Search results for "design."

showing 10 items of 5715 documents

2,3-Dihydrobenzofuran privileged structures as new bioinspired lead compounds for the design of mPGES-1 inhibitors

2016

International audience; 2,3-Dihydrobenzofurans are proposed as privileged structures and used as chemical platform to design small compound libraries. By combining molecular docking calculations and experimental verification of biochemical interference, we selected some potential inhibitors of microsomal prostaglandin E2 synthase (mPGES)-1. Starting from low affinity natural product 1, by our combined approach we identified the compounds 19 and 20 with biological activity in the low micromolar range. Our data suggest that the 2,3-dihydrobenzofuran derivatives might be suitable bioinspired lead compounds for development of new generation mPGES-1 inhibitors with increased affinity.

0301 basic medicine300323-Dihydrobenzofuran privileged structure; Cancer; Inflammation; Molecular docking; mPGES-1 inhibitors; Biochemistry; Clinical Biochemistry; Molecular Biology; Molecular Medicine; Organic Chemistry; Drug Discovery3003 Pharmaceutical Science; 3003Amino Acid MotifsClinical BiochemistryGene ExpressionPharmaceutical Science01 natural sciencesClinical biochemistryBiochemistry[ CHIM ] Chemical SciencesProtein Structure Secondary[ SDV.CAN ] Life Sciences [q-bio]/Cancerchemistry.chemical_compoundLow affinityDrug DiscoveryEnzyme Inhibitors23-Dihydrobenzofuran privileged structure; Molecular docking; mPGES-1 inhibitors; Cancer; InflammationProstaglandin-E SynthasesCancerAnti-Inflammatory Agents Non-SteroidalBiological activityProto-Oncogene Proteins c-metIntramolecular OxidoreductasesMolecular Docking SimulationMolecular dockingMolecular Medicinelipids (amino acids peptides and proteins)Cell SurvivalStereochemistryMolecular Sequence Data2Antineoplastic Agents[SDV.CAN]Life Sciences [q-bio]/Cancer3-Dihydrobenzofuran privileged structureInhibitory Concentration 50Structure-Activity Relationship03 medical and health sciencesCell Line TumorMicrosomesHumans[CHIM]Chemical SciencesMolecular BiologyBenzofuransInflammationNatural product010405 organic chemistryDrug Discovery3003 Pharmaceutical ScienceOrganic ChemistryEpithelial CellsmPGES-1 inhibitorsCombinatorial chemistryCombined approach0104 chemical sciences030104 developmental biologychemistryDrug DesignDrug Screening Assays Antitumor
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Long-term outcomes and predictive ability of non-invasive scoring systems in patients with non-alcoholic fatty liver disease.

2021

[Background & Aims] Non-invasive scoring systems (NSS) are used to identify patients with non-alcoholic fatty liver disease (NAFLD) who are at risk of advanced fibrosis, but their reliability in predicting long-term outcomes for hepatic/extrahepatic complications or death and their concordance in cross-sectional and longitudinal risk stratification remain uncertain.

0301 basic medicineAdultMalemedicine.medical_specialtyCirrhosisConcordanceSettore MED/12 - GASTROENTEROLOGIAHFSDiseaseBARDGastroenterologySeverity of Illness IndexTime03 medical and health sciences0302 clinical medicineFibrosisNon-alcoholic Fatty Liver DiseasePredictive Value of TestsInternal medicineNFSmedicineHumansIn patientAPRINSSHepatologybusiness.industryFatty liverNASHReproducibility of ResultsMiddle Agedmedicine.diseasePrognosisAPRI BARD FIB-4 HFS NASH NFS NSS Adult Area Under Curve Cross-Sectional Studies Female Humans Liver MaleMiddle Aged Non-alcoholic Fatty Liver DiseasePrognosis ROC CurveReproducibility of Results Research Design Severity of Illness Index Predictive Value of Tests Time030104 developmental biologyCross-Sectional StudiesLiverROC CurveResearch DesignArea Under CurveCohortAPRI; BARD; FIB-4; HFS; NASH; NFS; NSSFIB-4030211 gastroenterology & hepatologyFemalebusinessLiver cancerJournal of hepatology
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High-definition transcranial direct current stimulation to both primary motor cortices improves unimanual and bimanual dexterity.

2017

While most research on brain stimulation with transcranial direct current stimulation (tDCS) targets unimanual motor tasks, little is known about its effects on bimanual motor performance. This study aims to investigate the effects of tDCS on unimanual as well as bimanual motor dexterity. We examined the effects of bihemispheric anodal high-definition tDCS (HD-atDCS) on both primary motor cortices (M1) applied concurrent with unimanual and bimanual motor training. We then measured the effects with the Purdue Pegboard Test (PPT) and compared them to a sham stimulation. Between a pretest and posttest, 31 healthy, right-handed participants practiced the PPT on three consecutive days and receiv…

0301 basic medicineAdultMalemedicine.medical_specialtymedicine.medical_treatmentStimulationTranscranial Direct Current StimulationFunctional Laterality03 medical and health sciencesYoung Adult0302 clinical medicinePhysical medicine and rehabilitationmedicinePurdue Pegboard TestHumansTranscranial direct-current stimulationGeneral NeuroscienceMotor CortexRepeated measures designEvoked Potentials MotorHandElectric StimulationImproved performance030104 developmental biologyMotor SkillsBrain stimulationHigh definitionFemaleAnalysis of variancePsychology030217 neurology & neurosurgeryPsychomotor PerformanceCognitive psychologyNeuroscience letters
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Combination of metabolism measurement and a time-lapse system provides an embryo selection method based on oxygen uptake and chronology of cytokinesi…

2016

Objective To evaluate correlations between oxygen consumption (OC) measurements before and after embryo cytokinesis, observing OC during embryo cleavages and combining that information with morphokinetics to relate to implantation potential. Design Prospective cohort study. Setting University-affiliated private IVF unit. Patient(s) A total of 1,150 injected oocytes in 86 first oocyte donation cycles with embryo transfer on day 3. Intervention(s) None. Main Outcome Measurement(s) We analyzed the embryo OC and combined this data with the cytokinesis event, exact timing (in hours) of blastomeric cleavages, with the use of an incubator equipped with time-lapse videography, gathering a total of …

0301 basic medicineAdultmedicine.medical_specialtyanimal structuresTime FactorsAdolescentPregnancy RateCell SurvivalTransducersVideo RecordingBiologyTime-Lapse ImagingAndrologyEmbryo Culture Techniques03 medical and health sciencesYoung Adult0302 clinical medicinePredictive Value of TestsPregnancymedicineHumansEmbryo ImplantationProspective StudiesSperm Injections IntracytoplasmicCytokinesis030219 obstetrics & reproductive medicineMiniaturizationEmbryogenesisObstetrics and GynecologyEmbryoMetabolismEquipment DesignEmbryo TransferEmbryo MammalianEmbryo transferSurgeryOxygenPregnancy rate030104 developmental biologyTreatment OutcomeReproductive Medicineembryonic structuresFemaleSelection methodEnergy MetabolismEmbryo qualityCytokinesisFertility and sterility
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Does telomere length predict decline in physical functioning in older twin sisters during an 11-year follow-up?

2016

Background: Leucocyte telomere length (LTL) is known to be associated with mortality, but its association with age-related decline in physical functioning and the development of disability is less clear. This study examined the associations between LTL and physical functioning, and investigated whether LTL predicts level of physical functioning over an 11- year follow-up. Methods: Older mono- (MZ) and dizygotic (DZ) twin sisters (n=386) participated in the study. Relative LTL was measured by qPCR at baseline. Physical functioning was measured by 6-min walking distance and level of physical activity (PA). Walking distance was measured at baseline and at 3-year follow-up. PA was assessed by q…

0301 basic medicineAgingmissing data not at randomTwinsphysical activitysix-minute walking testENVIRONMENTAL-FACTORSDevelopmental psychologyPhysical functioningMAXIMAL WALKING SPEEDSix-minute walking testLeukocytesMedicinetwin studyFinlandtelomereHERITABILITYWOMENTwin studyASSOCIATIONGeneral MedicineMiddle AgedTelomere3142 Public health care science environmental and occupational healthSurvival RateCARDIOVASCULAR-DISEASEbiological agingDisease ProgressionFemalePhysical activityfyysinen toimintakykyMotor ActivityArticleBiological aging03 medical and health sciencesWalking distanceAGEDiseases in TwinsHumansMissing data not at randomMotor activityMobility LimitationMETAANALYSISAgedPhysical activitybusiness.industryMORTALITYDisease progressionRepeated measures designHeritabilityTwin study030104 developmental biology3121 General medicine internal medicine and other clinical medicineGeriatrics and GerontologyDANISH TWINSbusinessPhysical functioningDemographyForecasting
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Cytoprotective and antioxidant properties of organic selenides for the myelin-forming cells, oligodendrocytes.

2018

Abstract Here a new series of twenty-one organoselenides, of potential protective activity, were synthesized and tested for their intrinsic cytotoxicity, anti-apoptotic and antioxidant capacities in oligodendrocytes. Most of the organoselenides were able to decrease the ROS levels, revealing antioxidant properties. Compounds 5b and 7b showed a high glutathione peroxidase (GPx)-like activities, which were 1.5 folds more active than ebselen. Remarkably, compound 5a diminished the formation of the oligodendrocytes SubG1 peak in a concentration-dependent manner, indicating its anti-apoptotic properties. Furthermore, based on the SwissADME web interface, we performed an in-silico structure-activ…

0301 basic medicineAntioxidantCell Survivalmedicine.medical_treatmentMolecular ConformationApoptosisCrystallography X-RayProtective Agents01 natural sciencesBiochemistryAntioxidantsCell Line03 medical and health scienceschemistry.chemical_compoundMyelinMiceStructure-Activity RelationshipOrganoselenium CompoundsDrug DiscoverymedicineAnimalsCytotoxicityMolecular Biologychemistry.chemical_classification010405 organic chemistryEbselenGlutathione peroxidaseOrganic ChemistryNeurodegenerationCells oligodendrocytesmedicine.diseaseG1 Phase Cell Cycle Checkpoints0104 chemical sciencesOligodendroglia030104 developmental biologymedicine.anatomical_structurechemistryBiochemistryApoptosisDrug DesignReactive Oxygen SpeciesBioorganic chemistry
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Conceptual framework for precision cancer medicine in Germany: Consensus statement of the Deutsche Krebshilfe working group ‘Molecular Diagnostics an…

2020

Precision cancer medicine (PCM) holds great promises to offer more effective therapies to patients based on molecular profiling of their individual tumours. Although the PCM approach seems intuitive, multiple conceptional and structural challenges interfere with the broad implementation of PCM into clinical practice. Accordingly, concerted national and international efforts are needed to guide the further development and broad adoption of PCM in Germany. With support of the 'German Cancer Aid' (Deutsche Krebshilfe [DKH]) a task force 'Molecular Diagnostics and Therapy' was implemented. In two workshops supported by the DKH, delegates from the fourteen comprehensive cancer centresidentified …

0301 basic medicineCancer ResearchCollaborative strategyConsensusDelphi TechniqueComputer scienceMedizinAntineoplastic AgentsComputer-assisted web interviewing03 medical and health sciences0302 clinical medicineCancer MedicinePredictive Value of TestsGermanyNeoplasmsHumansProfiling (information science)Molecular Targeted TherapyPrecision MedicineTask forceMolecular diagnosticsPrecision medicineEngineering management030104 developmental biologyMolecular Diagnostic TechniquesOncologyConceptual frameworkResearch Design030220 oncology & carcinogenesisEuropean Journal of Cancer
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The calm before the storm: a report from the International Liver Cancer Association Congress 2015 – part 2

2016

International Liver Cancer Association Congress 2015, Paris, France, 4–6 September 2015 Since its creation 9 years ago, in 2007, the International Liver Cancer Association has focused on the multidisciplinary approach to liver cancer due to advances in hepatology science and care worldwide. In its 2015 annual conference, held on 4–6 September in Paris, France, the most recent progresses in the basic biology, management and treatment of liver cancer have been presented. This report, divided into two parts, introduces and critically reviews some of the most intriguing topics discussed at the meeting.

0301 basic medicineCancer Researchmedicine.medical_specialtyPathologysurvivalliver cancer03 medical and health sciences0302 clinical medicineInternal medicinestaging systemmedicineHCC; immunotherapy; liver cancer; management; prognosis; sorafenib; staging system; survival; trial design; Carcinoma Hepatocellular; Disease Management; Humans; Liver Neoplasms; Oncology; Cancer ResearchHumansHCCDisease management (health)Staging systembusiness.industryCarcinomaLiver NeoplasmsDisease ManagementHepatocellularGeneral MedicineHepatologymedicine.disease030104 developmental biologyOncologyFamily medicinetrial designsorafenib030211 gastroenterology & hepatologyimmunotherapyprognosisbusinessLiver cancermanagementFuture Oncology
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Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative tra…

2019

Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic…

0301 basic medicineCandidate geneEsophageal MucosaEsophageal NeoplasmsMedizinGene ExpressionGenome-wide association study0302 clinical medicineMathematical and Statistical TechniquesGeneticsMultidisciplinarySodium-Hydrogen Exchanger 3QStatisticsRGenomicsMetaanalysisGene Expression Regulation NeoplasticResearch Design030220 oncology & carcinogenesisPhysical SciencesMedicineResearch Articlemedicine.medical_specialtyScienceQuantitative Trait LociReplication StudiesContext (language use)BiologyAdenocarcinomaResearch and Analysis MethodsPolymorphism Single NucleotideMolecular Genetics03 medical and health sciencesBarrett EsophagusMolecular geneticsmedicineGeneticsGenome-Wide Association StudiesHumansGenetic Predisposition to DiseaseGene RegulationStatistical MethodsGeneMolecular BiologyGenetic associationProteinsBiology and Life SciencesComputational BiologyHuman Geneticsmedicine.diseaseGenome AnalysisRepressor Proteins030104 developmental biologyGenetic LociBarrett's esophagusExpression quantitative trait lociGenetics of DiseaseMathematicsGenome-Wide Association StudyPloS one
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Genetic susceptibility to angiotensin-converting enzyme-inhibitor induced angioedema: A systematic review and evaluation of methodological approaches.

2019

Angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II which causes vasoconstriction. ACE inhibitors reduce blood pressure by inhibiting ACE. A well-known adverse drug reaction to ACE inhibitors is ACE inhibitor-induced angioedema (ACEi-AE). Angioedema is a swelling of skin and mucosa, which can be fatal if the airway is compromised. We have performed a systematic review of the evidence suggesting that genetic polymorphisms are associated with ACEi-AE and evaluated the methodological approaches of the included studies. The Cochrane Database of Systematic Reviews, Google Scholar, and PubMed were searched. Studies investigating the association between genetic markers and…

0301 basic medicineCandidate geneHeredityACE inhibitorsGenome-wide association studyAngiotensin-Converting Enzyme InhibitorsBioinformatics030226 pharmacology & pharmacyBiochemistryDatabase and Informatics Methods0302 clinical medicineOutcome Assessment Health CareMedicine and Health SciencesDatabase SearchingMultidisciplinarybiologyQRDrugsEnzyme inhibitorsGenomicsResearch AssessmentGenetic MappingSystematic reviewResearch DesignMedicinemedicine.symptomResearch ArticleSystematic ReviewsScienceResearch and Analysis Methods03 medical and health sciencesAdverse ReactionsGenetic predispositionmedicineGenome-Wide Association StudiesGeneticsHumansGenetic Predisposition to DiseaseAngioedemaPharmacologyEvolutionary BiologyPolymorphism GeneticAngioedemaBiology and life sciencesPopulation Biologybusiness.industryCase-control studyComputational BiologyCorrectionAngiotensin-converting enzymeHuman GeneticsGenome AnalysisAngiotensin II030104 developmental biologyHaplotypesCase-Control Studiesbiology.proteinEnzymologyGenetic PolymorphismbusinessPopulation GeneticsPloS one
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