Search results for "Rapamycin"

showing 10 items of 44 documents

Regulation of GSK-3 activity by curcumin, berberine and resveratrol: Potential effects on multiple diseases.

2017

Natural products or nutraceuticals promote anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway. This review will focus on the effects of curcumin (CUR), berberine (BBR) and resveratrol (RES), on the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway, with a special focus on GSK-3. These natural products may regulate the pathway by multiple mechanisms including: reactive oxygen species (ROS), cytokine receptors, mirco-RNAs (miRs) and many others. CUR is present the root of turmeric (Curcuma longa). CUR is used in the treatment of many disorders, especially in those involving inflammatory p…

0301 basic medicineCancer ResearchCurcuminBerberinemTORC1PharmacologyResveratrolMechanistic Target of Rapamycin Complex 1Protective AgentsNatural product03 medical and health scienceschemistry.chemical_compoundGlycogen Synthase Kinase 3Phosphatidylinositol 3-KinasesBerberineGeneticNeoplasmsOsteoarthritisStilbenesGeneticsPTENHumansCurcumaMolecular BiologyProtein kinase BPI3K/AKT/mTOR pathwayInflammationNatural productsbiologyBerberine; Curcumin; Natural products; ResveratrolPTEN PhosphohydrolaseNeurodegenerative Diseasesbiology.organism_classification030104 developmental biologyBiochemistrychemistryGene Expression RegulationCardiovascular DiseasesResveratrolbiology.proteinCurcuminMolecular MedicineProto-Oncogene Proteins c-aktSignal Transduction
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A genome-wide transcriptional study reveals that iron deficiency inhibits the yeast TORC1 pathway

2019

Iron is an essential micronutrient that participates as a cofactor in a broad range of metabolic processes including mitochondrial respiration, DNA replication, protein translation and lipid biosynthesis. Adaptation to iron deficiency requires the global reorganization of cellular metabolism directed to optimize iron utilization. The budding yeast Saccharomyces cerevisiae has been widely used to characterize the responses of eukaryotic microorganisms to iron depletion. In this report, we used a genomic approach to investigate the contribution of transcription rates to the modulation of mRNA levels during adaptation of yeast cells to iron starvation. We reveal that a decrease in the activity…

IronSaccharomyces cerevisiaeBiophysicsRibosome biogenesisSaccharomyces cerevisiaeMechanistic Target of Rapamycin Complex 1Biochemistry03 medical and health sciencesStructural BiologyRibosomal proteinTranscription (biology)Gene Expression Regulation FungalLipid biosynthesisGeneticsHumansRNA MessengerPhosphorylationMolecular BiologyGene030304 developmental biology0303 health sciencesAnemia Iron-Deficiencybiology030306 microbiologyChemistryIron deficiencyRNA polymerasesRNATORbiology.organism_classificationAdaptation PhysiologicalYeastCell biologyDNA-Binding ProteinsGene Expression RegulationProtein BiosynthesisSignal transductionTranscription
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<p>Clinical Evaluation of Everolimus in the Treatment of Neuroendocrine Tumors of the Lung: Patient Selection and Special Considerations. A Sys…

2020

Abstract Neuroendocrine tumors (NETs) of the lung are well-differentiated neuroendocrine neoplasms (NENs) with a heterogeneous clinical behaviour. Unlike gastroenteropancreatic NENs where therapeutic armamentarium clearly increased over the last decade, everolimus represented the only clinical practical innovation for lung NET patients over the last years. Therefore, for lung NETs, a multidisciplinary discussion within a dedicated team remains critical for an adequate decision-making. Although the main regulatory authorities considered the everolimus-related evidence is enough to approve the drug in advanced lung NETs, several clinical features deserve to be discussed. In this review, we sy…

medicine.medical_specialtytargeted agentsEverolimusLungbusiness.industryContext (language use)Reviewrespiratory systemNeuroendocrine tumorseverolimusmedicine.diseaseatypical carcinoidClinical Practicelung NETtypical carcinoidmedicine.anatomical_structureOncologymammalian target of rapamycin (mTOR) inhibitormedicineTypical carcinoidIntensive care medicinebusinessAtypical carcinoidClinical evaluationmedicine.drugLung Cancer: Targets and Therapy
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Efficacy of Rapamycin as Inducer of Hb F in Primary Erythroid Cultures from Sickle Cell Disease and β-Thalassemia Patients.

2015

Phenotypic improvement of hemoglobinopathies such as sickle cell disease and β-thalassemia (β-thal) has been shown in patients with high levels of Hb F. Among the drugs proposed to increase Hb F production, hydroxyurea (HU) is currently the only one proven to improve the clinical course of these diseases. However, Hb F increase and patient's response are highly variable, indicating that new pharmacological agents could be useful for patients not responding to HU or showing a reduction of response during long-term therapy. In this study we evaluated the efficacy of rapamycin, a lypophilic macrolide used for the prevention of acute rejection in renal transplant recipients, as an inducer of Hb…

rapamycin β-Thalassemia
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Mboat7 down-regulation by hyper-insulinemia induces fat accumulation in hepatocytes.

2020

Background: Naturally occurring variation in Membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), encoding for an enzyme involved in phosphatidylinositol acyl-chain remodelling, has been associated with fatty liver and hepatic disorders. Here, we examined the relationship between hepatic Mboat7 down-regulation and fat accumulation. Methods: Hepatic MBOAT7 expression was surveyed in 119 obese individuals and in experimental models. MBOAT7 was acutely silenced by antisense oligonucleotides in C57Bl/6 mice, and by CRISPR/Cas9 in HepG2 hepatocytes. Findings: In obese individuals, hepatic MBOAT7 mRNA decreased from normal liver to steatohepatitis, independently of diabetes, inflammatio…

Research paperTGFβ Transforming Growth Factor BetaIntracellular SpaceCRISPR Clustered Regularly Interspaced Short Palindromic RepeatshHEPS Human HepatocytesMice0302 clinical medicineLPIAT1DAG Diacylglyceroli.p. Intraperitonealmedia_commonFatty AcidsGeneral Medicine3. Good health030220 oncology & carcinogenesisHOMA-IR homeostasis Model Assessment of Insulin ResistanceMPO morpholinolcsh:Medicine (General)medicine.medical_specialtyPE Phosphatidyl-EthanolamineNashGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesTNFα tumor Necrosis Factor AlphaLDL Low Density LipoproteinsHyperinsulinismNAFLDSD Standard Dietmedia_common.cataloged_instanceHumansCPT1 Carnitine Palmitoyltransferase IPhosphatidylinositolGene SilencingEuropean unionVLDL Very Low Density Lipoproteinlcsh:RhHSC Human Hepatic Stellate Cellsmedicine.diseaseLipid MetabolismOA Oleic AcidCI Confidence IntervalMboat7 Membrane bound O-acyltransferase domain containing 7MCD methionine choline deficient diet030104 developmental biologyEndocrinologychemistryCDP Cytidine-DiphosphateFOXO1 Forkhead Box protein O1NAFLD nonalcoholic fatty liver diseaseSteatohepatitisBMI Body Mass IndexCL CardiolipinAcyltransferases0301 basic medicineAlcoholic liver diseaseCXCL10 C-X-C Motif Chemokine 10lcsh:Medicinechemistry.chemical_compoundNon-alcoholic Fatty Liver DiseaseIFG Impaired Fasting GlucoseAPOB Apolipoprotein BNonalcoholic fatty liver diseasePIP Phosphatidyl-Inositol-PhosphateSteatohepatitisqRT-PCR quantitative Real Time Polymerase Chain ReactionMice Knockoutlcsh:R5-920ORO Oil Red O StainingPI PhosphatidylinositolFatty liverTM6SF2 Transmembrane 6 Superfamily Member 2PhospholipidTAG TriglyceridesNASH Nonalcoholic SteatohepatitisLipogenesisLPA Lyso-Phosphatidic AcidPhosphatidylinositolSignal TransductionPS Phosphatidyl-SerinePA Palmitic AcidALD alcoholic liver diseasePC Phosphatidylcholinei.v. IntravenousFATP1 Fatty Acid Transport Protein 1Models BiologicalInternal medicinemedicineAnimalsNonalcoholic fatty liver diseasePPARα Peroxisome Proliferator-Activated Receptor alphaObesityG3P Glyceraldehyde-3-PhosphateSREBP1c Sterol Regulatory Element-Binding Protein 1HDL High Density Lipoproteinsbusiness.industryPI3K Phosphatidylinositol 3 KinaseMembrane ProteinsNHEJ Non-Homologues End JoiningPNPLA3 Patatin-like Phospholipase Domain-containing-3MTTP Microsomal Triglyceride Transfer ProteinLPIAT1 Lysophosphatidylinositol Acyltransferase 1TMC4 Transmembrane Channel-Like 4Disease Models AnimalGene Expression RegulationHepatocytesFOXA2 Forkhead Box A2mTOR mammalian target of RapamycinSteatosisInsulin ResistancebusinessPG Phosphatidyl-GlycerolFABP1 Fatty Acid-Binding Protein 1 FAS Fatty Acid SynthaseT2DM Type 2 Diabetes MellitusEBioMedicine
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Pathogenesis and molecular mechanisms of anderson–fabry disease and possible new molecular addressed therapeutic strategies

2021

Anderson–Fabry disease (AFD) is a rare disease with an incidenceof approximately 1:117,000 male births. Lysosomal accumulation of globotriaosylceramide (Gb3) is the element characterizing Fabry disease due to a hereditary deficiency α-galactosidase A (GLA) enzyme. The accumulation of Gb3 causes lysosomal dysfunction that compromises cell signaling pathways. Deposition of sphingolipids occurs in the autonomic nervous system, dorsal root ganglia, kidney epithelial cells, vascular system cells, and myocardial cells, resulting in organ failure. This manuscript will review the molecular pathogenetic pathways involved in Anderson–Fabry disease and in its organ damage. Some studies reported that i…

ReviewConstriction Pathologicendothelial dysfunctionPathogenesisMicechemistry.chemical_compoundKCa3.1 activitypodocyturiaProtein IsoformsEndothelial dysfunctionBiology (General)SpectroscopyglobotriaosylceramideGlobosidesMicrogliabiologyTOR Serine-Threonine KinasesTrihexosylceramidesmiR-26a-5pGeneral MedicineMitochondriaComputer Science ApplicationsCell biologymiR-152-5pChemistrymedicine.anatomical_structureCerebrovascular CirculationAnderson–Fabry disease Endothelial dysfunction Globotriaosylceramide KCa3.1 activity MiR-1307-5p MiR-152-5p MiR-21-5p MiR-26a-5p Podocyturia Valvular dysfunctionmiR-21-5pSignal TransductionQH301-705.5GlobotriaosylceramideCatalysisInorganic ChemistryAutophagymedicineAnimalsHumansEnzyme Replacement TherapyPhysical and Theoretical ChemistryMolecular BiologyMechanistic target of rapamycinQD1-999PI3K/AKT/mTOR pathwaySphingolipidsAnderson–Fabry diseasebusiness.industryMicrocirculationOrganic ChemistryEndothelial Cellsmedicine.diseaseFabry diseaseSphingolipidMicroRNAschemistrymiR-1307-5palpha-Galactosidasebiology.proteinFabry DiseaseGlycolipidsvalvular dysfunctionLysosomesbusiness
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Inhalable polymeric microparticles as pharmaceutical porous powder for drug administration

2022

In this work, the production of inhalable polymeric microparticles with modulable porosity is described. The starting polymeric material was the PHEA-g-RhB-g-PLA graft copolymer, which was suitably processed by spray drying (SD). Thanks to the addition of AB (weight percentage equal to 10 and 20 % with respect to the polymer) in the liquid feed, three biocompatible matrices were obtained with an increasing porosity in terms of pore volume (from 0.015 to 0.024 cc/g) and pore average diameter (from 1.942 to 3.060 nm), a decreasing tapped density values (from 0.75 to 0.50), and favorable aerosolization characteristics. These differences were high-lighted also by a significant increase in the r…

Porous microparticlesDrug CarriersPolymersSettore CHIM/09 - Farmaceutico Tecnologico ApplicativoAdministration InhalationPharmaceutical SciencePulmonary administrationRapamycinPowdersParticle SizePorosityαβ-Poly(N-2-hydroxyethyl)-Dl-ASPARTAMIDE (PHEA)
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Effect of Sirolimus Exposure on the Need for Preemptive Antiviral Therapy for Cytomeglovirus Infection after Allogeneic Hematopoietic Stem Cell Trans…

2019

The current study evaluates the clinical effect of sirolimus exposure on the occurrence of cytomegalovirus (CMV) DNAemia necessitating preemptive antiviral therapy. A total of 167 consecutive recipients of reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) who received sirolimus- and tacrolimus-based graft-versus-host disease (GVHD) prophylaxis and whose CMV serostatus was positive for donors and/or recipients were included in this multicenter retrospective study. A parametric model with consecutive sirolimus blood levels describing the time to CMV DNAemia-RAT was developed using NONMEM version 7.4. Overall, 122 of 167 patients (73%) were all…

AdultMaleOncologymedicine.medical_specialtyPremedicationmedicine.medical_treatmentCongenital cytomegalovirus infectionHematopoietic stem cell transplantationAntiviral AgentsAllogeneic hematopoietic stem cells transplantationMechanistic target of rapamycin inhibitorQuantitative PCR03 medical and health sciences0302 clinical medicineTime-to-event analysisInternal medicineHumansTransplantation HomologousMedicineCumulative incidenceCytomegalovirus diseaseSurvival analysisRetrospective StudiesSirolimusTransplantationDose-Response Relationship Drugbusiness.industryHazard ratioHematopoietic Stem Cell TransplantationPK/PDvirus diseasesRetrospective cohort studyHematologyMiddle Agedmedicine.diseaseCytomegalovirus infectionsurgical procedures operativeCytomegalovirus DNAemia030220 oncology & carcinogenesisSirolimusCytomegalovirus InfectionsPreemptive antiviral therapySirolimus exposureFemalebusinessSerostatusImmunosuppressive Agents030215 immunologymedicine.drug
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Yeast Translation Elongation Factor eIF5A Expression Is Regulated by Nutrient Availability through Different Signalling Pathways

2020

Translation elongation factor eIF5A binds to ribosomes to promote peptide bonds between problematic amino acids for the reaction like prolines. eIF5A is highly conserved and essential in eukaryotes, which usually contain two similar but differentially expressed paralogue genes. The human eIF5A-1 isoform is abundant and implicated in some cancer types

MitochondrionBiotecnologialcsh:ChemistryPeptide Initiation FactorsGene Expression Regulation Fungalmitochondrial respirationGene expressionExpressió genèticaHap1Protein Isoformshemelcsh:QH301-705.5SpectroscopyChemistryRNA-Binding ProteinsTranslation (biology)Iron DeficienciesGeneral MedicineTORAerobiosisUp-RegulationComputer Science ApplicationsCell biologySnf1EIF5ASignal TransductionGene isoformSaccharomyces cerevisiae ProteinsIronCitric Acid CycleDown-RegulationSaccharomyces cerevisiaeMechanistic Target of Rapamycin Complex 1Models BiologicalArticleCatalysisInorganic ChemistryeIF5APhysical and Theoretical ChemistryMolecular BiologyTranscription factorGeneLysineOrganic ChemistryNutrientsMetabolismCarbonMetabolic Flux AnalysisGlucoselcsh:Biology (General)lcsh:QD1-999Fermentationgene expressionInternational Journal of Molecular Sciences
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Enhanced autophagic-lysosomal activity and increased BAG3-mediated selective macroautophagy as adaptive response of neuronal cells to chronic oxidati…

2019

Oxidative stress and a disturbed cellular protein homeostasis (proteostasis) belong to the most important hallmarks of aging and of neurodegenerative disorders. The proteasomal and autophagic-lysosomal degradation pathways are key measures to maintain proteostasis. Here, we report that hippocampal cells selected for full adaptation and resistance to oxidative stress induced by hydrogen peroxide (oxidative stress-resistant cells, OxSR cells) showed a massive increase in the expression of components of the cellular autophagic-lysosomal network and a significantly higher overall autophagic activity. A comparative expression analysis revealed that distinct key regulators of autophagy are upregu…

0301 basic medicineClinical BiochemistryLFQ Label-free quantificationLETM Leucine zipper and EF-hand containing transmembrane proteinmedicine.disease_causeBiochemistryCHX Cycloheximide0302 clinical medicineBNIP3 Bcl-2 interacting protein 3RAPA RapamycinPIK3C3 Class III PI3‐kinasePhosphorylationlcsh:QH301-705.5Neuronslcsh:R5-920PolyUB PolyubiquitinChemistryBAG3OPA1 Optic atrophy 1TOR Serine-Threonine KinasesWIPI1 WD repeat domain phosphoinositide-interacting protein 1ATG Autophagy relatedTFEB Transcription factor EBCell biologyMitochondriasiRNA Small interfering RNADLP1 Dynamin-like protein 1LAMP1 Lysosomal‐associated membrane protein 1PURO Puromycinlcsh:Medicine (General)Protein homeostasisResearch PaperBafA1 Bafilomycin A1LAMP2 Lysosomal‐associated membrane protein 2Proteasome Endopeptidase ComplexRAB18 Member RAS oncogeneTUB TubulinLC3 Light chain 3 proteinOxidative phosphorylationBAG3CTSD Cathepsin DModels BiologicalCell Line03 medical and health sciencesDownregulation and upregulationMacroautophagymedicineAutophagyHumansAdaptationBAG1 Bcl-2-associated athanogene 1BECN1 Beclin1PI3K/AKT/mTOR pathwayAdaptor Proteins Signal TransducingTEM Transmission electron microscopyHsp70 Heat shock protein 70Organic ChemistryAutophagyAutophagosomesmTOR Mammalian target of rapamycinHsp70Oxidative Stress030104 developmental biologyProteostasislcsh:Biology (General)CV CanavanineBAG3 Bcl-2-associated athanogene 3MTT (3-(45-Dimethylthiazol-2-yl)-25-Diphenyltetrazolium Bromide)Apoptosis Regulatory ProteinsLysosomes030217 neurology & neurosurgeryOxidative stressRedox Biology
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