BACKGROUND Ralstonia is a Gram-negative non-fermentative bacterium widespread in nature,and includes four species,Ralstonia pickettii,Ralstonia solanacearum,Ralstonia mannitolilytica,and Ralstonia insidiosa,which were...BACKGROUND Ralstonia is a Gram-negative non-fermentative bacterium widespread in nature,and includes four species,Ralstonia pickettii,Ralstonia solanacearum,Ralstonia mannitolilytica,and Ralstonia insidiosa,which were proposed in 2003.Ralstonia is mainly found in the external water environment,including municipal and medical water purification systems.This bacterium has low toxicity and is a conditional pathogen.It has been reported in recent years that infections due to Ralstonia are increasing.Previous studies have shown that most cases of infection are caused by Ralstonia pickettii,a few by Ralstonia mannitolilytica,and infections caused by Ralstonia insidiosa are rare.CASE SUMMARY A 2-year-old Chinese child suffered from intermittent fever and cough for 20 d and was admitted to hospital with bronchial pneumonia.Bronchoscopy and alveolar lavage fluid culture confirmed Ralstonia insidiosa pneumonia.The infection was well controlled after treatment with meropenem and azithromycin.CONCLUSION Ralstonia infections are increasing,and we report a rare case of Ralstonia insidiosa infection in a child.Clinicians should be vigilant about Ralstonia infections.展开更多
Objective： Yes Associated Protein （YAP） is a downstream effector that negatively regulated by Hippo kinase LATS1/2. As a transcriptional coactivator, YAP controls the transactivation of variety target genes to prom...Objective： Yes Associated Protein （YAP） is a downstream effector that negatively regulated by Hippo kinase LATS1/2. As a transcriptional coactivator, YAP controls the transactivation of variety target genes to promote cell proliferation which is a critical survival input for cancer cells, thus the inhibition of YAP function is a promising strategy to treat cancer patients. The aim of this study was to explore YAP inhibitors derived from natural products using a cell-based YAP-TEADs luciferase reporter assay and investigate the functional activities of the novel inhibitor. Methods： natural compounds were used by 8×GTIIC luciferase reporter assay to screen YAP inhibitor. Phosphorylation of YAP and AMPK were detected by Western Blotting. The target genes of YAP were determined through RT-PCR. Inhibition on HepG2 cells of screened compounds were assessed by the Sulforhodamine B （SRB） assay. Results： we found that Shikonin （derived from the traditional Chinese medical herb Zicao （Lithospermum erythrorhizon）） exerted significant suppression against the transcriptional activity of YAP （inhibition ratio=74.3%）, accompanied with increased phosphorylation of YAP protein upon within short-exposure to cancer cells. Shikonin treated on HepG2 induced phosphorylation of AMPK. In HepG2 cell lines, Shikonin exhibited a profound cytotoxicity in a concentration manner. Conclusion： our results indicated that the inhibition activity of Shikonin on YAP function was probably due to the activation of AMPK by phosphorylation. Moreover, Shikonin exhibited potent cytotoxicity on cancer cells. In summary, the present study identifies Shikonin as a novel natural inhibitor of YAP function and could be an anti-cancer drug candidate for cancer treatment.展开更多
文摘BACKGROUND Ralstonia is a Gram-negative non-fermentative bacterium widespread in nature,and includes four species,Ralstonia pickettii,Ralstonia solanacearum,Ralstonia mannitolilytica,and Ralstonia insidiosa,which were proposed in 2003.Ralstonia is mainly found in the external water environment,including municipal and medical water purification systems.This bacterium has low toxicity and is a conditional pathogen.It has been reported in recent years that infections due to Ralstonia are increasing.Previous studies have shown that most cases of infection are caused by Ralstonia pickettii,a few by Ralstonia mannitolilytica,and infections caused by Ralstonia insidiosa are rare.CASE SUMMARY A 2-year-old Chinese child suffered from intermittent fever and cough for 20 d and was admitted to hospital with bronchial pneumonia.Bronchoscopy and alveolar lavage fluid culture confirmed Ralstonia insidiosa pneumonia.The infection was well controlled after treatment with meropenem and azithromycin.CONCLUSION Ralstonia infections are increasing,and we report a rare case of Ralstonia insidiosa infection in a child.Clinicians should be vigilant about Ralstonia infections.
基金This work was supported National Key R＆D Program of China （No. 2017YFE0102200）, National Natural Science Foundation for Distinguished Young Scholar of China （81625024） and National Natural Science Foundation of China （81773753） to B. Yang.
文摘Objective： Yes Associated Protein （YAP） is a downstream effector that negatively regulated by Hippo kinase LATS1/2. As a transcriptional coactivator, YAP controls the transactivation of variety target genes to promote cell proliferation which is a critical survival input for cancer cells, thus the inhibition of YAP function is a promising strategy to treat cancer patients. The aim of this study was to explore YAP inhibitors derived from natural products using a cell-based YAP-TEADs luciferase reporter assay and investigate the functional activities of the novel inhibitor. Methods： natural compounds were used by 8×GTIIC luciferase reporter assay to screen YAP inhibitor. Phosphorylation of YAP and AMPK were detected by Western Blotting. The target genes of YAP were determined through RT-PCR. Inhibition on HepG2 cells of screened compounds were assessed by the Sulforhodamine B （SRB） assay. Results： we found that Shikonin （derived from the traditional Chinese medical herb Zicao （Lithospermum erythrorhizon）） exerted significant suppression against the transcriptional activity of YAP （inhibition ratio=74.3%）, accompanied with increased phosphorylation of YAP protein upon within short-exposure to cancer cells. Shikonin treated on HepG2 induced phosphorylation of AMPK. In HepG2 cell lines, Shikonin exhibited a profound cytotoxicity in a concentration manner. Conclusion： our results indicated that the inhibition activity of Shikonin on YAP function was probably due to the activation of AMPK by phosphorylation. Moreover, Shikonin exhibited potent cytotoxicity on cancer cells. In summary, the present study identifies Shikonin as a novel natural inhibitor of YAP function and could be an anti-cancer drug candidate for cancer treatment.
