Objective:To analyze the expressions of minichromosome maintenance protein 4(MCM4) and proliferating cell nuclear antigen (PCNA) in gastric cancer tissues, to explore the relationship between MCM4/PCNA and gastric cancer, and to investigate the possibility of MCM4/PCNA as a potential biomarker for gastric cancer.Methods:Bioinformatics methods were used to analyze the mRNA expressions of MCM4 and PCNA in gastric cancer tissues and adjacent normal tissues. The clinicopathological data of 69 patients with gastric cancer who underwent surgery were retrospectively analyzed. The expression levels of MCM4 and PCNA in gastric cancer tissues and adjacent normal tissues were detected by immunohistochemistry, and their relationship with the clinicopathological characteristics of gastric cancer patients was analyzed.Results:The mRNA levels of MCM4 and PCNA in gastric cancer tissues are significantly higher than those in adjacent normal tissues (all P<0.05). The expression of MCM4 is correlated with the tumor size of gastric cancer ( P=0.037), but there is no significant correlation with gender, age and tumor grade (all P>0.05). Both MCM4 and PCNA proteins are highly expressed in gastric cancer patients. Conclusions:The expression levels of MCM4 and PCNA have a clear correlation with the occurrence of gastric cancer. MCM4 and PCNA are expected to be potential biomarkers for the diagnosis and treatment of gastric cancer.

Human enterovirus 71 (EV71) is the main causative pathogen of hand, foot, and mouth disease (HFMD) in children. The epidemic of HFMD has been a public health problem in Asia-Pacific region for decades, and no vaccine and effective antiviral medicine are available. Curcumin has been used as a traditional medicine for centuries to treat a diversity of disorders including viral infections. In this study, we demonstrated that curcumin showed potent antiviral effect again EV71. In Vero cells infected with EV71, the addition of curcumin significantly suppressed the synthesis of viral RNA, the expression of viral protein, and the overall production of viral progeny. Similar with the previous reports, curcumin reduced the production of ROS induced by viral infection. However, the antioxidant property of curcumin did not contribute to its antiviral activity, since N-acetyl-l-cysteine, the potent antioxidant failed to suppress viral replication. This study also showed that extracellular signal-regulated kinase (ERK) was activated by either viral infection or curcumin treatment, but the activated ERK did not interfere with the antiviral effect of curcumin, indicating ERK is not involved in the antiviral mechanism of curcumin. Unlike the previous reports that curcumin inhibited protein degradation through ubiquitin-proteasome system (UPS), we found that curcumin had no impact on UPS in control cells. However, curcumin did reduce the activity of proteasomes which was increased by viral infection. In addition, the accumulation of the short-lived proteins, p53 and p21, was increased by the treatment of curcumin in EV71-infected cells. We further probed the antiviral mechanism of curcumin by examining the expression of GBF1 and PI4KB, both of which are required for the formation of viral replication complex. We found that curcumin significantly reduced the level of both proteins. Moreover, the decreased expression of either GBF1 or PI4KB by the application of siRNAs was sufficient to suppress viral replication. We also demonstrated that curcumin showed anti-apoptotic activity at the early stage of viral infection. The results of this study provide solid evidence that curcumin has potent anti-EV71 activity. Whether or not the down-regulated GBF1 and PI4KB by curcumin contribute to its antiviral effect needs further studies.