更新于：2024-11-01

Nrf2 x NFKB1

更新于：2024-11-01

基本信息

关联

项与 Nrf2 x NFKB1 相关的药物

AQP-1180

靶点

NFKB1 x Nrf2

作用机制

NFKB1 modulators [+1]

在研机构-

原研机构

Aquapharm Biodiscovery Ltd.

在研适应症-

非在研适应症

炎症

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 Nrf2 x NFKB1 相关的临床结果

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100 项与 Nrf2 x NFKB1 相关的转化医学

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0 项与 Nrf2 x NFKB1 相关的专利（医药）

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336

项与 Nrf2 x NFKB1 相关的文献（医药）

2024-12-01·Computational Biology and Chemistry

A comprehensive bioinformatic analysis of the role of TGF-β1-stimulated activating transcription factor 3 by non-coding RNAs during breast cancer progression

Article

作者: Preetha, Dilipkumar ; Selvamurugan, Nagarajan ; Saranya, Iyyappan ; Nivruthi, Sasi

A potent growth inhibitor for normal mammary epithelial cells is transforming growth factor beta 1 (TGF-β1). When breast tissues lose the anti-proliferative activity of this factor, invasion and bone metastases increase. Human breast cancer (hBC) cells express more activating transcription factor 3 (ATF3) when exposed to TGF-β1, and this transcription factor is essential for BC development and bone metastases. Non-coding RNAs (ncRNAs), including circular RNAs (circRNAs) and microRNAs (miRNAs), have emerged as key regulators controlling several cellular processes. In hBC cells, TGF-β1 stimulated the expression of hsa-miR-4653-5p that putatively targets ATF3. Bioinformatics analysis predicted that hsa-miR-4653-5p targets several key signaling components and transcription factors, including NFKB1, STAT1, STAT3, NOTCH1, JUN, TCF3, p300, NRF2, SUMO2, and NANOG, suggesting the diversified role of hsa-miR-4653-5p under physiological and pathological conditions. Despite the high abundance of hsa-miR-4653-5p in hBC cells, the ATF3 level remained elevated, indicating other ncRNAs could inhibit hsa-miR-4653-5p's activity. In silico analysis identified several circRNAs having the binding sites for hsa-miR-4653-5p, indicating the sponging activity of circRNAs towards hsa-miR-4653-5p. The study's findings suggest that TGF-β1 regulates circRNAs and hsa-miR-4653-5p, which in turn affects ATF3 expression, thus influencing BC progression and bone metastasis. Therefore, focusing on the TGF-β1/circRNAs/hsa-miR-4653-5p/ATF3 network could lead to new ways of diagnosing and treating BC.

2024-12-01·European Journal of Medicinal Chemistry

Andrographolide: A promising therapeutic agent against organ fibrosis

Review

作者: Wang, Wenhong ; Li, Ke ; Wu, Jiabin ; Xiao, Weihua ; Dai, Wei ; Xu, Yingying

Fibrosis is the terminal pathology of chronic illness in many organs, marked by excessive accumulation of extracellular matrix proteins. These changes influence organ function, ultimately resulting in organ failure. Although significant progress has been achieved in comprehending the molecular pathways responsible for fibrosis in the last decades, effective and approved clinical therapies for the condition are still lacking. Andrographolide is a diterpenoid isolated and purified mainly from the aboveground parts of the Andrographis paniculata plant, which possesses good effects of purging heat, detoxifying, antibacterial and anti-inflammatory. In-depth research has gradually confirmed the anticancer, antioxidant, antiviral and other effects of Andro so that it can play a preventive and therapeutic role in various diseases. Over the past few years, an increasing number of research findings have indicated that Andro exerts antifibrotic effects in various organs by acting on transforming growth factor-β/small mother against decapentaplegic protein, mitogen-activated protein kinases, nuclear factor-E2-related factor 2, nuclear factor kappa-B and other signalling molecules to inhibit inflammation, oxidative stress, epithelial-mesenchymal transition, fibroblast activation and collagen buildup. This review presents a compilation of findings regarding the antifibrotic impact of Andro in tissue and cell models in vitro and in vivo. Emphasis is placed on the potential therapeutic benefits of Andro in diseases related to organ fibrosis. Existing studies and cutting-edge technologies on Andro pharmacokinetics, toxicity and bioavailability are briefly discussed to provide evidence for accelerating its clinical conversion and adoption.

2024-12-01·International Journal of Biological Macromolecules

Structural characterization of the polysaccharides from Atractylodes chinensis (DC.) Koidz. and the protective effection against alcohol-induced intestinal injury in rats

Article

作者: Weng, Lili ; Chen, Yanan ; Sun, Jin ; Xiao, Chunping ; Wang, Bo ; Jiang, Yuxin ; Yang, Jingrong ; Chen, Tianli ; Luo, Haoming

A neutral polysaccharide, AP, with a weight-average molecular weight of 60.61 kDa, consisting mainly of arabinose and galactose, was isolated from the rhizomes of Atractylodes chinensis (DC.) Koidz. Methylation analyses and nuclear magnetic resonance spectroscopy indicated that the probable repeat unit of AP was →3,6)-α-D-Galp-(1→ residues and constituted the main chain, with a side chain of →5)-α-L-Araf-(1→ and terminal α-L-Araf attached to C-6 of the main chain. The protective activity and potential mechanisms of action of AP on the intestinal tract were investigated. AP improved intestinal oxidative stress injury and inflammatory responses by promoting the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway and inhibiting the toll-like receptor 4/myeloid differentiation primary response protein 88/nuclear factor-kappa B signaling pathway, but also repaired colonic mucosal injury and reduced intestinal leakage of endotoxins by promoting expression of the tight-junction proteins zonula occludens-1 and occludin. AP improved ecological dysregulation of the intestinal microbiota and promoted the growth of the potentially beneficial bacteria Lactobacillus_taiwanensis, Limosilactobacillus_reuteri and Akkermansia_muciniphila. AP promoted intestinal health by increasing the production of potentially beneficial metabolites such as short-chain fatty acids, Indole-3-propionic acid, and N-Eicosapentaenoyl tryptophan through metabolism (amino acids, lipids, carbohydrates). These results suggest that AP is a promising prebiotic in attenuating alcohol-induced intestinal damage.

项与 Nrf2 x NFKB1 相关的新闻（医药）

2023-07-22

·佰傲谷BioValley

14种衰老模型的特点

衰老是一种机体组织、器官、细胞多维度稳态失衡、功能退化的过程，其诱因复杂、表现多样，使人们对衰老的研究需要利用各种模型来模拟人体生理、病理过程，以此来揭示衰老机制，指导抗衰老策略。衰老的特征（Front. Cell Dev. Biol. 2022）体外模型类型特征复制性衰老：RS复制衰老模型饱和密度降低，细胞表面积、体积增加，细胞周期停滞，端粒缩短。化疗诱导衰老：CIS羟基脲诱导ROS增加，细胞增殖减少。Aβ1-42寡聚体AD模型ROS增加，PAI-1和p21的mRNA水平升高，SIRT1水平降低。D-半乳糖诱导ROS增加，炎症水平升高，p16、p21、p53基因表达增加，NRF2、HO-1减少。阿霉素诱导（DAN拓扑异构酶抑制剂）细胞周期停滞，DNA损伤增加，端粒缩短，p16lnk4a基因表达增加。Palbociclib诱导（CDK4/CDK6抑制剂）G0/G1停滞，细胞生长停滞Rb蛋白表达减少，IL-6、IL-8、CXCL1分泌增加。应激诱导早衰：SIPSX射线诱导不可逆的G1周期停滞，DNA损伤，IL-1β、IL-6、IL-8分泌增加紫外线（UVB）诱导生长停滞，线粒体DNA缺失衰老相关基因表达增加。H2O2诱导G1期停滞，端粒缩短，p21、gadd45基因表达增加t-BHP诱导生长停滞，线粒体DNA 4977-bp片段缺失，p21waf-1过度表达，Rb蛋白磷酸化受阻，衰老基因表达增加。乙醇诱导生长停滞，线粒体DNA 4977-bp片段缺失，p21waf-1过度表达，pRb无法磷酸化衰老相关基因表达增加。高氧诱导G1期停滞，端粒缩短，蛋白降解增加，脂褐质/蜡样质积累。癌基因诱导衰老：OISMos-过表达模型生长停滞，DNA损伤，p16INK4a上调，SA-β-gal阳性染色增加。B-RAF V600E模型细胞周期停滞，p16INK4a上调，SA-β-gal阳性染色增加。H-RAS G12V模型p16INK4a上调，Rb磷酸化程度降低，SA-β-gal阳性染色增加。抑制DNA甲基转移酶5-aza-2'-脱氧胞苷诱导模型生长抑制，p16表达增加，p53表达减少。抑制端粒酶活性SYUIQ-5诱导生长抑制，p16、p21、p27表达增加。细胞周期蛋白E过表达细胞周期停滞，DNA损伤增加。IMR90 ER: RAS模型生长停滞，衰老相关分泌表型（SASP）标志物表达增加。来自老年捐赠者具有衰老表型的iPSC衍生神经元来自老年供体的iPSC衍生神经元，具有衰老相关基因表达。具有衰老表型的诱导神经元来自老年供体成纤维细胞，具有年龄更依赖型转录组特征。体内模型类型特征快速衰老模型SAMPSAMP6：老年骨质疏松模型骨形成减少，骨髓脂肪增加，PPARγ、Sfrp4表达增加。SAMP8：AD模型年龄相关的学习、记忆障碍，Aβ沉积，自噬功能异常。SAMP10：神经退行性病变自发性大脑退化，学习、记忆、情绪障碍。理化因素诱导模型D-半乳糖ROS增加，炎性水平升高，线粒体功能障碍，细胞凋亡增加，p21、p53基因表达上调。AICI3认知功能显著降低，短期记忆受损、焦虑加剧、空间和参考记忆下降。D-半乳糖+AICI3记忆缺陷，神经元损伤，海马区caspase-3过度表达。D-半乳糖+NaNO2认知、记忆障碍，氧化应激增加，海马CA1、CA3、CA4区神经元损伤，精子质量下降，睾丸形态恶化。铁辐射感应持续性DNA损伤反应，SASP标记增加，IL-8产生增加。O3诱导胸腺萎缩，体重减轻，探索活性减少，氧化损伤增加。Wrn基因敲除：Werner综合征Wrn-/-，Trec-/-白发，脱发，白内障，骨质疏松，T2D，端粒缩短。Wrn△hel/△hel严重的心脏间质纤维化，胰岛素抵抗，高甘油三酯血症，癌症发病率增加，ROS增加，DNA损伤增加。Lmn突变：HGPSLmna L530P/L530P严重生长迟缓，脱发，骨质疏松，肌肉萎缩。Lmna HG/+生长缓慢，骨质疏松，脱发，偏脂营养不良。lmna G609G/G609G不孕，体重减轻，生长迟缓，脊柱弯曲，血管钙化，骨密度降低，胰岛素样生长因子减少。Zmpste24 -/-严重生长迟缓，扩张性心肌病，脂肪营养不良，肌肉营养不良，过早死亡。其他基因相关模型BubR1 H/H大脑胶质增生、白内障、心率失常，皮肤变薄，血管弹性降低，纤维化受损。Ndufs4 -/-利氏综合征相关神经退行性改变，嗜睡，共济失调，体重减轻，过早死亡。ERCC1 -/-ERCC1 △/-生长迟缓，共济失调，视力丧失，小脑发育不全，脑病，肾功能衰竭。Sod1 -/-白内障，听力丧失，皮肤变薄，脂质代谢紊乱，伤口愈合缺陷。Klotho -/-心血管损伤，动脉硬化，皮肤萎缩，肺气肿Xpd TTD/TTD骨质疏松，骨质硬化，脊柱后凸，恶病质，白发，不育，寿命缩短。mtDNA Polγ突变（PolG）体重减轻，脱发，听力丧失，骨密度的降低，贫血，心肌病。PolgA mut/mut骨质疏松，脊柱侧弯，贫血，心脏增大，生育能力降低。Nfkb1 -/-骨质疏松，脊柱后凸，骨质疏松，组织炎症，中枢神经系统神经胶质增生，寿命缩短。Terc -/-器官功能受损，组织萎陷，生育能力降低，寿命缩短。3xTg-ADAD模型记忆障碍，认知缺陷，突触功能障碍，海马神经元异常兴奋，淀粉样斑块和p-Tau沉积。Tg2576AD模型认知障碍，记忆丧失，氧化性脂质损伤，大脑炎症。长寿动物裸鼹鼠寿命长，健康，死亡率低。涡虫DNA修复机制高效，端粒酶活性强，具有非常好的再生能力，被认为是永生的。蝾螈‍清除衰老细胞能力、再生能力强。乌龟ROS清除速度快，端粒酶活性强，DNA修复机制高效。转基因延缓衰老Ames侏儒鼠，Prop1 df/dfProp1基因隐性点突变，垂体发育受损，体型变小，PI3K-Akt-mTOR通路下调。Snel侏儒鼠，Pit1 dw/dwPit1基因自发突变，垂体发育受损，体型变小，免疫衰老减少。参考资料Carrasco, E. et al. The role of T cells in age-related diseases. Nat. Rev. Immunol. 22, 97–111 (2022).decline in ageing. Nature 590, 122–128 (2021). 56. Brauning, A. et al. Aging of the immune system: focus on natural killer cells phenotype and functions. Cells 11, 1017 (2022)Franco, A. C., Aveleira, C. & Cavadas, C. Skin senescence: mechanisms and impact on whole-body aging. Trends Mol. Med. 28, 97–109 (2022). Sabbatini, M. et al. Aging hampers neutrophil extracellular traps (NETs) efficacy. Aging Clin. Exp. Res. 34, 2345–2353 (2022)Li, X., Li, C., Zhang, W. et al. Inflammation and aging: signaling pathways and intervention therapies. Sig Transduct Target Ther 8, 239 (2023). https://doi-org.libproxy1.nus.edu.sg/10.1038/s41392-023-01502-8 van de Wal, M. A. E. et al. Ndufs4 knockout mouse models of Leigh syndrome: pathophysiology and intervention. Brain 145, 45–63 (2022).Davies DM, van den Handel K, Bharadwaj S and Lengefeld J (2022), Cellular enlargement - A new hallmark of aging? Front. Cell Dev. Biol. 10:1036602. doi: 10.3389/fcell.2022.1036602·········点亮在看，传递信息♥

临床1期临床结果siRNA信使RNA