The methodology of science and technology is a theory concerning general scientific and technical research methods, and its essence belongs to the category of understanding and thinking. Through the study of science a...The methodology of science and technology is a theory concerning general scientific and technical research methods, and its essence belongs to the category of understanding and thinking. Through the study of science and technology methodologies and approaches on the general process of scientific research and technology research, one can grasp the mainstream of modern scientific thinking pattern and means, helping to solve the general regular problems of scientific and technological research. Starting from modern science and technology point of view, this article elaborated the impact of modern scientific progress had on the development of philosophical anthropology from different angles.展开更多
Post-translational modifications(PTMs)regulate the activity and functionality of RELA,but their role in the pathogenesis of liver fibrosis is unclear.This study was performed to understand the regulation mechanism of ...Post-translational modifications(PTMs)regulate the activity and functionality of RELA,but their role in the pathogenesis of liver fibrosis is unclear.This study was performed to understand the regulation mechanism of acetylation of RELA on liver inflammation and fibrosis in a model animal of innate glucose intolerance,largemouth bass,and to provide a potential target and biomarker for liver fibrosis therapy.We found that the acetylation of total proteins and RELA was significantly reduced in fibrotic livers of largemouth bass induced by a high-carbohydrate and high-fat diet(HCHFD)and CCL4 challenge.Furthermore,quantitative acetylome data showed that the K119 site of RELA was deacetylated in fibrotic livers compared to healthy controls.Subsequently,we reveal a new mechanism that SIRT7 deacetylates RELA at the K119 site in largemouth bass.RELA K119 deacetylation enhances RELA transcriptional activity by increasing its DNA-binding activity,and facilitates nuclear translocation of RELA,resulting in the overwhelming release of proinflammatory factors,and subsequently enhancing liver inflammation and fibrosis.Pharmacological inhibition of SIRT7 using a specific inhibitor restores the decreased acetylation of RELA in vivo and in vitro,and reduces the transcriptional activity,nuclear localization of RELA and the expression of its target genes,which ultimately attenuates liver inflammation and fibrosis.These findings uncover a novel mechanism underlying liver fibrosis involving SIRT7-mediated deacetylation of RELA to activate the proinflammatory gene program,and thus provide important insights and biomarkers into the effective strategies for limiting liver inflammation and fibrosis.展开更多
文摘The methodology of science and technology is a theory concerning general scientific and technical research methods, and its essence belongs to the category of understanding and thinking. Through the study of science and technology methodologies and approaches on the general process of scientific research and technology research, one can grasp the mainstream of modern scientific thinking pattern and means, helping to solve the general regular problems of scientific and technological research. Starting from modern science and technology point of view, this article elaborated the impact of modern scientific progress had on the development of philosophical anthropology from different angles.
基金supported by National Natural Sci-ence Foundation of China(32273141,32202954,32172981)Beijing Natural Science Foundation(6232038).
文摘Post-translational modifications(PTMs)regulate the activity and functionality of RELA,but their role in the pathogenesis of liver fibrosis is unclear.This study was performed to understand the regulation mechanism of acetylation of RELA on liver inflammation and fibrosis in a model animal of innate glucose intolerance,largemouth bass,and to provide a potential target and biomarker for liver fibrosis therapy.We found that the acetylation of total proteins and RELA was significantly reduced in fibrotic livers of largemouth bass induced by a high-carbohydrate and high-fat diet(HCHFD)and CCL4 challenge.Furthermore,quantitative acetylome data showed that the K119 site of RELA was deacetylated in fibrotic livers compared to healthy controls.Subsequently,we reveal a new mechanism that SIRT7 deacetylates RELA at the K119 site in largemouth bass.RELA K119 deacetylation enhances RELA transcriptional activity by increasing its DNA-binding activity,and facilitates nuclear translocation of RELA,resulting in the overwhelming release of proinflammatory factors,and subsequently enhancing liver inflammation and fibrosis.Pharmacological inhibition of SIRT7 using a specific inhibitor restores the decreased acetylation of RELA in vivo and in vitro,and reduces the transcriptional activity,nuclear localization of RELA and the expression of its target genes,which ultimately attenuates liver inflammation and fibrosis.These findings uncover a novel mechanism underlying liver fibrosis involving SIRT7-mediated deacetylation of RELA to activate the proinflammatory gene program,and thus provide important insights and biomarkers into the effective strategies for limiting liver inflammation and fibrosis.
