British Journal of Pharmacology最新文献

{"title":"Memantine-induced functional rewiring of the glutamate synapse in the striatum of dopamine transporter knockout rats","authors":"Lucia Caffino,&nbsp;Giorgia Targa,&nbsp;Francesca Mottarlini,&nbsp;Sarah Thielens,&nbsp;Beatrice Rizzi,&nbsp;Agnes Villers,&nbsp;Laurence Ris,&nbsp;Raul R. Gainetdinov,&nbsp;Damiana Leo,&nbsp;Fabio Fumagalli","doi":"10.1111/bph.17403","DOIUrl":"10.1111/bph.17403","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>Slow-acting biogenic amines, such as dopamine, are known to modulate fast neurotransmitters e.g. glutamate. In the striatum, dopamine (DA) interacts with glutamate, influencing neural excitability and promoting synaptic plasticity. The exact mechanism of such interaction is not fully understood. This study investigates, in detail, how dopamine overactivity in dopamine transporter knockout (DAT^−/−) rats, alters the homeostasis of the striatal glutamate synapse from a molecular, behavioural and functional point of view.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Experimental Approach</h3>\u0000 \u0000 <p>The expression, localisation, retention and electrophysiological properties of N-methyl-D-aspartate (NMDA) receptors as well as dendritic spine density and morphology were investigated in the striatum of DAT^−/− rats, at baseline and after treatment with the non-competitive NMDA receptor antagonist memantine (30 mg kg⁻¹).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key Results</h3>\u0000 \u0000 <p>Dopamine overactivity dramatically reorganises the striatal glutamate synapse, redistributing NMDA receptors in the synapse as typified by reduced synaptic availability and reduced expression of NMDA scaffolding proteins, as well as by increased GluN2B-containing NMDA receptors in the extra synapse. Such changes are accompanied by reduced spine density, suggesting dopamine-induced structural rearrangements. These results converge into a compromised plasticity, as shown by the impaired ability to promote long-term depression (LTD) in the striatum of DAT^−/−rats. Notably, memantine counteracts hyperlocomotion, reverses spine alterations and abolishes the extrasynaptic movements of NMDA receptors in the striatum of DAT^−/− rats, thus restoring functional LTD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion and Implications</h3>\u0000 \u0000 <p>A hyperdopaminergic condition seems to alter striatal homeostasis by increasing extrasynaptic NMDA receptors. These findings may be relevant to manipulate disorders characterised by elevated dopaminergic activity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"182 6","pages":"1377-1393"},"PeriodicalIF":6.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.17403","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799485","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":"DysRegNet: Patient-specific and confounder-aware dysregulated network inference towards precision therapeutics.","authors":"Johannes Kersting, Olga Lazareva, Zakaria Louadi, Jan Baumbach, David B Blumenthal, Markus List","doi":"10.1111/bph.17395","DOIUrl":"https://doi.org/10.1111/bph.17395","url":null,"abstract":"<p><strong>Background and purpose: </strong>Gene regulation is frequently altered in diseases in unique and patient-specific ways. Hence, personalised strategies have been proposed to infer patient-specific gene-regulatory networks. However, existing methods do not scale well because they often require recomputing the entire network per sample. Moreover, they do not account for clinically important confounding factors such as age, sex or treatment history. Finally, a user-friendly implementation for the analysis and interpretation of such networks is missing.</p><p><strong>Experimental approach: </strong>We present DysRegNet, a method for inferring patient-specific regulatory alterations (dysregulations) from bulk gene expression profiles. We compared DysRegNet to the well-known SSN method, considering patient clustering, promoter methylation, mutations and cancer-stage data.</p><p><strong>Key results: </strong>We demonstrate that both SSN and DysRegNet produce interpretable and biologically meaningful networks across various cancer types. In contrast to SSN, DysRegNet can scale to arbitrary sample numbers and highlights the importance of confounders in network inference, revealing an age-specific bias in gene regulation in breast cancer. DysRegNet is available as a Python package (https://github.com/biomedbigdata/DysRegNet_package), and analysis results for 11 TCGA cancer types are available through an interactive web interface (https://exbio.wzw.tum.de/dysregnet).</p><p><strong>Conclusion and implications: </strong>DysRegNet introduces a novel bioinformatics tool enabling confounder-aware and patient-specific network analysis to unravel regulatory alteration in complex diseases.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779529","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":"The paracetamol metabolite N-acetyl-4-benzoquinoneimine (NAPQI) prevents modulation of KV7 channels via G-protein coupled receptors by interference with PIP2 and Ca2+ sensitivity","authors":"Thomas Losgott,&nbsp;Oliver Kudlacek,&nbsp;Jae-Won Yang,&nbsp;Klaus W. Schicker,&nbsp;Stefan Boehm,&nbsp;Isabella Salzer","doi":"10.1111/bph.17419","DOIUrl":"10.1111/bph.17419","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>Paracetamol has been found to alleviate inflammatory pain by modulating K_V7 channels. Its metabolite N-acetyl-4-benzoquinoneimine (NAPQI) increases currents through these channels via a stretch of three cysteine residues in the channel S2–S3 linker. Through this effect, the excitability of neurons in the pain pathway is dampened. Inflammatory mediators, in turn, enhance the excitability of sensory neurons by inhibiting K_V7 channels. Here, a specific interaction between NAPQI and the so-called inflammatory soup was investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Experimental Approach</h3>\u0000 \u0000 <p>Currents through K_V7 channels were measured in sensory neurons and after heterologous expression in tsA201 cells. In addition, changes in cytosolic Ca²⁺ and in the distribution of PIP₂ (PI(4,5)P₂) between membrane and cytosol were determined by fluorescence microscopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key Results</h3>\u0000 \u0000 <p>NAPQI abolished Ca²⁺-mediated inhibitory effects of an ‘inflammatory soup’ containing ADP, ATP, bradykinin, histamine, 5-hydroxytryptamine, prostaglandin E₂, substance P and a PAR2 agonist on K_V7 channel currents in sensory neurons. Moreover, the increase of K_V7.2 channel currents by quenching of cytosolic Ca²⁺ as well as the current decrease by depletion of membrane PIP₂ was impaired by NAPQI. These effects were lost in mutant channels lacking the three cysteines in the S2–S3 linker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion and Implication</h3>\u0000 \u0000 <p>NAPQI targets the three-cysteine motif in the S2–S3 linker of K_V7.2 channels to counteract the signalling cascades employed by inflammatory mediators that inhibit these channels. In sensory neurons, this abolishes the closure of K_V7 channels by the inflammatory soup. This mechanism is likely involved in the alleviation of inflammatory pain by paracetamol.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"182 6","pages":"1341-1357"},"PeriodicalIF":6.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.17419","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766464","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":"V-domain immunoglobulin suppressor of T-cell activation and programmed death receptor 1 dual checkpoint blockade enhances antitumour immunity and survival in glioblastoma","authors":"Shasha Jin,&nbsp;Tao Li,&nbsp;Liu Liu,&nbsp;Ting Gao,&nbsp;Tingting Zhang,&nbsp;Dingyi Yuan,&nbsp;Jianwen Di,&nbsp;Zhanying Guo,&nbsp;Zhijie Luo,&nbsp;Haoliang Yuan,&nbsp;Jun Liu","doi":"10.1111/bph.17404","DOIUrl":"10.1111/bph.17404","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>The current therapy cannot meet the needs of glioblastoma (GBM). V-domain immunoglobulin suppressor of T-cell activation (VISTA) is significantly up-regulated in GBM patients; however, its therapeutic potential in GBM is still unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Experimental Approach</h3>\u0000 \u0000 <p>Flow cytometry was used to detect the expression of VISTA and the co-expression pattern of VISTA and programmed death receptor 1 (PD-1) on brain infiltrating lymphocytes of GBM mice. Monoclonal antibody therapy was used to evaluate the therapeutic effect of <i>α</i>-VISTA monotherapy and <i>α</i>-VISTA combined with <i>α</i>-PD-1 on GBM mice. Transcriptome analysis, flow cytometry, and immunofluorescence were used to detect changes of immune microenvironment in mouse brain tumours. Immunofluorescence and TCGA data analysis were used to further validate the combined treatment strategy on patient data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key Results</h3>\u0000 \u0000 <p>Compared with normal mice, the frequency of VISTA expression and co-expression of VISTA and PD-1 on tumour-infiltrating lymphocytes (TILs) in tumour-bearing mice was increased. Anti-VISTA monotherapy significantly up-regulated multiple immune stimulation-related pathways and moderately prolonged mouse survival time. Blocking the immune checkpoint VISTA and PD-1 significantly prolonged the survival time of mice and cured about 80% of the mice; CD8⁺ T cells played an important role in this process. In addition, we found that the expression of VISTA and PD-1 was significantly up-regulated in GBM patients by immunofluorescence, and patients with high expression of VISTA and PD-1 were associated with poor overall survival. This combination of blocking the immune checkpoint VISTA and PD-1 may achieve clinical transformation in GBM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"182 6","pages":"1306-1323"},"PeriodicalIF":6.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766466","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 “AQX-1125, small molecule SHIP1 activator inhibits bleomycin-induced pulmonary fibrosis”","authors":"","doi":"10.1111/bph.17416","DOIUrl":"10.1111/bph.17416","url":null,"abstract":"<p>\u0000 <span>J. Cross</span>, <span>G. R. Stenton</span>, <span>C. Harwig</span>, <span>C. Szabo</span>, <span>T. Genovese</span>, <span>R. Di Paola</span>, <span>E. Esposito</span>, <span>S. Cuzzocrea</span>, and <span>L. F. Mackenzie</span>, “ <span>AQX-1125, small molecule SHIP1 activator inhibits bleomycin-induced pulmonary fibrosis</span>,” <i>British Journal of Pharmacology</i> <span>174</span>, no. <span>18</span> (<span>2017</span>): <span>3045</span>–<span>3057</span>, https://doi.org/10.1111/bph.13934</p><p>In the published version of the article, duplication has been detected between the “30 mg•kg⁻¹” panel in Figure 1A and the “Sham” panel in Figure 1B. In the corrected Figure 1A, below, the “30 mg•kg⁻¹” panel has been replaced with the correct one.</p><p>The authors confirm that all the experimental results and corresponding conclusions mentioned in the paper remain unaffected.</p><p>The authors apologize for the mistake and for the inconvenience caused.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"182 3","pages":"924"},"PeriodicalIF":6.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.17416","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766441","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":"Targeting acetylated high mobility group box 1 protein (HMGB1) and toll-like receptor (TLR4) interaction to alleviate hypertension and neuroinflammation in fructose-fed rats.","authors":"Yu-Te Lin, Chiu-Yi Ho, Gwo-Ching Sun, Tzyy-Yue Wong, Michael Hsiao, Ching-Jiunn Tseng, Pei-Wen Cheng","doi":"10.1111/bph.17402","DOIUrl":"https://doi.org/10.1111/bph.17402","url":null,"abstract":"<p><strong>Background and purpose: </strong>Our previous study reported that fructose intake increased systemic blood pressure and reduced nitric oxide (NO) in the nucleus tractus solitarius (NTS) due to oxidative stress and neuroinflammation. However, it remains unclear how reactive oxygen species (ROS) reduce NO and how this process impacts neuroinflammation in the NTS. This study aimed at investigating the effect of ROS on acetylation of high mobility group box 1 protein (HMGB1) in the NTS of fructose-induced hypertensive rats.</p><p><strong>Experimental approach: </strong>Male Wistar-Kyoto (WKY) rats were fed with 10% fructose water to elevate blood pressure. Thereafter, CLI-095 and glycyrrhizic acid (GA) treatments were delivered for up to 2 weeks (1 mg·12 μL^-1·day^-1, by intracerebroventricular injection) to reduce the negative effects of toll-like receptor 4 (TLR4) and HMGB1 activation.</p><p><strong>Key results: </strong>Two weeks of CLI-095 and GA treatment reduced systemic blood pressure and significantly preserved neuronal and endothelial nitric oxide synthase (nNOS and eNOS) availability against the inflammatory insults of fructose consumption. Both CLI-095 and GA halted the interaction of acetylated HMGB1 and TLR4. Two weeks of CLI-095 and GA treatment markedly reduced NTS inflammation (pro-inflammatory cytokines and microglial activation) and lowered serum norepinephrine levels.</p><p><strong>Conclusion and implications: </strong>Our data reveal novel pharmacological properties for CLI-095 and GA, which improved blood pressure and inflammatory conditions by decreasing the interaction of acetylated HMGB1 with TLR4. These findings challenge the commonly accepted dogma that essential hypertension is specifically mediated by neuroinflammation due to acetylated HMGB1 coupling to TLR4.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766463","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":"TRPV4 stimulates colonic afferents through mucosal release of ATP and glutamate","authors":"Michelle Y. Meng,&nbsp;Luke W. Paine,&nbsp;David Sagnat,&nbsp;Ivana Bello,&nbsp;Sophie Oldroyd,&nbsp;Farideh Javid,&nbsp;Matthew T. Harper,&nbsp;James R. F. Hockley,&nbsp;Ewan St. John Smith,&nbsp;Róisín M. Owens,&nbsp;Laurent Alric,&nbsp;Etienne Buscail,&nbsp;Fraser Welsh,&nbsp;Nathalie Vergnolle,&nbsp;David C. Bulmer","doi":"10.1111/bph.17408","DOIUrl":"10.1111/bph.17408","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>Abdominal pain is a leading cause of morbidity for people living with gastrointestinal disease. Whereas the transient receptor potential vanilloid 4 (TRPV4) ion channel has been implicated in the pathogenesis of abdominal pain, the relative paucity of TRPV4 expression in colon-projecting sensory neurons suggests that non-neuronal cells may contribute to TRPV4-mediated nociceptor stimulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Experimental Approach</h3>\u0000 \u0000 <p>Changes in murine colonic afferent activity were examined using ex vivo electrophysiology in tissues with the gut mucosa present or removed. ATP and glutamate release were measured by bioluminescence assays from human colon organoid cultures and mouse colon. Dorsal root ganglion sensory neuron activity was evaluated by Ca²⁺ imaging when cultured alone or co-cultured with colonic mucosa.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key Results</h3>\u0000 \u0000 <p>Bath application of TRPV4 agonist GSK1016790A elicited a robust increase in murine colonic afferent activity, which was abolished by removing the gut mucosa. GSK1016790A promoted ATP and glutamate release from human colon organoid cultures and mouse colon. Inhibition of ATP degradation in mouse colon enhanced the afferent response to GSK1016790A. Pretreatment with purinoceptor or glutamate receptor antagonists attenuated and abolished the response to GSK1016790A when given alone or in combination, respectively. Sensory neurons co-cultured with colonic mucosal cells produced a marked increase in intracellular Ca²⁺ to GSK1016790A compared with neurons cultured alone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion and Implications</h3>\u0000 \u0000 <p>Our data indicate that mucosal release of ATP and glutamate is responsible for the stimulation of colonic afferents following TRPV4 activation. These findings highlight an opportunity to target the gut mucosa for the development of new visceral analgesics.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"182 6","pages":"1324-1340"},"PeriodicalIF":6.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.17408","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766465","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":"Genetic polymorphisms influencing antihypertensive drug responses","authors":"Jana El Cheikh,&nbsp;Fouad Hamed,&nbsp;Hana Rifi,&nbsp;Ali H. Dakroub,&nbsp;Ali Hussein Eid","doi":"10.1111/bph.17414","DOIUrl":"10.1111/bph.17414","url":null,"abstract":"<p>Hypertension is a major contributor to cardiovascular disease and its associated morbidity and mortality. The low efficacy observed with some anti-hypertensive therapies has been attributed partly to inter-individual genetic variability. This paper reviews the major findings regarding these genetic variabilities that modulate responses to anti-hypertensive therapies such as angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), diuretics, calcium channel blockers (CCBs) and β-adrenoceptor blockers. The importance of studying these genetic polymorphisms stems from the goal to optimise anti-hypertensive therapy for each individual patient, aiming for the highest efficacy and lowest risk of adverse effects. It is important to recognise that environmental and epigenetic factors can contribute to the observed variations in drug responses. Owing to the multigenic and multifactorial nature of drug responses, further research is crucial for translating these findings into clinical practice and the establishment of reliable recommendations.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"182 4","pages":"929-950"},"PeriodicalIF":6.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.17414","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766444","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":"EXPRESSION OF CONCERN: Rosiglitazone and 15-deoxy-Δ12,14-prostaglandin J2, ligands of the peroxisome proliferator-activated receptor-γ (PPAR-γ), reduce ischaemia/reperfusion injury of the gut","authors":"","doi":"10.1111/bph.17421","DOIUrl":"10.1111/bph.17421","url":null,"abstract":"<p><b>EXPRESSION OF CONCERN</b>: \u0000 <span>S. Cuzzocrea</span>, <span>B. Pisano</span>, <span>L. Dugo</span>, <span>A. Ianaro</span>, <span>N. S. A. Patel</span>, <span>R. Di Paola</span>, <span>T. Genovese</span>, <span>P. K. Chatterjee</span>, <span>M. Di Rosa</span>, <span>A. P. Caputi</span>, and <span>C. Thiemermann</span>, “ <span>Rosiglitazone and 15-deoxy-Δ^12,14-prostaglandin J₂, ligands of the peroxisome proliferator-activated receptor-γ (PPAR-γ), reduce ischaemia/reperfusion injury of the gut</span>,” <i>British Journal of Pharmacology</i> <span>140</span>, no. <span>2</span> (<span>2003</span>): <span>366</span>–<span>376</span>, https://doi.org/10.1038/sj.bjp.0705419.</p><p>This expression of concern is for the above article, published online on 2 February 2009 in Wiley Online Library (wileyonlinelibrary.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 expression of concern has been agreed due to third-party concerns related to the data presented in the article. Indicators for cloned image elements and inappropriate undeclared image modification were found in multiple image parts and several panels in Figures 1, 9, and 11. Due to the significant time elapsed since publication, the authors were unable to provide the original images. Therefore, the journal has decided to issue an Expression of Concern to inform and alert the readers.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"182 3","pages":"925"},"PeriodicalIF":6.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.17421","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766442","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":"Selected Abstracts from Pharmacology 2024","authors":"","doi":"10.1111/bph.17399","DOIUrl":"10.1111/bph.17399","url":null,"abstract":"&lt;p&gt;&lt;b&gt;16&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;The effect of fluoxetine on diffused intrinsic pontine glioma (DIPG), ICR-B169 cells and HSJD-DIPG-007 cells&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;span&gt;F. Javid&lt;/span&gt;&lt;/p&gt;&lt;p&gt;&lt;i&gt;Department of Pharmacy, University of Huddersfield&lt;/i&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;Introduction&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Diffuse intrinsic pontine glioma (DIPG) is an aggressive glial tumour with a median survival of 9–12 (Malbari, 2021; Van Genechten et al., 2024). Our previous studies have shown that fluoxetine (Prozac), the well-known antidepressant which is a selective serotonin uptake inhibitor (SSRI), induced cytotoxicity in human colon carcinoma cells (Marcinkute et al., 2019). The aim of the present study was to explore if fluoxetine could also induce cytotoxicity in patient-derived ICR-B169 2D and HSJD-DIPG-007 cells. These cells represent a type of diffuse intrinsic pontine glioma (DIPG). The cells were kindly donated by ICR.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Method&lt;/b&gt;&lt;/p&gt;&lt;p&gt;The ICR-B169 and HSJD-DIPG-007 cells were maintained and subcultured as per recommended guidelines. When cells reached 70% confluence, they were seeded in 96-well plates and treated with fluoxetine and temozolomide at different concentrations (1 nM–100 μM) or vehicle control. After 96 h contact time, cell viability was assessed using Cell-Titre Glo-2D assay. Experiments were repeated independently four times. Cell viability at each concentration was recorded and half maximal inhibitory concentration (IC50) was calculated. Results were expressed as the mean ± s.e. mean of N = 5.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Pre-treatment with fluoxetine (1 nM–100 μM) induced cytotoxicity in a concentration dependent manner in both cell lines. The cell viability was reduced when compared to control. The cytotoxicity was induced at micromolar range. The IC50s were 16.1 ± 1.9 and 11.3 ± 3.3 μM, compared with IC50s induced by temozolomide, 37.8 ± 2.4 and 55.61 ± 11.4, in ICR-B169 and HSJD-DIPG-007 cells, respectively.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Fluoxetine induced significant cytotoxicity at micromolar concentrations in brain cancer cells. Further studies should be carried out to investigate the mechanisms of action that underpin the observed in vitro cytotoxic effect.&lt;/p&gt;&lt;p&gt;&lt;b&gt;References&lt;/b&gt;&lt;/p&gt;&lt;p&gt;1. Malbari F. (2021). Pediatric Neuro-Oncology. 39(3):829-845.&lt;/p&gt;&lt;p&gt;2. Marcinkute M., et al. (2019). Fluoxetine selectively induces p53-independent apoptosis in human colorectal cancer cells. Eur J. Pharm., 857: 172441-172450.&lt;/p&gt;&lt;p&gt;3. Van Genechten T. et al., (2024). Adjuvant Wilms' tumour1-specific dendritic cell immunotherapy complementing conventional therapy for paediatric patients with high -grade glioma and diffused intrinsic pontin glioma: protocol of a monocentric phase I/II clinical trial Belgium. BMJ Open. 14(3):e077613.&lt;/p&gt;&lt;p&gt;&lt;b&gt;64&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;Modifying tumour blood vessels to improve cancer immunotherapy&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;span&gt;M. Hillgaertner&lt;/span&gt;&lt;sup&gt;1&lt;/sup&gt;, A. Gallimore&lt;sup&gt;1&lt;/sup&gt;, R. Andrews&lt;sup&gt;1&lt;/sup&gt;, A. Godkin&lt;sup&gt;1&lt;/sup&gt;, S. Milutinovic&lt;sup&gt;1&lt;/sup&gt;, S. Lauder&lt;s","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"182 3","pages":"692-923"},"PeriodicalIF":6.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bph.17399","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766460","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}