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Objectives Circulating miRNAs have been reported to have potential in detecting various diseases. However, few studies explored differentially expressed miRNAs in plasma of patients with pulmonary embolism (PE). Our study is to identify plasma miRNAs which can serve as potential biomarkers of PE. Materials and methods Exiqon miRCURY Ready-to-Use PCR Human panel I + II V1.M was conducted to identify differently expressed miRNAs in pooled plasma samples of PE patients compared with normal controls. Expressions of identified miRNAs were assessed in 37 PE patients as well as matched normal individuals followed by validation on six Beagle dogs by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results Twelve miRNAs were identified from the screening phase. Moreover, miR-134, previously reported related with PE, and hypoxia-induced miR-210 were also submitted to the validation phase. Only miR-28-3p was found significantly elevated in the plasma of PE patients. Compared with the level of plasma miR-28-3p of the dogs before PE, the elevated miR-28-3p did not alter significantly at 1, 2, 4 and 6 h after PE. The area under the receiver operating characteristic (ROC) curve of plasma miR-28-3p was 0.792 (95% confidence interval: 0.689–0.896). KEGG pathway analysis showed that miR-28-3p might involve in PE related pathways such as inositol phosphate metabolism and phosphatidylinositol signaling system. Conclusion Our study indicated that elevated plasma miR-28-3p could be used as a non-invasive and stable biomarker in the detection of PE. Further researches on the miRNA are warranted. [ABSTRACT FROM AUTHOR]

Cholestasis caused by bile secretion and excretion disorders is a serious manifestation of liver disease. With limited treatment methods, it affects millions of people worldwide. Huangqi decoction (HQD), an effective traditional Chinese medicine, is used to treat chronic cholestatic liver diseases. However, the action mechanisms of it were not fully elucidated. We aim to investigate the therapeutic effect of HQD, and its active component, astragalosides, against α-naphthylisothiocyanate (ANIT)-induced cholestasis in rats based on targeted metabolomics analysis and revel the potential mechanism. The therapeutic effect of HQD and astragalosides on ANIT-induced cholestasis model rats were evaluated by serum biochemical analysis. Liver damage was identified by histopathology. The levels of bile acids (BAs) and free fatty acids (FFAs) in serum and liver tissues were measured by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQMS). qRT-PCR and Western blot analysis were used to measure the expression of nuclear hormone receptor, membrane receptor and BA transporter protein in cholestatic rats before and after HQD and astragalosides treatment. The obtained data showed that the administration of ANIT caused obvious cholestasis with significantly increased intrahepatic retention of hydrophobic BAs and altered FFAs, which were consistent with the liver histopathological and serum biochemical findings. HQD and astragalosides treatment were able to attenuate ANIT-induced BAs and FFAs perturbation, ameliorate the impaired liver function, histopathological ductular reaction, and lipid peroxidation damage by ANIT. Elevated mRNA and protein expression of transporters related to BA metabolism and genes related to lipogenesis and lipid oxidation metabolism in cholestasis were attenuated or normalized by HQD and astragalosides treatment. Intervention by ANIT can significantly change the homeostasis of BAs and FFAs. HQD and astragalosides exerted a hepatoprotective effect against cholestatic liver injury by restoring the altered BA and FFA metabolism through the improvement of BA transporter, nucleus hormone receptor, and membrane receptor. Image 1 [ABSTRACT FROM AUTHOR]

Gut microbiome dysbiosis is closely associated with cholestatic liver disease. Huangqi decoction (HQD), a traditional herbal formula, has protection against cholestatic liver injury. However, the effect of HQD on gut microbiome remains unknown. To investigate the effect of HQD on 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) induced cholestatic liver injury and its effect on the gut microbiome profiles. Mice with DDC-induced cholestatic liver injury were treated with low and high doses of HQD for 8 weeks. Fecal samples were analyzed by 16 S ribosomal DNA sequencing. Barrier function as well as intestinal and hepatic inflammation was analyzed by real-time PCR and western blotting. HQD treatment ameliorated the DDC-induced liver injury and collagen deposition around hepatic bile ducts. Moreover, decreased diversity, reduced richness, and abnormal composition of intestinal microbiota of cholestatic mice were remarkably attenuated by HQD supplementation. Differences in bacterial abundance, including levels of Prevotellaceae_NK3B31_group , Alistipes , and Gordonibacter , were increased in DDC-induced mice, as compared with control mice, and were decreased after HQD treatment. Moreover, intestinal dysbiosis promoted disruption of the intestinal barrier in cholestatic mice. However, HQD treatment alleviated intestinal barrier dysfunction. Importantly, increased hepatic expression of pro-inflammatory factors and the NLRP3 inflammasome, which have a positive correlation with differential bacteria, were characteristics found in DDC-induced cholestatic mice that were alleviated upon treatment with HQD. HQD treatment alleviated gut microbiota dysbiosis, ameliorated the intestinal barrier dysfunction, inhibited liver inflammation, and protected against DDC-induced cholestatic liver injury. Image 1 [ABSTRACT FROM AUTHOR]