Gambogic acid suppresses inflammation in rheumatoid arthritis rats via PI3K/Akt/mTOR signaling pathway.

Gamboge is the dried resin secreted by the Garcinia maingayi gambogic tree and is a substance that may be used to treat a variety of diseases, exhibits anti­tumor and detoxification effects and prevents bleeding. The primary active constituent is gambogic acid. The present study aimed to investigate the anti­inflammatory effects of gambogic acid in rheumatoid arthritis (RA) rats and to elucidate the mechanisms by which these effects occur. The swelling degree, the clinical arthritic scoring and pain threshold measurements were used to evaluate the effects of gambogic acid on RA. ELISA kits and western blot analysis were used to investigate inflammatory processes and the expression of RA­associated proteins, respectively. The present results demonstrated that gambogic acid significantly inhibited the degree of right foot swelling, increased pain thresholds and reduced clinical arthritic scores of RA rats. Treatment with gambogic acid suppressed the activities of interleukin (IL)­1ß and IL­6, promoted the protein expression of phosphorylated (p)­Akt serine/threonine kinase (Akt), p­mammalian target protein of rapamycin (mTOR) and inhibited hypoxia­inducible factor­1α and vascular endothelial growth factor expression in RA rats. The results of the present study therefore suggest that the anti­inflammatory effects of gambogic acid in RA rats occur via regulation of the phosphoinositide 3­kinase/Akt/mTOR signaling pathway.

Antiproliferation potential of withaferin A on human osteosarcoma cells via the inhibition of G2/M checkpoint proteins.

Withaferin A (WA) is a well-known steroidal lactone of the medicinally important plant, Withania somnifera. This secondary metabolite has been noted for its anticancer effects against a number of human cancer cell lines. However, there are a limited number of studies investigating the growth inhibitory potential of WA against human osteosarcoma cells and the underlying molecular mechanisms. Thus, in the present study, the antiproliferative activities of WA, along with the underlying mechanisms of action, were investigated using flow cytometry for cell cycle distribution and western blot analysis for the assessment of various checkpoint proteins. In addition, the antiproliferative activity was evaluated using a sulforhodamine B assay, where MG-63 and U2OS human osteosarcoma cell lines were treated with different concentrations of WA. Furthermore, the mRNA expression levels of the checkpoint proteins in the WA-treated MG-63 and U2OS cells were examined. The results obtained corresponded with the western blot analysis results. Furthermore, WA was shown to significantly inhibit the proliferation of the two types of treated cell lines (MG-63 and U2OS). Flow cytometric analysis revealed that WA induced cell cycle arrest at the G2/M phase, which was associated with the inhibition of cyclin B1, cyclin A, Cdk2 and p-Cdc2 (Tyr15) expression and an increase in the levels of p-Chk1 (Ser345) and p-Chk2 (Thr68). In conclusion, the present study found that the antiproliferative potential of WA was associated with the induction of cell cycle arrest at the G2/M phase, which was a result of the attenuation of the expression levels of G2/M checkpoint proteins.

A new choice for the treatment of segmental tibial bone defects: intramedullary nail internal fixation combined adipose-derived stem cells technique.

The repair of various segmental tibial bone defects continues to be a challenging part of many reconstructive procedures. Many methods have been tried to repair the defects, followed by many complications and the results may be unsatisfied. Since 2001 Zuk et al. established human adipose-derived stem cells (hASCs) as a multipotent stem cell population with the ability to assume osteogenic phenotypes through chemically induced differentiation, hASCs represent a valuable tool for pharmacological and biological studies of osteoblast differentiation in vitro and bone development in vivo, and have been proved to be a useful source of stem cells in bone repair. Recently, hASCs have been found to repair both animals and human calvarial defects. In this paper, we hypothesize that hASCs cultured on custom scaffolds can be used to repair of tibial segmental bone defects with intramedullary nail internal fixed. Unlike current treatment modalities, it would promote the regeneration of tibial defects, provide structural support and allow for weight bearing and bony substitution over time.