目的·探讨中国汉族人群突触小体相关蛋白(synaptosomal-associated protein of 25000,SNAP25)基因与精神分裂症(schizophrenia,SZ)的相关性。方法·采用TaqMan探针基因分型技术对434例SZ患者(病例组)和432例健康对照(对照组)的...目的·探讨中国汉族人群突触小体相关蛋白(synaptosomal-associated protein of 25000,SNAP25)基因与精神分裂症(schizophrenia,SZ)的相关性。方法·采用TaqMan探针基因分型技术对434例SZ患者(病例组)和432例健康对照(对照组)的SNAP25基因5个单核苷酸多态性(single nucleotide polymorphism,SNP)位点(rs3746544、rs8636、rs362998、rs6039769、rs6077690)进行分型,比较病例组与对照组间的等位基因、基因型,不同遗传模式下基因型以及单倍型频率分布的差异。结果·rs362998和rs6039769等位基因频率分布在病例组与对照组之间差异有统计学意义(P=0.029,P=0.033),经Bonferroni校正后,差异均无统计学意义(均P>0.05);病例组与对照组间rs362998和rs3746544基因型分布的差异具有统计学意义(P=0.005,P=0.043),校正后rs362998差异仍有统计学意义(P=0.025),rs3746544差异无统计学意义(P>0.05)。rs362998位点在共显性和显性遗传模式下,基因型分布组间比较,差异有统计学意义(均P=0.003),校正后差异仍有统计学意义(均P=0.015);rs3746544位点在共显性和隐性遗传模式下,基因型分布组间比较,差异有统计学意义(P=0.042,P=0.012),校正后差异无统计学意义(均P>0.05)。由rs3746544-rs8636组成的所有单倍型在病例组与对照组间的频率分布差异均未见统计学意义(均P>0.05)。结论·在中国汉族人群中,SNAP25可能是SZ的易感基因,rs362998位点可能与SZ发病有关。展开更多
细胞自噬是将细胞内受损、变性、衰老的蛋白质或细胞器清除的过程,是细胞本身的代谢需要,也是某些细胞器的更新。自噬过程涉及膜融合。可溶性N-乙基马来酰亚胺敏感的融合蛋白附着蛋白受体(soluble N-ethylmaleimide-sensitive factor at...细胞自噬是将细胞内受损、变性、衰老的蛋白质或细胞器清除的过程,是细胞本身的代谢需要,也是某些细胞器的更新。自噬过程涉及膜融合。可溶性N-乙基马来酰亚胺敏感的融合蛋白附着蛋白受体(soluble N-ethylmaleimide-sensitive factor attachment protein receptor,SNARE)之间相互作用形成SNARE复合体参与膜融合。突触样相关蛋白25(synaptosomal-associated protein of 25 kDa,SNAP25)亚家族成员包括SNAP25、SNAP23、SNAP47和SNAP29,可与其他SNARE相互作用形成SNARE复合体从而参与自噬。本文着重对SNAP25亚家族中各成员如何参与自噬,以及在自噬中所起的作用进行综述,进而为SNAP25亚家族作为疾病治疗的新靶点提供策略。展开更多
目的:评价突触相关蛋白25基因(SNAP25)MnlI多态性与儿童注意缺陷多动障碍(ADHD)的关联性。方法:检索Pubmed、Embase、Web of Science、Google Scholar、中国知网、维普全文电子期刊、万方数据库和中国生物医学文献数据库,检索时限均为...目的:评价突触相关蛋白25基因(SNAP25)MnlI多态性与儿童注意缺陷多动障碍(ADHD)的关联性。方法:检索Pubmed、Embase、Web of Science、Google Scholar、中国知网、维普全文电子期刊、万方数据库和中国生物医学文献数据库,检索时限均为自建库至2019年11月,搜集SNAP25MnlI多态性与ADHD相关的研究。结果:本研究包含7项病例对照研究和8项传递不平衡检验。Meta分析显示,存在中度异质性(I^2=45.6%),因此采用随机效应模型分析,结果支持SNAP25MnlI多态性与儿童ADHD存在关联[OR(95%CI)=1.16(1.03~1.30),P<0.05]。按人种及研究类型进行亚组分析后,得到在白种人、病例对照研究中SNAP25MnlI多态性与儿童ADHD风险存在关联[OR(95%CI)=1.10(1.00~1.22)、1.38(1.11~1.70),均P<0.05]。结论:本研究提示在白种人中或采用病例对照研究的实验方法表明SNAP25MnlI多态性可能会增加儿童ADHD的风险。展开更多
BACKGROUND Hepatic ischemia-reperfusion(I/R)injury related to liver transplantation and hepatic resection remains a challenge in clinical practice.Accumulating evidence indicates that mitochondrial dysfunction is a cr...BACKGROUND Hepatic ischemia-reperfusion(I/R)injury related to liver transplantation and hepatic resection remains a challenge in clinical practice.Accumulating evidence indicates that mitochondrial dysfunction is a critical cause of I/R injury.The protein 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1(NIPSNAP1)is involved in the regulation of mitophagy and the recruitment of autophagy receptor proteins independent of PTEN induced putative kinase 1.AIM To clarify the protective mechanism of NIPSNAP1 against hepatic I/R,with a focus on mitophagy and mitochondrial dynamics,as well as the potential mechanism by which n6-methyladenosine(m6A)modification regulates NIPSNAP1.METHODS Mice were administered an adeno-associated virus in vivo and a hepatic I/R model was established via portal vein interruption followed by reperfusion to explore the effect of NIPSNAP1 on hepatic I/R.HepG2 cells were subjected to hypoxia/reoxygenation treatment in vitro.RESULTS We observed a significant downregulation of both NIPSNAP1 and insulin-like growth factor 2 mRNA-binding protein 2(IGF2BP2)expression in vivo and in vitro.NIPSNAP1 knockdown impaired mitophagy and disrupted mitochondrial dynamics;in contrast,NIPSNAP1 overexpression resulted in the opposite effects.Further studies revealed that IGF2BP2 functions as an m6A reader that targets and binds NIPSNAP1,thereby regulating its mRNA stability.CONCLUSION NIPSNAP1 prevents hepatic I/R injury by promoting mitophagy and maintaining mitochondrial homeostasis,serving as a novel target of the m6A reader IGF2BP2.Therefore,targeting the IGF2BP2/NIPSNAP1 axis may facilitate the development of better therapeutics for hepatic I/R.展开更多
文摘目的·探讨中国汉族人群突触小体相关蛋白(synaptosomal-associated protein of 25000,SNAP25)基因与精神分裂症(schizophrenia,SZ)的相关性。方法·采用TaqMan探针基因分型技术对434例SZ患者(病例组)和432例健康对照(对照组)的SNAP25基因5个单核苷酸多态性(single nucleotide polymorphism,SNP)位点(rs3746544、rs8636、rs362998、rs6039769、rs6077690)进行分型,比较病例组与对照组间的等位基因、基因型,不同遗传模式下基因型以及单倍型频率分布的差异。结果·rs362998和rs6039769等位基因频率分布在病例组与对照组之间差异有统计学意义(P=0.029,P=0.033),经Bonferroni校正后,差异均无统计学意义(均P>0.05);病例组与对照组间rs362998和rs3746544基因型分布的差异具有统计学意义(P=0.005,P=0.043),校正后rs362998差异仍有统计学意义(P=0.025),rs3746544差异无统计学意义(P>0.05)。rs362998位点在共显性和显性遗传模式下,基因型分布组间比较,差异有统计学意义(均P=0.003),校正后差异仍有统计学意义(均P=0.015);rs3746544位点在共显性和隐性遗传模式下,基因型分布组间比较,差异有统计学意义(P=0.042,P=0.012),校正后差异无统计学意义(均P>0.05)。由rs3746544-rs8636组成的所有单倍型在病例组与对照组间的频率分布差异均未见统计学意义(均P>0.05)。结论·在中国汉族人群中,SNAP25可能是SZ的易感基因,rs362998位点可能与SZ发病有关。
文摘细胞自噬是将细胞内受损、变性、衰老的蛋白质或细胞器清除的过程,是细胞本身的代谢需要,也是某些细胞器的更新。自噬过程涉及膜融合。可溶性N-乙基马来酰亚胺敏感的融合蛋白附着蛋白受体(soluble N-ethylmaleimide-sensitive factor attachment protein receptor,SNARE)之间相互作用形成SNARE复合体参与膜融合。突触样相关蛋白25(synaptosomal-associated protein of 25 kDa,SNAP25)亚家族成员包括SNAP25、SNAP23、SNAP47和SNAP29,可与其他SNARE相互作用形成SNARE复合体从而参与自噬。本文着重对SNAP25亚家族中各成员如何参与自噬,以及在自噬中所起的作用进行综述,进而为SNAP25亚家族作为疾病治疗的新靶点提供策略。
文摘目的:评价突触相关蛋白25基因(SNAP25)MnlI多态性与儿童注意缺陷多动障碍(ADHD)的关联性。方法:检索Pubmed、Embase、Web of Science、Google Scholar、中国知网、维普全文电子期刊、万方数据库和中国生物医学文献数据库,检索时限均为自建库至2019年11月,搜集SNAP25MnlI多态性与ADHD相关的研究。结果:本研究包含7项病例对照研究和8项传递不平衡检验。Meta分析显示,存在中度异质性(I^2=45.6%),因此采用随机效应模型分析,结果支持SNAP25MnlI多态性与儿童ADHD存在关联[OR(95%CI)=1.16(1.03~1.30),P<0.05]。按人种及研究类型进行亚组分析后,得到在白种人、病例对照研究中SNAP25MnlI多态性与儿童ADHD风险存在关联[OR(95%CI)=1.10(1.00~1.22)、1.38(1.11~1.70),均P<0.05]。结论:本研究提示在白种人中或采用病例对照研究的实验方法表明SNAP25MnlI多态性可能会增加儿童ADHD的风险。
基金Supported by the National Natural Science Foundation of China,No.82200658.
文摘BACKGROUND Hepatic ischemia-reperfusion(I/R)injury related to liver transplantation and hepatic resection remains a challenge in clinical practice.Accumulating evidence indicates that mitochondrial dysfunction is a critical cause of I/R injury.The protein 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1(NIPSNAP1)is involved in the regulation of mitophagy and the recruitment of autophagy receptor proteins independent of PTEN induced putative kinase 1.AIM To clarify the protective mechanism of NIPSNAP1 against hepatic I/R,with a focus on mitophagy and mitochondrial dynamics,as well as the potential mechanism by which n6-methyladenosine(m6A)modification regulates NIPSNAP1.METHODS Mice were administered an adeno-associated virus in vivo and a hepatic I/R model was established via portal vein interruption followed by reperfusion to explore the effect of NIPSNAP1 on hepatic I/R.HepG2 cells were subjected to hypoxia/reoxygenation treatment in vitro.RESULTS We observed a significant downregulation of both NIPSNAP1 and insulin-like growth factor 2 mRNA-binding protein 2(IGF2BP2)expression in vivo and in vitro.NIPSNAP1 knockdown impaired mitophagy and disrupted mitochondrial dynamics;in contrast,NIPSNAP1 overexpression resulted in the opposite effects.Further studies revealed that IGF2BP2 functions as an m6A reader that targets and binds NIPSNAP1,thereby regulating its mRNA stability.CONCLUSION NIPSNAP1 prevents hepatic I/R injury by promoting mitophagy and maintaining mitochondrial homeostasis,serving as a novel target of the m6A reader IGF2BP2.Therefore,targeting the IGF2BP2/NIPSNAP1 axis may facilitate the development of better therapeutics for hepatic I/R.
