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Direct intra-articular injection of mesenchymal stem cells (MSCs) has been proposed as a potential cell therapy for cartilage defects. This cell therapy relies on the survival of the implanted MSCs. However, the arduous local environment may limit cell viability after implantation, which would restrict the cells' regenerative capacity. Thus, it is necessary to reinforce the implanted cells against the unfavourable microenvironment in order to improve the efficacy of cell therapy. We examined whether the transduction of an anti-apoptotic protein, Bcl-xL, into MSCs could prevent cell death and improve the implantation efficiency of MSCs in a rabbit model. Our current findings demonstrate that the group treated with Bcl-xL-engineered MSCs could improve cartilage healing both morphologically and histologically when compared with the controls. These results suggest that intra-articular injection of Bcl-xL-engineered MSCs is a potential non-invasive therapeutic method for effectively treating cartilage defects of the knee.

Gambogic acid (GA) inhibits the proliferation of various human cancer cells. However, because of its water insolubility, the antitumor efficacy of GA is limited.Objectives.To investigate the antitumor activity of gambogic acid lysinate (GAL) and its mechanism.Methods.Inhibition of cell proliferation was determined by MTT assay; intracellular ROS level was detected by staining cells with DCFH-DA; cell apoptosis was determined by flow cytometer and the mechanism of GAL was investigated by Western blot.Results.GAL inhibited the proliferation of MCF-7 cells with IC50values 1.46 μmol/L comparable with GA (IC50, 1.16 μmol/L). GAL promoted the production of ROS; however NAC could remove ROS and block the effect of GAL. GAL inhibited the expression of SIRT1 but increased the phosphorylation of FOXO3a and the expression of p27Kip1. At knockdown of FOXO3a, cell apoptosis induced by GAL can be partly blocked. In addition it also enhanced the cleavage of caspase-3.Conclusions.GAL inhibited MCF-7 cell proliferation and induced MCF-7 cell apoptosis by increasing ROS level which could induce cell apoptosis by both SIRT1/FOXO3a/p27Kip1 and caspase-3 signal pathway. These results suggested that GAL might be useful as a modulation agent in cancer chemotherapy.

Background. Apoptosis associates with secondary brain injury after traumatic brain injury (TBI). This study posits that serum leukocyte apoptosis levels in acute TBI are predictive of outcome.Methods. Two hundred and twenty-nine blood samples from 88 patients after acute TBI were obtained on admission and on Days 4 and 7. Serial apoptosis levels of different leukocyte subsets were examined in 88 TBI patients and 27 control subjects.Results. The leukocyte apoptosis was significantly higher in TBI patients than in controls. Brief unconsciousness (P=0.009), motor deficits (P≤0.001), GCS (P≤0.001), ISS (P=0.001), WBC count (P=0.015), late apoptosis in lymphocytes and monocytes on Day 1 (P=0.004andP=0.022, resp.), subdural hemorrhage on initial brain CT (P=0.002), neurosurgical intervention (P≤0.001), and acute posttraumatic seizure (P=0.046) were significant risk factors of outcome. Only motor deficits (P=0.033) and late apoptosis in monocytes on Day 1 (P=0.037) were independently associated with outcome. A cutoff value of 5.72% of late apoptosis in monocytes was associated with poor outcome in acute TBI patients.Conclusion. There are varying degrees of apoptosis in patients following TBI and in healthy individuals. Such differential expression suggests that apoptosis in different leukocyte subsets plays an important role in outcome following injury.