BACKGROUND Circular RNAs(circRNAs)have attracted extensive attention as therapeutic targets in gastric cancer(GC).Circ_0003356 is known to be downregulated in GC tissues,but its cellular function and mechanisms remain...BACKGROUND Circular RNAs(circRNAs)have attracted extensive attention as therapeutic targets in gastric cancer(GC).Circ_0003356 is known to be downregulated in GC tissues,but its cellular function and mechanisms remain undefined.AIM To investigate the role of circ_0003356 in GC at the molecular and cellular level.METHODS Circ_0003356,miR-668-3p,and SOCS3 expression were assessed via quantitative real time-polymerase chain reaction(qRT-PCR).Wound healing,EdU,CCK-8,flow cytometry and transwell assays were used to analyze the migration,proliferation,viability,apoptosis and invasion of GC cells.The subcellular localization of circ_0003356 was monitored using fluorescence in situ hybridization.The interaction of circ_0003356 with miR-668-3p was confirmed using RIP-qRT-PCR,RNA pull-down,and dual luciferase reporter assays.We observed protein levels of genes via western blot.We injected AGS cells into the upper back of mice and performed immunohistochemistry staining for examining E-cadherin,N-cadherin,Ki67,and SOCS3 expressions.TUNEL staining was performed for the assessment of apoptosis in mouse tumor tissues.RESULTS Circ_0003356 and SOCS3 expression was downregulated in GC cells,whilst miR-668-3p was upregulated.Exogenous circ_0003356 expression and miR-668-3p silencing suppressed the migration,viability,proliferation,epithelial to mesenchy-mal transition(EMT)and invasion of GC cells and enhanced apoptosis.Circ_0003356 overexpression impaired tumor growth in xenograft mice.Targeting of miR-668-3p by circ_0003356 was confirmed through binding assays and SOCS3 was identified as a downstream target of miR-668-3p.The impacts of circ_0003356 on cell proliferation,apoptosis,migration,invasion and EMT were reversed by miR-668-3p up-regulation or SOCS3 downregulation in GC cells.CONCLUSION Circ_0003356 impaired GC development through its interaction with the miR-668-3p/SOCS3 axis.展开更多
BACKGROUND Type Ⅰ diabetes(T1D)is characterized by insulin loss caused by inflammatory cells that excessively infiltrate and destroy the pancreas,resulting in dysregulation of tissue homeostasis,mechanobiological pro...BACKGROUND Type Ⅰ diabetes(T1D)is characterized by insulin loss caused by inflammatory cells that excessively infiltrate and destroy the pancreas,resulting in dysregulation of tissue homeostasis,mechanobiological properties,and the immune response.The streptozotocin(STZ)-induced mouse model exhibits multiple features of human T1D and enables mechanistic analysis of disease progression.However,the relationship between the mechanochemical signaling regulation of STZ-induced T1D and macrophage migration and phagocytosis is unclear.AIM To study the mechanochemical regulation of STZ-induced macrophage response on pancreatic beta islet cells to gain a clearer understanding of T1D.METHODS We performed experiments using different methods.We stimulated isolated pancreatic beta islet cells with STZ and then tested the macrophage migration and phagocytosis.RESULTS In this study,we discovered that the integrin-associated surface factor CD47 played a critical role in immune defense in the STZ-induced T1D model by preventing pancreatic beta islet inflammation.In comparison with healthy mice,STZ-treated mice showed decreased levels of CD47 on islet cells and reduced interaction of CD47 with signal regulatory proteinα(SIRPα),which negatively regulates macrophage-mediated phagocytosis.This resulted in weakened islet cell immune defense and promoted macrophage migration and phagocytosis of target inflammatory cells.Moreover,lipopolysaccharide-activated human acute monocytic leukemia THP-1 cells also exhibited enhanced phagocytosis in the STZ-treated islets,and the aggressive attack of the inflammatory islets correlated with impaired CD47-SIRPαinteractions.In addition,CD47 overexpression rescued the pre-labeled targeted cells.CONCLUSION This study indicates that CD47 deficiency promotes the migration and phagocytosis of macrophages and provides mechanistic insights into T1D by associating the interactions between membrane structures and inflammatory disease progression.展开更多
Coronary heart disease(CHD)is a complex metabolic syndrome,resulting in atherosclerotic lesions in one or more coronary arteries.CHD is associated with high morbidity and mortality worldwide.Coronary artery bypass gra...Coronary heart disease(CHD)is a complex metabolic syndrome,resulting in atherosclerotic lesions in one or more coronary arteries.CHD is associated with high morbidity and mortality worldwide.Coronary artery bypass grafting(CABG)is the gold standard for invasive treatment of severe CHD,especially triple-vessel disease and left main disease.Saphenous veins(SVs)are typically used in CABG because of their sufficient length and convenience,but SV graft(SVG)failure is a common finding in patients.Approximately 20%of SVGs fail within 1 year after CABG,and the 10-year post-CA BG 1 patency rate is 60%.展开更多
Fiber-wireless(FiWi) access networks, which are a combination of fiber networks and wireless networks,have the advantages of both networks, such as high bandwidth, high security, low cost, and flexible access. However...Fiber-wireless(FiWi) access networks, which are a combination of fiber networks and wireless networks,have the advantages of both networks, such as high bandwidth, high security, low cost, and flexible access. However,with the increasing need for bandwidth and types of service from users, FiWi networks are still relatively incapable and ossified. To alleviate bandwidth tension and facilitate new service deployment, we attempt to apply network virtualization in FiWi networks, in which the network's control plane and data plane are separated from each other.Based on a previously proposed hierarchical model and service model for FiWi network virtualization, the process of service implementation is described. The performances of the FiWi access networks applying network virtualization are analyzed in detail, including bandwidth for links, throughput for nodes, and multipath flow transmission.Simulation results show that the FiWi network with virtualization is superior to that without.展开更多
基金Supported by Zhongshan Social Public Welfare and Basic Research Project,No. 200421093453685
文摘BACKGROUND Circular RNAs(circRNAs)have attracted extensive attention as therapeutic targets in gastric cancer(GC).Circ_0003356 is known to be downregulated in GC tissues,but its cellular function and mechanisms remain undefined.AIM To investigate the role of circ_0003356 in GC at the molecular and cellular level.METHODS Circ_0003356,miR-668-3p,and SOCS3 expression were assessed via quantitative real time-polymerase chain reaction(qRT-PCR).Wound healing,EdU,CCK-8,flow cytometry and transwell assays were used to analyze the migration,proliferation,viability,apoptosis and invasion of GC cells.The subcellular localization of circ_0003356 was monitored using fluorescence in situ hybridization.The interaction of circ_0003356 with miR-668-3p was confirmed using RIP-qRT-PCR,RNA pull-down,and dual luciferase reporter assays.We observed protein levels of genes via western blot.We injected AGS cells into the upper back of mice and performed immunohistochemistry staining for examining E-cadherin,N-cadherin,Ki67,and SOCS3 expressions.TUNEL staining was performed for the assessment of apoptosis in mouse tumor tissues.RESULTS Circ_0003356 and SOCS3 expression was downregulated in GC cells,whilst miR-668-3p was upregulated.Exogenous circ_0003356 expression and miR-668-3p silencing suppressed the migration,viability,proliferation,epithelial to mesenchy-mal transition(EMT)and invasion of GC cells and enhanced apoptosis.Circ_0003356 overexpression impaired tumor growth in xenograft mice.Targeting of miR-668-3p by circ_0003356 was confirmed through binding assays and SOCS3 was identified as a downstream target of miR-668-3p.The impacts of circ_0003356 on cell proliferation,apoptosis,migration,invasion and EMT were reversed by miR-668-3p up-regulation or SOCS3 downregulation in GC cells.CONCLUSION Circ_0003356 impaired GC development through its interaction with the miR-668-3p/SOCS3 axis.
基金Supported by the National Natural Science Foundation of China,No.31701179the China Postdoctoral Science Foundation,No.2016M591877。
文摘BACKGROUND Type Ⅰ diabetes(T1D)is characterized by insulin loss caused by inflammatory cells that excessively infiltrate and destroy the pancreas,resulting in dysregulation of tissue homeostasis,mechanobiological properties,and the immune response.The streptozotocin(STZ)-induced mouse model exhibits multiple features of human T1D and enables mechanistic analysis of disease progression.However,the relationship between the mechanochemical signaling regulation of STZ-induced T1D and macrophage migration and phagocytosis is unclear.AIM To study the mechanochemical regulation of STZ-induced macrophage response on pancreatic beta islet cells to gain a clearer understanding of T1D.METHODS We performed experiments using different methods.We stimulated isolated pancreatic beta islet cells with STZ and then tested the macrophage migration and phagocytosis.RESULTS In this study,we discovered that the integrin-associated surface factor CD47 played a critical role in immune defense in the STZ-induced T1D model by preventing pancreatic beta islet inflammation.In comparison with healthy mice,STZ-treated mice showed decreased levels of CD47 on islet cells and reduced interaction of CD47 with signal regulatory proteinα(SIRPα),which negatively regulates macrophage-mediated phagocytosis.This resulted in weakened islet cell immune defense and promoted macrophage migration and phagocytosis of target inflammatory cells.Moreover,lipopolysaccharide-activated human acute monocytic leukemia THP-1 cells also exhibited enhanced phagocytosis in the STZ-treated islets,and the aggressive attack of the inflammatory islets correlated with impaired CD47-SIRPαinteractions.In addition,CD47 overexpression rescued the pre-labeled targeted cells.CONCLUSION This study indicates that CD47 deficiency promotes the migration and phagocytosis of macrophages and provides mechanistic insights into T1D by associating the interactions between membrane structures and inflammatory disease progression.
基金This work was supported by a grant from the Tianjin Haihe Medical Scholars Fund.
文摘Coronary heart disease(CHD)is a complex metabolic syndrome,resulting in atherosclerotic lesions in one or more coronary arteries.CHD is associated with high morbidity and mortality worldwide.Coronary artery bypass grafting(CABG)is the gold standard for invasive treatment of severe CHD,especially triple-vessel disease and left main disease.Saphenous veins(SVs)are typically used in CABG because of their sufficient length and convenience,but SV graft(SVG)failure is a common finding in patients.Approximately 20%of SVGs fail within 1 year after CABG,and the 10-year post-CA BG 1 patency rate is 60%.
基金Project supported by the National Natural Science Foundation of China(Nos.61240040 and 61471053)
文摘Fiber-wireless(FiWi) access networks, which are a combination of fiber networks and wireless networks,have the advantages of both networks, such as high bandwidth, high security, low cost, and flexible access. However,with the increasing need for bandwidth and types of service from users, FiWi networks are still relatively incapable and ossified. To alleviate bandwidth tension and facilitate new service deployment, we attempt to apply network virtualization in FiWi networks, in which the network's control plane and data plane are separated from each other.Based on a previously proposed hierarchical model and service model for FiWi network virtualization, the process of service implementation is described. The performances of the FiWi access networks applying network virtualization are analyzed in detail, including bandwidth for links, throughput for nodes, and multipath flow transmission.Simulation results show that the FiWi network with virtualization is superior to that without.
