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相关概念视频

The JAK-STAT Signaling Pathway01:20

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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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M-Cdk Drives Transition Into Mitosis02:15

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Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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CDK8介导的炎症微环境加剧了骨关节炎的进展.

Zhongnan Lin1, Yining Xu1, Hongyi Jiang1

  • 1Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou Zhejiang Province China; Key Laboratory of Orthopedics of Zhejiang Province Wenzhou Zhejiang Province China; The Second Clinical School of Medicine Wenzhou Medical University Wenzhou Zhejiang Province China.

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概括

循环素依赖性激酶8 (CDK8) 通过通过NF-κB促进炎症SASP基因转录来驱动骨关节炎 (OA). 抑制CDK8降低SASP,提供了一个潜在的新关节炎治疗标.

关键词:
CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK8 CDK9 CDK8 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9 CDK9在 NF-κBB 中.骨关节炎是一种骨关节炎.转录延伸是指转录延长.转录法规 转录法规

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科学领域:

  • 生物化学 生物化学
  • 分子生物学分子生物学
  • 免疫学 免疫学 免疫学

背景情况:

  • 循环林依赖激酶8 (CDK8) 是一种转录调节剂,参与炎症过程.
  • CDK8在骨关节炎 (OA) 发病过程中的特定作用仍然在很大程度上未被探索.

研究的目的:

  • 为了调查CDK8是否与NF-κB合作,以调节衰老相关的分泌表型 (SASP) 基因转录.
  • 为了确定这种相互作用是否会加剧OA炎症微环境.
  • 为了阐明底层的分子机制.

主要方法:

  • 使用一个DMM手术小鼠模型用于OA.
  • 通过使用H&E染色,西部斑点,qRT-PCR,ELISA,PAM和Von Frey测试来评估OA病理和疼痛.
  • 采用光酶和ChIP测试来探索转录调节和延长机制.

主要成果:

  • CDK8通过NF-κB被招募到SASP促进器中,通过Rpb1 CTD酸化促进SASP转录.
  • 冠状细胞通过CDK8介导的SASP分泌增强了关节炎症,并驱动了骨质细胞分化.
  • 这个过程加剧了骨关节炎的严重程度.

结论:

  • 冠状细胞衍生的SASP显著导致OA的严重程度.
  • CDK8和NF-κB共同调节SASP转录,使CDK8抑制成为潜在的治疗策略.
  • 向CDK8提供了一种通过减少SASP分泌来治疗骨关节炎的新方法.