首页 > 最新文献

British Journal of Pharmacology最新文献

英文 中文
Elucidating the beneficial impact of exercise on chronic obstructive pulmonary disease and its comorbidities: Integrating proteomic and immunological insights. 阐明运动对慢性阻塞性肺病及其合并症的有益影响:整合蛋白质组学和免疫学观点。
IF 6.8 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-09-24 DOI: 10.1111/bph.17328
Xishuai Wang, Cong Liu, Ruining Liang, Yuehui Zhou, Xiliang Kong, Weichao Wang, Hongwei Wang, Lunan Zhao, Weina Niu, Chao Yi, Fugao Jiang

Background and purpose: Physical activity is an effective therapeutic protocol for treating chronic obstructive pulmonary disease (COPD). However, the mechanisms underlying the benefits of physical activity in COPD are not fully elucidated.

Experimental approach: In a mouse model of COPD, analysis of biological markers and lung proteomics identified the molecular pathways through which exercise ameliorates COPD.

Key results: Exercise improved pulmonary function, emphysema, small airway disease, pulmonary inflammation, glucose metabolic dysregulation, and insulin resistance in COPD mice. Proteomic analysis revealed 430 differentially expressed proteins (DEPs) between the COPD and COPD + Exercise (COPD + Ex) groups. GO analysis indicated that the enriched pathways were predominantly related to the immune response, inflammatory processes, insulin secretion, and glucose metabolic processes. GO analysis revealed IL-33 as a crucial target for the exercise-related amelioration of COPD. KEGG analysis showed that DEPs were significantly enriched in primary immunodeficiency, the intestinal immune network for IgA production, and the NF-κB signalling pathway. Exercise inhibited NF-κB activation by suppressing the CD14/TLR4/MyD88 and TNF-α/TNF-R1/TRAF2/5 pathways in COPD mice. Exercise inhibited expression of BCR, IgM, IgD, IgG, IgE, and IgA by suppressing B-cell receptor signalling. Exercise attenuated glucose metabolic dysregulation and insulin resistance through the suppression of proinflammatory mediators, including MHC I, MHC II, TNF-α, IFN-γ, and IL-1β, while concurrently increasing insulin expression. The qRT-PCR results were consistent with the proteomic results.

Conclusion and implications: In a mouse model, exercise improved COPD and its metabolic comorbidities through immune system regulation and inflammation suppression, offering insights into potential therapeutic targets.

背景和目的:体育锻炼是治疗慢性阻塞性肺病(COPD)的有效疗法。然而,体育锻炼对慢性阻塞性肺病有益的机制尚未完全阐明:实验方法:在慢性阻塞性肺病小鼠模型中,通过对生物标记物和肺蛋白质组学的分析,确定了运动改善慢性阻塞性肺病的分子途径:运动改善了慢性阻塞性肺病小鼠的肺功能、肺气肿、小气道疾病、肺部炎症、糖代谢失调和胰岛素抵抗。蛋白质组学分析显示,慢性阻塞性肺病组和慢性阻塞性肺病+运动(COPD + Ex)组之间存在430个差异表达蛋白(DEPs)。GO分析表明,富集的通路主要与免疫反应、炎症过程、胰岛素分泌和葡萄糖代谢过程有关。GO分析显示,IL-33是运动相关改善慢性阻塞性肺病的关键靶点。KEGG分析显示,DEPs在原发性免疫缺陷、产生IgA的肠道免疫网络和NF-κB信号通路中明显富集。运动通过抑制慢性阻塞性肺病小鼠的CD14/TLR4/MyD88和TNF-α/TNF-R1/TRAF2/5通路,抑制了NF-κB的激活。通过抑制 B 细胞受体信号传导,运动抑制了 BCR、IgM、IgD、IgG、IgE 和 IgA 的表达。运动通过抑制促炎介质,包括MHC I、MHC II、TNF-α、IFN-γ和IL-1β,减轻了葡萄糖代谢紊乱和胰岛素抵抗,同时增加了胰岛素的表达。qRT-PCR结果与蛋白质组结果一致:在小鼠模型中,运动通过调节免疫系统和抑制炎症改善了慢性阻塞性肺病及其代谢合并症,为潜在的治疗靶点提供了启示。
{"title":"Elucidating the beneficial impact of exercise on chronic obstructive pulmonary disease and its comorbidities: Integrating proteomic and immunological insights.","authors":"Xishuai Wang, Cong Liu, Ruining Liang, Yuehui Zhou, Xiliang Kong, Weichao Wang, Hongwei Wang, Lunan Zhao, Weina Niu, Chao Yi, Fugao Jiang","doi":"10.1111/bph.17328","DOIUrl":"10.1111/bph.17328","url":null,"abstract":"<p><strong>Background and purpose: </strong>Physical activity is an effective therapeutic protocol for treating chronic obstructive pulmonary disease (COPD). However, the mechanisms underlying the benefits of physical activity in COPD are not fully elucidated.</p><p><strong>Experimental approach: </strong>In a mouse model of COPD, analysis of biological markers and lung proteomics identified the molecular pathways through which exercise ameliorates COPD.</p><p><strong>Key results: </strong>Exercise improved pulmonary function, emphysema, small airway disease, pulmonary inflammation, glucose metabolic dysregulation, and insulin resistance in COPD mice. Proteomic analysis revealed 430 differentially expressed proteins (DEPs) between the COPD and COPD + Exercise (COPD + Ex) groups. GO analysis indicated that the enriched pathways were predominantly related to the immune response, inflammatory processes, insulin secretion, and glucose metabolic processes. GO analysis revealed IL-33 as a crucial target for the exercise-related amelioration of COPD. KEGG analysis showed that DEPs were significantly enriched in primary immunodeficiency, the intestinal immune network for IgA production, and the NF-κB signalling pathway. Exercise inhibited NF-κB activation by suppressing the CD14/TLR4/MyD88 and TNF-α/TNF-R1/TRAF2/5 pathways in COPD mice. Exercise inhibited expression of BCR, IgM, IgD, IgG, IgE, and IgA by suppressing B-cell receptor signalling. Exercise attenuated glucose metabolic dysregulation and insulin resistance through the suppression of proinflammatory mediators, including MHC I, MHC II, TNF-α, IFN-γ, and IL-1β, while concurrently increasing insulin expression. The qRT-PCR results were consistent with the proteomic results.</p><p><strong>Conclusion and implications: </strong>In a mouse model, exercise improved COPD and its metabolic comorbidities through immune system regulation and inflammation suppression, offering insights into potential therapeutic targets.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":"5133-5150"},"PeriodicalIF":6.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Targeting the NLRP3 inflammasome signalling for the management of atrial fibrillation. 针对 NLRP3 炎性体信号治疗心房颤动。
IF 6.8 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 Epub Date: 2024-06-15 DOI: 10.1111/bph.16470
Alisha Niskala, Jordi Heijman, Dobromir Dobrev, Thomas Jespersen, Arnela Saljic

Inflammatory signalling via the nod-like receptor (NLR) family pyrin domain-containing protein-3 (NLRP3) inflammasome has recently been implicated in the pathophysiology of atrial fibrillation (AF). However, the precise role of the NLRP3 inflammasome in various cardiac cell types is poorly understood. Targeting components or products of the inflammasome and preventing their proinflammatory consequences may constitute novel therapeutic treatment strategies for AF. In this review, we summarise the current understanding of the role of the inflammasome in AF pathogenesis. We first review the NLRP3 inflammasome pathway and inflammatory signalling in cardiomyocytes, (myo)fibroblasts and immune cells, such as neutrophils, macrophages and monocytes. Because numerous compounds targeting NLRP3 signalling are currently in preclinical development, or undergoing clinical evaluation for other indications than AF, we subsequently review known therapeutics, such as colchicine and canakinumab, targeting the NLRP3 inflammasome and evaluate their potential for treating AF.

通过类点头受体(NLR)家族含吡啶结构域蛋白-3(NLRP3)炎性体发出的炎症信号最近被认为与心房颤动(房颤)的病理生理学有关。然而,人们对 NLRP3 炎性体在各种心脏细胞类型中的确切作用还知之甚少。靶向炎性体的成分或产物并防止其促炎后果可能构成心房颤动的新型治疗策略。在本综述中,我们总结了目前对炎性体在房颤发病机制中作用的理解。我们首先回顾了 NLRP3 炎性体通路以及心肌细胞、成纤维细胞和免疫细胞(如中性粒细胞、巨噬细胞和单核细胞)中的炎性信号传导。由于许多靶向 NLRP3 信号的化合物目前正处于临床前开发阶段,或正针对心房颤动以外的其他适应症进行临床评估,因此我们随后回顾了针对 NLRP3 炎症体的已知疗法,如秋水仙碱和卡那单抗,并评估了它们治疗心房颤动的潜力。
{"title":"Targeting the NLRP3 inflammasome signalling for the management of atrial fibrillation.","authors":"Alisha Niskala, Jordi Heijman, Dobromir Dobrev, Thomas Jespersen, Arnela Saljic","doi":"10.1111/bph.16470","DOIUrl":"10.1111/bph.16470","url":null,"abstract":"<p><p>Inflammatory signalling via the nod-like receptor (NLR) family pyrin domain-containing protein-3 (NLRP3) inflammasome has recently been implicated in the pathophysiology of atrial fibrillation (AF). However, the precise role of the NLRP3 inflammasome in various cardiac cell types is poorly understood. Targeting components or products of the inflammasome and preventing their proinflammatory consequences may constitute novel therapeutic treatment strategies for AF. In this review, we summarise the current understanding of the role of the inflammasome in AF pathogenesis. We first review the NLRP3 inflammasome pathway and inflammatory signalling in cardiomyocytes, (myo)fibroblasts and immune cells, such as neutrophils, macrophages and monocytes. Because numerous compounds targeting NLRP3 signalling are currently in preclinical development, or undergoing clinical evaluation for other indications than AF, we subsequently review known therapeutics, such as colchicine and canakinumab, targeting the NLRP3 inflammasome and evaluate their potential for treating AF.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":"4939-4957"},"PeriodicalIF":6.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Evidence generation throughout paediatric medicines life cycle: findings from collaborative work between European Medicines Agency (EMA) and EUnetHTA on use of extrapolation. 整个儿科药品生命周期中的证据生成:欧洲药品管理局 (EMA) 与 EUnetHTA 在使用外推法方面的合作成果。
IF 6.8 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-22 DOI: 10.1111/bph.17396
Dominik Karres, María José Pino-Barrio, Sylvie Benchetrit, Norbert Benda, Pierre Cochat, Sara Galluzzo, Alejandro García-Solís, Sara Gonzalez, Roberto de Lisa, David Khan, Rita Lankester, Frederike Lentz, Pilar Angustias Martínez-Ortega, Simona Montilla, Daniel R Morales, Flora Musuamba Tshinanu, Sonia Pulido Sánchez, Ana Rossignoli Montero, Sabine Scherer, Andrew Thomson, Belén Torres Garrido, Denise Umuhire, Siri Wang, Ralph Bax, Niklas Hedberg

Drug development for children presents unique challenges and is highly regulated. Novel approaches, such as the use of extrapolation to address, for example, the need to avoid unethical studies, whilst supporting robust evidence generation have been developed in support of benefit/risk considerations by regulatory authorities. This is only one step in the decision-making process towards access, which in Europe also includes health technology assessment (HTA) bodies. Discussions related to evidentiary requirements in small populations using scientific evidence transfer have been identified as a priority action by European Medicines Agency/European Network for Health Technology Assessment 21 (EMA/EUnetHTA 21). We describe the outcome of this work and reflect on the discussions that had taken place on how to leverage prior knowledge through identifying and addressing uncertainties during life cycle management to support regulatory and HTA decision-making. Using examples, we explore the range of applications for evidence generation and offer regulatory and HTA insights on key design considerations for producing better evidence, reflecting our shared ambition. Early interactions with all respective stakeholders, particularly between regulators and HTA bodies are key to optimise data generation and utility in children. In Europe, the HTA regulation will offer opportunities for collaborations, which are important for all development efforts. We collaboratively explored the unique specific challenges relating to paediatric drug development, ethically and in its ability to leverage prior knowledge, as exemplified using extrapolation. Learnings from these offer opportunities to further develop methodology on how to leverage uncertainties across a product's life cycle for small populations generally.

儿童药物研发面临着独特的挑战,并且受到严格监管。监管机构已开发出一些新方法,例如使用外推法来解决避免不道德研究的需要,同时支持有力的证据生成,以支持效益/风险考虑。在欧洲,决策过程还包括卫生技术评估(HTA)机构。欧洲药品管理局/欧洲 21 世纪健康技术评估网络(EMA/EUnetHTA 21)已将有关使用科学证据转移的小群体证据要求的讨论确定为优先行动。我们介绍了这项工作的成果,并反思了关于如何通过识别和解决生命周期管理中的不确定性来利用已有知识以支持监管和 HTA 决策的讨论。通过实例,我们探讨了证据生成的应用范围,并就生成更好证据的关键设计考虑因素为监管和 HTA 提供了见解,反映了我们的共同愿望。与所有利益相关者,特别是监管机构和 HTA 机构之间的早期互动,是优化儿童数据生成和效用的关键。在欧洲,HTA 法规将提供合作机会,这对所有开发工作都很重要。我们共同探讨了与儿科药物开发有关的独特的具体挑战,包括伦理方面的挑战和利用已有知识的能力方面的挑战,外推法就是一个很好的例子。从中学到的知识为进一步开发方法提供了机会,这些方法涉及如何利用产品生命周期中的不确定性来解决小群体的普遍问题。
{"title":"Evidence generation throughout paediatric medicines life cycle: findings from collaborative work between European Medicines Agency (EMA) and EUnetHTA on use of extrapolation.","authors":"Dominik Karres, María José Pino-Barrio, Sylvie Benchetrit, Norbert Benda, Pierre Cochat, Sara Galluzzo, Alejandro García-Solís, Sara Gonzalez, Roberto de Lisa, David Khan, Rita Lankester, Frederike Lentz, Pilar Angustias Martínez-Ortega, Simona Montilla, Daniel R Morales, Flora Musuamba Tshinanu, Sonia Pulido Sánchez, Ana Rossignoli Montero, Sabine Scherer, Andrew Thomson, Belén Torres Garrido, Denise Umuhire, Siri Wang, Ralph Bax, Niklas Hedberg","doi":"10.1111/bph.17396","DOIUrl":"https://doi.org/10.1111/bph.17396","url":null,"abstract":"<p><p>Drug development for children presents unique challenges and is highly regulated. Novel approaches, such as the use of extrapolation to address, for example, the need to avoid unethical studies, whilst supporting robust evidence generation have been developed in support of benefit/risk considerations by regulatory authorities. This is only one step in the decision-making process towards access, which in Europe also includes health technology assessment (HTA) bodies. Discussions related to evidentiary requirements in small populations using scientific evidence transfer have been identified as a priority action by European Medicines Agency/European Network for Health Technology Assessment 21 (EMA/EUnetHTA 21). We describe the outcome of this work and reflect on the discussions that had taken place on how to leverage prior knowledge through identifying and addressing uncertainties during life cycle management to support regulatory and HTA decision-making. Using examples, we explore the range of applications for evidence generation and offer regulatory and HTA insights on key design considerations for producing better evidence, reflecting our shared ambition. Early interactions with all respective stakeholders, particularly between regulators and HTA bodies are key to optimise data generation and utility in children. In Europe, the HTA regulation will offer opportunities for collaborations, which are important for all development efforts. We collaboratively explored the unique specific challenges relating to paediatric drug development, ethically and in its ability to leverage prior knowledge, as exemplified using extrapolation. Learnings from these offer opportunities to further develop methodology on how to leverage uncertainties across a product's life cycle for small populations generally.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
EDITORIAL for BJP themed issue "noncoding RNA therapeutics". BJP 主题刊物《非编码 RNA 治疗学》编辑。
IF 6.8 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-21 DOI: 10.1111/bph.17365
Yvan Devaux, Serena Zacchigna, Rainer Schulz
{"title":"EDITORIAL for BJP themed issue \"noncoding RNA therapeutics\".","authors":"Yvan Devaux, Serena Zacchigna, Rainer Schulz","doi":"10.1111/bph.17365","DOIUrl":"https://doi.org/10.1111/bph.17365","url":null,"abstract":"","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Plasma miR-1-3p levels predict severity in hospitalized COVID-19 patients. 血浆 miR-1-3p 水平可预测 COVID-19 住院患者的病情严重程度。
IF 6.8 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-21 DOI: 10.1111/bph.17392
Paola Di Pietro, Angela Carmelita Abate, Carmine Izzo, Anna Laura Toni, Maria Rosaria Rusciano, Veronica Folliero, Federica Dell'Annunziata, Giovanni Granata, Valeria Visco, Benedetta Maria Motta, Alfonso Campanile, Carolina Vitale, Valeria Prete, Cristina Gatto, Giuliana Scarpati, Paolo Poggio, Gennaro Galasso, Pasquale Pagliano, Ornella Piazza, Gaetano Santulli, Gianluigi Franci, Albino Carrizzo, Carmine Vecchione, Michele Ciccarelli
{"title":"Plasma miR-1-3p levels predict severity in hospitalized COVID-19 patients.","authors":"Paola Di Pietro, Angela Carmelita Abate, Carmine Izzo, Anna Laura Toni, Maria Rosaria Rusciano, Veronica Folliero, Federica Dell'Annunziata, Giovanni Granata, Valeria Visco, Benedetta Maria Motta, Alfonso Campanile, Carolina Vitale, Valeria Prete, Cristina Gatto, Giuliana Scarpati, Paolo Poggio, Gennaro Galasso, Pasquale Pagliano, Ornella Piazza, Gaetano Santulli, Gianluigi Franci, Albino Carrizzo, Carmine Vecchione, Michele Ciccarelli","doi":"10.1111/bph.17392","DOIUrl":"https://doi.org/10.1111/bph.17392","url":null,"abstract":"","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Disruption of survivin protein expression by treatment with YM155 accelerates the resolution of neutrophilic inflammation. 用 YM155 治疗可破坏存活素蛋白的表达,从而加速中性粒细胞炎症的消退。
IF 6.8 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-20 DOI: 10.1111/bph.17375
Débora de Oliveira Fernandes, Jessica Rayssa Machado, Vinicius Amorim Beltrami, Anna Clara Paiva Menezes Dos Santos, Celso Martins Queiroz-Junior, Juliana Priscila Vago, Frederico Marianetti Soriani, Flávio Almeida Amaral, Mauro Martins Teixeira, Franciel Batista Felix, Vanessa Pinho

Background and purpose: Prolonged survival of neutrophils is essential for determining the progression and severity of inflammatory and immune-mediated disorders, including gouty arthritis. Survivin, an anti-apoptotic molecule, has been described as a regulator of cell survival. This study aims to examine the effects of YM155 treatment, a survivin selective suppressant, in maintaining neutrophil survival in vitro and in vivo experimental settings of neutrophilic inflammation.

Experimental approach: BALB/c mice were injected with monosodium urate (MSU) crystals and treated with YM155 (intra-articularly) at the peak of inflammatory response. Leukocyte recruitment, apoptosis neutrophil and efferocytosis were determined by knee joint wash cell morphology counting and flow cytometry. Resolution interval (Ri) was quantified by neutrophil infiltration, monitoring the amplitude and duration of the inflammation. Cytokine production was measured by ELISA. Mechanical hypernociception was assessed using an electronic von Frey aesthesiometer. Efferocytosis was evaluated in zymosan-induced neutrophilic peritonitis. Survivin and cleaved caspase-3 expression was determined in human neutrophils by flow cytometry.

Key results: Survivin was expressed in neutrophils during MSU-induced gout, and the treatment with YM155 reduced survivin expression and shortened Ri from ∼8 h observed in vehicle-treated mice to ∼5.5 h, effect accompanied by increased neutrophil apoptosis and efferocytosis, both crucial for the inflammation resolution. Reduced IL-1β and CXCL1 levels were also observed in periarticular tissue. YM155 reduced histopathological score and hypernociceptive response. In human neutrophils, lipopolysaccharide (LPS) increased survivin expression, whereas survivin inhibition with YM155 induced neutrophil apoptosis, with activation of caspase-3.

Conclusions and implications: Survivin may be a promising therapeutic target to control neutrophilic inflammation.

背景和目的:中性粒细胞的长期存活对于决定包括痛风性关节炎在内的炎症和免疫介导疾病的进展和严重程度至关重要。Survivin 是一种抗凋亡分子,已被描述为细胞存活的调节因子。本研究旨在考察 YM155(一种存活素选择性抑制剂)在体外和体内中性粒细胞炎症实验环境中维持中性粒细胞存活的效果:实验方法:给 BALB/c 小鼠注射单钠尿酸盐(MSU)结晶,并在炎症反应高峰期用 YM155(关节内)治疗。通过膝关节冲洗细胞形态计数和流式细胞术测定白细胞募集、中性粒细胞凋亡和流出。通过中性粒细胞浸润量化分辨间期(Ri),监测炎症的幅度和持续时间。细胞因子的产生是通过酶联免疫吸附法测定的。机械性痛觉减退是通过电子冯-弗雷痛觉计进行评估的。在紫霉素诱导的嗜中性粒细胞腹膜炎中评估了排泄功能。通过流式细胞术测定了人中性粒细胞中 Survivin 和裂解 Caspase-3 的表达:用YM155治疗可减少Survivin的表达,并将Ri从药物治疗小鼠的8小时缩短至5.5小时。在关节周围组织中也观察到了 IL-1β 和 CXCL1 水平的降低。YM155 降低了组织病理学评分和痛觉反应。在人中性粒细胞中,脂多糖(LPS)会增加存活素的表达,而用 YM155 抑制存活素会诱导中性粒细胞凋亡,并激活 caspase-3:Survivin 可能是控制中性粒细胞炎症的一个有前途的治疗靶点。
{"title":"Disruption of survivin protein expression by treatment with YM155 accelerates the resolution of neutrophilic inflammation.","authors":"Débora de Oliveira Fernandes, Jessica Rayssa Machado, Vinicius Amorim Beltrami, Anna Clara Paiva Menezes Dos Santos, Celso Martins Queiroz-Junior, Juliana Priscila Vago, Frederico Marianetti Soriani, Flávio Almeida Amaral, Mauro Martins Teixeira, Franciel Batista Felix, Vanessa Pinho","doi":"10.1111/bph.17375","DOIUrl":"https://doi.org/10.1111/bph.17375","url":null,"abstract":"<p><strong>Background and purpose: </strong>Prolonged survival of neutrophils is essential for determining the progression and severity of inflammatory and immune-mediated disorders, including gouty arthritis. Survivin, an anti-apoptotic molecule, has been described as a regulator of cell survival. This study aims to examine the effects of YM155 treatment, a survivin selective suppressant, in maintaining neutrophil survival in vitro and in vivo experimental settings of neutrophilic inflammation.</p><p><strong>Experimental approach: </strong>BALB/c mice were injected with monosodium urate (MSU) crystals and treated with YM155 (intra-articularly) at the peak of inflammatory response. Leukocyte recruitment, apoptosis neutrophil and efferocytosis were determined by knee joint wash cell morphology counting and flow cytometry. Resolution interval (Ri) was quantified by neutrophil infiltration, monitoring the amplitude and duration of the inflammation. Cytokine production was measured by ELISA. Mechanical hypernociception was assessed using an electronic von Frey aesthesiometer. Efferocytosis was evaluated in zymosan-induced neutrophilic peritonitis. Survivin and cleaved caspase-3 expression was determined in human neutrophils by flow cytometry.</p><p><strong>Key results: </strong>Survivin was expressed in neutrophils during MSU-induced gout, and the treatment with YM155 reduced survivin expression and shortened Ri from ∼8 h observed in vehicle-treated mice to ∼5.5 h, effect accompanied by increased neutrophil apoptosis and efferocytosis, both crucial for the inflammation resolution. Reduced IL-1β and CXCL1 levels were also observed in periarticular tissue. YM155 reduced histopathological score and hypernociceptive response. In human neutrophils, lipopolysaccharide (LPS) increased survivin expression, whereas survivin inhibition with YM155 induced neutrophil apoptosis, with activation of caspase-3.</p><p><strong>Conclusions and implications: </strong>Survivin may be a promising therapeutic target to control neutrophilic inflammation.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
GraphCPP: The new state-of-the-art method for cell-penetrating peptide prediction via graph neural networks. GraphCPP:通过图神经网络预测细胞穿透肽的最新方法。
IF 6.8 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-20 DOI: 10.1111/bph.17388
Attila Imre, Balázs Balogh, István Mándity

Background and purpose: Cell-penetrating peptides (CPPs) are short amino acid sequences that can penetrate cell membranes and deliver molecules into cells. Several models have been developed for their discovery, yet these models often face challenges in accurately predicting membrane penetration due to the complex nature of peptide-cell interactions. Hence, there is a need for innovative approaches that can enhance predictive performance.

Experimental approach: In this study, we present the application GraphCPP, a novel graph neural network (GNN) for the prediction of membrane penetration capability of peptides.

Key results: A new comprehensive dataset-dubbed CPP1708-was constructed resulting in the largest reliable database of CPPs to date. Comparative analyses with previous methods, such as MLCPP2, C2Pred, CellPPD and CellPPD-Mod, demonstrated the superior predictive performance of our model. Upon testing against other published methods, GraphCPP performs exceptionally, achieving 0.5787 Matthews correlation coefficient and 0.8459 area under the curve (AUC) values on one dataset. This means a 92.8% and 23.3% improvement in Matthews correlation coefficient and AUC measures respectively compared with the next best model. The capability of the model to effectively learn peptide representations was demonstrated through t-distributed stochastic neighbour embedding plots. Additionally, the uncertainty analysis revealed that GraphCPP maintains high confidence in predictions for peptides shorter than 40 amino acids. The source code is available at https://github.com/attilaimre99/GraphCPP.

Conclusion and implications: These findings indicate the potential of GNN-based models to improve CPP penetration prediction and it may contribute towards the development of more efficient drug delivery systems.

背景和目的:细胞穿透肽(CPPs)是一种能穿透细胞膜并将分子送入细胞的短氨基酸序列。目前已开发出多种用于发现它们的模型,但由于肽与细胞间相互作用的复杂性,这些模型在准确预测膜穿透性方面往往面临挑战。因此,我们需要能提高预测性能的创新方法:在本研究中,我们介绍了 GraphCPP 的应用,这是一种新型图神经网络(GNN),用于预测多肽的膜穿透能力:我们构建了一个新的综合数据集,称为 CPP1708,这是迄今为止最大的可靠 CPP 数据库。与以往方法(如 MLCPP2、C2Pred、CellPPD 和 CellPPD-Mod)的比较分析表明,我们的模型具有更优越的预测性能。在与其他已发布方法的对比测试中,GraphCPP 表现优异,在一个数据集上实现了 0.5787 的马修斯相关系数和 0.8459 的曲线下面积(AUC)值。这意味着与次佳模型相比,马修斯相关系数和 AUC 值分别提高了 92.8% 和 23.3%。该模型有效学习多肽表征的能力通过 t 分布随机相邻嵌入图得到了证明。此外,不确定性分析表明,GraphCPP 对短于 40 个氨基酸的肽的预测保持了很高的置信度。源代码见 https://github.com/attilaimre99/GraphCPP.Conclusion 和 implications:这些研究结果表明,基于 GNN 的模型具有改进 CPP 穿透预测的潜力,它可能有助于开发更高效的给药系统。
{"title":"GraphCPP: The new state-of-the-art method for cell-penetrating peptide prediction via graph neural networks.","authors":"Attila Imre, Balázs Balogh, István Mándity","doi":"10.1111/bph.17388","DOIUrl":"https://doi.org/10.1111/bph.17388","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cell-penetrating peptides (CPPs) are short amino acid sequences that can penetrate cell membranes and deliver molecules into cells. Several models have been developed for their discovery, yet these models often face challenges in accurately predicting membrane penetration due to the complex nature of peptide-cell interactions. Hence, there is a need for innovative approaches that can enhance predictive performance.</p><p><strong>Experimental approach: </strong>In this study, we present the application GraphCPP, a novel graph neural network (GNN) for the prediction of membrane penetration capability of peptides.</p><p><strong>Key results: </strong>A new comprehensive dataset-dubbed CPP1708-was constructed resulting in the largest reliable database of CPPs to date. Comparative analyses with previous methods, such as MLCPP2, C2Pred, CellPPD and CellPPD-Mod, demonstrated the superior predictive performance of our model. Upon testing against other published methods, GraphCPP performs exceptionally, achieving 0.5787 Matthews correlation coefficient and 0.8459 area under the curve (AUC) values on one dataset. This means a 92.8% and 23.3% improvement in Matthews correlation coefficient and AUC measures respectively compared with the next best model. The capability of the model to effectively learn peptide representations was demonstrated through t-distributed stochastic neighbour embedding plots. Additionally, the uncertainty analysis revealed that GraphCPP maintains high confidence in predictions for peptides shorter than 40 amino acids. The source code is available at https://github.com/attilaimre99/GraphCPP.</p><p><strong>Conclusion and implications: </strong>These findings indicate the potential of GNN-based models to improve CPP penetration prediction and it may contribute towards the development of more efficient drug delivery systems.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
NaHS alters synaptic plasticity proteins and enhances dendritic arborization to improve cognitive and motor deficits after traumatic brain injury in mice. NaHS 可改变突触可塑性蛋白并增强树突树轴化,从而改善小鼠脑外伤后的认知和运动障碍。
IF 6.8 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-19 DOI: 10.1111/bph.17386
Farheen Nasir, Priyanka Yadav, Thamil Mani Sivanandam

Background and purpose: Traumatic brain injury (TBI) is a complex medical condition affecting people globally. Hydrogen sulfide (H2S) is a recently discovered gaseous mediator and is dysregulated in the brain after TBI. Sodium hydrogen sulfide (NaHS), a known donor of H2S, is beneficial in various biological processes involving aging and diseases, including injury. It is neuroprotective against oxidative stress, neuroinflammation, and other secondary injury processes. However, the NaHS-H2S system has not been investigated as a regulator of injury-mediated synaptic plasticity proteins and the underlying mechanisms after TBI.

Experimental approach: We developed a model of TBI in Swiss albino mice to study the effects of exogenous H2S, administered as NaHS. We assessed cognitive function (Barnes maze and novel object recognition) and motor function (rotarod). Brain tissue was analysed with ELISA, qRT-PCR, immunoblotting, Golgi-cox staining, and immunofluorescence.

Key results: NaHS administration restored the injury-caused decline in H2S levels. Injury-mediated oxidative stress parameters were improved following NaHS. It down-regulated TBI biomarkers, ameliorated the synaptic marker proteins, and improved cognitive and motor deficits. These changes were accompanied by enhanced dendritic arborization and spine number. Restoration of N-methyl D-aspartate receptor subunits and diminished glutamate and calcium levels, along with marked changes in microtubule-associated protein 2 A and calcium/calmodulin-dependent protein kinase II, formed the basis of the underlying mechanism(s).

Conclusion and implications: Our findings suggest that NaHS could have therapeutic activity against TBI, as it ameliorated cognitive and motor deficits caused by changes in synaptic plasticity proteins and dendritic arborisation, in our model.

背景和目的:创伤性脑损伤(TBI)是一种复杂的医疗状况,影响着全球各地的人们。硫化氢(H2S)是最近发现的一种气体介质,在创伤性脑损伤后会在大脑中失调。硫化氢钠(NaHS)是一种已知的 H2S 供体,在涉及衰老和疾病(包括损伤)的各种生物过程中都有益处。它对氧化应激、神经炎症和其他继发性损伤过程具有神经保护作用。然而,NaHS-H2S 系统作为损伤介导的突触可塑性蛋白的调控因子及其在创伤性脑损伤后的内在机制尚未得到研究:我们在瑞士白化小鼠中建立了创伤性脑损伤模型,以研究外源 H2S(以 NaHS 的形式给药)的影响。我们评估了认知功能(巴恩斯迷宫和新物体识别)和运动功能(旋转木马)。通过酶联免疫吸附试验、qRT-PCR、免疫印迹、高尔基体-细胞毒染色和免疫荧光对脑组织进行了分析:主要结果:服用 NaHS 可恢复损伤导致的 H2S 水平下降。服用 NaHS 后,损伤介导的氧化应激参数得到改善。它下调了创伤性脑损伤生物标志物,改善了突触标志蛋白,并改善了认知和运动障碍。伴随这些变化的是树突轴化和脊柱数量的增加。N 甲基 D-天冬氨酸受体亚单位的恢复、谷氨酸和钙水平的降低,以及微管相关蛋白 2 A 和钙/钙调蛋白依赖性蛋白激酶 II 的明显变化,构成了潜在机制的基础:我们的研究结果表明,NaHS 对创伤性脑损伤具有治疗活性,因为在我们的模型中,NaHS 可改善因突触可塑性蛋白和树突轴化的变化而导致的认知和运动障碍。
{"title":"NaHS alters synaptic plasticity proteins and enhances dendritic arborization to improve cognitive and motor deficits after traumatic brain injury in mice.","authors":"Farheen Nasir, Priyanka Yadav, Thamil Mani Sivanandam","doi":"10.1111/bph.17386","DOIUrl":"https://doi.org/10.1111/bph.17386","url":null,"abstract":"<p><strong>Background and purpose: </strong>Traumatic brain injury (TBI) is a complex medical condition affecting people globally. Hydrogen sulfide (H<sub>2</sub>S) is a recently discovered gaseous mediator and is dysregulated in the brain after TBI. Sodium hydrogen sulfide (NaHS), a known donor of H<sub>2</sub>S, is beneficial in various biological processes involving aging and diseases, including injury. It is neuroprotective against oxidative stress, neuroinflammation, and other secondary injury processes. However, the NaHS-H<sub>2</sub>S system has not been investigated as a regulator of injury-mediated synaptic plasticity proteins and the underlying mechanisms after TBI.</p><p><strong>Experimental approach: </strong>We developed a model of TBI in Swiss albino mice to study the effects of exogenous H<sub>2</sub>S, administered as NaHS. We assessed cognitive function (Barnes maze and novel object recognition) and motor function (rotarod). Brain tissue was analysed with ELISA, qRT-PCR, immunoblotting, Golgi-cox staining, and immunofluorescence.</p><p><strong>Key results: </strong>NaHS administration restored the injury-caused decline in H<sub>2</sub>S levels. Injury-mediated oxidative stress parameters were improved following NaHS. It down-regulated TBI biomarkers, ameliorated the synaptic marker proteins, and improved cognitive and motor deficits. These changes were accompanied by enhanced dendritic arborization and spine number. Restoration of N-methyl D-aspartate receptor subunits and diminished glutamate and calcium levels, along with marked changes in microtubule-associated protein 2 A and calcium/calmodulin-dependent protein kinase II, formed the basis of the underlying mechanism(s).</p><p><strong>Conclusion and implications: </strong>Our findings suggest that NaHS could have therapeutic activity against TBI, as it ameliorated cognitive and motor deficits caused by changes in synaptic plasticity proteins and dendritic arborisation, in our model.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 endocannabinoid anandamide mediates anti-inflammatory effects through activation of NR4A nuclear receptors. 内源性大麻酰胺通过激活 NR4A 核受体介导抗炎作用。
IF 6.8 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-19 DOI: 10.1111/bph.17366
Tom Teichmann, Beatrice Pflüger-Müller, Virna Margarita Martín Giménez, Fiona Sailer, Henrik Dirks, Simonida Zehr, Timothy Warwick, Felix Brettner, Paola Munoz-Tello, Andreas Zimmer, Irmgard Tegeder, Dominique Thomas, Robert Gurke, Stefan Günther, Jan Heering, Ewgenij Proschak, Gerd Geisslinger, Iris-S Bibli, Dagmar Meyer Zu Heringdorf, Walter Manucha, Maike Windbergs, Stefan Knapp, Andreas Weigert, Matthias S Leisegang, Douglas Kojetin, Ralf P Brandes

Background and purpose: Endocannabinoids are lipid mediators, which elicit complex biological effects that extend beyond the central nervous system. Tissue concentrations of endocannabinoids increase in atherosclerosis, and for the endocannabinoid N-arachidonoyl-ethanolamine (anandamide, AEA), this has been linked to an anti-inflammatory function. In this study, we set out to determine the anti-inflammatory mechanism of action of AEA, specifically focusing on vascular smooth muscle cells.

Experimental approach: RNA-sequencing, RT-qPCR, LC-MS/MS, NanoBit, ChIP, microscale thermophoresis, NMR structural footprinting, Gal4 reporter gene assays and loss of function approaches in cell and ex vivo organ culture were used.

Key results: AEA pretreatment attenuated the cytokine-mediated induction of inflammatory gene expression such as CCL2. This effect was also observed in preparations obtained from cannabinoid receptor knockout mice and after pertussis toxin treatment. The anti-inflammatory effect of AEA required preincubation, suggesting an effect through gene induction. AEA increased the expression of the nuclear receptors NR4A1 and NR4A2. Knockdown and knockout of these receptors blocked the AEA-mediated anti-inflammatory effect in cell culture and aortic organ culture, respectively. Conversely, NR4A agonists (CsnB, C-DIM12) attenuated inflammatory gene expression. AEA binds to NR4A, and mutations in NR4A attenuated this effect. The interaction of AEA with NR4A caused recruitment of the nuclear corepressor NCoR1 to the CCL2 promoter, resulting in gene suppression.

Conclusion and implications: By binding to NR4A, AEA elicits an anti-inflammatory response in vascular smooth muscle cells. NR4A-binding by AEA analogues may represent novel anti-inflammatory agents.

背景和目的:内源性大麻素是一种脂质介质,它所产生的复杂生物效应超出了中枢神经系统的范围。动脉粥样硬化时,组织中的内源性大麻素浓度会增加,而内源性大麻素 N-丙烯酰乙醇胺(anandamide,AEA)与抗炎功能有关。在这项研究中,我们试图确定 AEA 的抗炎作用机制,特别是针对血管平滑肌细胞:实验方法:采用 RNA 序列测定、RT-qPCR、LC-MS/MS、NanoBit、ChIP、微尺度热泳、核磁共振结构足迹分析、Gal4 报告基因测定以及细胞和体外器官培养中的功能缺失方法:AEA 预处理可减轻细胞因子介导的炎症基因(如 CCL2)表达。在大麻素受体剔除小鼠的制备物中和百日咳毒素处理后也观察到了这种效果。AEA 的抗炎作用需要预孵育,这表明其作用是通过基因诱导产生的。AEA 增加了核受体 NR4A1 和 NR4A2 的表达。在细胞培养和主动脉器官培养中,敲除和剔除这些受体分别阻断了 AEA 介导的抗炎作用。相反,NR4A 激动剂(CsnB、C-DIM12)可减轻炎症基因的表达。AEA 与 NR4A 结合,而 NR4A 的突变会减弱这种效应。AEA 与 NR4A 的相互作用导致核核心抑制因子 NCoR1 募集到 CCL2 启动子,从而导致基因抑制:通过与 NR4A 结合,AEA 在血管平滑肌细胞中引起抗炎反应。与 NR4A 结合的 AEA 类似物可能是新型抗炎药物。
{"title":"The endocannabinoid anandamide mediates anti-inflammatory effects through activation of NR4A nuclear receptors.","authors":"Tom Teichmann, Beatrice Pflüger-Müller, Virna Margarita Martín Giménez, Fiona Sailer, Henrik Dirks, Simonida Zehr, Timothy Warwick, Felix Brettner, Paola Munoz-Tello, Andreas Zimmer, Irmgard Tegeder, Dominique Thomas, Robert Gurke, Stefan Günther, Jan Heering, Ewgenij Proschak, Gerd Geisslinger, Iris-S Bibli, Dagmar Meyer Zu Heringdorf, Walter Manucha, Maike Windbergs, Stefan Knapp, Andreas Weigert, Matthias S Leisegang, Douglas Kojetin, Ralf P Brandes","doi":"10.1111/bph.17366","DOIUrl":"https://doi.org/10.1111/bph.17366","url":null,"abstract":"<p><strong>Background and purpose: </strong>Endocannabinoids are lipid mediators, which elicit complex biological effects that extend beyond the central nervous system. Tissue concentrations of endocannabinoids increase in atherosclerosis, and for the endocannabinoid N-arachidonoyl-ethanolamine (anandamide, AEA), this has been linked to an anti-inflammatory function. In this study, we set out to determine the anti-inflammatory mechanism of action of AEA, specifically focusing on vascular smooth muscle cells.</p><p><strong>Experimental approach: </strong>RNA-sequencing, RT-qPCR, LC-MS/MS, NanoBit, ChIP, microscale thermophoresis, NMR structural footprinting, Gal4 reporter gene assays and loss of function approaches in cell and ex vivo organ culture were used.</p><p><strong>Key results: </strong>AEA pretreatment attenuated the cytokine-mediated induction of inflammatory gene expression such as CCL2. This effect was also observed in preparations obtained from cannabinoid receptor knockout mice and after pertussis toxin treatment. The anti-inflammatory effect of AEA required preincubation, suggesting an effect through gene induction. AEA increased the expression of the nuclear receptors NR4A1 and NR4A2. Knockdown and knockout of these receptors blocked the AEA-mediated anti-inflammatory effect in cell culture and aortic organ culture, respectively. Conversely, NR4A agonists (CsnB, C-DIM12) attenuated inflammatory gene expression. AEA binds to NR4A, and mutations in NR4A attenuated this effect. The interaction of AEA with NR4A caused recruitment of the nuclear corepressor NCoR1 to the CCL2 promoter, resulting in gene suppression.</p><p><strong>Conclusion and implications: </strong>By binding to NR4A, AEA elicits an anti-inflammatory response in vascular smooth muscle cells. NR4A-binding by AEA analogues may represent novel anti-inflammatory agents.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
RETRACTION: Cloricromene, a Coumarine Derivative, Protects Against Collagen-induced Arthritis in Lewis Rats. 回放:香豆素衍生物氯克罗孟能保护路易斯大鼠免受胶原蛋白诱发的关节炎。
IF 6.8 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-17 DOI: 10.1111/bph.17417
{"title":"RETRACTION: Cloricromene, a Coumarine Derivative, Protects Against Collagen-induced Arthritis in Lewis Rats.","authors":"","doi":"10.1111/bph.17417","DOIUrl":"https://doi.org/10.1111/bph.17417","url":null,"abstract":"","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
期刊
British Journal of Pharmacology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
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
×
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
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