Silymarin ameliorates peritoneal fibrosis by inhibiting the TGF-ß/Smad signaling pathway.

Peritoneal dialysis (PD) is the mainstay of treatment for renal failure replacement therapy. Although PD has greatly improved the quality of life of end-stage renal disease (ESRD) patients, long-term PD can lead to ultrafiltration failure, which in turn causes peritoneal fibrosis (PF). Silymarin (SM) is a polyphenolic flavonoid isolated from the milk thistle (Silybum marianum) species that has a variety of pharmacological actions, including antioxidant, anti-inflammatory, antiviral, and anti-fibrotic pharmacological activities. However, the effect of SM on PF and its potential mechanisms have not been clarified. The aim of this study was to investigate the preventive effect of SM on PF in vitro and in vivo as well as elucidate the underlying mechanisms. We established PF mouse models and human pleural mesothelial cell fibrosis in vitro by intraperitoneal injection of high-glucose peritoneal dialysis solution (PDS) or transforming growth factor-ß1 (TGF-ß1), and evaluated the effect of SM on peritoneal fibrosis in vivo and in vitro. We found that SM alleviated peritoneal dysfunction. Meanwhile, SM inhibited the expression of fibrotic markers (TGF-ß1, collagen I, fibronectin) and restored the expression of E-cadherin, BMP-7 in PF mice and TGF-ß1-treated Met-5A cells. Furthermore, SM markedly down-regulated the expression of TGF-ß1, p-Smad2, and p-Smad3 and up-regulated the expression of smad7. In conclusion, these findings suggested that SM may be an efficient and novel therapy for the prevention of PF through inhibition of TGF-ß/Smad signaling.

Genomic analysis, trajectory tracking, and field surveys reveal sources and long-distance dispersal routes of wheat stripe rust pathogen in China.

Identifying sources of phytopathogen inoculum and determining their contributions to disease outbreaks are essential for predicting disease development and establishing control strategies. Puccinia striiformis f. sp. tritici (Pst), the causal agent of wheat stripe rust, is an airborne fungal pathogen with rapid virulence variation that threatens wheat production through its long-distance migration. Because of wide variation in geographic features, climatic conditions, and wheat production systems, Pst sources and related dispersal routes in China are largely unclear. In the present study, we performed genomic analyses of 154 Pst isolates from all major wheat-growing regions in China to determine Pst population structure and diversity. Through trajectory tracking, historical migration studies, genetic introgression analyses, and field surveys, we investigated Pst sources and their contributions to wheat stripe rust epidemics. We identified Longnan, the Himalayan region, and the Guizhou Plateau, which contain the highest population genetic diversities, as the Pst sources in China. Pst from Longnan disseminates mainly to eastern Liupan Mountain, the Sichuan Basin, and eastern Qinghai; that from the Himalayan region spreads mainly to the Sichuan Basin and eastern Qinghai; and that from the Guizhou Plateau migrates mainly to the Sichuan Basin and the Central Plain. These findings improve our current understanding of wheat stripe rust epidemics in China and emphasize the need for managing stripe rust on a national scale.