Leech extract alleviates idiopathic pulmonary fibrosis by TGF-ß1/Smad3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Leech, as a traditional Chinese medicine for the treatment of blood circulation and blood stasis, was also widely used to cure pulmonary fibrosis in China. In clinical practice, some traditional Chinese medicine preparation such as Shui Zhi Xuan Bi Hua Xian Tang and Shui Zhi Tong Luo Capsule composed of leech, could improve the clinical symptoms and pulmonary function in patients with idiopathic pulmonary fibrosis (IPF). However, the material basis of the leech in the treatment of IPF were not yet clear. AIM OF THE STUDY: Screen out the components of leech that have the anti-pulmonary fibrosis effects, and further explore the therapeutic mechanism of the active components. MATERIALS AND METHODS: In this study, the different molecular weight components of leech extract samples were prepared using the semi-permeable membranes with different pore sizes. The therapeutic effects of the leech extract groups with molecular weight greater than 10 KDa (>10 KDa group), between 3 KDa and 10 KDa (3-10 KDa group), and less than 3 KDa (<3 KDa group) on pulmonary fibrosis were firstly investigated by cell proliferation and cytotoxicity assay (MTT), cell wound healing assay, immunofluorescence staining (IF) and Western blot (WB) assay through the TGF-ß1-induced fibroblast cell model. Then bleomycin-induced pulmonary fibrosis (BML-induced PF) mouse model was constructed to investigate the pharmacological activities of the active component group of leech extract in vivo. Pathological changes of the mouse lung were observed by hematoxylin-eosin staining (H&E) and Masson's trichrome staining (Masson). The hydroxyproline (HYP) content of lung tissues was quantified by HYP detection kit. The levels of extracellular matrix-related fibronectin (FN) and collagen type Ⅰ (Collagen Ⅰ), pyruvate kinase M2 (PKM2) monomer and Smad7 protein were determined via WB method. PKM2 and Smad7 protein were further characterized by IF assays. RESULTS: Using TGF-ß1-induced HFL1 cell line as a PF cell model, the in vitro results demonstrated that the >10 KDa group could significantly inhibited the cell proliferation and migration, downregulated the expression level of cytoskeletal protein vimentin and α-smooth muscle actin (α-SMA), and reduced the deposition of FN and Collagen Ⅰ. In the BML-induced PF mouse model, the >10 KDa group significantly reduced the content of HYP, downregulated the expression levels of FN and Collagen Ⅰ in lung tissues, and delayed the pathological changes of lung tissue structure. The results of WB and IF assays further indicated that the >10 KDa group could up-regulate the expression level of PKM2 monomer and Smad7 protein in the cellular level, thereby delaying the progression of pulmonary fibrosis. CONCLUSIONS: Our study revealed that the >10 KDa group was the main material basis of the leech extract that inhibited pulmonary fibrosis through TGF-ß1/Smad3 signaling pathway.

Effects of Anions and pH on the Stability of ZnO Nanorods for Photoelectrochemical Water Splitting.

This work demonstrates the improved stability of zinc oxide nanorods (ZnO NRs) for the photoanode of solar water splitting under voltage biases by the addition of borate or carbonate ions in the aqueous electrolyte with suitable pH ranges. The ZnO NRs prepared by the hydrothermal method are highly active and stable at pH 10.5 in both borate and carbonate buffer solutions, where a photocurrent higher than 99% of the initial value has been preserved after 1 h polarization at 1.5 V (vs reversible hydrogen electrode) under AM 1.5G. The optimal pH ranges with a minimum morphological change of ZnO NRs for photoelectrochemical (PEC) water splitting in borate and carbonate buffer solutions are 9-13 and 10-12, respectively. The working pH range for PEC water splitting on ZnO NR photoanodes can be extended to 8.5-12.5 by the combination of borate and carbonate anions. The lifetime of ZnO NR photoanodes can be synergistically prolonged for over an order of magnitude when the electrolyte is the binary electrolyte consisting of borate and carbonate in comparison with these two anions used individually. On the basis of the experimental results, a possible mechanism for the protective behavior of ZnO in borate and carbonate solutions is proposed. These findings can be used to improve the lifetime of other high-performance ZnO-based catalysts and to understand the photocorrosive and protective behaviors of ZnO NRs in the borate and carbonate solutions.

Side-chain conformations in the isomorphous polyfluorinated {4,4'-bis[(2,2-difluoroethoxy)methyl]-2,2'-bipyridine-κ2N,N'}dichloridopalladium and -platinum complexes.

The polyfluorinated title compounds, [MCl2(C16H16F4N2O2)] or [4,4'-(HCF2CH2OCH2)2-2,2'-bpy]MCl2 [M = Pd, (1), and M = Pt, (2)], have -C(Hα)2OC(Hß)2CF2H side chains with H-atom donors at the α and ß sites. The structures of (1) and (2) are isomorphous, with the nearly planar (bpy)MCl2 molecules stacked in columns. Within one column, π-dimer pairs alternate between a π-dimer pair reinforced with C-H...Cl hydrogen bonds (α,α) and a π-dimer pair reinforced with C-Hß...F(-C) interactions (abbreviated as C-Hß...F-C,C-Hß...F-C). The compounds [4,4'-(CF3CH2OCH2)2-2,2'-bpy]MCl2 [M = Pd, (3), and M = Pt, (4)] have been reported to be isomorphous [Lu et al. (2012). J. Fluorine Chem. 137, 54-56], yet with disorder in the fluorous regions. The molecules of (3) [or (4)] also form similar stacks, but with alternating π-dimer pairs between the (α,ß; α,ß) and (ß,ß) forms. Through (C-)H...Cl hydrogen-bond interactions, one molecule of (1) [or (2)] is expanded into an aggregate of two inversion-related π-dimer pairs, one pair in the (α,α) form and the other pair in the (C-Hß...F-C,C-Hß...F-C) form, with the plane normals making an interplanar angle of 58.24 (3)°. Due to the demands of maintaining a high coordination number around the metal-bound Cl atoms in molecule (1) [or (2)], the ponytails of molecule (1) [or (2)] bend outward; in contrast, the ponytails of molecule (3) [or (4)] bend inward.