Selectins are carbohydrate-binding cell adhesion molecules that play a major role in the initiation of inflammatory responses. Accumulaed evidence has suggested that heparin＇s anti-inflammatory effects are mainly med...Selectins are carbohydrate-binding cell adhesion molecules that play a major role in the initiation of inflammatory responses. Accumulaed evidence has suggested that heparin＇s anti-inflammatory effects are mainly mediated by blocking L-or P-selectin-initiated cell adhesion. Recently, we have reported that periodate-oxidized, borohydridereduced heparin （RO-heparln） can inhibit P-selectin-mediated acute inflammation. Here we further examined the effect of RO-heparin on the adhesion of L-selectin-mediated leukocytes to vascular endothelium under flow conditions in vivo and in vitro. The results show that RO-heparin with a low anticoagulant activity can effectively reduce leucocyte roiling on thioglycoUate-induced rat mesenterlc venules and L-selectin-metadiated neutrophil roiling on TNF-α-induced human umbilical vein endothelial cells（HUVECs） under flow conditions. Our findings suggest that the effect of RO-heparin on inflammatory responses is mainly a result of its inhibiting the interaction between P- or L-selectin and its ligands. The findings also suggest that RO-heparin may be useful in preventing inflammation diseases.展开更多
Objective： To compare carotid catheters blooddrawing and tail-cut blooddrawing in traumatizing rats and changing their intemal L-selectin. Methods： Two ways of bloodletting were selected to produce hemorrhagic shock...Objective： To compare carotid catheters blooddrawing and tail-cut blooddrawing in traumatizing rats and changing their intemal L-selectin. Methods： Two ways of bloodletting were selected to produce hemorrhagic shock models. Monoclonal antibody sign and flow cytometer were used to test neutrophil L-selectin dynamic expression in rats. Results： No remarkable differences were shown among different time points in neutrophil L-selectin expressing amount （ average fluorescence index） （ P 〉 0.05）. Compared with the normal control group, all cell surface expressions in empirical control group increased. Cell surface expressions reached the summit at 3 hours and kept the high level at 4-5 hours. A progressive increase of the mRNA expression peaked at 5 hours; the expressions in both groups of carotid catheters blooddrawing increased compared with normal control group, and remained stable after 3 hours compared with the Tail-cut Blooddrawing Group. Conclusion： L-sclectin expressions changed little in tail-cut blooddrawing rats, while carotid catheters resulted moderate or sever trauma. Therefore, it was suggested that it should not be set as hemorrhagic shock control model. As neutrophil L-selection expressions increased after trauma, the adhesion of leucocytes to the venule wall may be beneficial to the healing of wound and enhance the ability of anti-infection. The immediate increasing of neutrophil surface L-selectin expressions in this study was likely due to the direct release of Lselectin from cytoplasm granules that do not depend on protein synthesis.展开更多
An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(...An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein.This study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 on.the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches.MiR329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell lines.Additionally,a clinical comparison study was performed using the TCGA database.Subsequently,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments.When miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic bodies.The expression of proteins that indicate apoptosis increased simultaneously.The cell cycle was arrested in the G0/G1 phase,and the G1/S transition was blocked.The introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt pathway.Xenograf experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues decreased.MiR 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo.Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR 3293p.Summarizing these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcoma by inhibiting TCF7L1.展开更多
文摘Selectins are carbohydrate-binding cell adhesion molecules that play a major role in the initiation of inflammatory responses. Accumulaed evidence has suggested that heparin＇s anti-inflammatory effects are mainly mediated by blocking L-or P-selectin-initiated cell adhesion. Recently, we have reported that periodate-oxidized, borohydridereduced heparin （RO-heparln） can inhibit P-selectin-mediated acute inflammation. Here we further examined the effect of RO-heparin on the adhesion of L-selectin-mediated leukocytes to vascular endothelium under flow conditions in vivo and in vitro. The results show that RO-heparin with a low anticoagulant activity can effectively reduce leucocyte roiling on thioglycoUate-induced rat mesenterlc venules and L-selectin-metadiated neutrophil roiling on TNF-α-induced human umbilical vein endothelial cells（HUVECs） under flow conditions. Our findings suggest that the effect of RO-heparin on inflammatory responses is mainly a result of its inhibiting the interaction between P- or L-selectin and its ligands. The findings also suggest that RO-heparin may be useful in preventing inflammation diseases.
文摘Objective： To compare carotid catheters blooddrawing and tail-cut blooddrawing in traumatizing rats and changing their intemal L-selectin. Methods： Two ways of bloodletting were selected to produce hemorrhagic shock models. Monoclonal antibody sign and flow cytometer were used to test neutrophil L-selectin dynamic expression in rats. Results： No remarkable differences were shown among different time points in neutrophil L-selectin expressing amount （ average fluorescence index） （ P 〉 0.05）. Compared with the normal control group, all cell surface expressions in empirical control group increased. Cell surface expressions reached the summit at 3 hours and kept the high level at 4-5 hours. A progressive increase of the mRNA expression peaked at 5 hours; the expressions in both groups of carotid catheters blooddrawing increased compared with normal control group, and remained stable after 3 hours compared with the Tail-cut Blooddrawing Group. Conclusion： L-sclectin expressions changed little in tail-cut blooddrawing rats, while carotid catheters resulted moderate or sever trauma. Therefore, it was suggested that it should not be set as hemorrhagic shock control model. As neutrophil L-selection expressions increased after trauma, the adhesion of leucocytes to the venule wall may be beneficial to the healing of wound and enhance the ability of anti-infection. The immediate increasing of neutrophil surface L-selectin expressions in this study was likely due to the direct release of Lselectin from cytoplasm granules that do not depend on protein synthesis.
基金The Fund of National Cancer Center Research and Development(26-A-4),The Grants-in-Aid for Scientific Research(Grant Nos.15K10451,16K10866 and 16K20063)from Japan Society for the Promotion of Science.
文摘An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein.This study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 on.the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches.MiR329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell lines.Additionally,a clinical comparison study was performed using the TCGA database.Subsequently,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments.When miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic bodies.The expression of proteins that indicate apoptosis increased simultaneously.The cell cycle was arrested in the G0/G1 phase,and the G1/S transition was blocked.The introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt pathway.Xenograf experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues decreased.MiR 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo.Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR 3293p.Summarizing these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcoma by inhibiting TCF7L1.
