RESUMO
Acute liver failure (ALF) is a serious life-threatening condition. Mesenchymal stem cells (MSCs) may be an effective treatment for this condition and a good alternative to liver transplantation. Icaritin (ICT) is an active ingredient of the genus Epimedium, a traditional Chinese medicine, with the potential to enhance the proliferation of MSCs. The purpose of this study was to explore whether ICT increased the therapeutic effects of MSCs and explore its underlying mechanisms. For in vivo experiments, a rat ALF model was established by intraperitoneal injection of D(+)-galactosamine/ lipopolysaccharide. MSCs cocultured with ICT were used to treat ALF rats and the protective effects assessed as survival rate, levels of serum AST and ALT, and histological changes in liver tissue. For in vitro experiments, MSCs were treated in serum-free culture for 72 h to simulate the disruption of intrahepatic microcirculation. MSCs apoptosis was examined to determine whether ICT rescued impaired MSCs. The role of the hepatocyte growth factor (HGF)/c-Met pathway in MSCs was assessed by constructing genetically modified MSCs overexpressing c-Met and by using the c-Met receptor inhibitor (crizotinib). The results showed that MSCs increased the survival rate of ALF rats and reduced liver damage. MSCs cocultured with ICT exerted a greater therapeutic effect than MSCs alone. Further, the HGF/c-Met pathway played a key role in the antiapoptotic activity of MSCs, which was associated with the optimized efficacy of ICT. In conclusion, this study demonstrated that ICT enhances the therapeutic effect of MSCs in a model of ALF, improving the antiapoptotic potential of MSCs by upregulation of the HGF/c-Met pathway. The combination of stem cell therapy with traditional herbal extracts may improve MSC-based clinical applications.
RESUMO
DNA mismatch repair was proposed to play a pivotal role in the development and prognosis of colorectal cancer. However, the prognostic value of mismatch repair on colorectal cancer is still unknown. The PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched. The articles about mismatch repair (including hMLH1, hMSH2, hMSH3, hMSH6, hPMSH1, and hPMSH2) deficiency for the prognosis of patients with colorectal cancer were included in the study. The hazard ratio and its 95% confidence interval were used to measure the impact of mismatch repair deficiency on survival time. Twenty-one articles were included. The combined hazard ratio for mismatch repair deficiency on overall survival was 0.59 (95% confidence interval: 0.50-0.69) and that on disease-free survival was 0.57 (95% confidence interval: 0.43-0.75). In subgroup analysis, there were a significant association between overall survival and mismatch repair deficiency in Asian studies (hazard ratio: 0.67; 95% confidence interval: 0.50-0.91) and Western studies (hazard ratio: 0.56; 95% confidence interval: 0.46-0.67). For disease-free survival, the hazard ratios in Asian studies and Western studies were 0.55 (95% confidence interval: 0.38-0.81) and 0.62 (95% confidence interval: 0.50-0.78), respectively. Our meta-analysis indicated that mismatch repair could be used to evaluate the prognosis of patients with colorectal cancer.
