The nervous system function requires a precise but plastic neural architecture.The neuronal shape dictates how neurons interact with each other and with other cells,being the morphology of dendrites and axons the cent...The nervous system function requires a precise but plastic neural architecture.The neuronal shape dictates how neurons interact with each other and with other cells,being the morphology of dendrites and axons the central determinant of the functional properties of neurons and neural circuits.The topological and structural morphology of axons and dendrites defines and determines how synapses are conformed.The morphological diversity of axon and dendrite arborization governs the neuron’s inputs,synaptic integration,neuronal computation,signal transmission,and network circuitry,hence defining the particular connectivity and function of the different brain areas.展开更多
Objective： To evaluate the effect of Xuefu Zhuyu Capsule（血府逐瘀胶囊）-containing serum（XFZY-CS） on Eph B4/ephrin B2 and its reverse signal in human microvascular endothelial cell-1（HMEC-1）. Methods： XFZY-CS a...Objective： To evaluate the effect of Xuefu Zhuyu Capsule（血府逐瘀胶囊）-containing serum（XFZY-CS） on Eph B4/ephrin B2 and its reverse signal in human microvascular endothelial cell-1（HMEC-1）. Methods： XFZY-CS and the blank control serum were collected. HMEC-1 cells were randomly assigned to 6 groups including the concentration 1.25%, 2.5%, and 5% XFZY-CS groups and their blank serum control ones. The angiogenesis effect of XFZY-CS was tested with an in vitro tube formation assay and the best condition of pro-angiogenesis was determined. The effect of XFZY-CS on Eph B4/ephrin B2 and the reverse signal were determined by Western blot and real-time quantitative polymerase chain reaction, respectively; we also confirmed the results through activating and inhibiting the reverse signal by Eph B4/fc and pyrophosphatase/phosphodiesterase2（PP2）. Results： XFZY-CS promoted angiogenesis at the concentration of 2.5% corresponding serum after being cultured for 48 h, while inhibited angiogenesis at the concentration of 5% after culturing for 48 and 72 h. Under the 2.5% serum concentration, XFZY up-regulated the expression of Eph B4-m RNA at 12 h（P〈0.05）, and down-regulates its expression at 24 h（P〈0.01）. Protein expression of Eph B4 was apparently up-regulated at 12 h and down-regulated at 24 h. The phosphorylation of ephrin B2 increased at 9 h（P〈0.05）. In addition, 2.5% XFZY-CS played a similar role as the reverse signaling activator Eph B4/Fc ranging from 0.5 to 5 μg/m L（P〉0.05）. XFZY-CS also reduced the inhibitive effect of PP2 in limited periods. Conclusion： Eph B4/ephrin B2 was the upstream signal in the process of angiogenesis and its reverse signaling was responsible for XFZY＇s effect on promoting angiogenesis.展开更多
CD32a contributes to inflammation by interacting with CD137L to induce inflammatory dendritic cell differentiation.CD137 ligand(CD137L)is a costimulatory ligand that is expressed on antigen-presenting cells(APCs)and i...CD32a contributes to inflammation by interacting with CD137L to induce inflammatory dendritic cell differentiation.CD137 ligand(CD137L)is a costimulatory ligand that is expressed on antigen-presenting cells(APCs)and is important for enhancing T cell activation by crosslinking CD137 on activated T cells.1–3 While CD137 triggers a costimulatory signal in T cells,CD137L has been reported to trigger reverse signaling in APCs.4 In human monocytes,reverse CD137L signaling leads to the differentiation of dendritic cells(DCs),which are termed CD137L-DCs.展开更多
Background:The interaction between the metastatic microenvironment and tumor cells plays an important role in metastatic tumor formation.Platelets play pivotal roles in hematogenous cancer metastasis through tumor cel...Background:The interaction between the metastatic microenvironment and tumor cells plays an important role in metastatic tumor formation.Platelets play pivotal roles in hematogenous cancer metastasis through tumor cell-platelet interaction in blood vessels.Pancreatic ductal adenocarcinoma(PDAC)is a highly lethal malignancy distinguished by its notable tendency to metastasize to the liver.However,the role of platelet in the liver metastatic niche of PDAC remains elusive.This study aimed to elucidate the role of platelets and their interactions with tumor cells in the liver metastatic niche of PDAC.Methods:An mCherry niche-labeling system was established to identify cells in the liver metastatic niche of PDAC.Platelet depletion in a liver metastasis mouse model was used to observe the function of platelets in PDAC liver metastasis.Gain-of-function and loss-of-function of erythropoietin-producing hepatocellular receptor B1(Ephb1),tumor cell-platelet adhesion,recombinant protein,and tryptophan hydroxylase 1(Tph1)-knockout mice were used to study the crosstalk between platelets and tumor cells in the liver metastatic niche.Results:The mCherry metastatic niche-labeling system revealed the presence of activated platelets in the liver metastatic niche of PDAC patients.Platelet depletion decreased liver metastatic tumor growth in mice.Mechanistically,tumor cell-expressed EPHB1 and platelet-expressed Ephrin B1(EFNB1)mediated contact-dependent activation of platelets via reverse signaling-mediated AKT signaling activation,and in turn,activated platelet-released 5-HT,further enhancing tumor growth.Conclusion:We revealed the crosstalk between platelets and tumor cells in the liver metastatic niche of PDAC.Reciprocal tumor-platelet interaction mediated by the EPHB1-EFNB1 reverse signaling promoted metastatic PDAC outgrowth via 5-HT in the liver.Interfering the tumor-platelet interaction by targeting the EPHB1-EFNB1 axis may represent a promising therapeutic intervention for PDAC liver metastasis.展开更多
基金supported by the Wellcome Trust(grant No.103852).
文摘The nervous system function requires a precise but plastic neural architecture.The neuronal shape dictates how neurons interact with each other and with other cells,being the morphology of dendrites and axons the central determinant of the functional properties of neurons and neural circuits.The topological and structural morphology of axons and dendrites defines and determines how synapses are conformed.The morphological diversity of axon and dendrite arborization governs the neuron’s inputs,synaptic integration,neuronal computation,signal transmission,and network circuitry,hence defining the particular connectivity and function of the different brain areas.
基金Supported by the National Natural Science Foundation of China(No.81072933 and No.81173431)National Center for Complementary and Alternative Medicine/National Institutes of Health of USA(No.2K24 AT004095)
文摘Objective： To evaluate the effect of Xuefu Zhuyu Capsule（血府逐瘀胶囊）-containing serum（XFZY-CS） on Eph B4/ephrin B2 and its reverse signal in human microvascular endothelial cell-1（HMEC-1）. Methods： XFZY-CS and the blank control serum were collected. HMEC-1 cells were randomly assigned to 6 groups including the concentration 1.25%, 2.5%, and 5% XFZY-CS groups and their blank serum control ones. The angiogenesis effect of XFZY-CS was tested with an in vitro tube formation assay and the best condition of pro-angiogenesis was determined. The effect of XFZY-CS on Eph B4/ephrin B2 and the reverse signal were determined by Western blot and real-time quantitative polymerase chain reaction, respectively; we also confirmed the results through activating and inhibiting the reverse signal by Eph B4/fc and pyrophosphatase/phosphodiesterase2（PP2）. Results： XFZY-CS promoted angiogenesis at the concentration of 2.5% corresponding serum after being cultured for 48 h, while inhibited angiogenesis at the concentration of 5% after culturing for 48 and 72 h. Under the 2.5% serum concentration, XFZY up-regulated the expression of Eph B4-m RNA at 12 h（P〈0.05）, and down-regulates its expression at 24 h（P〈0.01）. Protein expression of Eph B4 was apparently up-regulated at 12 h and down-regulated at 24 h. The phosphorylation of ephrin B2 increased at 9 h（P〈0.05）. In addition, 2.5% XFZY-CS played a similar role as the reverse signaling activator Eph B4/Fc ranging from 0.5 to 5 μg/m L（P〉0.05）. XFZY-CS also reduced the inhibitive effect of PP2 in limited periods. Conclusion： Eph B4/ephrin B2 was the upstream signal in the process of angiogenesis and its reverse signaling was responsible for XFZY＇s effect on promoting angiogenesis.
基金supported by a grant(NMRC/BnB/018b/2015)from the National Medical Research Council of Singapore.
文摘CD32a contributes to inflammation by interacting with CD137L to induce inflammatory dendritic cell differentiation.CD137 ligand(CD137L)is a costimulatory ligand that is expressed on antigen-presenting cells(APCs)and is important for enhancing T cell activation by crosslinking CD137 on activated T cells.1–3 While CD137 triggers a costimulatory signal in T cells,CD137L has been reported to trigger reverse signaling in APCs.4 In human monocytes,reverse CD137L signaling leads to the differentiation of dendritic cells(DCs),which are termed CD137L-DCs.
基金Natural Science Foundation of Shanghai,Grant/Award Number:22ZR1460000Shanghai Municipal Health Commission,Grant/Award Number:202340202+1 种基金National Natural Science Foundation of China,Grant/Award Numbers:82073023,82103357,82173153,82230087,82273228,82303278,82350123,82372821,92168111Innovative research team of high-level local universities in Shanghai,Grant/Award Number:SHSMU-ZDCX20210802。
文摘Background:The interaction between the metastatic microenvironment and tumor cells plays an important role in metastatic tumor formation.Platelets play pivotal roles in hematogenous cancer metastasis through tumor cell-platelet interaction in blood vessels.Pancreatic ductal adenocarcinoma(PDAC)is a highly lethal malignancy distinguished by its notable tendency to metastasize to the liver.However,the role of platelet in the liver metastatic niche of PDAC remains elusive.This study aimed to elucidate the role of platelets and their interactions with tumor cells in the liver metastatic niche of PDAC.Methods:An mCherry niche-labeling system was established to identify cells in the liver metastatic niche of PDAC.Platelet depletion in a liver metastasis mouse model was used to observe the function of platelets in PDAC liver metastasis.Gain-of-function and loss-of-function of erythropoietin-producing hepatocellular receptor B1(Ephb1),tumor cell-platelet adhesion,recombinant protein,and tryptophan hydroxylase 1(Tph1)-knockout mice were used to study the crosstalk between platelets and tumor cells in the liver metastatic niche.Results:The mCherry metastatic niche-labeling system revealed the presence of activated platelets in the liver metastatic niche of PDAC patients.Platelet depletion decreased liver metastatic tumor growth in mice.Mechanistically,tumor cell-expressed EPHB1 and platelet-expressed Ephrin B1(EFNB1)mediated contact-dependent activation of platelets via reverse signaling-mediated AKT signaling activation,and in turn,activated platelet-released 5-HT,further enhancing tumor growth.Conclusion:We revealed the crosstalk between platelets and tumor cells in the liver metastatic niche of PDAC.Reciprocal tumor-platelet interaction mediated by the EPHB1-EFNB1 reverse signaling promoted metastatic PDAC outgrowth via 5-HT in the liver.Interfering the tumor-platelet interaction by targeting the EPHB1-EFNB1 axis may represent a promising therapeutic intervention for PDAC liver metastasis.
