Most of the deaths that occurred during two large outbreaks of Streptococcus suis infections in 1998 and 2005 in China were caused by streptococcal toxic shock syndrome (STSS), which is characterized by increased vascular permeability. Heparin-binding protein (HBP) is thought to mediate the vascular leakage. The purpose of this study was to investigate the detailed mechanism underlying the release of HBP and the vascular leakage induced by S. suis. Significantly higher serum levels of HBP were detected in Chinese patients with STSS than in patients with meningitis or healthy controls. Suilysin (SLY) is an exotoxin secreted by the highly virulent strain 05ZYH33, and it stimulated the release of HBP from the polymorphonuclear neutrophils and mediated vascular leakage in mice. The release of HBP induced by SLY was caused by a calcium influx-dependent degranulation. Analyses using a pharmacological approach revealed that the release of HBP induced by SLY was related to Toll-like receptor 4, p38 mitogen-activated protein kinase, and the 1-phosphatidylinositol 3-kinase pathway. It was also dependent on a G protein-coupled seven-membrane spanning receptor. The results of this study provide new insights into the vascular leakage in STSS associated with non-Group A streptococci, which could lead to the discovery of potential therapeutic targets for STSS associated with S. suis.
Endocan, which has been identified to be low expressed in gastric cancer, was found to be positively related to the differentiation level of gastric cancer in vivo and in vitro. In the present study, we aimed to investigate the role of endocan in gastric adenocarcinoma cell line SGC7901 by artificially upregualting or downregulating endocan expression using endocan recombinant vector or specific small interfering RNA (siRNA)-targeting endocan gene, respectively. The effects of endocan recombinant vector-mediated over-expressing and siRNA-mediated endocan silencing on the differentiation, migration, and apoptosis of SGC7901 cells were assessed. Furthermore, the primary molecular mechanisms of endocan were explored by testing the expression alterations of associated protein in SGC7901 along endocan over-expression or knockdown. We found that over-expression of endocan reduced the migration but promoted the differentiation and apoptosis of SGC7901 cells. While, knockdown of endocan did just the opposite. Some molecules were found to participate in endocan-mediated anti-tumor effects, such as p53, caspase 3, and MMP-9. In conclusion, our findings suggest that endocan plays an anti-carcinogenic role in gastric cancer development and progression and might serve as a prognostic biomarker as well as a potential therapeutic target for gastric cancer.
The recurrence and metastasis is one of the major reasons for malignant tumor treatment failure. Melatonin, a naturally occuring hormone, could reduce the recurrence and metastasis of various tumors. However, the underlying molecular mechanisms of melatonin on tumor metastasis inhibition have not been fully elucidated. In the present study, we explored J Cell Biochem. 2019;120:9781-9786.wileyonlinelibrary.com/journal/jcb
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