Spontaneous running wheel improves neuroprotection efficacy of ischemic postconditioning in mice following ischemia/reperfusion injury

Ischemic postconditioning(IP)has been shown to provide protection for ischemia/reperfusion(IR)injury,but its efficacy is limited.In this study we hypothesized that spontaneous running wheel(RW)could improve neuroprotection efficacy of IP for IR.We established mouse models of IR and showed that compared to Sham group,IR group had obvious brain infract and neurological dysfunction.In IR+IP group,brain infract and neurological dysfunction improved compared to IR group.However,in IR+IP+RW group brain infract and neurological dysfunction improved much better.TUNEL assay showed that IP but not RW significantly reduced the number of apoptotic cells after IR.However,the number of apoptotic cells was significantly reduced in RW+IP group.In addition,the levels of pro-apoptotic factors increased in IR group but significantly reduced in IR+IP+RW group,while the levels of antiapoptotic factors decreased in IR group but significantly increased in IR+IP+RW group.Moreover,in IR+IP+RW group,MDA level was further decreased and SOD level was further increased compared to IR+IP group.Finally,both PI3K inhibitor and STAT3 inhibitor significantly worsened brain infract and neurological dysfunction and promoted apoptosis in IR mice.In conclusion,RW combined with IP reduces brain infract and neurological dysfunction in mice after IR,and this is associated with enhanced anti-apoptotic and anti-oxidant benefits via the activation of PI3K and STAT3 pathways.

Epithelial-mesenchymal transition contributes to malignant phenotypes of circulating tumor cells derived from gastric cancer

Circulating tumor cells(CTCs)are crucial to tumor metastasis,and they usually undergo epithelial-mesenchymal transition(EMT)in order to disseminate from the primary tumor.However,very little is currently known about the relationship between EMT and malignant phenotypes of CTCs in the context of gastric cancer.Therefore,this study aimed to investigate the contribution of EMT to malignant phenotypes of CTCs derived from gastric cancer cells.We xenografted MKN28 gastric cancer cells pretreated with transforming growth factor-beta 1(TGFβ-1)into nude mice by intravenous injection.Next,we isolated CTCs from the blood of nude mice by gradient centrifugation and found that CTCs derived from MKN28 cells pretreated with TGFβ-1 had a significantly increased viability and invasion ability compared to MKN28 cells without TGFβ-1 treatment.Immunocytochemical staining showed lower expression of E-cadherin and higher expression of N-cadherin,vimentin,and β-catenin in CTCs derived from MKN28 cells pretreated with TGFβ-1.Furthermore,the expression of Wnt3a,β-catenin,cyclin D1,and c-Myc was significantly higher in CTCs derived from MKN28 cells pretreated with TGFβ-1.Taken together,these findings suggest that TGFβ promotes EMT and malignant phenotypes of gastric cancer cells.Furthermore,the malignant phenotypes of gastric cancer cells induced by TGFβ are maintained in CTCs derived from these cells.Targeting EMT in CTCs is a new approach to the treatment of gastric cancer relapse and metastasis.