British Journal of Pharmacology最新文献

{"title":"Repurposing tirbanibulin as an orally active E2-targeting entry inhibitor against Chikungunya virus","authors":"Jing-wen Gu,&nbsp;Yan-hua He,&nbsp;Yu-qing Ma,&nbsp;Wan-da Tang,&nbsp;Shu-dan Luo,&nbsp;Hai-lin Tang,&nbsp;Yan-yong Yang,&nbsp;Fu Gao,&nbsp;Ping Zhao","doi":"10.1111/bph.70642","DOIUrl":"10.1111/bph.70642","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background and purpose</h3>\u0000 \u0000 <p>Chikungunya virus (CHIKV) causes severe acute and chronic disease, yet no approved specific antiviral treatment exists. To rapidly identify potential treatments, we aimed to screen an FDA-approved drug library for inhibitors of CHIKV infection. Tirbanibulin, a dual-microtubule polymerization and Src kinase inhibitor, was assessed for its potential anti-CHIKV activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a high-throughput screen of an FDA-approved drug library. Mechanism-of-action studies included entry-step analysis, surface plasmon resonance (SPR) binding assays and molecular docking. <i>In vivo</i> efficacy was evaluated in lethal murine neuroinfection and CHIKV-induced arthritis models following oral administration of the candidate compound.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Experimental approach</h3>\u0000 \u0000 <p>Tirbanibulin exhibited nanomolar to low-micromolar antiviral activity (EC₅₀ range: 0.035–75.64 μM) across multiple cell lines, with high selective indices in key target HT22 and Huh7 cells. It acted at a post-attachment entry step, inhibiting clathrin-mediated endocytosis and potentially viral fusion. Surface plasmon resonance confirmed direct, high-affinity binding to the CHIKV E1 and E2 glycoprotein complex (K_D = 73 nM). In the lethal neuroinfection model, oral tirbanibulin significantly improved survival and reduced brain viral loads; in the arthritis model, it markedly attenuated footpad swelling and inflammatory pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion and implications</h3>\u0000 \u0000 <p>Tirbanibulin is a novel, orally bioavailable entry-stage inhibitor that directly targets the E2 glycoprotein. Multiple preclinical and clinical studies have confirmed its favourable oral bioavailability and safety. Given its established clinical safety profile, it represents a promising repurposing candidate for clinical evaluation against Chikungunya fever.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"183 21","pages":"6519-6533"},"PeriodicalIF":7.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700904","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}

{"title":"Direct evidence implicating the asymmetrical dimethylarginine (ADMA)-dimethylarginine dimethylaminohydrolase 1 (DDAH1) pathway in cerebrovascular dysfunction and stroke pathogenesis in mice","authors":"Arun Flynn,&nbsp;Alexandra Riddell,&nbsp;Ashton Bernard,&nbsp;Jennifer Haggarty,&nbsp;Stefan Weidt,&nbsp;Jawza Alenazi,&nbsp;Erika Trabold,&nbsp;Delyth Graham,&nbsp;Laura B. Dowsett,&nbsp;James Leiper,&nbsp;Alyson A. Miller","doi":"10.1111/bph.70556","DOIUrl":"10.1111/bph.70556","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS), whereas dimethylaminohydrolase 1 (DDAH1) is primarily responsible for its metabolism. However, the roles of DDAH1 in cerebrovascular regulation are poorly understood. Furthermore, despite evidence that elevated ADMA levels are associated with worse ischaemic stroke outcomes, there is a paucity of data showing causality. Therefore, this study aimed to address these knowledge gaps.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Experimental Approach</h3>\u0000 \u0000 <p>We examined the effect of an inhibitor of DDAH1 (L-257) on endothelial-nitric oxide-dependent vasodilator responses of mouse middle cerebral arteries (MCA), permeability of immortalised human cerebral endothelial cells and angiogenic activity of MCA. To test for a causal relationship between ADMA and stroke pathogenesis, we examined the effect of L-257 at a concentration that did not alter cardiovascular haemodynamics on infarct volume and functional outcomes in mice after MCA occlusion (MCAo).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key Results</h3>\u0000 \u0000 <p>In vitro, L-257 impaired vasodilator responses of MCA (<i>R</i>_max: ~50%), increased endothelial permeability (~1.5-fold) and impaired endothelial outgrowth of MCA (~40%). In vivo, L-257 (30 mg·kg⁻¹) increased ADMA levels without affecting haemodynamics and resulted in larger infarcts and greater deficits after 40-min transient MCAo (tMCAo). However, when mice were subjected to longer MCAo periods (65-min tMCAo or permanent MCAo) to generate moderate/severe insults, L-257 did not significantly affect outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion and Implications</h3>\u0000 \u0000 <p>DDAH1 contributes to the regulation of cerebrovascular endothelial-nitric oxide-regulated physiological processes in vitro. Furthermore, we provide direct evidence linking elevated ADMA levels and stroke pathogenesis; however, this relationship may be dependent on initial stroke severity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"183 21","pages":"6422-6443"},"PeriodicalIF":7.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.70556","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Receptor kinetics: Binding flux-based approaches offer complementary insight into how ligand binding evolves with time","authors":"Georges Vauquelin,&nbsp;Terry Kenakin,&nbsp;Dominique Maes","doi":"10.1111/bph.70622","DOIUrl":"10.1111/bph.70622","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>Binding kinetics are essentially based on rate constants. Yet, this view has been challenged by the idea that ‘binding fluxes’ are dynamic and therefore more relevant. Those fluxes refer to the rate at which a target/receptor changes from one state into another through ligand/drug binding or a conformational change. Besides acting as building blocks for many algebraic expressions, they also determine how the concentration of each individual target state evolves over time. Here we show that such fluxes offer additional opportunities for understanding and predicting ligand binding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Experimental approach</h3>\u0000 \u0000 <p>Simulated binding data are obtained by solving the relevant set of flux-based differential equations for increasingly complex ligand binding models over very small time intervals by Euler's method. As input, they require only ligand concentration(s) and rate constants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key results</h3>\u0000 \u0000 <p>Compared to often-complex algebraic expressions, binding fluxes allow more intuitive/inductive insight into different aspects of ligand binding such as the occurrence of transient binding overshoots and the effect of a closing lid over the ligand's binding pocket on ligand dissociation. These examples disclose fundamental principles that govern ligand binding and, above all, they highlight the essential role of rate constants in all the examined binding models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions and implications</h3>\u0000 \u0000 <p>Binding fluxes and rate constants complement each other: They respectively indicate how and why binding processes evolve in a certain fashion. The presented flux-based approaches have the advantage to address pre-equilibrium as well as equilibrium conditions and can be applied to any ligand-binding model.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"183 21","pages":"6444-6457"},"PeriodicalIF":7.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.70622","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thirty-day dapagliflozin therapy improves the nanomechanical properties of red blood cells in patients with type 1 diabetes","authors":"Patrycja Twardawa,&nbsp;Agata Kubisiak,&nbsp;Bartłomiej Matejko,&nbsp;Katarzyna Cyranka,&nbsp;Maxim Lushchyk,&nbsp;Joanna Hajduk,&nbsp;Sabina Krzyżowska,&nbsp;Maciej Tadeusz Małecki,&nbsp;Marta Targosz-Korecka,&nbsp;Tomasz Klupa","doi":"10.1111/bph.70613","DOIUrl":"10.1111/bph.70613","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>Sodium-glucose cotransporter 2 (SGLT2) selective inhibitors (flozins) are a class of antidiabetic drugs that improve glycaemic control and are associated with cardiovascular benefits, although the underlying mechanisms remain incompletely understood. This study aimed to explore potential mechanistic effects of dapagliflozin on erythrocyte nanomechanical properties in patients with type 1 diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Experimental Approach</h3>\u0000 \u0000 <p>The subject of this exploratory study is the nanomechanical properties of red blood cells (RBCs) in a pilot group of type 1 diabetes patients undergoing a thirty-day dapagliflozin treatment. Measurements were conducted on RBCs obtained from a homogeneous group of 31 adult patients with type 1 diabetes and 34 healthy control volunteers. The elastic modulus of erythrocytes was measured immediately after sample collection using the nanoindentation method with an atomic force microscopy probe. Data obtained before therapy (BT) and after therapy (AT) were compared with those from a control group of healthy volunteers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key Results</h3>\u0000 \u0000 <p>A reduction in RBC stiffness after treatment was observed, which could be related to diabetes duration. Notably, the most significant improvement occurred in patients with diabetes duration exceeding 10 years, a group at elevated cardiovascular risk. Subgroup analyses were descriptive and not powered for inferential comparisons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion and Implications</h3>\u0000 \u0000 <p>The observed improvement in the elastic modulus of erythrocytes following dapagliflozin therapy in patients with type 1 diabetes suggests that SGLT2 inhibitors could provide additional benefits for this patient group The results provide preliminary mechanistic insights that are consistent with the reported vascular effects of SGLT2 inhibitors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"183 21","pages":"6386-6403"},"PeriodicalIF":7.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618538","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}

{"title":"Honokiol regulates Acute respiratory distress syndrome (ARDS)-associated pulmonary fibrosis via the miR-19a-3p/POSTN axis","authors":"Weilun Liu,&nbsp;Hsiaohsuan Wang,&nbsp;Hsuanfu Kuo,&nbsp;Chiahung Yen,&nbsp;Modasang Hua,&nbsp;Chiayuan Chang,&nbsp;Zhiwei Xu,&nbsp;Ifan Liu,&nbsp;Chongchao Hsieh,&nbsp;Chihhsin Hsu,&nbsp;Chiayang Li,&nbsp;Shuchi Wang,&nbsp;Yunghsiang Chen,&nbsp;Menghsuan Cheng,&nbsp;Polen Liu","doi":"10.1111/bph.70580","DOIUrl":"10.1111/bph.70580","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>Acute respiratory distress syndrome (ARDS) and subsequent pulmonary fibrosis are associated with high mortality and limited treatment options. Periostin (POSTN) is a profibrotic mediator predicted to be regulated by microRNA-19a-3p (miR-19a-3p), but the relevance of this axis in ARDS-associated pulmonary fibrosis remains unclear. Honokiol (HKL), a phytochemical derived from <i>Magnolia officinalis</i>, possesses antioxidant and anti-inflammatory properties. This study investigated whether HKL modulates the miR-19a-3p/POSTN axis in ARDS-associated lung injury and fibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Experimental Approach</h3>\u0000 \u0000 <p>Serum POSTN and miR-19a-3p levels were measured in patients with ARDS and correlated with severity. Mechanistic studies were performed using a lipopolysaccharide (LPS)-induced lung injury mouse model and macrophage–epithelial and macrophage–fibroblast co-culture systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key Results</h3>\u0000 \u0000 <p>Patients with ARDS exhibited elevated serum POSTN and reduced miR-19a-3p, which were inversely correlated and associated with indices of disease severity. HKL attenuated LPS-induced lung injury and fibrotic responses, accompanied by reduced POSTN expression and preserved miR-19a-3p levels. Dual-luciferase reporter assays supported a regulatory interaction between miR-19a-3p and POSTN. HKL was associated with alterations in macrophage phenotype and reduced macrophage-associated POSTN expression. In co-culture systems, manipulation of miR-19a-3p in macrophages modulated epithelial apoptotic signalling and fibroblast activation. In vitro loss-of-function experiments suggested that miR-19a-3p contributes, at least in part, to HKL-associated protective effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion and Implications</h3>\u0000 \u0000 <p>The miR-19a-3p/POSTN axis may represent a regulatory pathway associated with ARDS-related lung injury and fibrosis. HKL attenuated experimental injury and fibrotic responses in association with this axis. These findings support further pharmacological investigation of HKL in ARDS-associated lung injury and fibrosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"183 21","pages":"6329-6351"},"PeriodicalIF":7.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.70580","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Stimulation of P2 purinergic receptors induces the release of eosinophil cationic protein and interleukin-8 from human eosinophils”","authors":"","doi":"10.1111/bph.70665","DOIUrl":"10.1111/bph.70665","url":null,"abstract":"<p>\u0000 <span>Idzko, M.</span>, <span>Panther, E.</span>, <span>Bremer, H.C.</span>, <span>Sorichter, S.</span>, <span>Luttmann, W.</span>, <span>Virchow, J.C.</span>, <span>Di Virgilio, F.</span>, <span>Herouy, Y.</span>, <span>Norgauer, J.</span> and <span>Ferrari, D.</span> (<span>2003</span>), <span>Stimulation of P2 purinergic receptors induces the release of eosinophil cationic protein and interleukin-8 from human eosinophils</span>. <i>British Journal of Pharmacology</i>, <span>138</span>: <span>1244</span>–<span>1250</span>. https://doi.org/10.1038/sj.bjp.0705145</p><p>The sixth author's name is incorrect. The correct name is J. Christian Virchow.</p><p>The online version of this article has been corrected accordingly.</p><p>We apologize for this error.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"183 21","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.70665","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adiponectin promotes AMPA receptor trafficking and enhances excitatory synaptic transmission at hippocampal synapses via AMP-activated protein kinase signalling","authors":"Alexandra Soca,&nbsp;Patricia Raposo Afonso,&nbsp;Valentin Morfin,&nbsp;James Cantley,&nbsp;Jenni Harvey","doi":"10.1111/bph.70600","DOIUrl":"10.1111/bph.70600","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>Peripherally derived adiponectin crosses the blood–brain barrier and targets severa0l brain regions. Adiponectin receptors are highly expressed in the hippocampus, and play a pro-cognitive role as adiponectin markedly influences the functioning of hippocampal synapses. Trafficking of AMPA receptors underlies activity-dependent hippocampal synaptic plasticity, but it is unclear if adiponectin influences this process. Here, we examined the effects of he adiponectin receptor agonist, AdipoRon, on AMPA receptor trafficking and hippocampal excitatory synaptic function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Experimental Approach</h3>\u0000 \u0000 <p>Immunocytochemistry combined with confocal microscopy was used to monitor the surface expression of the AMPA receptor subunit, GluA1, in hippocampal neurons cultured from neonatal (P0–4) rats. Extracellular field potential recordings were used to monitor excitatory synaptic transmission in hippocampal slices from juvenile male (P14–24) Sprague Dawley rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key Results</h3>\u0000 \u0000 <p>AdipoRon increased GluA1 surface expression and delivered GluA1-containing AMPA receptors to synapses. In hippocampal slices, AdipoRon increased excitatory synaptic transmission, maintained during recordings, and AdipoRon enhanced hippocampal long-term potentiation. Effects of AdipoRon on AMPA receptor trafficking involved AdipoRon receptors, as these effects were mirrored by the adiponectin receptor agonist, ADP355 and blocked by the antagonist, ADP400. AdipoRon-driven increases in surface GluA1 required GluN2A-containing NMDA receptor activation. Effects of AdipoRon on GluA1 expression and synaptic plasticity involved AMPK signalling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions and Implications</h3>\u0000 \u0000 <p>These data show that AdipoRon trafficked GluA1-containing AMPA receptors to synapses and facilitated hippocampal synaptic plasticity via activation of AMPK. These findings have important implications for the role of adiponectin in regulating hippocampal synaptic function in health and disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"183 21","pages":"6501-6518"},"PeriodicalIF":7.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.70600","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Up-regulation of the kinase LRRK2, in enteric glia contributes to mucosal barrier impairment in Parkinson's disease via secretory autophagy","authors":"Vanessa D'Antongiovanni,&nbsp;Clarissa Pierucci,&nbsp;Cristina Segnani,&nbsp;Chiara Ippolito,&nbsp;Clelia Di Salvo,&nbsp;Elena Lucarini,&nbsp;Luca Antonioli,&nbsp;Matteo Fornai,&nbsp;Nunzia Bernardini,&nbsp;Pascal Derkinderen,&nbsp;Carmelo Scarpignato,&nbsp;Carolina Pellegrini","doi":"10.1111/bph.70623","DOIUrl":"10.1111/bph.70623","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>Patients with Parkinson's disease (PD) show intestinal epithelial barrier (IEB) alterations, enteric gliosis and inflammation that could contribute to gastrointestinal symptoms. Moreover, changes in leucine rich-repeat kinase 2 (LRRK2) expression/activity have been associated with PD development and related intestinal inflammation. However, the molecular determinants linking LRRK2, enteric gliosis and IEB impairment remain unclear. Therefore, we investigated the role of LRRK2 in IEB changes associated with PD, focusing on its role in the interplay between enteric glial cells (EGCs) and intestinal epithelial cells (IECs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Experimental Approach</h3>\u0000 \u0000 <p>Human A53T α-synuclein transgenic (Tg) mice (9 months old) were provided a model of early PD. Central neuroinflammation was studied by IBA-1 staining. Intestinal motility, colonic α-synuclein and LRRK2 expression were assessed. Enteric gliosis was evaluated by detection of GFAP⁺ cells co-expressing LRRK2; IEB was tested by mucins detection and quantification of Muc-2, tight junction proteins and secretory autophagy. In vitro co-cultures between EGCs and IECs were performed to investigate glial LRRK2-mediated gut barrier alterations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key Results</h3>\u0000 \u0000 <p>A53T mice, without central neuroinflammation, showed intestinal disturbances, colonic α-synuclein accumulation and an increase in colonic GFAP⁺/LRRK2⁺ glial cells before brain pathology. Moreover, PD animals displayed IEB alterations and increased colonic autophagosomes, suggesting a shift towards secretory autophagy. In co-culture experiments, α-synuclein and lipopolysaccharide promoted enteric gliosis and LRRK2 up-regulation in glial cells, contributing to IEB impairment via secretory autophagy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions and Implications</h3>\u0000 \u0000 <p>These changes could influence bowel symptoms and central pathology associated with PD, via the gut-brain axis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"183 21","pages":"6534-6553"},"PeriodicalIF":7.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722950","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}

{"title":"RETRACTION: Oxaliplatin Responses in Colorectal Cancer Cells are Modulated by CHK2 Kinase Inhibitors","authors":"","doi":"10.1111/bph.70700","DOIUrl":"10.1111/bph.70700","url":null,"abstract":"<p><b>RETRACTION</b>: \u0000 <span>I. M. Pires</span>, <span>T. H. Ward</span>, and <span>C. Dive</span>, “ <span>Oxaliplatin Responses in Colorectal Cancer Cells are Modulated by CHK2 Kinase Inhibitors</span>,” <i>British Journal of Pharmacology</i> <span>159</span>, no. <span>6</span> (<span>2010</span>): <span>1326</span>–<span>1338</span>, https://doi.org/10.1111/j.1476-5381.2009.00607.x</p><p>The above article, published online on 12 March 2010 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Péter Ferdinandy; the British Pharmacological Society; and John Wiley and Sons Ltd.</p><p>Concerns were raised by a third party on PubPeer [1] that the p53 -phosphoS20 53kD band in Figure 3A contained an identical section between the UT and CHK2II lanes and that there was evidence of splicing in Figure 5A.</p><p>Not all original data for the article, including data from Figure 5, were still available. The editors recognize that, at the time of publication, the presentation of spliced blots may have been more common and that authors may not have had clear journal instructions that they must clearly indicate where splicing had been used for figures with western blots.</p><p>The editors reviewed data supplied by the authors relating to Figure 3A and determined that the published p53-phosphoS20 bands appeared to have been created from different regions of the original blot, aligning with blot lanes representing different experimental conditions than those reported, and so did not accurately represent the experiment as published. The authors report that this was due to an honest error during the construction of the figure for publication.</p><p><b>References</b></p><p>[1] Polystichum kungianum. Comments on “Oxaliplatin responses in colorectal cancer cells are modulated by CHK2 kinase inhibitors,” PubPeer, August 2025. https://pubpeer.com/publications/71CF13B37D21E0E2FF40146A3F502F.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"183 21","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.70700","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: Implications and Hidden Toxicity of Cardiometabolic Syndrome and Early-Stage Heart Failure in Carfilzomib-Induced Cardiotoxicity","authors":"","doi":"10.1111/bph.70699","DOIUrl":"10.1111/bph.70699","url":null,"abstract":"&lt;p&gt;\u0000 &lt;b&gt;RETRACTION&lt;/b&gt;: &lt;span&gt;P. Efentakis&lt;/span&gt;, &lt;span&gt;A. Varela&lt;/span&gt;, &lt;span&gt;S. Lamprou&lt;/span&gt;, &lt;span&gt;E.-D. Papanagnou&lt;/span&gt;, &lt;span&gt;M. Chatzistefanou&lt;/span&gt;, &lt;span&gt;A. Christodoulou&lt;/span&gt;, &lt;span&gt;C. H. Davos&lt;/span&gt;, &lt;span&gt;M. Gavriatopoulou&lt;/span&gt;, &lt;span&gt;I. Trougakos&lt;/span&gt;, &lt;span&gt;M. A. Dimopoulos&lt;/span&gt;, &lt;span&gt;E. Terpos&lt;/span&gt;, and &lt;span&gt;I. Andreadou&lt;/span&gt;, “ &lt;span&gt;Implications and Hidden Toxicity of Cardiometabolic Syndrome and Early-Stage Heart Failure in Carfilzomib-Induced Cardiotoxicity&lt;/span&gt;,” &lt;i&gt;British Journal of Pharmacology&lt;/i&gt; &lt;span&gt;181&lt;/span&gt;, no. &lt;span&gt;16&lt;/span&gt; (&lt;span&gt;2024&lt;/span&gt;): &lt;span&gt;2964&lt;/span&gt;–&lt;span&gt;2990&lt;/span&gt;, https://doi.org/10.1111/bph.16391&lt;/p&gt;&lt;p&gt;The above article, published online on 28 April 2024 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Péter Ferdinandy; the British Pharmacological Society; and John Wiley and Sons Ltd. A third party raised concerns on PubPeer [1] of duplicated echocardiographic recording images between Figure 9A and Supplementary Figure 5A as well as overlapping bands between Supplementary Figures 4A and 4C. The third party also detected reuse of a band in Figure 6D from an earlier article by some of the same authors [Efentakis et al. 2022 (https://doi.org/10.1097/HS9.0000000000000791)] and duplication of bands in Figures 3A and 10F with another article, by some of the same authors, which was under review at the same time [Efentakis et al. 2025 (https://doi.org/10.1007/s00395-024-01046-0)].&lt;/p&gt;&lt;p&gt;An investigation by the publisher and the editors confirmed these concerns and also found that echocardiographic recording images had been duplicated within Figure 9A, between Supplementary Figures 5A and 5E, and between Supplementary Figures 2A and 5A. Furthermore, an additional partial duplication between the GAPDH band in Supplementary Figure 4C and an alpha-actinen band in another article by some of the same authors [Efentakis et al. 2020 (https://doi.org/10.3390/ijms21155185)] was also detected.&lt;/p&gt;&lt;p&gt;The authors responded to an inquiry by the publisher and supplied original data. However, the explanations and data provided did not adequately resolve the concerns. The retraction has been agreed to because the evidence of image duplication in the article and with other articles compromises the editors' confidence in the results presented in the article. Author I. Andreadou passed away prior to the investigation of this article. All other authors disagree with the retraction. The authors further state that that the identified issues resulted from inadvertent errors in representative-image selection and figure assembly, rather than from unreliability of the underlying experimental data and maintain that the quantitative analyses and principal scientific conclusions remain unaffected.&lt;/p&gt;&lt;p&gt;&lt;b&gt;References&lt;/b&gt;&lt;/p&gt;&lt;p&gt;[1] René Aquarius. Comments on “Implications and hidden toxicity of cardiometabolic syndro","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"183 21","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.70699","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}