1  3750 92 INSULIN RESISTANCE IN POLYCYSTIC OVARY SYNDROME ACROSS VARIOUS TISSUES: AN UPDATED REVIEW OF PATHOGENESIS, EVALUATION, AND TREATMENT. POLYCYSTIC OVARY SYNDROME (PCOS) IS A COMMON ENDOCRINE DISORDER CHARACTERIZED BY CHRONIC OVULATION DYSFUNCTION AND OVERABUNDANCE OF ANDROGENS; IT AFFECTS 6-20% OF WOMEN OF REPRODUCTIVE AGE. PCOS INVOLVES VARIOUS PATHOPHYSIOLOGICAL FACTORS, AND AFFECTED WOMEN USUALLY HAVE SIGNIFICANT INSULIN RESISTANCE (IR), WHICH IS A MAJOR CAUSE OF PCOS. IR AND COMPENSATORY HYPERINSULINAEMIA HAVE DIFFERING PATHOGENESES IN VARIOUS TISSUES, AND IR VARIES AMONG DIFFERENT PCOS PHENOTYPES. GENETIC AND EPIGENETIC CHANGES, HYPERANDROGENAEMIA, AND OBESITY AGGRAVATE IR. INSULIN SENSITIZATION DRUGS ARE A NEW TREATMENT MODALITY FOR PCOS. WE SEARCHED PUBMED, GOOGLE SCHOLAR, ELSEVIER, AND UPTODATE DATABASES IN THIS REVIEW, AND FOCUSED ON THE PATHOGENESIS OF IR IN WOMEN WITH PCOS AND THE PATHOPHYSIOLOGY OF IR IN VARIOUS TISSUES. IN ADDITION, THE REVIEW PROVIDES A COMPREHENSIVE OVERVIEW OF THE CURRENT PROGRESS IN THE EFFICACY OF INSULIN SENSITIZATION THERAPY IN THE MANAGEMENT OF PCOS, PROVIDING THE LATEST EVIDENCE FOR THE CLINICAL TREATMENT OF WOMEN WITH PCOS AND IR.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
2  6713 30 VISCERAL ADIPOSITY SYNDROME. THE ASSOCIATION OF ANTHROPOMETRIC (WAIST CIRCUMFERENCE) AND HEMODYNAMIC (BLOOD PRESSURE) CHANGES WITH ABNORMALITIES IN GLUCOSE AND LIPID METABOLISM HAS BEEN MOTIVATION FOR A LOT OF DISCUSSIONS IN THE LAST 30 YEARS. NOWADAYS, BLOOD PRESSURE, BODY MASS INDEX/ABDOMINAL CIRCUMFERENCE, GLYCEMIA, TRIGLYCERIDEMIA, AND HDL-CHOLESTEROL CONCENTRATIONS ARE CONSIDERED IN THE DEFINITION OF METABOLIC SYNDROME, REFERRED AS VISCERAL ADIPOSITY SYNDROME (VAS) IN THE PRESENT REVIEW. HOWEVER, MORE THAN 250 YEARS AGO AN ASSOCIATION BETWEEN VISCERAL AND MEDIASTINAL OBESITY WITH HYPERTENSION, GOUT, AND OBSTRUCTIVE APNEA HAD ALREADY BEEN RECOGNIZED. EXPANSION OF VISCERAL ADIPOSE TISSUE SECONDARY TO CHRONIC OVER-CONSUMPTION OF CALORIES STIMULATES THE RECRUITMENT OF MACROPHAGES, WHICH ASSUME AN INFLAMMATORY PHENOTYPE AND PRODUCE CYTOKINES THAT DIRECTLY INTERFERE WITH INSULIN SIGNALING, RESULTING IN INSULIN RESISTANCE. IN TURN, INSULIN RESISTANCE (IR) MANIFESTS ITSELF IN VARIOUS TISSUES, CONTRIBUTING TO THE OVERALL PHENOTYPE OF VAS. FOR EXAMPLE, IN WHITE ADIPOSE TISSUE, IR RESULTS IN LIPOLYSIS, INCREASED FREE FATTY ACIDS RELEASE AND WORSENING OF INFLAMMATION, SINCE FATTY ACIDS CAN BIND TO TOLL-LIKE RECEPTORS. IN THE LIVER, IR RESULTS IN INCREASED HEPATIC GLUCOSE PRODUCTION, CONTRIBUTING TO HYPERGLYCEMIA; IN THE VASCULAR ENDOTHELIUM AND KIDNEY, IR RESULTS IN VASOCONSTRICTION, SODIUM RETENTION AND, CONSEQUENTLY, ARTERIAL HYPERTENSION. OTHER PLAYERS HAVE BEEN RECOGNIZED IN THE DEVELOPMENT OF VAS, SUCH AS GENETIC PREDISPOSITION, EPIGENETIC FACTORS ASSOCIATED WITH EXPOSURE TO AN UNFAVOURABLE INTRAUTERINE ENVIRONMENT AND THE GUT MICROBIOTA. MORE RECENTLY, EXPERIMENTAL AND CLINICAL STUDIES HAVE SHOWN THE AUTONOMIC NERVOUS SYSTEM PARTICIPATES IN MODULATING VISCERAL ADIPOSE TISSUE. THE SYMPATHETIC NERVOUS SYSTEM IS RELATED TO ADIPOSE TISSUE FUNCTION AND DIFFERENTIATION THROUGH BETA1, BETA2, BETA3, ALPHA1, AND ALPHA2 ADRENERGIC RECEPTORS. THE RELATION IS BIDIRECTIONAL: SYMPATHETIC DENERVATION OF ADIPOSE TISSUE BLOCKS LIPOLYSIS TO A VARIETY OF LIPOLYTIC STIMULI AND ADIPOSE TISSUE SEND INPUTS TO THE BRAIN. AN IMBALANCE OF SYMPATHETIC/PARASYMPATHETIC AND ALPHA2 ADRENERGIC/BETA3 RECEPTOR IS RELATED TO VISCERAL ADIPOSE TISSUE STORAGE AND INSULIN SENSITIVITY. THUS, IN ADDITION TO THE WELL-KNOWN FACTORS CLASSICALLY ASSOCIATED WITH VAS, ABNORMAL AUTONOMIC ACTIVITY ALSO EMERGES AS AN IMPORTANT FACTOR REGULATING WHITE ADIPOSE TISSUE, WHICH HIGHLIGHTS COMPLEX ROLE OF ADIPOSE TISSUE IN THE VAS.	2016	

3  6441 29 THERAPEUTIC APPROACHES FOR NONALCOHOLIC FATTY LIVER DISEASE: ESTABLISHED TARGETS AND DRUGS. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD), AS A MULTISYSTEMIC DISEASE, IS THE MOST PREVALENT CHRONIC LIVER DISEASE CHARACTERIZED BY EXTREMELY COMPLEX PATHOGENIC MECHANISMS AND MULTIFACTORIAL ETIOLOGY, WHICH OFTEN DEVELOPS AS A CONSEQUENCE OF OBESITY, METABOLIC SYNDROME. PATHOPHYSIOLOGICAL MECHANISMS INVOLVED IN THE DEVELOPMENT OF NAFLD INCLUDE DIET, OBESITY, INSULIN RESISTANCE (IR), GENETIC AND EPIGENETIC DETERMINANTS, INTESTINAL DYSBIOSIS, OXIDATIVE/NITROSATIVE STRESS, AUTOPHAGY DYSREGULATION, HEPATIC INFLAMMATION, GUT-LIVER AXIS, GUT MICROBES, IMPAIRED MITOCHONDRIAL METABOLISM AND REGULATION OF HEPATIC LIPID METABOLISM. SOME OF THE NEW DRUGS FOR THE TREATMENT OF NAFLD ARE INTRODUCED HERE. ALL OF THEM ACHIEVE THERAPEUTIC OBJECTIVES BY INTERFERING WITH CERTAIN PATHOPHYSIOLOGICAL PATHWAYS OF NAFLD, INCLUDING FIBROBLAST GROWTH FACTORS (FGF) ANALOGUES, PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPARS) AGONISTS, GLUCAGON-LIKE PEPTIDE-1 (GLP-1) AGONISTS, G PROTEIN-COUPLED RECEPTORS (GPCRS), SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS (SGLT-2I), FARNESOID X RECEPTOR (FXR), FATTY ACID SYNTHASE INHIBITOR (FASNI), ANTIOXIDANTS, ETC. THIS REVIEW DESCRIBES SOME PATHOPHYSIOLOGICAL MECHANISMS OF NAFLD AND ESTABLISHED TARGETS AND DRUGS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
4    74 36 A MULTIDISCIPLINARY APPROACH AND CURRENT PERSPECTIVE OF NONALCOHOLIC FATTY LIVER DISEASE: A SYSTEMATIC REVIEW. IN RECENT TIMES, NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) HAS BEEN CONSIDERED ONE OF THE MAJOR CAUSES OF LIVER DISEASE ACROSS THE WORLD. NAFLD IS DEFINED AS THE DEPOSITION OF TRIGLYCERIDES IN THE LIVER AND IS ASSOCIATED WITH OBESITY AND METABOLIC SYNDROME. HYPERINSULINEMIA, INSULIN RESISTANCE (IR), FATTY LIVER, HEPATOCYTE INJURY, UNBALANCED PROINFLAMMATORY CYTOKINES, MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, LIVER INFLAMMATION, AND FIBROSIS ARE THE MAIN PATHOGENESIS IN NAFLD. RECENT STUDIES SUGGEST THAT THE ACTION OF INTESTINAL MICROBIOTA THROUGH CHRONIC INFLAMMATION, INCREASED INTESTINAL PERMEABILITY, AND ENERGY UPTAKE PLAYS A VITAL ROLE IN NAFLD. MOREOVER, POLYCYSTIC OVARIAN SYNDROME ALSO CAUSES NAFLD DEVELOPMENT THROUGH IR. AGE, GENDER, RACE, ETHNICITY, SLEEP, DIET, SEDENTARY LIFESTYLE, AND GENETIC AND EPIGENETIC PATHWAYS ARE SOME CONTRIBUTING FACTORS OF NAFLD THAT CAN EXACERBATE THE RISK OF LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA (HCC) AND EVENTUALLY LEAD TO DEATH. NAFLD HAS VARIOUS PRESENTATIONS, INCLUDING FATIGUE, UNEXPLAINED WEIGHT LOSS, BLOATING, UPPER ABDOMINAL PAIN, DECREASED APPETITE, HEADACHE, ANXIETY, POOR SLEEP, INCREASED THIRST, PALPITATION, AND A FEELING OF WARMTH. SOME STUDIES HAVE SHOWN THAT NAFLD WITH SEVERE CORONAVIRUS DISEASE 2019 (COVID-19) HAS POOR OUTCOMES. THE GOLD STANDARD FOR NAFLD DIAGNOSIS IS LIVER BIOPSY. OTHER DIAGNOSTIC TOOLS ARE IMAGING TESTS, SERUM BIOMARKERS, MICROBIOTA MARKERS, AND TESTS FOR EXTRAHEPATIC COMPLICATIONS. THERE ARE NO SPECIFIC TREATMENTS FOR NAFLD. THEREFORE, THE MAIN CONCERN FOR NAFLD IS TREATING THE COMORBID CONDITIONS SUCH AS ANTI-DIABETIC AGENTS FOR TYPE 2 DIABETES MELLITUS, STATINS TO REDUCE HCC PROGRESSION, ANTIOXIDANTS TO PREVENT HEPATOCELLULAR DAMAGE, AND BARIATRIC SURGERY FOR PATIENTS WITH A BMI OF >40 KG/M(2) AND >35 KG/M(2) WITH COMORBIDITIES. LIFESTYLE AND DIETARY CHANGES ARE CONSIDERED PREVENTIVE STRATEGIES AGAINST NAFLD ADVANCEMENT. INADEQUATE TREATMENT OF NAFLD FURTHER LEADS TO CARDIAC CONSEQUENCES, SLEEP APNEA, CHRONIC KIDNEY DISEASE, AND INFLAMMATORY BOWEL DISEASE. IN THIS SYSTEMATIC REVIEW, WE HAVE BRIEFLY DISCUSSED THE RISK FACTORS, PATHOGENESIS, CLINICAL FEATURES, AND NUMEROUS CONSEQUENCES OF NAFLD. WE HAVE ALSO REVIEWED VARIOUS GUIDELINES FOR NAFLD DIAGNOSIS ALONG WITH EXISTING THERAPEUTIC STRATEGIES FOR THE MANAGEMENT AND PREVENTION OF THE DISEASE.	2022	
                                        
5  4455 23 MOLECULAR MECHANISMS FOR THE VICIOUS CYCLE BETWEEN INSULIN RESISTANCE AND THE INFLAMMATORY RESPONSE IN OBESITY. THE COMPREHENSIVE ANABOLIC EFFECTS OF INSULIN THROUGHOUT THE BODY, IN ADDITION TO THE CONTROL OF GLYCEMIA, INCLUDE ENSURING LIPID HOMEOSTASIS AND ANTI-INFLAMMATORY MODULATION, ESPECIALLY IN ADIPOSE TISSUE (AT). THE PREVALENCE OF OBESITY, DEFINED AS A BODY MASS INDEX (BMI) >/= 30 KG/M(2), HAS BEEN INCREASING WORLDWIDE ON A PANDEMIC SCALE WITH ACCOMPANYING SYNDEMIC HEALTH PROBLEMS, INCLUDING GLUCOSE INTOLERANCE, INSULIN RESISTANCE (IR), AND DIABETES. IMPAIRED TISSUE SENSITIVITY TO INSULIN OR IR PARADOXICALLY LEADS TO DISEASES WITH AN INFLAMMATORY COMPONENT DESPITE HYPERINSULINEMIA. THEREFORE, AN EXCESS OF VISCERAL AT IN OBESITY INITIATES CHRONIC LOW-GRADE INFLAMMATORY CONDITIONS THAT INTERFERE WITH INSULIN SIGNALING VIA INSULIN RECEPTORS (INSRS). MOREOVER, IN RESPONSE TO IR, HYPERGLYCEMIA ITSELF STIMULATES A PRIMARILY DEFENSIVE INFLAMMATORY RESPONSE ASSOCIATED WITH THE SUBSEQUENT RELEASE OF NUMEROUS INFLAMMATORY CYTOKINES AND A REAL THREAT OF ORGAN FUNCTION DETERIORATION. IN THIS REVIEW, ALL COMPONENTS OF THIS VICIOUS CYCLE ARE CHARACTERIZED WITH PARTICULAR EMPHASIS ON THE INTERPLAY BETWEEN INSULIN SIGNALING AND BOTH THE INNATE AND ADAPTIVE IMMUNE RESPONSES RELATED TO OBESITY. INCREASED VISCERAL AT ACCUMULATION IN OBESITY SHOULD BE CONSIDERED THE MAIN ENVIRONMENTAL FACTOR RESPONSIBLE FOR THE DISRUPTION IN THE EPIGENETIC REGULATORY MECHANISMS IN THE IMMUNE SYSTEM, RESULTING IN AUTOIMMUNITY AND INFLAMMATION.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
6  4188 32 METABOLIC ASSOCIATED FATTY LIVER DISEASE IN CHILDREN AND ADOLESCENTS: MECHANISMS OF A SILENT EPIDEMIC AND THERAPEUTIC OPTIONS. NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS NOW IDENTIFIED AS A HEPATIC SIGN OF METABOLIC SYNDROME AND IS THE MOST FREQUENT CAUSE OF CHRONIC LIVER DISEASE IN ALL AGES. IT IS ASSUMED THAT A GENETIC PREDISPOSITION ASSOCIATED WITH EPIGENETIC FACTORS PARTICIPATES IN THE EVOLUTION OF THIS CONDITION. VISCERAL OBESITY AND INSULIN RESISTANCE (IR) HAVE ALWAYS BEEN CONSIDERED THE MOST IMPORTANT CAUSATIVE FACTORS OF METABOLIC SYNDROME (METS) AND NAFLD, BUT CURRENTLY, THE INTERACTION BETWEEN GENETIC HERITAGE AND ENVIRONMENTAL FACTORS IS INCREASINGLY CONSIDERED FUNDAMENTAL IN THE GENESIS OF METABOLIC DISORDERS ASSOCIATED WITH NAFLD. IN FACT, IN PATIENTS WITH NAFLD, INSULIN RESISTANCE, ARTERIAL HYPERTENSION, ABDOMINAL OBESITY, DYSLIPIDEMIA AND REDUCED INTESTINAL PERMEABILITY HAVE OFTEN BEEN FOUND, AS WELL AS A HIGHER PREVALENCE OF CORONARY ARTERY DISEASE, OBSTRUCTIVE SLEEP APNEA, POLYCYSTIC OVARY SYNDROME AND OSTEOPENIA, WHICH DEFINE A METS FRAMEWORK. EARLY DIAGNOSIS IS NEEDED TO PREVENT DISEASE PROGRESSION THROUGH PRIMARILY LIFESTYLE INTERVENTIONS. UNFORTUNATELY, AT PRESENT, THERE ARE NO MOLECULES RECOMMENDED FOR PEDIATRIC PATIENTS. HOWEVER, SEVERAL NEW DRUGS ARE IN CLINICAL TRIALS. FOR THIS REASON, TARGETED STUDIES ON THE INTERACTION BETWEEN GENETICS AND ENVIRONMENTAL FACTORS INVOLVED IN THE DEVELOPMENT OF NAFLD AND METS AND ON THE PATHOGENETIC MECHANISMS THAT DETERMINE THE EVOLUTION IN NON-ALCOHOLIC STEATOHEPATITIS (NASH), SHOULD BE IMPLEMENTED. THEREFORE, IT IS DESIRABLE THAT FUTURE STUDIES MAY BE USEFUL IN IDENTIFYING PATIENTS AT RISK OF DEVELOPING NAFLD AND METS EARLY.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
7  4711 26 NON-ALCOHOLIC FATTY LIVER DISEASE IN OBESE CHILDREN AND ADOLESCENTS: A ROLE FOR NUTRITION? NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) HAS BECOME THE MOST COMMON CAUSE OF CHRONIC LIVER DISEASE IN CHILDREN, PARALLELING THE INCREASING PREVALENCE OF OBESITY WORLDWIDE. THE PATHOGENESIS OF PAEDIATRIC NAFLD IS NOT FULLY UNDERSTOOD, BUT IT IS KNOWN THAT OBESITY, NUTRITION, LIFESTYLE VARIABLES, GENETIC AND EPIGENETIC FACTORS MAY BE CAUSALLY INVOLVED IN THE DEVELOPMENT OF THIS COMMON METABOLIC LIVER DISEASE. IN PARTICULAR, OBESITY AND NUTRITION ARE AMONG THE STRONGEST RISK FACTORS FOR PAEDIATRIC NAFLD, WHICH MAY EXERT THEIR ADVERSE HEPATIC EFFECTS ALREADY BEFORE BIRTH. EXCESS ENERGY INTAKE INDUCES HYPERTROPHY AND HYPERPLASIA OF ADIPOSE TISSUE WITH SUBSEQUENT DEVELOPMENT OF SYSTEMIC INSULIN RESISTANCE, WHICH IS ANOTHER IMPORTANT RISK FACTOR FOR NAFLD. DIET COMPOSITION AND IN PARTICULAR SIMPLE CARBOHYDRATE INTAKE (ESPECIALLY HIGH FRUCTOSE INTAKE) MAY PROMOTE THE DEVELOPMENT OF NAFLD, WHEREAS NON-DIGESTIBLE CARBOHYDRATES (DIETARY FIBER), BY AFFECTING GUT MICROBIOTA, MAY FAVOUR THE INTEGRITY OF GUT WALL AND REDUCE INFLAMMATION, OPPOSING THIS PROCESS. SATURATED FAT INTAKE MAY ALSO PROMOTE NAFLD DEVELOPMENT, WHEREAS UNSATURATED FAT INTAKE HAS SOME BENEFICIAL EFFECTS. PROTEIN INTAKE DOES NOT SEEM TO AFFECT THE DEVELOPMENT OF NAFLD, BUT FURTHER INVESTIGATION IS NEEDED. IN CONCLUSION, LIFESTYLE MODIFICATIONS TO INDUCE WEIGHT LOSS, THROUGH DIET AND PHYSICAL ACTIVITY, REMAIN THE MAINSTAY OF TREATMENT FOR PAEDIATRIC NAFLD. THE USE OF DIETARY SUPPLEMENTS, SUCH AS OMEGA-3 FATTY ACIDS AND PROBIOTICS, NEEDS FURTHER STUDY BEFORE RECOMMENDATION.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
8  1373 19 DEVELOPMENTAL ORIGINS OF NONALCOHOLIC FATTY LIVER DISEASE. OBESE PREGNANT WOMEN MAY TRANSMIT THEIR METABOLIC PHENOTYPE TO OFFSPRING, LEADING TO A CYCLE OF OBESITY AND DIABETES OVER GENERATIONS. EARLY CHILDHOOD OBESITY PREDICTS NONALCOHOLIC FATTY LIVER DISEASE (NAFLD), THE MOST COMMON CHRONIC HUMAN LIVER DISEASE. THE FETUS MAY BE VULNERABLE TO STEATOSIS BECAUSE IMMATURE FETAL ADIPOSE DEPOTS ARE NOT AVAILABLE TO BUFFER THE EXCESS TRANSPLACENTAL LIPID DELIVERY IN MATERNAL OBESITY. IN ANIMAL MODELS, IN UTERO HIGH-FAT DIET EXPOSURE RESULTS IN AN INCREASE IN THE ACCUMULATION OF LIVER TRIGLYCERIDES IN OFFSPRING AND INCREASED HEPATIC OXIDATIVE STRESS AND APOPTOSIS, PERHAPS PRIMING THE LIVER FOR LATER DEVELOPMENT OF NAFLD. INNATE IMMUNE DYSFUNCTION AND NECROINFLAMMATORY CHANGES HAVE BEEN OBSERVED IN POSTNATAL OFFSPRING LIVER OF ANIMALS BORN TO HIGH-FAT-FED DAMS. POSTWEANING, LIVERS OF OFFSPRING EXPOSED TO MATERNAL HIGH-FAT FEEDING IN UTERO SHARE PATHOPHYSIOLOGIC FEATURES WITH HUMAN NAFLD, INCLUDING INCREASED DE NOVO LIPOGENESIS AND DECREASED FREE FATTY ACID OXIDATION. HUMAN STUDIES USING MAGNETIC RESONANCE IMAGING HAVE SHOWN THAT MATERNAL BMI PREDICTS INFANT INTRAHEPATOCELLULAR LIPID STORAGE, AS SEEN IN ANIMAL MODELS. THE GENERATIONAL TRANSFER OF NAFLD MAY OCCUR VIA EPIGENETIC CHANGES IN OFFSPRING LIVER. TRANSMISSION OF MICROBIOTA FROM MOTHER TO INFANT MAY IMPACT ENERGY RETENTION AND IMMUNE FUNCTION THAT CONTRIBUTE TO A PREDISPOSITION TO NAFLD.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
9  5460 22 RESEARCH PERSPECTIVES ON THE REGULATION AND PHYSIOLOGICAL FUNCTIONS OF FGF21 AND ITS ASSOCIATION WITH NAFLD. FIBROBLAST GROWTH FACTOR 21 (FGF21) IS A METABOLIC HORMONE PRIMARILY SECRETED FROM THE LIVER AND FUNCTIONS IN MULTIPLE TISSUES. VARIOUS TRANSCRIPTION FACTORS INDUCE FGF21 EXPRESSION IN THE LIVER, WHICH INDICATES THAT FGF21 IS A MEDIATOR OF MULTIPLE ENVIRONMENTAL CUES. FGF21 ALTERS METABOLISM UNDER STARVATION CONDITIONS, PROTECTS THE BODY FROM ENERGY DEPLETION, AND EXTENDS LIFE SPAN. PHARMACOLOGICAL ADMINISTRATION OF FGF21 ALLEVIATES DYSLIPIDEMIA AND INDUCES WEIGHT LOSS IN OBESE ANIMALS. IN ADDITION TO THE WELL-STUDIED FUNCTIONS OF FG21, SEVERAL LINES OF RECENT EVIDENCE INDICATE A POSSIBLE LINK BETWEEN FGF21 AND NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD). HIGH SERUM LEVELS OF FGF21 ARE ASSOCIATED WITH NAFLD AND ITS RISK FACTORS, SUCH AS ENDOPLASMIC RETICULUM STRESS AND CHRONIC INFLAMMATION. IN ADDITION, FGF21 ALLEVIATES THE MAJOR RISK FACTORS OF NAFLD, INCLUDING OBESITY, DYSLIPIDEMIA, AND INSULIN INSENSITIVITY. THUS, FGF21 IS A POTENTIAL DRUG CANDIDATE FOR DISEASES, SUCH AS NAFLD, DYSLIPIDEMIA, AND TYPE 2 DIABETES. IN THIS REVIEW, THE RESEARCH PERSPECTIVES OF FGF21 AND THERAPEUTIC POTENCIES OF FGF21 AS A MODULATOR OF NAFLD ARE SUMMARIZED.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
10  4892 33 OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: OXIDATIVE STRESS IN POLYCYSTIC OVARY SYNDROME. IN BRIEF: A GENETIC, EPIGENETIC, AND ENVIRONMENTAL ASSOCIATION EXISTS BETWEEN OXIDATIVE STRESS (OS) AND POLYCYSTIC OVARY SYNDROME (PCOS), EXPRESSED IN A MULTIFACETED CLINICAL PROFILE. THIS REVIEW SUMMARIZES AND DISCUSSES THE ROLE OF OS IN THE PATHOGENESIS OF PCOS SYNDROME, FOCUSING ON METABOLIC, REPRODUCTIVE, AND CANCER COMPLICATIONS. ABSTRACT: OXIDATIVE STRESS (OS), AN IMBALANCE BETWEEN OXIDANTS AND ANTIOXIDANTS IN CELLS, IS ONE OF MANY FACTORS PLAYING ESSENTIAL ROLES IN THE PATHOGENESIS OF POLYCYSTIC OVARY SYNDROME (PCOS). PCOS IS DESCRIBED MAINLY AS A DISPROPORTION OF REPRODUCTIVE HORMONES, LEADING TO CHRONIC ANOVULATION AND INFERTILITY IN WOMEN. INTERESTINGLY, OS IN PCOS MAY BE ASSOCIATED WITH MANY DISORDERS AND DISEASES. THIS REVIEW FOCUSES ON CHARACTERISTIC MARKERS OF OS IN PCOS AND THE RELATIONSHIP BETWEEN OS AND PCOS RELATED TO INSULIN RESISTANCE (IR), HYPERANDROGENEMIA, OBESITY, CHRONIC INFLAMMATION, CARDIOVASCULAR DISEASES, AND CANCER. INTERESTINGLY, IN PATIENTS WITH PCOS, AN INCREASE IN OXIDATIVE STATUS AND INSUFFICIENT COMPENSATION OF THE INCREASE IN ANTIOXIDANT STATUS BEFORE ANY CARDIOVASCULAR COMPLICATIONS ARE OBSERVED. MOREOVER, FREE RADICALS PROMOTE CARCINOGENESIS IN PCOS PATIENTS. HOWEVER, DESPITE THESE DATA, IT HAS NOT BEEN ESTABLISHED WHETHER OXYGEN STRESS INFLUENCES PCOS DEVELOPMENT OR A SECONDARY DISORDER RESULTING FROM HYPERGLYCEMIA, IR, AND CARDIOVASCULAR AND CANCER COMPLICATIONS IN WOMEN.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
11   241 30 ADIPOCYTE, IMMUNE CELLS, AND MIRNA CROSSTALK: A NOVEL REGULATOR OF METABOLIC DYSFUNCTION AND OBESITY. OBESITY IS CHARACTERIZED AS A COMPLEX AND MULTIFACTORIAL EXCESS ACCRETION OF ADIPOSE TISSUE (AT) ACCOMPANIED WITH ALTERATIONS IN THE IMMUNE RESPONSE THAT AFFECTS VIRTUALLY ALL AGE AND SOCIOECONOMIC GROUPS AROUND THE GLOBE. THE ABNORMAL ACCUMULATION OF AT LEADS TO SEVERAL METABOLIC DISEASES, INCLUDING NONALCOHOLIC FATTY LIVER DISORDER (NAFLD), LOW-GRADE INFLAMMATION, TYPE 2 DIABETES MELLITUS (T2DM), CARDIOVASCULAR DISORDERS (CVDS), AND CANCER. AT IS AN ENDOCRINE ORGAN COMPOSED OF ADIPOCYTES AND IMMUNE CELLS, INCLUDING B-CELLS, T-CELLS AND MACROPHAGES. THESE IMMUNE CELLS SECRETE VARIOUS CYTOKINES AND CHEMOKINES AND CROSSTALK WITH ADIPOKINES TO MAINTAIN METABOLIC HOMEOSTASIS AND LOW-GRADE CHRONIC INFLAMMATION. A NOVEL FORM OF ADIPOKINES, MICRORNA (MIRS), IS EXPRESSED IN MANY DEVELOPING PERIPHERAL TISSUES, INCLUDING ATS, T-CELLS, AND MACROPHAGES, AND MODULATES THE IMMUNE RESPONSE. MIRS ARE ESSENTIAL FOR INSULIN RESISTANCE, MAINTAINING THE TUMOR MICROENVIRONMENT, AND OBESITY-ASSOCIATED INFLAMMATION (OAI). THE ABNORMAL REGULATION OF AT, T-CELLS, AND MACROPHAGE MIRS MAY CHANGE THE FUNCTION OF DIFFERENT ORGANS INCLUDING THE PANCREAS, HEART, LIVER, AND SKELETAL MUSCLE. SINCE OBESITY AND INFLAMMATION ARE CLOSELY ASSOCIATED, THE DYSREGULATED EXPRESSION OF MIRS IN INFLAMMATORY ADIPOCYTES, T-CELLS, AND MACROPHAGES SUGGEST THE IMPORTANCE OF MIRS IN OAI. THEREFORE, IN THIS REVIEW ARTICLE, WE HAVE ELABORATED THE ROLE OF MIRS AS EPIGENETIC REGULATORS AFFECTING ADIPOCYTE DIFFERENTIATION, IMMUNE RESPONSE, AT BROWNING, ADIPOGENESIS, LIPID METABOLISM, INSULIN RESISTANCE (IR), GLUCOSE HOMEOSTASIS, OBESITY, AND METABOLIC DISORDERS. FURTHER, WE WILL DISCUSS A SET OF ALTERED MIRS AS NOVEL BIOMARKERS FOR METABOLIC DISEASE PROGRESSION AND THERAPEUTIC TARGETS FOR OBESITY.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
12  2699 29 EXCESS BODY WEIGHT: NOVEL INSIGHTS INTO ITS ROLES IN OBESITY COMORBIDITIES. EXCESS BODY WEIGHT IS A GLOBAL HEALTH PROBLEM DUE TO SEDENTARY LIFESTYLE AND UNHEALTHY DIET, AFFECTING 2 BILLION POPULATION WORLDWIDE. OBESITY IS A MAJOR RISK FACTOR FOR METABOLIC DISEASES. NOTABLY, THE METABOLIC RISK OF OBESITY LARGELY DEPENDS ON BODY WEIGHT DISTRIBUTION, OF WHICH VISCERAL ADIPOSE TISSUES BUT NOT SUBCUTANEOUS FATS ARE CLOSELY ASSOCIATED WITH OBESITY COMORBIDITIES, INCLUDING TYPE 2 DIABETES, NON-ALCOHOLIC FATTY LIVER DISEASE, CARDIOVASCULAR DISEASE AND CERTAIN TYPES OF CANCER. LATEST MULTI-OMICS AND MECHANISTICAL STUDIES REPORTED THE CRUCIAL INVOLVEMENT OF GENETIC AND EPIGENETIC ALTERATIONS, ADIPOKINES DYSREGULATION, IMMUNITY CHANGES, IMBALANCE OF WHITE AND BROWN ADIPOSE TISSUES, AND GUT MICROBIAL DYSBIOSIS IN MEDIATING THE PATHOGENIC ASSOCIATION BETWEEN VISCERAL ADIPOSE TISSUES AND COMORBIDITIES. IN THIS REVIEW, WE EXPLORE THE EPIDEMIOLOGY OF EXCESS BODY WEIGHT AND THE UP-TO-DATE MECHANISM OF HOW EXCESS BODY WEIGHT AND OBESITY LEAD TO CHRONIC COMPLICATIONS. WE ALSO EXAMINE THE UTILIZATION OF VISCERAL FAT MEASUREMENT AS AN ACCURATE CLINICAL PARAMETER FOR RISK ASSESSMENT IN HEALTHY INDIVIDUALS AND CLINICAL OUTCOME PREDICTION IN OBESE SUBJECTS. IN ADDITION, CURRENT APPROACHES FOR THE PREVENTION AND TREATMENT OF EXCESS BODY WEIGHT AND ITS RELATED METABOLIC COMORBIDITIES ARE FURTHER DISCUSSED.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
13  4314 28 MICRORNAS AS CONTROLLED SYSTEMS AND CONTROLLERS IN NON-ALCOHOLIC FATTY LIVER DISEASE. NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS A MULTI-FACETED CONDITION INCLUDING SIMPLE STEATOSIS ALONE OR ASSOCIATED WITH INFLAMMATION AND BALLOONING (NON-ALCOHOLIC STEATOHEPATITIS) AND EVENTUALLY FIBROSIS. THE NAFLD INCIDENCE HAS INCREASED OVER THE LAST TWENTY YEARS BECOMING THE MOST FREQUENT CHRONIC LIVER DISEASE IN INDUSTRIALIZED COUNTRIES. OBESITY, VISCERAL ADIPOSITY, INSULIN RESISTANCE, AND MANY OTHER DISORDERS THAT CHARACTERIZE METABOLIC SYNDROME ARE THE MAJOR PREDISPOSING RISK FACTORS FOR NAFLD. FURTHERMORE, DIFFERENT FACTORS, INCLUDING GENETIC BACKGROUND, EPIGENETIC MECHANISMS AND ENVIRONMENTAL FACTORS, SUCH AS DIET AND PHYSICAL EXERCISE, CONTRIBUTE TO NAFLD DEVELOPMENT AND PROGRESSION. SEVERAL LINES OF EVIDENCE DEMONSTRATE THAT SPECIFIC MICRORNAS EXPRESSION PROFILES ARE STRONGLY ASSOCIATED WITH SEVERAL PATHOLOGICAL CONDITIONS INCLUDING NAFLD. IN NAFLD, MICRORNA DEREGULATION IN RESPONSE TO INTRINSIC GENETIC OR EPIGENETIC FACTORS OR ENVIRONMENTAL FACTORS CONTRIBUTES TO METABOLIC DYSFUNCTION. IN THIS REVIEW WE FOCUSED ON MICRORNAS ROLE BOTH AS CONTROLLED AND CONTROLLERS MOLECULES IN NAFLD DEVELOPMENT AND/OR THEIR EVENTUAL VALUE AS NON-INVASIVE BIOMARKERS OF DISEASE.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
14  2862 27 FRUCTOSE-MEDIATED EFFECTS ON GENE EXPRESSION AND EPIGENETIC MECHANISMS ASSOCIATED WITH NAFLD PATHOGENESIS. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS A CHRONIC, FREQUENTLY PROGRESSIVE CONDITION THAT DEVELOPS IN RESPONSE TO EXCESSIVE HEPATOCYTE FAT ACCUMULATION (I.E., STEATOSIS) IN THE ABSENCE OF SIGNIFICANT ALCOHOL CONSUMPTION. LIVER STEATOSIS DEVELOPS AS A RESULT OF IMBALANCED LIPID METABOLISM, DRIVEN LARGELY BY INCREASED RATES OF DE NOVO LIPOGENESIS AND HEPATIC FATTY ACID UPTAKE AND REDUCED FATTY ACID OXIDATION AND/OR DISPOSAL TO THE CIRCULATION. FRUCTOSE IS A NATURALLY OCCURRING SIMPLE SUGAR, WHICH IS MOST COMMONLY CONSUMED IN MODERN DIETS IN THE FORM OF SUCROSE, A DISACCHARIDE COMPRISED OF ONE MOLECULE OF FRUCTOSE COVALENTLY BONDED WITH ONE MOLECULE OF GLUCOSE. A NUMBER OF OBSERVATIONAL AND EXPERIMENTAL STUDIES HAVE DEMONSTRATED DETRIMENTAL EFFECTS OF DIETARY FRUCTOSE CONSUMPTION NOT ONLY ON DIVERSE METABOLIC OUTCOMES SUCH AS INSULIN RESISTANCE AND OBESITY, BUT ALSO ON HEPATIC STEATOSIS AND NAFLD-RELATED FIBROSIS. DESPITE THE COMPELLING EVIDENCE THAT EXCESSIVE FRUCTOSE CONSUMPTION IS ASSOCIATED WITH THE PRESENCE OF NAFLD AND MAY EVEN PROMOTE THE DEVELOPMENT AND PROGRESSION OF NAFLD TO MORE CLINICALLY SEVERE PHENOTYPES, THE MOLECULAR MECHANISMS BY WHICH FRUCTOSE ELICITS EFFECTS ON DYSREGULATED LIVER METABOLISM REMAIN UNCLEAR. EMERGING DATA SUGGEST THAT DIETARY FRUCTOSE MAY DIRECTLY ALTER THE EXPRESSION OF GENES INVOLVED IN LIPID METABOLISM, INCLUDING THOSE THAT INCREASE HEPATIC FAT ACCUMULATION OR REDUCE HEPATIC FAT REMOVAL. THE AIM OF THIS REVIEW IS TO SUMMARIZE THE CURRENT RESEARCH SUPPORTING A ROLE FOR DIETARY FRUCTOSE INTAKE IN THE MODULATION OF TRANSCRIPTOMIC AND EPIGENETIC MECHANISMS UNDERLYING THE PATHOGENESIS OF NAFLD.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
15  4464 27 MOLECULAR MECHANISMS OF NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)/NONALCOHOLIC STEATOHEPATITIS (NASH). NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS ONE OF THE MOST COMMON CHRONIC LIVER DISEASES WORLDWIDE AND HAS GARNERED INCREASING ATTENTION IN RECENT DECADES. NAFLD IS CHARACTERIZED BY A WIDE RANGE OF LIVER CHANGES, FROM SIMPLE STEATOSIS TO NONALCOHOLIC STEATOHEPATITIS (NASH), CIRRHOSIS, AND HEPATOCELLULAR CARCINOMA. THE PATHOGENESIS OF NAFLD/NASH IS VERY COMPLICATED AND INVOLVES LIPID ACCUMULATION, INSULIN RESISTANCE, INFLAMMATION, AND FIBROGENESIS. IN ADDITION, NAFLD IS CLOSELY ASSOCIATED WITH COMPLICATIONS SUCH AS OBESITY, DYSLIPIDEMIA, AND TYPE 2 DIABETES. IN PARTICULAR, THE CLINICAL SPECTRUM, PATHOPHYSIOLOGY, AND THERAPEUTIC OPTIONS OF NAFLD SHARE MANY THINGS IN COMMON WITH DIABETES. INSULIN RESISTANCE IS AN UNDERLYING BASIS FOR THE PATHOGENESIS OF DIABETES AND NAFLD. THIS CHAPTER FOCUSES ON THE MOLECULAR MECHANISM INVOLVED IN THE PATHOGENESIS OF INSULIN RESISTANCE, DIABETES, AND NASH/NAFLD INCLUDING THOSE THAT DRIVE DISEASE PROGRESSION SUCH AS OXIDATIVE STRESS, GENETIC AND EPIGENETIC MECHANISMS, ADIPONECTIN, CYTOKINES, AND IMMUNE CELLS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
16  1341 31 DETANGLING THE INTERRELATIONS BETWEEN MAFLD, INSULIN RESISTANCE, AND KEY HORMONES. METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE (MAFLD) HAS INCREASINGLY BECOME A SIGNIFICANT AND HIGHLY PREVALENT CAUSE OF CHRONIC LIVER DISEASE, DISPLAYING A WIDE ARRAY OF RISK FACTORS AND PATHOPHYSIOLOGIC MECHANISMS OF WHICH ONLY A FEW HAVE SO FAR BEEN CLEARLY ELUCIDATED. A BIDIRECTIONAL INTERACTION BETWEEN HORMONAL DISCREPANCIES AND METABOLIC-RELATED DISORDERS, INCLUDING OBESITY, TYPE 2 DIABETES MELLITUS (T2DM), AND POLYCYSTIC OVARIAN SYNDROME (PCOS) HAS BEEN DESCRIBED. SINCE THE CHANGE IN NOMENCLATURE FROM NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) TO MAFLD IS BASED ON THE CLEAR IMPACT OF METABOLIC ELEMENTS ON THE DISEASE, THE RECIPROCAL INTERACTIONS OF HORMONES SUCH AS INSULIN, ADIPOKINES (LEPTIN AND ADIPONECTIN), AND ESTROGENS HAVE STRONGLY POINTED TO THE INTRINSIC LINKS THAT LEAD TO THE HETEROGENEOUS EPIDEMIOLOGY, CLINICAL PRESENTATIONS, AND RISK FACTORS INVOLVED IN MAFLD IN DIFFERENT POPULATIONS. THE OBJECTIVE OF THIS WORK IS TWOFOLD. FIRSTLY, THERE IS A BRIEF DISCUSSION REGARDING THE CHANGE IN NOMENCLATURE AS WELL AS EPIDEMIOLOGY, RISK FACTORS, AND PATHOPHYSIOLOGIC MECHANISMS OTHER THAN HORMONAL EFFECTS, WHICH INCLUDE NUTRITION AND THE GUT MICROBIOME, AS WELL AS GENETIC AND EPIGENETIC INFLUENCES. SECONDLY, WE REVIEW THE BASIS OF THE MOST IMPORTANT HORMONAL FACTORS INVOLVED IN THE DEVELOPMENT AND PROGRESSION OF MAFLD THAT ACT BOTH INDEPENDENTLY AND IN AN INTERRELATED MANNER.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
17  5366 24 RECENT ADVANCES IN LEAN NAFLD. AS THE PREDOMINANT TYPE OF CHRONIC LIVER DISEASE, THE GROWING PREVALENCE OF NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) HAS BECOME A CONCERN WORLDWIDE. ALTHOUGH OBESITY PLAYS THE MOST PIVOTAL ROLE IN NAFLD, APPROXIMATELY 10-20% OF INDIVIDUALS WITH NAFLD WHO ARE NOT OVERWEIGHT OR OBESE (BMI < 25 KG/M2, OR BMI < 23 KG/M2 IN ASIANS) HAVE "LEAN NAFLD." LEAN INDIVIDUALS WITH NAFLD HAVE A LOWER PREVALENCE OF DIABETES, HYPERTENSION, HYPERTRIGLYCERIDEMIA, CENTRAL OBESITY, AND METABOLIC SYNDROME THAN NONLEAN INDIVIDUALS WITH NAFLD, BUT HIGHER FIBROSIS SCORES AND RATES OF CARDIOVASCULAR MORBIDITY AND ALL-CAUSE MORTALITY IN ADVANCED STAGES. THE PATHOPHYSIOLOGICAL MECHANISMS OF LEAN NAFLD REMAIN POORLY UNDERSTOOD. STUDIES HAVE SHOWN THAT LEAN NAFLD IS MORE CORRELATED WITH FACTORS SUCH AS ENVIRONMENTAL, GENETIC SUSCEPTIBILITY, AND EPIGENETIC REGULATION. THIS REVIEW WILL EXAMINE THE WAY IN WHICH THE RESEARCH PROGRESS AND CHARACTERISTIC OF LEAN NAFLD, AND EXPLORE THE FUNCTION OF EPIGENETIC MODIFICATION TO PROVIDE THE BASIS FOR THE CLINICAL TREATMENT AND DIAGNOSIS OF LEAN NAFLD.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
18  1721 27 DYSREGULATION OF AUTOPHAGY ACTS AS A PATHOGENIC MECHANISM OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) INDUCED BY COMMON ENVIRONMENTAL POLLUTANTS. NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) HAS BEEN THE MOST COMMON CHRONIC LIVER DISEASE IN THE WORLD, INCLUDING THE DEVELOPING COUNTRIES. NAFLD IS METABOLIC DISEASE WITH SIGNIFICANT LIPID DEPOSITION IN THE HEPATOCYTES OF THE LIVER, WHICH IS USUALLY ASSOCIATED WITH OXIDATIVE STRESS, INFLAMMATION AND FIBROGENESIS, AND INSULIN RESISTANCE. PROGRESSIVE NAFLD CAN DEVELOP INTO NON-ALCOHOLIC STEATOHEPATITIS (NASH) OR HEPATOCELLULAR CARCINOMA. THE CURRENT EVIDENCE PROPOSES THAT ENVIRONMENTAL POLLUTANTS PROMOTE DEVELOPMENT AND PROGRESSION OF NAFLD, AND AUTOPHAGY PLAYS A VITAL ROLE BUT IS MULTIFACTORIAL AFFECTED IN NAFLD. IN THIS REVIEW, WE ANALYZED ON THE REGULATIONS OF COMMON ENVIRONMENTAL POLLUTANTS ON AUTOPHAGY IN NAFLD. TO CLARIFY THE INVOLVED ROLES OF AUTOPHAGY, WE DISCUSSED THE DYSREGULATION OF AUTOPHAGY BY ENVIRONMENTAL POLLUTANTS IN ADIPOSE TISSUE AND GUT, AND THEIR INTERACTIONS WITH LIVER, AS WELL AS EPIGENETIC REGULATION ON AUTOPHAGY BY ENVIRONMENTAL POLLUTANTS. FURTHERMORE, PROTECTIVE ROLES OF POTENTIAL THERAPEUTIC TREATMENTS ON THE MULTIPLE-HITS OF AUTOPHAGY IN NAFLD WERE DESCRIPTED.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
19  4326 25 MICRORNAS IN THE PATHOGENESIS OF NONALCOHOLIC FATTY LIVER DISEASE. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD), OR, MORE ACCURATELY, METABOLIC ASSOCIATED FATTY LIVER DISEASE, ACCOUNTS FOR A LARGE PROPORTION OF CHRONIC LIVER DISORDERS WORLDWIDE AND IS CLOSELY ASSOCIATED WITH OTHER CONDITIONS SUCH AS CARDIOVASCULAR DISEASE, OBESITY, AND TYPE 2 DIABETES MELLITUS. NAFLD RANGES FROM SIMPLE STEATOSIS TO NONALCOHOLIC STEATOHEPATITIS (NASH) AND CAN PROGRESS TO CIRRHOSIS AND, EVENTUALLY, ALSO HEPATOCELLULAR CARCINOMA. THE MORBIDITY AND MORTALITY ASSOCIATED WITH NAFLD ARE INCREASING RAPIDLY YEAR ON YEAR. CONSEQUENTLY, THERE IS AN URGENT NEED TO UNDERSTAND THE ETIOLOGY AND PATHOGENESIS OF NAFLD AND IDENTIFY EFFECTIVE THERAPEUTIC TARGETS. MICRORNAS (MIRNAS), IMPORTANT EPIGENETIC FACTORS, HAVE RECENTLY BEEN PROPOSED TO PARTICIPATE IN NAFLD PATHOGENESIS. HERE, WE REVIEW THE ROLES OF MIRNAS IN LIPID METABOLISM, INFLAMMATION, APOPTOSIS, FIBROSIS, HEPATIC STELLATE CELL ACTIVATION, INSULIN RESISTANCE, AND OXIDATIVE STRESS, KEY FACTORS THAT CONTRIBUTE TO THE OCCURRENCE AND PROGRESSION OF NAFLD. ADDITIONALLY, WE SUMMARIZE THE ROLE OF MIRNA-ENRICHED EXTRACELLULAR VESICLES IN NAFLD. THESE MIRNAS MAY COMPRISE SUITABLE THERAPEUTIC TARGETS FOR THE TREATMENT OF THIS CONDITION.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
20  5104 22 POLYCYSTIC OVARIAN SYNDROME. WOMEN WITH PCOS PRESENT WITH SIGNS OF CHRONIC ANOVULATION, HYPERANDROGENISM, AND METABOLIC ABNORMALITIES. THE NIH RECENTLY EMBRACED THE ROTTERDAM CRITERIA TO BROADLY IDENTIFY ALL THE PHENOTYPES OF PCOS. WOMEN WITH PCOS ARE OFTEN OBESE WITH INSULIN RESISTANCE AND HENCE HAVE AN INCREASED SUSCEPTIBILITY TO GLUCOSE INTOLERANCE AND TYPE 2 DIABETES. FUTURE RESEARCH SHOULD FOCUS ON THE GENETIC, EPIGENETIC, AND ENVIRONMENTAL DETERMINANTS OF PCOS TO DEVELOP NEW THERAPIES TO ADDRESS THE PREVENTION OF THIS DISORDER AND ITS LONG-TERM COMPLICATIONS.	2015