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NF-κB信号通路 | “狗(Gold)大户”7个小目标的衰老科学竞赛奖金,谁会是最后的赢家?

NF-κB信号通路 | “狗(Gold)大户”7个小目标的衰老科学竞赛奖金,谁会是最后的赢家? 丰信生命科学
2024-11-19
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导读:NF-kB是与衰老最相关的转录因子,NF-κB信号通路是热门研究领域:①癌症、免疫逃逸;②NF-kB信号通路激活或抑制酶发现;③NF-κB靶向药物开发;④慢性炎症性疾病和自身免疫;⑤细胞衰老·····


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:

1

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。

2

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。

3

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;

4

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。

5

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。

······

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-κBIGF-1mTOR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。



Hot


多因子检测试剂盒

NF-κB信号通路相关探究试剂盒

1

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





2

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。


3

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

······

磷酸化检测ELISA:

Phospho-NF-KB p65 (S536) ELISA Kit,货号:PEL-NFKBP65-S536

Phospho-NF-KB p65 (S536) ELISA and Total NF-KB p65 Kit,货号:PEL-NFKBP65-S536-T

Human Phospho-I-kappa B alpha (S32) ELISA Kit,货号:PEL-IKBa-S32

Human Phospho-I-kappa B alpha (S32) and Total I-kappa B alpha ELISA Kit,货号:PEL-IKBa-S32-T

······



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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RayBio®抗体芯片近期部分学术引用

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2017 Nature Communications 16.6 Application of bio-orthogonal proteome labeling to cell transplantation and heterochronic parabiosis
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2017 Nature 64.8 Cytoplasmic chromatin triggers inflammation in senescence and cancer
2017 Nature Medicines 82.9 Dickkopf-1 promotes hematopoietic regeneration via direct and niche-mediated mechanisms
2018 Acta Biomaterialia 9.7 Manipulation of the response of human endothelial  colony-forming cells by focal adhesion assembly using gradient nanopattern plates
2018 Journal for Immuno Therapy of Cancer 10.9 Randomized phase II trial of autologous dendritic cell vaccines   versus autologous tumor cell vaccines in metastatic melanoma 5-year  follow up and additional analyses
2018 Arthritis & Rheumatology 13.3 Myogenic Progenitor Cells Exhibit Type I Interferon–Driven Proangiogenic Properties and Molecular Signature During Juvenile  Dermatomyositis
2018 Hepatology 13.5 Identification and Therapeutic Intervention of Coactivated Anaplastic Lymphoma Kinase, Fibroblast Growth Factor Receptor 2, and  Ephrin  Type-A Receptor 5 Kinases in Hepatocellular Carcinoma
2018 Hepatology 13.5 Sphingosine kinase 1 promotes liver fibrosis by preventing miR-19b-3p-mediated inhibition of CCR2
2018 Cell Host & Microbe 30.3 Listeria Adhesion Protein Induces Intestinal Epithelial Barrier Dysfunction for Bacterial Translocation 
2018 Cell 64.5 CD10+ GPR77+ cancer-associated fibroblasts promote cancer formation and chemoresistance by sustaining cancer stemness
2019 Theranostics 12.4 Monoclonal Antibody againstCXCL1 (HL2401) as a Novel Agent in Suppressing IL6 Expression and Tumoral Growth
2019 Neurology 9.9 Changes in cerebralautoregulation and blood biomarkers after remote ischemic preconditioning
2019 Nature Communications 16.6 Altered respiratory virome and serum cytokine profile associated with recurrent respiratory tract infections in children
2019 Nature Communications 16.6 Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling
2019 Nature Cell Biology 21.3 NAD+ metabolism governs the proinflammatory  senescence-associated secretome
2019 Nature Medicine 82.9 Stress–glucocorticoid–TSC22D3 axis compromises therapy-induced antitumor immunity
2019 Cell Research 44.1 Sodium oligomannate therapeutically remodels gutmicrobiota and suppresses gut bacterial amino acids-shaped neuroinflammation toinhibit  Alzheimer’s disease progression
2019 Cell 64.5 Regional activation of myosin II in cancer cells drives tumor  progression via a secretory cross-talk with the immune microenvironment
2020 Theranostics 12.4 Targeting the STING pathway in tumor-associated macrophages regulates innate immune sensing of gastric cancer cells
2020 Theranostics 12.4 Plasma protein-based signature predicts distant metastasis and inductionchemotherapy benefit in Nasopharyngeal Carcinoma
2020 Molecular Therapy 12.4 HLSC-Derived Extracellular Vesicles Attenuate Liver Fibrosis and Inflammation in a Murine Model of Non-alcoholic Steatohepatitis
2020 Acta Pharmaceutica Sinica B 14.5 Chrysin serves as a novel inhibitor of DGKa/FAK interaction to suppress the malignancy of esophageal squamous cellcarcinoma (ESCC)
2020 Journal of Extracellular Vesicles 16 Small extracellular vesicles derived from human mesenchymal stromal cells prevent group 2 innatelymphoid cell-dominant allergic airway  inflammation through delivery ofmiR-146a-5p
2020 Nature Communications 16.6 Distinct effects of generalanesthetics on lung metastasis mediated by IL-6/JAK/STAT3 pathway in mouse models
2020 Molecular Cell 16.6 Ectosomal PKM2 Promotes HCC by Inducing Macrophage Differentiation and Remodeling the Tumor Microenvironment
2020 Immunity 32.4 Excessive polyamine generation in keratinocytes promotes self-RNA sensing by dendritic cells in psoriasis
2021 Pharmacological Research 9.3 Affiliated Hospital of Integrated Traditional Chinese and WesternMedicine, Nanjing University of Chinese Medicine
2021 Theranostics 12.4 Intravenous transplantationof olfactory ensheathing cells reduces neuroinflammation after spinal cordinjury via interleukin-1 receptor  antagonist
2021 Theranostics 12.4 Tumor suppressor DRD2 facilitates M1 macrophages and restricts NF-κB signaling to trigger pyroptosis in breast cancer
2021 Hepatology 13.5 Group-2 Innate LymphoidCells Promote Hepatocellular Carcinoma Progression via CXCL2-Neutrophil Induced Immunosuppression
2021 Nature Cell Biology 21.3 m6A-independent genome-wide METTL3 and METTL14  redistribution drives the  senescence-associated secretory phenotype
2021 Signal Transduction and Targeted Therapy 39.3 Mutant KRAS triggers functional reprogramming of tumor-associated macrophages in colorectal cancer
2021 Cancer Cell 50.3 Three subtypes of lung cancer fibroblasts define distinct therapeutic paradigms
2022 Journal for ImmunoTherapy of Cancer 10.9 Longitudinal plasma proteomic profiling of patients with non-small cell lung cancer undergoing immune checkpoint blockade
2022 PNAS 11.1 Plasma metabolome and cytokine profile reveal glycylproline modulating antibody fading in convalescent COVID-19 patients
2022 Advanced Science 15.1 Mouse Modeling Dissecting Macrophage–BreastCancer Communication Uncovered Roles of PYK2 in Macrophage Recruitment and Breast Tumorigenesis
2022 Nature Microbiology 28.3 Multi-omics analyses of airway host–microbe interactions in chronic obstructive pulmonary disease identify potential therapeutic interventions
2023 Nature Metabolism 20.8 TREM2hiresident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis
2023 Journal of Hematology & Oncology 28.5 LCN2 secreted by tissue-infiltrating neutrophils induces the ferroptosis and wasting of adipose and muscle tissues in lung cancer cachexia
2023 Cancer Cell 50.3 Tissue factor is a critical regulator of radiation therapy-induced glioblastoma remodeling


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Year Journal 2023 IF Article  Title
2017 Science Translational Medicine 17.1 Detection of early pancreatic ductal adenocarcinoma using thrombospondin-2 and CA19-9 blood markers
2017 JAMA Internal Medicine 39.0 Association of Ozone Exposure With Cardiorespiratory Pathophysiologic Mechanisms in Healthy Adults
2017 Journal of Clinical Investigation 15.9 Thrombin promotes diet-induced obesity through fibrin-driven inflammation 
2017 Nature Medicine 82.9 Targeting CASP8 and FADD-like apoptosis regulator ameliorates nonalcoholic steatohepatitis in mice and nonhuman primates 
2017 Nature Communications 16.6 Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflammasome activation via ANT1-dependent mitochondrial homeostasis
2018 Nature 64.8 Disruption of a self-amplifying catecholamine loop reduces cytokine release syndrome
2018 Autophagy 13.3 HSPA5 negatively regulates lysosomal activity through ubiquitination of MUL1 in head and neck cancer 
2020  Annals of Surgery 9.0 Plasma miR-181a-5p Downregulation Predicts Response and Improved Survival After FOLFIRINOX in Pancreatic Ductal Adenocarcinoma
2020 Nature Communications 16.6 Plasma levels of DPP4 activity and sDPP4 are dissociated from inflammation in mice and humans
2020 Nature Communications 16.6 Chemotaxis-driven delivery ofnano-pathogenoids for co mplete eradication oftumorspost-phototherapy
2020 Nature Communications 16.6 Receptor-targetedengineered probiotics mitigatele thal Listeria infection
2020 Brain Behavior and Immunity 15.1 Increased vulnerability to impulsive behavior after streptococcal antigen exposure and antibiotic treatment in rats
2020 Cell Metabolism 29.0 Defined p16High Senescent Cell Types Are Indispensablefor Mouse Healthspan
2020 Immunity 32.4 Interleukin-33 Promotes Serotonin Release from Enterochromaffin Cells for Intestinal Homeostasis
2020 Cell 64.5 Mortality Risk Profiling of Staphylococcus aureus Bacteremia by Multi-omic Serum Analysis Reveals Early Predictive and Pathogenic Signatures
2021 Journal of Clinical Investigation 15.9 Mutant SF3B1 promotes AKT-and NF-KB-driven mammary tumorigenesis
2022 Biomaterials 14.0 Dual-functionalhydrogel systemfor spinal cordr egeneration with sustained  releaseofarylsulfataseBalleviatesfibrotic mi croenvironment and promotes  axonalregeneration






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