Acta Pharmaceutica Sinica. B最新文献

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A novel C-3-substituted oleanolic acid benzyl amide derivative exhibits therapeutic potential against influenza A by targeting PA–PB1 interactions and modulating host macrophage inflammation 一种新的c -3取代齐墩果酸苄基酰胺衍生物通过靶向PA-PB1相互作用和调节宿主巨噬细胞炎症,显示出治疗甲型流感的潜力
IF 14.6 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.05.031
Kunyu Lu , Jianfu He , Chongjun Hong , Haowei Li , Jiaai Ruan , Jinshen Wang , Haoxing Yuan , Binhao Rong , Chan Yang , Gaopeng Song , Shuwen Liu
{"title":"A novel C-3-substituted oleanolic acid benzyl amide derivative exhibits therapeutic potential against influenza A by targeting PA–PB1 interactions and modulating host macrophage inflammation","authors":"Kunyu Lu ,&nbsp;Jianfu He ,&nbsp;Chongjun Hong ,&nbsp;Haowei Li ,&nbsp;Jiaai Ruan ,&nbsp;Jinshen Wang ,&nbsp;Haoxing Yuan ,&nbsp;Binhao Rong ,&nbsp;Chan Yang ,&nbsp;Gaopeng Song ,&nbsp;Shuwen Liu","doi":"10.1016/j.apsb.2025.05.031","DOIUrl":"10.1016/j.apsb.2025.05.031","url":null,"abstract":"<div><div>The influenza A virus (IAV), renowned for its high contagiousness and potential to catalyze global pandemics, poses significant challenges due to the emergence of drug-resistant strains. Given the critical role of RNA polymerase in IAV replication, it stands out as a promising target for anti-IAV therapies. In this study, we identified a novel C-3-substituted oleanolic acid benzyl amide derivative, <strong>A5</strong>, as a potent inhibitor of the PA<sub>C</sub>–PB1<sub>N</sub> polymerase subunit interaction, with an IC<sub>50</sub> value of 0.96 ± 0.21 μmol/L. <strong>A5</strong> specifically targets the highly conserved PA<sub>C</sub> domain and demonstrates remarkable efficacy against both laboratory-adapted and clinically isolated IAV strains, including multidrug-resistant strains, with EC<sub>50</sub> values ranging from 0.60 to 1.83 μmol/L. Notably, when combined with oseltamivir, <strong>A5</strong> exhibits synergistic effects both <em>in vitro</em> and <em>in vivo</em>. In a murine model, dose-dependent administration of <strong>A5</strong> leads to a significant reduction in IAV titers, resulting in a high survival rate among treated mice. Additionally, <strong>A5</strong> treatment inhibits virus-induced Toll-like receptor 4 activation, attenuates cytokine responses, and protects against IAV-induced inflammatory responses in macrophages. In summary, <strong>A5</strong> emerges as a novel inhibitor with high efficiency and broad-spectrum anti-influenza activity.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4156-4173"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chemical knockdown of Keap1 and homoPROTAC-ing allergic rhinitis Keap1基因的化学表达下调与同质protac治疗变应性鼻炎的关系
IF 14.6 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.05.025
Jianyu Yan , Tianyu Wang , Ruizhi Yu , Lijuan Xu , Hongming Shao , Tengfei Li , Zhe Wang , Xudong Cha , Zhenyuan Miao , Chengguo Xing , Ke Xu , Huanhai Liu , Chunlin Zhuang
{"title":"Chemical knockdown of Keap1 and homoPROTAC-ing allergic rhinitis","authors":"Jianyu Yan ,&nbsp;Tianyu Wang ,&nbsp;Ruizhi Yu ,&nbsp;Lijuan Xu ,&nbsp;Hongming Shao ,&nbsp;Tengfei Li ,&nbsp;Zhe Wang ,&nbsp;Xudong Cha ,&nbsp;Zhenyuan Miao ,&nbsp;Chengguo Xing ,&nbsp;Ke Xu ,&nbsp;Huanhai Liu ,&nbsp;Chunlin Zhuang","doi":"10.1016/j.apsb.2025.05.025","DOIUrl":"10.1016/j.apsb.2025.05.025","url":null,"abstract":"<div><div>Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule <strong>8</strong> encompasses robust capacity to degrade Keap1 as a homoPROTAC<sup>KEAP1</sup>. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC<sup>KEAP1</sup> led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4137-4155"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
AI-integrated IQPD framework of quality prediction and diagnostics in small-sample multi-unit pharmaceutical manufacturing: Advancing from experience-driven to data-driven manufacturing 小样本多单位制药生产中质量预测和诊断的ai集成IQPD框架:从经验驱动向数据驱动的制造推进
IF 14.6 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.06.001
Kaiyi Wang , Xinhai Chen , Nan Li , Huimin Feng , Xiaoyi Liu , Yifei Wang , Yanfei Wu , Yufeng Guo , Shuoshuo Xu , Lu Yao , Zhaohua Zhang , Jun Jia , Zhishu Tang , Zhisheng Wu
{"title":"AI-integrated IQPD framework of quality prediction and diagnostics in small-sample multi-unit pharmaceutical manufacturing: Advancing from experience-driven to data-driven manufacturing","authors":"Kaiyi Wang ,&nbsp;Xinhai Chen ,&nbsp;Nan Li ,&nbsp;Huimin Feng ,&nbsp;Xiaoyi Liu ,&nbsp;Yifei Wang ,&nbsp;Yanfei Wu ,&nbsp;Yufeng Guo ,&nbsp;Shuoshuo Xu ,&nbsp;Lu Yao ,&nbsp;Zhaohua Zhang ,&nbsp;Jun Jia ,&nbsp;Zhishu Tang ,&nbsp;Zhisheng Wu","doi":"10.1016/j.apsb.2025.06.001","DOIUrl":"10.1016/j.apsb.2025.06.001","url":null,"abstract":"<div><div>The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human–Cyber–Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4193-4209"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dual-ferroptosis induction-based microneedle patches for enhanced chemodynamic/photothermal combination therapy against triple-negative breast cancer 基于双铁下垂诱导的微针贴片用于增强化疗/光热联合治疗三阴性乳腺癌
IF 14.6 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.05.034
Yujie Wang , Zhaoyou Chu , Peisan Wang , Tao Li , Yu Jin , Silong Wu , Xiaowei Song , Weinan Zhang , Miaomiao Yang , Zhengbao Zha , Haisheng Qian , Yan Ma
{"title":"Dual-ferroptosis induction-based microneedle patches for enhanced chemodynamic/photothermal combination therapy against triple-negative breast cancer","authors":"Yujie Wang ,&nbsp;Zhaoyou Chu ,&nbsp;Peisan Wang ,&nbsp;Tao Li ,&nbsp;Yu Jin ,&nbsp;Silong Wu ,&nbsp;Xiaowei Song ,&nbsp;Weinan Zhang ,&nbsp;Miaomiao Yang ,&nbsp;Zhengbao Zha ,&nbsp;Haisheng Qian ,&nbsp;Yan Ma","doi":"10.1016/j.apsb.2025.05.034","DOIUrl":"10.1016/j.apsb.2025.05.034","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a “brake-release and accelerator-pressing” approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu<sup>2+</sup>) and iron ions (Fe<sup>3+</sup>) were liberated from Cu-PB. The direct chelation of Cu<sup>2+</sup> and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the “brake-release” strategy). The release of Cu<sup>2+</sup> and Fe<sup>3+</sup> ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the “accelerator-pressing” strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4210-4224"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nanocoated bacterial carriers enhance oral bacteriophage delivery efficiency 纳米包被细菌载体提高口腔噬菌体递送效率
IF 14.6 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.05.037
Yingui Cao , Aodi Jiang , Qiang Gao , Bo Xiao
{"title":"Nanocoated bacterial carriers enhance oral bacteriophage delivery efficiency","authors":"Yingui Cao ,&nbsp;Aodi Jiang ,&nbsp;Qiang Gao ,&nbsp;Bo Xiao","doi":"10.1016/j.apsb.2025.05.037","DOIUrl":"10.1016/j.apsb.2025.05.037","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4319-4321"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A simple widely applicable hairy root transformation method for gene function studies in medicinal plants 一种简单、广泛适用于药用植物基因功能研究的毛状根转化方法
IF 14.6 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.03.038
Xue Cao , Zhenfen Qin , Panhui Fan , Sifan Wang , Xiangxiao Meng , Huihua Wan , Wei Yang , Shilin Chen , Hui Yao , Weiqiang Chen , Wei Sun
{"title":"A simple widely applicable hairy root transformation method for gene function studies in medicinal plants","authors":"Xue Cao ,&nbsp;Zhenfen Qin ,&nbsp;Panhui Fan ,&nbsp;Sifan Wang ,&nbsp;Xiangxiao Meng ,&nbsp;Huihua Wan ,&nbsp;Wei Yang ,&nbsp;Shilin Chen ,&nbsp;Hui Yao ,&nbsp;Weiqiang Chen ,&nbsp;Wei Sun","doi":"10.1016/j.apsb.2025.03.038","DOIUrl":"10.1016/j.apsb.2025.03.038","url":null,"abstract":"<div><div>Genetic transformation is a fundamental tool in molecular biology research of medicinal plants. Tailoring transgenic technologies to each distinct medicinal plant would necessitate a substantial investment of time and effort. Here, we present a simple hairy root transformation method that does not require sterile conditions, utilizing <em>Agrobacterium rhizogenes</em> strain K599 and the visible RUBY reporter system. Transgenic hairy roots were obtained for six tested medicinal plant species, roots or rhizomes of which have recognized medicinal value, spanning four botanical families and six genera (<em>Platycodon grandiflorus</em>, <em>Atractylodes macrocephala</em>, <em>Scutellaria baicalensis</em>, <em>Codonopsis pilosula</em>, <em>Astragalus membranaceus</em>, and <em>Glycyrrhiza uralensis</em>). Furthermore, two previously identified <em>Glycyrrhiza uralensis</em> UGTs that convert liquiritigenin into liquiritin in heterologous systems were studied <em>in planta</em> using the method. Our results indicate that overexpression of <em>GuUGT1</em> but not <em>GuUGT10</em> and Cas9-mediated knockout of <em>GuUGT1</em> profoundly influenced the accumulation of liquiritin and isoliquiritin in licorice roots. Therefore, the method described here represents a simple, rapid and widely applicable hairy root transformation method that enables fast gene functional study in medicinal plants.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4300-4305"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling the renoprotective mechanisms of self-assembled herbal nanoparticles from Scutellaria barbata and Scleromitrion diffusum in acute kidney injury: A nano-TCM approach 揭示黄芩和弥散硬骨自组装纳米颗粒对急性肾损伤的保护机制:纳米中医方法
IF 14.6 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.05.024
Lunyue Xia , Qunfang Yang , Kangzhe Fu , Yutong Yang , Kaiyue Ding , Yuexue Huo , Lanfang Zhang , Yunong Li , Borong Zhu , Peiyu Li , Yijie Huo , Liang Sun , Ya Liu , Haigang Zhang , Tao Liu , Wenjun Shan , Lin Zhang
{"title":"Unveiling the renoprotective mechanisms of self-assembled herbal nanoparticles from Scutellaria barbata and Scleromitrion diffusum in acute kidney injury: A nano-TCM approach","authors":"Lunyue Xia ,&nbsp;Qunfang Yang ,&nbsp;Kangzhe Fu ,&nbsp;Yutong Yang ,&nbsp;Kaiyue Ding ,&nbsp;Yuexue Huo ,&nbsp;Lanfang Zhang ,&nbsp;Yunong Li ,&nbsp;Borong Zhu ,&nbsp;Peiyu Li ,&nbsp;Yijie Huo ,&nbsp;Liang Sun ,&nbsp;Ya Liu ,&nbsp;Haigang Zhang ,&nbsp;Tao Liu ,&nbsp;Wenjun Shan ,&nbsp;Lin Zhang","doi":"10.1016/j.apsb.2025.05.024","DOIUrl":"10.1016/j.apsb.2025.05.024","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is a critical clinical condition characterized by rapid renal function decline, with high morbidity, mortality, and healthcare costs. Traditional Chinese medicine (TCM) has shown potential effects on mitigating oxidative stress and programmed cell death in AKI models. <em>Scutellaria barbata</em> D. Don (SB) and <em>Scleromitrion diffusum</em> (Willd.) R. J. Wang (SD), a classic TCM herbal pair exhibited anti-inflammatory and antioxidant activities. Using advanced chromatographic separation technology, we enriched the effective fractions of water extracts from SB–SD, obtaining self-assembled herbal nanoparticles (SB and SD nanoparticles, SSNPs) rich in flavonoids and terpenoids. These SSNPs demonstrated robust antioxidant properties <em>in vitro</em> and mitigated AKI progression <em>in vivo</em> by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Oral administration of SSNPs in mice resulted in absorption into the bloodstream, formation of a protein corona, reduced macrophage phagocytosis, and enhanced bioavailability and renal targeting. Furthermore, we investigated the self-assembly principle of SSNPs using representative flavonoids and terpenoids. Kinetic studies and <em>in situ</em> transmission electron microscopy (<em>in situ</em> TEM) revealed that these compounds self-assemble <em>via</em> supramolecular forces like hydrogen bonding and <em>π–π</em> interactions, forming stable nanostructures. This study elucidates the renoprotective effects and mechanisms of SB and SD, and provides a novel approach for the development of TCM-based nanomedicines, highlighting the potential of nano-TCM in AKI treatment.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4265-4284"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The protein arginine methyltransferase PRMT1 ameliorates cerebral ischemia–reperfusion injury by suppressing RIPK1-mediated necroptosis and apoptosis 蛋白精氨酸甲基转移酶PRMT1通过抑制ripk1介导的坏死坏死和细胞凋亡改善脑缺血再灌注损伤
IF 14.6 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.06.005
Tengfei Liu , Gan Huang , Xin Guo , Qiuran Ji , Lu Yu , Runzhe Zong , Yiquan Li , Xiaomeng Song , Qingyi Fu , Qidi Xue , Yi Zheng , Fanshuo Zeng , Ru Sun , Lin Chen , Chengjiang Gao , Huiqing Liu
{"title":"The protein arginine methyltransferase PRMT1 ameliorates cerebral ischemia–reperfusion injury by suppressing RIPK1-mediated necroptosis and apoptosis","authors":"Tengfei Liu ,&nbsp;Gan Huang ,&nbsp;Xin Guo ,&nbsp;Qiuran Ji ,&nbsp;Lu Yu ,&nbsp;Runzhe Zong ,&nbsp;Yiquan Li ,&nbsp;Xiaomeng Song ,&nbsp;Qingyi Fu ,&nbsp;Qidi Xue ,&nbsp;Yi Zheng ,&nbsp;Fanshuo Zeng ,&nbsp;Ru Sun ,&nbsp;Lin Chen ,&nbsp;Chengjiang Gao ,&nbsp;Huiqing Liu","doi":"10.1016/j.apsb.2025.06.005","DOIUrl":"10.1016/j.apsb.2025.06.005","url":null,"abstract":"<div><div>Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4014-4029"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
APOE2 reduces risk of Alzheimer's disease by protection of lysosomes from lipid overloading APOE2通过保护溶酶体免受脂质超载而降低阿尔茨海默病的风险
IF 14.6 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.03.001
Jing Feng , Xiwen Ma , Jianping Ye
{"title":"APOE2 reduces risk of Alzheimer's disease by protection of lysosomes from lipid overloading","authors":"Jing Feng ,&nbsp;Xiwen Ma ,&nbsp;Jianping Ye","doi":"10.1016/j.apsb.2025.03.001","DOIUrl":"10.1016/j.apsb.2025.03.001","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4306-4308"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of WAC alleviates the chondrocyte proinflammatory secretory phenotype and cartilage degradation via H2BK120ub1 and H3K27me3 coregulation 抑制WAC可通过H2BK120ub1和H3K27me3的协同调节减轻软骨细胞促炎分泌表型和软骨降解
IF 14.6 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.06.015
Peitao Xu , Guiwen Ye , Xiaojun Xu , Zhidong Liu , Wenhui Yu , Guan Zheng , Zepeng Su , Jiajie Lin , Yunshu Che , Yipeng Zeng , Zhikun Li , Pei Feng , Qian Cao , Zhongyu Xie , Yanfeng Wu , Huiyong Shen , Jinteng Li
{"title":"Inhibition of WAC alleviates the chondrocyte proinflammatory secretory phenotype and cartilage degradation via H2BK120ub1 and H3K27me3 coregulation","authors":"Peitao Xu ,&nbsp;Guiwen Ye ,&nbsp;Xiaojun Xu ,&nbsp;Zhidong Liu ,&nbsp;Wenhui Yu ,&nbsp;Guan Zheng ,&nbsp;Zepeng Su ,&nbsp;Jiajie Lin ,&nbsp;Yunshu Che ,&nbsp;Yipeng Zeng ,&nbsp;Zhikun Li ,&nbsp;Pei Feng ,&nbsp;Qian Cao ,&nbsp;Zhongyu Xie ,&nbsp;Yanfeng Wu ,&nbsp;Huiyong Shen ,&nbsp;Jinteng Li","doi":"10.1016/j.apsb.2025.06.015","DOIUrl":"10.1016/j.apsb.2025.06.015","url":null,"abstract":"<div><div>Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4064-4077"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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