Accumulating evidence reports that bone marrow-derived endothelial progenitor cells (EPCs) regulate angiogenesis, postnatal neovascularization and tumor metastasis. It has been suggested that understanding the molecular targets and pharmacological functions of natural products is important for novel drug discovery. Tanshinone IIA is a major diterpene quinone compound isolated from Danshen (Salvia miltiorrhiza) and is widely used in traditional Chinese medicine (TCM). Evidence indicates that tanshinone IIA modulates angiogenic functions in human umbilical vein endothelial cells. However, the anti-angiogenic activity of tanshinone IIA in human EPCs has not been addressed. Here, we report that tanshinone IIA dramatically suppresses vascular endothelial growth factor (VEGF)-promoted migration and tube formation of human EPCs, without cytotoxic effects. We also show that tanshinone IIA markedly inhibits VEGF-induced angiogenesis in the chick embryo chorioallantoic membrane (CAM) model. Importantly, tanshinone IIA significantly attenuated microvessel formation and the expression of EPC-specific markers in the in vivo Matrigel plug assay in mice. Further, we found that tanshinone IIA inhibits EPC angiogenesis through the PLC, Akt and JNK signaling pathways. Our report is the first to reveal that tanshinone IIA reduces EPC angiogenesis both in vitro and in vivo. Tanshinone IIA is a promising natural product worthy of further development for the treatment of cancer and other angiogenesis-related pathologies.
Background. The dynamic hip screw (DHS) with the addition of an angular stable trochanter-stabilizing plate (TSP) has been considered the ideal treatment for the unstable intertrochanteric fracture type. However, there have been few comparisons between DHS+TSP augmentation with intramedullary (IM) nailing. The aim of this retrospectively registered study was to compare the clinical outcomes of patients with the unstable type of intertrochanteric fractures treated with DHS+TSP or IM nailing (proximal femoral nail antirotation (PFNA)). Methods. From June 2013 to April 2018, 358 patients with proximal femur fracture AO/OTA type 31A2 and 31A3 treated with PFNA or DHS+TSP and followed for ≥10 months postoperatively were included. The surgical-dependent outcome evaluation included the operation time, intraoperative blood loss, postoperative decrease in hemoglobin, and blood transfusion amount. Functional status was also measured. Radiographic findings and postoperative complications were recorded and analyzed. Result. The operation time was significantly shorter in the DHS+TSP group than that in the PFNA group for both A2 and A3 fractures (A2 type: 84.0 vs.96.4 min; p<0.05; A3 type: 102.4 vs.116.1 min; p<0.05). Postoperative decrease in hemoglobin was more significant in the PFNA group than that in the DHS+TSP group for both fracture types (A2 type: −1.88 vs. −1.29 (mg/dL); p<0.05; A3 type: −1.63 vs. −1.04 (mg/dL); p<0.05). However, the patients treated with DHS+TSP had significantly more residual pain than those treated with PFNA during the final follow-up (Visual Analog Scale score, A2 type: 28.4 vs.23.2; p<0.05; A3 type: 27.5 vs.23.6; p<0.05) and complained of greater implant irritation. Conclusion. We found that DHS+TSP was associated with less operation time and less postoperative decrease in hemoglobin but more residual pain and implant irritation than those of PFNA. As a treatment for unstable intertrochanteric fracture, DHS+TSP provided ideal surgical outcomes which were not inferior to the PFNA.
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