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Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.
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Neointimal hyperplasia after vascular injury is a representative complication of restenosis. Endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) is involved in the pathogenesis of vascular intimal hyperplasia. PARP16, a member of the poly(ADP-ribose) polymerases family, is correlated with the nuclear envelope and the ER. Here, we found that PERK and IRE1
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OBJECTIVE:To study the protective effects and the mechanism of Rabdosia serra water extract(RWE)on hepatic fibrosis(HF)induced by carbon tetrachloride(CCl4)in rats. METHODS:Sixty male SD rats were randomly divided into normal group,model group,colchicine group(0.12 mg/kg),and RWE low-dose,medium-dose and high-dose groups(4,8,16 g/kg,by crude drug),with 10 rats in each group. Except for intraperitoneal injection of olive oil for normal group,other groups were given 40% CCl4olive oil solution intraperitoneally to induce HF model. Since the first day of modeling,each treatment group was given relevant medicine (10 mL/kg) intragastrically, while normal group and model group were given constant volume of water intragastrically,once a day,for consecutive 6 weeks. After medication,biochemical process or ELISA were used to determine the contents of ALT,AST,HA,LN,PCⅢ and Ⅳ-C in serum,the activities or contents of SOD,GSH-Px,MDA,TNF-α,IL-6 and IL-1β in liver tissue. Pathological changes of liver tissue in rats were observed by HE staining. The expression of α-SMA and TGF-β1 in liver tissue were detected by Western blot. RESULTS:Compared with normal group,the contents of ALT,AST,LN,HA,PCⅢ and Ⅳ-C in serum,the contents of MDA,TNF-α,IL-6 and IL-1β in liver tissue were all increased significantly in model group (P＜0.01);the activities of SOD and GSH-Px in liver tissue were decreased significantly(P＜0.01). Liver fibrosis was obvious, and the relative expression of α-SMA and TGF-β 1were increased significantly (P＜0.01). Compared with model group,the contents of ALT,AST,HA,LN,PCⅢ and Ⅳ-C in serum as well as the contents of MDA,TNF-α and IL-6 in liver tissue in colchicines group and RWE groups,the contents of IL-1 β in liver tissue of rats in colchicines group,RWE medium-dose and high-dose groups were all decreased significantly (P＜0.05 or P＜0.01). The activities of SOD and GSH-Px in liver tissue of rats were increased significantly in colchicines group and RWE groups(P＜0.05 or P＜0.01). The fibrosis degree of liver tissue was significantly reduced, while the relative expression of α-SMA and TGF-β 1decreased significantly (P＜0.01). CONCLUSIONS:RWE can protect CCl4-induced HF model rats,the mechanism of which may be associated with regulating lipid metabolism,relieving liver lipid peroxidation injury and anti-oxidative stress response,inhibiting the release of inflammatory factors and the expression of TGF-β1.
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Aim To investigate metabolomic profiles of acute myocardial ischemia (AMI) in rat plasma and explore the intervention effects and its mechanism of leonurine using a metabolomics approach based on nuclear magnetic resonance (NMR).Methods The plasma metabolomic characteristics in rats of sham group,AMI model group,and leonurine-treated group were detected by 1H NMR,and the different metabolites between AMI group and sham group or leonurine-treated group were analyzed by pattern recognition and multivariate data analysis.Results Orthogonal partial least squares discriminant analysis (OPLS-DA) demonstrated that six metabolites related to AMI were screened out,including alanine,lysine,glycine,creatine,N-acetyl glycoprotein,and O-acetyl glycoprotein and all their levels were elevated in AMI group compared to sham group.Treatment of leonurine decreased the levels of alanine,lysine,and glycine,and increased the levels of choline,phosphocholine,and scyllo-inositol compared with the model group.Conclusions Leonurine can improve amino acid metabolism disorder under AMI conditions and enhance the function of choline and inositol pathway,which may explain its cardioprotective effect.The developed metabolomics approach in this study is a powerful tool for the investigation of the cardioprotective effect of leonurine and provide a new insight to understand its pharmacological mechanism.
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Objective To develop a liquid chromatography-mass spectrometry (LC-MS) method for the determination of S-allyl-L-cystein in extraction of garlic. Methods A LC-MS method was established on a ZORBAX Eclipse XDB-C8(4.6 mm×250 mm, 5 μm)column with the mobile phase consisting of 1‰ formic acid water-methanol (95:5), flow rate of 0.8 mL/min and detection with post-column splitting. The split ratio was 2:1, column temperature was set at 25 ℃. The mass spectrometer equipped with ESI and the ion source was operated in negative mode. The dry gas flow was 10.0 L/min, the nebulizer pressure was 30 psig, and the vaporizer temperature was 350 ℃. SIM detector, S-allyl-L-cystein m/z 160 and S-allyl-L-cystein sulfoxide m/z 176. Results The calibration curves showed good linearity in the range of 0.062 5-2 μg/mL of S-allyl-L-cystein. The detection limit was 0.01 μg/mL. The within-day RSD was 4.11% and the day-to-day RSD was 4.49%.The average recovery for S-allyl-L-cystein was 101.63%. Conclusions The method is simple and accurate. It is adapted to determine and analyze S-allyl-L-cystein in extraction of garlic and the average content of S-allyl-L-cystein is 0.514 μg/mg.