ABSTRACT
Objective:To investigate the effect of plasma-derived exosomes on the function of human venous endothelial cells in normal and rheumatoid arthritis patients.Methods:The plasma of healthy controls and rheumatoid arthritis patients was collected, and the surface protein markers were identified by transmission electron microscopy (TEM) and NTA. The effects of exosomes on endothelial cell proliferation and migration and invasion were detected by CCK8, cell scratch, Transwell chamber experiments; real time polymerase chain reaction (RT-PCR). The changes of cell secretion hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF) content were detected. The comparison between the two groups was performed by t test. Results:The double concave disc-like cystic vesicles were observed by transmission electron microscopy, nanoparticle tracking analysis (NTA) showed that the diameter was about 50-150 nm. Western blotting showed that the relative molecular weights of flotillin1 and CD81, on the surface of plasma exosomes were 47 000 and 26 000, respectively. Endothelial cell activity decreased with the increase of exosomes concentration, but the difference between the two groups was not significant( t=1.86, P>0.05). Compared with normal human con-exo, ra-exo significantly inhibited endothelial cell migration [(2.24±0.23) vs (1.46±0.13), t=6.60, P<0.05], reduced invasive capacity [(0.673±0.030) vs (0.827±0.030), t=8.11, P<0.05] in patients with rheumatoid arthritis. In addition, the ability to secrete HIF-1a, VEGF cytokines was decreased significantly, the difference was statistically significant [(0.706±0.020) vs (0.908±0.040), t=10.10, P<0.05; (0.692±0.010) vs (0.841±0.020), t=14.90, P<0.05]. Conclusion:The exosomes from plasma may play an important role in RA and vascular injury.
ABSTRACT
Breast cancer is a malignant tumor that occurs in the epithelial tissues of the breast gland. The cause of the disease is not fully understood and may be related to genetic, endocrine and other factors. For estrogen or progesterone receptor-positive early breast cancer, endocrine therapy is efficient, simple, and fewer side-effect, so endocrine therapy plays an important role in the treatment for early breast cancer. But most of them will develop drug-resistant after 8 to 14 months and have to combine with chemotherapy or molecule targeted therapy. However, there are still different ideas in the effects of endocrine therapy drugs alone or in combination with chemotherapy or molecule targeted drugs, pre-menopausally or post-menopausally.