Protective effect of Ganoderic acid A on adjuvant-induced arthritis.

The purpose of the experiment was to explore the effect of Ganoderic acid A (GAA) on adjuvant-induced arthritis in rats. In this study, the rat model of collagen-induced rheumatoid arthritis (CIA) was established with type II collagen plus Freund's complete adjuvant. Arthritis index, joint pathology, toe swelling, hemorheology, synovial cell apoptosis, related cytokines and JAK3/STAT3 and nuclear factor-κB (NF-κB) signaling pathway were measured in rats. We found that GAA can significantly inhibit the arthritis index, improve joint pathology, reduce toe swelling, improve blood rheology, improve synovial cell apoptosis, and restore related cytokine negative regulation JAK3/STAT3 and NF-κB signaling pathways. In conclusion, GAA has an obvious therapeutic effect on joint inflammation of toes in CIA model rats, which may be due to the regulation of JAK3/STAT3 and NF-κB signaling pathway.

Three-dimensional-printed titanium alloy porous scaffold combined with trans-cinnamaldehyde for repairing osteonecrosis of the femoral head in a dog model.

Osteonecrosis of the femoral head (ONFH) is a common disorder that may be idiopathic, caused by trauma, or associated with alcohol or glucocorticoid use. The goals of early treatment include delaying or avoiding hip replacement, but there are no effective treatments for early-stage disease. The aim of the present study was to evaluate the effects of treatment with 3D-printed porous titanium alloy scaffold combined with daily intraperitoneal trans-cinnamaldehyde (TCA) in a dog model of ONFH. Four weeks after creation of the ONFH model, MRI examination of the femoral head showed the characteristic "double line sign" of ONFH, verifying the validity of our model. After another 12 weeks, femoral head specimens were harvested and examined by gross inspection; micro-computed tomography; histologic staining (hematoxylin and eosin; Masson); immunohistochemical analysis and quantitative real-time polymerase chain reaction analysis. Gross inspection of the femoral head in untreated ONFH animals at 16 weeks after model creation showed pale, exfoliating articular cartilage and disordered trabecular bone. Treatment with 3D-printed titanium alloy porous scaffold combined with TCA ameliorated the pathologic ONFH changes and significantly reduced inmature bone tissue as well as imature collagen in the femoral head, as shown by Masson staining. This treatment also increased VEGF, BMP2, ß-catenin, b-FGF, and RUNX2 expression and decreased PPARγ expression, compared with untreated ONFH. In conclusion, 3D-printed titanium alloy porous scaffold combined with TCA can effectively improve ONFH, which may be related to local repair. This provides the theoretical basis for a new treatment strategy for ONFH.

Soluplus(®) micelles as a potential drug delivery system for reversal of resistant tumor.

Inhibiting or circumventing drug resistance by using drug delivery systems (DDSs) such as micelles has attracted significant attention recently. In this present study, a polyvinyl caprolactam-polyvinyl acetate-polyethylene (Soluplus(®)) micelle was developed as the delivery system for doxorubicin (DOX) and evaluated both in vitro and in vivo. In vitro, Soluplus(®) micelles could significantly enhance the cellular accumulation of DOX in MCF-7/DOX cells, meanwhile, P-glycoprotein (P-gp)-mediated drug efflux was inhibited which was also verified in the membrane fluidity study. And MCF-7/DOX cells were found to be more susceptible to the cytotoxic effects of DOX-M. In vivo, both the P-gp inhibitors verapamil and Soluplus(®) could improve the cytotoxicity of DOX·HCl in MCF-7/DOX tumor-bearing mice, which were further certified by the effect of Soluplus(®) on P-gp inhibition. Furthermore, the excellent antitumor efficacy of DOX-M by intravenous injection was also observed, which indicated that the P-gp inhibition effect of Soluplus(®) could enhance the susceptibility of resistant tumor to DOX in vivo. In conclusion, our study suggested that Soluplus(®) micelles might be an applicable drug delivery system for enhancing the antitumor efficacy of P-gp substrates.

Overexpression of astrocyte-elevated gene-1 is associated with ovarian cancer development and progression.

It has previously been reported that astrocyte­elevated gene­1 (AEG­1) has a critical role in the regulation of tumor development, and/or progression. However, the functional significance of AEG­1 in human ovarian cancer remains unclear. The present study conducted an immunohistochemical analysis of ovarian tissues, and the association between AEG­1 protein expression, clinicopathological features and outcomes were investigated. The gain or loss of AEG­1 function was also examined, through exogenous overexpression or knockdown of expression by small interfering RNA, in ovarian cancer cells. Normal ovarian tissue exhibited very little or no AEG­1 immunoreactivity, whereas high expression levels of AEG­1 were detected in 12.7% of cystadenomas, 30.0% of borderline tumors, and 71.2% of ovarian carcinomas, respectively, as determined by immunohistochemistry. Statistical analyses demonstrated a significant correlation of AEG­1 expression with differentiation (P=0.001), lymph node metastasis (P=0.008) and clinical staging (P=0.002). In addition, the overall survival time of patients with higher AEG­1 expression levels was markedly shorter, as compared with patients with lower expression levels of AEG­1 (P=0.001). Multivariate analysis indicated that AEG­1 expression was an independent prognostic indicator of the survival of patients with ovarian cancer. Furthermore, exogenous overexpression of AEG­1 in ovarian cancer cells was shown to significantly enhance cell proliferation, adhesion and invasion. Conversely, silencing AEG­1 expression caused an inhibition of cell growth, adhesion and invasion. The results of the present study indicate that AEG­1 is a valuable biomarker for the prediction of ovarian cancer prognosis, and AEG­1 inhibition may be a potential therapeutic strategy for ovarian cancer treatment.