Abstract. Perineural invasion (PNI) is a striking biological behavior observed in salivary adenoid cystic carcinoma (SACC). The present study was designed to establish a co-culture model of SACC cells with Schwann cells (SCs), and then study epithelial-mesenchymal transition (EMT) and the Schwann-like differentiation of SACC cells to investigate the likely molecular mechanism of PNI. The co-culture models of SCs with tumor cells (SACC-83, SACC-LM and MEC-1) were established using a Transwell system. An elevated concentration of brain-derived neurotrophic factor (BDNF) was detected by ELISA assay in the co-cultured medium of the SACC-83 group and SACC-LM group rather than the MEC-1 group. The EMT process and Schwann-like differentiation in SACC-83 cells were analyzed by RT-PCR, western blotting, immunofluorescence, photography, and migration and perineural invasion assays. The SACC-83 cells under the co-culture condition with SCs changed to a mesenchymal morphology and had higher migration and invasion capabilities compared with the solely cultured SACC-83 cells, accompanied by the downregulation of E-cadherin and upregulation of N-cadherin and vimentin. The co-cultured SACC-83 cells also developed Schwann-like differentiation with increased expression of SC markers, S100A4 and GFAP. However, inhibition of tropomyosin-related kinase B (TrkB) by K252a markedly blocked these effects. Additionally, the expression and correlation of TrkB, E-cadherin and S100A4 were analyzed by immunohistochemistry in 187 primary SACC cases. The levels of TrkB and S100A4 expression were both positively associated with PNI in the SACC cases, while E-cadherin expression was negatively associated with PNI. Elevated expression of TrkB was significantly correlated with the downregulated expression of E-cadherin and the upregulated expression of S100A4 in the SACC cases. Our results suggest that SCs play a pivotal role in the PNI process by inducing the EMT process and the Schwann-like differentiation of SACC cells via the BDNF/TrkB axis. Interruption of the interreaction between SACC cells and SCs by targeting the BDNF/TrkB axis may be a potential strategy for anti-PNI therapy in SACC.

Objectives: To review the cases of accidental aspiration and ingestion of foreign objects during dental procedure, and to emphasize the importance of thorough documentation of the accidents. Methods: A comprehensive search on (dental procedure/treatment/practice), (aspiration/inhalation), and (ingestion/ swallow) was performed for all years before 1st October 2014 available. The statistic analysis was made on the variables including journals and reported year, patients' age, gender, general conditions, dental procedure and location for procedure, foreign objects, site of involvement, possible causes, anesthesia during procedure and treatment, symptoms, treatment time and treatment modality, follow-up, and so on. Results: A total of 617 cases reported by 45 articles from 37 kinds of journals were included and analyzed. Most reports made detailed record. While some important variables were recorded incompletely, including patient's general conditions, location for procedure, clinical experience of the involving dentists, tooth position of procedure, possible causes, and anesthesia during procedure and treatment for the accident. Conclusions: Aspiration and ingestion of foreign objects are rare and risky complication during dental procedure. Each accident should have thorough documentation so as to provide enough information for the treatment and prevention.

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Engineered bone substitutes are being extensively explored in response to growing demand. However, the angiogenesis that occurs during bone formation is often overlooked in scaffold design. In this novel study, we incorporated two small interfering RNAs (siRNAs), ie, small interfering RNA targets casein kinase 2 interaction protein 1 (siCkip-1) and small interfering RNA targets soluble VEGF receptor 1 (siFlt-1), which can promote osteogenesis and angiogenesis, into a chitosan sponge. This scaffold could maintain siRNAs for over 2 weeks in neutral phosphate-buffered saline and degraded rapidly in the presence of lysozyme. The chitosan sponge with siCkip-1 and siFlt-1 in vitro bioactivity was investigated using mesenchymal stem cells. Target genes were significantly suppressed, and osteocalcin, alkaline phosphatase, and vascular endothelial growth factor were significantly upregulated. Alizarin Red staining revealed that mineralization of the extracellular matrix was markedly enhanced by dual transfection. Further analysis by immunofluorescence confirmed that the siRNA-modified scaffold simultaneously improved the expression of osteocalcin and von Willebrand factor. In vivo testing in a skull critical-size defect model showed marked bone regeneration in rats treated with siCkip-1 and siFlt-1. In conclusion, chitosan sponge containing osteogenic and angiogenic siRNAs may be used as a scaffold for bone regeneration. The dual siRNA concept may also be useful in the biofunctionalization of other materials.

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Salivary adenoid cystic carcinoma (SACC) is the most frequent salivary gland malignancy with a unique characteristic that has been named perineural invasion (PNI). EMMPRIN is a transmembrane glycoprotein that has been demonstrated to promote PNI in SACC. Slug, one of the most effective promoters of the epithelial-to-mesenchymal transition (EMT), has been found to be associated with PNI in SACC. The aim of the present study was to investigate the roles and relationships of Slug, EMMPRIN, and E-cadherin in the PNI process of SACC. The expression levels of Slug, EMMPRIN, and E-cadherin in 115 primary SACC cases were statistically analyzed by immunohistochemistry. Simultaneously, the SACC cell line SACC-83 was transfected with recombinant plasmids of silencing Slug (si-Slug) and/or silencing EMMPRIN (si-EMMPRIN). The functions of Slug and EMMPRIN in the EMT and PNI process were assessed by reverse transcription PCR (RT-PCR), western blotting, morphological observation, scratch test, migration assay, and in vitro perineural invasion assay. The immunohistochemical statistics revealed that the high expression of Slug and EMMPRIN and the low expression of E-cadherin were significantly associated with the PNI of SACC (P < 0.05). Slug expression was significantly associated with EMMPRIN expression (P < 0.05), and Slug expression and EMMPRIN expression were both significantly negatively associated with E-cadherin expression (P < 0.05). Slug and EMMPRIN silencing both significantly inhibited EMMPRIN expression but promoted E-cadherin expression in SACC-83 cells (P < 0.01). The series of in vitro assays revealed that silencing of Slug, EMMPRIN, or both induced cell morphology changes and inhibited tumor cell motility and PNI ability in SACC-83 cells (P < 0.01). These results suggested that Slug silencing could inhibit the EMT process by downregulating EMMPRIN and then upregulating E-cadherin in the PNI process of SACC. The present study indicated that Slug and EMMPRIN are potential biomarkers and therapeutic targets for the diagnosis and treatment of PNI in human SACC.

The data presented herein are connected to our research article (doi: 10.1016/j.biocel.2017.04.012) [1], in which we investigated the functional connections between the urokinase receptor (uPAR), and the ezrin/radixin/moesin (ERM) proteins, moesin and merlin [1]. Firstly, a model of action is proposed that enlightens how uPAR regulates distal integrins. In addition, data show the effects of expressing wild-type moesin or permanently active T558D mutant of moesin on angiogenesis and morphology of human aortic endothelial cells (HAEC). Additional data compare the effects of urokinase (uPA, the main ligand of uPAR) on the same cells. Lastly, we provide technical data demonstrating the effects of specific siRNA for moesin and merlin on moesin and merlin expression, respectively.