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Both collagen fibres and nanohydroxyapatite crystals have anisotropic magnetisation, which allows them to be oriented by a high magnetic field. Highly oriented nanohydroxyapatite/collagen composites were prepared using a high magnetic field combined with in situ synthesis. These highly oriented composites were investigated and compared with conventional composites. The results showed that the collagen fibres in the magnetically induced highly oriented nanohydroxyapatite/collagen composites had a preferred orientation and smaller molecular spacing, while the nanohydroxyapatite crystals were tightly adhered along the collagen fibre surface. The magnetically induced composites exhibited superior resistance to swelling and degradation along with high compressive strength. This artificial composite, with a structure and composition similar to natural bone, represents a new idea for improving materials for vertical or horizontal bone augmentation.

Abstract Background Tumor cell expression of Toll-like receptors (TLRs) can promote inflammation and cell survival in the tumor microenvironment. Toll-like receptor 4 (TLR4) signaling in tumor cells can mediate tumor cell immune escape and tumor progression, and it is regarded as one of the mechanisms for chronic inflammation in tumorigenesis and progression. The expression of TLR4 in human breast cancer cell line MDA-MB-231 and its biological function in the development and progression of breast cancer have not been investigated. We sought to characterize the expression of TLR1-TLR10 in the established human breast cancer cell line MDA-MB-231, and to investigate the biological roles of TLR4 in breast cancer cells growth, survival, and its potential as a target for breast cancer therapy. Methods TLRs mRNA and protein expressions were detected in human breast cancer cell line MDA-MB-231 by RT-PCR, real-time PCR and flow cytometry (FCM). RNA interference was used to knockdown the expression of TLR4 in MDA-MB-231. MDA-MB-231 transfected with the vector pGenesil-1 and the vector containing a scrambled siRNA were as controls. Recombinant plasmids named TLR4AsiRNA, TLR4BsiRNA and TLR4CsiRNA specific to TLR4 were transfected into human breast cancer cell line MDA-MB-231 with Lipfectamine™2000 reagent. TLR4 mRNA and protein expressions were investigated by RT-PCR, real-time PCR, FCM and immunofluorescence after silence. MTT analysis was performed to detect cell proliferation and FCM was used to detect the secretion of inflammatory cytokines in supernatant of transfected cells. Results The human breast cancer cell line MDA-MB-231 was found to express TLR1-TLR10 at both the mRNA and protein levels. TLR4 was found to be the highest expressed TLR in MDA-MB-231. TLR4AsiRNA, TLR4BsiRNA and TLR4CsiRNA were found to significantly inhibit TLR4 expression in MDA-MB-231 at both mRNA and protein levels as compared to vector control(vector transfected cells). TLR4AsiRNA mediated the strongest effect. Knockdown of TLR4 gene in MDA-MB-231 resulted in a dramatic reduction of breast cancer cell viability. The cytokines which were secreted by the TLR4 silenced cells, such as IL-6 and IL-8, also decreased significantly as compared with vector control. No significant difference was observed in siRNA control (Recombinant plasmid named ScrambledsiRNA transfected cells) compared to vector control. Conclusions These studies identified the expression levels of multiple TLRs in human breast cancer cell line MDA-MB-231 and demonstrated that knockdown of TLR4 could actively inhibit proliferation and survival of breast cancer cells. Taken together, our results suggest RNAi-directed targeting of TLR4 may be a beneficial strategy for breast cancer therapy.

As a chemotherapy agent, cisplatin (DDP) is often associated with drug resistance and gastrointestinal toxicity, factors that severely limit therapeutic efficacy in patients with ovarian cancer (OC). Naringin has been shown to increase sensitivity to cisplatin, but whether the intestinal microbiota is associated with this effect has not been reported so far. In this study, we applied a humanized mouse model for the first time to evaluate the reversal of cisplatin resistance by naringin, as well as naringin combined with the microbiota in ovarian cancer. The results showed that naringin combined with Bifidobacterium animalis subsp. lactis NCU-01 had an inhibitory effect on the tumor, significantly reducing tumor size ( p <0.05), as well as the concentrations of serum tumor markers CA125 and HE4, increased the relative abundance of Bifidobacterium and Bacteroides , inhibit Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)-induced intestinal inflammation and increase the expression of intestinal permeability-associated proteins ZO-1 ( p <0.001) and occludin ( p <0.01). In conclusion, the above data demonstrate how naringin combined with Bifidobacterium animalis subsp. lactis NCU-01 reverses cisplatin resistance in ovarian cancer by modulating the intestinal microbiota, inhibiting the TLR4/NF-κB signaling pathway and modulating the p38MAPK signaling pathway., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)