7篇
您的检索式：作者名="Stephen Tomlinson"
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| 1 | Complement C3 activation regulates the production of tRNA-derived fragments Gly-tRFs and promotes alcohol-induced liver injury and steatosis显示文摘Complement is known to play a role in alcoholic fatty liver disease (AFLD), but the underlying mechanisms are poorly understood, thereby constraining the development of a rational approach for therapeutic intervention in the complement system. C3 deficiency has been shown to impart protective effects against ethanol-induced hepatic steatosis and inflammation. Here we demonstrate a protection effect in wild-type mice by treatment with CR2-Crry, a specific inhibitor of C3 activation. The expression of glycine transfer (t) RNA-derived fragments (Gly-tRFs) is upregulated in ethanol-fed mice and inhibition of Gly-tRFs in vivo decreases chronic ethanol feeding-induced hepatosteatosis without affecting inflammation. The expression of Gly-tRF was downregulated in C3-deficient or CR2-Crry-treated mice, but not in C5-deficient mice;Gly-tRF expression was restored by the C3 activation products C3a or Asp (C3a-des-Arg) via the regulation of CYP2E1. Transcriptome profiling of hepatic tissues showed that Gly-tRF inhibitors upregulate the expression of sirtuin1 (Sirt1) and subsequently affect downstream lipogenesis and β-oxidation pathways. Mechanistically, Gly-tRF interacts with AGO3 to downregulate Sirt1 expression via sequence complementarity in the 3′ UTR. Notably, the expression levels of C3d, CYP2E1 and Gly-tRF are upregulated, whereas Sirt1 is decreased in AFLD patients compared to healthy controls. Collectively, our findings suggest that C3 activation products contribute to hepatosteatosis by regulating the expression of Gly-tRF. Complement inhibition at the C3 activation step and treatment with Gly-tRF inhibitors may be potential and precise therapeutic approaches for AFLD. | Fudi Zhong Zhigao Hu Keqing Jiang Biao Lei Zhan Wu Guandou Yuan Hongliang Luo Chunqiang Dong Bo Tang Chaowen Zheng Shuai Yang Yonglian Zeng Zhenya Guo Shuiping Yu Huizhao Su Guo Zhang Xiaoqiang Qiu Stephen Tomlinson Songqing He | 2019 | Cell Research2019，29，7： | 14 |
| 2 | A complement-dependent balance between hepatic ischemia/reperfusion injury and liver regeneration in mice显示文摘 | He Songqing Atkinson Carl Qiao Fei Cianflone Katherine Chen Xiaoping Tomlinson Stephen | 2009 | Journal of Clinical Investigation2009，，8： | 2 |
| 3 | Clashing metaphors about classroom teachers: toward a systematic typology for the language teaching field显示文摘 | Rebecca L Oxford Stephen Tomlinson Ana Barcelos Cassandra Harrington Roberta Z Lavine Amany Saleh Ana Longhini | 1998 | System1998，，1： | 1 |
| 4 | Enhancement of Concentration Limits of Detection in CE and CE-MS: A Review of On-line Sample Extraetion, Cleanup, Analyte Preconcentration, and Microreactor Technology显示文摘 | Tomlinson Andy J Guzman Norberto A Naylor Stephen | 1995 | Capillary Electrophoresis1995，2，6： | 1 |
| 5 | Edward Lee Thorndike and John Dewey on the Science of Education显示文摘 | Stephen Tomlinson | 1997 | Oxford Review of Education1997，，3： | 1 |
| 6 | Low penetrance breast cancer predisposition SNPs are site specific显示文摘 | Niall Mcinerney Gabrielle Colleran Andrew Rowan Axel Walther Ella Barclay Sarah Spain Angela M. Jones Stephen Tuohy Catherine Curran Nicola Miller Michael Kerin Ian Tomlinson Elinor Sawyer | 2009 | Breast Cancer Research and Treatment2009，，1： | 1 |
| 7 | Edward Lee Thorndike and John Dewey on the science of education 显示文摘 | Tomlinson Stephen | 1997 | Oxford Review of Education1997，23，3： | 1 |
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