In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands ...In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.展开更多
Ten-eleven translocation(TET)family proteins(TETs),specifically,TET1,TET2 and TET3,can modify DNA by oxidizing 5-methylcytosine(5mC)iteratively to yield 5-hydroxymethylcytosine(5hmC),5-formylcytosine(5fC),and 5-carbox...Ten-eleven translocation(TET)family proteins(TETs),specifically,TET1,TET2 and TET3,can modify DNA by oxidizing 5-methylcytosine(5mC)iteratively to yield 5-hydroxymethylcytosine(5hmC),5-formylcytosine(5fC),and 5-carboxycytosine(5caC),and then two of these intermediates(5fC and 5caC)can be excised and return to unmethylated cytosines by thymine-DNA glycosylase(TDG)-mediated base excision repair.Because DNA methylation and demethylation play an important role in numerous biological processes,including zygote formation,embryogenesis,spatial learning and immune homeostasis,the regulation of TETs functions is complicated,and dysregulation of their functions is implicated in many diseases such as myeloid malignancies.In addition,recent studies have demonstrated that TET2 is able to catalyze the hydroxymethylation of RNA to perform post-transcriptional regulation.Notably,catalytic-independent functions of TETs in certain biological contexts have been identified,further highlighting their multifunctional roles.Interestingly,by reactivating the expression of selected target genes,accumulated evidences support the potential therapeutic use of TETs-based DNA methylation editing tools in disorders associated with epigenetic silencing.In this review,we summarize recent key findings in TETs functions,activity regulators at various levels,technological advances in the detection of 5hmC,the main TETs oxidative product,and TETs emerging applications in epigenetic editing.Furthermore,we discuss existing challenges and future directions in this field.展开更多
基金supported by the National Science Foundation of China(82160647)Hainan Clinical Medical Research Center Project(LCYX202310)+1 种基金Hainan Provincial Major Science and Technology Projects(ZDKJ202004)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-023).
文摘In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.
基金This work was supported by the National Natural Science Foundation of China(32201229)Shanghai Pujiang Program(21PJ1409100)+1 种基金GuangCi Professorship Program of Ruijin Hospital Shanghai Jiao Tong University School of Medicine,Nanning Yongjiang Plan Program,the Science and Technology Commission of Shanghai Municipality(20JC1410100)Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20211801).We thank Nanning Jiuzhouyuan Biotechnology Co.Ltd.and Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases.
文摘Ten-eleven translocation(TET)family proteins(TETs),specifically,TET1,TET2 and TET3,can modify DNA by oxidizing 5-methylcytosine(5mC)iteratively to yield 5-hydroxymethylcytosine(5hmC),5-formylcytosine(5fC),and 5-carboxycytosine(5caC),and then two of these intermediates(5fC and 5caC)can be excised and return to unmethylated cytosines by thymine-DNA glycosylase(TDG)-mediated base excision repair.Because DNA methylation and demethylation play an important role in numerous biological processes,including zygote formation,embryogenesis,spatial learning and immune homeostasis,the regulation of TETs functions is complicated,and dysregulation of their functions is implicated in many diseases such as myeloid malignancies.In addition,recent studies have demonstrated that TET2 is able to catalyze the hydroxymethylation of RNA to perform post-transcriptional regulation.Notably,catalytic-independent functions of TETs in certain biological contexts have been identified,further highlighting their multifunctional roles.Interestingly,by reactivating the expression of selected target genes,accumulated evidences support the potential therapeutic use of TETs-based DNA methylation editing tools in disorders associated with epigenetic silencing.In this review,we summarize recent key findings in TETs functions,activity regulators at various levels,technological advances in the detection of 5hmC,the main TETs oxidative product,and TETs emerging applications in epigenetic editing.Furthermore,we discuss existing challenges and future directions in this field.
