Frontiers in Pharmacology最新文献

{"title":"A post-marketing pharmacovigilance study of triazole antifungals: adverse event data mining and analysis based on the FDA adverse event reporting system database.","authors":"Yalan Tian, Min Jin, Hong Ning","doi":"10.3389/fphar.2025.1462510","DOIUrl":"10.3389/fphar.2025.1462510","url":null,"abstract":"<p><strong>Background: </strong>To explore and analyze post-marketing adverse drug event (ADE) signals for voriconazole, posaconazole, and isavuconazole, and to compare the safety differences among the three drugs, aiming to provide insights for rational clinical use.</p><p><strong>Methods: </strong>Using the Open Vigil 2.1 online tool, extract adverse drug event (ADE) report data for voriconazole, posaconazole, and isavuconazole from the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) database from the time the drugs were marketed up to the third quarter of 2023. Employ the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods for data mining. Filter out ADE signals detected by both the ROR and PRR methods, and categorize these ADE signals by System Organ Class (SOC) according to the Medical Dictionary for Regulatory Activities (MedDRA 26.0).</p><p><strong>Results: </strong>A total of 8,898 ADE reports with voriconazole as the primary suspect drug were retrieved, 1,948 for posaconazole, and 944 for isavuconazole. From the basic analysis of the adverse event reports, male patients (50.31%) outnumber female patients (32.11%). In terms of age, the majority of patients are over 45 years old (52.72%). The reports primarily come from the United States, Japan, France, China, and other countries. A total of 607 ADE signals were identified, with 402 for voriconazole, 159 for posaconazole, and 46 for isavuconazole. Voriconazole ADEs primarily involved the following SOCs: Investigations (9.45%), Eye Disorders (8.46%), and Nervous System Disorders (7.21%); Posaconazole ADEs primarily involved the following SOCs: Investigations (13.84%), General Disorders and Administration Site Conditions (11.95%), and Nervous System Disorders (6.29%); Isavuconazole ADEs primarily involved the following SOCs: General Disorders and Administration Site Conditions (15.22%), Hepatobiliary Disorders (10.87%), and Blood and Lymphatic System Disorders (10.87%).</p><p><strong>Conclusion: </strong>Voriconazole, posaconazole, and isavuconazole all potentially pose safety risks related to hepatobiliary disorders and cardiac disorders. Additionally, voriconazole carries a higher safety risk for eye disorders and nervous system disorders. Newly discovered ADE signals not mentioned in the drug package inserts include voriconazole-induced rhabdomyolysis, posaconazole-induced peripheral neuropathy, and isavuconazole-induced visual impairment and mental confusion. These findings are significant for guiding rational clinical use of these medications.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1462510"},"PeriodicalIF":4.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364239","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":"Chemical characterization and encapsulation of <i>Ganoderma pfeifferi</i> extract with cytotoxic properties.","authors":"Jan Šťastný, Ángela Morellá-Aucejo, Tomáš Skala, Andrea Bernardos, Petr Maršík, Araceli Lérida-Viso, Jaroslav Matějka, Anna Mascellani Bergo, María Dolores Marcos, Ramón Martínez-Máñez, Ivan Jablonský, Pavel Klouček","doi":"10.3389/fphar.2025.1526502","DOIUrl":"10.3389/fphar.2025.1526502","url":null,"abstract":"<p><p>Mushrooms of the genus <i>Ganoderma</i> are known for diverse biological activities, demonstrated both traditionally and experimentally. Their secondary metabolites have shown cytotoxic potential across different cancer cell lines. Besides exploration of the most active components in different species or genotypes, new formulation techniques are in development. In recent years, there has been a growing interest in the use of nanomaterials because of significant potential for pharmacology applications as substance carriers. Applying nanoparticles may enhance the medicinal effect of the mushroom substances. This study investigated the cytotoxic properties of <i>Ganoderma</i> species methanolic extracts against the HeLa cancer cell line. Notably, the extract obtained from <i>Ganoderma pfeifferi</i> demonstrated the highest activity and was further used for encapsulation within synthesized mesoporous silica nanoparticles MCM-41. Subsequently, the cytotoxic effect of the loaded MCM-41 to the free form of extract was compared. The obtained results indicate successful encapsulation, and similar activity comparing encapsulated form to free extracts (IC₅₀ 16.6 μg/mL and 20.5 μg/mL, respectively). In addition, the four unique compounds were identified as applanoxidic acid A, applanoxidic acid G, ganoderone A, and ganoderone B in the <i>G. pfeifferi.</i> This study is an essential prerequisite for further steps like nanoparticle functionalization for sustained or on-command delivery of these natural extracts.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1526502"},"PeriodicalIF":4.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364297","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":"Global bibliometric analysis of traditional Chinese medicine regulating gut microbiota in the treatment of diabetes from 2004 to 2024.","authors":"Jieling Liang, Xiaojuan Lin, Xin Liao, Xi Chen, Ying Zhou, Lin Zhang, Yunyun Qin, Haoru Meng, Zhongwen Feng","doi":"10.3389/fphar.2025.1533984","DOIUrl":"10.3389/fphar.2025.1533984","url":null,"abstract":"<p><strong>Objectives: </strong>The therapeutic efficacy of Traditional Chinese Medicine (TCM) in modulating gut microbiota for diabetes treatment has garnered increasing scholarly attention. This study aims to meticulously examine current research trajectories and focal areas from 2004 to 2024, providing a foundational framework for future inquiries.</p><p><strong>Methods: </strong>A comprehensive search of documents published between 2004 and 2024 was conducted using the Web of Science database. The resulting data were analyzed and visualized using R software, VOSviewer, and CiteSpace.</p><p><strong>Results: </strong>The study included a total of 751 documents. From 2004 to 2022, the number of annual publications showed a continuous upward trend (2004: n = 1 to 2022: n = 159), and the number of publications in 2023 (n = 141) decreased slightly from the previous year. China emerged as the leading country in terms of article publications (n = 430). Additionally, the United States played a prominent role in international research collaborations. Frontiers in Pharmacology (n = 31) was the most frequently published journal, while Nature (n = 1,147) achieved the highest citation count. Key identified keywords included obesity, insulin resistance, inflammation, and oxidative stress.</p><p><strong>Conclusion: </strong>Three key research focuses in this domain include: the therapeutic effects of active constituents in TCM on diabetes via gut microbiota modulation, the underlying mechanisms through which TCM influences gut microbiota in diabetes management, and the targeted regulation of specific gut bacterial populations by TCM in the treatment of diabetes.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1533984"},"PeriodicalIF":4.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364313","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":"A review on eye diseases induced by blue light: pathology, model, active ingredients and mechanisms.","authors":"Yuan Yan, Yiyao Wu, Yu Zhao, Yaguang Yang, Guangtao An, Zhidong Liu, Dongli Qi","doi":"10.3389/fphar.2025.1513406","DOIUrl":"10.3389/fphar.2025.1513406","url":null,"abstract":"<p><p>Blue light induced eye damage (BLED) belongs to modern diseases. It is an ophthalmic disease caused by prolonged exposure to electronic devices or screens containing a large amount of high-energy short waves (blue light). Specific symptoms include dryness and discomfort in the eyes, blurred vision, headache, insomnia, and in severe cases, it may also cause various eye diseases such as cataracts and glaucoma. At present, the development of health products and drugs for eye blue light injury faces many difficulties. Therefore, further exploration and research are needed on the pathogenesis, pathophysiology, and pharmacological mechanisms of blue light injury. Natural medicine ingredients and preparations have unique advantages in targeting eye blue light injury fatigue products due to their multi-component synergistic effects, overall regulation, and mild and safe characteristics. Starting from the disease-related mechanisms and pathophysiological characteristics of eye blue light injury, this article elucidates the pharmacological mechanisms of various drugs for treating eye blue light injury. At the same time, it reviews the research on <i>in vitro</i> cultured cell and animal model conditions for blue light injury eyes, in order to provide reference for subsequent blue light injury modeling experiments. And explore future research directions to provide new ideas and methods for the prevention and treatment of BLED.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1513406"},"PeriodicalIF":4.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364245","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":"Comparative efficacy and safety of 20 intravenous pharmaceutical intervention for prevention of etomidate-induced myoclonus: a systematic review and Bayesian network meta-analysis.","authors":"Lu Chen, Pengxiang Zhou, Zhengqian Li, Ziyang Wu, Suodi Zhai","doi":"10.3389/fphar.2024.1507616","DOIUrl":"10.3389/fphar.2024.1507616","url":null,"abstract":"<p><strong>Objective: </strong>To compare the efficacy and safety of pharmaceutical interventions to prevent etomidate-induced myoclonus (EIM), providing the optimal intervention for clinical practice.</p><p><strong>Methods: </strong>PubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, WanFang database, and SinoMed database were searched from the inception to sixth May 2024. We included randomized controlled trials (RCTs) comparing intravenous pharmaceutical interventions to prevent EIM with placebo, no intervention, or another pharmaceutical intervention.</p><p><strong>Results: </strong>Forty-eight RCTs involving 4,768 participants randomly assigned to 20 intravenous pharmaceutical interventions and normal saline were included. Granisetron (odds ratio [OR]: 0.01, 95% confidence interval [CI]: 0.00 to 0.06; one study, moderate certainty) and oxycodone (OR: 0.01, 95% CI: 0.00 to 0.05; three studies, low certainty) was found to be the most effective intervention in reducing the risk of EIM and ranked highest in terms of surface under the cumulative ranking values (94.4% and 89.7% probability), followed by sufentanil (76.5% probability) and remifentanil (74.8% probability). Further subgroup analysis of EIM at mild, moderate-to-severe levels highlighted granisetron and oxycodone as the favorable interventions for reducing EIM. For safety outcomes, the synthesized results indicated that opioids were associated with a higher risk of adverse events (AEs), while no severe AEs were observed.</p><p><strong>Conclusion: </strong>Moderate-to-low certainty evidence indicated that granisetron and oxycodone may represent the optimal intervention for reducing the risk of overall and moderate-to-severe EIM with a reasonable safety profile, providing the potential interventions for clinical practice.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=291275.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1507616"},"PeriodicalIF":4.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364210","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":"A ketogenic diet regulates microglial activation to treat drug addiction.","authors":"Jie Ji, Yi Tang","doi":"10.3389/fphar.2025.1462699","DOIUrl":"10.3389/fphar.2025.1462699","url":null,"abstract":"<p><p>Drug addiction is a chronic and potentially deadly disease that is considered a global health problem and describes the alteration of brain function by psychostimulant drugs through changes in the reward system. However, there is still no ideal strategy for the management of drug addiction. Previous studies have suggested that microglia are involved in events associated with neuroplasticity and memory, which are also related to drug addiction. Many studies have shown that psychoactive substances may act directly on immune cells, altering their function and inducing the production of various inflammatory mediators. In recent years, a ketogenic diet (KD) was shown to have therapeutic benefits as a dietary therapy for a variety of neurological disorders. With respect to drug addiction, studies have shown that a KD can alleviate glucose metabolism disorders caused by alcohol use disorders by increasing ketone metabolism, thereby reducing withdrawal symptoms. This finding indicates the potential of a KD as a treatment for drug addiction, since a KD may promote the transition of microglia to a predominantly anti-inflammatory state through several mechanisms. Here, we discuss recent research showing that a KD plays a variety of roles in controlling microglia-mediated inflammation, opening new treatment avenues to treat drug addiction. This succinct analysis offers evidence of the enormous potential of a KD to treat drug addiction through the inhibition of microglial activation.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1462699"},"PeriodicalIF":4.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364220","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":"Integrated serum metabolomics and network pharmacology reveal molecular mechanism of Qixue Huazheng formula on peritoneal fibrosis.","authors":"Xiaohui Meng, Li Sheng, Yongqing You, Huibo Dai, Manshu Yu, Funing Wang, Ziren Zhou, Yun Shan, Meixiao Sheng","doi":"10.3389/fphar.2025.1515038","DOIUrl":"10.3389/fphar.2025.1515038","url":null,"abstract":"<p><strong>Background: </strong>Peritoneal fibrosis (PF) causes peritoneal dialysis (PD) withdrawal due to ultrafiltration failure. Qixue Huazheng formula (QXHZF), comprising <i>Astragalus membranaceus</i>, <i>Centella asiatica</i>, and <i>Ligusticum sinense</i>, is applied to treat PD-related peritoneum injury related; however, the active components, core genes, and underlying mechanism involved remain unclear.</p><p><strong>Methods: </strong>The anti-PF effects of QXHZF were verified <i>in vivo</i> and <i>in vitro</i>. Targets underlying QXHZF-mediated improvement of PD-induced PF were predicted using network pharmacology analysis. Metabolites associated with QXHZF treatment of PD-related PF were analyzed by serum metabolomics. Integration of network pharmacology and serum metabolomics findings identified potentially important pathways, metabolites, and targets, and molecular docking studies confirmed the interactions of key components and targets. Western blotting (WB), quantitative real-time PCR (qRT-PCR), TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and flow cytometry were conducted.</p><p><strong>Results: </strong>QXHZF had potent therapeutic efficacy against PF according to WB, qRT-PCR, and pathological section examination. Network pharmacological analysis indicated that multiple QXHZF compounds contributed to improving PF by modulating various targets and pathways. Differential metabolites were identified by serum metabolomics analysis. Integrated data analysis indicated that steroid hormone biosynthesis, the Ras signaling pathway, apoptosis, and estrogen signaling contributed to the effects of QXHZF. Metabolite-target network and molecular docking analyses revealed that QXHZF can bind to estrogen receptor 1 (ESR1) and rapidly accelerated fibrosarcoma 1 (RAF1) through its components. WB demonstrated that QXHZF treatment reversed activation of the above-mentioned signaling pathways, thereby inhibiting PD fluid-induced PF.</p><p><strong>Conclusion: </strong>QXHZF can significantly ameliorate PD-induced PF and may regulate estrogen signaling, the Ras pathway, and apoptosis in this context.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1515038"},"PeriodicalIF":4.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364316","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":"Better understanding the phenotypic effects of drugs through shared targets in genetic disease networks.","authors":"Elena Díaz-Santiago, Aurelio A Moya-García, Jesús Pérez-García, Raquel Yahyaoui, Christine Orengo, Florencio Pazos, James R Perkins, Juan A G Ranea","doi":"10.3389/fphar.2024.1470931","DOIUrl":"10.3389/fphar.2024.1470931","url":null,"abstract":"<p><strong>Introduction: </strong>Most drugs fail during development and there is a clear and unmet need for approaches to better understand mechanistically how drugs exert both their intended and adverse effects. Gaining traction in this field is the use of disease data linking genes with pathological phenotypes and combining this with drugtarget interaction data.</p><p><strong>Methods: </strong>We introduce methodology to associate drugs with effects, both intended and adverse, using a tripartite network approach that combines drug-target and target-phenotype data, in which targets can be represented as proteins and protein domains.</p><p><strong>Results: </strong>We were able to detect associations for over 140,000 ChEMBL drugs and 3,800 phenotypes, represented as Human Phenotype Ontology (HPO) terms. The overlap of these results with the SIDER databases of known drug side effects was up to 10 times higher than random, depending on the target type, disease database and score threshold used. In terms of overlap with drug-phenotype pairs extracted from the literature, the performance of our methodology was up to 17.47 times greater than random. The top results include phenotype-drug associations that represent intended effects, particularly for cancers such as chronic myelogenous leukemia, which was linked with nilotinib. They also include adverse side effects, such as blurred vision being linked with tetracaine.</p><p><strong>Discussion: </strong>This work represents an important advance in our understanding of how drugs cause intended and adverse side effects through their action on disease causing genes and has potential applications for drug development and repositioning.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1470931"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255424","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":"Efferocytosis-related gene IL33 predicts prognosis and immune response and mediates proliferation and migration <i>in vitro</i> and <i>in vivo</i> of breast cancer.","authors":"Xiao He, Xianjie Cheng, Zhun Zhang, Lanhui Chen, Changjun Xie, Mengjie Tang","doi":"10.3389/fphar.2025.1533571","DOIUrl":"10.3389/fphar.2025.1533571","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Breast cancer (BRCA) has a high incidence among women, with poor prognosis and high mortality, which is increasing year by year. Efferocytosis is a process of phagocytosis of abnormal cells and is of great value in tumor research. Our study seeks to create a predictive model for BRCA using efferocytosis-related genes (ERGs) to explore the significance of efferocytosis in this disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this research, Differential analysis, and univariate Cox regression were employed to identify genes linked to prognosis in BRCA patients. Then the BRCA patients were categorized into distinct groups using consensus clustering based on prognosis genes. Survival analysis, PCA, and t-SNE were performed to verify these groups. The enrichment of metabolic pathways within the detected clusters was evaluated using gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA). Additionally, single-sample GSEA (ssGSEA) was used to examine changes in immune infiltration and enrichment. A risk prognostic model was constructed utilizing multivariable Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) analyses, and subsequently validated its predictive accuracy by stratifying patients according to the median risk score. Ultimately, some crucial independent prognostic genes were pinpointed and their expression, roles, and immune characteristics were explored in both laboratory and live models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Findings revealed 52 differentially expressed genes (DEGs), of which 21 were significantly linked to BRCA outcomes. These 21 genes were utilized for consensus clustering to categorize BRCA patients into two subtypes. Subtype B was linked to a worse prognosis compared to Subtype A, though both subtypes were distinguishable. The enriched pathways were mainly concentrated in Subtype A and were actively expressed in this group. Following this, a prognostic risk model was constructed using five risk genes, which was proven to possess significant predictive value. A significant link was identified between the immune microenvironment and the risk-associated genes and scores. IL33 was identified as an independent prognostic gene with important research value. Its &lt;i&gt;in vivo&lt;/i&gt; expression results aligned with the data analysis findings, showing low expression in BRCA. Furthermore, overexpression of IL33 significantly inhibited BRCA growth and motility &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;, while also enhancing their vulnerability to destruction by activated CD8&lt;sup&gt;+&lt;/sup&gt; T cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The ERG-based risk model effectively predicts the prognosis of BRCA patients and shows a strong link with the immune microenvironment. IL33 stands out as a significant prognostic marker, crucial in the onset and advancement of BRCA. This highlights the necessity for additional studies and indicates that IL33 might be a potential target for BRCA treatment.&lt;","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1533571"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254663","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":"Pirfenidone regulates seizures through the HMGB1/TLR4 axis to improve cognitive functions and modulate oxidative stress and neurotransmitters in PTZ-induced kindling in mice.","authors":"Mansi Dahalia, Sparsh Gupta, Haya Majid, Divya Vohora, Nidhi","doi":"10.3389/fphar.2024.1528032","DOIUrl":"10.3389/fphar.2024.1528032","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy is a neurological disorder characterized by recurrent seizures due to abnormal electrical activity in the brain. Pirfenidone, an antifibrotic drug, has shown anti-inflammatory and antioxidant properties in various disease models, including neurological conditions. However, its potential anticonvulsant effects have not been thoroughly explored. This study aims to evaluate the anticonvulsant potential of pirfenidone in a pentylenetetrazol-induced kindling model of epilepsy, focusing on its effect on seizure activity, cognition, antioxidant profiles, inflammatory markers, neurotransmitter balance, liver enzyme levels, and histopathological changes.</p><p><strong>Methods: </strong>Healthy male Swiss albino mice were subjected to an acute Increasing Current Electroshock test and chronic pentylenetetrazol-kindling model. Pirfenidone was administered at doses of 100, 200, and 300 mg/kg, orally, with sodium valproate as a standard drug. Seizure severity and cognitive function were assessed in the pentylenetetrazol-kindling model, along with biochemical assays that evaluated antioxidant enzymes, inflammatory markers, neurotransmitter levels, and liver enzyme levels. Histopathological changes were also assessed in the hippocampus and cortex of experimental mice.</p><p><strong>Results: </strong>Pirfenidone at 200 mg/kg and 300 mg/kg significantly increased Seizure Threshold Current in the Increasing Current Electroshock test, indicating a protective effect against seizures. In the pentylenetetrazol-kindling model, pirfenidone delayed seizure onset and reduced severity, with the 300 mg/kg dose showing the strongest impact. Pirfenidone also demonstrated significant improvements in cognitive function, as evidenced by enhanced performance in passive avoidance and elevated plus maze tests. Antioxidant profiles showed increased levels of superoxide dismutase, catalase, and reduced glutathione, with a corresponding reduction in malondialdehyde and acetylcholinesterase levels. Pirfenidone significantly reduced pro-inflammatory cytokines including interleukin-6, interleukin-1β, transforming growth factor-β, tumor necrosis factor- α, high-mobility group box-1, and toll-like receptor-4, elevated gamma-aminobutyric acid, decreased glutamate levels, modulated aspartate aminotransferase and alanine aminotransferase levels. Histopathological analysis revealed that pirfenidone ameliorated cellular disintegration and neuronal damage in the hippocampus and cortex.</p><p><strong>Conclusion: </strong>Pirfenidone shows potential as an anticonvulsant, anti-inflammatory, hepatoprotective, and neuroprotective agent, with additional benefits in improving cognition and oxidative stress profiles in epilepsy treatment. Further studies are required to explore its long-term safety and efficacy.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1528032"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255429","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}