Acute ischemic stroke is a highly prevalent and disabling disease with poor prognosis.Neuronal death is a major feature after a stroke.PANoptosis is a newly reported pattern of cell death,characterized by pyroptosis,a...Acute ischemic stroke is a highly prevalent and disabling disease with poor prognosis.Neuronal death is a major feature after a stroke.PANoptosis is a newly reported pattern of cell death,characterized by pyroptosis,apoptosis,and necroptosis,that plays an important role in the pathophysiological process after ischemic brain injury.However,its precise underlying mechanisms have not yet been fully elucidated.This study aimed to clarify the function of S100 calcium-binding protein A10 in neuronal PANoptosis after ischemic brain damage and to investigate the impact and mechanism of sonic hedgehog and S100 calcium-binding protein A10 on PANoptosis.The results showed that S100 calcium-binding protein A10 was significantly upregulated in both cellular and animal models of ischemic stroke.Knockdown of S100 calcium-binding protein A10 exacerbated PANoptosis and the levels of PANoptosis-related proteins following cerebral ischemia damage.Sonic hedgehog treatment increased S100 calcium-binding protein A10 and inhibited the increase in PANoptosis induced by S100 calcium-binding protein A10 knockdown.The findings suggest that sonic hedgehog intervention mitigated neuronal PANoptosis ensuing from ischemic stroke.The combination of S100 calcium-binding protein A10 and sonic hedgehog demonstrated promise for developing an effective therapy against cerebral ischemic stroke,which would have significant potential for future clinical applications.展开更多
了解陕西省手足口病(Hand,foot and mouth disease,HFMD)的致病病原体柯萨奇病毒A10型(CV-A10)的流行特征及VP1区基因特征。对2014年收集的HFMD病例标本,通过荧光定量PCR检测确定肠道病毒型别,对CV-A10引起的HFMD流行特征进行描述性分...了解陕西省手足口病(Hand,foot and mouth disease,HFMD)的致病病原体柯萨奇病毒A10型(CV-A10)的流行特征及VP1区基因特征。对2014年收集的HFMD病例标本,通过荧光定量PCR检测确定肠道病毒型别,对CV-A10引起的HFMD流行特征进行描述性分析。使用RD细胞进行病毒分离,RT-PCR扩增CV-A10的VP1区基因片段并进行序列测定,使用Meg Align软件进行核苷酸及氨基酸的同源性分析,并使用MEGA5.0软件构建系统进化树。2014年CV-A10是陕西HFMD病原谱中的第三大病原,占其他肠道病毒的57.71%,13例重症HFMD病例的致病病原体鉴定为CV-A10,占重症病例的9.03%。CV-A10感染HFMD病例以≤3岁年龄组儿童为主(83.07%),男女性别比为1.15∶1。发病时间主要集中在4～7月。实验室分离出101株CV-A10,覆盖全省10市(区)。完成测序的18株CV-A10核苷酸和氨基酸同源性分别为94.0%～100.0%和97.3%～100.0%,与A型原型株的核苷酸和氨基酸同源性分别为76.2%～77.5%和91.9%～93.0%,与近年来河北、湖南和河南地区流行株具有较高的同源性。系统进化显示陕西CV-A10分离株属于C基因型。CV-A10是2014年陕西HFMD的优势病原,能引起重症HFMD,本次分离到的CV-A10毒株均属于C基因型。展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171456(to QY),and 81971229(to QY)the Natural Science Foundation of Chongqing,No.CSTC2021JCYJ-MSXMX0263(to QY)Doctoral Innovation Project of The First Affiliated Hospital of Chongqing Medical University,Nos.CYYY-BSYJSCXXM-202318(to JW)and CYYY-BSYJSCXXM-202327(to HT).
文摘Acute ischemic stroke is a highly prevalent and disabling disease with poor prognosis.Neuronal death is a major feature after a stroke.PANoptosis is a newly reported pattern of cell death,characterized by pyroptosis,apoptosis,and necroptosis,that plays an important role in the pathophysiological process after ischemic brain injury.However,its precise underlying mechanisms have not yet been fully elucidated.This study aimed to clarify the function of S100 calcium-binding protein A10 in neuronal PANoptosis after ischemic brain damage and to investigate the impact and mechanism of sonic hedgehog and S100 calcium-binding protein A10 on PANoptosis.The results showed that S100 calcium-binding protein A10 was significantly upregulated in both cellular and animal models of ischemic stroke.Knockdown of S100 calcium-binding protein A10 exacerbated PANoptosis and the levels of PANoptosis-related proteins following cerebral ischemia damage.Sonic hedgehog treatment increased S100 calcium-binding protein A10 and inhibited the increase in PANoptosis induced by S100 calcium-binding protein A10 knockdown.The findings suggest that sonic hedgehog intervention mitigated neuronal PANoptosis ensuing from ischemic stroke.The combination of S100 calcium-binding protein A10 and sonic hedgehog demonstrated promise for developing an effective therapy against cerebral ischemic stroke,which would have significant potential for future clinical applications.
文摘了解陕西省手足口病(Hand,foot and mouth disease,HFMD)的致病病原体柯萨奇病毒A10型(CV-A10)的流行特征及VP1区基因特征。对2014年收集的HFMD病例标本,通过荧光定量PCR检测确定肠道病毒型别,对CV-A10引起的HFMD流行特征进行描述性分析。使用RD细胞进行病毒分离,RT-PCR扩增CV-A10的VP1区基因片段并进行序列测定,使用Meg Align软件进行核苷酸及氨基酸的同源性分析,并使用MEGA5.0软件构建系统进化树。2014年CV-A10是陕西HFMD病原谱中的第三大病原,占其他肠道病毒的57.71%,13例重症HFMD病例的致病病原体鉴定为CV-A10,占重症病例的9.03%。CV-A10感染HFMD病例以≤3岁年龄组儿童为主(83.07%),男女性别比为1.15∶1。发病时间主要集中在4～7月。实验室分离出101株CV-A10,覆盖全省10市(区)。完成测序的18株CV-A10核苷酸和氨基酸同源性分别为94.0%～100.0%和97.3%～100.0%,与A型原型株的核苷酸和氨基酸同源性分别为76.2%～77.5%和91.9%～93.0%,与近年来河北、湖南和河南地区流行株具有较高的同源性。系统进化显示陕西CV-A10分离株属于C基因型。CV-A10是2014年陕西HFMD的优势病原,能引起重症HFMD,本次分离到的CV-A10毒株均属于C基因型。
