British Journal of Pharmacology最新文献

{"title":"New biosensors and transgenic mice for multiplex cGMP imaging.","authors":"Markus Wolters, Martin Thunemann, Barbara Birk, Susanne Feil, Viacheslav O Nikolaev, Moritz Lehners, Robert Feil","doi":"10.1111/bph.70193","DOIUrl":"https://doi.org/10.1111/bph.70193","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cyclic guanosine monophosphate (cGMP) is a versatile second messenger that is important for human (patho-)physiology and pharmacotherapy. Live-cell imaging of cGMP with biosensors allows to elucidate its spatiotemporal dynamics in real time under close-to-native conditions. However, to monitor two separate cGMP pools or cGMP/cAMP crosstalk in the same cell, the respective biosensors must be spectrally compatible.</p><p><strong>Experimental approach: </strong>We describe two new Förster/fluorescence resonance energy transfer (FRET)-based cGMP indicators, membrane-targeted mcGi500 and red-shifted cytosolic red-cGi500, as well as two transgenic mouse lines for global and cell type-specific expression of mcGi500. The performance of the new biosensors was characterised in permeabilised and intact primary vascular smooth muscle cells and compared side-by-side with existing cGMP sensors.</p><p><strong>Key results: </strong>Both mcGi500 and red-cGi500 had a high selectivity for cGMP over cAMP and detected cGMP with about 3 times higher sensitivity than the current 'gold standard', cytosolic cGi500. Red-cGi500 allowed robust detection of cGMP in intact vascular smooth muscle cells. By combining red-cGi500 with the 'green' cAMP sensor Epac1-camps, cGMP and cAMP could be co-imaged in the same cells.</p><p><strong>Conclusions and implications: </strong>Together, our data suggest that red-cGi500 and mcGi500 as well as the mcGi500 transgenic mouse lines are useful tools for advanced cGMP imaging, including multiplex imaging of potential cGMP compartments and crosstalk between cGMP and other signalling molecules.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069224","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":"Decoding fatal toxic effects in checkpoint inhibitor therapy using real-world pharmacovigilance data and machine learning.","authors":"Dongxue Yan, Beibei Lyu, Jie Yu, Siqi Bao, Zicheng Zhang, Meng Zhou, Jie Sun","doi":"10.1111/bph.70195","DOIUrl":"https://doi.org/10.1111/bph.70195","url":null,"abstract":"<p><strong>Background and purpose: </strong>Immune checkpoint inhibitors (ICIs) improve cancer outcomes but are also associated with immune-related adverse events (irAEs), which pose significant challenges for clinical management.</p><p><strong>Experimental approach: </strong>An observational pharmacovigilance analysis on FDA Adverse Event Reporting System was performed to identify ICI-related adverse event (AE) signals. Fatality kinetics simulation and multivariate logistic regression were used to investigate patterns of fatal AEs and multisignal involvement. A machine learning framework, SAFE-ICI, was developed to predict short-term risk and outcomes of fatal irAEs occurring within the first 90 days of ICI therapy.</p><p><strong>Key results: </strong>The analysis identified 358 significant AE signals associated with ICI therapies across 18 organ systems. PD-1/PD-L1 therapies were associated with 54 fatal irAEs, including 23 in non-small cell lung cancer (NSCLC), 5 in melanoma, 6 in renal cell carcinoma (RCC) and 20 in other cancers. Combination therapies were associated with 20 fatal irAEs, including 3 in NSCLC, 6 in melanoma, 7 in RCC and 4 in other cancers, with stable involvement of multiple AE signals. The SAFE-ICI model demonstrated robust performance in predicting fatal irAE risk, successfully stratifying patients into low- and high-risk phenotypes with significantly different survival benefits, in both the discovery and holdout validation cohorts.</p><p><strong>Conclusion and implications: </strong>Our findings highlight the potential of machine learning to improve pharmacovigilance systems and aid clinicians in enhancing patient outcomes during ICI therapy.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063385","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":"Beyond TGFβ inhibition: Chitosan oligosaccharide targets PGC-1α-mediated mitochondrial repair to combat pulmonary fibrosis.","authors":"Huan He, Youtao Xu, Xinru Chen, Jiawen Wu, Xianpeng Zhong, Xiyu Li, Yuanrui He, Cong Wang, Jing Qiao","doi":"10.1111/bph.70190","DOIUrl":"https://doi.org/10.1111/bph.70190","url":null,"abstract":"<p><strong>Background and purpose: </strong>Pulmonary fibrosis is a progressive fatal disease with no therapies addressing upstream epithelial injury. Mitochondrial dysfunction drives pulmonary fibrosis pathogenesis through bioenergetic collapse, oxidative stress and chronic inflammation, perpetuating irreversible fibrosis. Although chitosan oligosaccharides exhibit mitochondrial protective effects, their therapeutic potential and mechanism in pulmonary fibrosis remain unexplored.</p><p><strong>Experimental approach: </strong>Using pirfenidone as a clinical benchmark, we assessed the efficacy and mechanisms of chitosan oligosaccharides in a bleomycin-induced pulmonary fibrosis mouse model and two human primary alveolar epithelial cell (AEC) subtypes: - functional type I (AEC-I) and reparative type II (AEC-II). Bleomycin and transforming growth factor beta 1 (TGFβ1) were employed to model AEC-I apoptosis and AEC-II epithelial-mesenchymal transition (EMT), respectively.</p><p><strong>Key results: </strong>Orally administered chitosan oligosaccharides alleviated pulmonary fibrosis pathophysiology, outperforming pirfenidone at equivalent doses. Chitosan oligosaccharides attenuated epithelial remodelling by inhibiting AEC-I apoptosis and compensatory EMT of AEC-II, reducing collagen deposition and alveolar damage. Mechanistically, chitosan oligosaccharides promoted mitochondrial renewal and functional recovery through activation of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/PTEN-induced putative kinase 1 (PINK1)/nuclear factor erythroid 2-related factor 1 (NRF1) axis, restoring bioenergetics and redox homeostasis. Pharmacological PGC-1α inhibition abolished these benefits, confirming pathway dependency.</p><p><strong>Conclusion and implications: </strong>This study defines a mitochondrial repair mechanism for chitosan oligosaccharides in pulmonary fibrosis via PGC-1α/PINK1/NRF1 activation, directly targeting epithelial injury. It establishes carbohydrate-based mitochondrial precision intervention as a transformative strategy for fibrosis, surpassing conventional TGFβ inhibition in addressing upstream pathology.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069186","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":"Paradoxical mitochondrial effects of nitric oxide synthase inhibition following oxygen-glucose deprivation-reoxygenation (OGD/R) in endothelial cells and neurons.","authors":"Venkata N Sure, Siva S V P Sakamuri, Lokanatha Orgunati, Raed Ageeli, Walter L Murfee, Prasad V G Katakam","doi":"10.1111/bph.70187","DOIUrl":"https://doi.org/10.1111/bph.70187","url":null,"abstract":"<p><strong>Background and purpose: </strong>Current dogma in stroke is that neuronal nitric oxide synthase (NOS1) exacerbates ischaemic brain injury, while endothelial nitric oxide synthase (NOS3) is protective. However, oxidative stress from ischaemia-reperfusion and oxygen-glucose deprivation-reoxygenation (OGD/R) is known to uncouple NOS, leading to increased production of reactive oxygen species (ROS). This study investigated whether the inhibition of NOS uncoupling in rat brain microvascular endothelial cells (BMECs) and neurons is cytoprotective against OGD/R-induced injury.</p><p><strong>Experimental approach: </strong>All experiments were conducted in both BMECs and neurons under normoxic conditions and following OGD/R, with or without NOS inhibition. Cell viability was assessed using Cell Counting Kit-8. Electron spin resonance spectrometry measured ROS and NO production, while mitochondrial membrane potential (MMP) was evaluated using rhodamine 123 fluorescence. Oxygen consumption rate (OCR) was measured to assess mitochondrial respiration.</p><p><strong>Key results: </strong>NOS inhibition improved post-OGD/R survival in BMECs and neurons accompanied by a reduction in NOS-derived ROS. Interestingly, while BMECs showed both ROS-producing uncoupled NOS and NO-producing coupled NOS, neurons showed NO-producing NOS only. Under normoxic conditions, NOS inhibition reduced mitochondrial respiration in BMECs but increased OCR in neurons. OGD/R led to impaired mitochondrial respiration in both BMECs and neurons, with further reductions observed following NOS inhibition.</p><p><strong>Conclusions and implications: </strong>NOS inhibition in BMECs and neurons elicit distinct mitochondrial effects under normoxia but promotes identical paradoxical suppression of mitochondrial respiration in response to OGD/R. NOS uncoupling instigates post-OGD/R cellular injury in both BMECs and neurons and is a potential therapeutic target in stroke.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051706","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":"State-dependent regulation of the K_v7.2 channel voltage sensor by QO-58.","authors":"Richard Kanyo, Shawn M Lamothe, Thomas M Hammond, Harley T Kurata","doi":"10.1111/bph.70186","DOIUrl":"https://doi.org/10.1111/bph.70186","url":null,"abstract":"<p><strong>Background and purpose: </strong>K_V7(KCNQ) potassium channels are key modulators of neuronal excitability, and promising targets for development of drugs for epilepsy and pain. We investigated a candidate K_V7 drug, QO-58, which has been previously described but has an unclear mechanism of action.</p><p><strong>Experimental approach: </strong>Targeted mutations or chimeric rearrangements of K_V7 channels were used to investigate potential sites of drug binding. K_V7 channels were expressed in Xenopus oocytes or HEK cells for electrophysiology and pharmacological characterisation.</p><p><strong>Key results: </strong>QO-58 shares characteristic features of other voltage sensor domain (VSD)-targeted potentiators. These include subtype specificity for K_V7.2 over K_V7.3, prominent state-dependent actions, and marked deceleration of closure of K_V7.2. VSD mutations influence the actions of QO-58 and another VSD-targeted drug, ICA-069673. Interestingly, K_V7.2[F168L] mutation, previously shown to abolish ICA-069673 sensitivity, does not weaken QO-58 actions. However, K_V7.2[F168W] reduces QO-58 effects, while preserving sensitivity to ICA-069673. This finding indicates subtle differences in the interaction of these drugs with the VSD binding site.</p><p><strong>Conclusions and implications: </strong>Key contacts underlying sensitivity to VSD-targeted potentiators may vary significantly depending on the chemical and steric features of the drug. We anticipate that further investigation of VSD-targeted drugs will continue to clarify the complex pharmacophore of the VSD binding pocket in K_V7 channels.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039082","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":"Correction to “Behavioural and pharmacokinetic analysis of heroin and cocaine self-administration: Effects of timeout on self-administration and choice in male rats”","authors":"","doi":"10.1111/bph.70212","DOIUrl":"10.1111/bph.70212","url":null,"abstract":"<p>\u0000 <span>D'Ottavio, G.</span>, <span>Pezza, S.</span>, <span>Modoni, J.</span>, <span>Reverte, I.</span>, <span>Marchetti, C.</span>, <span>Zenoni, S.F.</span>, <span>De Pirro, S.</span>, <span>Maftei, D.</span>, <span>Lattanzi, R.</span>, <span>Esposito, G.</span>, <span>Ragozzino, D.</span>, <span>Merlo, E.</span>, <span>Venniro, M.</span>, <span>Ciccocioppo, R.</span>, <span>Fumagalli, F.</span>, <span>Milella, M. S.</span>, <span>Badiani, A.</span>, <span>Boix, F.</span>, &amp; <span>Caprioli, D.</span> (<span>2025</span>). <span>Behavioural and pharmacokinetic analysis of heroin and cocaine self-administration: Effects of timeout on self-administration and choice in male rats</span>. <i>British Journal of Pharmacology</i>, <span>182</span>(<span>13</span>), <span>2968</span>–<span>2985</span>. https://doi.org/10.1111/bph.70023</p><p>The funding statement for this article was missing. The below funding statement has been added to the article:</p><p>Open access funding provided by BIBLIOSAN.</p><p>We apologize for this error.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"182 21","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/bph.70212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039071","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":"Daucosterol ameliorates acute inflammation and fibrosis following myocardial infarction via regulation of the ZBTB16 protein.","authors":"Shihao Sheng, Pingping Wu, Chao Wu, Huimin Su, Zhiqing Guo, Ruisi Wang, Jiaxin Li, Yajun Duan, Shuang Zhang, Likun Ma","doi":"10.1111/bph.70174","DOIUrl":"https://doi.org/10.1111/bph.70174","url":null,"abstract":"<p><strong>Background and purpose: </strong>Myocardial infarction (MI) is accompanied by acute release of numerous inflammatory factors, leading to fibrosis and ultimately cardiac dysfunction. Daucosterol (DAU), a natural sterol compound, has been demonstrated to have anti-inflammatory properties and the ability to mitigate liver fibrosis. This study aims to investigate the therapeutic potential of DAU in MI and explores the underlying mechanisms.</p><p><strong>Experimental approach: </strong>Various doses of DAU were administered to mice before MI. The cardioprotective effects of DAU were evaluated at both in vivo and in vitro levels.</p><p><strong>Key results: </strong>In surgically-induced MI mouse models, DAU treatment reduced cardiac inflammation, attenuated myocardial fibrosis and improved cardiac function. Mechanistically, ZBTB16 expression was significantly suppressed in MI and reversed by DAU treatment by RNA-seq analysis and validation. Specifically, by restoring ZBTB16 protein levels, DAU inhibited S100A8 expression through transcriptional regulation of S100A8 by ZBTB16, thereby alleviating cardiac inflammation and fibrosis. Depletion of ZBTB16 exacerbated cardiac dysfunction in mice.</p><p><strong>Conclusion and implications: </strong>DAU alleviates post-infarction cardiac inflammation and fibrosis through modulation of ZBTB16/S100A8, thereby improving post-infarction cardiac remodelling and protecting heart function.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028928","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":"P2X7 receptor antagonism suppresses epileptiform-like activity in an inflammation-primed human iPSC-derived neuron model of drug-resistant epilepsy.","authors":"Jaideep Kesavan, Yitao Wang, Klaus Dinkel, Michael Hamacher, Jochen H M Prehn, David C Henshall, Tobias Engel","doi":"10.1111/bph.70167","DOIUrl":"https://doi.org/10.1111/bph.70167","url":null,"abstract":"<p><strong>Background and purpose: </strong>Neuroinflammation is increasingly recognised to contribute to drug-resistant epilepsy. Activation of ATP-gated P2X7 receptors has emerged as an important upstream mechanism, and increased P2X7 receptor expression is present in the seizure focus in rodent models and patients. Pharmacological antagonists of P2X7 receptors attenuate seizures in rodents, but this has not been explored in human neural networks.</p><p><strong>Experimental approach: </strong>Human neurons were differentiated from two human induced pluripotent stem cell (hiPSC) lines. P2X7 receptor function on neurons was assessed via the calcium transients evoked by the agonist BzATP. Acute or chronic models of epileptiform-like events were generated by exposing hiPSC cultures to the GABA_A receptor antagonist picrotoxin or a cocktail of picrotoxin and neuroinflammatory agents, with or without P2X7 receptor antagonists. Epileptiform-like activity was measured via single cell patch-clamp recordings.</p><p><strong>Key results: </strong>BzATP application (300 μM) resulted in increased calcium influx in hiPSC-derived neurons which was blocked by the P2X7 receptor antagonists JNJ-47965567 (100 nM) and AFC-5128 (30 nM). Single-cell patch-clamp recordings showed that, while treatment with AFC-5128 did not reduce epileptiform-like activity triggered by picrotoxin alone, AFC-5128 reduced the severity of epileptiform-like activity under inflammatory conditions. Notably, epileptiform-like events in the inflammation-primed picrotoxin model were refractory to the anti-seizure medication carbamazepine alone but were reduced by the co-application of carbamazepine with AFC-5128.</p><p><strong>Conclusions and implications: </strong>Our findings demonstrate anti-seizure effects of targeting P2X7 receptors in a human neuronal network model of epilepsy and suggest P2X7 receptor-based treatments may be effective add-on treatments for controlling drug-resistant seizures.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032804","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":"Cholinergic G protein-coupled bile acid receptor 1 (TGR5/GPBA) in the medial septal orchestrates adult hippocampal neurogenesis and cognition in Alzheimer's disease mice","authors":"Rui-Zhe Nie,&nbsp;Qi-Lu Zhang,&nbsp;Xin-Ru Tan,&nbsp;Shan-Shan Hu,&nbsp;Xin-Ting Zhou,&nbsp;Wei-Kai Jiang,&nbsp;Bo-Wei Guo,&nbsp;Xian Cao,&nbsp;Dan-Hua Yuan,&nbsp;Yan Long,&nbsp;Hao Hong,&nbsp;Su-Su Tang","doi":"10.1111/bph.70185","DOIUrl":"10.1111/bph.70185","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>The pathological role of the bile acid receptor TGR5/GPBA in Alzheimer's disease (AD) is not fully understood. We investigated the pharmacological effects and mechanisms of TGR5 in AD model mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Experimental Approach</h3>\u0000 \u0000 <p>TGR5 expression was assessed in AD mice using immunofluorescence and immunoblotting. Bidirectional modulation of TGR5 expression was achieved via stereotaxic delivery of adeno-associated virus vectors, while localized pharmacological activation was conducted through intracerebral cannula implantation. Cognition was evaluated using the Morris water maze and novel object recognition test. Adult hippocampal neurogenesis was assessed via immunofluorescence. Neuronal activity was analysed using immunofluorescence, fibre photometry and chemogenetics-coupled fibre photometry. Acetylcholine dynamics were monitored using fibre photometry, both alone and in combination with chemogenetic manipulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key Results</h3>\u0000 \u0000 <p>TGR5 expression was selectively decreased in the medial septal (MS) cholinergic neurons during middle-late AD stages. Bidirectional genetic regulation of TGR5 in MS cholinergic neurons significantly affected cognition and adult hippocampal neurogenesis in mice. Pharmacological activation of TGR5 in the MS not only increased cholinergic neuronal activity and acetylcholine release, but also enhanced DG glutamatergic neuronal activity, acetylcholine levels and neurogenesis in AD mice. TGR5 modulated cognition and neurogenesis via the MS^{cholinergic(ChAT)}→ DG^{glutamatergic(Glu)} circuit. Furthermore, α7 nAChRs in the DG were involved in TGR5-mediated improvements in cognition and neurogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion and Implications</h3>\u0000 \u0000 <p>Our findings demonstrate that TGR5 in MS cholinergic neurons is critical during the middle-late stage of AD and provide valuable insights into the underlying neuronal circuit mechanisms. TGR5 (GPBA) represents a potential therapeutic target for AD treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"182 21","pages":"5409-5429"},"PeriodicalIF":7.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028980","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":"EXPRESSION OF CONCERN: Nitropravastatin Stimulates Reparative Neovascularisation and Improves Recovery from Limb Ischaemia in Type-1 Diabetic Mice","authors":"","doi":"10.1111/bph.70199","DOIUrl":"10.1111/bph.70199","url":null,"abstract":"&lt;p&gt;\u0000 &lt;b&gt;Expression of Concern:&lt;/b&gt; &lt;span&gt;C. Emanueli&lt;/span&gt;, &lt;span&gt;A. Monopoli&lt;/span&gt;, &lt;span&gt;N. Kraenkel&lt;/span&gt;, &lt;span&gt;M. Meloni&lt;/span&gt;, &lt;span&gt;S. Gadau&lt;/span&gt;, &lt;span&gt;I. Campesi&lt;/span&gt;, &lt;span&gt;E. Ongini&lt;/span&gt;, and &lt;span&gt;P. Madeddu&lt;/span&gt;, “ &lt;span&gt;Nitropravastatin Stimulates Reparative Neovascularisation and Improves Recovery from Limb Ischaemia in Type-1 Diabetic Mice&lt;/span&gt;,” &lt;i&gt;British Journal of Pharmacology&lt;/i&gt; &lt;span&gt;150&lt;/span&gt;, no. &lt;span&gt;7&lt;/span&gt; (&lt;span&gt;2007&lt;/span&gt;): &lt;span&gt;873&lt;/span&gt;–&lt;span&gt;882&lt;/span&gt;, https://doi.org/10.1038/sj.bjp.0707142&lt;/p&gt;&lt;p&gt;This Expression of Concern is for the above article, published online on 12 March 2007, in Wiley Online Library (http://onlinelibrary.wiley.com/), and has been issued by agreement between the journal Editor-in-Chief, Péter Ferdinandy; the British Pharmacological Society; and John Wiley &amp; Sons Ltd. The publisher received a report from a third party which indicated that two of the actin bands in Figure 5A showed evidence of splicing and duplication. An investigation by the publisher also detected these same concerns. The authors responded to an inquiry by the publisher and confirmed this duplication, as well as an additional error in Figure 6 where the Akt panels for pravastatin and NCX6550 had been swapped. The authors provided examples of the original western blot data and the densitometry data for the representative western blot images. They also requested a correction, to replace the erroneous images in Figures 5A and 6 with corrected representative western blots.&lt;/p&gt;&lt;p&gt;A review of these data by the journal editors found that, while the provided western blot data corresponded with the results presented in the article, the error bar of the published Statin graph in Figure 5B appeared to not match the quantification presented in the article. Additional concerns were raised that other data were included in the summary bar graph in addition to what was shown by the two representative immunoblots, but this was not clear based on the data provided. In response, the authors stated that the quantification shown in the graph should not be expected to derive from the densitometry data extracted from two samples based on other studies conducted at the author's institution during this period. However, original experimental records and data which would support this claim were no longer available due to the age of the article.&lt;/p&gt;&lt;p&gt;The parties have agreed that, based on the available data, they were not able to validate the data in Figure 5. Publishing a correction to replace the immunoblots in Figures 5A and 6 with corrected data was therefore not considered appropriate. The journal decided to issue this Expression of Concern to inform and alert the readers of the results of the investigation.&lt;/p&gt;&lt;p&gt;Author C. Emanueli disagrees with the Expression of Concern and stated that the densitometry performed on the provided bands was consistent with the published data, even though statistical s","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"182 20","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/bph.70199","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999787","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}