
7 亿人民币科学竞赛
Healthspan
给你7亿人民币,你是否能在7年内找到调控人类衰老的奥秘?
据WHO统计,人口老龄化速度逐年递增,是每一个国家都将面临的挑战。
从生物医学角度来看,衰老是各种分子和细胞损伤随时间逐步积累的结果,这会导致生理上的衰弱及各种疾病发生。
2023年11月29日,Xprize基金会发布了一项名为Healthspan的健康科学竞赛,奖金1.01亿美金,旨在探索更加健康的老龄化模式,希望老年人能肌肉、神经、免疫等各个方面恢复10至20年的年轻状态。
截止目前,全球已经有超400个团队参赛,其中包含CRISPR技术的先驱之一George M. Church团队,以及由于基因编辑婴儿事件备受争议的贺建奎······
那么最终7亿得主是谁?我们人类的老年生活水准又会提高到什么程度?时间会给我们答案,但不能太慢!
那么如何加速衰老机制调控机理的探索?
Aging
衰老最相关的通路
NF-kB,是与衰老最相关的转录因子[1],p65/p50异源二聚体是典型的NF-κB二聚体,已知可导致多种基因的转录,p65的缺失,可修复DNA损伤,使小鼠胚胎成纤维细胞有能力避免衰老[2]。
此外,NF-κB 还在中枢神经系统等多个组织的发育和活动中发挥作用。NF-κB 信号的失调与克罗恩病、溃疡性结肠炎和类风湿性关节炎等炎症性和自身免疫性疾病相关。除了炎症性疾病外,该通路的持续激活还与哮喘以及许多癌症形式(如白血病、淋巴瘤、结肠癌和卵巢癌)有关。因此,越来越多的科研人员开始聚焦于NF-κB信号通路的研究。
目前最热门的领域有以下几类:
NF-kB 在癌症和免疫逃逸中的作用:最新的研究表明,NF-κB 在癌症中发挥着重要作用,能够使肿瘤细胞逃避免疫系统的攻击。NF-κB 信号通路帮助肿瘤细胞产生免疫抑制分子,从而阻止免疫细胞攻击肿瘤细胞。
可以激活或抑制 NF-kB 信号通路的酶的发现:研究人员已经发现有些新发现的酶可以向 NF-κB 通路成分添加(或去除)磷酸基团,从而影响其活性。理解这些酶对于设计能够精确调节 NF-κB 活性的药物至关重要。
NF-κB 靶向药物开发:研究人员现在正在开发选择性 NF-κB 抑制剂,针对通路中的特定步骤,而不是广泛抑制 NF-κB(这可能会抑制必要的免疫功能)开发特定药物;
NF-κB 在慢性炎症性疾病和自身免疫中的作用:NF-κB 激活在慢性炎症性疾病中很常见,它即使在没有感染的情况下也会持续引发炎症。这种慢性炎症随着时间的推移可能导致组织损伤。
NF-κB 在细胞衰老中的作用:最新研究表明,过度活跃的 NF-κB 信号传导能够加速细胞衰老,并进一步导致与年龄相关的疾病如骨质疏松症和心血管疾病的发生。
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衰老相关NF-κB通路快速研究工具
RayBio具有多种针对机制研究的高通量多因子微量功能性蛋白质表达检测试剂盒,包含和衰老相关的NF-κB、IGF-1、mTOR等通路,可以帮助科学家从DNA损伤、氧化应激、免疫、炎症等方方面面对细胞衰老、机体衰老进行全面探究。
多因子检测试剂盒
NF-κB信号通路相关探究试剂盒
NF-kappa B Pathway Screening Array
货号:AAH-BLG-NFK
一次性筛选检测90个人NF-κB信号通路中的所有相关蛋白的表达水平,可用于衰老相关疾病研究中NF-κB通路中标志物筛选、上下游调控因子探索等。
技术原理:荧光标记抗原抗体结合
可选载体:载玻片
检测样本:人类血清、血浆、细胞上清、细胞裂解物、组织裂解物……
检测仪器:玻璃芯片扫描仪(Cy3荧光、分辨率≤20μm)
检测样本用量(参考,具体可以结合实际情况调整)
血清/血浆:100μL
细胞上清等无需浓缩的液体样本:1mL
细胞上清/洗液等需浓缩液体样本:10mL
组织/细胞裂解蛋白量:30μg
Human/Mouse NF-κB Pathway Phosphorylation Array C1
货号:AAH-NFKB-1
一次性检测人或小鼠样本中11个NF-κB相关核心细胞因子的热门氨基酸磷酸化位点的磷酸化水平。
技术原理:磷酸化抗体双抗夹心法
可选载体:NC膜
检测样本:人/小鼠细胞裂解物、组织裂解物……
检测仪器:WB曝光仪
检测样本用量(参考,具体可以结合实际情况调整)
组织/细胞裂解蛋白量:500μg
检测靶标:
文献应用:
Zhang, Xuehong et al. “Identification of a novel HOOK3-FGFR1 fusion gene involved in activation of the NF-kappaB pathway.” Cancer cell international vol. 22,1 40. 26 Jan. 2022
大连医科大在破译FGFR1融合的转录组学特征为FGFR1重排患者开辟新的治疗策略中,利用磷酸化抗体阵列验证核因子- kappab (NF-kappaB)信号的激活状态,发现p65 (Ser 536)、IKBalpha (Ser 32)磷酸化程度增加。
Human NF-κB Array C2
货号:AAH-NFKB-2
一次检测筛选人的NF-κB信号通路中的34个靶标蛋白的表达水平。
技术原理:双抗夹心法
可选载体:NC膜
检测样本:人类血清、血浆、细胞上清、细胞裂解物、组织裂解物……
检测仪器:WB曝光仪
检测样本用量(参考,具体可以结合实际情况调整)
血清/血浆:500μL
细胞上清等无需浓缩的液体样本:1mL
细胞上清/洗液等需浓缩液体样本:10mL
组织/细胞裂解蛋白量:500μg
检测靶标:
其他产品
ELISA
转录因子活性检测ELISA:
① Human NF-KappaB p65 Activity Assay Kit,货号:TFEH-p65
② Human NF-κB RelB Activity Assay Kit,货号:TFEH-RELB
③ Human NF-KappaB p50 Activity Assay Kit,货号:TFEH-p50
④ Human NF-κB p52 Activity Assay Kit,货号:TFEH-p52
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磷酸化检测ELISA:
① Phospho-NF-KB p65 (S536) ELISA Kit,货号:PEL-NFKBP65-S536
② Phospho-NF-KB p65 (S536) ELISA and Total NF-KB p65 Kit,货号:PEL-NFKBP65-S536-T
③ Human Phospho-I-kappa B alpha (S32) ELISA Kit,货号:PEL-IKBa-S32
④ Human Phospho-I-kappa B alpha (S32) and Total I-kappa B alpha ELISA Kit,货号:PEL-IKBa-S32-T
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参考文献
[1] Adler, Adam S et al. “Motif module map reveals enforcement of aging by continual NF-kappaB activity.” Genes & development vol. 21,24 (2007): 3244-57
[2] Wang, Jingxin et al. “RelA/p65 functions to maintain cellular senescence by regulating genomic stability and DNA repair.” EMBO reports vol. 10,11 (2009): 1272-8.
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