Pharmacological research最新文献_第8页

The molecular receptor NKBB enhances the persistence and anti-hepatocellular carcinoma activity of GPC3 CAR-T cells

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-01 DOI: 10.1016/j.phrs.2025.107619

Minghao Sui , Tiantian Liu , Xuanli Song , Ji Li , Han Ding , Yuqian Liu , Xinyu Wang , Huimin Liu , Yuchan Xue , Jianni Qi , Miao Zhang , Songbo Zhao , Qiang Zhu

Chimeric antigen receptor (CAR) T cells have encouraging results in the treatment of hematological malignancies. However, CAR-T therapy still faces numerous challenges against solid tumors, such as hepatocellular carcinoma (HCC), owing to heterogeneous antigen expression in tumor cells, limited persistence of CAR-T cells, etc. Therefore, to treat HCC more effectively, we connected the molecular receptor NKBB to a second-generation glypican-3 (GPC3) CAR to construct GC3328z-NKBB CAR-T cells, which have double specific targets of GPC3 and NKG2DLs (natural killer group 2, member D ligands), dual co-stimulation of CD28 and 41BB, and a single CD3ζ chain. Our study showed that the molecular receptor NKBB conferred GPC3 CAR-T cells with enhanced migration and infiltration abilities towards HCC, higher central memory T (T_CM) cell proportion and proliferation capacity, and reduced exhaustion level. GC3328z-NKBB CAR-T cells exhibited improved cytotoxicity against HCC cells and prolonged persistence. The cathepsin L/interleukin-17 (CTSL/IL-17) axis contributed to the superior anti-HCC activity of GC3328z-NKBB CAR-T cells. Overall, the molecular receptor NKBB significantly increased the persistence of GPC3 CAR-T cells, and GC3328z-NKBB CAR-T cells possessed potent anti-HCC activity in mice, providing a new strategy for the potential improvement of adoptive T cell therapy in the treatment of HCC.

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引用次数: 0

Promising LOX proteins for cartilage-targeting osteoarthritis therapy

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-01 DOI: 10.1016/j.phrs.2025.107627

Luca Morici , Eric Allémann , Olivier Jordan , Ines Nikolić

Osteoarthritis (OA) is the most affected joint disease worldwide, touching millions of people every year. It is caused by a progressive degeneration of articular cartilage, causing pain and limited mobility. Among the pathways involved in cartilage homeostasis, “LOX” proteins (referring to three distinct protein families, very often confused in the literature) play a prominent role. The lipoxygenase enzyme family is involved in the inflammatory process of OA by inducing the production of several pro-inflammatory leukotrienes. Lectin-like oxidized low-density lipoprotein family are receptors located at the surface of chondrocytes, which interact with their ligand, ox-LDL, activating several catabolic pathways involved in OA pathophysiology. Finally, lysyl oxidase and lysyl oxidase-like are enzymes expressed intracellularly (in chondrocytes' cytoplasm) involved in elastin biosynthesis and collagen cross-linking in cartilage extracellular matrix. EMA and FDA have not yet approved any drug targeting the LOX proteins. In particular, today lysyl oxidase-like 2 is considered as a new promising target for OA modifying therapy. This review clarifies the main roles of different LOX proteins involved in the progression of OA. Potential LOX inhibitoion strategies for drug development in advanced OA therapy, particularly for local intraarticular delivery, were listed and discussed for each target type. This review, therefore, proposes promising strategies for future drug development in OA treatment.

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引用次数: 0

Targeting protein kinase C-α prolongs survival and restores liver function in sepsis: Evidence from preclinical models

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-01 DOI: 10.1016/j.phrs.2025.107581

Ling Xiong , Dustin Beyer , Na Liu , Tina Lehmann , Sophie Neugebauer , Sascha Schaeuble , Oliver Sommerfeld , Philipp Ernst , Carl-Magnus Svensson , Sandor Nietzsche , Sebastian Scholl , Tony Bruns , Nikolaus Gaßler , Markus H. Gräler , Marc Thilo Figge , Gianni Panagiotou , Michael Bauer , Adrian T. Press

Sepsis is a life-threatening organ failure resulting from a poorly regulated infection response. Organ dysfunction includes hepatic involvement, weakening the immune system due to excretory liver failure, and metabolic dysfunction, increasing the death risk. Although experimental studies correlated excretory liver functionality with immune performance and survival rates in sepsis, the proteins and pathways involved remain unclear. This study identified protein kinase C-α (PKCα) as a novel target for managing excretory liver function during sepsis. Using a preclinical murine sepsis model, we found that both PKCα knockout and the use of a PKCα-inhibitor midostaurin successfully restored liver function without hindering the host’s response or ability to clear the pathogen, highlighting PKCα’s vital role in excretory liver failure. In septic animals, both approaches significantly boosted survival rates. Midostaurin is the clinically approved active pharmaceutical ingredient in Rydapt, approved for the adjuvant treatment of FTL3-mutated AML. Here, it reduced plasma bile acids and related inflammation in those patients, opening a translational avenue for therapeutics in sepsis. Conclusively, our research underscores the significance of PKCα in controlling excretory liver function during inflammation. This suggests that targeting this protein could restore liver function without compromising the immune system, thereby decreasing sepsis mortality and supporting the recent paradigm that the liver is a hub for the host response to infection that might, in the future, result in novel host-directed therapies supporting the current state-of-the-art intensive care medicine in patients with sepsis-associated liver failure.

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引用次数: 0

The roles of cannabis potency and gender in cannabis dependence and anxiety in recent cannabis users with trauma exposure histories 大麻效价和性别在近期有创伤暴露史的大麻使用者大麻依赖和焦虑中的作用。

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-01 DOI: 10.1016/j.phrs.2025.107586

T. Snooks , S.H. Stewart , P. Romero-Sanchiz , S. DeGrace , S.P. Barrett , H.C.R. Bernusky , P.G. Tibbo

Over the past 20 years, levels of Δ9-tetrahydrocannabinol (THC) in cannabis have significantly increased, while levels of cannabidiol (CBD) have increased much less in comparison. Cannabis with higher THC potency (commonly assessed via THC:CBD ratio) may increase the risk for cannabis dependence and trigger/exacerbate anxiety. However, few studies of cannabis potency effects on cannabis dependence and anxiety have examined gender moderation. Additionally, there are issues with how cannabis potency is calculated via the THC:CBD ratio that may contribute to inconsistencies in the literature. N = 202 (55.8 % women) recent cannabis users (>1 g in the past month) with trauma histories – a group at high risk for anxiety and cannabis dependence – completed an online survey including a self-report measure of THC and CBD levels in participants’ typically-used cannabis product. Cannabis potency was calculated as THC:CBD ratio (THC%/CBD%) and as relative THC proportion (THC%/[THC%+CBD%]). Cannabis dependence and anxiety levels were self-reported on the Cannabis Use Disorder Identification Test-Revised (CUDIT-R) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Consistent with prior findings in the general population, cannabis potency was significantly positively correlated with cannabis dependence, p = .002, and anxiety levels, p = .020, but only when assessed via THC proportion and not THC:CBD ratio. Consistent with prior research, women reported significantly higher anxiety levels but also unexpectedly, higher THC:CBD ratios, than men. No significant gender differences were found in the associations of either potency measure with either outcome variable. Results are consistent with recent reports of gender convergence in cannabis use prevalence. Additionally, these results identify relative THC proportion as a superior predictor of adverse cannabis and anxiety outcomes than the THC:CBD ratio in both men and women.

在过去的20年里，大麻中Δ9-tetrahydrocannabinol （THC）的含量显著增加，而大麻二酚（CBD）的含量相比之下增加得少得多。四氢大麻酚效价较高的大麻（通常通过四氢大麻酚：CBD的比例来评估）可能会增加大麻依赖的风险，引发/加剧焦虑。然而，很少有关于大麻效力对大麻依赖和焦虑的影响的研究审查了性别节制。此外，如何通过THC:CBD的比例来计算大麻的效力也存在问题，这可能会导致文献中的不一致。N = 202（55.8%为女性）最近有创伤史的大麻使用者（过去一个月有110克）——这是一个焦虑和大麻依赖的高风险群体——完成了一项在线调查，其中包括参与者通常使用的大麻产品中四氢大麻酚和CBD水平的自我报告。大麻效价计算为THC:CBD比（THC%/CBD%）和THC相对比（THC%/[THC%+CBD%]）。大麻依赖和焦虑水平分别在大麻使用障碍识别测试（CUDIT-R）和广泛性焦虑障碍-7 （GAD-7）中自我报告。与先前在一般人群中的发现一致，大麻效力与大麻依赖显著正相关，p =。002，焦虑水平，p =。020，但仅以THC比例评估，而不以THC:CBD比例评估。与之前的研究一致，女性报告的焦虑水平明显高于男性，但出乎意料的是，四氢大麻酚：CBD的比例也高于男性。在两种效价测量与两种结果变量的关联中，没有发现显著的性别差异。结果与最近关于大麻使用率性别趋同的报告相一致。此外，这些结果表明，在男性和女性中，THC的相对比例比THC:CBD的比例更能预测大麻和焦虑的不良后果。

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引用次数: 0

Phenolic acids from Anisopus mannii modulates phosphofructokinase 1 to improve glycemic control in patients with type 2 diabetes: A double-blind, randomized, clinical trial 甘露醇异丙参酚酸调节磷酸果糖激酶1改善2型糖尿病患者血糖控制：一项双盲、随机、临床试验

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-01 DOI: 10.1016/j.phrs.2025.107602

Peter U. Amadi , Justice O. Osuoha , Chidi N. Ekweogu , Suha J. Jarad , Esienanwan E. Efiong , Prince C. Odika , Chioma Ejiofor , Oluchi Aloy-Amadi , Govind S. Gill , Chiamaka W. Adumekwe , Ailun Gaowa , Dawei Zhang , Barbora de Courten , Emmanuel N. Agomuo

Phenolic acid-rich fraction from Anisopus mannii (PhAM) contains abundance of ferulic acid, gallic acid, protocatechuic acid, and syringic acid. Among other glycolytic enzymes, in vitro, PhAM counteracted the binding of sodium orthovanadate to phosphofructokinase 1 (PFK-1), improving its activities. In a rat model of diet-induced diabetes, PhAM monotherapy reduced HbA1c by an average of 0.63 % and fasting plasma glucose by 25 mg/dl. This herb rescued β-cells from streptozotocin-mediated destruction, thereby improving glycemic control. Supported by the preclinical trial, eighty-five patients with type 2 diabetes (T2D) receiving first-line medications were enrolled in a double-blind, randomized, placebo-controlled trial with a 90 % power level. Patients were randomized into a placebo group or either of the following two treatment groups: oral administration of 12 mg or 20 mg/kg body weight of PhAM once every 48 h for 6 months. Both treatments were well tolerated. At the endpoint, more than 70 % of patients achieved a 0.5 – 2.0 decrease in HbA1c levels and a > 20 mg/dl decrease in fasting blood glucose, meeting the pre-specified primary outcome. 66 % of patients treated with 20 mg PhAM achieved the < 7 % HbA1c and HOMA-IR of > 1.0 goal. respectively. Our study shows that PhAM can supplement first-line medications to achieve target glycemic control within 6 months.

甘露异丙醇富酚酸组分含有丰富的阿魏酸、没食子酸、原儿茶酸和丁香酸。在其他糖酵解酶中，在体外，PhAM抵消了原钒酸钠与磷酸果糖激酶1 （PFK-1）的结合，提高了其活性。在饮食诱导的糖尿病大鼠模型中，PhAM单药治疗使HbA1c平均降低0.63 %，空腹血糖平均降低25 mg/dl。这种草药从链脲佐菌素介导的破坏中拯救β细胞，从而改善血糖控制。在临床前试验的支持下，85名接受一线药物治疗的2型糖尿病（T2D）患者参加了一项双盲、随机、安慰剂对照试验，功率水平为90% %。患者被随机分为安慰剂组或以下两个治疗组之一：每48 h口服12 mg或20 mg/kg体重的PhAM一次，持续6个月。两种治疗方法均耐受良好。在终点，超过70% %的患者HbA1c水平降低0.5 - 2.0，空腹血糖降低> 20 mg/dl，达到预定的主要结局。使用20 mg PhAM治疗的患者中，66% %达到了 1.0的目标。分别。我们的研究表明，PhAM可以补充一线药物，在6个月内达到目标血糖控制。

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引用次数: 0

A systematic review of Aspilia africana (Pers.) C.D. adams traditional medicinal uses, phytoconstituents, bioactivities, and toxicities 非洲白杨（Aspilia africana）的系统综述传统医药用途，植物成分，生物活性和毒性。

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-01 DOI: 10.1016/j.phrs.2025.107590

Roggers Gang , Denis Okello , Yeongjun Ban , Youngmin Kang

Aspilia africana (Pers.) C. D. Adams, popularly referred to as wild sunflower, has been used for generations across several African communities to treat various diseases, including malaria, wounds, osteoporosis, diabetes mellitus, gastric ulcers, measles, tuberculosis, stomach ache, rheumatic pains, and gonorrhea. This study aimed to systematically and critically compile data on the traditional medicinal uses, phytochemistry, bioactivities, botanical descriptions, and toxicities of A. africana. Relevant research findings were retrieved and organized from various databases, including PubMed and ScienceDirect, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. To date, 149 phytochemicals have been identified from various A. africana parts and they primarily belong to the classes of terpenoids, lipids, hydrocarbons, phenolics, and esters. The extracts and bioactive phytochemicals of A. africana have revealed several pharmacological properties, including antimalarial, anticancer, wound healing, anti-inflammatory, antidiabetic, and antimicrobial activities. However, the major components responsible for these bioactivities and their mechanisms of action in some diseases have not yet been clearly identified. Additionally, toxicity and clinical trial data for A. africana are limited with most toxicological assessments being acute in nature. Therefore, further research on the mechanisms of action of the pure bioactive phytochemicals and toxicity of A. africana are necessary to better understand its efficacy and safety. Taken together, this study provides comprehensive information on the traditional medicinal uses, phytochemistry, bioactivities, and toxicity of A. africana, and a reference for future studies, relevant to the development of therapeutic products.

非洲白杨c.d.亚当斯，通常被称为野生向日葵，在几个非洲社区被世代用来治疗各种疾病，包括疟疾、伤口、骨质疏松症、糖尿病、胃溃疡、麻疹、肺结核、胃痛、风湿病和淋病。本研究旨在系统地、批判性地整理非洲草的传统药用、植物化学、生物活性、植物描述和毒性等方面的资料。根据系统评价和荟萃分析指南的首选报告项目，从包括PubMed和ScienceDirect在内的各种数据库检索和组织相关研究结果。迄今为止，已从非洲南芥的不同部位鉴定出了149种植物化学物质，它们主要属于萜类、脂类、碳氢化合物、酚类和酯类。非洲南芥的提取物和生物活性植物化学物质具有抗疟、抗癌、伤口愈合、抗炎、抗糖尿病和抗菌等药理作用。然而，这些生物活性的主要成分及其在某些疾病中的作用机制尚未明确确定。此外，非洲古猿的毒性和临床试验数据有限，大多数毒理学评估本质上是急性的。因此，有必要进一步研究其纯活性植物化学物质的作用机制和毒性，以更好地了解其有效性和安全性。本研究为非洲麻的传统药用、植物化学、生物活性和毒性等方面提供了全面的信息，并为今后的研究提供了参考。

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引用次数: 0

Metabolic and epigenetic regulation of macrophage polarization in atherosclerosis: Molecular mechanisms and targeted therapies 动脉粥样硬化中巨噬细胞极化的代谢和表观遗传调控：分子机制和靶向治疗。

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-01 DOI: 10.1016/j.phrs.2025.107588

Pinglian Yang , Xiaoling Rong , Zhechang Gao , Jiaojiao Wang , Zhiping Liu

Atherosclerosis, a multifactorial progressive inflammatory disease, is the common pathology underlying cardiovascular and cerebrovascular diseases. The macrophage plasticity is involved in the pathogenesis of atherosclerosis. With the advance of metabolomics and epigenetics, metabolites/metabolic and epigenetic modification such as DNA methylation, histone modification and noncoding RNA, play a crucial role in macrophage polarization and the progression of atherosclerosis. Herein, we provide a comprehensive review of the essential role of metabolic and epigenetic regulation, as well as the crosstalk between the two in regulating macrophage polarization in atherosclerosis. We also highlight the potential therapeutic strategies of regulating macrophage polarization via epigenetic and metabolic modifications for atherosclerosis, and offer recommendations to advance our knowledge of the roles of metabolic-epigenetic crosstalk in macrophage polarization in the context of atherosclerosis. Fundamental studies that elucidate the mechanisms by which metabolic and epigenetic regulation of macrophage polarization influence atherosclerosis will pave the way for novel therapeutic approaches.

动脉粥样硬化是一种多因素进行性炎症性疾病，是心脑血管疾病的常见病理基础。巨噬细胞可塑性参与动脉粥样硬化的发病机制。随着代谢组学和表观遗传学的发展，DNA甲基化、组蛋白修饰和非编码RNA等代谢物/代谢和表观遗传修饰在巨噬细胞极化和动脉粥样硬化的进展中起着至关重要的作用。在此，我们就代谢和表观遗传调控在动脉粥样硬化中巨噬细胞极化调控中的重要作用以及两者之间的相互作用进行了综述。我们还强调了通过表观遗传和代谢修饰调节巨噬细胞极化对动脉粥样硬化的潜在治疗策略，并提出了建议，以提高我们对动脉粥样硬化背景下巨噬细胞极化中代谢-表观遗传串扰的作用的认识。阐明巨噬细胞极化代谢和表观遗传调控影响动脉粥样硬化机制的基础研究将为新的治疗方法铺平道路。

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引用次数: 0

Erratum to the ‘Long non-coding RNAs-sphingolipid metabolism nexus: Potential targets for cancer treatment’ Pharmacol. Res. 210 (December) (2024) 107539

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-01 DOI: 10.1016/j.phrs.2025.107629

Yan Chen , Jing Dai , Peng Chen , Quan Dai , Ya Chen , Yuying Li , Man Lu , Shugang Qin , Qiuju Wang

引用次数: 0

Ginsenosides Rg1, Rb1 and rare ginsenosides: Promising candidate agents for Parkinson's disease and Alzheimer's disease and network pharmacology analysis 人参皂苷Rg1， Rb1和稀有人参皂苷：帕金森病和阿尔茨海默病的有希望的候选药物和网络药理学分析。

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-01 DOI: 10.1016/j.phrs.2025.107578

Mingchun Jiang , Jiaxin Chi , Yifan Qiao , Jinpeng Wang , Zhixin Zhang , Jia Liu , Xinhao Sheng , Liangjie Yuan

Ginseng has been commonly used as a traditional Chinese medicine in Asian countries for thousands of years. Ginsenosides are the main pharmacologically active ingredients isolated from ginseng and have neuroprotective effects in the treatment of neurodegenerative disorders, such as Parkinson's disease (PD) and Alzheimer's disease (AD). To summarise and investigate the protective roles of ginsenosides and their underlying mechanisms in PD and AD, we used ‘‘Ginsenoside”, ‘‘Parkinson's disease”, ‘‘Alzheimer's disease”, ‘‘anti-inflammatory”, ‘‘antioxidant”, and ‘‘apoptosis” as keywords to search and extract relevant literature information from scientific databases such as Elsevier, PubMed, and Google Scholar databases. In particular, we used network pharmacology to identify the potential targets of ginsenosides Rg1 and Rb1 in PD and AD. By analysing the existing research advances and network pharmacology results, we found that the neuroprotective effects of ginsenosides, primarily mediated through anti-inflammation, anti-apoptosis and anti-oxidative stress, etc, may be associated with the PI3K/Akt, BDNF/TrkB, MAPKs, NF-κB, Nrf2 and Wnt/β-catenin signalling pathways. This review systematically summarises the different roles and mechanisms of ginsenosides Rg1, Rb1, and rare ginsenosides in PD and AD and provides new strategies for the treatment of neurodegenerative disorders. Network pharmacology provides a new research paradigm for the treatment of PD and AD using Rg1 and Rb1.

人参作为一种传统中药在亚洲国家被广泛使用了数千年。人参皂苷是从人参中分离出来的主要药理活性成分，在治疗神经退行性疾病，如帕金森病（PD）和阿尔茨海默病（AD）中具有神经保护作用。为了总结和探讨人参皂苷在PD和AD中的保护作用及其机制，我们以“人参皂苷”、“帕金森病”、“阿尔茨海默病”、“抗炎”、“抗氧化”和“细胞凋亡”为关键词，从Elsevier、PubMed、谷歌Scholar等科学数据库中检索并提取相关文献信息。特别是，我们使用网络药理学来确定人参皂苷Rg1和Rb1在PD和AD中的潜在靶点。通过分析已有研究进展和网络药理学结果，我们发现人参皂苷主要通过抗炎症、抗凋亡、抗氧化应激等途径发挥神经保护作用，可能与PI3K/Akt、BDNF/TrkB、MAPKs、NF-κB、Nrf2和Wnt/β-catenin信号通路有关。本文系统综述了人参皂苷Rg1、Rb1和稀有人参皂苷在PD和AD中的不同作用和机制，并为神经退行性疾病的治疗提供新的策略。网络药理学为Rg1和Rb1治疗PD和AD提供了新的研究范式。

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引用次数: 0

Scutellarin inhibits pyroptosis via selective autophagy degradation of p30/GSDMD and suppression of ASC oligomerization 黄芩苷通过选择性自噬降解p30/GSDMD和抑制ASC寡聚来抑制焦亡。

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-01 DOI: 10.1016/j.phrs.2025.107605

Danyue Li , Weilv Xu , Suhui He , Xinyue Li , Yumeng Wang , Qian Lv , Nan Chen , Lu Dong , Feng Guo , Fushan Shi

Most of the pyroptosis inhibitors targeted Gasdermin D (GSDMD) are functioning by restraining GSDMD-N (p30) oligomerization. For the first time, this work discovered a pyroptosis inhibitor taking effect by degrading p30 and GSDMD. As the principal bioactive constituent in Erigeron breviscapus, scutellarin (SCU) assumes a pivotal role in the realm of anti-inflammatory processes. In this study, SCU demonstrated efficacy in hindering pyroptosis mediated by the NOD-like receptor protein 3 (NLRP3) inflammasome, absent in melanoma 2 (AIM2) inflammasome, NLR-family CARD-containing protein 4 (NLRC4) inflammasome, and that activated through the non-canonical pathway. The inhibitory effect is achieved by thwarting apoptosis-associated speck-like protein containing CARD (ASC) oligomerization and inducing the ubiquitin-dependent selective autophagy of p30/GSDMD. Throughout the autophagic process, SCU facilitates selective autophagy of the pyroptosis executor p30/GSDMD through K33-linked polyubiquitination at Lys51 catalyzed by the E3 ligase tripartite motif-containing 21 (TRIM21). This process contributes to the recognition of p30/GSDMD by the cargo receptor sequestosome 1 (SQSTM1)/p62. The characteristic positions SCU as a prospective clinical intervention for a broader spectrum of inflammatory-related disorders.

大多数针对GSDMD的焦亡抑制剂是通过抑制GSDMD- n （p30）寡聚化来起作用的。本工作首次发现了一种通过降解p30和GSDMD起作用的焦亡抑制剂。作为灯盏花中的主要生物活性成分，灯盏花苷（SCU）在抗炎过程中起着举足轻重的作用。在本研究中，SCU显示出阻碍由nod样受体蛋白3 （NLRP3）炎症体介导的焦亡的有效性，该炎症体在黑色素瘤2 （AIM2）炎症体中缺失，nlr家族含card蛋白4 （NLRC4）炎症体中缺失，并通过非规范途径激活。抑制作用是通过抑制凋亡相关的含有CARD （ASC）的斑点样蛋白寡聚化和诱导p30/GSDMD的泛素依赖性选择性自噬来实现的。在整个自噬过程中，SCU通过E3连接酶tripartite motif-containing 21 （TRIM21）催化的Lys51位点K33-linked多泛素化，促进了焦亡执行子p30/GSDMD的选择性自噬。这个过程有助于货物受体sequestosome 1 (SQSTM1)/p62识别p30/GSDMD。这一特征使SCU成为更广泛的炎症相关疾病的前瞻性临床干预手段。

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引用次数: 0