Protective Effects of Sweroside on IL-1ß-Induced Inflammation in Rat Articular Chondrocytes Through Suppression of NF-κB and mTORC1 Signaling Pathway.

Sweroside (SW), as a bioactive herbal ingredient, has anti-inflammatory effects. Protective effects of SW on IL-1ß-stimulated articular chondrocytes, however, has not been fully understood. This study was to explore the anti-inflammatory effects and further to investigate the possible mechanism underlying SW effect on IL-1ß-stimulated rat articular chondrocytes. Rat articular chondrocytes were cultured with or without SW for 1 h, and then stimulated with IL-1ß for 24 h. ELISA analysis was used to measure the production of NO and PGE2. Western blot was to detect the expression of iNOS and COX-2. Furthermore, the mRNA expression of MMP-1, MMP3, MMP13, and ADAMTS-5 were measured by q-PCR. These results demonstrated that SW significantly inhibited IL-1ß-induced NO and PGE2 production, as well as MMP-1, MMP3, MMP13, and ADAMTS-5 mRNA expression. Moreover, SW also suppressed IL-1ß-induced NF-κB activation and iκ-B degradation, S6K1 and S6 phosphorylation. In conclusion, these results strongly demonstrated that the anti-inflammatory activity of SW is in part mediated by suppressing NF-κB and mTORC1 signaling, which was expected to be a promising drug target of osteoarthritis therapy.

Tenuigenin promotes the osteogenic differentiation of bone mesenchymal stem cells in vitro and in vivo.

Osteoporosis, which is a systemic skeletal disease characterized by low bone mineral density and microarchitectural deterioration of bone quality, is a global and increasing public health problem. Recent studies have suggested that Tenuigenin (TEN), a class of native compounds with numerous biological activities such as anti-resorptive properties, exerts protective effects against postmenopausal bone loss. The present study aims to investigate the osteogenic effects of TEN on bone mesenchymal stem cells (BMSCs) in vitro and in vivo. Alkaline phosphatase (ALP) activity/staining, Alizarin red staining and the expression of osteogenic markers, including runt-related transcription factor 2, osterix, osteocalcin, collagen Iα1, ß-catenin and glycogen synthase kinase-3ß were investigated in primary femoral BMSCs from C57/BL6 mice cultured under osteogenic conditions for 2 weeks to examine the effects of TEN. An ovariectomized (OVX) mouse model was used to investigate the effect of TEN treatment for 3 months in vivo. We found that ALP activity, mineralized nodules and the expression of osteogenic markers were increased and WNT/ß-catenin signaling was enhanced in vitro and in vivo. Bone parameters, including trabecular thickness, trabecular number and bone mineral density were higher in the OVX+TEN group than in control OVX mice. Our results suggest the therapeutic potential of TEN for the treatment of patients with postmenopausal osteoporosis.

[The modified restriction of amino acids of HVR1, HVR2, HVR5, HVR7 in human adenovirus serotype 3 hexon].

The limitation of traditional Ad vectors result in wide application of capsid-incorporation of antigens into adenovirus capsid proteins, but usually it can't rescue virus successfully when we engineered the hypervariable regions (HVRs) of hexon in adenovirus serotype 3(Ad3) vector. So we deleted or retained some amino acids in HVR1, HVR2, HVR5, HVR7 predicted by bioinformatics, constructed recombinant Ad3 vector pBRAddeltaE3GFP-mHexon, and transfected it into AD293 cell to confirm the influence on the virus rescue. These data of amino acids that can be deleted or retained in the HVRs of Ad3 vector should provide operating foundation for antigen capsid-incorporation strategy in human adenovirus serotype 3, and also lay the groundwork for application of expressing foreign antigens in the hexon of human adenovirus serotype 3 as a platform of multivalent vaccine vectors.