Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso...Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.展开更多
目的探讨bcl-2、bcl-6、CD10在弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DL-BCL)中的表达及意义。方法应用免疫组织化学SP法,检测60例弥漫性大B细胞淋巴瘤标本中bcl-2、bcl-6、CD10蛋白的表达水平。结果bcl-2、bcl-6、CD10...目的探讨bcl-2、bcl-6、CD10在弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DL-BCL)中的表达及意义。方法应用免疫组织化学SP法,检测60例弥漫性大B细胞淋巴瘤标本中bcl-2、bcl-6、CD10蛋白的表达水平。结果bcl-2、bcl-6、CD10在60例弥漫性大B细胞淋巴瘤中的表达率分别为55.0%(33/60)、48.3%(29/60)、46.7%(28/60),其中CD10(+)/bcl-6(+)15例,25%;CD10(+)/bcl-6(-)13例,21.7%;CD10(-)/bcl-6(+)14例,23.3%;CD10(-)/bcl-6(-)18例,30%。CD10(+)/bcl-6(+)与CD10(-)/bcl-6(-)中bcl-2的表达差异具有统计学意义。结论bcl-2有望成为DLBCL亚分类的指标。展开更多
目的探讨bcl-2、bcl-6、CD10、MUM1在弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中的表达及与亚分类的关系。方法应用免疫组织化学S-P法,检测60例弥漫性大B细胞淋巴瘤标本中bcl-2、bcl-6、CD10、MUM1蛋白的表达水平。结...目的探讨bcl-2、bcl-6、CD10、MUM1在弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中的表达及与亚分类的关系。方法应用免疫组织化学S-P法,检测60例弥漫性大B细胞淋巴瘤标本中bcl-2、bcl-6、CD10、MUM1蛋白的表达水平。结果bcl-2、bcl-6、CD10、MUM1在60例弥漫性大B细胞淋巴瘤中的表达率分别为55.0%(33/60)、48.3%(29/60)、46.7%(28/60)、58.3%(35/60),其中GCB占55.0%(33/60),non-GCB占45.0%(27/60)。GCB、non-GCB中bcl-2的表达差异具有显著性。在non-GCB中,bcl-6+与bcl-6-的病例bcl-2表达的差异具有显著性。结论该组病例GCB所占的比率超过non-GCB,bcl-2在DLBCL亚分类中可能具有一定的作用。展开更多
弥漫大B细胞淋巴瘤（diffused large B cell lym-plaoma,DLBCL）是非霍奇金淋巴瘤（NHL）中最大的一个亚群,是成人最常见的NHL[1],约占NHL总数的30%～40%[2].在WHO关于淋巴系统肿瘤的分类[3]中,DLBCL被定义为：B细胞起源的,有大的肿瘤细...弥漫大B细胞淋巴瘤（diffused large B cell lym-plaoma,DLBCL）是非霍奇金淋巴瘤（NHL）中最大的一个亚群,是成人最常见的NHL[1],约占NHL总数的30%～40%[2].在WHO关于淋巴系统肿瘤的分类[3]中,DLBCL被定义为：B细胞起源的,有大的肿瘤细胞,具有侵袭性临床表现,需要高效力化疗的一组恶性淋巴瘤,这类肿瘤发生于淋巴结内或结外,可原发或继发于其他低度恶性淋巴瘤的演进[4].展开更多
基金supported by the National Natural Science Foundation of China,Nos.82071008(to BL)and 82004001(to XJ)Medical Science and Technology Program of Health Commission of Henan Province,No.LHGJ20210072(to RQ)Science and Technology Department of Henan Province,No.212102310307(to XJ)。
文摘Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
文摘目的探讨bcl-2、bcl-6、CD10在弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DL-BCL)中的表达及意义。方法应用免疫组织化学SP法,检测60例弥漫性大B细胞淋巴瘤标本中bcl-2、bcl-6、CD10蛋白的表达水平。结果bcl-2、bcl-6、CD10在60例弥漫性大B细胞淋巴瘤中的表达率分别为55.0%(33/60)、48.3%(29/60)、46.7%(28/60),其中CD10(+)/bcl-6(+)15例,25%;CD10(+)/bcl-6(-)13例,21.7%;CD10(-)/bcl-6(+)14例,23.3%;CD10(-)/bcl-6(-)18例,30%。CD10(+)/bcl-6(+)与CD10(-)/bcl-6(-)中bcl-2的表达差异具有统计学意义。结论bcl-2有望成为DLBCL亚分类的指标。
文摘目的探讨bcl-2、bcl-6、CD10、MUM1在弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中的表达及与亚分类的关系。方法应用免疫组织化学S-P法,检测60例弥漫性大B细胞淋巴瘤标本中bcl-2、bcl-6、CD10、MUM1蛋白的表达水平。结果bcl-2、bcl-6、CD10、MUM1在60例弥漫性大B细胞淋巴瘤中的表达率分别为55.0%(33/60)、48.3%(29/60)、46.7%(28/60)、58.3%(35/60),其中GCB占55.0%(33/60),non-GCB占45.0%(27/60)。GCB、non-GCB中bcl-2的表达差异具有显著性。在non-GCB中,bcl-6+与bcl-6-的病例bcl-2表达的差异具有显著性。结论该组病例GCB所占的比率超过non-GCB,bcl-2在DLBCL亚分类中可能具有一定的作用。
文摘弥漫大B细胞淋巴瘤（diffused large B cell lym-plaoma,DLBCL）是非霍奇金淋巴瘤（NHL）中最大的一个亚群,是成人最常见的NHL[1],约占NHL总数的30%～40%[2].在WHO关于淋巴系统肿瘤的分类[3]中,DLBCL被定义为：B细胞起源的,有大的肿瘤细胞,具有侵袭性临床表现,需要高效力化疗的一组恶性淋巴瘤,这类肿瘤发生于淋巴结内或结外,可原发或继发于其他低度恶性淋巴瘤的演进[4].
