Frontiers in Pharmacology最新文献

{"title":"Challenges and hope: latest research trends in the clinical treatment and prognosis of liposarcoma.","authors":"Hongliang Liu, Xi Wang, Xiaoyu Wang, Fabo Qiu, Bin Zhou","doi":"10.3389/fphar.2025.1529755","DOIUrl":"10.3389/fphar.2025.1529755","url":null,"abstract":"<p><p>Liposarcoma, as a complex disease, is characterized by intricate interactions between distinct histopathological subtypes and corresponding clinical outcomes, emphasizing the necessity of personalized approaches in diagnosis and treatment strategies. This malignant tumor originating from adipose tissue is classified into different subtypes with specific molecular markers, which not only distinguish them but also guide treatment directions. The main approach for treating liposarcoma is surgical resection, with the aim of complete excision and achieving clean margins (R0 resection) to minimize the risk of recurrence. This surgical principle emphasizes the critical need for precise preoperative planning, and in certain cases, the integration of neoadjuvant therapy may be needed to reduce the tumor to a surgically manageable size. In addition to surgery, systemic therapy plays a key role in the advanced stages of the disease, especially when resistance to traditional treatment arises. The emergence of novel systemic therapies, including chemotherapy, targeted therapy, and immunotherapy, has opened new avenues for treating this challenging malignancy. These systemic therapies are selected on the basis of the specific molecular features of the tumor, highlighting the importance of detailed molecular diagnostics. As our understanding of the molecular basis of liposarcoma deepens, integrating clinical and molecular features is crucial for optimizing treatment outcomes. This comprehensive approach, which combines surgical precision with systemic therapy innovations, will change the treatment landscape for patients with liposarcoma, advancing toward more personalized and effective treatment strategies.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1529755"},"PeriodicalIF":4.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150077","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 research on the utilization of population pharmacokinetic model: a bibliometric analysis from 2000 to 2024.","authors":"Yucheng Yao, Liyuan Zhang, Dan Chen, Shiran Qin, Mingyu Meng, Qiuyan Guo","doi":"10.3389/fphar.2025.1548023","DOIUrl":"10.3389/fphar.2025.1548023","url":null,"abstract":"<p><strong>Objective: </strong>Population pharmacokinetic (PPK) model is capable of identifying the factors that influence the variability of pharmacokinetic (PK) profiles and the degree of their influence, effectively reduces unexplained variability, and demonstrates excellent predictive ability. PPK model has been successfully constructed in several populations for a variety of drugs. However, no study has yet conducted a bibliometric analysis of publications related to the PPK model. This study aims to provide a comprehensive overview of the research progress and hotspots in the field of PPK model research through bibliometric methods.</p><p><strong>Methods: </strong>A systematic search of the Web of Science database was conducted to collect articles and reviews related to the PPK model between 2000 and 2024. We then analyzed the data using Bibliometrix R package, Microsoft Office Excel, CiteSpace and VOSviewers.</p><p><strong>Results: </strong>Between 2000 and 2024, we identified a total of 6,125 papers and 128,856 citations. The average annual growth rate of the relevant publications was 10.35%, showing continued growth momentum. These research outputs are concentrated in North America, Western Europe, and East Asia, with USA leading the way with 2,340 publications and having the highest H-index (93) and total citations (54,965). Uppsala University and <i>British Journal of Clinical Pharmacology</i> are the institutions with the highest publication output and the most influential journals, respectively. Most of the funding agencies are from the USA and the subject categories for most publications are Pharmacology Pharmacy. In terms of author contributions, professor Karlsson MO is the leader in the field with 149 publications. In addition, wo found that \"critically ill patients,\" \"tacrolimus,\" \"machine learning,\" \"external evaluation,\" \"polymyxin b,\" \"voriconazole,\" \"extracorporeal membrane oxygenation,\" \"dose optimization\" and \"model-informed precision dosing\" are current research hotspots and future research trends.</p><p><strong>Conclusion: </strong>This study is the first comprehensive overview of the development of PPK model and research hotspots using bibliometric methods. Our findings provide researchers, especially beginners, with insights into the application area of PPK model, helping them to grasp key information in the field.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1548023"},"PeriodicalIF":4.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150113","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":"Understanding the ancient classic and famous prescriptions <i>via</i> the property of Chinese materia medica.","authors":"Dan Qin, He Zhang, Bin Du, Hui Wang, Ligang Liu, Yun Wang","doi":"10.3389/fphar.2025.1551531","DOIUrl":"10.3389/fphar.2025.1551531","url":null,"abstract":"<p><strong>Background: </strong>Ancient classic and famous prescriptions (ACFPs), derived from traditional Chinese medicine (TCM) classics, are widely utilized due to their precise therapeutic effects and distinctive clinical advantages. Existing research predominantly focuses on individual prescriptions, and there is lack of systematic exploration of medication patterns within the official ACFPs catalog. The property of Chinese materia medica (PCMM), a multidimensional representation of medicinal properties, offers a novel perspective for systematically analyzing TCM formulas.</p><p><strong>Objective: </strong>In this study, we aim to investigate the implicit medication patterns of ACFPs from the PCMM perspective, establish a feature extraction model based on the property combination of Chinese materia medica (PCCMM), and evaluate its effectiveness in representing and reconstructing ACFPs.</p><p><strong>Methods: </strong>Based on the Chinese Pharmacopoeia (ChP), we constructed a CMM-PCCMM network as the forward feature extraction process. We formulated the backward process as a constrained combinatorial optimization problem to rebuild ACFPs from their PCCMMs. We evaluated the performance of PCCMM in reconstructing ACFPs using the Jaccard similarity coefficient. Furthermore, we tested the capability of PCCMM to distinguish ACFPs from random pseudo-formulas and classify ACFPs according to deficiency syndromes. Finally, we conducted frequency analysis, association rule analysis, distance analysis, and correlation analysis to explore the implicit medication patterns of ACFPs based on PCCMM.</p><p><strong>Results: </strong>Numerical experiments showed that PCCMM effectively represented and reconstructed ACFPs, achieving an average Jaccard similarity coefficient above 0.8. PCCMM outperformed the nomenclature of CMM in distinguishing ACFPs from random pseudo-formulas and classifying deficiency syndromes. Frequency analysis revealed that high-frequency CMMs were mainly tonic medicines, whereas high-frequency PCCMMs predominantly mapped to the even-sweet-spleen meridian. The association rule analysis based on PCCMM yielded significantly more implicit compatibility rules than CMM alone. Distance and correlation analyses identified synergistic CMM pairs and PCCMM pairs, such as <i>Jujubae Fructus</i> (Dazao) and <i>Zingiberis Rhizoma Recens</i> (Shengjiang), which is consistent with clinical experience.</p><p><strong>Conclusion: </strong>The PCCMM-based feature extraction model provides a quasi-equivalent representation of TCM formulas, effectively capturing implicit medication patterns within ACFPs. PCCMM outperforms traditional CMM methods in formula reconstruction, classification, and medication pattern mining. This study offers novel insights and methodologies for systematically understanding TCM formulas, guiding clinical application, and facilitating the design and optimization of new TCM formulas.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1551531"},"PeriodicalIF":4.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150080","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":"Evaluation of the pharmacokinetic interactions of montmorillonite powder or loperamide on pyrotinib in healthy volunteers.","authors":"Yike Wang, Dai Li, Tong Zhang, Sumei Xu, Yanxin Zhang, Kaijing Zhao, Shaorong Li, Kai Shen, Xiaomin Li, Pingsheng Xu","doi":"10.3389/fphar.2025.1563556","DOIUrl":"10.3389/fphar.2025.1563556","url":null,"abstract":"<p><strong>Aims: </strong>To investigate the potential pharmacokinetic interactions of montmorillonite powder or loperamide on pyrotinib.</p><p><strong>Methods: </strong>This study was a single-center, open-label, single-dose, fixed-sequence clinical trial conducted with healthy volunteers. The participants were divided into two groups (A and B), each consisting of 18 subjects. Both groups received a single oral dose of 400 mg of pyrotinib on day 1. On day 9, Group A received a single dose of 400 mg of pyrotinib followed by 3 g of montmorillonite powder 2 h later, while Group B received a single dose of pyrotinib and 4 mg of loperamide after breakfast on day 9, followed by single oral doses of 2 mg of loperamide at 2 and 4 h post-administration. Blood samples were collected to determine pyrotinib blood concentrations.</p><p><strong>Results: </strong>In Group A, the combination treatment with montmorillonite powder resulted in a decrease in C_max, AUC_0-t, and AUC_0-∞ by 26.7%, 33.1%, and 32.4%, respectively, compared to pyrotinib alone. In Group B, the combination treatment with loperamide had minimal impact on pyrotinib's absorption rate but slightly increased AUC_0-t and AUC_0-∞ by approximately 18% and 19%, respectively, while decreasing CL/F and prolonging the t_1/2.</p><p><strong>Conclusion: </strong>Even when montmorillonite powder was administered 2 h after pyrotinib dosing, it still reduced systemic exposure of pyrotinib by 32.4% in AUC_0-∞. In contrast, loperamide increased pyrotinib exposure by 19% in AUC_0-∞ when used together. Based on these findings, loperamide is recommended for symptom control, while montmorillonite powder should not be co-administered with pyrotinib or any drug requiring optimal absorption.</p><p><strong>Clinical trial registration: </strong>[ClinicalTrials.gov], identifier [NCT05252546].</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1563556"},"PeriodicalIF":4.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156659","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":"Osmotic laxatives do not alter dabigatran plasma concentration in healthy volunteers - a randomized, controlled, cross-over trial.","authors":"Matthias Weiss-Tessbach, Al Medina Dizdarevic, Alexander Kupis, Thorsten Bischof, Christa Firbas, Peter Quehenberger, Ulla Derhaschnig, Max Frimmel, Bernd Jilma, Christian Schoergenhofer","doi":"10.3389/fphar.2025.1579014","DOIUrl":"10.3389/fphar.2025.1579014","url":null,"abstract":"<p><strong>Background: </strong>Laxatives are among the most commonly used pharmacological agents worldwide. Available data indicate a significant potential for clinically relevant drug-drug interactions. We hypothesized that osmotic laxatives may reduce the oral bioavailability of the direct oral anticoagulant dabigatran and thereby its anticoagulant effects.</p><p><strong>Methods: </strong>In the first part of this single-centre, randomized, double-blind, crossover trial, 24 healthy volunteers received 150 mg dabigatran with placebo (10 g glucose) or 20 g lactulose. In the second, open label part, eight of these 24 healthy volunteers were randomly assigned to receive dabigatran with either 27.6 g macrogol, 30 g flaxseeds, or to receive 20 g lactulose 4-h after dabigatran intake. We measured dabigatran plasma concentrations using an ecarin-based chromogenic assay and calculated the pharmacokinetic parameters. Statistical analysis was performed using a linear mixed-effects model on log-transformed AUC values.</p><p><strong>Results: </strong>The main pharmacokinetic parameters AUC, C_max, T_max, or t_1/2 did not differ significantly between most treatment periods. A reduction in AUC was observed with flaxseed compared to placebo. Dabigatran's pharmacokinetics remained unaffected by concomitant intake of lactulose or macrogol. There was a high inter- and intra-individual variability in the pharmacokinetics of dabigatran.</p><p><strong>Conclusion: </strong>In this study osmotic laxatives such as lactulose, macrogol or flaxseeds did not affect the pharmacokinetics of dabigatran in healthy individuals. These findings support the safe concurrent use of dabigatran with osmotic laxatives.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1579014"},"PeriodicalIF":4.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150143","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":"Hydrogen sulfide as a new therapeutic target of pulmonary hypertension: an overview with update on immunomodulation.","authors":"Xue-Xue Zhu, Chen-Yang Zhao, Qing-Bo Lu, Ao-Yuan Zhang, Xin-Yu Meng, Jia-Bao Su, Guo Chen, An-Jing Xu, Hai-Jian Sun, Xiao-Wei Nie","doi":"10.3389/fphar.2025.1510275","DOIUrl":"10.3389/fphar.2025.1510275","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is a complex and progressive vascular disease characterized by elevated pulmonary arterial pressure (PAP) and vascular resistance, leading to right ventricular failure and, ultimately, death. Current therapies primarily focus on vasodilation and symptom management, but there remains a critical need for treatments that address the underlying pathophysiological mechanisms of PH. Numerous studies have identified hydrogen sulfide (H₂S) as a potential therapeutic target in PH. Traditionally recognized for its toxic effects at high concentrations, H₂S is now known to play crucial roles in various physiological processes, including vasodilation, anti-inflammation, and antioxidation, which are relevant to PH pathogenesis. Given its multifaceted roles in the pathophysiology of PH, H₂S represents a promising therapeutic target. Strategies to enhance endogenous H₂S production or administer exogenous H₂S donors are being explored as potential treatments for PH. These approaches aim to harness the vasodilatory, anti-inflammatory, antioxidant, and anti-remodeling properties of H₂S to mitigate disease progression and improve patient outcomes. Future research should focus on optimizing H₂S-based therapies and exploring their clinical efficacy and safety in PH patients.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1510275"},"PeriodicalIF":4.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150139","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 mechanisms and targets of proton pump inhibitors-induced osteoporosis through network toxicology, molecular docking, and molecular dynamics simulations.","authors":"Yaqi Mu, Yaqi Zhou, Xinan Zhang, Yiming Shao","doi":"10.3389/fphar.2025.1592048","DOIUrl":"10.3389/fphar.2025.1592048","url":null,"abstract":"<p><strong>Background: </strong>Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related disorders, but long-term use has been increasingly associated with an elevated risk of osteoporosis. However, the underlying molecular mechanisms and specific targets of PPIs-induced bone loss remain poorly understood. This study aimed to explore the molecular mechanisms and key genes of PPIs-induced osteoporosis using network toxicology, molecular docking, and molecular dynamics simulations.</p><p><strong>Methods: </strong>We identified common targets of four widely used PPIs (omeprazole, lansoprazole, pantoprazole, and rabeprazole) and osteoporosis by screening large-scale biological databases. A protein-protein interaction network was constructed, and key hub genes were determined based on topological parameters such as degree, betweenness centrality, and closeness centrality. Enrichment analysis was performed to explore the biological processes, cellular components, molecular functions, and KEGG pathways associated with the overlapping targets. Molecular docking was conducted to evaluate the binding affinities between PPIs and their potential targets, and molecular dynamics simulations were employed to assess the stability of these interactions over time.</p><p><strong>Results: </strong>We identified 35 potential targets for omeprazole-induced osteoporosis, 39 for lansoprazole, 29 for pantoprazole, and 29 for rabeprazole. Topological analysis of the protein-protein interaction networks revealed the hub genes for each PPI: epidermal growth factor receptor (EGFR) for omeprazole, estrogen receptor 1 (ESR1) for lansoprazole, EGFR for pantoprazole, and Proto-oncogene tyrosine-protein kinase SRC for rabeprazole. Molecular docking demonstrated strong and stable binding affinities between PPIs and their respective targets, with binding energies all below -5 kcal/mol. Molecular dynamics simulations confirmed the structural stability of these complexes, characterized by low root mean square deviation and root mean square fluctuation values and consistent hydrogen bond formation.</p><p><strong>Conclusion: </strong>This study identified EGFR, ESR1, and SRC as key regulatory genes in PPIs-induced osteoporosis, highlighting their roles in bone metabolism. The stable interactions between PPIs and these targets suggest their involvement in bone loss, providing a foundation for future experimental validation.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1592048"},"PeriodicalIF":4.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150109","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":"Fuzheng Jiedu granules against disease progression among high-risk adults with non-severe COVID-19: a multicenter retrospective cohort study.","authors":"Qiaoli Hua, Danwen Zheng, Jingwei Shui, Tong Zhang, Shengle Qin, Hanhong Zhang, Bo Yu, Longde Wang, Hailang He, Xinghua Tan, Qiumin Chen, Yang Yang, Weng Heng, Yihang Cai, Xiaohua Xu, Qing Liu, Yuntao Liu, Rongyuan Yang, Zhongde Zhang","doi":"10.3389/fphar.2025.1523004","DOIUrl":"10.3389/fphar.2025.1523004","url":null,"abstract":"<p><strong>Background: </strong>Fuzheng Jiedu (FZJD) granules are widely used to treat coronavirus disease (COVID-19) since their market approval, but their clinical effectiveness remains uncertain. In this study, we aimed to evaluate the effectiveness of FZJD in reducing disease progression in high-risk adults with COVID-19.</p><p><strong>Methods: </strong>A multicenter, retrospective cohort study involving high-risk adults with non-severe COVID-19 was conducted in China from May 2021 to December 2022. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2200058097; https://www.chictr.org.cn/bin/project/edit?pid=160010). Patients were categorized into two groups based on the administration of FZJD granules. The outcomes included disease progression, mechanical ventilation, intensive care unit (ICU) admission, and mortality. Propensity-score analyses and multivariable regression were performed to assess the effectiveness of FZJD granules. The effectiveness was further analyzed in different subgroups.</p><p><strong>Results: </strong>A total of 1,644 patients (54.7% female patients; mean age, 62.3 years) were included, with 27.4% (451/1,644) receiving FZJD granules. After propensity score matching (PSM), 320 FZJD granule receivers and 320 non-receivers were matched. Those receiving FZJD granules were associated with lower risks of disease progression [adjusted odds ratio (OR), 0.21; 95% confidence interval (CI), 0.06-0.73], mechanical ventilation (OR, 0.15; 95% CI, 0.03-0.66), and ICU admission (OR, 0.08; 95% CI, 0.01-0.64) than those not receiving FZJD granules. The lower risk of disease progression in the FZJD group was confirmed by multivariable regression analysis and various propensity-score analyses. Furthermore, subgroup analyses demonstrated significant treatment benefits in patients with moderate COVID-19 at admission (no progression to severe disease) or in those who were not fully vaccinated (OR, 0.06; 95% CI, 0.01-0.50).</p><p><strong>Conclusion: </strong>FZJD administration was significantly associated with a reduced risk of disease progression in high-risk adults with mild-to-moderate COVID-19.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1523004"},"PeriodicalIF":4.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150111","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":"Mucoprotectants and gut barrier: mechanisms of action and clinical applications in IBS. Is there a possible role?","authors":"Francesco Rettura, Christian Lambiase, Riccardo Tedeschi, Antonio Grosso, Lorenzo Cancelli, Angelo Ricchiuti, Andrea Bottari, Luca Giacomelli, Nicola de Bortoli, Massimo Bellini","doi":"10.3389/fphar.2025.1538791","DOIUrl":"10.3389/fphar.2025.1538791","url":null,"abstract":"<p><p>Impaired gut barrier function plays a pivotal role in the pathophysiology of irritable bowel syndrome (IBS), particularly in IBS with diarrhea. Mucoprotectants, such as xyloglucan, gelatin tannate and pea protein tannins, offer a novel therapeutic approach by restoring intestinal permeability and reducing inflammation. This review assesses preclinical and clinical evidence supporting mucoprotectants in IBS with diarrhea management. Preclinical studies indicate their efficacy in reducing intestinal permeability and inflammation, while clinical trials demonstrate improvements in stool consistency, abdominal pain and bloating. Despite these promising results, comparative studies are needed to establish the superiority of specific mucoprotectants and their optimal use in clinical practice.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1538791"},"PeriodicalIF":4.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150141","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":"CDK4/6 inhibitors in breast cancer therapy: mechanisms of drug resistance and strategies for treatment.","authors":"Tong Gao, Ying Sun, Ping Leng, Donghua Liu, Qie Guo, Jing Li","doi":"10.3389/fphar.2025.1549520","DOIUrl":"10.3389/fphar.2025.1549520","url":null,"abstract":"<p><p>Dysregulated cell cycle progression is a well-established hallmark of cancer, driving the development of targeted antitumor therapies that intervene at specific phases of the cell cycle. Among these therapeutic targets, cyclin-dependent kinases 4 and 6 (CDK4/6) have emerged as critical regulators of cell cycle progression, with their aberrant activation being strongly implicated in tumorigenesis and cancer progression. Currently, multiple CDK4/6 inhibitors have received clinical approval for hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, demonstrating dual therapeutic mechanisms through both cell cycle arrest and enhancement of antitumor immunity. However, clinical implementation faces two major challenges: the inevitable development of acquired resistance during prolonged treatment, and the need for optimized combination strategies with other anticancer agents to achieve synergistic efficacy. This review systematically examines the molecular mechanisms underlying CDK4/6 inhibitor function and characterizes currently approved therapeutic agents. Importantly, it synthesizes recent discoveries regarding resistance mechanisms, including dysregulated cell cycle checkpoints, compensatory signaling pathway activation, and tumor microenvironment adaptations. Furthermore, we critically evaluate emerging combination therapeutic approaches targeting these resistance mechanisms. By integrating mechanistic insights with clinical evidence, this analysis aims to provide actionable strategies for overcoming therapeutic resistance and maximizing the clinical potential of CDK4/6 inhibitors in breast cancer management.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1549520"},"PeriodicalIF":4.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150076","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}