Our results showed that the metabolic changes in cows with clinical ketosis involve complex metabolic networks and signal transduction. These results are important for future studies elucidating the pathogenesis, diagnosis, and prevention of clinical ketosis in dairy cows.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis of cancer cells and is verified effective to various cancers. However, a variety of breast cancer cell lines are resistant to TRAIL and the mechanisms of resistance are largely unknown. In our present experiment, we successfully utilized breast cancer cell line MDA-MB-231 to establish TRAIL-resistant cell line. We found resistance to TRAIL could induce epithelial-mesenchymal transition (EMT) and enhance invasiveness. We further demonstrated PTEN was down-regulated in TRAIL-resistant cells. Silencing miR-221, PTEN expression was up-regulated, the process of EMT could be reversed, and the ability of migration and invasion were correspondingly weakened. We also demonstrated knockdown of miR-221 could reverse resistance to TRAIL partially by targeting PTEN. Our findings suggest that resistance to TRAIL could induce EMT and enhance invasiveness by suppressing PTEN via miR-221. Re-expression of miR-221 or targeting PTEN might serve as potential therapeutic approaches for the treatment of Trail-resistant breast cancer.

Background: About 70% of human breast cancers express estrogen receptor α (ERα) and in this kind of breast cancer estrogen plays an important role. Estrogen independent growth has been reported to promote resistance to one of the selective estrogen receptor modulators (SERMs) tamoxifen which is clinically the first line treatment for patients with ERα-positive breast cancer. The resistance of tamoxifen is a major problem in the clinical management of breast cancer. Methods: We used MCF-7 cells with ectopic expression of MDTH in this study. MTT, clone formation and tumor formation in nude mice methods were utilized to confirm the role of MTDH in estrogen-independent growth and tamoxifen resistance. Flow cytometry, western blot and siRNA were used to study the detailed mechanisms. Results: We found that MTDH could mediate estrogen-independent growth and induce resistance to tamoxifen in ERα-positive breast cancer cells. MTDH could reduce the expression of PTEN, up-regulate AKT and BCL2 and inhibit the apoptosis induced by tamoxifen. Conclusion: Our study indicated that MTDH was a candidate marker to predict the clinical efficacy of tamoxifen and targeting MTDH would overcome the resistance to tamoxifen in breast cancer cells.

The (1)H-NMR spectroscopy can be used to understand the pathogenesis of MF and identify biomarkers of the disease.