预约演示

更新于：2025-05-07

FGB

更新于：2025-05-07

基本信息

别名

FGB、Fibrinogen beta chain、fibrinogen, B beta polypeptide

+ [1]

简介

Cleaved by the protease thrombin to yield monomers which, together with fibrinogen alpha (FGA) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the antibacterial immune response via both innate and T-cell mediated pathways.

关联

项与 FGB 相关的药物

99mTc-biciromab

比西单抗

靶点

FGB

作用机制

FGB抑制剂

在研机构-

原研机构

Janssen Global Services LLC

在研适应症-

非在研适应症

血栓栓塞

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

Indium (111In) Biciromab(Janssen Global Services LLC)

靶点

FGB

作用机制

FGB抑制剂

在研机构-

原研机构

Janssen Global Services LLC

在研适应症-

非在研适应症-

最高研发阶段-

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 FGB 相关的临床结果

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100 项与 FGB 相关的转化医学

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0 项与 FGB 相关的专利（医药）

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592

项与 FGB 相关的文献（医药）

2025-04-01·Ecotoxicology and Environmental Safety

Acute exposure of perchlorate on zebrafish larvae: Neurotoxicity during development

Article

作者: He, Qingnan ; Zhao, Mingyi ; Xue, Xiaoran ; Hu, Lin ; Yang, Yang ; Zhang, Zaiqiu

OBJECTIVEThis study aimed to assess the acute developmental toxicity of perchlorate exposure and identify its manifestation of neurotoxicity in zebrafish (Danio rerio) model.METHODSZebrafish larvae were exposed to sodium perchlorate at early developmental stages and the phenotypes of various developmental abnormalities were observed and recorded. Neurodevelopmental toxicity has been studied in particular in terms of central nervous system apoptosis, peripheral motor abnormalities, and abnormal autonomic motor behavior. Samples were processed for pathological, transcriptomic, and PCR analyses.RESULTSAcute exposure of zebrafish larvae to perchlorate resulted in developmental toxicity in a concentration-dependent manner. Heart rate abnormality (33 %), slow blood flow (37 %), abnormal size of liver (23 %), delayed yolk absorption (70 %), and abnormal body pigmentation (100 %) were observed in the 3.83 mg/mL group. Heart edema (10 %), heart rate abnormality (60 %), slow blood flow (67 %), abnormal size of liver (77 %), delayed yolk absorption (100 %), abnormalities in intestinal morphology (30 %), abnormal body pigmentation (100 %), and shorter body length (47 %) were observed in the 4.03 mg/mL group. Developmental neurotoxicity was characterized by brain apoptosis, damage to the central nervous system (P < 0.01) and peripheral motor neurons (P < 0.0001), and reduced autonomous motor distance (P < 0.01). Transcriptomic analysis revealed that c3a.1, c5, fga, fgb, and fgg were upregulated in the complement and coagulation cascades, and the mRNA levels of c3a.1, dusp1, slc2a6, purba, and klf9 were found upregulated in PCR.CONCLUSIONAcute perchlorate exposure on zebrafish larvae caused various developmental toxicity in a concentration-dependent manner, notably neurotoxicity. We believed the immunological and inflammatory responses were involved.

2025-02-01·Zhongguo shi yan xue ye xue za zhi

[Molecular Pathogenic Mechanism Study of Two Cases of Inherited Dysfibrinogenemia].

Article

作者: Wang, Min ; Jiang, Ao-Shuang ; Liu, Hong-Jun ; Wei, Nan ; Zhu, Li-Juan ; Chen, Tian-Ping ; Qu, Li-Jun ; Zhu, Cheng-Lin

题目2例遗传性异常纤维蛋白原血症分子致病机制研究.目的对两个遗传性异常纤维蛋白原血症家系进行基因分析，探讨分子发病机制。.方法检测先证者及其家系成员凝血相关指标。用PCR法扩增纤维蛋白原FGA、FGB、FGG外显子及其侧翼序列，测序寻找突变位点；用SIFT、PolyPhen2、LRT、ReVe、MutationTaster、phyloP、phastCons生物信息学软件预测突变位点功能；用PyMOL和Clustal X分析变异蛋白质结构及氨基酸保守性。.结果家系1先证者凝血酶时间（TT）为37.00 s，纤维蛋白原活性（Fg∶C）降低至0.52 g/L；家系2先证者TT为20.30 s，Fg∶C低于正常范围，为1.00 g/L。基因分析结果显示，家系1先证者FGA基因存在c.80T>C杂合突变，导致27位苯丙氨酸突变为丝氨酸（Phe27Ser）；家系2先证者FGG基因存在c.1007T>A杂合突变，导致336位甲硫氨酸突变为赖氨酸（Met336Lys）。生物信息学软件预测分析提示两个变异均为有害变异；PyMOL突变模型提示，家系1先证者Aα链Phe27Ser和家系2先证者γ链Met336Lys，引起空间结构改变，导致蛋白稳定性降低；Clustal X结果显示，Aα链Phe27和γ链Met336在同源物种间高度保守。.结论FGA基因c.80T>C及FGG基因c.1007T>A杂合突变，均为致病性变异，引起遗传性异常纤维蛋白原血症。.

2025-02-01·Journal of Stroke and Cerebrovascular Diseases

Mendelian randomization assessing causal relationship between fibrinogen levels and ischemic stroke

Article

作者: Lepert, Louise ; Han, Thang Sieu ; Mughal, Sana ; Ken-Dror, Gie ; Sharma, Pankaj ; Hills, Emily ; Khanna, Tanya

OBJECTIVEHigh fibrinogen levels are associated with an increased risk of ischaemic stroke (IS). We used mendelian randomisation (MR) to explore a potential causal relationship.MATERIALS AND METHODSData for assessing the relationship between gene variant, disease and biological levels needed for a MR approach was collected using a meta-analytical approach. Inverse-variance weighted (IVW) approach was used for the main analyses and alternative approach for sensitivity analyses. The relationship between fibrinogen levels and IS was assessed using Odds Ratio (OR), while mean difference (g/L) was used for the relationship between SNP (rs1800790) and fibrinogen levels.RESULTSThe variant FGB rs1800790 SNP was interrogated as an instrumental variable of fibrinogen levels. A meta-analysis with 24 studies (12 case-control and 12 cohort studies, totalling 20,902 cases and 76,510 controls was conducted. Homozygotes (AG) of rs1800790 have 0.14g/L (95%CI: 0.08-0.19, P<0.001) and minor allele (AA) have 0.18g/L (95%CI: 0.01-0.35, P=0.037) higher levels of plasma fibrinogen concentration compared with homozygous for the major allele (GG). The risk of IS was significantly increased in 1-g/L (OR=1.83, 95%CI: 0.92-3.62, P=0.084), or 1-SD of fibrinogen levels (OR=1.39, 95%CI: 1.03-1.87, P=0.030), or above median levels (OR=1.22, 95%CI: 1.02-1.46, P=0.029) or categorical levels tertiles (OR=1.50, 95%CI: 1.26-1.79, P<0.001). Each 1-g/L increase in fibrinogen levels was causally associated with a higher risk of ischemic stroke (OR=2.28, 95%CI: 1.53-3.03, P<0.001) in the Mendelian randomisation analysis.CONCLUSIONSElevated fibrinogen levels are a causative risk factor for ischaemic stroke with each 1g/L increase doubling its risk.

项与 FGB 相关的新闻（医药）

2023-06-08

·生物谷

EVTOP技术研究微升生物体液循环EV中的磷酸化蛋白质组特征

一、摘要|导读：许多生物过程离不开动态的蛋白质磷酸化调节，因此监测循环生物体液中与疾病相关的磷酸化事件意义非凡，然而，由于磷酸酶的存在使得监测生物体液中磷酸化蛋白的变化极具挑战性。近期，东南大学W. Andy Tao教授团队在Angewandte Chemie在线发表了题为Profiling Phosphoproteome Landscape in Circulating Extracellular Vesicles from Microliters of Biofluids through Functionally Tunable Paramagnetic Separation的研究文章。该研究介绍了一种功能可调的材料和方法：从细胞外囊泡到磷酸化蛋白-------EVTOP(Extracellular Vesicles To Phosphoproteins)，它实现了一步法分离、提取和消化EV蛋白，并富集了磷酸化肽段，而且只需微量的起始生物液。用钛(IV)离子功能化的磁珠和穿膜肽八精氨酸（ R8+）有效地分离EV，同时R8+提供了亲水表面以在裂解过程中保留EV蛋白。随后磁珠上消化的同时将EVTOP转化为纯Ti(IV)离子表面，有效地富集了磷酸化肽。这个简化的超灵敏平台能够仅用几个μL血浆就能定量500个独特的EV磷酸化肽，用100μL脑脊液（CSF）就能定量1,200多个磷酸化肽。该团队还探讨了小容量CSF监测原发性中枢神经系统淋巴瘤(PCNSL，Primary Central Nervous System Lymphoma)化疗效果的临床应用，为临床的广泛应用提供了有力工具。二、实验|设计和方法图1. 实验流程示意图上图简要展示了该团队从微量体液中分离肠道病毒并原位富集磷酸化肽用于深度磷酸化蛋白质组图谱的研究方法。三、结果|创新点图2. 关于EVTOP磁珠制备及EV分离的表征EVTOP设计充分利用了EV的双层磷脂层结构，包括自组装的疏水尾部和亲水性磷酸盐头部，并考虑了直接在珠上的样品的下游工艺。该方法特殊在：(I)磁珠被Ti(IV)离子和 R8+功能化，为有效分离EV提供协同亲和力；(Ⅱ)带正电的Ti(IV)离子和 R8+通过疏水-亲水(HILIC)相互作用提供亲水表面，在EV裂解过程中保留EV蛋白；(Ⅲ)珠上消化产生多肽并同时将 R8+从珠子上切割下来；(Ⅳ)EVTOP只在表面吸附了Ti(IV)离子，实现了磷酸化肽在LC-MS分析中的特异性富集化。EVTOP的主要特点是能够通过同一磁珠上官能团的相互作用和转化，实现从生物液体到浓缩EV磷酸化肽的所有样品制备步骤。一步法在MS分析前不需要任何清理或除盐步骤，最大限度地减少了样品损失，从而能够利用微升临床样品实现极其灵敏和定量的磷酸化蛋白质组学。该团队考察了三种功能化磁珠以及超速离心法对EV的捕获。根据三种EV标志物(CD9、Flotillin 1和β-Actin)的WB结果，EV分离效率的顺序是EVTOP>仅R8+>仅Ti(IV)>超速离心法，其中EVTOP最有效。图3. 胰酶处理EVTOP磁珠对EV捕获率的影响经胰酶消化后的EVTOP磁珠的捕获EV效率明显下降，同时Zeta电位发生变化。WB结果和质谱学鉴定进一步证实了R8+和Ti(IV)离子的重要作用。通过在胰酶消化过程中同时切割R8+，EVTOP被转化为纯Ti(IV)离子磁珠。PCNSL是一种罕见的仅限于中枢神经系统的非霍奇金淋巴瘤亚型，作为一种具有复杂发病机制的高度异质性疾病，PCNSL的分子特征至关重要，CSF是准确评估疾病的理想微创生物液体。以前使用大量CSF样本的尝试只发现了少量的磷酸化蛋白。为了展示EVTOP的临床应用，该团队首先使用EVTOP方法分析了21例PCNSL患者和21例匹配的非PCNSL对照CSF样本的EV磷酸化蛋白质组学定量。图4.临床CSF样本本分析过程及结果。该团队总共从CSF样本 EVs中鉴定出3,344个磷酸化肽，代表689个磷酸化蛋白，其中160个磷酸化蛋白在PCNSL患者中上调。GO、KEGG途径和PPI分析表明，上调的磷酸化蛋白参与神经肽激素活性、透明质酸结合和多种信号途径，如Wnt信号和PI3K-Akt途径。其中一些上调的磷酸化蛋白被报道为PCNSL和其他癌症的潜在生物标记物，如骨桥蛋白(SPP1)，组织蛋白B(CTSB)，纤维连接蛋白(FN1)，CD44，Tenascin-X(TNX)，肉豆蔻酰化丙氨酸C-激酶底物(Marcks)和Testican-3(SPOCK3)。图5.已识别的EV磷酸化蛋白作为潜在的生物标志物评估PCNSL化疗结果的可行性。该团队选择了11名PCNSL患者的独立队列，这些患者最初接受大剂量甲氨蝶呤治疗，总体临床反应良好。分别于化疗前和化疗后采集CSF标本100ug。然后对CSF样本进行EVTOP程序以获得EV磷酸化肽。使用TimeTOF Pro仪上的平行反应监测和平行累积-连续碎裂(PRM-FASEF)相结合的方法来监测化疗前后这些上调的磷酸化蛋白的强度变化。排除了重复性相对较差、产物离子覆盖率较低、缺乏生物学意义(无疾病或相关生物途径关联)的磷酸化肽。发现10个磷酸化蛋白【SPP1、促甲状腺激素释放激素原(TRH)、Tenascin-C(TNC)、硒蛋白P(SEPP1)、纤维蛋白原β链(FGB/FIBB)、层粘连蛋白β1(Lamb1)、TNX、富组氨酸糖蛋白(HRG)、高尔基相关蛋白1B(GAK1B)和胰岛素样生长因子结合蛋白5(fbp5/IBP5)】在化疗后显示出明显的信号减少。此外，Reatcome/KEGG通路分析和PPI分析表明，这其中6个属于脑组织，这些生物标记物大多参与PI3K-Akt、PI3K-Akt-mTOR和其他重要的信号通路，据报道与PCNSL的发生和发展有关，并成为各种癌症和神经退行性疾病的治疗靶点。磷酸化蛋白SPP1、TRH、TNC、SEPP1、IBP5和TNX与神经系统疾病相关，其中SPP1是PCNSL筛查的生物标志物。该团队能够从治疗前和治疗后的100μL CSF样本中定量它们的事实，突显了EVTOP方法的强大和未来应用的巨大潜力。四、总结|讨论该研究介绍的EVTOP磁珠有希望用于处理大样本批次、有限样本材料和具有挑战性的生物样本的临床筛查和生物标记物发现。该研究展示了EVTOP用于使用微量生物流体进行EV磷酸化蛋白质组谱分析的优势，未来改进该方法可以扩展到含有其他翻译后修饰的EV多肽的富集化，例如糖基化、乙酰化和其他修饰。EVTOP由于其超高灵敏度和稳定性，可以作为一种临床程序来筛选或靶向循环EVs中的功能蛋白，用于疾病诊断。参考文献：Jie Sun, et al, Profiling Phosphoproteome Landscape in Circulating Extracellular Vesicles from Microliters of Biofluids through Functionally Tunable Paramagnetic Separation, Angew. Chem. Int. Ed. 2023, e202305668DOI: 10.1002/anie.202305668https://doi.org/10.1002/anie.202305668

临床研究