No abstract

Sesamin, a bioactive component extracted from sesame, has been reported to exert anti-inflammatory and anti-oxidant effects. In this study, we evaluated the anti-inflammatory effects of sesamin on IL-1β-stimulated human osteoarthritis chondrocytes and investigated the possible mechanism. Results demonstrated that sesamin treatment significantly inhibited PGE2 and NO production induced by IL-1β. Sesamin inhibited MMP1, MMP3, and MMP13 production in IL-1β-stimulated chondrocytes. Sesamin also inhibited IL-1β-induced phosphorylation of NF-κB p65 and IκBa. Meanwhile, sesamin was found to up-regulate the expression of Nrf2 and HO-1. However, Nrf2 siRNA reversed the anti-inflammatory effects of sesamin. In conclusion, our results suggested that sesamin showed anti-inflammatory effects in IL-1β-stimulated chondrocytes by activating Nrf2 signaling pathway.

Designing the new microstructure is an effective way to accelerate the biomedical application of magnesium (Mg) alloys. In this study, a novel Mg–8Er–1Zn alloy with profuse nano-spaced basal plane stacking faults (SFs) was prepared by combined processes of direct-chill semi-continuous casting, heat-treatment and hot-extrusion. The formation of SFs made the alloy possess outstanding comprehensive performance as the biodegradable implant material. The ultimate tensile strength (UTS: 318 MPa), tensile yield strength (TYS: 207 MPa) and elongation (21%) of the alloy with SFs were superior to those of most reported degradable Mg-based alloys. This new alloy showed acceptable biotoxicity and degradation rate (0.34 mm/year), and the latter could be further slowed down through optimizing the microstructure. Most amazing of all, the uniquely uniform in vitro/vivo corrosion behavior was obtained due to the formation of SFs. Accordingly we proposed an original corrosion mechanism for the novel Mg alloy with SFs. The present study opens a new horizon for developing new Mg-based biomaterials with highly desirable performances.

Ample cell adhesion to scaffolds is essential for effective bone tissue engineering. Chitosan/hydroxyapatite (CS/HA) scaffolds with channel-shaped and spherically shaped pore morphologies were prepared via in situ compositing hybridization in combination with lyophilization. The sizes of channel-shaped and spherically shaped pores of the CS/HA scaffolds were 150-650 µm and 3-15 µm, respectively. The RGD peptide (Arg-Gly-Asp) was bound to the surface of CS/HA scaffolds via physical adsorption. More than 63% of RGD present in a PBS solution spontaneously adsorbed onto CS/HA scaffolds. High numbers of viable bone marrow stromal cells (BMSCs) were observed by confocal and fluorescence microscopy for cells cultured on CS/HA scaffolds with and without RGD for 3 days. BMSCs on CS/HA scaffolds with RGD (RGD-CS/HA) were incubated for 4 h under standard culture conditions, and the degree of cell adhesion was calculated. Cell adhesion to RGD-CS/HA scaffolds with different RGD concentrations was 71.6% and 80.7%, respectively. This was 30.9% and 47.5% higher than adhesion to the CS/HA scaffold without RGD, respectively. BMSCs cultured on the scaffolds for 14 days with osteogenic supplements expressed 103% higher alkaline phosphatase on the RGD-CS/HA scaffold (0.001 97 ± 0.000 31 U/L/ng), than on the unmodified scaffold (0.000 97 ± 0.000 25 U/L/ng) (p < 0.01), indicating that a RGD peptide significantly promotes osteogenic differentiation of BMSCs on CS/HA scaffolds. The results of this study indicate that RGD-CS/HA scaffolds promote initial cell adhesion, spread and differentiation toward an osteogenic phenotype.

Because of improving treatments and survival, 40% to 58% of patients with bone metastases from nonsmall cell lung cancer (NSCLC) will suffer from at least one skeletal-related event (SRE), affecting their quality of life, but the natural history of SRE is poorly understood. The study aimed to examine the factors involved in SRE-free survival (SRS) and overall survival (OS) of patients with NSCLC and bone metastases.This was a retrospective study of 211 patients with bone metastasis from NSCLC and treated at the Tumor Hospital Affiliated to Harbin Medical University between January 2007 and January 2012. OS and SRS were evaluated by the Kaplan–Meier method. The factors associated with SRS and OS were examined using multivariate Cox analyses.The 1 year OS was 55.9% and the median OS was 30 months (range, 1–98 months). Multivariate analyses showed that clinical staging at initial diagnosis (P < .001) and SRE (P = .033) were independently associated with OS, and clinical staging at initial diagnosis (P = .009), bone pain (P = .008), primary tumor radiotherapy (P < .001), and chemotherapy (P = .031) were independently associated with SRS. Stage I, II, and III patients under biphosphonate therapy fared better than those without biphosphonate treatment, but there was no difference for stage IV patients.The identification of factors associated with OS and SRS of patients with NSCLC and bone metastases should provide new clues for a better management of these patients.

No abstract

Surgical repair of bone defects remains challenging, and the search for alternative procedures is ongoing. Devices made of Mg for bone repair have received much attention owing to their good biocompatibility and mechanical properties. We developed a new type of scaffold made of a Mg-Zn-Ca alloy with a shape that mimics cortical bone and can be filled with morselized bone. We evaluated its durability and efficacy in a rabbit ulna-defect model. Three types of scaffold-surface coating were evaluated: group A, no coating; group B, a 10-μm microarc oxidation coating; group C, a hydrothermal duplex composite coating; and group D, an empty-defect control. X-ray and micro-computed tomography(micro-CT) images were acquired over 12 weeks to assess ulnar repair. A mechanical stress test indicated that bone repair within each group improved significantly over time (P < 0.01). The degradation behavior of the different scaffolds was assessed by micro-CT and quantified according to the amount of hydrogen gas generated; these measurements indicated that the group C scaffold better resisted corrosion than did the other scaffold types (P < 0.05). Calcein fluorescence and histology revealed that greater mineral densities and better bone responses were achieved for groups B and C than for group A, with group C providing the best response. In conclusion, our Mg-Zn-Ca-alloy scaffold effectively aided bone repair. The group C scaffold exhibited the best corrosion resistance and osteogenesis properties, making it a candidate scaffold for repair of bone defects.

We previously demonstrated that gambogic acid (GA) is a promising chemotherapeutic compound for human osteosarcoma treatment. The aim of this study was to detect whether the combination of lower-dose GA (0.3 mg/L) and cisplatin (CDDP) (1 mg/L) could perform a synergistic effect on inhibiting tumor in four osteosarcoma cell lines. Our results showed that the combination between GA at lower dose and CDDP significantly exerts a synergistic effect on inhibiting the cellular viability in MG63, HOS, and U2OS cells. In contrast, an antagonistic character was detected in SAOS2 cells exposed to the combined use of lower-dose GA (0.3 mg/L) and CDDP (1 mg/L). Then, analysis of cell cycle showed the combination of both drugs significantly induced the G2/M phase arrest, without any difference relative to GA treatment alone, in MG63 cells. Flow-cytometric analysis of cell apoptosis displayed that the apoptotic rate in the combination group is higher than that in GA treatment alone in MG63, HOS, and U2OS cells. The combined use of both drugs had no effect on mitochondrial membrane potential, but promoted the apoptosis-inducing function through triggering of CDDP in the three cell lines. By measurement of mitochondrial membrane potential, the activity of caspase-3 and the expressions of caspase-8 and caspase-9, it was showed that the apoptosis-promoting effect of the combined use of both drugs could be dependent on the death receptor apoptosis pathway, not dependent on the mitochondria apoptosis mechanism. This research, for the first time, demonstrates that GA could increase the chemotherapeutic effect of CDDP in human osteosarcoma treatment through inducing the cell cycle arrest and promoting cell apoptosis.