ABSTRACT
A novel pair of Z/E isomeric compounds with unprecedented carbon skeleton were isolated from an aqueous extract of Aspongopus chinensis Dallas by macroporous resin, silica gel, and semi-preparative high performance liquid chromatography (HPLC). Their structures were identified by nuclear magnetic resonance (NMR), Infrared spectroscopy (IR), Mass spectroscopy (MS) and other spectroscopic methods as (Z)-3-(but-1″-en-1″-yl)-1-(2ʹ-hydroxyethyl)-4-propylpyridin-1-ium, namely aspongopyridine A, and (E)-3-(but-1″-en-1″-yl)-1-(2ʹ-hydroxyethyl)-4-propylpyridin-1-ium, namely aspongopyridine B, respectively. Besides, the anti-inflammatory, anti-tumor, acetylcholinesterase inhibition and butyrylcholinesterase inhibition activities of the compounds 1 and 2 were evaluated. The results showed that compounds 1 and 2 have no anti-inflammatory, anti-tumor, and butyrylcholinesterase inhibition activities instead of weak acetylcholinesterase inhibition activity.
ABSTRACT
Aim To investigate the effects of acid sphingomyelinase(ASMase)on high-fat induced nonalcoholic fatty liver disease in mice and its regulation of PPARα- PGC-1α pathway. Methods ASMase knockout mice based on C57BL/6 background were constructed. Closed group heterozygotes were obtained through hybridized with wild-type mice(ASMase+/-),together with the littermate WT mice were prepared for NAFLD model in this study. The experiment was divided into four groups:WT+Chow:the WT mice were fed with normal diet for 12 weeks; WT+HFD:the WT mice were fed with high-fat diet for 12 weeks; ASMase+/-+Chow:the ASMase+/- mice were fed with normal diet for 12 weeks; ASMase+/- +HFD:the ASMase+/- mice were fed with high fat diet for 12 weeks. Biochemical method was used to detect serum TC,TG and liver TC,TG contents and liver function such as ALT and AST. Oil red staining,HE staining,Masson staining and Sirius red staining were performed to detect liver lipid accumulation,hepatocyte morphology and liver fibrosis. AmplexTM red sphingomyelinase kit was applied to detect ASMase activity. Western blot was performed to detect protein expressions of ASMase,PPARα,PGC-1α and CPT1. Results WT+HFD group displayed hypercholesterolemia and liver dysfunction. Levels of liver triglyceride(TG)were significantly higher than those in WT+Chow group(P<0.05 or P<0.01). Meanwhile,the hepatocytes showed marked steatosis,balloon-like changes,and fibrosis. Protein expression and activity of ASMase in liver increased significantly(P<0.01 or P<0.001),whereas CPT1,PPARα and PGC-1α expressions were not statistically significant compared with matched control group. Heterozygously ASMase-deficient mice reduced the elevated liver TG induced by HFD,as well as improving balloon-like changes and liver fibrosis. Furthermore,the expressions of PPARα,PGC-1α and CPT1 were up-regulated in ASMase+/- +HFD mice compared with WT+Chow group.Conclusions ASMase promotes hepatic steatosis and fibrosis,which may be related to its inhibition of PPARα-PGC-1α pathway.
ABSTRACT
<p><b>OBJECTIVE</b>The relationship between stroke/thromboembolic events (TEs) and bleeding as well as age-related risk factors are not fully clear in elderly patients with atrial fibrillation (AF). This study aimed to evaluate the clinical features, incidence and risk factors of stroke and bleeding in elderly AF patients.</p><p><b>METHOD</b>A total of 220 elderly AF patients [mean age (83.1 ± 0.6) years] were followed for (3.2 ± 0.8) years. The CHA(2)DS(2)-VASc score, the HAS-BLED score, annual major bleeding risk and the annual stroke were analyzed.</p><p><b>RESULT</b>The CHA(2)DS(2)-VASc score in patients with 65-79, 80-89 and ≥ 90 years old groups were 2.9 ± 0.2, 5.2 ± 0.2 and 5.6 ± 0.2, respectively (P < 0.001) and the HAS-BLED score were 2.1 ± 0.1, 3.2 ± 0.1 and 3.6 ± 0.1, respectively (P < 0.001), both significantly increased with aging. The annual major bleeding risk increased similarly as the annual stroke risk in the very elderly AF patients (patients 80-89 years old: bleeding risk 3.7 %, stroke risk 6.7 %; patients ≥ 90 years old: 8.7 % and 9.8 %, respectively). The combination of CHA(2)DS(2)-VASc and HAS-BLED could identify those patients with high risk for stroke and bleeding correctly. Twelve (5.5%) patients experienced "bidirectional events" (concomitant TE and haemorrhage), of whom 9 (75.0 %) suffered recurrent TEs.</p><p><b>CONCLUSION</b>The bleeding risk increased similarly as the thromboembotic risk with increasing age in the elderly AF patients, "bidirectional events" is not common but related with worse outcome in elderly AF patients.</p>