTYLE CHANGES, ALONE OR WITH THE NECESSARY TREATMENTS, COULD REDUCE THE RISK OF MORTALITY OR THE DETERIORATION OF QUALITY OF LIFE. IN OUR RECENT WORK, WE SUMMARIZED THE ROLE OF TWO CENTRAL FACTORS, I.E., APPROPRIATE LEVELS OF VITAMIN D AND SIRT1, WHICH ARE CONNECTED TO ADEQUATE LIFESTYLES WITH BENEFICIAL EFFECTS ON THE PREVENTION AND CONTROL OF NON-COMMUNICABLE DISEASES. BOTH OF THESE FACTORS HAVE RECEIVED INCREASED ATTENTION IN RELATION TO THE COVID-19 PANDEMIC AS THEY BOTH TAKE PART IN REGULATION OF THE MAIN METABOLIC PROCESSES, I.E., LIPID/GLUCOSE/ENERGY HOMEOSTASIS, OXIDATIVE STRESS, REDOX BALANCE, AND CELL FATE, AS WELL AS IN THE HEALTHY REGULATION OF THE IMMUNE SYSTEM. VITAMIN D AND SIRT1 HAVE DIRECT AND INDIRECT INFLUENCE OF THE REGULATION OF TRANSCRIPTION AND EPIGENETIC CHANGES AND ARE RELATED TO CYTOPLASMIC SIGNALING PATHWAYS SUCH AS PLC/DAG/IP3/PKC/MAPK, MEK/ERK, INSULIN/MTOR/CELL GROWTH, PROLIFERATION; LEPTIN/PI3K-AKT-MTORC1, AKT/NFKB/COX-2, NFKB/TNFALPHA, IL-6, IL-8, IL-1BETA, AND AMPK/PGC-1ALPHA/GLUT4, AMONG OTHERS. THROUGH THEIR PROPER REGULATION, THEY MAINTAIN NORMAL BODY WEIGHT, LIPID PROFILE, INSULIN SECRETION AND SENSITIVITY, BALANCE BETWEEN THE PRO- AND ANTI-INFLAMMATORY PROCESSES UNDER NORMAL CONDITIONS AND INFECTIONS, MAINTAIN ENDOTHELIAL HEALTH; BALANCE CELL DIFFERENTIATION, PROLIFERATION, AND FATE; AND BALANCE THE CIRCADIAN RHYTHM OF THE CELLULAR METABOLISM. THE ROLE OF THESE TWO MOLECULES IS INTERCONNECTED IN THE MOLECULAR NETWORK, AND THEY REGULATE EACH OTHER IN SEVERAL LAYERS OF THE HOMEOSTASIS OF ENERGY AND THE CELLULAR METABOLISM. BOTH HAVE A CENTRAL ROLE IN THE MAINTENANCE OF HEALTHY AND BALANCED IMMUNE REGULATION AND REDOX REACTIONS; THEREFORE, THEY COULD CONSTITUTE PROMISING TARGETS EITHER FOR PREVENTION OR AS COMPLEMENTARY THERAPIES TO ACHIEVE A BETTER QUALITY OF LIFE, AT ANY AGE, FOR HEALTHY PEOPLE AND PATIENTS UNDER CHRONIC CONDITIONS. 2023 11 1258 23 CURRENT UNDERSTANDING OF OSTEOARTHRITIS PATHOGENESIS AND RELEVANT NEW APPROACHES. OSTEOARTHRITIS (OA) IS THE MOST COMMON DEGENERATIVE JOINT DISEASE THAT CAUSES PAINFUL SWELLING AND PERMANENT DAMAGE TO THE JOINTS IN THE BODY. THE MOLECULAR MECHANISMS OF OA ARE CURRENTLY UNKNOWN. OA IS A HETEROGENEOUS DISEASE THAT AFFECTS THE ENTIRE JOINT, AND MULTIPLE TISSUES ARE ALTERED DURING OA DEVELOPMENT. TO BETTER UNDERSTAND THE PATHOLOGICAL MECHANISMS OF OA, NEW APPROACHES, METHODS, AND TECHNIQUES NEED TO BE USED TO UNDERSTAND OA PATHOGENESIS. IN THIS REVIEW, WE FIRST FOCUS ON THE EPIGENETIC REGULATION OF OA, WITH A PARTICULAR FOCUS ON DNA METHYLATION, HISTONE MODIFICATION, AND MICRORNA REGULATION, FOLLOWED BY A SUMMARY OF SEVERAL KEY MEDIATORS IN OA-ASSOCIATED PAIN. WE THEN INTRODUCE SEVERAL INNOVATIVE TECHNIQUES THAT HAVE BEEN AND WILL CONTINUE TO BE USED IN THE FIELDS OF OA AND OA-ASSOCIATED PAIN, SUCH AS CRISPR, SCRNA SEQUENCING, AND LINEAGE TRACING. NEXT, WE DISCUSS THE TIMELY UPDATES CONCERNING CELL DEATH REGULATION IN OA PATHOLOGY, INCLUDING PYROPTOSIS, FERROPTOSIS, AND AUTOPHAGY, AS WELL AS THEIR INDIVIDUAL ROLES IN OA AND POTENTIAL MOLECULAR TARGETS IN TREATING OA. FINALLY, OUR REVIEW HIGHLIGHTS NEW DIRECTIONS ON THE ROLE OF THE SYNOVIAL LYMPHATIC SYSTEM IN OA. AN IMPROVED UNDERSTANDING OF OA PATHOGENESIS WILL AID IN THE DEVELOPMENT OF MORE SPECIFIC AND EFFECTIVE THERAPEUTIC INTERVENTIONS FOR OA. 2022 12 3108 18 GENOMICS OF PAIN IN OSTEOARTHRITIS. OSTEOARTHRITIS (OA) ACCOUNTS FOR THE MAJORITY OF THE DISEASE BURDEN FOR MUSCULOSKELETAL DISORDERS AND IS ONE OF THE LEADING CAUSES OF DISABILITY WORLDWIDE. THIS DISABILITY IS THE RESULT NOT OF THE CARTILAGE LOSS THAT DEFINES OA RADIOGRAPHICALLY, BUT OF THE CHRONIC PAIN WHOSE PRESENCE DEFINES SYMPTOMATIC OA. IT IS BECOMING CLEAR THAT MANY GENES, EACH WITH A SMALL EFFECT SIZE, CONTRIBUTE TO THE RISK OF DEVELOPING OA. HOWEVER, THE GENETICS OF OA PAIN ARE ONLY JUST STARTING TO BE EXPLORED. THIS REVIEW WILL DESCRIBE THE FIRST GENES TO HAVE BEEN IDENTIFIED IN GENOMIC STUDIES OF OA PAIN, AS WELL AS THE POSSIBLE DUAL ROLES OF GENES PREVIOUSLY IDENTIFIED IN GENOMIC STUDIES OF OA IN THE CONTEXT OF PAIN. DIFFICULTIES ASSOCIATED WITH ATTEMPTING TO CHARACTERISE THE GENETICS OF OA PAIN WILL BE DISCUSSED AND PROMISING FUTURE AVENUES OF RESEARCH INTO GENETIC AND EPIGENETIC FACTORS AFFECTING OA PAIN DESCRIBED. 2013 13 3404 23 HOW EPIGENETICS IMPACTS ON HUMAN DISEASES. EPIGENETICS IS A RAPIDLY GROWING FIELD OF BIOLOGY THAT STUDIES THE CHANGES IN GENE EXPRESSION THAT ARE NOT DUE TO ALTERATIONS IN THE DNA SEQUENCE BUT RATHER THE CHEMICAL MODIFICATIONS OF DNA AND ITS ASSOCIATED PROTEINS. EPIGENETIC MECHANISMS CAN PROFOUNDLY INFLUENCE GENE EXPRESSION, CELL DIFFERENTIATION, TISSUE DEVELOPMENT, AND DISEASE SUSCEPTIBILITY. UNDERSTANDING EPIGENETIC CHANGES IS ESSENTIAL TO ELUCIDATE THE MECHANISMS UNDERLYING THE INCREASINGLY RECOGNIZED ROLE OF ENVIRONMENTAL AND LIFESTYLE FACTORS IN HEALTH AND DISEASE AND THE INTERGENERATIONAL TRANSMISSION OF PHENOTYPES. RECENT STUDIES SUGGEST EPIGENETICS MAY BE CRITICAL IN VARIOUS DISEASES, FROM CARDIOVASCULAR DISEASE AND CANCER TO NEURODEVELOPMENTAL AND NEURODEGENERATIVE DISORDERS. EPIGENETIC MODIFICATIONS ARE POTENTIALLY REVERSIBLE AND COULD PROVIDE NEW THERAPEUTIC AVENUES FOR TREATING THESE DISEASES USING EPIGENETIC MODULATORS. MOREOVER, EPIGENETICS PROVIDE INSIGHT INTO DISEASE PATHOGENESIS AND BIOMARKERS FOR DISEASE DIAGNOSIS AND RISK STRATIFICATION. NEVERTHELESS, EPIGENETIC INTERVENTIONS HAVE THE POTENTIAL FOR UNINTENDED CONSEQUENCES AND MAY POTENTIALLY LEAD TO INCREASED RISKS OF UNEXPECTED OUTCOMES, SUCH AS ADVERSE DRUG REACTIONS, DEVELOPMENTAL ABNORMALITIES, AND CANCER. THEREFORE, RIGOROUS STUDIES ARE ESSENTIAL TO MINIMIZE THE RISKS ASSOCIATED WITH EPIGENETIC THERAPIES AND TO DEVELOP SAFE AND EFFECTIVE INTERVENTIONS FOR IMPROVING HUMAN HEALTH. THIS ARTICLE PROVIDES A SYNTHETIC AND HISTORICAL VIEW OF THE ORIGIN OF EPIGENETICS AND SOME OF THE MOST RELEVANT ACHIEVEMENTS. 2023 14 5038 19 PHARMACOGENETICS OF CHRONIC PAIN AND ITS TREATMENT. THIS PAPER REVIEWS THE IMPACT OF GENETIC VARIABILITY OF DRUG METABOLIZING ENZYMES, TRANSPORTERS, RECEPTORS, AND PATHWAYS INVOLVED IN CHRONIC PAIN PERCEPTION ON THE EFFICACY AND SAFETY OF ANALGESICS AND OTHER DRUGS USED FOR CHRONIC PAIN TREATMENT. SEVERAL CANDIDATE GENES HAVE BEEN IDENTIFIED IN THE LITERATURE, WHILE THERE IS USUALLY ONLY LIMITED CLINICAL EVIDENCE SUBSTANTIATING FOR THE PENETRATION OF THE TESTING FOR THESE CANDIDATE BIOMARKERS INTO THE CLINICAL PRACTICE. FURTHER, THE PAIN-PERCEPTION REGULATION AND MODULATION ARE STILL NOT FULLY UNDERSTOOD, AND THUS MORE COMPLEX KNOWLEDGE OF GENETIC AND EPIGENETIC BACKGROUND FOR ANALGESIA WILL BE NEEDED PRIOR TO THE CLINICAL USE OF THE CANDIDATE GENETIC BIOMARKERS. 2013 15 6913 18 [VARIOUS PATHWAYS LEADING TO THE PROGRESSION OF CHRONIC LIVER DISEASES]. AS THE RESULT OF VARIOUS EFFECTS (VIRUSES, METABOLIC DISEASES, NUTRITIONAL FACTORS, TOXIC AGENTS, AUTOIMMUNE PROCESSES) ABNORMAL LIVER FUNCTION, LIVER STEATOSIS AND CONNECTIVE TISSUE REMODELING MAY DEVELOP. PROGRESSION OF THIS PROCESS IS COMPLEX INCLUDING VARIOUS PATHWAYS AND A NUMBER OF FACTORS. THE AUTHORS SUMMARIZE THE FACTORS INVOLVED IN THE PROGRESSION OF CHRONIC LIVER DISEASE. THEY DESCRIBE THE ROLE OF CELLS AND THE PRODUCED INFLAMMATORY MEDIATORS AND CYTOKINES, AS WELL AS THE RELATIONSHIP BETWEEN THE DISEASE AND THE INTESTINAL FLORA. THEY EMPHASIZE THE ROLE OF OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION AND CELL DEATH IN DISEASE PROGRESSION. INSULIN RESISTANCE AND MICRO-ELEMENTS (IRON, COPPER) IN RELATION TO LIVER DAMAGE ARE ALSO DISCUSSED, AND GENETIC AND EPIGENETIC ASPECTS UNDERLYING DISEASE PROGRESSION ARE SUMMARIZED. DISCOVERY OF NOVEL TREATMENT OPTIONS, ASSESSMENT OF THE EFFECTIVENESS OF TREATMENT, AS WELL AS THE SUCCESS AND PROPER TIMING OF LIVER TRANSPLANTATION MAY DEPEND ON A BETTER UNDERSTANDING OF THE PROCESS OF DISEASE PROGRESSION. 2016 16 1405 22 DIETARY FACTORS AND EPIGENETIC REGULATION FOR PROSTATE CANCER PREVENTION. THE ROLE OF EPIGENETIC ALTERATIONS IN VARIOUS HUMAN CHRONIC DISEASES HAS GAINED INCREASING ATTENTION AND HAS RESULTED IN A PARADIGM SHIFT IN OUR UNDERSTANDING OF DISEASE SUSCEPTIBILITY. IN THE FIELD OF CANCER RESEARCH, E.G., GENETIC ABNORMALITIES/MUTATIONS HISTORICALLY WERE VIEWED AS PRIMARY UNDERLYING CAUSES; HOWEVER, EPIGENETIC MECHANISMS THAT ALTER GENE EXPRESSION WITHOUT AFFECTING DNA SEQUENCE ARE NOW RECOGNIZED AS BEING OF EQUAL OR GREATER IMPORTANCE FOR ONCOGENESIS. METHYLATION OF DNA, MODIFICATION OF HISTONES, AND INTERFERING MICRORNA (MIRNA) COLLECTIVELY REPRESENT A CADRE OF EPIGENETIC ELEMENTS DYSREGULATED IN CANCER. TARGETING THE EPIGENOME WITH COMPOUNDS THAT MODULATE DNA METHYLATION, HISTONE MARKS, AND MIRNA PROFILES REPRESENTS AN EVOLVING STRATEGY FOR CANCER CHEMOPREVENTION, AND THESE APPROACHES ARE STARTING TO SHOW PROMISE IN HUMAN CLINICAL TRIALS. ESSENTIAL MICRONUTRIENTS SUCH AS FOLATE, VITAMIN B-12, SELENIUM, AND ZINC AS WELL AS THE DIETARY PHYTOCHEMICALS SULFORAPHANE, TEA POLYPHENOLS, CURCUMIN, AND ALLYL SULFUR COMPOUNDS ARE AMONG A GROWING LIST OF AGENTS THAT AFFECT EPIGENETIC EVENTS AS NOVEL MECHANISMS OF CHEMOPREVENTION. TO ILLUSTRATE THESE CONCEPTS, THE CURRENT REVIEW HIGHLIGHTS THE INTERACTIONS AMONG NUTRIENTS, EPIGENETICS, AND PROSTATE CANCER SUSCEPTIBILITY. IN PARTICULAR, WE FOCUS ON EPIGENETIC DYSREGULATION AND THE IMPACT OF SPECIFIC NUTRIENTS AND FOOD COMPONENTS ON DNA METHYLATION AND HISTONE MODIFICATIONS THAT CAN ALTER GENE EXPRESSION AND INFLUENCE PROSTATE CANCER PROGRESSION. 2011 17 5109 27 POLYPHENOL-RELATED EPIGENETIC MODIFICATIONS IN OSTEOARTHRITIS: CURRENT THERAPEUTIC PERSPECTIVES. THE HYALINE CARTILAGE IS AN AVASCULAR, ANEURAL AND ALYMPHATIC TISSUE WITH A LIMITED ABILITY TO REPAIR ITSELF. WHEN THE CARTILAGE IS EXPOSED TO SOME KIND OF INJURY, IT USUALLY TRIGGERS OSTEOARTHRITIS (OA), A PREVALENT AND DEGENERATIVE JOINT DISEASE CLOSELY RELATED TO AGING. OA IS BOTH COMPLEX AND MULTIFACTORIAL, AND IS THE MOST COMMON FORM OF ARTHRITIS, BEING POSITIONED AS A MAJOR CAUSE OF PAIN AND DYSFUNCTION IN THE WORLD. IN ADDITION, HIGH OA PREVALENCE CAN GREATLY AFFECT WORK CAPACITY, MAKING THIS DISEASE A SIGNIFICANT SOCIAL PROBLEM, THEREFORE, ITS PREVENTION AND TREATMENT BECOMES A PRIORITY. AT THIS TIME, THERE ARE NUMEROUS THERAPEUTIC STRATEGIES AVAILABLE TO IMPROVE HYALINE CARTILAGE REPAIR BY USING CHONDROCYTES OR MESENCHYMAL CELLS, BUT NEITHER IS EFFECTIVE ENOUGH TO GENERATE FUNCTIONAL AND DURABLE TISSUE REPARATION OVER TIME. IN OA, CHONDROCYTES HAVE AN ABERRANT GENE EXPRESSION AND PHENOTYPE, RESULTING IN A LOSS OF BALANCE BETWEEN ANABOLIC AND CATABOLIC PROCESSES. ENVIRONMENTAL INFLUENCES SUCH AS RADIATION, INFECTION, SMOKING, NUTRIENTS, TOXINS AND STRESS CAN AFFECT GENE EXPRESSION PATTERNS, WHICH MAY CONSTITUTE RISK FACTORS FOR VARIOUS CHRONIC AND DEGENERATIVE DISEASES, SUCH AS OA. IN ADDITION, CONSIDERABLE EVIDENCE SHOWS THAT EPIGENETIC MECHANISMS PLAY AN IMPORTANT ROLE IN OA CHONDROGENESIS AND PATHOGENESIS. NATURAL PLANT-DERIVED PRODUCTS SUCH AS POLYPHENOLS, WHICH ARE SECONDARY METABOLITES CONSIDERED TO HAVE POTENTIAL ACTIVITY TO BLOCK INFLAMMATION IN SEVERAL DEGENERATIVE DISEASES, CAN STIMULATE EPIGENETIC MODIFICATIONS, AND MAY PROVIDE NEW THERAPEUTIC TARGETS AND COST-EFFECTIVE TREATMENTS. THIS REVIEW AIMS TO PRESENT VARIOUS POLYPHENOLBASED THERAPIES CURRENTLY USED FOR THE TREATMENT OF SEVERAL PROGRESSIVE DISEASES, INCLUDING OA. 2016 18 3593 27 IMPLICATION OF THE MEDITERRANEAN DIET ON THE HUMAN EPIGENOME. EPIGENETICS, DEFINED AS "HEREDITARY CHANGES IN GENE EXPRESSION THAT OCCUR WITHOUT ANY CHANGE IN THE DNA SEQUENCE", CONSISTS OF VARIOUS EPIGENETIC MARKS, INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS, AND NON-CODING RNAS. THE EPIGENOME, WHICH HAS A DYNAMIC STRUCTURE IN RESPONSE TO INTRACELLULAR AND EXTRACELLULAR STIMULI, HAS A KEY ROLE IN THE CONTROL OF GENE ACTIVITY, SINCE IT IS LOCATED AT THE INTERSECTION OF CELLULAR INFORMATION ENCODED IN THE GENOME AND MOLECULAR/CHEMICAL INFORMATION OF EXTRACELLULAR ORIGIN. THE FOCUS SHIFT OF STUDIES TO EPIGENETIC REPROGRAMMING HAS LED TO THE FORMATION AND PROGRESSIVE IMPORTANCE OF A CONCEPT CALLED "NUTRIEPIGENETICS", WHOSE AIM IS TO PREVENT DISEASES BY INTERVENING ON NUTRITION STYLE. AMONG THE DIET TYPES ADOPTED IN THE WORLD, THE RENOWNED MEDITERRANEAN DIET (MD), BEING RICH IN UNSATURATED FATTY ACIDS AND CONTAINING HIGH LEVELS OF WHOLE GRAIN FOODS AND LARGE QUANTITIES OF FRUITS, VEGETABLES, AND LEGUMES, HAS SHOWN NUMEROUS ADVANTAGES IN EXCLUDING CHRONIC DISEASES. ADDITIONALLY, THE FACT THAT THIS DIET IS RICH IN POLYPHENOLS WITH HIGH ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES HAS AN UNDENIABLE EFFECT IN TURNING SOME CELLULAR PATHWAYS AGAINST THE DISEASE. IT IS ALSO APPARENT THAT THE EFFECTS OF POLYPHENOLS ON THE EPIGENOME CAUSE CHANGES IN MECHANISMS SUCH AS DNA METHYLATION AND HISTONE ACETYLATION/DEACETYLATION, WHICH HAVE A REGULATORY EFFECT ON GENE REGULATION. THIS REVIEW PRESENTS THE EFFECTS OF LONG-TERM CONSUMPTION OF NUTRIENTS FROM THE MD ON THE EPIGENOME AND DISCUSSES THE BENEFITS OF THIS DIET IN THE TREATMENT AND EVEN PREVENTION OF CHRONIC DISEASES. 2022 19 2049 20 EPIGENETIC CODE AND POTENTIAL EPIGENETIC-BASED THERAPIES AGAINST CHRONIC DISEASES IN DEVELOPMENTAL ORIGINS. ACCUMULATED FINDINGS HAVE DEMONSTRATED THAT THE EPIGENETIC CODE PROVIDES A POTENTIAL LINK BETWEEN PRENATAL STRESS AND CHANGES IN GENE EXPRESSION THAT COULD BE INVOLVED IN THE DEVELOPMENTAL PROGRAMMING OF VARIOUS CHRONIC DISEASES IN LATER LIFE. MEANWHILE, BASED ON THE FACT THAT EPIGENETIC MODIFICATIONS ARE REVERSIBLE AND CAN BE MANIPULATED, THIS PROVIDES A UNIQUE CHANCE TO DEVELOP MULTIPLE NOVEL EPIGENETIC-BASED THERAPEUTIC STRATEGIES AGAINST MANY CHRONIC DISEASES IN EARLY DEVELOPMENTAL PERIODS. THIS ARTICLE WILL GIVE A SHORT REVIEW OF RECENT FINDINGS OF PRENATAL INSULT-INDUCED EPIGENETIC CHANGES IN DEVELOPMENTAL ORIGINS OF SEVERAL CHRONIC DISEASES, AND WILL ATTEMPT TO PROVIDE AN OVERVIEW OF THE CURRENT EPIGENETIC-BASED STRATEGIES APPLIED IN THE EARLY PREVENTION, DIAGNOSIS AND POSSIBLE THERAPIES FOR HUMAN CHRONIC DISEASES. 2014 20 2333 19 EPIGENETIC REGULATION OF INFLAMMATION: THE METABOLOMICS CONNECTION. EPIGENETIC FACTORS ARE CONSIDERED THE REGULATOR OF COMPLEX MACHINERY BEHIND INFLAMMATORY DISORDERS AND SIGNIFICANTLY CONTRIBUTED TO THE EXPRESSION OF INFLAMMATION-ASSOCIATED GENES. EPIGENETIC MODIFICATIONS MODULATE VARIATION IN THE EXPRESSION PATTERN OF TARGET GENES WITHOUT AFFECTING THE DNA SEQUENCE. THE CURRENT KNOWLEDGE OF EPIGENETIC RESEARCH FOCUSED ON THEIR ROLE IN THE PATHOGENESIS OF VARIOUS INFLAMMATORY DISEASES THAT CAUSES MORBIDITY AND MORTALITY WORLDWIDE. INFLAMMATORY DISEASES ARE CATEGORIZED AS ACUTE AND CHRONIC BASED ON THE DISEASE SEVERITY AND ARE REGULATED BY THE EXPRESSION PATTERN OF VARIOUS GENES. HENCE, UNDERSTANDING THE ROLE OF EPIGENETIC MODIFICATIONS DURING INFLAMMATION PROGRESSION WILL CONTRIBUTE TO THE DISEASE OUTCOMES AND THERAPEUTIC APPROACHES. THIS REVIEW ALSO FOCUSES ON THE METABOLOMICS APPROACH ASSOCIATED WITH THE STUDY OF INFLAMMATORY DISORDERS. INFLAMMATORY RESPONSES AND METABOLIC REGULATION ARE HIGHLY INTEGRATED AND VARIOUS ADVANCED TECHNIQUES ARE ADOPTED TO STUDY THE METABOLIC SIGNATURE MOLECULES. HERE WE DISCUSS SEVERAL METABOLOMICS APPROACHES USED TO LINK INFLAMMATORY DISORDERS AND EPIGENETIC CHANGES. WE PROPOSED THAT DECIPHERING THE MECHANISM BEHIND THE INFLAMMATION-METABOLISM LOOP MAY HAVE IMMENSE IMPORTANCE IN BIOMARKERS RESEARCH AND MAY ACT AS A PRINCIPAL COMPONENT IN DRUG DISCOVERY AS WELL AS THERAPEUTIC APPLICATIONS. 2022