Cancer-induced bone pain (CIBP) is a common clinical problem in breast cancer patients with bone metastasis. Recent studies shows chemokines are novel targets for treatment of CIBP. In this study, we intra-tibial inoculated with Walker 256 rat mammary gland carcinoma cells into rat bone to established metastatic breast cancer. Then we measured the expression of CXCL10 in the spinal cord of metastatic bone cancer rats, investigated the role of CXCL10 in the development of CIBP, and the underlying mechanism. Results revealed that after intra-tibial inoculation with Walker 256 cells, rats showed up-regulation of CXCL10 and its receptor CXCR3 in the spinal cord. Interestingly, intrathecally injection of recombinant CXCL10 protein induced mechanical allodynia in naïve rats. Blocking the function of CXCL10/CXCR3 pathway via anti-CXCL10 antibody or CXCR3 antagonist prevented the development of CIBP and microglial activation. Moreover, CXCL10-induced mechanical allodynia was rescued by minocycline treatment during the late-stage of CIBP, days 10-14. The regulation of CXCL10 expression involved microglial activation in a manner of autocrine positive feedback. These results suggest that CXCL10 may be a necessary algogenic molecule, especially in the development of CIBP. Its function was partly mediated via spinal microglial activation. This study provides a novel insight into the biological function of chemokine CXCL10 in the molecular mechanism underlying cancer pain. It also provides new target for clinical treatment of metastatic breast cancer-induced bone pain in future.

Superparamagnetic multi-walled carbon nanotubes (mMWCNTs) were prepared by filling multi-walled carbon nanotubes (MWCNTs) with iron oxide, and further modified by linking polyamidoamine (PAMAM) dendrimers (mMWCNTs-PAMAM) on the surface. Then, mMWCNTs-PAMAM was employed as the carrier and successfully immobilized Burkholderia cepacia lipase (BCL) via a covalent method (BCL-mMWCNTs-G3). The maximum activity recovery of the immobilized lipase was 1,716% and the specific activity increased to 77,460 U/g-protein, 17-fold higher than that of the free enzyme. The immobilized lipase displayed significantly enhanced thermostability and pH-resistance, and could efficiently catalyze transesterification to produce biodiesel at a conversion rate of 92.8%. Moreover, it possessed better recycling performance. After 20 cycles of repeated used, it still retained ca. 90% of its original activity, since the carbon nanotube−enzyme conjugates could be easily separated from the reaction mixture by using a magnet. This study provides a new perspective for biotechnological applications by adding a magnetic property to the unique intrinsic properties of nanotubes.

A simple and versatile delivery platform for peptide and protein based on physically cross-linked poly (vinyl alcohol) (PVA) hydrogels containing insulin-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles was successfully fabricated. The particle morphology and size were characterized by SEM and laser light scattering method, respectively. Results showed that these particles had a mean diameter of 615 nm with a narrow size distribution and homogeneous particle production. The protein encapsulation efficiency was 72.6%. When insulin-loaded PLGA nanoparticles were administered intraperitoneally as a single dose (20 U/kg) to streptozotocin-induced diabetic mouse, blood glucose levels of these mice decreased and it could be sustained at such levels over 24 h. In vitro release further indicated that entrapment of the nanoparticles into the PVA hydrogels causes a reduction in both the release rate and the total amount of insulin released, which suggesting that PLGA nanoparticles entrapped into the PVA hydrogels showed more suitable controlled release kinetics for protein delivery.

A new hybrid nanoflower biocatalyst was synthesized using the organic component of Burkholderia cepacia lipase and inorganic component of calcium phosphate.