Sphingosine kinase 1 knockout alleviates hepatic ischemia/reperfusion injury by attenuating inflammation and oxidative stress in mice

Background: Hepatic ischemia/reperfusion(I/R) injury remains a significant problem in clinical practice. Sphingosine kinase 1(Sph K1) phosphorylates sphingosine to sphingosine-1-phosphate(S1 P) which participates in multiple bioactive processes. However, little is known about the role of Sph K1 in hepatic I/R injury. This study aimed to investigate the effect of Sph K1 knockout on liver I/R injury and to explore underlying mechanisms. Methods: Sph K1 knockout and wild type mice were subjected to 70% partial hepatic I/R. Serum alanine aminotransferase was determined to indicate the degree of liver damage. Hematoxylin-eosin staining and TUNEL assay were used to assess histological changes and hepatocellular apoptosis, respectively. Immunohistochemistry was performed to detect the expression and translocation of phosphorylated p65 and signal transducer and activator of transcription 3(STAT3). Western blotting was used to determine the expression of S1 P receptor 1(S1 PR1), phosphorylated p65 and STAT3. Real-time PCR was used to demonstrate the changes of proinflammatory cytokines. Oxidative stress markers were also determined through biochemical assays. Results: Sph K1 knockout significantly ameliorated I/R-induced liver damage, mitigated liver tissue necrosis and apoptosis compared with wild type control. I/R associated inflammation was alleviated in Sph K1 knockout mice as demonstrated by attenuated expression of S1 PR1 and reduced phosphorylation of nuclear factor kappa B p65 and STAT3. The proinflammatory cytokines interleukin-1 β, interleukin-6 and tumor necrosis factor-α were also inhibited by Sph K1 genetic deletion. The oxidative stress markers were lower in Sph K1 knockout mice after I/R injury than wild type mice. Conclusions: Knockout of Sph K1 significantly alleviated damage after hepatic I/R injury, possibly through inhibiting inflammation and oxidative stress. Sph K1 may be a novel and potent target in clinical practice in I/R-related liver injury.

SIRT1通过降低NF-kB p65表达减轻异烟肼致人肝细胞损伤的研究

目的探讨沉默信息调节因子1(SIRT1)在异烟肼致人肝细胞损伤中的作用。方法培养人正常肝细胞HL-7702,实验分为6组:空白对照组、异烟肼组、异烟肼+SIRT1激动剂组、SIRT1激动剂对照组、异烟肼+SIRT1抑制剂组、SIRT1抑制剂对照组。取各组细胞上清液测定丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)含量;实时荧光定量聚合酶链反应(q RT-PCR)检测肝细胞SIRT1、NF-k B p65 mRNA表达水平;酶联免疫吸附法(ELISA)检测SIRT1、核转录因子k B(NF-k B p65)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)蛋白表达水平。结果与空白对照组比较,异烟肼组细胞SIRT1的mRNA和蛋白表达下降(P<0.05),其下游靶基因NF-k B p65的mRNA和蛋白表达升高(P<0.05),炎症因子IL-6、TNF-α蛋白表达水平升高(P<0.05)。加入SIRT1激动剂可减轻异烟肼引起的炎症反应,加入SIRT1抑制剂可使NF-k B p65、IL-6、TNF-α表达水平进一步升高从而加重细胞的炎症损伤。结论异烟肼诱导肝细胞损伤过程中,降低SIRT1水平,增加炎症因子的表达。SIRT1的激活可以通过降低NF-k B p65表达进而减轻肝细胞损伤的发生。

A new alvarezsaurid dinosaur from the Late cretaceous Qiupa Formation of Luanchuan,Henan Province,central China

An alvarezsaurid dinosaur skeleton was discovered from the Late Cretaceous Qiupa Formation of Luanchuan,Henan Province of eenttral China.It represents a new alvarezsaurid dinosaur Qiupanykus zhangi gen.et sp.nov.A phylogenetic analysis recovers Qiupanykus nested within the unresolved clade,which includes Asian and north American taxa.The skeleton of the new specimen is preserved in association with eggshells.The eggshell morphologies show that these eggs belong to oviraptorid eggs,skeletal remains of which were discovered from the same area.The alvarezsaurid skeleton associated with eggshell fragments may indicate that these eggs were broken by the strong thumb-claws of the former and that alvarezsaurid dinosaurs may be egg-eaters.

Manufacturing and characterizing of CCTO/SEBS dielectric elastomer as capacitive strain sensors

Calcium copper titanate(CCTO)/polystyrenepolyethylene-polybutylene-poly styrene(SEBS)dielectric elastomers were prepared via blending method.A capacitive strain sensor using CCTO/SEBS as dielectric layer and polyaniline-dodecylbenzensulfonic acid(PANI-DB S A)/SEBS as electrodes was designed and manufactured by thermoforming process.X-ray diffractometer(XRD),scanning electron microscopy(SEM)and Raman spectra analyses were carried out;no impurities were found in the composite and CCTO particles were well dispersed.The dielectric tests showed that the samples filled with 20 wt%CCTO have their permittivity improved by 70%.The capacitive strain sensors have a stabilized capacitance variety range at different strain ranges or stretch speeds,and could remain synchronized after 500-time-stretching,showing high reproducibility.

Study on products and reaction paths for synthesis of 3,4-dihydro-2H-3-phenyl-1,3-benzoxazine from phenol,aniline and formaldehyde

To study the synthesis of 3,4-dihydro-2H-3-phenyl-1,3-benzoxazine(benzoxazine),the reaction paths of phenol,aniline and formaldehyde were investigated by analyzing the synthesis crude products.With the aid of high-performance liquid chromatography(HPLC),chromatographic column and preparative HPLC,seven compounds originated from the crude products were obtained and their chemical structures were elucidated.Possible reaction paths are proposed based on these compounds.Results show that Nhydroxymethyl aniline(HMA) derived from the reaction of formaldehyde and aniline is probably the key intermediate during the reaction.HMA can react with itself or other reactants to form other intermediates,such as 1,3,5-triphenyl-1,3,5-triazinane and 2-((phenylamino)methyl)phenol,and further form benzoxazine and byproducts.

The investigation of the stability of DNA-b-PPO vesicles formed through frame guided assembly

Frame-guided assembly is a novel assembly method which can control the shape and size of vesicles accurately. It has been reported that the DNA-b-PPO vesicles could be stable over two weeks. In this communication we have introduced restriction sites of EcoR1 in the interior DNA scaffold to the formed vesicles in order to further study their stability. Dynamic light scattering(DLS), transmission electron microscope(TEM) and fluorescence spectrum were used to characterize the digestion process. The final results revealed that the vesicles were still stable even after two weeks cultivated with EcoR1, which suggests potential in future biological applications.

Design and properties of calcium copper titanate/poly(dimethyl siloxane) dielectric elastomer composites

The high phase content of inorganic dielectric fillings will give a strong electric driving force and hard matrix. That is a contradiction in enhancing the electrodeformation of dielectric elastomers(DEs). Therefore, in this paper, by focusing on how to approach a balance between these and finding an effective way to tune the electric response of the DEs, the theoretical calculation and experimental investigation based on calcium copper titanate(CCTO)/poly(dimethyl siloxane)(PDMS) were carried out. It is found that CCTO with a smaller particle size shows a larger dielectric parameter. With smaller CCTO particle as the fillings, the fabricated elastomer composite would approach to a low modulus by a proper CCTO phase morphology in the matrix.

Design and preparation of highly crystalline K-intercalated W@PCN:an efficient material for aniline elimination

In this paper,we designed and prepared the polymeric carbon nitride-supported tungsten(W@PCN)materials.They were employed as the catalysts for photocatalytic oxidation of aniline in water.During the process,H_(2)O_(2)was initially generated via the PCN-catalyzed hydrophotolysis.Catalyzed by supported tungsten,aniline was oxidized by the in situ generated H_(2)O_(2)to obtain less toxicpoly aniline.