BMC Pharmacology & Toxicology最新文献

{"title":"AMD1, a cardiotoxicity target for Maduramicin.","authors":"Zi-Feng Xie, Han-Meng Liu, Jia-Fan Zhao, Yuan Gao, Yuan-Long Zhao, Jia-Yue Zheng, Xiao-Wei Pei, Ning Zhang, Ge Tian","doi":"10.1186/s40360-025-00897-0","DOIUrl":"10.1186/s40360-025-00897-0","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to investigate AMD1 cardiotoxicity function for Maduramicin (Mad).</p><p><strong>Methods: </strong>SD rats were divided into control (Control) group and Mad treatment (3.5 mg/kg) group (Mad). After treatment with Mad for seven days, the levels of LDH and CK-MB in serum were detected, H&E staining and TUNEL staining were performed. In vitro, 1.0 μm Mad was used for the subsequently experiment, observing cell apoptosis from Flow cytometry. Caspase-3 and AMD1 were detected in Western blotting. Flow cytometry and Western blotting were also performed after use of siRNA-AMD1-1. Then, analysis AMD1 potential function in cardiotoxicity from bioinformatics techniques including GO, KEGG, PPI, immune infiltration and molecular docking.</p><p><strong>Result: </strong>Maduramicin has myocardial toxic effects in vivo and vitro, which with AMD1 raised. When AMD1 was knocked down, toxic effects of Mad were alleviated. Apoptosis, proliferation and inflammation were the major pathophysiological changes in myocardial apoptosis process with AMD1-knockdown. This process involved in IL1A, IL1B, PTGS2, VEGFA, VEGFC and HBEFG, as hub genes related AMD1 cardiotoxicity function for Maduramicin. AMD1 was knocked down, their microenvironment changes: Effector memory CD4 T cell and Natural killer cell were more infiltrated, and Mast cell were less infiltrated.</p><p><strong>Conclusion: </strong>Mad exerted cardiotoxic effects by upregulating the AMD1 gene, which may be associated with cell apoptosis, proliferation and inflammatory response. AMD1 also had cardiotoxicity function, by the impact of both myocardial cells and the microenvironment they live.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"55"},"PeriodicalIF":2.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic role of melatonin on acrylamide-induced neurotoxicity via reducing ER stress, inflammation, and apoptosis in a rat model.","authors":"Yusuf Dag, Serkan Yildirim, Emin Sengul, Furkan Aykurt, Melahat Gok, Ali Cinar","doi":"10.1186/s40360-025-00900-8","DOIUrl":"10.1186/s40360-025-00900-8","url":null,"abstract":"<p><p>This study examined the antioxidant, anti-inflammatory, and neuroprotective effects of melatonin (MEL) against acrylamide (ACR)-induced neurotoxicity in Sprague-Dawley rats. The experimental groups included control, ACR, MEL10+ACR, MEL20+ACR, and MEL20. MEL at doses of 10 and 20 mg/kg, and ACR at 50 mg/kg, were administered intraperitoneally for 14 days. On the 15th day, locomotor activity was assessed, and brain tissues were analyzed biochemically, molecularly, and histopathologically. ACR exposure decreased locomotor activity, increased malondialdehyde (MDA) and reduced glutathione (GSH) levels, indicating oxidative stress, and decreased antioxidant enzyme activities (SOD, GPx, CAT). High-dose MEL (MEL20+ACR) effectively reduced lipid peroxidation and restored antioxidant enzyme activities. MEL treatment also suppressed proinflammatory cytokines (TNF-α, IL-1β, IL-6) and neuronal nitric oxide synthase (nNOS), demonstrating anti-inflammatory effects. Furthermore, MEL mitigated ACR-induced neurotoxicity by reducing acetylcholinesterase (AChE) and monoamine oxidase (MAO) levels. ER stress markers (GRP78, ATF4, ATF6, sXBP1, CHOP) and apoptotic markers (Bax, Caspase-3) were elevated following ACR exposure but were suppressed by MEL. Additionally, MEL reduced ACR-induced increases in 8-hydroxy-2-deoxyguanosine (8-OHdG) and glial fibrillary acidic protein (GFAP), markers of DNA damage and astrocyte activation, respectively. These findings underscore the potential of MEL to counteract ACR-induced neurotoxicity through its comprehensive antioxidant, anti-inflammatory, and neuroprotective actions.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"57"},"PeriodicalIF":2.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of potential molecular subtypes and signatures of thyroid eye disease based on angiogenesis-related gene analysis.","authors":"Zixuan Wu, Jun Peng, Xi Long, Kang Tan, Xiaolei Yao, Qinghua Peng","doi":"10.1186/s40360-025-00880-9","DOIUrl":"10.1186/s40360-025-00880-9","url":null,"abstract":"<p><strong>Background: </strong>Thyroid eye disease (TED) is an autoimmune inflammatory disorder of the orbit, associated with a range of potential clinical sequelae. Tumor cells in TED overexpress pro-angiogenic factors, driving the formation of heterogeneous and immature neovascularization. This dysregulated angiogenesis often leads to a hypoxic microenvironment due to insufficient perfusion. Despite its importance, the role of angiogenesis-related genes (ARGs) in TED pathophysiology remains poorly understood.</p><p><strong>Methods: </strong>To bridge this knowledge gap, our study aimed to identify and validate ARGs implicated in TED using a comprehensive bioinformatics strategy. By intersecting differential gene expression analyses with a curated list of 103 known ARGs, we aimed to pinpoint those with potential roles in TED. Advanced methodologies, including GSEA and GSVA, facilitated an in-depth exploration of the biological functions and pathways associated with these ARGs. Further refinement through Lasso regression and SVM-RFE enabled the identification of key hub genes and the evaluation of their diagnostic potential for TED. Additionally, we investigated the relationship between these hub ARGs and relevant clinical parameters. To corroborate our findings, we analyzed expression data from datasets GSE58331 and GSE105149, focusing on the six ARGs identified as potentially crucial to TED pathology.</p><p><strong>Results: </strong>Our investigation unveiled six ARGs (CRIP2, DUSP1, CTSL, DOCK5, ERAP1, SCG2) as intimately connected to TED. Functional analyses highlighted their involvement in processes such as response to ameboidal-type cell migration, epithelial cell migration, epithelium migration. Importantly, the diagnostic capabilities of these ARGs demonstrated promising efficacy in distinguishing TED from non-affected states.</p><p><strong>Conclusions: </strong>This study identifies six ARGs as novel biomarker candidates for TED, elucidating their potential roles in the disease's pathogenesis.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"53"},"PeriodicalIF":2.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative safety signals of dopamine agonists: psychiatric and cardiovascular risks derived from FDA adverse event reporting system (FAERS) data.","authors":"Li Mu, Jing Xu, Xiaomei Ye, Yongxian Jiang, Zhanmiao Yi","doi":"10.1186/s40360-025-00886-3","DOIUrl":"10.1186/s40360-025-00886-3","url":null,"abstract":"<p><strong>Background: </strong>Dopamine receptor agonists (DAs) are widely used as first-line therapeutic agents for Parkinson's disease. However, comparative clinical trials assessing their safety profiles are limited. This study aims to compare adverse event (AE) data across various DAs to inform personalized treatment strategies.</p><p><strong>Methods: </strong>AE reports with DAs as the \"primary suspicion (PS)\" were extracted from the FDA Adverse Event Reporting System (FAERS) database, covering 67 quarters from the second quarter of 2007 to the fourth quarter of 2023. Four disproportionality analysis methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS), were employed to evaluate the risk of AEs.</p><p><strong>Results: </strong>A total of 19,745,533 DA-related AEs reports were analyzed. The six DAs-pramipexole, ropinirole, cabergoline, rotigotine, bromocriptine and apomorphine-generated 269, 246, 202, 163, 146, and 135 preferred terms positive signals, respectively. Non-ergot DAs (pramipexole, ropinirole, rotigotine and apomorphine) were primarily associated with psychiatric disorders and reported more hallucinations than ergot-derived dopamine agonists (ergot-DAs), with ropinirole showing a slightly higher signal intensity than pramipexole (ROR = 15.76 vs. 11.23). Pramipexole demonstrated the most significant signal for impulse control disorders (ICDs). Compared with pramipexole and ropinirole, rotigotine generally exhibits milder signals in terms of psychiatric disorders such as hallucinations, ICDs, and sleep-related AEs. Administration site-related AEs were more prominent in rotigotine and apomorphine users. Ergot-DAs exhibited higher signal intensities for cardiac disorders, with cabergoline also showing a notable signal for amnestic symptoms (ROR = 340.54), which is not mentioned in the drug label.</p><p><strong>Conclusion: </strong>This study elucidates the distinct safety profiles of six DAs. Non-ergot DAs are primarily associated with psychiatric AEs, while administration-related AEs are more notable for rotigotine and apomorphine. Ergot-DAs present a higher risk for cardiac valvulopathies. These findings highlight the importance of individualized treatment considerations in clinical practice, emphasizing the need to formulate appropriate treatment plans on patients' specific conditions.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"54"},"PeriodicalIF":2.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Aspirin plus clopidogrel versus cilostazol -based triple antiplatelet therapy in patients with ischemic heart disease undergoing PCI: a systematic review and meta-analysis of randomized controlled trials.","authors":"Ramez M Odat, Mushood Ahmed, Sakhr Alshwayyat, Ayham Mohammad Hussein, Taif Haitham AlSaraireh, Ahmad M Molhem, Ali O Aldamen, Malak Ababneh, Bishr Quwaider, Hritvik Jain, Jehad A Yasin, Hamdah Hanifa, Raheel Ahmed","doi":"10.1186/s40360-025-00891-6","DOIUrl":"10.1186/s40360-025-00891-6","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"52"},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A disproportionality analysis of real-world events from the FDA Adverse Event Reporting System (FAERS) for Atezolizumab.","authors":"Zhuoyang Li, Ning Zhu, Yuwei Liu, Yan Yu, Tianhong Wang, Congcong Zou, Siman Wang, Xiaofeng Ou","doi":"10.1186/s40360-025-00879-2","DOIUrl":"10.1186/s40360-025-00879-2","url":null,"abstract":"<p><strong>Background: </strong>An increasing number of clinical studies have highlighted the use of atezolizumab in tumor immunotherapy. However, There is still a lack of comprehensive research on its associated adverse events (AEs). To improve our understanding of its toxicological profile and to provide valuable clinical insights regarding into the effectiveness of immunotherapy, this study utilized data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) to conduct a retrospective analysis of AEs linked to atezolizumab.</p><p><strong>Methods: </strong>We extracted the reports of AEs related to atezolizumab from the FAERS database from the first quarter of 2004 to the first quarter of 2024. We quantified them using the reporting odds ratio (ROR) and proportional reporting ratio (PRR), along with chi-square value (χ²), and conducted systematic classification of the AE signal mining results through SAS 9.4 software.</p><p><strong>Results: </strong>A total of 19,563 valid reports were incorporated, involving 20 distinct system organ class categories. The AEs related to atezolizumab, reported at the preferred term level, mainly encompassed anemia [ROR 2.33, 95% confidence interval (CI) lower limit 2.09, PRR 2.31, χ² 255.977], febrile neutropenia (ROR 2.81, 95% CI lower limit 2.50, PRR 2.79, χ² 333.586), neutrophil count decreased (ROR 2.14, 95% CI lower limit 1.89, PRR 2.13, χ² 150.688), white blood cell count decreased (ROR 2.35, 95% CI lower limit 2.03, PRR 2.34, χ² 136.673), sepsis (ROR 2.21, 95% CI lower limit 1.91, PRR 2.20, χ² 117.741), alanine aminotransferase increased (ALT) (ROR 2.86, 95% CI lower limit 2.44, PRR 2.85, χ² 180.031), and aspartate aminotransferase increased (AST) (ROR 2.79, 95% CI lower limit 2.38, PRR 2.78, χ² 170.955).</p><p><strong>Conclusions: </strong>Apart from various degrees of hepatotoxicity, such as increased ALT and AST, the immune-related hematological toxicity of atezolizumab should also be noted. In clinical practice, healthcare providers should always be vigilant for the occurrence of such medication-related AEs and take measures to enhance the safety of clinical medication use.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"51"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational study on the mechanism of small molecules inhibiting NLRP3 with ensemble docking and molecular dynamic simulations.","authors":"Pingyang Qin, Yuzhen Niu, Jizheng Duan, Ping Lin","doi":"10.1186/s40360-025-00851-0","DOIUrl":"10.1186/s40360-025-00851-0","url":null,"abstract":"<p><p>NLRP3 (Nucleotide-binding oligomerization domain, LRR and pyrin domain-containing protein 3) is a pivotal regulator of inflammation, with strong implications in gout, neurodegenerative diseases, and various inflammatory conditions. Consequently, the exploration of NLRP3 inhibitors is of great significance for the treatment of diseases. MCC950, NP3-146, compound (3), and YQ128 are four highly bioactive NLRP3 inhibitors that show great potential; however, their mechanism of action is currently limited to targeting the ATP binding region (NACHT site) of the NLRP3 protein. To gain deeper insights into the defining features of NLRP3 inhibitors and to develop more potent inhibitors, it is imperative to elucidate the interaction mechanism between NLRP3 and these inhibitors. In this study, we employ a comprehensive computational approach to investigate the binding mechanism between NLRP3 and representative inhibitors. Utilizing the molecular mechanics/generalized Born surface area (MM/GBSA) method, we calculate the binding free energy and pinpoint the key residues involved in the binding of the four inhibitors to NLRP3. The decomposition of binding free energy by the MM/GBSA method reveals that the residues Val71, Arg195, Ile255, Phe419, Arg422, and Met505, situated around the binding pocket, play a crucial role in conferring the high bioactivity of NLRP3 inhibitors. Furthermore, pharmacophore analysis of the four NLRP3 complexes indicates that the primary interaction between the inhibitors and NLRP3 was mainly hydrophobic interaction. Our study provides a profound understanding of the interaction mechanism between NLRP3 and its inhibitors, identifies the key residues involved, and provides theoretical guidance for the design of more efficient NLRP3 inhibitors.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"49"},"PeriodicalIF":2.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrointestinal toxicity of antibody-drug conjugates: a pharmacovigilance study using the FAERS database.","authors":"Yanshuo Shi, Kaiqing Yao, Jianqun Zhao, Yuanyuan Yue, Huizhen Wu","doi":"10.1186/s40360-025-00877-4","DOIUrl":"10.1186/s40360-025-00877-4","url":null,"abstract":"<p><strong>Background: </strong>Antibody-drug conjugate (ADC) product specifications identify gastrointestinal adverse reactions. Nevertheless, there is a scarcity of comparative studies pertaining to these side effects of similar medications. Special attention is warranted for adverse drug reactions (ADRs) affecting the gastrointestinal system that are inadequately documented in the drug literature.</p><p><strong>Aims: </strong>Utilizing the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), data mining was conducted to analyze gastrointestinal adverse reactions associated with ADCs. This analysis aimed to provide evidence supporting the safe use of ADCs in medical institutions.</p><p><strong>Methods: </strong>We utilized the Openvigil 2.1 platform to extract adverse event data reported for each ADC from the FAERS database, covering the period from the drug's launch until the second quarter of 2024. For data analysis, we employed the reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods.</p><p><strong>Results: </strong>A total of 23,886 adverse event reports were retrieved, with nine ADCs identified as the primary suspected drugs, including 1,517 reports of gastrointestinal adverse events linked to ADCs. The average patient age was 59.69 years, with a higher prevalence of female patients (919 patients, 60.58%) than male patients (319 patients, 24.32%). The gastrointestinal toxicity intensity, ranked from highest to lowest, was as follows: inotuzumab ozogamicin (IO) with ROR = 11.12 and PRR = 10.68, gemtuzumab ozogamicin (GO) with ROR = 7.87 and PRR = 7.54, polatuzumab vedotin (PV) with ROR = 6.47 and PRR = 6.20, brentuximab vedotin (BV) with ROR = 5.79 and PRR = 5.61, sacituzumab govitecan (SG) with ROR = 5.19 and PRR = 4.61, mirvetuximab soravtansine (MS) with ROR = 4.37 and PRR = 3.80, trastuzumab deruxtecan (TD) with ROR = 4.22 and PRR = 3.63, trastuzumab emtansine (TE) with ROR = 3.93 and PRR = 3.85, and enfortumab vedotin (EV) with ROR = 3.26 and PRR = 3.02. Adverse events resulted in 237 deaths, 43 life-threatening cases, and 439 initial or prolonged hospitalizations, with TD being the top ranking for deaths and hospitalizations, followed by TE, which presented the highest mortality rate due to adverse events. The most frequent adverse events were nausea (506 cases), diarrhea (262 cases), vomiting (216 cases), ascites (112 cases), colitis (90 cases), pancreatitis (52 cases), and intestinal obstruction (37 cases).</p><p><strong>Conclusions: </strong>ADCs may increase the risk of gastrointestinal adverse events and thus require vigilant monitoring in clinical practice.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"50"},"PeriodicalIF":2.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prodelphinidin B-2,3,3\"-O-gallate via chemical oxidation of epigallocatechin-3-gallate shows high efficacy inhibiting triple-negative breast cancer cells.","authors":"Jing Wang, Yuna Wang, Shuanggou Zhang, Hongtao Hu, Ruohan Zhang, Chengting Zi, Jun Sheng, Peiyuan Sun","doi":"10.1186/s40360-025-00883-6","DOIUrl":"10.1186/s40360-025-00883-6","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer is a clinically aggressive malignancy with poorer outcomes versus other subtypes of breast cancer. Numerous reports have discussed the use of epigallocatechin-3-gallate (EGCG) against various types of cancer. However, the effectiveness of EGCG is limited by its high oxidation and instability. The Notch pathway is critical in breast cancer development and prognosis, and its inhibition is a potential treatment strategy.</p><p><strong>Results: </strong>In this study, we investigated the effects of prodelphinidin B-2,3,3''-O-gallate (named PB2,3,3''/OG or compound 2) via chemical oxidation of EGCG on cell viability and the Notch1 signaling pathway in breast cancer cells. We found that compound 2 showed significant cytotoxicity against triple-negative breast cancer cells, with the half maximal inhibitory concentration (IC₅₀) values ranging 20-50 µM. In MDA-MB453 cells, compound 2 inhibited proliferation, clone formation, and the expression of proteins involved in the Notch1 signaling pathway. Furthermore, compound 2 induced cell cycle arrest and apoptosis. Consistent with the results of in-vitro experiments, treatment with compound 2 significantly reduced tumor growth. Mechanistically, compound 2 directly bound to Notch1 with high binding affinity (dissociation constant: K_D=4.616 × 10^- 6 M).</p><p><strong>Conclusion: </strong>Our finding suggested that compound 2 may be a promising agent for the development of novel anti-cancer therapy options.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"48"},"PeriodicalIF":2.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety analysis of romiplostim, eltrombopag, and avatrombopag post-market approval: a pharmacovigilance study based on the FDA Adverse Event Reporting System.","authors":"Xiaoling Wang, Yunsong Li, Wei Zhuang","doi":"10.1186/s40360-025-00873-8","DOIUrl":"10.1186/s40360-025-00873-8","url":null,"abstract":"<p><strong>Background: </strong>Romiplostim, eltrombopag, and avatrombopag, as new-generation thrombopoietin receptor agonists (TPO-RAs), have been widely used in the treatment of immune thrombocytopenia (ITP). Given their similar efficacy, a comprehensive evaluation of their safety is crucial for optimizing treatment choices. This study aims to explore the potential safety issues of three major drugs for treating ITP: romiplostim, eltrombopag, and avatrombopag, thereby providing references and research directions for subsequent high-quality clinical studies.</p><p><strong>Methods: </strong>We retrieved data from the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2018 to the second quarter of 2023. Using reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multiple gamma poisson shrinkage (MGPS), we mined and analyzed adverse events (AEs) associated with romiplostim, eltrombopag, and avatrombopag. The Designated Medical Event (DME) list from the European Medicines Agency (EMA) was used to screen out the DME of three drugs. Venn analysis was used to screen the specific AEs of each drug.</p><p><strong>Results: </strong>The study included 2,851 cases of romiplostim, 10,297 cases of eltrombopag, and 973 cases of avatrombopag. Venn analysis revealed nine common AEs across the three drugs. The number of significant specific AEs associated with romiplostim, eltrombopag, and avatrombopag were 58, 98, and 15 respectively. DMEs for romiplostim included autoimmune haemolytic anaemia (ROR = 6.1, n = 3), haemolytic anaemia (ROR = 8.13, n = 7), sudden hearing loss (ROR = 5.24, n = 3), haemolysis (ROR = 3.89, n = 3). DMEs for eltrombopag included hepatic infection (ROR = 9.56, n = 6), granulocytopenia (ROR = 2.91, n = 4), autoimmune haemolytic anaemia (ROR = 3.03, n = 5), haemolytic anaemia (ROR = 3.46, n = 10), haemolysis (ROR = 4.65, n = 12), hepatic failure (ROR = 2.51, n = 23). Not a single DME was found for avatrombopag.</p><p><strong>Conclusion: </strong>This study indicates that eltrombopag manifests significant safety signals within the hepatic system. This implies that monitoring liver function during treatment is advisable. Avatrombopag shows relatively lower hepatotoxicity signals; however, further large-scale studies are needed to validate these observations. Moreover, both romiplostim and eltrombopag therapies may be linked to a risk of sudden hearing loss or deafness, which merits clinical attention. These findings offer crucial safety references for clinical drug use. Nevertheless, the causal relationship between the drugs and AEs necessitates further in-depth investigation.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"46"},"PeriodicalIF":2.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}