AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in vario...AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.展开更多
文摘目的探讨胃癌组织中EB病毒的感染状况,分析其与小核核糖核蛋白多肽A(Small nuclear ribonucleoprotein polypeptide A,SNRPA)及端粒沉默破坏因子1样蛋白(Disruptor of telomeric silencing 1-like,DOT1L)表达的相关性。方法收集2022年2月至2025年5月南阳市第一人民医院收治的280例胃癌患者的癌组织及癌旁正常组织标本。分析EB病毒感染与患者临床病理特征的关系,比较EB病毒感染阳性组与阴性组中SNRPA、DOT1L的表达水平,采用Spearman分析EB病毒感染与癌组织SNRPA、DOT1L表达的相关性,受试者工作(Receiver operating characteristic,ROC)曲线分析SNRPA、DOT1L对胃癌EB病毒感染的诊断价值。结果280例胃癌患者癌组织标本中EB病毒阳性者33例,阳性率11.79%(33/280);胃癌患者EB病毒感染与淋巴结转移相关(P<0.05);SNRPA与DOT1L在胃癌组织中的表达均高于癌旁组织,EB病毒感染组SNRPA与DOT1L的表达均高于EB病毒未感染组(P<0.05);Spearman相关性分析显示,癌组织SNRPA、DOT1L表达与EB病毒感染呈正相关(r=0.709、0.658,P<0.05)。ROC曲线显示,SNRPA、DOT1L、两种指标联合评估胃癌EB病毒感染的曲线下面积(Area Under the Curve,AUC)分别为0.807、0.773、0.886。结论EB病毒感染与胃癌患者淋巴结转移、SNRPA、DOT1L表达水平有关,联合检测SNRPA、DOT1L可提高胃癌EB病毒感染的诊断效能。
基金江西省自然科学基金项目(编号:20202BAB206075)江西省教育厅科技项目(编号:GJJ201202)江西中医药大学中西医结合一级学科平台(Discipline of Chinese and Western Integrative Medicine,Jiangxi University of Chinese Medicine)。
基金supported by the National Natural Science Foundation of China,Nos.81870921(to YW),81974179(to ZZ),82271320(to ZZ),82071284(to YT)National Key R&D Program of China,No.2022YFA1603600(to ZZ),2019YFA0112000(to YT)+1 种基金Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY).
文摘AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.
