Fyn kinase-dependent cellular events were related with skeletal muscle denervation. In the present study, we used a combination of techniques to measure ER stability and the related Gβ1γ2 trafficking following muscl...Fyn kinase-dependent cellular events were related with skeletal muscle denervation. In the present study, we used a combination of techniques to measure ER stability and the related Gβ1γ2 trafficking following muscle mobilization, and demonstrated a temporally and Fyn-dependent up-regulation of Ca2+ level in the mobilized muscle. In parallel, Fyn activity in ER was gradually decreased, which was accompanied by enhanced PTP1B activity and expressions of ER proteins (calnexin, Grp94, cyclophilin, and Hsp70). Moreover, during muscle mobilization, there was more membrane protein breakdown than protein synthesis, which probably featured robust Gβ1γ2 internalization, and Rab1-dependent transport into ER compartment;the signaling was related to disruption of PI3K-Akt signaling and decrement of muscular functions. Then, Gβ1γ2 trafficking is a key component necessary for the early recovery processes regarding muscle atrophy, which would be the therapeutic consideration for muscle repair and regeneration.展开更多
Anti virulence strategy has been considered as one of the most promising approaches to combat drug-rcesistant bacterial infections.Porc-forming toxins(PFTs)are the largest class of bacterial toxins,inficting their vir...Anti virulence strategy has been considered as one of the most promising approaches to combat drug-rcesistant bacterial infections.Porc-forming toxins(PFTs)are the largest class of bacterial toxins,inficting their virulence ffect through creating pores on the cell membrane.However,curent solutions for eliminating PFTs are mostly designed based on their molecular structure,requiring customized design for different interactions.In the present study,we employed erythroliposome(denoted as RM-PL),a biomimetic platform constructed by artificial lipid membranes and natural erythrocyle membranes,to necutralize different hemolytic PFTs regardless of their molecular structure.When tested with model PFTs,including a-hemolysin,listeriolysin O,and streptolysin O,RM-PL could completely inhibit toxin-induced hemolysis in a concentration-dependent manner.In vivo studies further confirmed that RM-PL.could eficiently neuralize various toxins and save animals'lives without causing damage to 0rgans or tissues.In addition,we explored the underlying mechanisms of this efficient detoxification ability and found that it was mainly macrophages in the spleen and the liver that took up RM-PL-absorbed toxins through a variety of endocytosis pathways and digested them in lysosomes.In summary,the biomimetic RM-PL presented a promising system for broad-spectrum and powerful toxin neutralization with a mech-anism of lysosome-mediaed loxin degradation.展开更多
Oncolytic virotherapy(OVT)is a novel type of immunotherapy that induces anti-tumor responses through selective self-replication within cancer cells and oncolytic virus(OV)-mediated immunostimulation.Notably,talimogene...Oncolytic virotherapy(OVT)is a novel type of immunotherapy that induces anti-tumor responses through selective self-replication within cancer cells and oncolytic virus(OV)-mediated immunostimulation.Notably,talimogene laherparepvec(T-Vec)developed by the Amgen company in 2015,is the first FDA-approved OV product to be administered via intratumoral injection and has been the most successful OVT treatment.However,the systemic administration of OVs still faces huge challenges,including in vivo pre-existing neutralizing antibodies and poor targeting delivery efficacy.Recently,state-of-the-art progress has been made in the development of systemic delivery of OVs,which demonstrates a promising step toward broadening the scope of cancer immunotherapy and improving the clinical efficacy of OV delivery.Herein,this review describes the general characteristics of OVs,focusing on the action mechanisms of OVs as well as the advantages and disadvantages of OVT.The emerging multiple systemic administration approaches of OVs are summarized in the past five years.In addition,the combination treatments between OVT and traditional therapies(chemotherapy,thermotherapy,immunotherapy,and radiotherapy,etc.)are highlighted.Last but not least,the future prospects and challenges of OVT are also discussed,with the aim of facilitating medical researchers to extensively apply the OVT in the cancer therapy.展开更多
文摘Fyn kinase-dependent cellular events were related with skeletal muscle denervation. In the present study, we used a combination of techniques to measure ER stability and the related Gβ1γ2 trafficking following muscle mobilization, and demonstrated a temporally and Fyn-dependent up-regulation of Ca2+ level in the mobilized muscle. In parallel, Fyn activity in ER was gradually decreased, which was accompanied by enhanced PTP1B activity and expressions of ER proteins (calnexin, Grp94, cyclophilin, and Hsp70). Moreover, during muscle mobilization, there was more membrane protein breakdown than protein synthesis, which probably featured robust Gβ1γ2 internalization, and Rab1-dependent transport into ER compartment;the signaling was related to disruption of PI3K-Akt signaling and decrement of muscular functions. Then, Gβ1γ2 trafficking is a key component necessary for the early recovery processes regarding muscle atrophy, which would be the therapeutic consideration for muscle repair and regeneration.
基金supported by the National Natural Science Foundation of China(81773283).
文摘Anti virulence strategy has been considered as one of the most promising approaches to combat drug-rcesistant bacterial infections.Porc-forming toxins(PFTs)are the largest class of bacterial toxins,inficting their virulence ffect through creating pores on the cell membrane.However,curent solutions for eliminating PFTs are mostly designed based on their molecular structure,requiring customized design for different interactions.In the present study,we employed erythroliposome(denoted as RM-PL),a biomimetic platform constructed by artificial lipid membranes and natural erythrocyle membranes,to necutralize different hemolytic PFTs regardless of their molecular structure.When tested with model PFTs,including a-hemolysin,listeriolysin O,and streptolysin O,RM-PL could completely inhibit toxin-induced hemolysis in a concentration-dependent manner.In vivo studies further confirmed that RM-PL.could eficiently neuralize various toxins and save animals'lives without causing damage to 0rgans or tissues.In addition,we explored the underlying mechanisms of this efficient detoxification ability and found that it was mainly macrophages in the spleen and the liver that took up RM-PL-absorbed toxins through a variety of endocytosis pathways and digested them in lysosomes.In summary,the biomimetic RM-PL presented a promising system for broad-spectrum and powerful toxin neutralization with a mech-anism of lysosome-mediaed loxin degradation.
基金This work was supported by the National Key R&D Program of China(No.2019YFC1316104)the National Natural Science Foundation of China(Nos.81871960,82073368,and 82073777)+2 种基金Liaoning Revitalization Talents Program(Nos.XLYC2007071 and XLYC1808017)China Postdoctoral Science Foundation(No.2020M680986)General Project of Liaoning Provincial Department of Education(No.JKZ0927).
文摘Oncolytic virotherapy(OVT)is a novel type of immunotherapy that induces anti-tumor responses through selective self-replication within cancer cells and oncolytic virus(OV)-mediated immunostimulation.Notably,talimogene laherparepvec(T-Vec)developed by the Amgen company in 2015,is the first FDA-approved OV product to be administered via intratumoral injection and has been the most successful OVT treatment.However,the systemic administration of OVs still faces huge challenges,including in vivo pre-existing neutralizing antibodies and poor targeting delivery efficacy.Recently,state-of-the-art progress has been made in the development of systemic delivery of OVs,which demonstrates a promising step toward broadening the scope of cancer immunotherapy and improving the clinical efficacy of OV delivery.Herein,this review describes the general characteristics of OVs,focusing on the action mechanisms of OVs as well as the advantages and disadvantages of OVT.The emerging multiple systemic administration approaches of OVs are summarized in the past five years.In addition,the combination treatments between OVT and traditional therapies(chemotherapy,thermotherapy,immunotherapy,and radiotherapy,etc.)are highlighted.Last but not least,the future prospects and challenges of OVT are also discussed,with the aim of facilitating medical researchers to extensively apply the OVT in the cancer therapy.
