BackgroundBoth total astragalus saponins (AST) and it’s main component astragaloside IV (ASIV) have been used in China as cardiovascular protective medicines. However, the anti-inflammatory activities that are beneficial for cardiovascular health have never been compared directly and the molecular mechanisms remain unresolved. This study was conducted to compare the inhibitory effects of these drugs on TNFα-induced cell responses, related signaling pathways, and the underlying mechanisms in mouse arterial endothelial cells.Methodology/Principal FindingsReal-time qRT-PCR was performed to determine the expression of cell adhesion molecule (CAM) genes. Immunofluorescent staining was used to detect the nuclear translocation of transcription factor NF-κB-p65. Western Blot analysis was used to identify TNFα-induced NF-κB-p65 phosphorylation, IκBα degradation, and caspase-3 cleavage. Cell surface proteins were isolated and TNFα receptor-1(TNFR1) expression was determined. The results suggest that both AST and ASIV attenuate TNFα-induced up-regulation of CAMs mRNA and upstream nuclear translocation and phosphorylation of NF-κB-p65. However, TNFR1-mediated IκBα degradation, cleavage of caspase-3 and apoptosis were inhibited only by AST. These differences in the actions of AST and ASIV could be explained by the presence of other components in AST, such as ASII and ASIII, which also had an inhibitory effect on TNFR1-induced IκBα degradation. Moreover, AST, but not ASIV, was able to reduce TNFR1 protein level on the cell surface. Furthermore, mechanistic investigation demonstrated that TNFR1-mediated IκBα degradation was reversed by the use of TAPI-0, an inhibitor of TNFα converting enzyme (TACE), suggesting the involvement of TACE in the modulation of surface TNFR1 level by AST.ConclusionASIV was not a better inhibitor than AST, at least on the inhibition of TNFα-induced inflammatory responses and TNFR1-mediated signaling pathways in AECs. The inhibitory effect of AST was caused by the reduction of cell surface TNFR1 level, and TACE could be involved in this action.

The aim of the present study was to construct tissue-engineered laryngeal cartilage with a hollow, semi-flared shape using a poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHH) scaffold. Porous PHBHH was prepared and formed into a hollow, semi-flared shape, and the cell-material composites were cultured for one week in vitro prior to implantation in vivo. Cells of the nine rabbits of the experimental group were filled and encapsulated in the myofascial flap-shaping material composite for in situ implantation. The three rabbits in the control group were treated with the shaping material without the chondrocytes. Cartilage regeneration was assessed at six, 12 and 18 weeks after surgery. In the experimental group, the shape and porosity of the material were ideal, the cells exhibited good adhesion with the material and the myofascial flap blood supply was rich. The engineered laryngeal cartilage with the hollow, semi-flared shape was ideally formed, and the cartilage formed at six weeks after the surgery. Further maturation of the cartilage was observed at 12 and 18 weeks after the surgery. PHBHH was a suitable material for the formation of a hollow, semi-flared shape with good cellular compatibility. Myofascial flap filling and wrapping can be used to build tissue-engineered laryngeal cartilage with a hollow, semi-flared shape.

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