The NSC-34 cell line is a widely recognized motor neuron model and various neuronal differentiation protocols have been exploited. Under previously reported experimental conditions, only part of the cells resemble dif...The NSC-34 cell line is a widely recognized motor neuron model and various neuronal differentiation protocols have been exploited. Under previously reported experimental conditions, only part of the cells resemble differentiated neurons;however, they do not exhibit extensive and time-prolonged neuritogenesis, and maintain their duplication capacity in culture. The aim of the present work was to facilitate long-term and more homogeneous neuronal differentiation in motor neuron–like NSC-34 cells. We found that the antimitotic drug cytosine arabinoside promoted robust and persistent neuronal differentiation in the entire cell population. Long and interconnecting neuronal processes with abundant growth cones were homogeneously induced and were durable for up to at least 6 weeks in culture. Moreover, cytosine arabinoside was permissive, dispensable, and mostly irreversible in priming NSC-34 cells for neurite initiation and regeneration after mechanical dislodgement. Finally, the expression of the cell proliferation antigen Ki67 was inhibited by cytosine arabinoside, whereas the expression levels of neuronal growth associated protein 43, vimentin, and motor neuron–specific p75, Islet2, homeobox 9 markers were upregulated, as confirmed by western blot and/or confocal immunofluorescence analysis. Overall, these findings support the use of NSC-34 cells as a motor neuron model for properly investigating neurodegenerative mechanisms and prospectively identifying neuroprotective strategies.展开更多
心血管损伤与修复依赖于多种细胞的募集、增殖与分化。CD34^(+)细胞作为一类以分化簇34(cluster of differentiation34,CD34)蛋白为标志物的异质性细胞群体,长期被视为心血管再生与修复的关键靶点。该类细胞可展现出高度的异质性与多向...心血管损伤与修复依赖于多种细胞的募集、增殖与分化。CD34^(+)细胞作为一类以分化簇34(cluster of differentiation34,CD34)蛋白为标志物的异质性细胞群体,长期被视为心血管再生与修复的关键靶点。该类细胞可展现出高度的异质性与多向分化潜能,在特定的微环境信号调控下,能够分化为内皮细胞、平滑肌细胞、成纤维细胞、炎症细胞等多种谱系,在内皮修复、组织纤维化、免疫调节等过程中发挥重要作用。在心血管疾病中CD34^(+)细胞可介导双重调控作用:既能促进组织修复与再生,又可能加剧病理损伤。尽管CD34^(+)细胞疗法在心血管疾病中已具有良好的治疗潜力,但其向临床转化的过程仍面临诸多挑战与瓶颈。基于此,该文系统梳理了CD34^(+)细胞的来源、分化轨迹与功能异质性,总结其在心血管基础研究与临床转化中的最新进展,旨在为深化疾病机制理解、开发新型精准治疗策略提供新视角。展开更多
目的:探讨IL-34对ApoE-/-小鼠动脉粥样硬化(AS)和炎症反应的影响。方法:给予高脂饲料喂养的雄性ApoE-/-小鼠20只分为两组,每组10只。实验组隔天1次腹腔注射200 ng重组IL-34(rIL-34),对照组隔天1次腹腔注射0.3 mL PBS,干预12周。检测小...目的:探讨IL-34对ApoE-/-小鼠动脉粥样硬化(AS)和炎症反应的影响。方法:给予高脂饲料喂养的雄性ApoE-/-小鼠20只分为两组,每组10只。实验组隔天1次腹腔注射200 ng重组IL-34(rIL-34),对照组隔天1次腹腔注射0.3 mL PBS,干预12周。检测小鼠血清总胆固醇(TC),甘油三酯(TG)及高密度脂蛋白胆固醇(HDL-C);油红O染色评估小鼠主动脉AS形成情况;免疫组化法检测主动脉根部斑块炎症细胞(CD3+T细胞和Mac-3+巨噬细胞)浸润情况;流式细胞术检测脾脏T细胞亚群;ELISA法和Bio-Plex系统检测小鼠血清细胞炎性因子IL-1β、TNF-α、IFN-γ、IL-6、IL-4、IL-10、TGF-β1和IL-17A水平;qRT-PCR法检测小鼠主动脉弓上述细胞因子mRNA的表达水平。结果:两组小鼠血脂水平差异无统计学意义(P>0.05))。与对照组比较,实验组小鼠血清IL-34水平增加,主动脉和主动脉根部斑块面积增加,斑块内CD3+T细胞和Mac-3+巨噬细胞浸润增多,脾脏Th17细胞亚群比例升高,血清IL-1β、TNF-α、IFN-γ、IL-6和IL-17A水平升高,主动脉弓IL-1β、TNF-α、IFN-γ、IL-6和IL-17A mRNA表达水平升高(P均<0.05)。结论:IL-34可升高脾脏Th17细胞亚群比例,促进炎症因子表达,有助于小鼠AS形成。展开更多
目的观察重症肺结核患者治疗前血清白蛋白(albumin,ALB)、白介素-34(interleukin-34,IL-34)表达水平,并分析血清ALB、IL-34水平与重症肺结核患者预后之间可能的相关性。方法回顾性分析,收集郑州市第六人民医院2021年1月—2023年8月收治...目的观察重症肺结核患者治疗前血清白蛋白(albumin,ALB)、白介素-34(interleukin-34,IL-34)表达水平,并分析血清ALB、IL-34水平与重症肺结核患者预后之间可能的相关性。方法回顾性分析,收集郑州市第六人民医院2021年1月—2023年8月收治的112例重症肺结核患者资料,根据患者预后情况(入院开始接受治疗持续6个月内生存情况)分组,将25例死亡患者纳入预后不良组,87例生存患者纳入预后良好组,比较不同预后情况患者基线资料和治疗前血清ALB、IL-34水平,采用Cox风险模型和限制性立方样条法分析血清ALB、IL-34与重症肺结核患者预后的关系,并使用相对超危险度比(relative excess risk due to interaction,RERI)、归因比(attributable proportion,AP)以及交互作用指数(synergy index,SI)分析血清ALB、IL-34水平对重症肺结核患者预后的交互作用。结果不同预后患者基线资料比较,差异无统计学意义(P>0.05);预后不良组治疗前血清γ-干扰素(interferon-γ,IFN-γ)、ALB水平低于预后良好组,血清C-反应蛋白(C-reactive protein,CRP)、IL-34高于预后良好组,差异有统计学意义(P<0.05)。IFN-γ、CRP、ALB、IL-34的偏残差和时间秩次的Pearson相关性分析结果表明均满足PH假设(r=-0.068、-0.066、-0.210、0.186,P>0.05),经Cox生存回归分析结果显示,重症肺结核患者预后与入院时血清IFN-γ、ALB表达下调,血清CRP、IL-34表达上调有关(P<0.05)。经剂量反应分析结果显示,重症肺结核患者治疗前血清ALB、IL-34水平与预后不良的关联强度呈线性剂量反应关系(P<0.05)。血清ALB、IL-34对重症肺结核患者不良预后的发生存在负向交互作用,血清ALB低表达且IL-34高表达时不良预后风险是血清ALB高表达且IL-34低表达时的26.523倍。结论重症肺结核患者预后不良风险较高,入院时血清ALB呈低表达、IL-34呈高表达,这种异常的ALB低表达、IL-34高表达与患者不良预后有关,且二者对患者预后的影响呈交互作用。展开更多
基金supported by FATALSDrug Project [Progetti di Ricerca@CNR SAC.AD002.173.058] from National Research Council,Italy (to CV)。
文摘The NSC-34 cell line is a widely recognized motor neuron model and various neuronal differentiation protocols have been exploited. Under previously reported experimental conditions, only part of the cells resemble differentiated neurons;however, they do not exhibit extensive and time-prolonged neuritogenesis, and maintain their duplication capacity in culture. The aim of the present work was to facilitate long-term and more homogeneous neuronal differentiation in motor neuron–like NSC-34 cells. We found that the antimitotic drug cytosine arabinoside promoted robust and persistent neuronal differentiation in the entire cell population. Long and interconnecting neuronal processes with abundant growth cones were homogeneously induced and were durable for up to at least 6 weeks in culture. Moreover, cytosine arabinoside was permissive, dispensable, and mostly irreversible in priming NSC-34 cells for neurite initiation and regeneration after mechanical dislodgement. Finally, the expression of the cell proliferation antigen Ki67 was inhibited by cytosine arabinoside, whereas the expression levels of neuronal growth associated protein 43, vimentin, and motor neuron–specific p75, Islet2, homeobox 9 markers were upregulated, as confirmed by western blot and/or confocal immunofluorescence analysis. Overall, these findings support the use of NSC-34 cells as a motor neuron model for properly investigating neurodegenerative mechanisms and prospectively identifying neuroprotective strategies.
文摘心血管损伤与修复依赖于多种细胞的募集、增殖与分化。CD34^(+)细胞作为一类以分化簇34(cluster of differentiation34,CD34)蛋白为标志物的异质性细胞群体,长期被视为心血管再生与修复的关键靶点。该类细胞可展现出高度的异质性与多向分化潜能,在特定的微环境信号调控下,能够分化为内皮细胞、平滑肌细胞、成纤维细胞、炎症细胞等多种谱系,在内皮修复、组织纤维化、免疫调节等过程中发挥重要作用。在心血管疾病中CD34^(+)细胞可介导双重调控作用:既能促进组织修复与再生,又可能加剧病理损伤。尽管CD34^(+)细胞疗法在心血管疾病中已具有良好的治疗潜力,但其向临床转化的过程仍面临诸多挑战与瓶颈。基于此,该文系统梳理了CD34^(+)细胞的来源、分化轨迹与功能异质性,总结其在心血管基础研究与临床转化中的最新进展,旨在为深化疾病机制理解、开发新型精准治疗策略提供新视角。
文摘目的:探讨IL-34对ApoE-/-小鼠动脉粥样硬化(AS)和炎症反应的影响。方法:给予高脂饲料喂养的雄性ApoE-/-小鼠20只分为两组,每组10只。实验组隔天1次腹腔注射200 ng重组IL-34(rIL-34),对照组隔天1次腹腔注射0.3 mL PBS,干预12周。检测小鼠血清总胆固醇(TC),甘油三酯(TG)及高密度脂蛋白胆固醇(HDL-C);油红O染色评估小鼠主动脉AS形成情况;免疫组化法检测主动脉根部斑块炎症细胞(CD3+T细胞和Mac-3+巨噬细胞)浸润情况;流式细胞术检测脾脏T细胞亚群;ELISA法和Bio-Plex系统检测小鼠血清细胞炎性因子IL-1β、TNF-α、IFN-γ、IL-6、IL-4、IL-10、TGF-β1和IL-17A水平;qRT-PCR法检测小鼠主动脉弓上述细胞因子mRNA的表达水平。结果:两组小鼠血脂水平差异无统计学意义(P>0.05))。与对照组比较,实验组小鼠血清IL-34水平增加,主动脉和主动脉根部斑块面积增加,斑块内CD3+T细胞和Mac-3+巨噬细胞浸润增多,脾脏Th17细胞亚群比例升高,血清IL-1β、TNF-α、IFN-γ、IL-6和IL-17A水平升高,主动脉弓IL-1β、TNF-α、IFN-γ、IL-6和IL-17A mRNA表达水平升高(P均<0.05)。结论:IL-34可升高脾脏Th17细胞亚群比例,促进炎症因子表达,有助于小鼠AS形成。
文摘目的观察重症肺结核患者治疗前血清白蛋白(albumin,ALB)、白介素-34(interleukin-34,IL-34)表达水平,并分析血清ALB、IL-34水平与重症肺结核患者预后之间可能的相关性。方法回顾性分析,收集郑州市第六人民医院2021年1月—2023年8月收治的112例重症肺结核患者资料,根据患者预后情况(入院开始接受治疗持续6个月内生存情况)分组,将25例死亡患者纳入预后不良组,87例生存患者纳入预后良好组,比较不同预后情况患者基线资料和治疗前血清ALB、IL-34水平,采用Cox风险模型和限制性立方样条法分析血清ALB、IL-34与重症肺结核患者预后的关系,并使用相对超危险度比(relative excess risk due to interaction,RERI)、归因比(attributable proportion,AP)以及交互作用指数(synergy index,SI)分析血清ALB、IL-34水平对重症肺结核患者预后的交互作用。结果不同预后患者基线资料比较,差异无统计学意义(P>0.05);预后不良组治疗前血清γ-干扰素(interferon-γ,IFN-γ)、ALB水平低于预后良好组,血清C-反应蛋白(C-reactive protein,CRP)、IL-34高于预后良好组,差异有统计学意义(P<0.05)。IFN-γ、CRP、ALB、IL-34的偏残差和时间秩次的Pearson相关性分析结果表明均满足PH假设(r=-0.068、-0.066、-0.210、0.186,P>0.05),经Cox生存回归分析结果显示,重症肺结核患者预后与入院时血清IFN-γ、ALB表达下调,血清CRP、IL-34表达上调有关(P<0.05)。经剂量反应分析结果显示,重症肺结核患者治疗前血清ALB、IL-34水平与预后不良的关联强度呈线性剂量反应关系(P<0.05)。血清ALB、IL-34对重症肺结核患者不良预后的发生存在负向交互作用,血清ALB低表达且IL-34高表达时不良预后风险是血清ALB高表达且IL-34低表达时的26.523倍。结论重症肺结核患者预后不良风险较高,入院时血清ALB呈低表达、IL-34呈高表达,这种异常的ALB低表达、IL-34高表达与患者不良预后有关,且二者对患者预后的影响呈交互作用。
