European journal of pharmacology最新文献

{"title":"Programmed cell death: A pivotal player in pulmonary arterial hypertension","authors":"Wan-Hong Li ,&nbsp;Wan-Jing Ma ,&nbsp;Wei Zhang ,&nbsp;Shu-Ning Zhao ,&nbsp;Xin-Miao Zhao ,&nbsp;Chen-Hao Ma ,&nbsp;Ming-Ze Xi ,&nbsp;Hui Sun","doi":"10.1016/j.ejphar.2025.177934","DOIUrl":"10.1016/j.ejphar.2025.177934","url":null,"abstract":"<div><div>Pulmonary arterial hypertension (PAH) is a chronic and progressive pulmonary vascular disease with an extremely high mortality rate. The pathogenesis of PAH is characterized by a progressive increase in vascular resistance due to the excessive proliferation of pulmonary arterial endothelial cells and pulmonary artery smooth muscle cells, which leads to uncompensated remodeling of the right ventricle and, ultimately, right heart failure. However, the molecular mechanisms behind pulmonary arterial hypertension have been much elucidated, but effective therapeutic agents are rare. Programmed cell death (PCD) is an intrinsic cellular process tightly regulated by specific genetic mechanisms, which is usually identified with apoptosis, autophagy, but its scope has been gradually expanded with pyroptosis, ferroptosis, and necroptosis. Both traditional forms of PCD and novel forms have been implicated in the pathogenesis of PAH. In order to gain a more comprehensive understanding of the pathogenesis and progression of PCD in PAH, this review comprehensively summarized the association between various PCDs and PAH and discussed the role of endothelial and smooth muscle cells in this, as well as the crosstalk, which will contribute to the development of innovative and targeted diagnostic and therapeutic approaches.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1003 ","pages":"Article 177934"},"PeriodicalIF":4.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The opioid receptor antagonist naloxonazine uncovers the pronounced ventilatory stimulant effects of fentanyl in freely-moving rats.","authors":"Paulina M Getsy, Gregory A Coffee, Santhosh M Baby, Walter J May, Fraser Henderson, Tej Nakashe, Zackery T Knauss, Hubert V Forster, Matthew R Hodges, Stephen J Lewis","doi":"10.1016/j.ejphar.2025.177925","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.177925","url":null,"abstract":"<p><p>We previously reported that administration of an opioid receptor antagonist elicits pronounced increases in minute ventilation in rats where the respiratory effects of previously administered fentanyl had resolved. Thus, fentanyl induces the activation of an opioid receptor-dependent inhibitory system and a non-opioid receptor-dependent excitatory system - two systems with on-going counter-balancing effects on breathing. The objective of the present study was to determine whether administration of the potent, centrally-acting opioid receptor antagonist, naloxonazine (NLZ), during fentanyl-induced suppression of respiration, elicits an overshoot of breathing - above baseline values - suggesting the presence of an on-going excitatory ventilatory control system. The intravenous administration of 25, 50 or 75 μg/kg doses of fentanyl to separate groups of male Sprague Dawley rats elicited pronounced dose-dependent reductions in frequency of breathing, tidal volume, and minute ventilation. NLZ (1.5 mg/kg, IV) given 5 minutes after the injection of 25, 50 or 75 μg/kg doses of fentanyl - the timepoint in which the ventilatory depressant effects of fentanyl were most pronounced - elicited overshoots in frequency of breathing, tidal volume, and minute ventilation, as well as many other parameters including, peak inspiratory and expiratory flows and inspiratory and expiratory drives. This overshoot in breathing, which lasted for 20-30 min, was associated with minor increases in the non-eupneic breathing index (NEBI), suggesting that the responses were not accompanied by unwanted effects on respiratory timing and mechanics. Understanding the mechanism(s) by which this non-opioid receptor-dependent excitatory ventilatory system acts may lead to the development of novel ventilatory stimulants.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177925"},"PeriodicalIF":4.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Exploring monoamine oxidase B in nitric oxide dysregulation and vascular disease\" [Europ. J. Pharmacol. 1002 (2025) 1-7 177863].","authors":"Vijay Elipay, Atanu Mandal, Sanjiv Singh","doi":"10.1016/j.ejphar.2025.177903","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.177903","url":null,"abstract":"","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177903"},"PeriodicalIF":4.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IRAS/Nischarin is associated with attenuated deficit of cognition during morphine abstinence in mice","authors":"Shuo Li ,&nbsp;Xiao-qin Zhang ,&nbsp;Chuan-chuan Liu ,&nbsp;Ying-xian Shi ,&nbsp;Zhi-yuan Wang ,&nbsp;Ning Wu ,&nbsp;Jin Li ,&nbsp;Fei Li","doi":"10.1016/j.ejphar.2025.177928","DOIUrl":"10.1016/j.ejphar.2025.177928","url":null,"abstract":"<div><div>Opioid withdrawal leads to impairments in cognitive functions that are now recognized as a major negative consequence and a key target for intervention in drug addiction. Imidazoline receptor antisera-selected (IRAS) protein is a candidate for the I1 imidazoline receptor. Studies have revealed that IRAS plays an important part in the development of morphine tolerance and dependence. Whether IRAS affects cognitive deficits caused by morphine during abstinence is not known. We investigated the effects of IRAS knockout on natural reward seeking, spatial memory, and reversal learning in male mice during the morphine withdrawal. We demonstrated that morphine abstinence led to the impairments of these cognitive functions. IRAS knockout mitigated the dysfunction of morphine abstinence on natural reward seeking, reduced the decline in spatial memory acquisition and retrieval caused by morphine withdrawal, and alleviated impairments in reversal learning abilities. Notably, mice with IRAS knockout demonstrated a significant increase in hippocampal neuron spine density and a marked enhancement of long-term potentiation in the CA1 region compared with their wild-type littermates during abstinence. IRAS knockout led to the activation of cyclic adenosine monophosphate-dependent protein kinase A and increased phosphorylation of the AMPA receptor GluR1 at Ser845, as well as the NMDA receptor subunits NR2A and NR2B, in the hippocampus. Together, our findings underscore the critical role of IRAS in modulating synaptic plasticity and cognitive deficits induced by morphine abstinence. IRAS could be a regulatory target for mitigating the cognitive impairments associated with opioid dependence.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1003 ","pages":"Article 177928"},"PeriodicalIF":4.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144580655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reprogramming inflammation: Mechanisms and therapeutic targeting of eicosanoids and pro-resolving mediators","authors":"Oluwafunke R. Kolawole ,&nbsp;Khosrow Kashfi","doi":"10.1016/j.ejphar.2025.177924","DOIUrl":"10.1016/j.ejphar.2025.177924","url":null,"abstract":"<div><div>Inflammation is a fundamental biological response to infection or tissue injury aimed at restoring homeostasis. While acute inflammation is typically self-limited and resolves through endogenous mechanisms, persistent or dysregulated inflammation underlies many chronic diseases, including atherosclerosis, arthritis, and cancer. Eicosanoids, lipid mediators derived from polyunsaturated fatty acids, orchestrate both the initiation and resolution of inflammation. Their biosynthesis is initiated by phospholipase A₂ (PLA₂) enzymes, which release arachidonic acid from membrane phospholipids, feeding into the cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) pathways. These pathways generate many bioactive mediators, including pro-inflammatory prostaglandins and leukotrienes, as well as anti-inflammatory and pro-resolving molecules such as lipoxins, resolvins, protectins, and maresins. Notably, the CYP-derived epoxyeicosatrienoic acids (EETs) and their downstream metabolism by soluble epoxide hydrolase (sEH) represent an underappreciated axis in inflammation regulation. Emerging evidence suggests that specialized pro-resolving mediators (SPMs) are not simply anti-inflammatory but act in the low picomolar to nanomolar range to actively promote the resolution phase through immunomodulation, tissue repair, and restoration of barrier function. Aspirin, in addition to its COX-inhibitory effects, can trigger the biosynthesis of epimeric SPMs; however, the concentrations required and their clinical relevance remain under investigation. This review provides a comprehensive analysis of the enzymatic pathways governing eicosanoid biosynthesis, the cellular and molecular events involved in the resolution of inflammation, and current therapeutic strategies aimed at modulating this lipid mediator network. Special attention is given to PLA₂ and sEH as upstream regulatory nodes, as well as to the challenges and prospects of resolution-based pharmacology.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1003 ","pages":"Article 177924"},"PeriodicalIF":4.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Significance of ALDH3A2, a mitochondrial metabolism and glycolysis related gene, in pulmonary arterial hypertension","authors":"Wan-Jing Ma ,&nbsp;Wan-Hong Li ,&nbsp;Xin-Miao Zhao ,&nbsp;Wei Zhang ,&nbsp;Hui Sun","doi":"10.1016/j.ejphar.2025.177923","DOIUrl":"10.1016/j.ejphar.2025.177923","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to identify critical genes related to mitochondrial metabolism (MM) and glycolysis in the progression of pulmonary arterial hypertension (PAH) through transcriptomic analysis and molecular biology methods.</div></div><div><h3>Methods</h3><div>Based on data from the Gene Expression Omnibus (GEO) database, differentially expressed genes (DEGs) from lung tissues of PAH patients were compared to controls. Gene set enrichment analysis (GSEA) was performed for functional annotation and pathway enrichment. Using weighted correlation network analysis (WGCNA), we developed a gene expression network that led to the construction of a diagnostic model for identifying PAH from control individuals. Monocrotaline (MCT)-induced PAH rats were utilized to validate target genes. We examined the protective effects of aldehyde dehydrogenase 3 family member A2 (ALDH3A2) on rat pulmonary artery smooth muscle cells (RPASMCs) in <em>vitro,</em> utilizing proliferation, cell cycle, and migration tests.</div></div><div><h3>Results</h3><div>405 genes were upregulated, and 488 genes were downregulated in PAH patients. WGCNA limited the list to three hub genes, with ALDH3A2 as the only gene associated with MM and glycolysis. ALDH3A2 expression in PAH rats was decreased compared to controls, and ALDH3A2 overexpression significantly suppressed RPASMCs' proliferation/anti-apoptosis, and cell cycle progression at S + G2/M. In addition, overexpression of ALDH3A2 inhibited hypoxia-induced migration. We observed that ALDH3A2 overexpression inhibited glycolytic relative agents (HK2 and PGK1) and lactate dehydrogenase in RPASMCs subjected to hypoxia.</div></div><div><h3>Conclusions</h3><div>The ALDH3A2 gene has emerged as a critical biological regulator for MM and glycolysis in PAH by reducing proliferation, cell cycle, migration, and glycolysis of RPASMCs.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1003 ","pages":"Article 177923"},"PeriodicalIF":4.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydroxypropyl-β-cyclodextrin inclusion complex improves the percutaneous therapeutic effect of eugenol on psoriasis mice","authors":"Yanyan Guo ,&nbsp;Yingxue Yue ,&nbsp;Huanhuan Wang ,&nbsp;Ziyi Zhong ,&nbsp;Bin Chen ,&nbsp;Luan Shu ,&nbsp;Jing Wang ,&nbsp;Zhenhai Zhang","doi":"10.1016/j.ejphar.2025.177921","DOIUrl":"10.1016/j.ejphar.2025.177921","url":null,"abstract":"<div><div>The insolubility and volatility of eugenol (EG) limit its clinical application. In this study, cyclodextrin (CD) was used to encapsulate EG and hydroxypropyl-β-cyclodextrin (HP-β-CD) with lower binding energy was selected by comparison. The preparation process optimization and characterization showed that the EG-HP-β-CD inclusion complex could be successfully prepared. More importantly, inclusion complex can significantly increase the solubility and stability of EG. In addition, <em>in vitro</em> release and transdermal studies, inclusion complex gel release curve conformed to the Higuchi equation, and the cumulative release rate reached 80 % at 24 h, which provided good sustained release properties. Notably, inclusion complex gel increased EG skin retention by reducing the transdermal permeation rate and cumulative permeation amount. It was verified in the mouse psoriasis model that the inclusion complex gel group had better efficacy. By comparison, the epidermal thickness and inflammatory infiltration of inclusion complex group were improved, which was closely related to drug skin retention. The anti-inflammatory effect was revealed by regulating the expression of IL-17 A, IL-1β, IL-6, IL-23, and TNF-α, participating in JAK1/STAT3 pathway. The results provide a new idea and theoretical basis for the formulation design of volatile oil transdermal therapy for psoriasis.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1003 ","pages":"Article 177921"},"PeriodicalIF":4.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular protective properties of the natural product eugenol","authors":"Xin-yu Liu ,&nbsp;Yun-ke Nie ,&nbsp;Yang Liu ,&nbsp;Mei Chen","doi":"10.1016/j.ejphar.2025.177929","DOIUrl":"10.1016/j.ejphar.2025.177929","url":null,"abstract":"<div><div>Medicinal herbs have long been used in traditional medicine and their multi-featured bioactivities against the pathophysiology of chronic diseases are currently being extensively investigated in both experimental and clinical settings. Eugenol, a versatile small molecule and the primary phenolic component of clove essential oil, has low toxicity and has been widely used across the food industry, biomedical research, pharmaceuticals, cosmetics, and dental care. It exhibits a wide array of therapeutic properties involving anti-inflammatory, antioxidant, antimicrobial, anticarcinogenic, analgesic, repellent, and insecticidal effects. Recent studies have revealed additional properties of this compound, thereby confirming its broad-spectrum cardioprotective effects. Notably, eugenol can reduce cardiovascular risk factors such as hyperlipidemia, insulin resistance, and hypertension. Due to these beneficial features, eugenol protects against endothelial injury, acts as an anti-atherosclerotic agent, and helps prevent thrombosis and platelet aggregation. Eugenol also acts as a contributor to enhanced vasodilation and ventricular diastole by blocking adrenergic receptors and calcium channels, while also protecting against hypertension, pulmonary arterial hypertension, heart failure, and chemotherapy-induced cardiotoxicity. Despite eugenol's significant therapeutic potential, its low aqueous solubility, instability, and susceptibility to chemical and enzymatic modifications limit its bioavailability. The current review aims to offer novel insights into its underlying cardioprotective mechanisms. Nanotechnology-based drug delivery offers a promising approach for the effective utilisation of eugenol and facilitates the transition from preclinical studies to clinical trials.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1003 ","pages":"Article 177929"},"PeriodicalIF":4.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cantharidin Induces Pyroptosis in triple-negative breast cancer cells via vitamin D receptor-targeted inhibition and activation of ROS/caspase/GSDME axis","authors":"Lianghong Zhou ,&nbsp;Peng Zhao ,&nbsp;Ting Zhou ,&nbsp;Meijun Chen ,&nbsp;Zili Feng ,&nbsp;Yang Pan ,&nbsp;Feng Xiao ,&nbsp;Xiaojiang Hao ,&nbsp;Hui Song ,&nbsp;Jue Yang","doi":"10.1016/j.ejphar.2025.177927","DOIUrl":"10.1016/j.ejphar.2025.177927","url":null,"abstract":"<div><div>Cantharidin, a natural small-molecule compound with anticancer activity, has been reported to induce programmed cell death in various cancers. However, its molecular targets in triple-negative breast cancer (TNBC) remain unclear. This study explored the mechanism and potential target of Cantharidin in TNBC. Cantharidin significantly reduced TNBC cell viability and triggered pyroptosis, as indicated by membrane bubbling, lactate dehydrogenase (LDH) release, membrane damage, and increased annexin V⁻/PI⁺ and annexin V⁺/PI⁺ populations. Mechanistically, it activated the Caspase-9/Caspase-3/GSDME axis, elevated intracellular reactive oxygen species (ROS), and suppressed the JAK2/STAT3 pathway. Molecular docking predicted a strong binding affinity between Cantharidin and the vitamin D receptor (VDR) (binding energy: 7.1 kcal/mol), further supported by Molecular Dynamics (MD) simulations, MM/PBSA calculations, and confirmed by drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) assays. Western blotting showed that Cantharidin downregulated VDR protein expression. These findings identify VDR as a direct target of Cantharidin and highlight its potential as a potent pyroptosis inducer for TNBC therapy.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1003 ","pages":"Article 177927"},"PeriodicalIF":4.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-216a-5p inhibits proliferation, migration, and enhances oxaliplatin sensitivity by targeting ZBTB2 in gastric cancer cells","authors":"Xiao-Yun Wang ,&nbsp;Hai-Long Guo ,&nbsp;Qian-Huang Lin ,&nbsp;Jing Li ,&nbsp;Rong Yang ,&nbsp;Pei-Dong Shi ,&nbsp;Jun-Feng Zhang ,&nbsp;Bo-Shun Wan ,&nbsp;Ting Yang","doi":"10.1016/j.ejphar.2025.177918","DOIUrl":"10.1016/j.ejphar.2025.177918","url":null,"abstract":"<div><h3>Background</h3><div>Although miR-216a-5p is linked to tumour progression and chemoresistance, its mechanistic contributions to gastric cancer (GC) remain undefined. This study sought to clarify the role of miR-216a-5p in GC progression and its impact on oxaliplatin (OXA) resistance.</div></div><div><h3>Methods</h3><div>MiR-216a-5p expression in GC specimens and cell lines was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics and dual-luciferase reporter assays were employed to identify and, subsequently, validate <em>ZBTB2</em> as a direct target of miR-216a-5p, which was further confirmed through RNA immunoprecipitation, Western blot, and qRT-PCR analyses. <em>In vitro</em> functional assays, including proliferation, migration, and drug sensitivity assays, assessed the effects of miR-216a-5p and <em>ZBTB2</em> on GC cells. Rescue experiments further elucidated the miR-216a-5p/ZBTB2 regulatory axis. Additionally, <em>in vivo</em> experiments substantiated these findings.</div></div><div><h3>Results</h3><div>Quantitative analyses revealed substantial downregulation of miR-216a-5p in both clinical GC samples and cellular models relative to matched non-neoplastic mucosal tissues and normal epithelial controls. Functional assays demonstrated that miR-216a-5p inhibited GC cell proliferation and migration while enhancing their sensitivity to OXA. Mechanistically, miR-216a-5p directly targeted and downregulated <em>ZBTB2</em>, thereby modulating GC cell growth and chemoresistance. Rescue experiments confirmed that <em>ZBTB2</em> overexpression partially reversed the effects of miR-216a-5p on GC cells. <em>In vivo</em> studies further supported the tumour-suppressive role of miR-216a-5p and its regulation of <em>ZBTB2</em>.</div></div><div><h3>Conclusion</h3><div>This study demonstrated that miR-216a-5p suppresses GC by inhibiting cell proliferation, migration, and OXA resistance through the downregulation of <em>ZBTB2</em>. Our findings underscored miR-216a-5p′s role as a potential molecular target for improving chemotherapy efficacy against GC.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1003 ","pages":"Article 177918"},"PeriodicalIF":4.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}