A Human Active Lower Limb Model for Chinese Pedestrian Safety Evaluation

A subsystem impactor test for pedestrian lower limb injury evaluation has been brought in China New Car Assessment Protocol(CNCAP).Concerning large anthropometr...     

3,3′,4,5′-Tetramethoxy-trans-stilbene Improves Insulin Resistance by Activating the IRS/PI3K/Akt Pathway and Inhibiting Oxidative Stress

The potential anti-diabetic effect of resveratrol derivative, 3,3′,4,5′-tetramethoxy-trans-stilbene (3,3′,4,5′-TMS) and its underlying mechanism in high glucose (HG) and dexamethasone (DXMS)-stimulated insulin-resistant HepG2 cells (IR-HepG2) were investigated. 3,3′,4,5′-TMS did not reduce the cell viability of IR-HepG2 cells at the concentrations of 0.5–10 µM. 3,3′,4,5′-TMS increased the potential of glucose consumption and glycogen synthesis in a concentration-dependent manner in IR-HepG2 cells. 3,3′,4,5′-TMS ameliorated insulin resistance by enhancing the phosphorylation of glycogen synthase kinase 3 beta (GSK3β), inhibiting phosphorylation of insulin receptor substrate-1 (IRS-1), and activating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in IR-HepG2 cells. Furthermore, 3,3′,4,5′-TMS significantly suppressed levels of reactive oxygen species (ROS) with up-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) expression. To conclude, the beneficial effect of 3,3′,4,5′-TMS against insulin resistance to increase glucose consumption and glycogen synthesis was mediated through activation of IRS/PI3K/Akt signaling pathways in the IR-HepG2 cells, accomplished with anti-oxidative activity through up-regulation of Nrf2.     

Lithocholic acid inhibits dendritic cell activation by reducing intracellular glutathione via TGR5 signaling

Dendritic cells (DCs) are the major antigen-presenting cells and play an important role in autoimmune uveitis. Emerging evidence suggests that bile acids (BAs) regulate DCs maturation. However, the underlying mechanisms by which BAs regulate the function of DCs still need to be clarified. Here, we demonstrate that lithocholic acid (LCA) inhibits the production of pro-inflammatory cytokines and the expression of surface molecules in bone marrow-derived dendritic cells (BMDCs). LCA attenuates the severity of EAU by modulating the maturation of splenic CD11C⁺MHCII^high DCs. Notably, Takeda G-protein coupled receptor 5 (TGR5) deficiency partially reverses the inhibitory effect of LCA on DCs in vitro and in vivo. TGR5 activation also downregulates the NF-κB and MAPK pathways by inhibiting glutathione production and inducing oxidative stress in DCs, which leads to apoptosis and autophagy in DCs. In addition, LCA or INT-777 treatment increases the TGR5 expression in monocyte-derived dendritic cells (MD-DCs) of patients with active BD, whereas both LCA and TGR5 agonists inhibit the activation of MD-DCs. These results suggest that LCA and TGR5 agonists might be potential therapeutic drugs for the treatment of autoimmune uveitis.     

shRNA‑mediated knockdown of KNTC1 inhibits non-small-cell lung cancer through regulating PSMB8

In view of the important roles played by Kinetochore proteins in mitosis, we believed that they may contribute to the development and progression of human cancers, which has been reported recently elsewhere. Kinetochore-associated 1 (KNTC1) participates in the segregation of sister chromatids during mitosis, the effects of which on non-small-cell lung cancer (NSCLC) remain unclear. Here, we sought to identify the biological significance of KNTC1 in NSCLC. KNTC1 protein expression in NSCLC tissues was investigated by immunohistochemistry. Lentivirus delivered short hairpin RNA (shRNA) was utilized to establish KNTC1 silence NSCLC cell lines. The effects of KNTC1 depletion on NSCLC cell proliferation, migration, apoptosis, and tumor formation were analyzed by MTT assay, wound-healing assay, transwell assay, flow cytometry assay, and in nude mouse models in vivo. After KNTC1 reduction, NSCLC cell viability, proliferation, migration, and invasion were restrained. A xenograft tumor model was also provided to demonstrate the inhibited tumorigenesis in NSCLC. In addition, the downstream mechanism analysis indicated that KNTC1 depletion was positively associated with PSMB8. The findings of the present study suggested that KNTC1 may have a pivotal role in mediating NSCLC progression and may act as a novel therapeutic target for NSCLC.Subject terms: Non-small-cell lung cancer, Cell migration     

植被恢复过程中芒萁覆盖对侵蚀红壤氮组分的影响

氮素是限制陆地生态系统生产力的重要因子。采用时空代换法,以红壤侵蚀区未治理、恢复12年和30年的马尾松林为研究对象,对比分析了林下芒萁覆盖地与裸地表层土壤之间氮同位素、不同形态氮组分含量以及不同组分氮含量所占比例之间的差异。结果表明:在所有马尾松林中,芒萁覆盖增加了表层土壤的全氮含量,δ~(15)N值则比林下裸地显著降低了33. 8%—83.1%(P0.05)。随着恢复年限增加,林下芒萁覆盖地表层土壤δ~(15)N值显著下降,而林下裸露地δ~(15)N值没有显著变化(P0.05)。不同恢复年限马尾松林的芒萁覆盖地表层土壤微生物生物量氮、可溶性有机氮和铵态氮含量显著高于林下裸地(P 0.05),而硝态氮含量则显著低于林下裸地(P0.05)。随恢复年限增加,表层土壤微生物生物量氮、可溶性有机氮、铵态氮含量均呈增加趋势,而硝态氮含量则呈下降趋势,不同形态氮占全氮比例表现为:微生物生物量氮铵态氮可溶性有机氮硝态氮。相关分析表明土壤δ~(15)N值与硝态氮极显著正相关,与其他氮组分极显著负相关(P0.01)。由此可见,与林下裸地相比,芒萁覆盖在植被恢复过程中有助于提高表层土壤中全氮、微生物生物量氮、可溶性有机氮和铵态氮含量,降低硝态氮的淋溶损失风险,促进土壤氮保持和积累,从而有利于退化红壤生态系统的恢复。     

Phosphorylation on tyrosine-15 of p34(Cdc2) by ErbB2 inhibits p34(Cdc2) activation and is involved in resistance to taxol-induced apoptosis

ErbB2 overexpression confers resistance to taxol-induced apoptosis by inhibiting p34(Cdc2) activation. One mechanism is via ErbB2-mediated upregulation of p21(Cip1), which inhibits Cdc2. Here, we report that the inhibitory phosphorylation on Cdc2 tyrosine (Y)15 (Cdc2-Y15-p) is elevated in ErbB2-overexpressing breast cancer cells and primary tumors. ErbB2 binds to and colocalizes with cyclin B-Cdc2 complexes and phosphorylates Cdc2-Y15. The ErbB2 kinase domain is sufficient to directly phosphorylate Cdc2-Y15. Increased Cdc2-Y15-p in ErbB2-overexpressing cells corresponds with delayed M phase entry. Expressing a nonphosphorylatable mutant of Cdc2 renders cells more sensitive to taxol-induced apoptosis. Thus, ErbB2 membrane RTK can confer resistance to taxol-induced apoptosis by directly phosphorylating Cdc2.     

Chronic Helicobacter pylori Infection Does Not Significantly Alter the Microbiota of the Murine Stomach

We examined the impact of Helicobacter pylori infection on the murine gastric microbiota by culture and terminal-restriction fragment length polymorphism and found that neither acute nor chronic H. pylori infection substantially affected the gastric microbial composition. Interestingly, the total H. pylori burden detected by real-time PCR was significantly higher than that revealed by viable counts, suggesting that the antigenic load sustaining H. pylori-induced gastritis could be considerably higher than previously believed.