IntroductionIschemia-reperfusion injury (IRI) is a serious complication of hepatectomy and liver transplantation. The aim of this study was to evaluate the protective effects of salvianolic acid-A (Sal-A) against IRI-induced hepatocellular injury.Material and methodsForty rats were randomly divided into the following four groups: (1) sham group, (2) IR group, (3) Sal-A(10) group and (4) Sal-A(20) group. After 90 min of ischemia and 6 h of reperfusion, serum alanine aminotransferease (ALT) and apartate aminotransferase (AST) levels were measured; the amounts of malondialdehyde (MDA) and superoxide dismutase (SOD) in the liver tissue were determined; the expression of Bcl-2 and caspase-3 was detected and the severity of apoptosis, inflammation and pathological alterations were evaluated. Also apoptosis and mRNA and protein levels of TLR4 (toll-like receptor 4) were tested.ResultsThe serum aminotransferases, hepatic MDA concentration, and apoptotic cells in the IR group were significantly higher than in the sham group (p < 0.01), whereas the Sal-A group values were lower than in the IR group (p < 0.05). Compared with the IR group, the Sal-A groups had significantly higher Bcl-2 expression and downregulated cleaved caspase-3 expression in liver tissue. Moreover, increased mRNA and protein levels of TLR4 in IR rats and Sal-A could improve the increased mRNA and protein levels of TLR4.ConclusionsSal-A had a synergistically protective effect on the liver tissue against IRI that might be due to decreased oxidative stress, inflammation, hepatocellular apoptosis and include, at least in part, the regulation of TLR4.

FoxM1 is involved in the regeneration of several organs after injury and expressed in the intestinal mucosa. The intrinsic mechanism of FoxM1 activity in the mucosa after intestinal ischemia/reperfusion (I/R) injury has not been reported. Therefore, we investigated the role of FoxM1 in mediating intestinal mucosa regeneration after I/R injury. Expression of FoxM1 and the proliferation of intestinal mucosa epithelial cells were examined in rats with intestinal I/R injury and an IEC-6 cell hypoxia/reperfusion (H/R) model. The effects of FoxM1 inhibition or activation on intestinal epithelial cell proliferation were measured. FoxM1 expression was consistent with the proliferation of intestinal epithelial cells in the intestinal mucosa after I/R injury. Inhibition of FoxM1 expression led to the downregulation of Ki-67 expression mediated by the inhibited expression of Nurr1, and FoxM1 overexpression promoted IEC-6 cell proliferation after H/R injury through activating Nurr1 expression. Furthermore, FoxM1 directly promoted the transcription of Nurr1 by directly binding the promoter of Nurr1. Further investigation showed low expression levels of FoxM1, Nurr1, and Ki-67 in the intestinal epithelium of patients with intestinal ischemic injury. FoxM1 acts as a critical regulator of intestinal regeneration after I/R injury by directly promoting the transcription of Nurr1. The FoxM1/ Nurr1 signaling pathway represents a promising therapeutic target for intestinal I/R injury and related clinical diseases.

Low expression of claudin-1 is associated with TNM III-IV stage and poor prognosis of CRC patients. Low expression of claudin-1 is not associated with gender, tumors' differentiation depth of invasion and lymph node involvement of CRC patients.

Expression of FoxM1 is associated with TNM stage, depth of invasion, lymph node metastasis and poor prognosis of the patients with GC.