Decidual small extracellular vesicles induce trophoblast invasion by upregulating N-cadherin.

Small extracellular vesicles (sEVs) are important mediators of cell-to-cell communication involved in the successful establishment of a pregnancy. Human decidual stromal cells play a key role in regulating trophoblast invasion. Nevertheless, the regulatory functions of decidual stromal cells-derived sEVs in human trophoblast cells are still unclear. In this study, primary human decidual stromal cells were isolated, and immortalized human endometrial stromal cell line (HESCs) were decidualized into human decidual stromal cells (HDSCs) using hormonal cocktail containing medroxy progesterone 17-acetate (MPA), estrogen and cAMP analog. HDSC-sEVs were isolated from both primary human decidual stromal cells and immortal HDSCs, respectively, and identified by transmission electron microscopy and western blotting. EV uptake assay indicated that HDSC-sEVs could be uptaken by trophoblast cells. HDSC-sEVs could increase the invasiveness and the expression level of N-cadherin of trophoblast cells with elevated phosphorylation of SMAD2 and SMAD3 in the cells. Silencing of N-cadherin could block cell invasion induced by HDSC-sEVs, while knockdown of SMAD2 and SMAD3 could inhibit the upregulation of N-cadherin in trophoblast cells. Taken together, our results suggested a regulatory effect of HDSC-sEVs in the invasion of trophoblast cells, and HDSC-sEVs may be important mediators of trophoblasts during embryo implantation and placentation.

[Clinical study of treating knee osteoarthritis (Bi syndrome of knee) by massage combined Chinese materia medica footbath fumigation and washing].

OBJECTIVE: To evaluate the clinical efficacy of treating knee osteoarthritis (KOA, Bi syndrome of knee) by massage combined Chinese materia medica (CMM) footbath fumigation and washing, and to observe the changes of the Lysholm knee score (LKSS). METHODS: Totally 61 patients with grade I to III KOA were randomly assigned to two groups, the treatment group and the control group. Patients in the treatment group were treated with massage combined CMM footbath fumigation and washing, while those in the control group were treated with oral administration of meloxicam. They were treated for 20 days (times). The LKSS was assessed before treatment, 10 days of treatment, by the end of the treatment, and 1 month after treatment. RESULTS: (1) The therapeutic efficacy in the treatment group was superior to that in the control group (P < 0.05). Thirteen cases were clinically controlled, with 11 markedly effective, 6 effective, and 1 ineffective in the treatment group, while 5 cases were clinically controlled, with 11 markedly effective, 10 effective, and 4 ineffective in the control group. (2) The LKSS: The post-treatment LKSS was higher than that before treatment in the two groups. The LKSS at 10 days (times) of treatment was lower in the treatment group than in the control group, but with no statistical difference (P > 0.05). The LKSS by the end of the treatment was higher in the treatment group than in the control group (P < 0.05). (3) The case number of patients in need of receiving the treatment again within 1-month follow-up and the difference between the LKSS at follow-ups and that by the end of the treatment were lower in the treatment group than in the control group (P < 0.01). CONCLUSION: Massage combined CMM footbath fumigation and washing had better clinical efficacy on patients suffering from KOA.