Upregulated microRNA-126 induces apoptosis of dental pulp stem cell via mediating PTEN-regulated Akt activation.

INTRODUCTION: Human dental pulp stem cells (DPSCs) have potential applications in regenerative medicine. The molecular mechanisms underlying DPSCs viability and apoptosis are not completely understood. Here, we investigated the role of miR-126 in DPSCs viability and apoptosis. MATERIAL AND METHODS: Senescent DPSCs were compared with early passage DPSCs. real-time PCR and microARRAY were performed to identify the differential expression of miR-126, and western blot was performed to detect the expression of PTEN. MTT assay was utilized to reveal the proliferative rate of both senescent and early passage DPSCs. Flow cytometry was used to examine the apoptotic rate of DPSCs. Dual-luciferase reporter assay was carried out to detect the interaction of miR-126 and PTEN. RESULTS: Senescent DPSCs showed a high level of apoptosis. Further study showed that miR-126 is upregulated in senescent DPSCs and its overexpression in early passaged DPSCs induced apoptosis. Phosphatase and tensin homolog gene (PTEN) was identified as a target of miR-126. PTEN was downregulated in senescent DPSCs, whereas miR-126 inhibition upregulated PTEN level, and subsequently activated Akt pathway and suppressed the apoptotic phenotype of senescent DPSCs. In addition, PTEN overexpression rescued apoptosis of DPSCs at later stage. CONCLUSION: Our results demonstrate that the miR-126-PTEN-Akt axis plays a key role in the regulation of DPSCs apoptosis and provide a candidate target to improve the functional and therapeutic potential of DPSCs.

Significance of decreased serum interleukin-10 levels in the progression of cerebral infarction.

Anti-inflammatory cytokine and its serological detection may have an important role in the process of cardiovascular and cerebrovascular diseases. We investigated whether serum interleukin-10 (IL-10) is associated with cerebral infarction or not in the general population. Identified comprehensive searching was performed covering PubMed, EMBASE, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine, and China National Knowledge Infrastructure databases. Two reviewers extracted data and assessed studies independently. Information was extracted separately and classed into Asians and Caucasians. Summary standardized mean differences (SMDs) with 95 % confidence intervals (CI) were used with the utilization of Z test. Nine studies ranged from 2003 to 2014 were collected for meta-analysis. Results identified a negative association between serum IL-10 levels and cerebral infarction (SMD = 1.80, 95 % CI 0.79-2.81, P < 0.001). Country-subgroup analysis showed that low IL-10 level may be the main risk factor for cerebral infarction in India (SMD = 1.44, 95 % CI 1.13-1.75, P < 0.001) and Croatia (SMD = 2.96, 95 % CI 2.48-3.44, P < 0.001). In the ethnicity-stratified subgroup analysis, serum IL-10 levels were negatively correlated with cerebral infarction in Asians (SMD = 2.52, 95 % CI 0.47-4.57, P = 0.016), while not in Caucasians (P > 0.05). The lower serum IL-10 concentration was significantly associated with an increased likelihood of cerebral infarction in this meta-analysis. More prospective studies should be conducted to provide stronger evidence justifying the use of IL-10 as new biomarker to identify a predisposition toward cerebral infarction.

Inhibitory effect of piperlonguminine/ dihydropiperlonguminine on the production of amyloid beta and APP in SK-N-SH cells.

The study was undertaken to explore whether piperlonguminine/dihydropiperlonguminine could inhibit the production of amyloidbeta (Abeta) in human neuroblastoma cells (SK-N-SH) and to examine the underlying mechanism of this effect. Piperlonguminine/dihydropiperlonguminine components (1:0.8) were extracted from Futokadsura stem, and then used to treat SK-N-SH cells at three different concentrations: 3.13 microg/ml, 6.25 microg/ml and 12.50 microg/ml. Subsequently, the production of Abeta42 and Abeta40 were measured by Western blot analysis and enzyme linked immunosorbent assay (ELISA). On the other hand, the expressions of amyloid precursor protein (APP), Notch1 (Notch intracellular domain) and beta-site amyloid precursor protein cleavage enzyme (BACE-1) were also examined by Western blot assay. The activities of beta-secretase and gamma-secretase were detected at the same time. Furthermore, Abeta42 level was detected by immunocytochemistry staining. We demonstrated that the treatment of piperlonguminine/dihydropiperlonguminine could significantly decrease the levels of APP, Abeta42 and Abeta40 peptide in SK-N-SH cells, despite the fact that the activities of beta-secretase and gamma-secretase were not affected significantly. These data suggest that piperlonguminine/dihydropiperlonguminine components could significantly inhibit the level of APP, Abeta42 and Abeta40 peptide without affecting the activity of beta-secretase and gamma-secretase in SK-N-SH cells.

Effects of silencing Id-1 in cell culture of human adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a slow growing but highly invasive cancer with a high recurrence rate. Id (inhibitor of DNA binding) proteins are dominant regulators of basic helix-loop-helix transcription factors that control malignant cell behavior in many different tissues. This study aimed to identify the potential role of inhibiting DNA binding-1 (Id-1) in human salivary adenoid cystic carcinoma (SACC) progression. First, we compared the Id-1 protein expression in a human salivary adenoid cystic carcinoma cell line (ACCM) against three other cell lines and found that Id-1 protein expression in ACCM to be significantly higher. Then we measured Id-1 mRNA and protein expression in ACCM before and after RNA interference (RNAi), which showed successful inhibition of Id-1. Further studies then demonstrated that the proliferation and invasiveness of ACCM cells were dramatically down-regulated, and increased numbers of apoptotic cells were detected after Id-1 silencing. Consequently, our data suggest that Id-1 is a potential target in the treatment of human salivary adenoid cystic carcinoma.