Frontiers in Pharmacology最新文献

{"title":"The potential of ARL4C and its-mediated genes in atherosclerosis and agent development.","authors":"Dan Liu, Jie Wang, Shuangshuang Zhang, Hongfei Jiang, Yudong Wu, Chao Wang, Wujun Chen","doi":"10.3389/fphar.2025.1513340","DOIUrl":"10.3389/fphar.2025.1513340","url":null,"abstract":"<p><p>Foam cells are the risk factors for atherosclerosis. Recently, ARL4C, a member of the ADP-ribosylation factor family of GTP-binding proteins, was found to promote cholesterol efflux to decrease foam cell formation, suggesting that ARL4C may be a new promising target for the treatment of atherosclerosis. In fact, ARL4C regulated the expression of multiple atherosis-related genes, including ABCA1, ALDH1A3, ARF6, ENHO, FLNA, LRP6, OSBPL5, Snail2, and SOX2. Many agents, including ABCA1 agonists (CS-6253, IMM-H007, RG7273, and R3R-01), FLNA antagonist sumifilam, LRP6 inhibitor BI-905677 and agonist SZN-1326, and SOX2 inhibitor STEMVAC, were investigated in clinical trials. Targeting these genes could improve the success rate of drug development in clinical trials. Indeed, many agents could regulate ARL4C expression, including LXR/RXR agonists, Ac-LDL, sucrose, T9-t11-CLA, and miR-26. Downregulation of ARL4C with siRNA and anti-sense oligonucleotide (ASO), such as ASO-1316, is developing in preclinical research for the treatment of lung adenocarcinoma, liver cancer, and colorectal cancer. Thus, ARL4C and its regulated genes may be a potential target for drug development. Thus, we focus on the role of ARL4C and its-mediated genes in atherosclerosis and agent development, which provide insights for the identification, research, and drug development of novel targets.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1513340"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771898","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":"Unraveling human transferrin-tryptamine interactions: a computational and biophysical approach to Alzheimer's disease therapeutics.","authors":"Mohammed Alrouji, Mohammed S Alshammari, Taghreed A Majrashi, Azna Zuberi, Moyad Shahwan, Akhtar Atiya, Anas Shamsi","doi":"10.3389/fphar.2025.1540736","DOIUrl":"10.3389/fphar.2025.1540736","url":null,"abstract":"<p><p>Neurodegeneration is a progressive loss of neurons that leads to affected cognitive and motor functions and is characterized by neurodegenerative disorders (NDs). Human transferrin (Htf) is a blood plasma glycoprotein that binds to iron and regulates the free iron in biological fluids. Free iron is a potent neurotoxin associated with the generation of Reactive oxygen species (ROS) and is ultimately linked to oxidative stress and neuronal damage. Thus, targeting iron homeostasis is an attractive strategy for the management of NDs, viz. Alzheimer's disease (AD). Tryptamine (Trp) is a naturally occurring monoamine, that has demonstrated promising roles in AD therapeutics. The present study aims to delineate the binding mechanism of Trp with Htf employing computational and spectroscopic approaches. Molecular docking ascertained the vital residues governing the Htf-Trp complex formation. Further, Molecular dynamic (MD) studies ascertained the structural dynamics and stability of the complex, implying that the binding of Trp causes minimal structural alterations in Htf, suggestive of the stability of the complex. The results from fluorescence spectroscopy demonstrated the binding of Trp with Htf with a binding constant (<i>K</i>) of 0.48 × 10⁶ M^-1, validating the <i>in silico</i> observations. This study provides a platform to understand the binding mechanism that may lead to novel therapeutic approaches targeting AD.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1540736"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771903","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":"Development and validation of the HPLC-MS/MS method and its application to the pharmacokinetic study for the Mongolian drug Sendeng-4 in rat blood plasma.","authors":"Pu Bai, Yu Dong","doi":"10.3389/fphar.2025.1547415","DOIUrl":"10.3389/fphar.2025.1547415","url":null,"abstract":"<p><strong>Abstract: </strong>Sendeng-4 is a Mongolian drug. The Mongolian people have been using it to treat rheumatoid arthritis. At present, an increasing number of Han people are paying attention to the anti-rheumatoid effect of Sendeng-4. However, information on the pharmacokinetics of Sendeng-4 is limited, which limits its wide application in China.</p><p><strong>Objective: </strong>Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established to study the pharmacokinetics of Sendeng-4.</p><p><strong>Method: </strong>MS/MS with a negative ionization mode (ESI-) and multiple reaction monitoring at m/z 300.95→193.09 and 317.08→192.10 were detected for (2R, 3R)-dihydromyricetin and myricetin, respectively. The pharmacokinetic parameters were analyzed by DAS 2.0.</p><p><strong>Result: </strong>The results showed that the plasma concentration time (C-T) curves of (2R, 3R)-dihydromyricetin and myricetin showed double peaks. The T_max value of (2R, 3R)-dihydromyricetin and myricetin in both groups was 3 h. In absorption, the AUC_(0-∞) values of (2R, 3R)-dihydromyricetin and myricetin in the normal group and the arthritis model group were 16.151 ± 2.670 mg·h/L vs. 11.331 ± 0.749 mg·h/L and 2.626 ± 0.400 mg·h/L vs. 2.213 ± 0.388 mg·h/L, respectively. In the distribution, the Vz/F values of (2R, 3R)-dihydromyricetin and myricetin in the normal group and the arthritis model group were 8.212 L/kg vs. 1.744 L/kg and 5.252 L/kg vs. 10.568 L/kg, respectively. In metabolism, the MRT (0-∞) values of (2R, 3R)-dihydromyricetin and myricetin in the normal group and the arthritis model group were 6.848 h vs. 3.476 h and 5.661 h vs. 8.959 h, respectively. In excretion, the CLz/F values of (2R, 3R)-dihydromyricetin and myricetin in the normal group and the arthritis model group were 0.021 vs. 0.024 L/min/kg and 0.018 vs. 0.021 L/min/kg, respectively. There were significant variations in the absorption levels, distribution levels, and elimination rate of (2R, 3R)-dihydromyricetin and myricetin after the administration of Sendeng-4.</p><p><strong>Conclusion: </strong>The study laid the foundation for the subsequent study of pharmacokinetics of Sendeng-4 in humans. The results of this study will contribute to a better understanding of the activity and clinical application of Sendeng-4 and other related traditional Mongolian drug prescriptions.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1547415"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771960","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":"Metformin as a disease-modifying therapy in osteoarthritis: bridging metabolism and joint health.","authors":"Iryna Halabitska, Pavlo Petakh, Oleksandr Kamyshnyi","doi":"10.3389/fphar.2025.1567544","DOIUrl":"10.3389/fphar.2025.1567544","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) and impaired glucose tolerance (IGT) frequently coexist, leading to compounded clinical and metabolic challenges. This study investigates the effects of metformin in improving both clinical outcomes (pain, stiffness, physical function) and metabolic parameters (inflammatory markers, lipid profile, BMI) in patients with knee OA and IGT.</p><p><strong>Methods: </strong>The study included 60 patients diagnosed with knee OA and IGT. Participants were divided into two groups: 26 patients received standard OA treatment without metformin (Without Metf), while 34 received metformin (500 mg twice daily) for 3 months, in addition to standard treatment (With Metf). Clinical assessments (WOMAC, Lequesne Algofunctional Index, KOOS, VAS) and metabolic markers (CRP, NLR, SOD, lipid profile, BMI) were measured before treatment, after 1 month, and after 3 months.</p><p><strong>Results: </strong>The With Metf group showed significantly greater improvements in pain, stiffness, physical function, and quality of life compared to the Without Metf group. Metformin also led to significant reductions in inflammatory markers and improvements in lipid profiles and metabolic health indicators. The With Metf group demonstrated enhanced BMI, waist-to-hip ratio, and waist-to-height ratio. Furthermore, the need for increased NSAID doses was predicted by factors such as pain severity and inflammatory markers.</p><p><strong>Conclusion: </strong>Metformin effectively alleviates osteoarthritis symptoms and improves metabolic health in patients with both OA and IGT. Further research is needed to explore its long-term effects on joint health, inflammatory markers, and its potential role in OA management in patients without IGT.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1567544"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771964","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":"Functional tumor-derived exosomes in NSCLC progression and clinical implications.","authors":"Yuxin Gao, Jun Xie, Zhenya Yang, Mengxi Li, Hongfan Yuan, Rui Li","doi":"10.3389/fphar.2025.1485661","DOIUrl":"10.3389/fphar.2025.1485661","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and remains one of the leading causes of cancer-related mortality worldwide. The high mortality rate is primarily driven by delayed diagnosis, rapid metastasis, and frequent recurrence. Tumor-derived exosomes (TEXs) have emerged as critical mediators in NSCLC progression, offering valuable insights into the tumor microenvironment. Exosomes are small membrane vesicles that facilitate intercellular communication and transport bioactive molecules, including proteins, RNAs, and DNAs, thereby reflecting the genetic complexity of tumors. These exosomes play a key role in promoting tumor metastasis, epithelial-mesenchymal transition (EMT), neovascularization, drug resistance, and immune evasion, all of which are pivotal in the development of NSCLC. This review explores the diverse roles of TEXs in NSCLC progression, focusing on their involvement in pre-metastatic niche formation, tissue metastasis, and immune modulation. Specifically, we discuss the roles of exosome-associated RNAs and proteins in NSCLC, and their contribute to tumor growth and metastasis. Furthermore, we explore the potential of TEXs as biomarkers for NSCLC, emphasizing their application in diagnosis, prognosis, and prediction of resistance to targeted therapies and immunotherapies.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1485661"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771678","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":"<i>Akkermansia muciniphila</i> ameliorates olanzapine-induced metabolic dysfunction-associated steatotic liver disease via PGRMC1/SIRT1/FOXO1 signaling pathway.","authors":"Hui Chen, Ting Cao, ChenQuan Lin, ShiMeng Jiao, YiFang He, ZhenYu Zhu, QiuJin Guo, RenRong Wu, HuaLin Cai, BiKui Zhang","doi":"10.3389/fphar.2025.1550015","DOIUrl":"10.3389/fphar.2025.1550015","url":null,"abstract":"<p><p><i>Akkermansia muciniphila</i> (AKK), classified as \"lean bacteria,\" has emerged as a promising candidate for ameliorating metabolic disorders, including obesity, diabetes, and liver disease. In this study, we investigated the therapeutic potential of AKK to counteract metabolic dysfunctions induced by Olanzapine (OLZ), a first-class antipsychotic known for its high therapeutic efficacy but also its association with metabolic disturbances, particularly Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Previous studies have implicated progesterone receptor membrane component 1 (PGRMC1) as a key player in antipsychotic-induced metabolic side effects. Using male C57BL/6J mice fed a high-fat diet, we assessed the effects of AKK supplementation on OLZ-induced metabolic disturbances. Key parameters such as body weight, hepatic injury markers, glucose tolerance, insulin resistance, and lipid metabolism were analyzed. The study revealed that AKK supplementation reduced hepatic lipid accumulation, oxidative stress, and insulin resistance, while normalizing lipid and glucose metabolism. These effects are likely mediated through the restoration of PGRMC1/SIRT1/FOXO1 signaling pathway by AKK. Additionally, changes in gut microbiota composition, including a reduction in pathogenic bacteria such as <i>Lactococcus</i> and enrichment of beneficial bacteria, were observed. Overall, the study suggests that AKK has therapeutic potential to counteract OLZ-induced MASLD by modulating gut microbiota and key metabolic pathways, making it a promising strategy for managing metabolic side effects in patients receiving antipsychotic treatment.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1550015"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771880","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":"The real-world analysis of adverse events with azacitidine: a pharmacovigilance study based on the FAERS and WHO-VigiAccess databases.","authors":"Zhaorui Wang, Linlin Guo, Youfu He, Baiquan Zhang, Yang Wang, Juan Ding","doi":"10.3389/fphar.2025.1555838","DOIUrl":"10.3389/fphar.2025.1555838","url":null,"abstract":"<p><strong>Background: </strong>Azacitidine is used to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It acts as a cytosine analog and DNA methyltransferase inhibitor, inducing DNA hypomethylation to reverse epigenetic modifications and restore normal gene expression. However, adverse events (AEs) associated with azacitidine are mainly reported in clinical trials, with limited real-world evidence. This study aims to assess the AE profile of azacitidine by utilizing data from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and WHO-VigiAccess databases.</p><p><strong>Methods: </strong>We extracted adverse event (AE) reports related to azacitidine from the FAERS and WHO-VigiAccess databases, covering the period from the drug's market introduction to the third quarter of 2024. We used statistical methods including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) to analyze the association between azacitidine and documented AEs.</p><p><strong>Results: </strong>The investigation unveiled 16,056 azacitidine-related adverse event (AE) reports from FAERS and 19,867 reports from WHO-VigiAccess. The median duration for the occurrence of these AEs during the observation period was 36 days, with an interquartile range (IQR) spanning from 11 to 126 days. Our statistical analysis identified 27 organ systems associated with AEs induced by azacitidine. Among these, the notable System Organ Classes (SOCs) that met four specific criteria included: infections and infestations, blood and lymphatic system disorders, and neoplasms benign, malignant, and unspecified (including cysts and polyps). Four algorithms identified 443 significant disproportionality preferred terms (PTs), including previously unreported AEs such as death, sepsis, septic shock, respiratory failure, cardiac failure, tumor lysis syndrome, bone marrow failure, interstitial lung disease, and pericarditis. Analysis from the WHO-VigiAccess database showed a ROR of 3.65 and a PRR of 3.30 for the SOC of infections and infestations.</p><p><strong>Conclusion: </strong>This research not only confirms the widely acknowledged AEs linked to azacitidine but also uncovers several potentially new safety concerns noted in actual clinical practice. These results may offer important vigilance information for clinicians and pharmacists when addressing safety issues associated with azacitidine.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1555838"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771900","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":"Traditional usages, chemical metabolites, pharmacological activities, and pharmacokinetics of <i>Boesenbergia rotunda</i> (L.) Mansf.: a comprehensive review.","authors":"Yan Wang, Juanjuan Wen, Feng Liu, Xiujuan Peng, Gang Xu, Mingliang Zhang, Zhuangzhuang Huang","doi":"10.3389/fphar.2025.1527210","DOIUrl":"10.3389/fphar.2025.1527210","url":null,"abstract":"<p><p><i>Boesenbergia rotunda</i>: (L.) Mansf. (family Zingiberaceae), also known as fingerroot, is a medicinal and food plant that is widely distributed in southern China, Southeast Asia, and South Asia. It is a traditional herb and spice that is also known for its beneficial effects on <i>Qi</i>, appetite, stagnation and pain relief. The objective of this study is to conduct a comprehensive and systematic review of the botanical characteristics, traditional applications, phytochemical metabolites, pharmacological properties, toxicology, quality control measures, pharmacokinetics, and clinical applications of <i>B. rotunda</i>. A bibliometric analysis of current studies on <i>B. rotunda</i> was also conducted to facilitate further exploration and utilization of <i>B. rotunda</i> in the functional food and pharmaceutical industries. These data were collected from PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure doctoral and master's theses and other books and scientific databases by searching the keywords <i>Boesenbergia rotunda</i>. Phytochemical analysis has revealed the presence of flavonoids, monoterpenes, alkaloids, aromatic metabolites, phenols, and other metabolites in <i>B. rotunda</i>, exhibiting a wide range of biological activities such as anti-cancer, nephroprotective, anti-inflammatory, anti-bacterial, hepatoprotective, anti-obesity, and anti-oxidant effects, both <i>in vivo</i> and <i>in vitro</i>. In this paper, the research of <i>B. rotunda</i> is discussed in depth by combining traditional application and modern pharmacological research, aiming to provide valuable reference for the future research and practical application of <i>B. rotunda</i>.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1527210"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771901","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":"Immune checkpoint inhibitors-induced pancreatitis: a systematic review and real-world pharmacovigilance analysis.","authors":"Wei Fang, Huanping Wang, Xiaoran Zhang, Hongxia Zhu, Wei Yan, Yang Gao","doi":"10.3389/fphar.2025.1426847","DOIUrl":"10.3389/fphar.2025.1426847","url":null,"abstract":"<p><strong>Purpose: </strong>Immune checkpoint inhibitors-induced pancreatitis (ICIs-P) is an uncommon immune-related adverse event. The available evidence consists mostly of case reports, case series, and narrative reviews. This research focuses on the clinical characteristics and management options for ICIs-P to provide a practice-based global perspective on this disease.</p><p><strong>Methods: </strong>Five electronic databases were systematically reviewed to identify the relevant studies. Furthermore, we performed a disproportionality analysis utilizing OpenVigil 2.1 to interrogate the United States Food and Drug Administration's Adverse Event Reporting System (FAERS) database.</p><p><strong>Results: </strong>A total of 61 patients from 58 studies were included in this study. Most patients with ICIs-P were males (60.7%). Most patients received anti-PD-1/PD-L1 monotherapy (78.7%) or anti-PD-1/PD-L1 monotherapy in conjunction with CTLA-4 blockade (19.7%). The median time from the initiation of immune checkpoint inhibitors treatment to pancreatitis was 108 days (range 52-278). Most cases were severe or life-threatening (G3-G4; 64.0%). Corticosteroids were administered to 73.8% of the patients during the treatment of pancreatitis. Regarding treatment outcomes, ICIs-P was reversible in most cases (83.6%), despite the 8.2% relapse and 8.2% deaths. We identified 606 reports of pancreatitis associated with ICIs in the FAERS database, with the greatest proportion of males (50.7%), 62.0% of PD-1 inhibitors, and 22.1% of all reports of death or life-threatening outcomes. Signals indicating pancreatitis were observed across all ICIs, with particular emphasis on Cemiplimab, Pembrolizumab and Nivolumab.</p><p><strong>Conclusion: </strong>By using a pharmacovigilance database, we discovered an elevated risk of pancreatitis following ICIs therapy, especially with PD-1 inhibitors. Meanwhile, risk factors for ICIs-P remain poorly understood, and diagnosis is challenging. Which may manifest as asymptomatic elevated pancreatic enzyme levels or clinical pancreatitis. Patients with pancreatitis symptoms should have their lipase and amylase levels and radiology evaluated. Diagnosis should be made by excluding other causes. Steroids are the cornerstone of ICIs-P treatment and slow dose reduction is recommended to reduce recurrence.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1426847"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771753","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":"Cyperotundone promotes chemosensitivity of breast cancer via SRSF1.","authors":"Chao Li, Lin Wang, Zhaoyun Liu, Xinzhao Wang, Luhao Sun, Xiang Song, Zhiyong Yu","doi":"10.3389/fphar.2025.1510161","DOIUrl":"10.3389/fphar.2025.1510161","url":null,"abstract":"<p><p>Breast cancer is among the most common malignancies and the leading cause of cancer-related deaths in women. SRSF1 proteins belong to an important splicing factor (SF) family and bind to different splicing regulatory elements (SREs) to promote or inhibit splicing, such as oncogenic splice-switching of PTpMT1, which promoting the progression of cancer. Cyperotundone (CYT) is the major bioactive component of sedge and reported to exhibit multiple biological functions, including its potent cytotoxic effect on breast cancer cells. However, the detailed impact and molecular mechanisms of CYT in breast cancer remain poorly understood. This study aimed to investigate the effects of CYT on breast cancer drug resistance and to explore the molecular mechanisms. CYT significantly suppressed the <i>in vitro</i> and <i>in vivo</i> growth of BC cells without affecting the normal cells at different doses (P < 0.001), induced cell apoptosis, and inhibited the migration and invasion of drug-resistant BC. In comparison with the mono treatment with CYT, combination of CYT and doxorubicin (Dox) enhanced the effects. CYT treatment regulated the RNA and protein levels of epithelial mesenchymal transition (EMT) biomarkers, suppressed the sphere formation ability and expression of cancer stem cell biomarkers in drug resistant BC cells. Results from transcriptome sequencing analysis and experiments identified significantly decreased SRSF1 level in drug resistant cells after CYT treatment. RNA and protein levels of SRSF1 and MYO1B were higher in drug resistant BC cells (P < 0.01). SRSF1 regulated alternative splicing of MYO1B to enhance the ability of drug resistance. Knockdown of SRSF1 significantly decreased expression of full-length MYO1B protein in drug-resistant BC cells (<i>P</i> < 0.05). Overexpression of SRSF1 and MYO1B revered the inhibitory effects of CYT. In conclusion, CYT repressed the growth and metastasis of BC cells and recovered drug sensitivity, through SRSF1-regulated the alternative splicing of MYO1B RNAs, which may represent a novel molecular mechanism to overcome drug resistance in breast cancer. Targeting SRSF1 or MYO1B may be identified as a novel molecular mechanism to against drug resistant in breast cancer.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1510161"},"PeriodicalIF":4.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771885","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}