揭示 Upadacitinib 对 Sjogren's 综合征的治疗靶点和分子机制。

IF 2.3 Q3 ENGINEERING, BIOMEDICAL Biomedical Engineering and Computational Biology Pub Date : 2024-10-23 eCollection Date: 2024-01-01 DOI:10.1177/11795972241293519
Youguo Yang, Yuan Liu, Xiaofen Li, Yongping Zeng, Weiqian He, Juan Zhou
{"title":"揭示 Upadacitinib 对 Sjogren's 综合征的治疗靶点和分子机制。","authors":"Youguo Yang, Yuan Liu, Xiaofen Li, Yongping Zeng, Weiqian He, Juan Zhou","doi":"10.1177/11795972241293519","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Upadacitinib, a selective Janus associated kinase 1 (JAK-1) inhibitor, can be prescribed particularly for the clinical treatment with Crohn's disease or rheumatoid arthritis. It is clinically observed that upadacitinib has been found with potential therapeutic effectiveness on Sjogren's syndrome (SS). However, the anti-SS targets and mechanisms involved in upadacitinib treatment remain uninvestigated.</p><p><strong>Materials and methods: </strong>Thus, this study was designed to identify therapeutic targets and mechanisms of upadacitinib for treating SS through conducting network pharmacology and molecular docking analyses.</p><p><strong>Results: </strong>In total, we identified 298 upadacitinib-related target genes, 1339 SS-related targets before collecting 56 overlapped target genes and 12 hub target genes. Upadacitinib largely exerted the critical biological processes including regulation of microenvironment homeostasis, inflammatory response, and cell apoptosis, and largely acted on pivotal molecular mechanisms including hypoxia-inducible factor 1 (HIF-1) signaling pathway, apoptosis pathway, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, or Th17 cell differentiation pathway. Molecular docking data suggested that upadacitinib exhibited the high affinities with signal transducer and activator of transcription 3 (STAT3), HIF1A, poly(ADP-ribose) polymerase 1 (PARP1) target proteins, in which the structural interactions between upadacitinib and STAT3, HIF1A, PARP1 showed potential therapeutic activities against SS.</p><p><strong>Conclusion: </strong>In conclusion, upadacitinib possesses the bright anti-inflammatory and anti-apoptotic activities on SS, and this study can provide a theoretical basis for clinical therapy of SS using upadacitinib.</p>","PeriodicalId":42484,"journal":{"name":"Biomedical Engineering and Computational Biology","volume":"15 ","pages":"11795972241293519"},"PeriodicalIF":2.3000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528621/pdf/","citationCount":"0","resultStr":"{\"title\":\"Uncovering the Therapeutic Target and Molecular Mechanism of Upadacitinib on Sjogren's Syndrome.\",\"authors\":\"Youguo Yang, Yuan Liu, Xiaofen Li, Yongping Zeng, Weiqian He, Juan Zhou\",\"doi\":\"10.1177/11795972241293519\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Upadacitinib, a selective Janus associated kinase 1 (JAK-1) inhibitor, can be prescribed particularly for the clinical treatment with Crohn's disease or rheumatoid arthritis. It is clinically observed that upadacitinib has been found with potential therapeutic effectiveness on Sjogren's syndrome (SS). However, the anti-SS targets and mechanisms involved in upadacitinib treatment remain uninvestigated.</p><p><strong>Materials and methods: </strong>Thus, this study was designed to identify therapeutic targets and mechanisms of upadacitinib for treating SS through conducting network pharmacology and molecular docking analyses.</p><p><strong>Results: </strong>In total, we identified 298 upadacitinib-related target genes, 1339 SS-related targets before collecting 56 overlapped target genes and 12 hub target genes. Upadacitinib largely exerted the critical biological processes including regulation of microenvironment homeostasis, inflammatory response, and cell apoptosis, and largely acted on pivotal molecular mechanisms including hypoxia-inducible factor 1 (HIF-1) signaling pathway, apoptosis pathway, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, or Th17 cell differentiation pathway. Molecular docking data suggested that upadacitinib exhibited the high affinities with signal transducer and activator of transcription 3 (STAT3), HIF1A, poly(ADP-ribose) polymerase 1 (PARP1) target proteins, in which the structural interactions between upadacitinib and STAT3, HIF1A, PARP1 showed potential therapeutic activities against SS.</p><p><strong>Conclusion: </strong>In conclusion, upadacitinib possesses the bright anti-inflammatory and anti-apoptotic activities on SS, and this study can provide a theoretical basis for clinical therapy of SS using upadacitinib.</p>\",\"PeriodicalId\":42484,\"journal\":{\"name\":\"Biomedical Engineering and Computational Biology\",\"volume\":\"15 \",\"pages\":\"11795972241293519\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-10-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528621/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomedical Engineering and Computational Biology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1177/11795972241293519\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"ENGINEERING, BIOMEDICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical Engineering and Computational Biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/11795972241293519","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0

摘要

目的:乌达帕替尼是一种选择性 Janus 相关激酶 1(JAK-1)抑制剂,特别适用于克罗恩病或类风湿性关节炎的临床治疗。临床观察发现,奥达帕替尼对 Sjogren's 综合征(SS)具有潜在疗效。然而,奥达替尼治疗SS的抗SS靶点和机制仍未得到研究:因此,本研究旨在通过开展网络药理学和分子对接分析,确定乌达替尼治疗SS的治疗靶点和机制:结果:我们共发现了 298 个达达替尼相关靶基因、1339 个 SS 相关靶基因,然后收集了 56 个重叠靶基因和 12 个枢纽靶基因。奥达替尼在很大程度上影响了微环境稳态调节、炎症反应和细胞凋亡等关键生物学过程,并在很大程度上作用于缺氧诱导因子1(HIF-1)信号通路、细胞凋亡通路、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路或Th17细胞分化通路等关键分子机制。分子对接数据表明,乌达替尼与信号转导和转录激活因子3(STAT3)、HIF1A、聚(ADP-核糖)聚合酶1(PARP1)靶蛋白具有高亲和力,其中乌达替尼与STAT3、HIF1A、PARP1之间的结构相互作用显示出对SS的潜在治疗活性:总之,奥达替尼对SS具有明显的抗炎和抗凋亡活性,该研究可为奥达替尼对SS的临床治疗提供理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Uncovering the Therapeutic Target and Molecular Mechanism of Upadacitinib on Sjogren's Syndrome.

Objective: Upadacitinib, a selective Janus associated kinase 1 (JAK-1) inhibitor, can be prescribed particularly for the clinical treatment with Crohn's disease or rheumatoid arthritis. It is clinically observed that upadacitinib has been found with potential therapeutic effectiveness on Sjogren's syndrome (SS). However, the anti-SS targets and mechanisms involved in upadacitinib treatment remain uninvestigated.

Materials and methods: Thus, this study was designed to identify therapeutic targets and mechanisms of upadacitinib for treating SS through conducting network pharmacology and molecular docking analyses.

Results: In total, we identified 298 upadacitinib-related target genes, 1339 SS-related targets before collecting 56 overlapped target genes and 12 hub target genes. Upadacitinib largely exerted the critical biological processes including regulation of microenvironment homeostasis, inflammatory response, and cell apoptosis, and largely acted on pivotal molecular mechanisms including hypoxia-inducible factor 1 (HIF-1) signaling pathway, apoptosis pathway, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, or Th17 cell differentiation pathway. Molecular docking data suggested that upadacitinib exhibited the high affinities with signal transducer and activator of transcription 3 (STAT3), HIF1A, poly(ADP-ribose) polymerase 1 (PARP1) target proteins, in which the structural interactions between upadacitinib and STAT3, HIF1A, PARP1 showed potential therapeutic activities against SS.

Conclusion: In conclusion, upadacitinib possesses the bright anti-inflammatory and anti-apoptotic activities on SS, and this study can provide a theoretical basis for clinical therapy of SS using upadacitinib.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
1
审稿时长
8 weeks
期刊最新文献
Computer-Aided Discovery of Abrus precatorius Compounds With Anti-Schistosomal Potential. Synthesis and Application of Sustainable Tricalcium Phosphate Based Biomaterials From Agro-Based Materials: A Review. A Physical Framework to Study the Effect of Magnetic Fields on the Spike-Time Coding. On Mechanical Behavior and Characterization of Soft Tissues. Construction of Prognostic Prediction Models for Colorectal Cancer Based on Ferroptosis-Related Genes: A Multi-Dataset and Multi-Model Analysis.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1