Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim ...Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as well.Molecular docking simulations revealed that between catalytic core residues and the compound.The treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor(MC1R),microphthalmia-associated transcription factor(MITF),tyrosinase(TYR),TYR-related protein-1(TRP-1)and TRP-2 in B16 cells.Both PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 cells.Also in vivo glabridin therapy significantly reduced hyperpigmentation,epidermal thickening,roughness and inflammation induced by frequent UVA exposure in mice skins,thus beneficial for skin healthcare.These data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin,rationalizing the application of the natural compound for skin healthcare.展开更多
A gain-of-function mutation in the fibroblast growth factor receptor 3 gene(FGFR3)results in achondroplasia(ACH),the most frequent form of dwarfism.Constitutive activation of FGFR3 impairs bone formation and elongatio...A gain-of-function mutation in the fibroblast growth factor receptor 3 gene(FGFR3)results in achondroplasia(ACH),the most frequent form of dwarfism.Constitutive activation of FGFR3 impairs bone formation and elongation and many signal transduction pathways.Identification of new and relevant compounds targeting the FGFR3 signaling pathway is of broad importance for the treatment of ACH,and natural plant compounds are prime drug candidate sources.Here,we found that the phenolic compound(-)-epicatechin,isolated from Theobroma cacao,effectively inhibited FGFR3’s downstream signaling pathways.Transcriptomic analysis in an Fgfr3 mouse model showed that ciliary mRNA expression was modified and influenced significantly by the Indian hedgehog and PKA pathways.(-)-Epicatechin is able to rescue mRNA expression impairments that control both the structural organization of the primary cilium and ciliogenesis-related genes.In femurs isolated from a mouse model(Fgfr3^(Y367C/+))of ACH,we showed that(-)-epicatechin eliminated bone growth impairment during 6 days of ex vivo culture.In vivo,we confirmed that daily subcutaneous injections of(-)-epicatechin to Fgfr3^(Y367C/+) mice increased bone elongation and rescued the primary cilium defects observed in chondrocytes.This modification to the primary cilia promoted the typical columnar arrangement of flat proliferative chondrocytes and thus enhanced bone elongation.The results of the present proof-of-principle study support(-)-epicatechin as a potential drug for the treatment of ACH.展开更多
Yttrium iron garnet, Y3Fe5O12 (YIG) powders were synthesized by mechanochemical processing (MCP) from different iron sources (FeO, Fe2O3 and Fe3O4) mixed with Y2O3, followed by a heat treatment. The aim of this work i...Yttrium iron garnet, Y3Fe5O12 (YIG) powders were synthesized by mechanochemical processing (MCP) from different iron sources (FeO, Fe2O3 and Fe3O4) mixed with Y2O3, followed by a heat treatment. The aim of this work is to demonstrate that MCP followed by annealing at very low temperatures (as compared with the classic solid state reaction) can induce the formation of nanostructured YIG. The effect of iron source on final structure was also studied. X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize the synthesized powders. The precursors mixed in a stoichiometric ratio to obtain YIG were milled at room temperature in a shaker mixer mill with a ball:powder weight ratio of 10:1. A partial synthesis of YIG was achieved after 9 h of milling time by using the three sources of iron;however, a significant fraction of the product was the perovskite YFeO3. The largest yield of YIG was obtained by using FeO. In all cases a single garnet phase could only be completely obtained after an annealing process at 900?C, around 400?C lower than the typical temperatures to prepare the material by solid state reaction. An analysis of the microstrain and lattice parameters associated with peak displacements is discussed.展开更多
Stoichiometric mixtures of FeO and Y2O3 were milled and heat treated to obtain yttrium iron garnet, Y3Fe5O12. Two types of heating systems were used: one, a spark plasma sintering machine and the second, an electrical...Stoichiometric mixtures of FeO and Y2O3 were milled and heat treated to obtain yttrium iron garnet, Y3Fe5O12. Two types of heating systems were used: one, a spark plasma sintering machine and the second, an electrical oven. The magnetic properties of the resulting specimens have been analyzed and discussed as a function of the grain size and the particles’ morphology. The partial formation of garnet and orthoferrite phases was revealed on the obtained powder through microstructural analyses after 9 h of ball milling. The milled powders were transformed into the orthoferrite phase after the SPS-treatment at 700°C and 900°C. Magnetic-saturation studies revealed magnetic responses up to 12.7 emu/g for specimens SPS-treated at 700°C, whereas 2.1 emu/g for samples SPS-treated at 900°C. Conventionally treated specimens at 700°C developed 0.36 emu/g of magnetization, while 0.93 emu/g was registered for those treated at 900°C.展开更多
基金supported by the Inner Mongolia Autonomous Region Science and Technology Revitalization Foundation (2021CG0029)the National Natural Science Foundation of China (22178070)
文摘Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as well.Molecular docking simulations revealed that between catalytic core residues and the compound.The treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor(MC1R),microphthalmia-associated transcription factor(MITF),tyrosinase(TYR),TYR-related protein-1(TRP-1)and TRP-2 in B16 cells.Both PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 cells.Also in vivo glabridin therapy significantly reduced hyperpigmentation,epidermal thickening,roughness and inflammation induced by frequent UVA exposure in mice skins,thus beneficial for skin healthcare.These data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin,rationalizing the application of the natural compound for skin healthcare.
基金Supported by Association Franco-Chinoise pour la Recherche Scientinque and Techinque(AFCRST)and National Natural Science Foundation of China(20275014)
基金This program received a state subsidy managed by the National Research Agency under the “Investments for the Future” Program bearing the reference ANR-10-IAHU-01Some of the work presented here was funded by the European Community’s Seventh Framework Program under grant agreement 602300 (the SYBIL program (https://www.sybil-fp7.eu/) is funded by the MRC (MC_UU_000007/9))
文摘A gain-of-function mutation in the fibroblast growth factor receptor 3 gene(FGFR3)results in achondroplasia(ACH),the most frequent form of dwarfism.Constitutive activation of FGFR3 impairs bone formation and elongation and many signal transduction pathways.Identification of new and relevant compounds targeting the FGFR3 signaling pathway is of broad importance for the treatment of ACH,and natural plant compounds are prime drug candidate sources.Here,we found that the phenolic compound(-)-epicatechin,isolated from Theobroma cacao,effectively inhibited FGFR3’s downstream signaling pathways.Transcriptomic analysis in an Fgfr3 mouse model showed that ciliary mRNA expression was modified and influenced significantly by the Indian hedgehog and PKA pathways.(-)-Epicatechin is able to rescue mRNA expression impairments that control both the structural organization of the primary cilium and ciliogenesis-related genes.In femurs isolated from a mouse model(Fgfr3^(Y367C/+))of ACH,we showed that(-)-epicatechin eliminated bone growth impairment during 6 days of ex vivo culture.In vivo,we confirmed that daily subcutaneous injections of(-)-epicatechin to Fgfr3^(Y367C/+) mice increased bone elongation and rescued the primary cilium defects observed in chondrocytes.This modification to the primary cilia promoted the typical columnar arrangement of flat proliferative chondrocytes and thus enhanced bone elongation.The results of the present proof-of-principle study support(-)-epicatechin as a potential drug for the treatment of ACH.
文摘Yttrium iron garnet, Y3Fe5O12 (YIG) powders were synthesized by mechanochemical processing (MCP) from different iron sources (FeO, Fe2O3 and Fe3O4) mixed with Y2O3, followed by a heat treatment. The aim of this work is to demonstrate that MCP followed by annealing at very low temperatures (as compared with the classic solid state reaction) can induce the formation of nanostructured YIG. The effect of iron source on final structure was also studied. X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize the synthesized powders. The precursors mixed in a stoichiometric ratio to obtain YIG were milled at room temperature in a shaker mixer mill with a ball:powder weight ratio of 10:1. A partial synthesis of YIG was achieved after 9 h of milling time by using the three sources of iron;however, a significant fraction of the product was the perovskite YFeO3. The largest yield of YIG was obtained by using FeO. In all cases a single garnet phase could only be completely obtained after an annealing process at 900?C, around 400?C lower than the typical temperatures to prepare the material by solid state reaction. An analysis of the microstrain and lattice parameters associated with peak displacements is discussed.
文摘Stoichiometric mixtures of FeO and Y2O3 were milled and heat treated to obtain yttrium iron garnet, Y3Fe5O12. Two types of heating systems were used: one, a spark plasma sintering machine and the second, an electrical oven. The magnetic properties of the resulting specimens have been analyzed and discussed as a function of the grain size and the particles’ morphology. The partial formation of garnet and orthoferrite phases was revealed on the obtained powder through microstructural analyses after 9 h of ball milling. The milled powders were transformed into the orthoferrite phase after the SPS-treatment at 700°C and 900°C. Magnetic-saturation studies revealed magnetic responses up to 12.7 emu/g for specimens SPS-treated at 700°C, whereas 2.1 emu/g for samples SPS-treated at 900°C. Conventionally treated specimens at 700°C developed 0.36 emu/g of magnetization, while 0.93 emu/g was registered for those treated at 900°C.
