Antihepatofibrotic Effects of Aqueous Extract of Prunella vulgaris on Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats.

Prunella vulgaris has been widely used in the folk medicine of Northeastern Asian countries for the treatment of acute liver injury and infectious hepatitis. In the present study, the protective effect of aqueous extract from P. vulgaris was investigated on carbon tetrachloride-induced hepatic fibrosis in vivo. Our data showed that the administration of aqueous extract from P. vulgaris at doses of 50, 100, and 200 mg/kg significantly reduced the elevated serum levels of alanine aminotransferase, aspartate aminotransferase, type III precollagen, and hyaluronic acid in rats with hepatic fibrosis. In addition, aqueous extract from P. vulgaris also reduced the incidence of liver lesions and the formation of fibrous septa, and remarkably decreased the serum levels of inflammatory cytokines, platelet derived growth factor, interleukin-4, interleukin-8, and tumor necrosis factor alpha. Furthermore, aqueous extract from P. vulgaris significantly inhibited the activation of hepatic stellate cells by regulating the expression of α smooth muscle actin, transforming growth factor ß 1, and smad2 and also decreased the deposition of extracellular matrix proteins via regulating the expressions of tissue inhibitor of metalloproteinase-1, matrix metalloproteinase-2,-13. Real-time polymerase chain reaction further revealed that post-treatment with aqueous extract from P. vulgaris decreased the elevated levels of miR-34a and miR-199a-5p in hepatic fibrosis rats. These results demonstrated that aqueous extract from P. vulgaris alleviates carbon tetrachloride-induced hepatic fibrosis by inhibiting the activation of hepatic stellate cells, promoting collagenolysis and regulating fibrosis-related microRNAs.

Nucleoporin 85 interacts with influenza A virus PB1 and PB2 to promote its replication by facilitating nuclear import of ribonucleoprotein.

Transcription and replication of the influenza A virus (IAV) genome take place in the nucleus of infected cells, which rely on host factors to aid viral ribonucleoprotein (vRNP) to cross the nuclear pore complex (NPC) and complete the bidirectional nucleocytoplasmic trafficking. Here, we showed that nucleoporin 85 (NUP85), a component of NPC, interacted with RNP subunits polymerase basic 1 (PB1) and polymerase basic 2 (PB2) in an RNA-dependent manner during IAV infection. Knockdown of NUP85 delayed the nuclear import of vRNP, PB1 and PB2, inhibiting polymerase activity and ultimately suppressing viral replication. Further analysis revealed that NUP85 assisted the binding of PB1 to nuclear transport factor Ran-binding protein 5 (RanBP5) and the binding of PB2 to nuclear transport factor importin α1 and importin α7. We also found that NUP85 expression was downregulated upon IAV infection. Together, our study demonstrated that NUP85 positively regulated IAV infection by interacting with viral PB1 and PB2, which may provide new insight into the process of vRNP nuclear import and a novel target for effective antivirals.

Transcriptome profiling and pathway analysis of hepatotoxicity induced by tris (2-ethylhexyl) trimellitate (TOTM) in mice.

Tris (2-ethylhexyl) trimellitate (TOTM) is commonly used as an alternative plasticizer for medical devices. But very little information was available on its biological effects. In this study, we investigated toxicity effects of TOTM on hepatic differential gene expression analyzed by using high-throughput sequencing analysis for over-represented functions and phenotypically anchored to complementary histopathologic, and biochemical data in the liver of mice. Among 1668 candidate genes, 694 genes were up-regulated and 974 genes were down-regulated after TOTM exposure. Using Gene Ontology analysis, TOTM affected three processes: the cell cycle, metabolic process and oxidative activity. Furthermore, 11 key genes involved in the above processes were validated by real time PCR. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these genes were involved in the cell cycle pathway, lipid metabolism and oxidative process. It revealed the transcriptome gene expression response to TOTM exposure in mouse, and these data could contribute to provide a clearer understanding of the molecular mechanisms of TOTM-induced hepatotoxicity in human.