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showing 10 items of 360 documents

In Vivo siRNA Delivery to Immunosuppressive Liver Macrophages by alpha-Mannosyl-Functionalized Cationic Nanohydrogel Particles

2020

Macrophages are the front soldiers of the innate immune system and are vital for immune defense, tumor surveillance, and tissue homeostasis. In chronic diseases, including cancer and liver fibrosis, macrophages can be forced into an immunosuppressive and profibrotic M2 phenotype. M2-type macrophages overexpress the mannose receptor CD206. Targeting these cells via CD206 and macrophage repolarization towards an immune stimulating and antifibrotic M1 phenotype through RNA interference represents an appealing therapeutic approach. We designed nanohydrogel particles equipped with mannose residues on the surface (ManNP) that delivered siRNA more efficiently to M2 polarized macrophages compared t…

0301 basic medicineLiver CirrhosissiRNA deliveryTHP-1 Cellsmedicine.medical_treatmentmannose targetingMice0302 clinical medicineDrug Delivery SystemsFibrosisMacrophageM2 macrophagesRNA Small Interferinglcsh:QH301-705.5Tissue homeostasisMice Inbred BALB CChemistryHydrogelsGeneral MedicineHep G2 CellsLiver030220 oncology & carcinogenesisFemaleimmunotherapyMannose receptorMannose ReceptorReceptors Cell Surfacegene knock-downArticlenanohydrogels03 medical and health sciencesImmune systemIn vivomedicineImmune ToleranceAnimalsHumanscancerLectins C-TypeInnate immune systemMacrophagesfibrosisImmunotherapyMacrophage Activationmedicine.disease030104 developmental biologyMannose-Binding LectinsRAW 264.7 Cellslcsh:Biology (General)Cancer researchNanoparticlesMannose
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CD16+ Macrophages Mediate Fibrosis in Inflammatory Bowel Disease.

2017

Background and Aims Fibrosis is a common complication of Crohn's disease [CD], and is related to dysregulated tissular repair following inflammation, in which macrophages play a central role. We have previously observed that STAT6-/- mice present delayed mucosal recovery after 2,4,6-trinitrobenzenesulfonic acid [TNBS]-induced colitis due to a deficiency in reparatory interleukin-4 [IL4]/STAT6-dependent M2 macrophages, which can be reverted by the exogenous transfer of this cell type. In the present study, we analyse the role of STAT6-dependent macrophages in intestinal fibrosis. Methods Colitis was induced by weekly intra-rectal administration of TNBS [6 weeks] to STAT6-/- mice and wild-typ…

0301 basic medicineMaleCell CountInflammatory bowel diseaseMiceCrohn DiseaseFibrosisMacrophageIntestinal MucosaCells CulturedMice Knockouteducation.field_of_studyMice Inbred BALB Cintegumentary systemGastroenterologyGeneral MedicineColitisColonic NeoplasmsFemalemedicine.symptomMannose ReceptorAdultAdolescentColonPopulationInflammationReceptors Cell SurfaceCD1603 medical and health sciencesYoung AdultProto-Oncogene Proteinsparasitic diseasesmedicineAnimalsHumansLectins C-TypeColitiseducationInterleukin 4business.industryMacrophagesReceptors IgGmedicine.diseaseFibrosisWnt Proteins030104 developmental biologyMannose-Binding LectinsTrinitrobenzenesulfonic AcidImmunologyInterleukin-4businessSTAT6 Transcription FactorJournal of Crohn'scolitis
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NKCC1-Mediated GABAergic Signaling Promotes Postnatal Cell Death in Neocortical Cajal-Retzius Cells.

2016

During early development, a substantial proportion of central neurons undergoes programmed cell death. This activity-dependent process is essential for the proper structural and functional development of the brain. To uncover cell type-specific differences in the regulation of neuronal survival versus apoptosis, we studied activity-regulated cell death in Cajal-Retzius neurons (CRNs) and the overall neuronal population in the developing mouse cerebral cortex. CRNs in the upper neocortical layer represent an early-born neuronal population, which is important for cortical development and largely disappears by apoptosis during neonatal stages. In contrast to the overall neuronal population, ac…

0301 basic medicineMaleProgrammed cell deathCognitive NeuroscienceApoptosisNeocortexReceptors Cell SurfaceBiologygamma-Aminobutyric acid03 medical and health sciencesCellular and Molecular NeuroscienceMice0302 clinical medicinemedicineAnimalsLectins C-TypeGABAergic NeuronsCells Culturedgamma-Aminobutyric AcidMice KnockoutNeocortexGABAA receptorDepolarizationInterstitial Cells of CajalReceptors GABA-AMice Inbred C57BL030104 developmental biologymedicine.anatomical_structurenervous systemAnimals NewbornCerebral cortexApoptosisFemaleSignal transductionNeuroscience030217 neurology & neurosurgerymedicine.drugSignal TransductionCerebral cortex (New York, N.Y. : 1991)
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Sng1 associates with Nce102 to regulate the yeast Pkh–Ypk signalling module in response to sphingolipid status

2016

International audience; All cells are delimited by biological membranes, which are consequently a primary target of stress-induced damage. Cold alters membrane functionality by decreasing lipid fluidity and the activity of membrane proteins. In Saccharomyces cerevisiae, evidence links sphingolipid homeostasis and membrane phospholipid asymmetry to the activity of the Ypk1/2 proteins, the yeast orthologous of the mammalian SGK1-3 kinases. Their regulation is mediated by different protein kinases, including the PDK1 orthologous Pkh1/2p, and requires the function of protein effectors, among them Nce102p, a component of the sphingolipid sensor machinery. Nevertheless, the mechanisms and the act…

0301 basic medicineMyriocinOrm2Saccharomyces-cerevisiaeMembrane propertiesFatty Acids MonounsaturatedGlycogen Synthase Kinase 3Bacteriocins[SDV.IDA]Life Sciences [q-bio]/Food engineeringHomeostasisPhosphorylationMicroscopy ConfocalbiologyEffectorPlasma-membraneActin cytoskeleton[ SDV.IDA ] Life Sciences [q-bio]/Food engineeringPhospholipid translocationTransmembrane proteinCell biologyCold TemperatureBiochemistryP-type atpasesSignal transductionCold stressCell-wall integrityProtein BindingSignal TransductionProteins slm1Saccharomyces cerevisiae ProteinsPhospholipid translocationHigh-pressureSaccharomyces cerevisiaeImmunoblottingFluorescence PolarizationSaccharomyces cerevisiaeSignallingModels Biological3-Phosphoinositide-Dependent Protein Kinases03 medical and health sciencesBudding yeastMolecular BiologySphingolipids030102 biochemistry & molecular biologyTryptophan permeasePhospholipid flippingMembrane ProteinsCell Biologybiology.organism_classificationActin cytoskeletonSphingolipidYeast030104 developmental biologyMembrane proteinMutationPeptidesReactive Oxygen Species
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Evaluation of Second-line Anti-VEGF after First-line Anti-EGFR Based Therapy in RAS Wild-Type Metastatic Colorectal Cancer: The Multicenter “SLAVE” S…

2020

: Background: The optimal anti-angiogenic strategy as second-line treatment in RAS wild-type metastatic colorectal cancer (mCRC) treated with anti-EGFR (Epidermal Growth Factor Receptor) based first-line treatment is still debated. Methods: This multicenter, real-world, retrospective study is aimed at evaluating the effectiveness of second-line Bevacizumab- and Aflibercept-based treatments after an anti-EGFR based first-line regimen. Clinical outcomes measured were: objective response rate (ORR), progression free survival (PFS), overall survival (OS) and adverse events (AEs) profiles. Results: From February 2011 to October 2019, 277 consecutive mCRC patients received Bevacizumab-based (228,…

0301 basic medicineOncologyCancer Researchmedicine.medical_specialtyBevacizumabColorectal cancerAnti-angiogenicCetuximablcsh:RC254-282Article03 medical and health sciences0302 clinical medicineInternal medicinemedicinePanitumumabProgression-free survivalAfliberceptRAS wild-type mCRCPerformance statusCetuximabbusiness.industryPanitumumabanti-angiogenicsmedicine.diseaselcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogensBevacizumabRegimen030104 developmental biologyOncology030220 oncology & carcinogenesissecond-line treatmentbusinessAfliberceptaflibercept; anti-angiogenics; bevacizumab; cetuximab; panitumumab; ras wild-type mcrc; second-line treatmentmedicine.drugCancers
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A targeted proteomics investigation of the obesity paradox in venous thromboembolism

2021

Abstract The obesity paradox, the controversial finding that obesity promotes disease development but protects against sequelae in patients, has been observed in venous thromboembolism (VTE). The aim of this investigation was to identify a body mass–related proteomic signature in VTE patients and to evaluate whether this signature mediates the obesity paradox in VTE patients. Data from the Genotyping and Molecular Phenotyping in Venous ThromboEmbolism Project, a prospective cohort study of 693 VTE patients, were analyzed. A combined end point of recurrent VTE or all-cause death was used. Relative quantification of 444 proteins was performed using high-throughput targeted proteomics technolo…

0301 basic medicineOncologyProteomicsmedicine.medical_specialtyDisease030204 cardiovascular system & hematologyThrombosis and Hemostasis03 medical and health sciences0302 clinical medicineRisk FactorsInternal medicinemedicineHumansLectins C-Typecardiovascular diseasesObesityProspective StudiesReceptors ImmunologicProspective cohort studyGenotypingMembrane Glycoproteinsbusiness.industryLeptinHazard ratioHematologyVenous Thromboembolismmedicine.diseaseObesityConfidence interval030104 developmental biologyMatrix Metalloproteinase 2businessObesity paradox
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The best strategy for RAS wild-type metastatic colorectal cancer patients in first-line treatment: A classic and Bayesian meta-analysis

2018

Background: At present, there is uncertainty on the best systemic treatment in first-line setting for RAS wild-type (WT) metastatic colorectal cancer (mCRC) patients. Indeed, several chemotherapy and biologics combinations showed an improvement on survival. We performed a systematic review with a pair-wise and bayesan meta-analysis to rank the best strategy for these patients. Methods: A systematic literature search through March 2017 was performed to evaluate the association between several treatment combinations and overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicity rate (TR) in RAS WT mCRC patients. Data were extracted from studies and pooled…

0301 basic medicineOncologymedicine.medical_specialtyColorectal cancermedicine.medical_treatmentBayesian probabilitySidednessDisease-Free Survival03 medical and health sciences0302 clinical medicineInternal medicineAntineoplastic Combined Chemotherapy ProtocolsmedicineHumansIn patientMeta-analysiSystemic chemotherapyNeoplasm MetastasisRAS wild-typeChemotherapyVbusiness.industryMetastatic colorectal cancerWild typeBayes TheoremHematologymedicine.diseaseNeoadjuvant TherapyFirst line treatmentMeta-analysisSafety profileGenes ras030104 developmental biologyOncology030220 oncology & carcinogenesisMeta-analysisSystemic chemotherapy.Colorectal Neoplasmsbusiness
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Pulmonary Adenocarcinoma With Enteric Differentiation: Immunohistochemistry and Molecular Morphology

2018

Pulmonary adenocarcinoma with enteric differentiation (PAED) is a rare subtype of lung adenocarcinoma recently recognized in the WHO classification. It is defined as an adenocarcinoma in which the enteric component exceeds 50% and have to show the expression of at least 1 immunohistochemical marker of enteric differentiation. Although the definition of this tumor type is very important, above all in the differential diagnosis between a primary lung tumor and a metastasis of colorectal adenocarcinoma, this cancer still lacks a distinctive immunohistochemical and molecular signature. We recruited the largest series in the literature of PAEDs according to the morphology and the positivity for …

0301 basic medicinePathologymedicine.medical_specialtyLung NeoplasmsHistologyintestinal-type adenocarcinomaCellular differentiationDNA Mutational AnalysisThyroid Nuclear Factor 1AdenocarcinomaBiologymedicine.disease_causePathology and Forensic MedicineMetastasisDiagnosis DifferentialProto-Oncogene Proteins p21(ras)03 medical and health sciences0302 clinical medicineKRASBiomarkers TumormedicineHumansCDX2 Transcription FactorPathology Molecularenteric lung adenocarcinoma intestinal-type adenocarcinoma CDX-2 CDX2 KRASLungKeratin-7entericCancerCell DifferentiationPulmonary adenocarcinoma with enteric differentiation (PAED)lung adenocarcinomamedicine.diseaseCDX-2ImmunohistochemistryMedical Laboratory Technology030104 developmental biologymedicine.anatomical_structureCDX2Alveolar Epithelial Cells030220 oncology & carcinogenesisMutationAdenocarcinomaImmunohistochemistryKRASDifferential diagnosisColorectal Neoplasms
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Cytomegalovirus vector expressing RAE-1γ induces enhanced anti-tumor capacity of murine CD8+ T cells

2017

Designing of CD8 T cell vaccines which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show a robust potential of a cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE-1γ as CD8 T cell-based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE-1γ delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD-1. Expression of RAE-1γ by the CMV vector potentiated expansion of KLRG1+ CD8 T cells wi…

0301 basic medicineTumor vaccine [RAE-1γ]medicine.medical_treatmentT cellImmunologyGenetic VectorsProgrammed Cell Death 1 ReceptorMelanoma ExperimentalCytomegalovirusEpitopes T-LymphocyteBiologyCD8-Positive T-LymphocytesCancer VaccinesArticleCMV vectorNKG2DImmunomodulation03 medical and health sciencesMiceImmune systemTIGITKLRG1+ CD8+ T cellsNeoplasmsmedicineImmunology and AllergyCytotoxic T cellAnimalsHumansRAE-1γ : Tumor vaccineLectins C-TypeReceptors ImmunologicαTIGIT ; CMV vector ; KLRG1+ CD8+ T cells ; NKG2D ; RAE-1γ : Tumor vaccineBIOMEDICINE AND HEALTHCARE. Basic Medical Sciences.Membrane ProteinsImmunotherapyNKG2DVirology3. Good healthKiller Cells NaturalDisease Models Animal030104 developmental biologymedicine.anatomical_structureImmunizationAnimals NewbornFemaleαTIGITImmunotherapyBIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti.CD8
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High Bacterial Agglutination Activity in a Single-CRD C-Type Lectin from Spodoptera exigua (Lepidoptera: Noctuidae)

2017

Lectins are carbohydrate-interacting proteins that play a pivotal role in multiple physiological and developmental aspects of all organisms. They can specifically interact with different bacterial and viral pathogens through carbohydrate-recognition domains (CRD). In addition, lectins are also of biotechnological interest because of their potential use as biosensors for capturing and identifying bacterial species. In this work, three C-type lectins from the Lepidoptera Spodoptera exigua were produced as recombinant proteins and their bacterial agglutination properties were characterized. The lowest protein concentration producing bacterial agglutination against a panel of different Gram+ an…

0301 basic medicineagglutinationlcsh:BiotechnologyClinical BiochemistryMicrobial Sensitivity TestsSpodopteraSpodopteraC-type lectin; agglutination; CRD; bacterial detection; <i>E. coli</i>ArticleMicrobiologylaw.inventionbacterial detectionLepidoptera genitalia03 medical and health sciences0302 clinical medicinelawC-type lectinlcsh:TP248.13-248.65Agglutination TestsExiguaEscherichia coliAnimalsLectins C-TypeAmino Acid SequenceConserved SequencePhylogenybiologyE. coliCRDGeneral Medicinebiology.organism_classificationImmunity InnateC-type lectinAgglutination (biology)030104 developmental biologyRecombinant DNANoctuidaeInsect ProteinsProtein concentration030215 immunologybiotechnology
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