Semaphorins have been recently targeted as new molecules directly implicated in the cell-cell communication that occurs between osteoclasts and osteoblasts. Overexpression of certain semaphorins, such as semaphorin4D (sema4D), is found in an osteoporotic phenotype and plays a key role in osteoclast activity by suppressing osteoblast maturation, thus significantly altering the bone modeling cycle. In the present study, we fabricate a site-specific bone-targeting drug-delivery system from polymeric nanoparticles with the incorporation of siRNA interference molecule for sema4D and demonstrate their cellular uptake and intracellular trafficking within osteoclasts, thus preventing the suppression of osteoblast activity. We then demonstrate in an osteoporotic animal model induced by ovariectomy that weekly intravenous injections led to a significantly greater number of active osteoblasts at the bone surface, resulting in higher bone volume in compromised animals. The findings from the present study demonstrate a novel and promising site-specific therapeutic option for the treatment of osteoporosis via interference of the sema4D-plexin cell communication pathway between osteoclasts and osteoblasts.

Up to now, the molecular mechanisms underlying the stemness of prostate cancer stem cells (PCSCs) are still poorly understood. In this study, we demonstrated that microRNA-7 (miR-7) appears to be a novel tumor-suppressor miRNA, which abrogates the stemness of PCSCs and inhibits prostate tumorigenesis by suppressing a key stemness factor KLF4. MicroRNA-7 is down-regulated in prostate cancer cells compared to non-tumorigenic prostate epithelial cells. Restoration of miR-7 suppresses the expression of the stemness factor KLF4 in PCSCs and inhibits prostate tumorigenesis both in vitro and in vivo. Interestingly, the suppression of the stemness of PCSCs by miR-7 is sustained for generations in xenografts. Analysis of clinical samples also revealed a negative correlation between miR-7 expression and prostate tumor progression. Mechanistically, overexpression of miR-7 may lead to a cell cycle arrest but not apoptosis, which seems achieved via suppressing the KLF4/PI3K/Akt/p21 pathway. This study identifies miR-7 as a suppressor of PCSCs' stemness and implicates its potential application for PCa therapy.

Facile synthesis of Ru supported on WO3 nanosheets for highly selective cellulose hydrogenolysis to ethylene glycol.

Osteoporosis is one of the most widely occurring bone disorders characterized by low bone mineral density and poor bone strength. Strontium ranelate, as a treatment option, has received significant attention in recent years due to its ability to halt the progress of osteoporosis by simultaneously improving bone formation and reducing bone resorption. Although much emphasis has been given to the treatment of osteoporosis and fracture prevention using pharmacological agents, much less attention has been placed on the repair of critical-sized bone fractures caused by osteoporosis. The aim of the present study was to prepare strontium-incorporated mesoporous bioactive glass (Sr-MBG) scaffolds in order to combine the therapeutic effects of Sr 2+ ions on osteoporosis with the bioactivity of MBG to regenerate osteoporotic-related fractures. Prior to animal implantation, the effects of Sr-containing ionic products from Sr-MBG scaffolds on the proliferation and differentiation of bone marrow stromal cells (BMSCs) from osteoporotic bone were investigated in an in vitro culture system. The results showed that Sr-MBG scaffolds significantly increased the proliferation of BMSCs in a concentration dependent manner and were able to stimulate the expression of osteoblast differentiation markers including Alpl, Col1a1, Runx2 and Bglap as assessed by real-time PCR. Critical sized femur defects in ovariectomised rats were created to simulate an osteoporotic phenotype. At time points 2, 4 and 8 weeks post-implantation, the in vivo osteogenetic efficiency was systematically evaluated by mCT analysis, hematoxylin and eosin staining, and immunohistochemistry (type I collagen). The results showed that the incorporation of Sr into MBG scaffolds significantly stimulated new bone formation in osteoporotic bone defects when compared to MBG scaffolds alone. Furthermore, it was generally found that Sr release in blood was maintained at a very low level and the Sr, Si, Ca and P excretion by urine operated in an a similar manner to blank control animals. Our results suggested that Sr-MBG scaffolds could be a promising biomaterial for regenerating osteoporosis-related fractures by the release of Sr-containing ionic products. Fig. 5 The 3D microarchitectural parameters analyzed by m-CT. Data are presented as mean AE SD and analyzed by one-way ANOVA and SNK tests.Fig. 6 Representative sections of HE staining demonstrate the healing defects filled with MBG, 2.5% Sr-MBG and 5% Sr-MBG. The box on the right top gives magnification of local details. Arrows: new generated bone, stars: filled scaffold, scale bar: 200 mm.