ffect of Isorhamnetin against Influenza Fig 6. In vivo antiviral activity of isorhamnetin against influenza virus infection. The rate of loss in body weight of six-week-old female miceafter influenza A/PR/8/34 virus infection and isorhamnetin treatment, and Tamiflu was used as a positive anti-influenza material; P < 0.05. The survival rate in six-week-old female mice after influenza A/PR/8/34 virus infection and flavonoids treatment. P < 0.05. doi:10.1371/journal.pone.0121610.g006 17 / 21 Antiviral Effect of Isorhamnetin against Influenza Fig 7. Schematic diagram represents the detailed mechanism of isorhamnetin in its antiviral activity against influenza A virus. Isorhamnetin possesses potent direct or indirect anti-influenza activity via direct suppression of virus adsorption onto host cells and NA activity or indirect inhibition of the expression of influenza A surface proteins, virus-induced ROS generation and ERK phosphorylation, and the autophagic changes after influenza A virus infection. doi:10.1371/journal.pone.0121610.g007 Our study suggests that isorhamnetin is a natural compound with anti-influenza effects in vitro and in vivo via direct HA and NA inhibition, direct or indirect inhibition of the expression of viral HA and NA genes, and suppression of PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19763407 virus-induced autophagy, ROS generation, and ERK phosphorylation. ~~ Wnt signalling is a complex pathway involved in the regulation of a range of biological processes ranging from cell proliferation and differentiation to embryogenesis, tissue formation and regulation of stem cell niches . In humans Wnt proteins consist of a class of nineteen evolutionary conserved, glycosylated and lipid modified proteins each harbouring a cysteine rich domain . The primary receptor for Wnt ligands are the Frizzleds, a family of ten G-protein like 7- transmembrane spanning receptors. Frizzleds have an extended N-terminal region harbouring a cysteine rich domain which is required for Wnt reception . In Canonical Wnt/-catenin signalling, Wnt proteins interact with a receptor complex comprised of Frizzled /Low density lipoprotein receptor-related protein located on the cell membrane . When activated by Wnt ligands, LRP becomes phosphorylated at multiple sites. The activated Fz/LRP receptor complex recruits Axin to the cell membrane ; this causes the sequestration of several other intracellular proteins required for Wnt signalling modulation, including glycogen synthase kinase-3, Dishevelled and Adenomatous Polyposis Coli. In the absence of an external Wnt signal GSK-3, Dsh and APC form a destruction complex that regulates the cytoplasmic pool of the transcriptional regulator -catenin by successive phosphorylation which marks -catenin for proteasome degradation . In the presence of a Wnt signal the destruction complex dissociates and is deactivated; as a result active -catenin accumulates in the cytoplasm and nucleus. Nuclear -catenin acts as a transcriptional regulator and interacts with the lymphoid enhancer-binding factor 1/T-cell specific transcription PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19763404 factor family of transcription factors which bind to and activate Wnt DHA responsive genes with TCF/LEF binding sites. Human Mesenchymal Stem Cells are multipotent stem cells involved in bone and cartilage formation during development. As such, these cells are of great interest for orthopaedic tissue engineering . Wnt signalling has been shown to elicit different outcomes on cell fate depending on the cell type and Wnt concentration . Human MSC have
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