Quercetin encapsulated in folic acid-modified liposomes is therapeutic against osteosarcoma by non-covalent binding to the JH2 domain of JAK2 Via the JAK2-STAT3-PDL1.

Osteosarcoma (OS) is a malignant solid tumor prone to lung metastasis that occurs in adolescents aged 15-19 years. Neoadjuvant chemotherapy and surgical treatment aimed at curing OS have gained limited progress over the last 30 years. Exploring new effective second-line therapies for OS patients is a serious challenge for researchers. Quercetin, a multiple biologically active polyphenolic flavonoid, has been used in tumor therapy. However, the exact mechanism of quercetin is still unknown, which limits the application of quercetin. In the current study, we found that quercetin could inhibit JAK2 through the JH2 domain in a non-covalent manner, resulting in the inhibition of OS proliferation and immune escape via the JAK2-STAT3-PD-L1 signaling axis. More importantly, to overcome the shortcomings of quercetin, including low water solubility and low oral availability, we encapsulated it with folic acid-modified liposomes. The transportation of quercetin by folic acid-modified liposomes may provide a feasible strategy to cure OS.

Cellulose synthesis genes CESA6 and CSI1 are important for salt stress tolerance in Arabidopsis.

Two salt hypersensitive mutants she1 and she2 were identified through genetic screening. SHE1 encodes a cellulose synthase CESA6 while SHE2 encodes a cellulose synthase-interactive protein CSI1. Both of them are involved in cellulose deposition. Our results demonstrated that the sustained cellulose synthesis is important for salt stress tolerance in Arabidopsis.

Endoprosthetic reconstruction of the proximal humerus after tumour resection with polypropylene mesh.

PURPOSE: The purpose of this study was to evaluate the functional outcomes and complications of endoprosthesis-PPP mesh composite reconstruction after bone tumour resection of the proximal humerus. METHODS: We retrospectively analysed 18 patients treated in our department with endoprosthesis-PPP mesh composite reconstruction after bone tumour resection of the proximal humerus between March 2005 and October 2010. Sixteen patients (16/18) were followed up for 56 months (range, 30-96 months). The pre- and post-operative pain severity was assessed according to a 10-cm visual analogue scale (VAS). The clinical results of functional improvement were assessed by Musculoskeletal Tumour Society (MSTS) score at the time of final follow-up. Moreover, we also analysed complications associated with the reconstruction procedure. RESULTS: Most patients experienced some alleviation of pain two weeks after the reconstruction surgery. The mean MSTS upper extremity functional outcome score at the time of final follow-up was 20 (66.7 %, range, 16-27). Mean shoulder abduction was 36° (range, 18-125°) and mean shoulder flexion was 39° (range, 21-120°). Local recurrence occurred in only one patient (6.25 %), aseptic prosthesis loosening occurred in one patient (6.25 %) and anterior subluxation occurred in one patient (6.25 %). CONCLUSIONS: The capsule reconstruction on the basis of PPP mesh can significantly reduce the recurrence rate of glenohumeral joint instability, which may offer an alternative for the capsule reconstruction after bone tumour resection of the proximal humerus.

Bone cement filling combined with lumbo-iliac screw internal fixation in the treatment of benign sacroiliac joint tumours.

BACKGROUND: To investigate the method of reconstruction of the sacroiliac joint in patients who underwent benign tumour curettage and analyse the effect of internal fixation with lumbo-iliac screws and connecting rod insertion after filling the defect with bone cement. METHODS: Twenty-four patients with benign sacroiliac joint tumours underwent curettage and filling of the defect with bone cement, followed by lumbo-iliac screw and connecting rod insertion. The visual analogue scale (VAS) was used to assess pain, and the Musculoskeletal Tumour Society (MSTS) score was used to assess hip function. RESULTS: All patients were followed-up for 24-96 months (average, 42.2 months). The postoperative VAS score was significantly lower than the preoperative score (p < 0.05), while the postoperative MSTS score was significantly higher than the preoperative score (p < 0.05). One patient had delayed healing of the surgical incision; no complications occurred in the remaining patients. CONCLUSION: For benign sacroiliac joint tumours, the combination of filling of defects with bone cement and internal lumbo-iliac fixation can relieve pain quickly, and achieve good limb function.

A thermoresponsive polydiolcitrate-gelatin scaffold and delivery system mediates effective bone formation from BMP9-transduced mesenchymal stem cells.

Successful bone tissue engineering requires at the minimum sufficient osteoblast progenitors, efficient osteoinductive factors, and biocompatible scaffolding materials. We previously demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most potent factors in inducing osteogenic differentiation of mesenchymal stem cells (MSCs). Here, we investigated the potential use of a biodegradable citrate-based thermosensitive macromolecule, poly(polyethyleneglycol citrate-co-N-isopropylacrylamide) (PPCN) mixed with gelatin (PPCNG) as a scaffold for the delivery of BMP9-stimulated MSCs to promote localized bone formation. The addition of gelatin to PPCN effectively enhanced the cell adhesion and survival properties of MSCs entrapped within the gel in 3D culture. Using the BMP9-transduced MSC line immortalized mouse embryonic fibroblasts (iMEFs), we found that PPCNG facilitated BMP9-induced osteogenic differentiation of iMEFs in vivo and promoted the formation of well-ossified and vascularized trabecular bone-like structures in a mouse model of ectopic bone formation. Histologic evaluation revealed that vascularization of the bony masses retrieved from the iMEFs + PPCNG group was significantly more pronounced than that of the direct cell injection group. Accordingly, vascular endothelial growth factor (VEGF) expression was shown to be significantly higher in the bony masses recovered from the iMEFs + PPCNG group. Taken together, our results suggest that PPCNG may serve as a novel biodegradable and injectable scaffold and carrier for gene and cell-based bone tissue engineering.

Designer self-assembling peptide nanofiber scaffolds containing link protein N-terminal peptide induce chondrogenesis of rabbit bone marrow stem cells.

Designer self-assembling peptide nanofiber hydrogel scaffolds have been considered as promising biomaterials for tissue engineering because of their excellent biocompatibility and biofunctionality. Our previous studies have shown that a novel designer functionalized self-assembling peptide nanofiber hydrogel scaffold (RLN/RADA16, LN-NS) containing N-terminal peptide sequence of link protein (link N) can promote nucleus pulposus cells (NPCs) adhesion and three-dimensional (3D) migration and stimulate biosynthesis of type II collagen and aggrecan by NPCs in vitro. The present study has extended these investigations to determine the effects of this functionalized LN-NS on bone marrow stem cells (BMSCs), a potential cell source for NP regeneration. Although the functionalized LN-NS cannot promote BMSCs proliferation, it significantly promotes BMSCs adhesion compared with that of the pure RADA16 hydrogel scaffold. Moreover, the functionalized LN-NS remarkably stimulates biosynthesis and deposition of type II collagen and aggrecan. These data demonstrate that the functionalized peptide nanofiber hydrogel scaffold containing link N peptide as a potential matrix substrate will be very useful in the NP tissue regeneration.