Licochalcone A Potently Inhibits Tumor Necrosis Factor ␣- Induced Nuclear Factor-B Activation through the Direct Inhibition of IB Kinase Complex Activation

ABSTRACT Glycyrrhiza inflata has been used as a traditional medicine with anti-inflammatory activity; however, its mechanism has not been fully understood. Licochalcone A is a major and biogenetically characteristic chalcone isolated from G. inflata. Here, we found that licochalcone A strongly inhibited tumor necrosis (TNF)-␣-induced nuclear localization, DNA binding activity, and the transcriptional activity of nuclear factor-B (NF-B). Whereas licochalcone A had no effect on the recruitment of receptor-interacting protein 1 and IB kinase ␤ (IKK␤) to TNF receptor I by TNF-␣, it significantly inhibited TNF-␣-induced IB kinase complex (IKK) activation and inhibitor of nuclear factor-B degradation. It is interesting that we found that the cysteine residue at position 179 of IKK␤ is essential for licochalcone A-induced IKK inhibition, because licochalcone A failed to affect the kinase activity of the IKK␤ (C179A) mutant. In contrast, a structurally related compound, echinatin, failed to inhibit TNF-␣-induced IKK activation and NF-B activation, suggesting that the 1,1-dimethy-2-propenyl group in licochalcone A is important for the inhibition of NF-B. In addition, TNF-␣-induced expression of inflammatory cytokines CCL2/ monocyte chemotactic protein-1and CXCL1/KC was clearly inhibited by licochalcone A but not echinatin. Taken together, licochalcone A might contribute to the potent anti-inflammatory effect of G. inflata through the inhibition of IKK activation

小児がんの子どものQOL向上に関する事例研究 : アイソレーターを利用した支援の検証

小児科病棟に車椅子型アイソレーターが導入され,これにより,清潔隔離中の子どもがこれまでに実現できなかった外出や登校など,子ども本来の「ふつうの生活」を尊重しうる様々な取り組みが可能となった.今回,アイソレーターを利用した子どもの家族に対して面接調査を実施し,アイソレーターを利用した支援が小児がんの子どものQOL向上に繋がるかを検証した.その結果,(1)生活が拡大しその子どもらしい「ふつうの生活」に近づける.(2)発達課題の達成に繋がる.(3)子どもと家族の絆が深まる.(4)家族のQOL向上の一助となることが示唆された

Antiviral Effects of Geranylgeranylacetone: Enhancement of MxA Expression and Phosphorylation of PKR during Influenza Virus Infection

A cyclic polyisoprenoid compound, geranylgeranylacetone (GGA), has been used as antiulcer drug. GGA is also a potent inducer of heat shock proteins (HSPs). HSPs are considered to induce an antiviral effect; however, the detailed mechanism is unknown. To determine whether GGA might show antiviral activity and what the mechanism is, the effect of GGA against influenza virus (strain PR8) infection in vivo and in vitro was investigated. The results demonstrated that GGA treatment strongly suppressed the deleterious consequences of PR8 replication and was accompanied by an increase in HSP70 gene expression in mice. Results from in vitro analyses demonstrated that GGA significantly inhibited the synthesis of PR8-associated proteins and prominently enhanced expression of human myxovirus resistance 1 (MxA) followed by increased HSP70 transcription. Moreover, GGA augmented the expression of an interferon-inducible double-strand RNA-activated protein kinase (PKR) gene and promoted PKR autophosphorylation and concomitantly α subunit of eukaryotic initiation factor 2 phosphorylation during PR8 infection. It is proposed that GGA-induced HSP70 has potent antiviral activity by enhancement of antiviral factors and can clinically achieve protection from influenza virus infection

Knockdown of proteolipid protein 2 or focal adhesion kinase with an artificial microRNA reduces growth and metastasis of B16BL6 melanoma cells

Proteolipid protein 2 (PLP2) promotes the metastasis of B16F10 cells in an experimental metastasis model. However, the effect of PLP2 on spontaneous metastasis has yet to be demonstrated, and whether PLP2 may become a new therapeutic target for malignant tumors is as yet unknown. In this study, PLP2 or focal adhesion kinase (FAK) microRNA-based short hairpin RNAs (miRNAs) were used as target molecules to specifically reduce the expression of PLP2 or FAK in B16BL6 cells. In vitro, the knockdown of PLP2 or FAK significantly inhibited cell proliferation, adhesion, migration and invasion. In a spontaneous metastatic tumor model using a footpad injection, the knockdown of PLP2 or FAK markedly inhibited the proliferation of the primary tumor and prevented tumor cells from invading the popliteal lymph nodes. The results indicate that downregulation of PLP2 or FAK may improve outcomes of malignant tumor therapy