Frontiers in Pharmacology最新文献

{"title":"Combined opioid-sodium aescinate therapy in blunt thoracic trauma: retrospective evaluation.","authors":"Jun Zhang, Yijie Yan, Zhiyu Guan","doi":"10.3389/fphar.2025.1623916","DOIUrl":"https://doi.org/10.3389/fphar.2025.1623916","url":null,"abstract":"<p><strong>Background: </strong>Effective analgesia is crucial for patients with blunt thoracic trauma, yet the optimal analgesic approach remains controversial. This study aimed to evaluate the efficacy of opioids combined with Sodium Aescinate in blunt thoracic trauma management.</p><p><strong>Methods: </strong>Fifty patients with blunt thoracic trauma were randomly assigned to receive either opioids alone (morphine hydrochloride sustained-release tablets (MHST), Group A) or opioids combined with Sodium Aescinate (Group B). Pain scores, respiratory parameters, complications, and hospitalization metrics were assessed.</p><p><strong>Results: </strong>When pain number rating scale (NRS) scores reached ≤4, Group B required significantly lower opioid doses throughout therapy. Group B demonstrated significantly higher FEV1, FVC, and arterial PO2, and lower PCO2 compared to Group A, while respiratory rates remained similar between groups. Opioid-related complications (nausea, constipation) were significantly reduced in Group B, which also experienced shorter hospital stays and lower costs.</p><p><strong>Conclusion: </strong>This study demonstrated synergism between opioids and Sodium Aescinate in providing effective analgesia. The combination therapy offers an efficient and economical approach for pain management in blunt thoracic trauma, with improved respiratory function and reduced opioid-related complications.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1623916"},"PeriodicalIF":4.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232095","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":"ADAM17 as a promising therapeutic target: from structural basis to inhibitor discovery in human diseases.","authors":"Lisa Liu, Erkang Tian, Shuqi Quan, Chongying Su, Jiawei Zhou, Sijia Hu, Nanyan Bian, Shufang Du, Juan Li","doi":"10.3389/fphar.2025.1640090","DOIUrl":"https://doi.org/10.3389/fphar.2025.1640090","url":null,"abstract":"<p><p>A disintegrin and metalloproteinase 17 (ADAM17) is a transmembrane protease that regulates diverse physiological processes by shedding membrane-bound proteins, including cytokines, their receptors, and adhesion molecules. A mounting body of evidence has emerged linking ADAM17 to the pathogenesis of various diseases, including inflammation, cancer, cardiovascular and neurodegenerative diseases, highlighting its potential as a therapeutic target. This review offers a comprehensive overview of the molecular structure and biological functions of ADAM17, emphasizing its role in human diseases and therapeutic strategies that target ADAM17 activity. Recent advances in the development of ADAM17-targeting agents, including small-molecule inhibitors, monoclonal antibodies, and endogenous regulatory proteins, are discussed with a focus on the structural basis of their activity, with the aim of informing and guiding future drug discovery efforts.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1640090"},"PeriodicalIF":4.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232107","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":"Constructing Scissor+ risk model to predict prognosis and immunotherapy responses in PAAD by integrating bulk and single-cell RNA sequencing data.","authors":"Gaofei Zhang, Jiao Yu, Fan Zhang, Fang Wang, Congya Zhou","doi":"10.3389/fphar.2025.1646840","DOIUrl":"https://doi.org/10.3389/fphar.2025.1646840","url":null,"abstract":"<p><strong>Background: </strong>This study focused on epithelial cells to construct a prognostic risk model and provide targeted insights into responses to immunotherapy.</p><p><strong>Methods: </strong>Single-cell RNA sequencing (scRNA-seq) was clustered using Uniform Manifold Approximation and Projection (UMAP) and a risk model was developed through Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Kaplan-Meier analysis was performed to evaluate the prognosis of PAAD. The biological characteristics of LIPH were assessed using CCK-8, colony formation and Transwell assays.</p><p><strong>Results: </strong>Eight major cell clusters were identified, revealing two developmental trajectories for malignant epithelial cells from primary to metastases. Epithelial cells were categorized into Scissor+ and Scissor- subtypes, with Scissor+ epithelial cells exhibiting more complex cellular communication with TME cells. Furthermore, we successfully developed a risk model for PAAD patients based on the Scissor findings. The prognosis for PAAD patients in the high-risk group was significantly poorer within both the TCGA and ICGC cohorts. Differences were observed in the populations of naïve B cells, CD8 T cells, M0 macrophages, and activated dendritic cells in different groups. Knockdown of LIPH significantly inhibited the growth and invasion of PAAD cells.</p><p><strong>Conclusion: </strong>These findings underscore the significance of this risk model in predicting prognosis and immunotherapy responses, and enhancing understanding of tumor microenvironment (TME) heterogeneity in PAAD metastases.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1646840"},"PeriodicalIF":4.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232020","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":"Advancing drug safety in psychiatry: insights from pharmacogenomics of hypersensitivity reactions.","authors":"Hamid A Alhaj, Jana Samara, Alyamama Alnamous, Rama Karima, Maha Saber-Ayad","doi":"10.3389/fphar.2025.1651898","DOIUrl":"https://doi.org/10.3389/fphar.2025.1651898","url":null,"abstract":"<p><p>Drug hypersensitivity reactions (DHRs) to psychiatric medications represent a significant clinical challenge, often resulting in treatment discontinuation, poor adherence, and compromised patient outcomes. Pharmacogenomics has emerged as a promising field for understanding and mitigating these adverse effects by identifying genetic predispositions that affect drug metabolism, immune responses, and individual susceptibility. This narrative review explores the multifaceted mechanisms underlying DHRs, with a focus on immunological pathways, particularly T cell-mediated responses, drug metabolite formation, and genetic risk factors. Among these, human leukocyte antigen (HLA) alleles and polymorphisms in cytochrome P450 (CYP450) enzymes are critical contributors to hypersensitivity development. We provide a comprehensive analysis of pharmacogenomic associations with commonly prescribed psychiatric drugs, including anticonvulsants (e.g., carbamazepine, lamotrigine), selective serotonin reuptake inhibitors (SSRIs), and novel agents such as vortioxetine, psilocybin, and esketamine. Additionally, we examine antipsychotics, including clozapine and newer agents like aripiprazole, brexpiprazole, and cariprazine, highlighting specific gene-drug interactions and known risk alleles such as <i>HLA-B*15:02, HLA-A*31:01</i>, and variants in <i>CYP2D6</i> and <i>CYP1A2</i>. These findings underscore the value of pharmacogenomic testing in predicting and preventing serious DHRs, such as Stevens-Johnson Syndrome, toxic epidermal necrolysis, agranulocytosis, and hepatotoxicity. The review also addresses clinical implementation, discussing the role of pre-emptive genetic screening, emerging guidelines from international consortia such as CPIC and DPWG, and real-world challenges, including variability in test accessibility, ethical concerns, and a lack of standardized protocols across regions. Recent advances in next-generation sequencing and multiomic approaches offer new opportunities to improve predictive accuracy and personalize psychiatric treatment further. Finally, we highlight the importance of population-specific research and global collaboration to close the evidence gap, particularly in underrepresented regions like the Middle East. This review emphasizes the transformative potential of pharmacogenomics in optimizing psychiatric drug therapy, enhancing safety, and ultimately improving patient-centered care.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1651898"},"PeriodicalIF":4.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232070","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":"Exploring the top 30 drugs associated with drug-induced thrombotic microangiopathy based on the FDA adverse event reporting system.","authors":"Yi Yin, Fanmin Meng, Yanjiao Fan","doi":"10.3389/fphar.2025.1658963","DOIUrl":"https://doi.org/10.3389/fphar.2025.1658963","url":null,"abstract":"<p><strong>Background: </strong>Drug-induced thrombotic microangiopathy (TMA) significantly impacts patient health and quality of life. This study aims to conduct an exploratory analysis of TMA reports and the most frequently associated drugs in the FDA Adverse Event Reporting System (FAERS) database.</p><p><strong>Methods: </strong>We analyzed FAERS reports associated with TMA from the first quarter of 2004 to the fourth quarter of 2024. A disproportionality analysis was conducted to detect significant safety signals. Potential causative drugs were identified, and the top 30 medications with the highest number of TMA reports and strongest signal strengths were ranked accordingly.</p><p><strong>Results: </strong>Analysis of 22,375,298 reports in the FAERS database identified 13,748 cases of thrombotic microangiopathy (TMA). Among the top 30 medications potentially associated with drug-induced TMA, antineoplastic and immunomodulatory agents predominated both in reporting frequency and signal strength metrics. Disproportionality analysis specifically revealed multiple drugs not currently labeled for TMA risk, with antineoplastic agents comprising the majority. Notably, several less frequently implicated agents - including micafungin, foscarnet, ketoprofen, and atovaquone - also demonstrated significant associations. These pharmacovigilance signals require cautious interpretation given the inherent limitations in establishing definitive causality through spontaneous reporting data.</p><p><strong>Conclusion: </strong>Our comprehensive analysis of drug rankings and signal strengths associated with TMA in FAERS underscores the critical role of pharmacovigilance in identifying and understanding drug-induced TMA. These findings necessitate further research to validate the observed associations and to develop effective risk management strategies, ultimately improving patient outcomes. This study provides valuable evidence to support the accurate clinical identification of drug-related TMA.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1658963"},"PeriodicalIF":4.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232073","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 gastrointestinal adverse effects of GLP-1 receptor agonists and multi-target analogs in type 2 diabetes: a Bayesian network meta-analysis.","authors":"Xingmiao Xie, Shuiyuan Yang, Shuzhen Deng, Yuying Liu, Zhibin Xu, Binghong He","doi":"10.3389/fphar.2025.1613610","DOIUrl":"https://doi.org/10.3389/fphar.2025.1613610","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to evaluate and compare the gastrointestinal adverse effects associated with different GLP-1 receptor agonists (GLP-1RAs) and multi-target analogs in patients with type 2 diabetes mellitus (T2DM) using a Bayesian network meta-analysis.</p><p><strong>Methods: </strong>A systematic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov was conducted to identify randomized controlled trials (RCTs) assessing the gastrointestinal adverse events of GLP-1RAs in T2DM patients. Inclusion criteria included adult patients with confirmed T2DM receiving any GLP-1RA, with the outcomes focused on gastrointestinal adverse events such as nausea, vomiting, diarrhea, constipation, dyspepsia, and reduced appetite. Bayesian network meta-analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the comparison of gastrointestinal side effects among different GLP-1RAs.</p><p><strong>Results: </strong>A total of 48 RCTs involving 27,729 participants were included in the analysis. The overall incidence of gastrointestinal adverse events was 11.66%, with nausea being the most frequent (21.49%) and reduced appetite the least frequent (5.49%). Tirzepatide had the highest risk of inducing nausea and diarrhea, while dulaglutide and lixisenatide had the lowest risks. Exenatide exhibited the highest incidence of vomiting, while dulaglutide showed a lower risk. Semaglutide demonstrated a significantly higher risk of diarrhea compared to other GLP-1RAs.</p><p><strong>Conclusion: </strong>This study highlights significant differences in the gastrointestinal adverse event profiles of various GLP-1RAs. Tirzepatide exhibited the highest risk of gastrointestinal side effects, whereas dulaglutide and exenatide showed relatively better tolerability. These findings provide valuable insights for clinicians to make informed treatment decisions, emphasizing the importance of individualized therapy based on patient tolerance.</p><p><strong>Systematic review registration: </strong>CRD42024592308.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1613610"},"PeriodicalIF":4.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232050","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":"Cannabidiol combined with GABAergic drugs but not with sodium channel blockers prevents the development of drug-resistance seizures in a preclinical model.","authors":"Monserrat Fuentes-Mejia, Maximiliano J Fallico, Alan Talevi, Luciana Gavernet, Sandra A Orozco-Suárez, Luisa Rocha","doi":"10.3389/fphar.2025.1644018","DOIUrl":"https://doi.org/10.3389/fphar.2025.1644018","url":null,"abstract":"<p><p>Drug resistance affects 30% of patients with epilepsy. Cannabidiol (CBD) decreases the expression of drug-resistant seizures in specific syndromes. However, it is unknown if CBD prevents the development of drug-resistant condition in epilepsy. This research was conducted to investigate if subchronic administration of CBD with sodium channel blockers modifies the mortality associated with clonic-tonic seizures and the development of the drug-resistant phenotype induced by subchronic administration of 3-mercaptopropionic acid (3-MP) in rats. These effects were compared with those elicited by antiseizure medications acting on the GABA_A receptors. Male Wistar rats were used to evaluate CBD combined with different antiseizure medications (phenobarbital, diazepam, valproic acid, lamotrigine and oxcarbazepine) during the repetitive administration of 3-MP. The mortality rate and development of drug-resistant seizures were estimated. Computational experiments explored interactions between CBD and sodium channel blockers in the NaV1.7 receptor. Subchronic administration of CBD alone did not modify neither the mortality rate nor the development of drug-resistant seizures. CBD combined with phenobarbital or diazepam reduced the mortality rate and prevalence of drug-resistant seizures. In contrast, coadministration of CBD with valproic acid or lamotrigine did not modify neither the mortality rate nor the expression of drug-resistant seizures. Contrariwise, combining CBD with oxcarbazepine at ED₅₀ increases the incidence of drug-resistant seizures. Computational experiments suggested that CBD acting on NaV1.7 interferes with the action of sodium channel blockers and precludes their inhibitory effects. Our results indicate that repeated administration of CBD with GABAergic antiseizure medications, but not sodium channel blockers, decreases the mortality and prevents the development of the drug-resistant phenotype induced by repeatedly provoked severe seizures.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1644018"},"PeriodicalIF":4.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232112","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":"Exploration of the role of <i>Fomitopsis officinalis Ames</i> in the treatment of gastric cancer using network pharmacology, molecular docking, and in vitro experiments.","authors":"Xue Guan, Dazhong Chen","doi":"10.3389/fphar.2025.1656365","DOIUrl":"https://doi.org/10.3389/fphar.2025.1656365","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Gastric cancer (GC) is one of the most common malignant tumors worldwide, with approximately one million people diagnosed with gastric cancer each year. Although the incidence and mortality rates of gastric cancer have decreased in recent years, it remains the third leading cause of cancer-related deaths globally. &lt;i&gt;Fomes officinalis Ames&lt;/i&gt; (FOA), also known as A LI HONG or deciduous matsutake, the dried fruiting body of medicinal polypore fungus belongs to the Polyporaceae family. It is traditionally used in Chinese medicine to relieve coughs and asthma, dispelling wind and dampness, reducing swelling, and alleviating pain. However, the role of FOA in the treatment of gastric cancer remains unknown. This study systematically elaborates on the therapeutic effect of FOA triterpenic acids on human gastric cancer MKN-45 cells, providing a theoretical basis for their development as natural-sourced anti-tumor drugs. Future research could further explore their molecular targets, tap into the application value of FOA triterpenic acids in the comprehensive treatment of GC, and offer new strategies for the integrated traditional Chinese and Western medicine treatment of GC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this study, a network pharmacology approach was employed to identify relevant targets from drug and disease-related databases. The five active components of FOA were retrieved from the Swiss Target Prediction (http://www.swisstargetprediction.ch/) database, and 379 drug active component targets were predicted. A total of 14,092 gastric cancer targets were retrieved from the GeneCards (https://www.genecards.org/) database using the keyword \"gastric cancer\". Venny 2.1 was used to analyze the intersections, and a protein-protein interaction (PPI) network was constructed. The PPI network contains 328 nodes and 4,486 edges. Core targets were visualized and analyzed using Cytoscape software. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to elucidate the associated biological functions and signaling pathways. Meanwhile, molecular docking of core targets with the main chemical components of FOA was performed using AutoDock software. Finally, &lt;i&gt;in vitro&lt;/i&gt; experiments were conducted using human gastric cancer MKN-45 cells to validate the findings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Network pharmacology and molecular docking studies have shown that the triterpenic acid components in FOA exhibit strong molecular binding affinity with the core targets CASP3 and EGFR. They also predict that FOA may exert anti-gastric cancer effects by regulating pathways such as neuroactive ligand-receptor interaction and cancer-related pathways. Additionally, a method for extracting and purifying FOA triterpenic acids was successfully established, with its methodological validation meeting the required standards; chromatographic peaks of triterpenic acid indicator components","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1656365"},"PeriodicalIF":4.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232115","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":"Rational design of indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors featuring 1,2,3-triazole derivatives with enhanced anti-inflammatory and analgesic efficacy.","authors":"Qingying Liu, Xixi Hou, Yueliang Wang, Mingyue Tian, Baoyu He, Jingjing Guo, Jianxue Yang","doi":"10.3389/fphar.2025.1574007","DOIUrl":"https://doi.org/10.3389/fphar.2025.1574007","url":null,"abstract":"<p><p>This study applied a target-based drug design approach focused on the IDO1 enzyme, which features a heme active site. By introducing a 1,2,3-triazole moiety capable of coordinating with the ferrous ion in heme, a series of 2H-benzo[b][1,4]oxazin-3(4H)-one derivatives were designed. Enzyme assays demonstrated that these compounds generally inhibited IDO1 activity, with Compound <b>14e</b> showing the most potent effect, achieving an IC₅₀ value of 3.63 μM. Molecular docking studies indicated that the 1,2,3-triazole ring in Compound <b>14e</b> is positioned directly above the heme, forming a coordination bond with the ferrous ion. Additionally, it engages in π-π interactions with Phe263, while the amide group of the 2H-benzo[b][1,4]oxazin-3(4H)-one scaffold forms hydrogen bonds with Lys238. <i>In vivo</i> experiments in mice showed that Compound <b>14e</b> significantly reduced CFA-induced upregulation of Iba1 in the spinal dorsal horn and alleviated mechanical hypersensitivity, thermal hyperalgesia, and spontaneous pain. Moreover, treatment with Compound <b>14e</b> led to a significant reduction in the levels of pro-inflammatory cytokines TNF-α and IL-1β in CFA-treated mice. Importantly, Compound <b>14e</b> demonstrated a favorable safety profile, with no observed toxicity in major organs, highlighting its potential as a promising anti-inflammatory and analgesic agent targeting IDO1.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1574007"},"PeriodicalIF":4.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232128","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":"Multidisciplinary administrative-professional-technical interventions to optimize antibiotic use and reduce resistance in a tertiary general hospital.","authors":"Jingjing Han, Meiyu Shen, Yan Rao","doi":"10.3389/fphar.2025.1592158","DOIUrl":"https://doi.org/10.3389/fphar.2025.1592158","url":null,"abstract":"<p><strong>Introduction: </strong>Antimicrobial stewardship (AMS) is a cornerstone of global antimicrobial resistance (AMR) strategies. However, substantial differences exist in AMS implementation approaches and effectiveness among medical institutions across nations and regions. This study aimed to evaluate strategies focused on antimicrobial usage and AMR in a tertiary general hospital.</p><p><strong>Methods: </strong>This study was conducted in two phases: the baseline phase (January to June in 2023) and the intervention phase (July 2023 to June 2024). During the intervention phase, an innovative AMS strategy integrating multidisciplinary administrative, professional, and technical interventions was implemented to reduce antibiotic use and control antimicrobial resistance.</p><p><strong>Results: </strong>After intervention, the antimicrobial usage rate among inpatients decreased from 56.01% to 52.71% (<i>P</i> < 0.001). The antibiotic use density (AUD) decreased from 50.15 to 35.76 Defined Daily Doses (DDDs) per 100 patient-days (<i>P</i> < 0.001). The antimicrobial usage rates and AUD dropped significantly in medical, surgical, obstetrics and gynecology wards. Moreover, the intervention effect in pediatric wards displayed complex seasonal variation. The AUD for most antibiotic classes was significantly lower after the intervention. The detection rates of carbapenem-resistant <i>Klebsiella pneumoniae</i> and <i>Acinetobacter baumannii</i> decreased from 26.00% to 17.53% and 89.58% to 62.93%, respectively.</p><p><strong>Conclusion: </strong>The findings indicate that a multifaceted AMS strategy, integrating multidisciplinary administrative, professional, and technical interventions, offers a potentially effective strategy for reducing antimicrobial usage and combating AMR in the tertiary general hospital.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1592158"},"PeriodicalIF":4.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232132","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}