Andrographolide alleviates paraquat-induced acute lung injury by activating the Nrf2/HO-1 pathway.

Objectives: Paraquat (PQ), a highly effective and rapidly non-selective herbicide, mainly targets the lungs and causes acute lung injury (ALI). So far, the scarcity of effective drug candidates against PQ-induced ALI remains a big challenge. Andrographolide (Andro), with its anti-inflammatory and antioxidant activities, has been demonstrated to alleviate ALI. Nevertheless, whether Andro could alleviate the PQ-mediated ALI remains unknown. Therefore, this study will explore the effects as well as the possible mechanism of Andro against ALI caused by PQ. Materials and Methods: C57BL/6J mice were injected with 20 mg/kg PQ intraperitoneally to establish an ALI model. PQ-treated MLE-12 cells were applied to a vitro model. Nuclear factor erythroid like-2 (Nrf2) was knocked out to explore the specific effects of the Nrf2/ Heme oxygenase-1 (OH-1) pathway in the protection of Andro against ALI caused by PQ. Results: Andro significantly reduced lung damage and the ratio of Wet/Dry (W/D) weight, decreased MDA, IL-6, IL-1ß, and TNF-ɑ levels, reversed the decrease of CAT and SOD levels, and inhibited apoptosis caused by PQ. Andro obviously increased the ratio of Bcl-2/Bax while reducing caspase-3 and cleaved caspase-3 levels. Furthermore, Andro dramatically elevated the antioxidant proteins Nrf2, NQO-1, and HO-1 levels compared with the PQ group. This experiment demonstrated that Andro reduced ROS and inhibited apoptosis, induced by PQ in MLE-12 cells, by inducing Nrf2/HO-1 pathway activation. Conclusion: Andro effectively ameliorates oxidant stress and apoptosis in ALI caused by PQ, possibly through inducing Nrf2/HO-1 pathway activation.

Homogeneous preparation of water-soluble products from chitin under alkaline conditions and their cell proliferation in vitro.

The purpose of this study was to prepare water-soluble products by homogeneous depolymerization of chitin with H2O2 under alkaline conditions and investigate their potential application in wound healing. For the first time, water-soluble products were successfully prepared using a chitin-NaOH/urea solution; the products were chitosans with molecular weights (Mw) of 3.48-33.5 kDa and degrees of deacetylation (DD) > 0.5. Their Mw, DD and yield were affected by the reaction temperature, reaction time, concentration of H2O2 and chitin DD. The deacetylation and depolymerization of chitin were achieved simultaneously. The depolymerization of chitin was caused by hydrogen abstraction of HO, whereas the deacetylation resulted from the cleavage of amide bonds by HO- and HO2-, although the latter played a more important role. All water-soluble chitosans markedly promoted the proliferation of human skin fibroblast (HSF) cells, but they inhibited the proliferation of human keratinocyte cells. For the proliferation of HSF, a low concentration of chitosans was important. In addition, water-soluble chitosans with an Mw of 3.48-16.4 kDa markedly stimulated the expression of growth factors such as PDGF and TGF-ß by macrophages. Water-soluble chitosans could be used as a potential active component in wound dressings.

Improvement of Astragalin on Spermatogenesis in Oligoasthenozoospermia Mouse Induced by Cyclophosphamide.

More than 40% of infertile men are diagnosed with oligoasthenozoospermia and the incidence is still rising, but the effective treatments are not been found until now. Astragalin, one of the main active ingredients in traditional Chinese medicine, may be effective in the treatment of oligoasthenozoospermia. This study investigated the pharmacological effects of astragalin for treatment of oligoasthenozoospermia in male mice, induced by cyclophosphamide (CTX). Male mice were intraperitoneally injected by CTX (50 mg/kg), and astragalin (30 mg/kg) was given via oral gavage once daily. RNA-seq analysis highlighted astragalin upregulated gene expression of anti-apoptosis (AKT1and BCL2-XL), cell proliferation (ETV1, MAPKAPK2, and RPS6KA5) and synthesis of testosterone (STAR, CYP11A1, and PRKACB), but downregulated gene expression of cell apoptosis (BAD, BCL-2, CASPASE9, and CASPASE3) in mouse testis. Astragalin also significantly reversed the reduction in body weight, reproductive organs index, and sperm parameters (sperm concentration, viability, and motility) induced by CTX, and restored testicular abnormal histopathologic morphology induced by CTX. Furthermore, astragalin dramatically rescued the gene expression related to spermatogenesis (AKT1, BCL-2, CASPASE9, CASPASE3, MAPKAPK2, RPS6KA5, STAR, and PRKACB), and increased the level of testosterone by improving related proteins (STAR, CYP11A1, PRKACB) for oligoasthenozoospermia induced by CTX. In conclusion, astragalin may be a potential beneficial agent for oligoasthenozoospermia by increasing the testosterone levels in testis.

Polymerization mechanism of natural lacquer sap with special phase structure.

Lacquer sap is a water-in-oil natural emulsion with high viscosity. In nature, it exudes from the phloem of lacquer tree to repair its wounds in the presence of O2. So far, it is unclear how rapid and smooth polymerization of urushiol is achieved in such a viscous sap. Here, we find that there is a diffuse interface layer with 2.43 nm of thickness between two phases. The interface layer consists of urushiol, urushiol-laccase complex, urushiol-stellacyanin complex and water-insoluble glycoprotein. Polymerization of urushiol is realized by multicomponent synergistic effect. Radicals are first formed by laccase-catalyzed oxidation of urushiol at the interface layer, then are transferred to the urushiol oil phase via wate-insoluble glycoprotein and initiate the polymerization of urushiol there. Stellacyanin inhibits the formation of certain radicals and controls the concentration of phenoxy radicals at the interface layer. Through the inhibition of radicals by stellacyanin and the electron transfer mediated by water-insoluble glycoprotein, the polymerization of urushiol at the interface layer is inhibited. This ensures that O2 can continuously penetrate into the aqueous phase to oxidize the reduced laccase so that the urushiol polymerization can continue smoothly. This polymerization mechanism provides an idea for developing new chemical reaction systems.

Prognostic Value of Quantitative Perfusion Parameters by Enhanced Ultrasound in Endometrial Cancer.

BACKGROUND Tumor perfusion is significantly associated with the development and aggressiveness of endometrial cancer. The aim of this study was to assess the prognostic value of quantitative perfusion parameters measured by contrast-enhanced ultrasonography (CEUS) in endometrial cancer before surgery. MATERIAL AND METHODS A total of 223 patients with endometrial cancer were included between 1 May 1 2013 and 1 May 1 2017 for preoperative CEUS. The mean enhancement rate (ER) was calculated as enhancement intensity (EI)/rise time (RT) results from time­intensity curve (TIC) during CEUS. After a mean follow-up of 33.5±9.9 months, the correlation of ER and postoperative overall survival (OS) and disease-free survival (DFS) was analyzed using univariate and multivariate analysis. RESULTS The optimal cutoff ER value predicting survival based on the ROC curve was 1.8 dB/s. Kaplan-Meier univariate analysis demonstrated that a patient with a high ER level had worse DFS and OS than those with a low ER (DFS, P<0.01; OS, P<0.05). In multivariate analysis, ER was confirmed as an independent predictor for both recurrence (HR, 1.68; 95% CI: 1.01-7.73) and OS (HR, 1.98; 95%CI: 1.01-7.83) for patients with endometrial cancer (both P<0.05). CONCLUSIONS Perfusion variables measured by CEUS are significantly useful predictive factor for postoperative survival in endometrial cancer.