1  5686 85 SICKLE CELL DISEASE: CLINICAL PRESENTATION AND MANAGEMENT OF A GLOBAL HEALTH CHALLENGE. SICKLE CELL DISEASE IS AN AUTOSOMAL RECESSIVE, MULTISYSTEM DISORDER, CHARACTERISED BY CHRONIC HAEMOLYTIC ANAEMIA, PAINFUL EPISODES OF VASO-OCCLUSION, PROGRESSIVE ORGAN FAILURE AND A REDUCED LIFE EXPECTANCY. SICKLE CELL DISEASE IS THE MOST COMMON MONOGENETIC DISEASE, WITH MILLIONS AFFECTED WORLDWIDE. IN WELL-RESOURCED COUNTRIES, COMPREHENSIVE CARE PROGRAMS HAVE INCREASED LIFE EXPECTANCY OF SICKLE CELL DISEASE PATIENTS, WITH ALMOST ALL INFANTS SURVIVING INTO ADULTHOOD. THERAPEUTIC OPTIONS FOR SICKLE CELL DISEASE PATIENTS ARE HOWEVER, STILL SCARCE. PREDICTORS OF SICKLE CELL DISEASE SEVERITY AND A BETTER UNDERSTANDING OF PATHOPHYSIOLOGY AND (EPI)GENETIC MODIFIERS ARE WARRANTED AND COULD LEAD TO MORE PRECISE MANAGEMENT AND TREATMENT. THIS REVIEW PROVIDES AN EXTENSIVE SUMMARY OF THE PATHOPHYSIOLOGY AND MANAGEMENT OF SICKLE CELL DISEASE AND ENCOMPASSES THE CHARACTERISTICS, COMPLICATIONS AND CURRENT AND FUTURE TREATMENT OPTIONS OF THE DISEASE.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
2  4761 22 NRF2 SENSITIZES FERROPTOSIS THROUGH L-2-HYDROXYGLUTARATE-MEDIATED CHROMATIN MODIFICATIONS IN SICKLE CELL DISEASE. SICKLE CELL DISEASE (SCD) IS A CHRONIC HEMOLYTIC AND SYSTEMIC HYPOXIA CONDITION WITH CONSTANT OXIDATIVE STRESS AND SIGNIFICANT METABOLIC ALTERATIONS. HOWEVER, LITTLE IS KNOWN ABOUT THE CORRELATION BETWEEN METABOLIC ALTERATIONS AND THE PATHOPHYSIOLOGICAL SYMPTOMS. HERE, WE REPORT THAT NRF2, A MASTER REGULATOR OF CELLULAR ANTIOXIDANT RESPONSES, REGULATES THE PRODUCTION OF THE METABOLITE L-2-HYDROXYGLUTARATE (L2HG) TO MEDIATE EPIGENETIC HISTONE HYPERMETHYLATION FOR GENE EXPRESSION INVOLVED IN METABOLIC, OXIDATIVE, AND FERROPTOTIC STRESS RESPONSES IN SCD. MECHANISTICALLY, NRF2 WAS FOUND TO REGULATE THE EXPRESSION OF L2HG DEHYDROGENASE (L2HGDH) TO MEDIATE L2HG PRODUCTION UNDER HYPOXIA. GENE EXPRESSION PROFILE ANALYSIS INDICATED THAT REACTIVE OXYGEN SPECIES (ROS) AND FERROPTOSIS RESPONSES WERE THE MOST SIGNIFICANTLY AFFECTED SIGNALING PATHWAYS AFTER NRF2 ABLATION IN SCD. NRF2 SILENCING AND L2HG SUPPLEMENTATION SENSITIZE HUMAN SICKLE ERYTHROID CELLS TO ROS AND FERROPTOSIS STRESS. THE ABSENCE OF NRF2 AND ACCUMULATION OF L2HG SIGNIFICANTLY AFFECT HISTONE METHYLATION FOR CHROMATIN STRUCTURE MODIFICATION AND REDUCE THE ASSEMBLY OF TRANSCRIPTION COMPLEXES ON DOWNSTREAM TARGET GENES TO REGULATE ROS AND FERROPTOSIS RESPONSES. FURTHERMORE, PHARMACOLOGICAL ACTIVATION OF NRF2 WAS FOUND TO HAVE PROTECTIVE EFFECTS AGAINST ROS AND FERROPTOSIS STRESS IN SCD MICE. OUR DATA SUGGEST A NOVEL MECHANISM BY WHICH NRF2 REGULATES L2HG LEVELS TO MEDIATE SCD SEVERITY THROUGH ROS AND FERROPTOSIS STRESS RESPONSES, SUGGESTING THAT TARGETING NRF2 IS A VIABLE THERAPEUTIC STRATEGY FOR AMELIORATING SCD SYMPTOMS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
3  5518 20 RISK FACTORS AND FUTURE DIRECTIONS FOR PREVENTING AND DIAGNOSING EXERTIONAL RHABDOMYOLYSIS. EXERTIONAL RHABDOMYOLYSIS MAY OCCUR WHEN AN INDIVIDUAL IS SUBJECTED TO STRENUOUS PHYSICAL EXERCISE. IT IS OCCASIONALLY ASSOCIATED WITH MYOGLOBINURIA (I.E. "COLA-COLORED" URINE) ALONGSIDE MUSCLE PAIN AND WEAKNESS. THE PATHOPHYSIOLOGY OF EXERTIONAL RHABDOMYOLYSIS INVOLVES STRIATED MUSCLE DAMAGE AND THE RELEASE OF CELLULAR COMPONENTS INTO EXTRACELLULAR FLUID AND BLOODSTREAM. THIS CAN CAUSE ACUTE RENAL FAILURE, ELECTROLYTE ABNORMALITIES, ARRHYTHMIAS AND POTENTIALLY DEATH. EXERTIONAL RHABDOMYOLYSIS IS OBSERVED IN HIGH-PERFORMANCE ATHLETES WHO ARE SUBJECTED TO INTENSE, REPETITIVE AND/OR PROLONGED EXERCISE BUT IS ALSO OBSERVED IN UNTRAINED INDIVIDUALS AND HIGHLY TRAINED OR ELITE GROUPS OF MILITARY PERSONNEL. SEVERAL RISK FACTORS HAVE BEEN REPORTED TO INCREASE THE LIKELIHOOD OF THE CONDITION IN ATHLETES, INCLUDING: VIRAL INFECTION, DRUG AND ALCOHOL ABUSE, EXERCISE IN INTENSELY HOT AND HUMID ENVIRONMENTS, GENETIC POLYMORPHISMS (E.G. SICKLE CELL TRAIT AND MCARDLE DISEASE) AND EPIGENETIC MODIFICATIONS. THIS ARTICLE REVIEWS SEVERAL OF THESE RISK FACTORS AND PROPOSES SCREENING PROTOCOLS TO IDENTIFY INDIVIDUAL SUSCEPTIBILITY TO EXERTIONAL RHABDOMYOLYSIS AS WELL AS THE RELEVANCE OF PROTEOMICS FOR THE EVALUATION OF POTENTIAL BIOMARKERS OF MUSCLE DAMAGE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
4  2819 16 FILARIAL AND WOLBACHIA GENOMICS. FILARIAL NEMATODE PARASITES, THE CAUSATIVE AGENTS FOR A SPECTRUM OF ACUTE AND CHRONIC DISEASES INCLUDING LYMPHATIC FILARIASIS AND RIVER BLINDNESS, THREATEN THE WELL-BEING AND LIVELIHOOD OF HUNDREDS OF MILLIONS OF PEOPLE IN THE DEVELOPING REGIONS OF THE WORLD. THE 2007 PUBLICATION ON A DRAFT ASSEMBLY OF THE 95-MB GENOME OF THE HUMAN FILARIAL PARASITE BRUGIA MALAYI- REPRESENTING THE FIRST HELMINTH PARASITE GENOME TO BE SEQUENCED - HAS BEEN FOLLOWED IN RAPID SUCCESSION BY PROJECTS THAT HAVE RESULTED IN THE GENOME SEQUENCING OF SIX ADDITIONAL FILARIAL SPECIES, SEVEN NONFILARIAL NEMATODE PARASITES OF ANIMALS AND NEARLY 30 PLANT PARASITIC AND FREE-LIVING SPECIES. PARALLEL TO THE GENOMIC SEQUENCING, TRANSCRIPTOMIC AND PROTEOMIC PROJECTS HAVE FACILITATED GENOME ANNOTATION, EXPANDED OUR UNDERSTANDING OF STAGE-ASSOCIATED GENE EXPRESSION AND PROVIDED A FIRST LOOK AT THE ROLE OF EPIGENETIC REGULATION OF FILARIAL GENOMES THROUGH MICRORNAS. THE EXPANSION IN FILARIAL GENOMICS WILL ALSO PROVIDE A SIGNIFICANT ENRICHMENT IN OUR KNOWLEDGE OF THE DIVERSITY AND VARIABILITY IN THE GENOMES OF THE ENDOSYMBIOTIC BACTERIUM WOLBACHIA LEADING TO A BETTER UNDERSTANDING OF THE GENETIC PRINCIPLES THAT GOVERN FILARIAL-WOLBACHIA MUTUALISM. THE GOAL HERE IS TO PROVIDE AN OVERVIEW OF THE TRENDS AND ADVANCES IN FILARIAL AND WOLBACHIA GENOMICS.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
5  4979 21 PATHOPHYSIOLOGY AND TREATMENT OF SICKLE CELL DISEASE. CURRENT TREATMENT AND UNDERSTANDING OF SICKLE CELL DISEASE REQUIRE AN APPRECIATION FOR THE COMPLEXITY OF ITS BASIC PATHOPHYSIOLOGY. THE CLINICAL MANIFESTATIONS OF VASO-OCCLUSION RESULT FROM A DYNAMIC COMBINATION OF ABNORMALITIES IN HEMOGLOBIN STRUCTURE AND FUNCTION, RED BLOOD CELL MEMBRANE INTEGRITY, ERYTHROCYTE DENSITY, ENDOTHELIAL ACTIVATION, MICROVASCULAR TONE, INFLAMMATORY MEDIATORS, AND COAGULATION FACTORS. EXISTING AND EMERGING THERAPIES ADDRESS EACH OF THESE BIOLOGIC ALTERATIONS, INDIVIDUALLY AND COLLECTIVELY. EXAMPLES INCLUDE INDUCTION OF FETAL HEMOGLOBIN, MODULATION OF ERYTHROCYTE HYDRATION, AUGMENTATION OF NITRIC OXIDE, CHRONIC TRANSFUSION, STEM CELL TRANSPLANTATION, AND GENE THERAPY. UNDERSTANDING THE PLEIOTROPIC AND EPIGENETIC FACTORS INFLUENCING DISEASE PHENOTYPE MAY LEAD TO MORE TARGETED APPLICATION OF THESE THERAPIES.	2005	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
6  5763 14 SOME COMMENTS ON MASOCHISM AND THE DELUSION OF OMNIPOTENCE FROM A DEVELOPMENTAL PERSPECTIVE. THIS PAPER EXPLORES THE RELATION OF THE DELUSION OF OMNIPOTENCE TO MASOCHISM AND SUGGESTS THAT THIS FANTASY CONSTITUTES A MAJOR COMPONENT OF THE RESISTANCE SO PROMINENT IN WORK WITH MASOCHISTIC PATIENTS. THE CONNECTIONS AMONG MASOCHISM, OMNIPOTENCE, NEGATIVE THERAPEUTIC REACTION, AND CLINGING TO PAIN ARE DISCUSSED. THE CLASSICAL VIEW HAS BEEN THAT THE FAILURE OF INFANTILE OMNIPOTENCE FORCES THE CHILD TO TURN TO REALITY. OUR EXPERIENCE WITH MASOCHISTIC PATIENTS SUGGESTS THAT IT IS THE REAL FAILURE TO ACHIEVE COMPETENT INTERACTIONS WITH OTHERS THAT FORCES THE CHILD TO TURN TO OMNIPOTENT SOLUTIONS. THE DISTINCTION IS MADE BETWEEN FANTASIES THAT ENHANCE THE REAL CAPACITIES OF THE SELF AND THOSE AIMED AT DENYING AND TRANSFORMING THE PAIN AND INADEQUACY OF THE MOTHER-CHILD RELATIONSHIP. THE EPIGENETIC TRANSFORMATIONS OF OMNIPOTENT FANTASIES THROUGH ALL LEVELS OF DEVELOPMENT ARE DESCRIBED. THE PATIENT'S NEED TO PROTECT THE OMNIPOTENT FANTASY IS DISCUSSED IN RELATION TO RESISTANCE AT EACH PHASE OF ANALYSIS.	1991	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
7  1679 21 DRUG RESISTANCE IN GIARDIA DUODENALIS. GIARDIA DUODENALIS IS A MICROAEROPHILIC PARASITE OF THE HUMAN GASTROINTESTINAL TRACT AND A MAJOR CONTRIBUTOR TO DIARRHEAL AND POST-INFECTIOUS CHRONIC GASTROINTESTINAL DISEASE WORLD-WIDE. TREATMENT OF G. DUODENALIS INFECTION CURRENTLY RELIES ON A SMALL NUMBER OF DRUG CLASSES. NITROHETEROCYCLICS, IN PARTICULAR METRONIDAZOLE, HAVE REPRESENTED THE FRONT LINE TREATMENT FOR THE LAST 40 YEARS. NITROHETEROCYCLIC-RESISTANT G. DUODENALIS HAVE BEEN ISOLATED FROM PATIENTS AND CREATED IN VITRO, PROMPTING CONSIDERABLE RESEARCH INTO THE BIOMOLECULAR MECHANISMS OF RESISTANCE. THESE COMPOUNDS ARE REDOX-ACTIVE AND ARE BELIEVED TO DAMAGE PROTEINS AND DNA AFTER BEING ACTIVATED BY OXIDOREDUCTASE ENZYMES IN METABOLICALLY ACTIVE CELLS. IN THIS REVIEW, WE EXPLORE THE MOLECULAR PHENOTYPES OF NITROHETEROCYCLIC-RESISTANT G. DUODENALIS DESCRIBED TO DATE IN THE CONTEXT OF THE PROTIST'S UNUSUAL GLYCOLYTIC AND ANTIOXIDANT SYSTEMS. WE PROPOSE THAT RESISTANCE MECHANISMS ARE LIKELY TO EXTEND WELL BEYOND CURRENTLY DESCRIBED RESISTANCE-ASSOCIATED ENZYMES (I.E., PYRUVATE FERREDOXIN OXIDOREDUCTASES AND NITROREDUCTASES), TO INCLUDE NAD(P)H- AND FLAVIN-GENERATING PATHWAYS, AND POSSIBLY REDOX-SENSITIVE EPIGENETIC REGULATION. MECHANISMS THAT ALLOW G. DUODENALIS TO TOLERATE OXIDATIVE STRESS MAY LEAD TO RESISTANCE AGAINST BOTH OXYGEN AND NITROHETEROCYCLICS, WITH IMPLICATIONS FOR CLINICAL CONTROL. THE PRESENT REVIEW HIGHLIGHTS THE POTENTIAL FOR SYSTEMS BIOLOGY TOOLS AND ADVANCED BIOINFORMATICS TO FURTHER INVESTIGATE THE MULTIFACETED MECHANISMS OF NITROHETEROCYCLIC RESISTANCE IN THIS IMPORTANT PATHOGEN.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
8   760 18 CASZ1: CURRENT IMPLICATIONS IN CARDIOVASCULAR DISEASES AND CANCERS. CASTOR ZINC FINGER 1 (CASZ1) IS A C2H2 ZINC FINGER FAMILY PROTEIN THAT HAS TWO SPLICING VARIANTS, CASZ1A AND CASZ1B. IT IS INVOLVED IN MULTIPLE PHYSIOLOGICAL PROCESSES, SUCH AS TISSUE DIFFERENTIATION AND ALDOSTERONE ANTAGONISM. GENETIC AND EPIGENETIC ALTERNATIONS OF CASZ1 HAVE BEEN CHARACTERIZED IN MULTIPLE CARDIOVASCULAR DISORDERS, SUCH AS CONGENITAL HEART DISEASES, CHRONIC VENOUS DISEASES, AND HYPERTENSION. HOWEVER, LITTLE IS KNOWN ABOUT HOW CASZ1 MECHANICALLY PARTICIPATES IN THE PATHOGENESIS OF THESE DISEASES. OVER THE PAST DECADES, AT FIRST GLANCE, PARADOXICAL INFLUENCES ON CELL BEHAVIORS AND PROGRESSIONS OF DIFFERENT CANCER TYPES HAVE BEEN DISCOVERED FOR CASZ1, WHICH MAY BE EXPLAINED BY A "DOUBLE-AGENT" ROLE FOR CASZ1. IN THIS REVIEW, WE DISCUSS THE PHYSIOLOGICAL FUNCTION OF CASZ1, AND FOCUS ON THE ASSOCIATION OF CASZ1 ABERRATIONS WITH THE PATHOGENESIS OF CARDIOVASCULAR DISEASES AND CANCERS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
9  1401 13 DIETARY AND PHARMACOLOGICAL TREATMENT OF ABDOMINAL PAIN IN IBS. THIS REVIEW INTRODUCES THE PRINCIPLES OF VISCERAL SENSATION AND APPRAISES THE CURRENT APPROACHES TO MANAGEMENT OF VISCERAL PAIN IN FUNCTIONAL GI DISEASES, PRINCIPALLY IBS. THESE APPROACHES INCLUDE DIETARY MEASURES INCLUDING FIBRE SUPPLEMENTATION, LOW FERMENTABLE OLIGOSACCHARIDES, DISACCHARIDES, MONOSACCHARIDES AND POLYOLS DIET, AND PHARMACOLOGICAL APPROACHES SUCH AS ANTISPASMODICS, PEPPERMINT OIL, ANTIDEPRESSANTS (TRICYCLIC AGENTS, SELECTIVE SEROTONIN REUPTAKE INHIBITORS), 5-HT(3) RECEPTOR ANTAGONISTS (ALOSETRON, ONDANSETRON, RAMOSETRON), NON-ABSORBED ANTIBIOTIC (RIFAXIMIN), SECRETAGOGUES (LUBIPROSTONE, LINACLOTIDE), MU-OPIOID RECEPTOR (OR) AND KAPPA-OR AGONIST, DELTA-OR ANTAGONIST (ELUXADOLINE), HISTAMINE H1 RECEPTOR ANTAGONIST (EBASTINE), NEUROKININ-2 RECEPTOR ANTAGONIST (IBODUTANT) AND GABAERGIC AGENTS (GABAPENTIN AND PREGABALIN). EFFICACY AND SAFETY ARE DISCUSSED BASED ON PIVOTAL TRIALS OR PUBLISHED SYSTEMATIC REVIEWS AND META-ANALYSIS, EXPRESSING ORS OR RELATIVE RISKS AND THEIR 95% CIS. POTENTIAL NEW APPROACHES MAY BE BASED ON RECENT INSIGHTS ON MUCOSAL EXPRESSION OF GENES, AND MICRORNA AND EPIGENETIC MARKERS IN HUMAN BIOPSIES AND IN ANIMAL MODELS OF VISCERAL HYPERSENSITIVITY.THE OBJECTIVES OF THIS REVIEW ARE TO APPRAISE THE PHYSIOLOGY AND ANATOMY OF GUT SENSATION AND THE EFFICACY IN THE RELIEF OF VISCERAL PAIN (TYPICALLY IN IBS) OF SEVERAL CLASSES OF THERAPIES. THESE INCLUDE FERMENTABLE OLIGOSACCHARIDES, DISACCHARIDES, MONOSACCHARIDES AND POLYOLS (FODMAPS) AND DIFFERENT CLASSES OF MEDICATIONS (BOX 1). BOX 1CLASSES OF PHARMACOLOGICAL AGENTS FOR VISCERAL PAINANTIDEPRESSANTS (TRICYCLIC AGENTS, SELECTIVE SEROTONIN REUPTAKE INHIBITORS)PEPPERMINT OIL5-HT(3) RECEPTOR ANTAGONISTS (ALOSETRON, ONDANSETRON, RAMOSETRON)NON-ABSORBED ANTIBIOTIC (RIFAXIMIN)SECRETAGOGUES (LUBIPROSTONE, LINACLOTIDE)MU-OPIOID RECEPTOR (OR) AND KAPPA-OR AGONIST AND DELTA-OR ANTAGONIST (ELUXADOLINE)HISTAMINE H1 RECEPTOR ANTAGONIST (EBASTINE)NEUROKININ-2 RECEPTOR ANTAGONIST (IBODUTANT)GABAERGIC AGENTS (GABAPENTIN AND PREGABALIN).	2017	
                                                                                                                                                                                                                                                                              
10   681 20 BRAIN LIPOTOXICITY OF PHYTANIC ACID AND VERY LONG-CHAIN FATTY ACIDS. HARMFUL CELLULAR/MITOCHONDRIAL ACTIVITIES IN REFSUM DISEASE AND X-LINKED ADRENOLEUKODYSTROPHY. IT IS INCREASINGLY UNDERSTOOD THAT IN THE AGING BRAIN, ESPECIALLY IN THE CASE OF PATIENTS SUFFERING FROM NEURODEGENERATIVE DISEASES, SOME FATTY ACIDS AT PATHOLOGICALLY HIGH CONCENTRATIONS EXERT DETRIMENTAL ACTIVITIES. TO STUDY SUCH ACTIVITIES, WE HERE ANALYZE GENETIC DISEASES, WHICH ARE DUE TO COMPROMISED METABOLISM OF SPECIFIC FATTY ACIDS, EITHER THE BRANCHED-CHAIN PHYTANIC ACID OR VERY LONG-CHAIN FATTY ACIDS (VLCFAS). MICROMOLAR CONCENTRATIONS OF PHYTANIC ACID OR OF VLCFAS DISTURB THE INTEGRITY OF NEURAL CELLS BY IMPAIRING CA(2+) HOMEOSTASIS, ENHANCING OXIDATIVE STRESS OR DE-ENERGIZING MITOCHONDRIA. FINALLY, THESE COMBINED HARMFUL ACTIVITIES ACCELERATE CELL DEATH. MITOCHONDRIA ARE MORE SEVERELY TARGETED BY PHYTANIC ACID THAN BY VLCFAS. THE INSERTION OF VLCFAS INTO THE INNER MEMBRANE DISTORTS THE ARRANGEMENT OF MEMBRANE CONSTITUENTS AND THEIR FUNCTIONAL INTERACTIONS. PHYTANIC ACID EXERTS SPECIFIC PROTONOPHORIC ACTIVITY, INDUCES REACTIVE OXYGEN SPECIES (ROS) GENERATION, AND REDUCES ATP GENERATION. A CLEAR INHIBITION OF THE NA(+), K(+)-ATPASE ACTIVITY BY PHYTANIC ACID HAS ALSO BEEN REPORTED. IN ADDITION TO THE INSTANTANEOUS EFFECTS, A CHRONIC EXPOSURE OF BRAIN CELLS TO LOW MICROMOLAR CONCENTRATIONS OF PHYTANIC ACID MAY PRODUCE NEURONAL DAMAGE IN REFSUM DISEASE BY ALTERING EPIGENETIC TRANSCRIPTIONAL REGULATION. MYELIN-PRODUCING OLIGODENDROCYTES RESPOND WITH PARTICULAR SENSITIVITY TO VLCFAS. DELETERIOUS ACTIVITY OF VLCFAS ON ENERGY-DEPENDENT MITOCHONDRIAL FUNCTIONS DECLINES WITH INCREASING THE HYDROCARBON CHAIN LENGTH (C22:0 > C24:0 > C26:0). IN CONTRAST, THE REVERSE SEQUENCE HOLDS TRUE FOR CELL DEATH INDUCTION BY VLCFAS (C22:0 < C24:0 < C26:0). IN ADRENOLEUKODYSTROPHY, THE UPTAKE OF VLCFAS BY PEROXISOMES IS IMPAIRED BY DEFECTS OF THE ABCD1 TRANSPORTER. STUDYING MITOCHONDRIA FROM ABCD1-DEFICIENT AND WILD-TYPE MICE PROVES THAT THE ENERGY-DEPENDENT FUNCTIONS ARE NOT ALTERED IN THE DISEASE MODEL. THUS, A DEFECTIVE ABCD1 APPARENTLY EXERTS NO OBVIOUS ADAPTIVE PRESSURE ON MITOCHONDRIA. FURTHER RESEARCH HAS TO ELUCIDATE THE DETAILED MECHANISTIC BASIS FOR THE FAILURES CAUSING FATTY ACID-MEDIATED NEURODEGENERATION AND SHOULD HELP TO PROVIDE POSSIBLE THERAPEUTIC INTERVENTIONS.	2016	

11   238 17 ADENOSINE KINASE: A KEY REGULATOR OF PURINERGIC PHYSIOLOGY. ADENOSINE (ADO) IS AN ESSENTIAL BIOMOLECULE FOR LIFE THAT PROVIDES CRITICAL REGULATION OF ENERGY UTILIZATION AND HOMEOSTASIS. ADENOSINE KINASE (ADK) IS AN EVOLUTIONARY ANCIENT RIBOKINASE DERIVED FROM BACTERIAL SUGAR KINASES THAT IS WIDELY EXPRESSED IN ALL FORMS OF LIFE, TISSUES AND ORGAN SYSTEMS THAT TIGHTLY REGULATES INTRACELLULAR AND EXTRACELLULAR ADO CONCENTRATIONS. THE FACILE ABILITY OF ADK TO ALTER ADO AVAILABILITY PROVIDES A "SITE AND EVENT" SPECIFICITY TO THE ENDOGENOUS PROTECTIVE EFFECTS OF ADO IN SITUATIONS OF CELLULAR STRESS. IN ADDITION TO MODULATING THE ABILITY OF ADO TO ACTIVATE ITS COGNATE RECEPTORS (P1 RECEPTORS), NUCLEAR ADK ISOFORM ACTIVITY HAS BEEN LINKED TO EPIGENETIC MECHANISMS BASED ON TRANSMETHYLATION PATHWAYS. PREVIOUS DRUG DISCOVERY RESEARCH HAS TARGETED ADK INHIBITION AS A THERAPEUTIC APPROACH TO MANAGE EPILEPSY, PAIN, AND INFLAMMATION. THESE EFFORTS GENERATED MULTIPLE CLASSES OF HIGHLY POTENT AND SELECTIVE INHIBITORS. HOWEVER, CLINICAL DEVELOPMENT OF EARLY ADK INHIBITORS WAS STOPPED DUE TO APPARENT MECHANISTIC TOXICITY AND THE LACK OF SUITABLE TRANSLATIONAL MARKERS. NEW INSIGHTS REGARDING THE POTENTIAL ROLE OF THE NUCLEAR ADK ISOFORM (ADK-LONG) IN THE EPIGENETIC MODULATION OF MALADAPTIVE DNA METHYLATION OFFERS THE POSSIBILITY OF IDENTIFYING NOVEL ADK-ISOFORM SELECTIVE INHIBITORS AND NEW INTERVENTIONAL STRATEGIES THAT ARE INDEPENDENT OF ADO RECEPTOR ACTIVATION.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
12  3598 10 IMPLICATIONS ON HYPNOTHERAPY: NEUROPLASTICITY, EPIGENETICS AND PAIN. WE PROVIDE A BRIEF REVIEW ABOUT THE SIGNIFICANCE OF HYPNOSIS WITH RESPECT TO APPLICATIONS AND PHYSIOLOGICAL PROCESSES IN HYPNOTHERAPY. OUR REVIEW CONCLUDES THAT HYPNOSIS IS A PROMISING METHOD TO MANAGE ACUTE AND CHRONIC PAIN. IN ADDITION, WE DISCUSS INDICATIONS POINTING TOWARD THE VIEW THAT HYPNOSIS CAN INDUCE CHANGES IN NEUROPLASTICITY POSSIBLY INVOLVING EPIGENETIC MECHANISMS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
13  2640 23 EPIGENOMIC AND TRANSCRIPTIONAL PROFILING IDENTIFIES IMPAIRED GLYOXYLATE DETOXIFICATION IN NAFLD AS A RISK FACTOR FOR HYPEROXALURIA. EPIGENETIC MODIFICATIONS (E.G. DNA METHYLATION) IN NAFLD AND THEIR CONTRIBUTION TO DISEASE PROGRESSION AND EXTRAHEPATIC COMPLICATIONS ARE POORLY EXPLORED. HERE, WE USE AN INTEGRATED EPIGENOME AND TRANSCRIPTOME ANALYSIS OF MOUSE NAFLD HEPATOCYTES AND IDENTIFY ALTERATIONS IN GLYOXYLATE METABOLISM, A PATHWAY RELEVANT IN KIDNEY DAMAGE VIA OXALATE RELEASE-A HARMFUL WASTE PRODUCT AND KIDNEY STONE-PROMOTING FACTOR. DOWNREGULATION AND HYPERMETHYLATION OF ALANINE-GLYOXYLATE AMINOTRANSFERASE (AGXT), WHICH DETOXIFIES GLYOXYLATE, PREVENTING EXCESSIVE OXALATE ACCUMULATION, IS ACCOMPANIED BY INCREASED OXALATE FORMATION AFTER METABOLISM OF THE PRECURSOR HYDROXYPROLINE. VIRAL-MEDIATED AGXT TRANSFER OR INHIBITING HYDROXYPROLINE CATABOLISM RESCUES EXCESSIVE OXALATE RELEASE. IN HUMAN STEATOTIC HEPATOCYTES, AGXT IS ALSO DOWNREGULATED AND HYPERMETHYLATED, AND IN NAFLD ADOLESCENTS, STEATOSIS SEVERITY CORRELATES WITH URINARY OXALATE EXCRETION. THUS, THIS WORK IDENTIFIES A REDUCED CAPACITY OF THE STEATOTIC LIVER TO DETOXIFY GLYOXYLATE, TRIGGERING ELEVATED OXALATE, AND PROVIDES A MECHANISTIC EXPLANATION FOR THE INCREASED RISK OF KIDNEY STONES AND CHRONIC KIDNEY DISEASE IN NAFLD PATIENTS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
14  2649 16 EPIGENOMIC, GENOMIC, AND TRANSCRIPTOMIC LANDSCAPE OF SCHWANNOMATOSIS. SCHWANNOMATOSIS (SWNTS) IS A GENETIC CANCER PREDISPOSITION SYNDROME THAT MANIFESTS AS MULTIPLE AND OFTEN PAINFUL NEURONAL TUMORS CALLED SCHWANNOMAS (SWNS). WHILE GERMLINE MUTATIONS IN SMARCB1 OR LZTR1, PLUS SOMATIC MUTATIONS IN NF2 AND LOSS OF HETEROZYGOSITY IN CHROMOSOME 22Q HAVE BEEN IDENTIFIED IN A SUBSET OF PATIENTS, LITTLE IS KNOWN ABOUT THE EPIGENOMIC AND GENOMIC ALTERATIONS THAT DRIVE SWNTS-RELATED SWNS (SWNTS-SWNS) IN A MAJORITY OF THE CASES. WE PERFORMED MULTIPLATFORM GENOMIC ANALYSIS AND ESTABLISHED THE MOLECULAR SIGNATURE OF SWNTS-SWNS. WE SHOW THAT SWNTS-SWNS HARBOR DISTINCT GENOMIC FEATURES RELATIVE TO THE HISTOLOGICALLY IDENTICAL NON-SYNDROMIC SPORADIC SWNS (NS-SWNS). WE DEMONSTRATE THE EXISTENCE OF FOUR DISTINCT DNA METHYLATION SUBGROUPS OF SWNTS-SWNS THAT ARE ASSOCIATED WITH SPECIFIC TRANSCRIPTIONAL PROGRAMS AND TUMOR LOCATION. WE SHOW SEVERAL NOVEL RECURRENT NON-22Q DELETIONS AND STRUCTURAL REARRANGEMENTS. WE DETECTED THE SH3PXD2A-HTRA1 GENE FUSION IN SWNTS-SWNS, WITH PREDOMINANCE IN LZTR1-MUTANT TUMORS. IN ADDITION, WE IDENTIFIED SPECIFIC GENETIC, EPIGENETIC, AND ACTIONABLE TRANSCRIPTIONAL PROGRAMS ASSOCIATED WITH PAINFUL SWNTS-SWNS INCLUDING PIGF, VEGF, MEK, AND MTOR PATHWAYS, WHICH MAY BE HARNESSED FOR MANAGEMENT OF THIS SYNDROME.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
15  3862 18 ISOPATHIC USE OF AUTO-SARCODE OF DNA AS ANTI-MIASMATIC HOMEOPATHIC MEDICINE AND MODULATOR OF GENE EXPRESSION? INTRODUCTION: IN ADDITION TO THE FOUR PILLARS OF HOMEOPATHY, VITALISM AND THE MIASMATIC THEORY ARE OFTEN USED TO EXPLAIN THE HEALTH-DISEASE PROCESS. ACCORDING TO HAHNEMANN'S CONCEPTS, HOMEOPATHIC MIASMS ARE THE MAIN OBSTACLE TO THE CURE OF CHRONIC DISEASES, WITH PSORA BEING THE FUNDAMENTAL CAUSE OF ALL FORMS OF DISEASES. ACCORDING TO MODERN GENETICS, THE DISEASE-PROMOTING EPIGENETIC ALTERATIONS ARE THE FUNDAMENTAL CAUSE OF THE MANIFESTATION OF CHRONIC DISEASES. OBJECTIVE: THIS ARTICLE DEVELOPS A PHILOSOPHICAL-SCIENTIFIC CORRELATION BETWEEN CHRONIC MIASMS AND DISEASE-PROMOTING EPIGENETIC MODIFICATIONS, AIMING TO JUSTIFY THE ISOPATHIC USE OF AUTO-SARCODE OF AN INDIVIDUAL'S DNA AS HOMEOPATHIC MEDICINE. RESULTS: BASED ON THE STUDY OF HOMEOPATHIC DOCTRINE AND EPIGENETICS, A CONCEPTUAL AND FUNCTIONAL CORRELATION IS OBSERVED BETWEEN HOMEOPATHIC CHRONIC MIASMS AND DISEASE-PROMOTING EPIGENETIC MODIFICATIONS. ADDITIONALLY, SEVERAL EXPERIMENTAL STUDIES SUGGEST THAT HOMEOPATHY'S MECHANISM OF ACTION MAY BE BY MODULATING GENE EXPRESSION. CONCLUSIONS: BY THE PHILOSOPHICAL-SCIENTIFIC CORRELATIONS DESCRIBED, IT IS INFERRED THAT DISEASE-PROMOTING EPIGENETIC ALTERATIONS ARE THE BIOLOGICAL REPRESENTATION OF THE CHRONIC MIASMS, SUGGESTING THE ISOPATHIC USE OF AUTO-SARCODE OF DNA AS HOMEOPATHIC THERAPEUTIC MODULATOR OF GENE EXPRESSION FOR THE MANAGEMENT OF CHRONIC DISEASES.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
16  5154 22 PRAKRITI-BASED MEDICINE: A STEP TOWARDS PERSONALIZED MEDICINE. THE CONCEPT OF PERSONALIZED MEDICINE HAS BEEN AROUND FOR AS LONG AS PEOPLE HAVE BEEN PRACTICING MEDICINE. FROM CHARAKA TO HIPPOCRATES, ALL HAVE PRACTICED THE PERSONALIZED APPROACH FOR TREATING A DISEASE. IN THE 21(ST) CENTURY, PERSONALIZED MEDICINE IS ALL ABOUT DNA. WHEREAS THE SINGLE NUCLEOTIDE POLYMORPHISM (SNP) AND EPIGENETIC FACTORS INFLUENCE DRUG RESPONSE AND FORM THE BASIS OF PERSONALIZED MEDICINE, THE TRIDOSHA THEORY FORMS THE BASIS OF PRAKRITI-BASED MEDICINE. IT IS WELL ESTABLISHED BY NOW THAT WESTERN ALLOPATHIC MEDICINE IS EXCELLENT IN HANDLING ACUTE MEDICAL CRISES, WHEREAS AYURVEDA HAS SUCCESSFULLY DEMONSTRATED AN ABILITY TO MANAGE CHRONIC DISORDERS THAT WESTERN MEDICINE HAS BEEN UNABLE TO CURE. WITH EFFECTIVE INTEGRATION OF 'OMICS' PRAKRITI-BASED MEDICINE CAN PLAY A VITAL ROLE IN THIS CHANGING SCENARIO OF GLOBAL HEALTH WISDOM AS AYURVEDA OFFERS ITS MODALITIES BY WAY OF AHARA (DIET), VIHARA (LIFESTYLE), AND AUSHADHI (MEDICATION), WHICH ARE THE THREE PILLARS OF PRAKRITI-BASED MEDICINE MAKING IT A HOLISTIC SCIENCE. PRAKRITI-BASED MEDICINE AND OTHER TRADITIONAL MEDICINE SYSTEMS HAVE THE POTENTIAL TO OFFER REMEDIES TO THE CHALLENGING HEALTH ISSUES LIKE ADVERSE DRUG REACTIONS, DRUG WITHDRAWALS, AND ECONOMIC DISPARITIES AMONG FEW. AN INTEGRATIVE GLOBAL APPROACH COULD DO WONDERS TO HEALTH SCIENCES BENEFITING A BROAD SPECTRUM OF PATIENTS.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
17  3845 12 IS AGING A "RETRO"SPECTIVE EVENT? REACTIVATION OF ENDOGENOUS RETROVIRUSES (ERVS), THE RELICS OF ANCIENT INFECTIONS, HAS BEEN IMPLICATED IN A NUMBER OF DISEASE CONTEXTS. IN THIS ISSUE OF CELL, LIU ET AL. SHOW HOW REACTIVATION OF ERVS IN OLD AGE CAN INDUCE SENESCENCE. THIS AWAKENING OF ERVS IS ASSOCIATED WITH THEIR EPIGENETIC DEREPRESSION AND CONTRIBUTES TO AGE-ASSOCIATED CHRONIC INFLAMMATION.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
18  5501 23 REWRITING THE EPIGENETIC CODE FOR TUMOR RESENSITIZATION: A REVIEW. IN CANCER CHEMOTHERAPY, ONE AXIOM, WHICH HAS PRACTICALLY SOLIDIFIED INTO DOGMA, IS THAT ACQUIRED RESISTANCE TO ANTITUMOR AGENTS OR REGIMENS, NEARLY INEVITABLE IN ALL PATIENTS WITH METASTATIC DISEASE, REMAINS UNALTERABLE AND IRREVERSIBLE, RENDERING THERAPEUTIC RECHALLENGE FUTILE. HOWEVER, THE INTRODUCTION OF EPIGENETIC THERAPIES, INCLUDING HISTONE DEACETYLASE INHIBITORS (HDACIS) AND DNA METHYLTRANSFERASE INHIBITORS (DNMTIS), PROVIDES ONCOLOGISTS, LIKE COMPUTER PROGRAMMERS, WITH NEW TECHNIQUES TO "OVERWRITE" THE MODIFIABLE SOFTWARE PATTERN OF GENE EXPRESSION IN TUMORS AND CHALLENGE THE "ONE AND DONE" TREATMENT PRESCRIPTION. TAKING THE EPIGENETIC CODE-AS-SOFTWARE ANALOGY A STEP FURTHER, IF CHEMORESISTANCE IS THE PRODUCT OF MULTIPLE NONGENETIC ALTERATIONS, WHICH DEVELOP AND ACCUMULATE OVER TIME IN RESPONSE TO TREATMENT, THEN THE POSSIBILITY TO HACK OR TWEAK THE OPERATING SYSTEM AND FALL BACK ON A "SYSTEM RESTORE" OR "UNDO" FEATURE, LIKE THE ARROW ICON IN THE WINDOWS XP TOOLBAR, RECONFIGURING THE TUMOR TO ITS BASELINE NONRESISTANT STATE, HOLDS TREMENDOUS PROMISE FOR TURNING ADVANCED, METASTATIC CANCER FROM A FATAL DISEASE INTO A CHRONIC, LIVABLE CONDITION. THIS REVIEW AIMS 1) TO EXPLORE THE POTENTIAL MECHANISMS BY WHICH A GROUP OF SMALL MOLECULE AGENTS INCLUDING HDACIS (ENTINOSTAT AND VORINOSTAT), DNMTIS (DECITABINE AND 5-AZACYTIDINE), AND REDOX MODULATORS (RRX-001) MAY REPROGRAM THE TUMOR MICROENVIRONMENT FROM A REFRACTORY TO A NONREFRACTORY STATE, 2) HIGHLIGHT SOME RECENT FINDINGS, AND 3) DISCUSS WHETHER THE CURRENT "ONCE BURNED FOREVER SPURNED" PARADIGM IN THE TREATMENT OF METASTATIC DISEASE SHOULD BE REVISED TO PROMOTE ACTIVE RESENSITIZATION ATTEMPTS WITH FORMERLY FAILED CHEMOTHERAPIES.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
19  3626 17 IN-SILICO DISCOVERY OF DUAL ACTIVE MOLECULE TO RESTORE SYNAPTIC WIRING AGAINST AUTISM SPECTRUM DISORDER VIA HDAC2 AND H3R INHIBITION. METAL-DEPENDENT HISTONE DEACETYLASES (HDACS) ARE ESSENTIAL EPIGENETIC REGULATORS; THEIR MOLECULAR AND PHARMACOLOGICAL ROLES IN MEDICALLY CRITICAL DISEASES SUCH AS NEUROPSYCHIATRIC DISORDERS, NEURODEGENERATION, AND CANCER ARE BEING STUDIED GLOBALLY. HDAC2'S DIFFERENTIAL EXPRESSION IN THE CENTRAL NERVOUS SYSTEM MAKES IT AN APPEALING THERAPEUTIC TARGET FOR CHRONIC NEUROLOGICAL DISEASES LIKE AUTISM SPECTRUM DISORDER. IN THIS STUDY, WE IDENTIFIED H3R INHIBITOR MOLECULES THAT ARE COMPUTATIONALLY EFFECTIVE AT BINDING TO THE HDAC2 METAL-COORDINATED BINDING SITE. THE STUDY HIGHLIGHTS THE IMPORTANCE OF PITOLISANT IN SCREENING THE POTENTIAL H3R INHIBITORS BY USING A HYBRID WORKFLOW OF LIGAND AND RECEPTOR-BASED DRUG DISCOVERY. THE SCREENED LEAD COMPOUNDS WITH PUBCHEM SIDS 103179850, 103185945, AND 103362074 SHOW VIABLE BINDING WITH HDAC2 IN SILICO. THE IMPORTANCE OF LIGAND CONTACTS WITH THE ZN2+ ION IN THE HDAC2 CATALYTIC SITE IS ALSO DISCUSSED AND INVESTIGATED FOR A SIGNIFICANT ROLE IN ENZYME INHIBITION. THE PROPOSED H3R INHIBITORS 103179850, 103185945, AND 103362074 ARE ESTIMATED AS DUAL-ACTIVE MOLECULES TO BLOCK THE HDAC2-MEDIATED DEACETYLATION OF THE EAAT2 GENE (SLC1A2) AND H3R-MEDIATED SYNAPTIC TRANSMISSION IRREGULARITY AND ARE, THEREFORE, OPEN FOR EXPERIMENTAL VALIDATION.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
20  3157 21 GLYCEMIC MEMORY. PURPOSE OF REVIEW: THE MISTAKE OF PREDICTING THE FUTURE IS PERHAPS NOT TENDING TO REPRESSED OR PAST MEMORIES. HAMLET'S 17TH-CENTURY SOLILOQUY 'THE HEARTACHE AND THE THOUSAND NATURAL SHOCKS, THAT FLESH IS HEIR TO', (3.1. 7-8) IS A TALE THAT LOOKS BEYOND THE PRESENT BY LINKING THE PAST WITH THE FUTURE. THE PRESENT ARTICLE EXAMINES THE RESURGENCE IN THE FIELD TO UNDERSTAND GENE-REGULATING EPIGENETIC CHANGES CONFERRING GLYCEMIC MEMORY. RECENT FINDINGS: CHROMATIN MODIFICATIONS ARE CRITICAL IN REGULATING GENOME STRUCTURE AND FUNCTION AND DESPITE THE SIGNIFICANT ADVANCES OF RECENT YEARS IN IDENTIFYING THE ENZYMES-MEDIATING CHEMICAL CHANGES TO HISTONE TAILS AND THE DNA TEMPLATE, THE PRECISE REGULATION OF GENE EXPRESSION REMAINS INCOMPLETE IN MODELS OF HEALTH AND DIABETIC COMPLICATIONS. SUMMARY: DISPELLING THE MYTH THAT ALL GENOMES ARE DRIVEN AND RESPOND EQUALLY, EXPERIMENTAL RESEARCH IS NOW UNCOVERING THE FUNCTION OF ENZYMES CONFERRING CHROMATIN MODIFICATIONS. WHATEVER THE ROLE OF THE EPIGENOME, SHOWING ITS INVOLVEMENT IN GLYCEMIC SIGNALING IS THE FIRST STEP TO NEW STRATEGIES AND TARGETS TO DEVELOP THERAPIES THAT PREVENT, RETARD OR REVERSE THE LONG-TERM DELETERIOUS END-ORGAN EFFECTS OF CHRONIC, INTERMITTENT AND PRIOR HYPERGLYCEMIA.	2012