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相关概念视频

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

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The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
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PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
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Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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Notch Signaling Pathway03:14

Notch Signaling Pathway

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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
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Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

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Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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史无前例的美罗特类药物通过准NF-κB和PI3K信号通路来发挥抗炎作用.

Yuqian Tang1, Die Yan1, Chuxing Liang1

  • 1Key Laboratory of Chinese Medicinal Resource from Lingnan, Ministry of Education, Key Laboratory of Chronic Disease Prevention and Control of Traditional Chinese Medicine of Guangdong Higher Education Institutes, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, P. R. China.

Organic letters
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概括

这项研究从真菌中分离出了新型的美罗特类物质,揭示了独特的碳骨架. 化合物1和6通过抑制氧化的产生和关键的炎症信号通路,表现出强大的抗炎作用.

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科学领域:

  • 自然产品化学 自然产品化学
  • 药用化学 医学化学
  • 菌生物技术是一种真菌生物技术.

背景情况:

  • 梅罗特类是复杂的天然产品,来自于美酸盐和石基酸盐路径.
  • 菌生物转化是产生结构多样化的二次代谢产物的强大工具.
  • 了解新型天然产品的抗炎潜力对于药物发现至关重要.

研究的目的:

  • 从共生真菌中分离和描述前所未有的美罗特类.
  • 调查这些新型化合物的抗炎活性.
  • 阐明其抗炎作用背后的分子机制.

主要方法:

  • 使用色谱和光谱技术对美罗特类的隔离和结构阐明.
  • 在使用RAW 264.7巨细胞系的体外抗炎试验中.
  • 西方斑分析用于评估炎症标记物和信号蛋白的表达.

主要成果:

  • 确定了四种新型的美罗特类 (1-10) 具有独特的化碳环系统.
  • 化合物1-3采用5/3/6/6/6系统,4-5采用6/6/6四环架构,6采用5/3/6/6/5五环架构,7-10采用6/6/6/5架构.
  • 化合物1和6显著抑制了氧化 (NO) 生产,超过了阳性对照印米他.
  • 化合物1和6降低了可诱导的氧化合成酶 (iNOS) 的调节,并抑制了NF-κB,PI3K和IκB-α酸化.

结论:

  • 这种共生真菌产生了结构多样化和前所未有的美罗特类.
  • 化合物1和6具有强大的抗炎性质.
  • 抗炎作用通过抑制iNOS表达和调节NF-κB和PI3K/Akt.等关键炎症信号通路来调节.