Development and Application of Digital Human Models in the Field of Vehicle Collisions: A Review.

In the human-vehicle-road system of collisions, the human is the most important factor, and digital human models (DHMs) are developed with the aim of preventing or at least reducing human injury. Because most of the relevant literature is focused mainly on collisions in traffic accidents (TAs), only some of the literature reviewed in this paper involves research results on other aspects of collisions. In this review, based on the background of DHMs and the application of DHMs regarding human injury biomechanics in collisions field, research results regarding the development of DHMs are described, the methods for verifying such models are introduced, and the application of the research results is discussed based on the aspect of human injury biomechanics. From the research literature, the development and validation of DHMs and their application in human injury biomechanics are summarized, and future research trends are proposed and discussed.

Apatinib suppresses breast cancer cells proliferation and invasion via angiomotin inhibition.

Breast cancer is a leading cause of cancer-related death in the women worldwide. Apatinib is a novel tyrosine kinase inhibitor that selectively binds and inhibits vascular endothelial growth factor receptor 2 (VEGFR-2). The clinical trials have demonstrated the objective efficacy of Apatinib against metastatic breast cancer. However, the underlying mechanism is not well established. In the present study, the breast cell lines, BT-474 and MCF-7, were investigated. The effect of Apatinib on the cell viability was determined using CCK-8 assay. The migration, invasion, cell cycle distribution and the downstream signaling of VEGFR-2 in the cells were determined after 48 h treatment with this drug. Subsequently, Vector of angiomotin (AMOT) cDNA was transfected into MCF-7 cells. The cells were either exposed to Apatinib or vehicle and then examined for cell viabilities, migration, invasion, cell cycle distribution and the downstream signaling of VEGFR-2. Apatinib demonstrated a dose-dependent, significant inhibition of cell viabilities, migration and invasion of BT-474 and MCF-7 cells, with an increase in the percentage of cells in G1 phase and a decrease in S phase. In addition, in MCF-7 cells, Apatinib decreased AMOT expression, accompanied with the decreased expression of LATS1/2, YAP, ERK1/2 phosphorylation and cyclin D1. The inhibitory effect of Apatinib on the cell activities and protein expressions were significantly suppressed by AMOT overexpression. The results of this study indicated that Apatinib inhibited MCF-7 cell proliferation and invasion through AMOT/VEGFR-2 pathway.

X-linked inhibitor of apoptosis-associated factor l (XAFl) enhances the sensitivity of colorectal cancer cells to cisplatin.

The purpose of present study was to investigate the roles of X-linked inhibitor of apoptosis-associated factor l (XAFl) in regulation apoptosis of colorectal cancer (CRC) cells after treatment with cisplatin (DDP). A total of ten paired cancerous and non-cancerous tissues were collected from patients with CRC after surgery. The levels of XAFl protein were detected by Western blot. Primary CRC cells were separated from cancer tissues, and its viability or apoptosis after treatment with DDP was determined with MTT or Annexin V/PI assays, respectively. Furthermore, we either up-regulated transfecting a XAF1 overexpression vector or down-regulated XAF1 by siRNA interference. And then, the XAF1 levels and its sensitivity to cisplatin were assessed. XAFl had a lower expression in the cancerous tissues from samples T1, T2 and T3 than their paired non-cancerous tissues N1, N2 and N3. However, the expression of XAF1 was not detected in samples T4 and N1. XAF1 levels in cancer tissues significantly decreased in comparison with normal tissues. Cell abilities of primary cells were significantly decreased in a dose-dependent manner, after treatment with a series concentrations of cisplatin (2, 5, 10 µg/mL) for 48 h. Although, after down-expression of XAFl by siRNA, cisplatin caused a significant decreases in apoptosis rates in CRC cells. The up-regulation of XAF1 distinctly increased apoptosis in CRC cells administered by cisplatin (P < 0.001). The XAFl could promoted apoptosis and enhanced chemotherapy sensitivity to cisplatin in CRC cells.

Combination of gefitinib and DNA methylation inhibitor decitabine exerts synergistic anti-cancer activity in colon cancer cells.

Despite recent advances in the treatment of human colon cancer, the chemotherapy efficacy against colon cancer is still unsatisfactory. In the present study, effects of concomitant inhibition of the epidermal growth factor receptor (EGFR) and DNA methyltransferase were examined in human colon cancer cells. We demonstrated that decitabine (a DNA methyltransferase inhibitor) synergized with gefitinib (an EGFR inhibitor) to reduce cell viability and colony formation in SW1116 and LOVO cells. However, the combination of the two compounds displayed minimal toxicity to NCM460 cells, a normal human colon mucosal epithelial cell line. The combination was also more effective at inhibiting the AKT/mTOR/S6 kinase pathway. In addition, the combination of decitabine with gefitinib markedly inhibited colon cancer cell migration. Furthermore, gefitinib synergistically enhanced decitabine-induced cytotoxicity was primarily due to apoptosis as shown by Annexin V labeling that was attenuated by z-VAD-fmk, a pan caspase inhibitor. Concomitantly, cell apoptosis resulting from the co-treatment of gefitinib and decitabine was accompanied by induction of BAX, cleaved caspase 3 and cleaved PARP, along with reduction of Bcl-2 compared to treatment with either drug alone. Interestingly, combined treatment with these two drugs increased the expression of XIAP-associated factor 1 (XAF1) which play an important role in cell apoptosis. Moreover, small interfering RNA (siRNA) depletion of XAF1 significantly attenuated colon cancer cells apoptosis induced by the combination of the two drugs. Our findings suggested that gefitinib in combination with decitabine exerted enhanced cell apoptosis in colon cancer cells were involved in mitochondrial-mediated pathway and induction of XAF1 expression. In conclusion, based on the observations from our study, we suggested that the combined administration of these two drugs might be considered as a novel therapeutic regimen for treating colon cancer.