Bone marrow mesenchymal stem cell-derived extracellular vesicles containing miR-181d protect rats against renal fibrosis by inhibiting KLF6 and the NF-κB signaling pathway.

Recent studies have investigated the ability of extracellular vesicles (EVs) in regulating neighboring cells by transferring signaling molecules, such as microRNAs (miRs) in renal fibrosis. EVs released by bone marrow mesenchymal stem cells (BMSCs) contain miR-181d, which may represent a potential therapy for renal fibrosis. miR-181d has been speculated to regulate Krüppel-like factor 6 (KLF6), which activates the nuclear factor-kappa B (NF-κB) signaling pathway. Luciferase assays were performed to confirm the relationship between miR-181d and KLF6. Gain- and loss-of-function studies in vivo and in vitro were performed to assess the effect of BMSC-derived EVs (BMSC-EVs), which contained miR-181d, on KLF6, NF-κB, and renal fibrosis. Transforming growth factor-ß (TGF-ß)-induced renal tubular epithelial HK-2 cells were treated with EVs derived from BMSCs followed by evaluation of collagen type IV α1 (Col4α1), Collagen I and α-smooth muscle actin (α-SMA) as indicators of the extent of renal fibrosis. Renal fibrosis was induced in rats by unilateral ureteral obstruction (UUO) followed by the subsequent analysis of fibrotic markers. BMSC-EVs had higher miR-181d expression. Overexpression of miR-181d correlated with a decrease in KLF6 expression as well as the levels of IκBα phosphorylation, α-SMA, Col4α1, TGF-ßR1 and collagen I in HK-2 cells. In vivo, treatment with miR-181d-containing BMSC-derived EVs was able to restrict the progression of fibrosis in UUO-induced rats. Together, BMSC-EVs suppress fibrosis in vitro and in vivo by delivering miR-181d to neighboring cells, where it targets KLF6 and inhibits the NF-κB signaling pathway.

[Health Risk Assessment of Tunnel Workers Based on the Investigation and Analysis of Occupational Exposure to PM10].

The health risk of tunnel workers' occupational exposure to PM10, was evaluated applying public health exposure evaluation nodel. A questionnaire survey of 250 tunnel workers was conducted in a construction site of Ma-zhu Highway in Hubei Province, and the concentrations of PM10 were monitored. The results showed that the PM10 exposure concentrations of different types of tunnel workers were extremely high. Compared with the limited value, the PM10 exposure concentrations were 83 times, 18 times, 8 times, 9 times Emd 9 times for excavation workers, blasting workers, supporting workers, slag-out workers and secondary-lining workers, respectively. For secondary-lining workers, the average daily exposure time was the longest, which was 11.48 h x d(-1), and the energy metabolism rate was also the highest, which was 1067.43 kj x (m2 x h)(-1). Regarding the inhalation rates, secondary-lining workers could be classified to high-level working intensity, and the other four types of tunnel workers could he classified to middle-level working intensity. The health risk assessment results showed that all tunnel workers had health risk. High exposure concentration of PM10 was the main reason for excavation workers' highest hazard quotient, and it was the same for the blasting workers. The reason for secondary-lining workers' high hazard quotient was that they had higher inhalation rates and longer average daily exposure time. In order to reduce the health risk of tunnel workers, firstly the workers should be equipped with appropriate respiratory protective equipment; secondly an appropriate tunnel working standard should be developed to set a reasonable working-years for reducing the exposure time.