Hirudin Ameliorates Renal Interstitial Fibrosis via Regulating TGF-ß1/Smad and NF-κB Signaling in UUO Rat Model.

PURPOSE: Hirudin, a polypeptide structure containing 65 amino acids, is a potent natural thrombin inhibitor with anticoagulant property extracted from Hirudo medicinalis. It has been reported to have anti-inflammatory and antifibrotic property. Here we explored the renoprotective effect of hirudin on unilateral ureteral obstruction (UUO) induced renal interstitial fibrosis (RIF). METHODS: Rats were randomly divided into five groups: sham group, UUO alone group, and three UUO + hirudin-treatment groups (10, 20, or 40 IU/kg/d, for 14 continuous days). At the end of the experiment period, animals were sacrificed. Pathologic changes in renal specimens were observed using hematoxylin and eosin (HE) staining and Masson staining. The expressions of collagen III (Col III), fibronectin (FN), α-smooth muscle actin (α-SMA), protease-activated receptor 1 (PAR-1), and proteins in the TGF-ß1/Smad and NF-κB pathways in renal tissues were examined by immunohistochemistry and/or Western blotting. RESULTS: HE and Masson staining showed that hirudin-treated UUO rats had lower extent of renal injury and deposition of extracellular matrix (ECM) in renal interstitium than those in the UUO group. The results of immunohistochemistry and WB indicated decreased protein expressions of Col III, FN, α-SMA, PAR-1, and inflammatory markers such as tumor necrosis factor-α and interleukin-6 after hirudin treatment. Furthermore, hirudin reduced the expressions of transforming growth factor ß1 (TGF-ß1), phosphorylated-Smad2, and phosphorylated-Smad3 in the UUO model. In parallel, we found inhibited nuclear factor-κB (NF-κB) signaling after hirudin treatment, with downregulated protein expressions of P65, phosphorylated-P65, and phosphorylated-iκBα and increased iκBα. CONCLUSION: Hirudin improves kidney injury and suppresses inflammatory response and ECM accumulation in UUO rats; its underlying mechanism may be associated with the inhibition of TGF-ß1/Smad and NF-κB signaling.

Long-Term Coffee Monoculture Alters Soil Chemical Properties and Microbial Communities.

Long-term monoculture severely inhibits coffee plant growth, decreases its yield and results in serious economic losses in China. Here, we selected four replanted coffee fields with 4, 18, 26 and 57 years of monoculture history in Hainan China to investigate the influence of continuous cropping on soil chemical properties and microbial communities. Results showed long-term monoculture decreased soil pH and organic matter content and increased soil EC. Soil bacterial and fungal richness decreased with continuous coffee cropping. Principal coordinate analysis suggested monoculture time was a major determinant of bacterial and fungal community structures. Relative abundances of bacterial Proteobacteria, Bacteroidetes and Nitrospira and fungal Ascomycota phyla decreased over time. At genus level, potentially beneficial microbes such as Nitrospira and Trichoderma, significantly declined over time and showed positive relationships with coffee plant growth in pots. In conclusion, continuous coffee cropping decreased soil pH, organic matter content, potentially beneficial microbes and increased soil EC, which might lead to the poor growth of coffee plants in pots and decline of coffee yields in fields. Thus, developing sustainable agriculture to improve soil pH, organic matter content, microbial activity and reduce the salt stress under continuous cropping system is important for coffee production in China.

Icariin-treated human umbilical cord mesenchymal stem cells decrease chronic liver injury in mice.

Human umbilical cord mesenchymal stem cells (hUMSCs) have been shown to have multiple differentiation potentials. However, a key problem is that only a small number of hUMSCs can migrate to damaged tissue after transplantation. According to "The Theory of Kidney Essence" in Traditional Chinese Medicine, some traditional Chinese medicines used for tonifying the kidneys can be applied in promoting the differentiation and migration of stem cells in vivo. Our previous study demonstrated that icariin (ICA) could up-regulate the pluripotent genes of hUMSCs in vitro and induce cell migration in mice in an acute kidney injury model in vivo. The aim of this study was to investigate the effects of ICA-induced hUMSCs in chronic liver injury (CLI) caused by carbon tetrachloride (CCl4). CLI was induced by intraperitoneal injection of CCl4. ICA-treated hUMSCs were transplanted via intra-venous injection. The animals were followed for survival, biochemistry analysis and pathology. The results show that ICA-treated hUMSCs accelerate the recovery of liver function in mice with CLI. In addition, ICA-treated hUMSCs increase the anti-oxidant activities in liver and prevent the progression to hepatic fibrosis. Moreover, ICA induces the migration of hUMSCs to the injured liver tissue. In conclusion, these data demonstrate that ICA-treated hUMSCs exhibit recovery and protective properties in the mice model of CCl4-induced CLI.