Frontiers in Pharmacology最新文献

{"title":"Low-molecular-weight heparins utilization in pregnant and postpartum women: a real-world analysis in China (2016-2021).","authors":"Hao-Ran Liu, Kai Sun, Tao Zeng, Xian-Li Wang","doi":"10.3389/fphar.2025.1519051","DOIUrl":"10.3389/fphar.2025.1519051","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to examine trends in low-molecular-weight heparin (LMWH) use for managing pregnancy-associated venous thromboembolism (VTE) and to explore the correlation between pregnancy-related VTE risk factors and LMWH prescription rates.</p><p><strong>Methods: </strong>This was a cross-sectional study that analyzed prescription data from pregnant and postpartum women using LMWH to manage VTE, collected during 2016-2021. Risk factors associated with VTE were analyzed. Separately comparing the number of prescriptions, prescription cost, defined daily doses (DDDs), and defined daily cost (DDC) of seven LMWH.</p><p><strong>Results: </strong>This study included 41,885 prescriptions, with the average age of patients being 32 ± 4.69 years old. The most common risk factors for VTE during pregnancy and the postpartum period in this study included advanced age (>35 years old), cesarean section, diabetes, miscarriage, and preterm birth, accounting for 28.61%, 25.60%, 18.34%, 17.31%, and 13.63% respectively. There was a 173% increase in LMWH prescription costs during the study period. In terms of number of prescriptions, prescription cost, and DDDs, enoxaparin sodium, nadroparin calcium, and low-molecular-weight heparin calcium consistently ranked in the top three from 2019 to 2021. In terms of DDC, low-molecular-weight heparin sodium, dalteparin sodium, and enoxaparin sodium were the lowest.</p><p><strong>Conclusion: </strong>From 2016 to 2021, both the number of prescriptions and the total prescription costs for the management of VTE during pregnancy and the postpartum period increased. Enoxaparin sodium, nadroparin calcium, and low-molecular-weight heparin calcium were the most common LMWH. Advanced age (>35 years old), cesarean section, diabetes, miscarriage, and preterm birth were the most common pregnancy-related VTE risk factors linked to LMWH prescription.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1519051"},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803074","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":"Atractylenolide-I restore intestinal barrier function by targeting the S100A9/AMPK/mTOR signaling pathway.","authors":"Chen Chen, Bingjie Sun, Keming Chen, Han Bao, Yu Tao, Jinyong Zhou, Xiaomin Yuan, Linhai He, Zhihua Lu, Kaidi Chen, Yang Li, Chengli Yu, Yugen Chen, Yinan Zhang","doi":"10.3389/fphar.2025.1530109","DOIUrl":"10.3389/fphar.2025.1530109","url":null,"abstract":"<p><p>Impaired intestinal epithelial barrier function is closely associated with the pathogenesis of ulcerative colitis (UC). Atractylenolide-I (AT-I), a major sesquiterpene derived from the herb <i>Atractylodes macrocephala</i> Koidz., has been reported to alleviate DSS-induced colitis in mice. This study aims to investigated the protective effects of AT-1 on intestinal epithelial barrier function and elucidate it's underlying mechanisms. <i>In vivo</i>, an acute colitis model was established in mice, and transcriptomic analysis to identify differentially expressed genes. <i>In vitro</i>, overexpression plasmids and recombinant protein were used to evaluate their effects on intestinal barrier function, and further analysis of its potential mechanisms.The study found that AT-1 ameliorate DSS-induced acute ulcerative colitis, exhibiting protective effects on the intestinal barrier. Transcriptomic analysis revealed that AT-1 significantly modulated the expression of S100A8 and S100A9. Further investigations indicated that S100A9, rather than S100A8, mediated the expression of tight junction proteins, meanwhile, AT-1 reduces neutrophil activation and subsequent release of S100A9. Mechanistically, recombinant human S100A9 protein was found to induce a decrease in intracellular Ca²⁺ concentration, while AT-1 regulated the expression of tight junction proteins <i>via</i> modulation of the AMPK/mTOR signaling pathway. AT-1 enhances the recovery of DSS-induced intestinal barrier dysfunction by regulating the recombinant human S100A9 protein-mediated AMPK/mTOR signaling pathway. This study provides new insights into the pathogenesis of ulcerative colitis and suggests potential therapeutic strategies for its treatment.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1530109"},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802994","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":"Chitinase 3-like protein 1 deficiency ameliorates drug-induced acute liver injury by inhibition of neutrophil recruitment through lipocalin-2.","authors":"Ji Hye Kim, In Jun Yeo, Dong Ju Son, Sang Bae Han, Do Young Yoon, Dong Hun Lee, Jin Tae Hong","doi":"10.3389/fphar.2025.1548832","DOIUrl":"10.3389/fphar.2025.1548832","url":null,"abstract":"<p><p>Chitinase-3-like protein 1 (Chi3l1) is a member of the mammalian Chitinase-like protein family, and several studies reported that Chi3l1 is associated with various inflammatory diseases as well as liver diseases. Acetaminophen (APAP) is usually used for antipyretic drug, but its overdose induces acute liver injury (ALI). Several studies reported that subsequent inflammatory responses of the immune system play a critical role in the severity and outcome of APAP-induced ALI. In the present study, we investigated the role of Chi3l1 and its mechanism during APAP-induced ALI using Chi3l1 knock-out (KO) mice. We explored the function of Chi3l1 using APAP-injected KO mice and sought proteins associated with Chi3l1 through biological research data program for investigating mechanism. Liver histological analysis revealed that APAP-induced ALI was attenuated in KO mice compared to wild-type (WT) mice. We observed that APAP-induced neutrophil infiltration was decreased in the liver of KO mice compared to WT mice. To investigate this mechanism, we sought proteins potentially associated with Chi3l1 by mRNA sequencing and protein correlation analysis data. We found lipocalin-2 (Lcn2) and examined Chi3l1, Lcn2, and their relationship in the APAP-induced ALI model using recombinant proteins and antibodies. Our results suggest that Chi3l1 deficiency ameliorates APAP-induced liver injury through abrogating Lcn2-mediated neutrophil infiltration in the liver.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1548832"},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803033","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":"Blind docking methods have been inappropriately used in most network pharmacology analysis.","authors":"Xinhao Che, Lei Zhang","doi":"10.3389/fphar.2025.1566772","DOIUrl":"10.3389/fphar.2025.1566772","url":null,"abstract":"<p><p>Network pharmacology methods have bridged the gap between traditional Chinese medicine (TCM) theory and contemporary pharmacological research and have been widely used in the study of multi-component, multi-target mechanisms of action of TCM. Molecular docking <i>in silico</i> is typically used after network analysis to validate the binding between protein targets and active components of TCM. However, unreasonable docking methods, especially the abuse of blind docking, have raised doubts about the docking results. This paper expresses concern about the above phenomenon based on a comprehensive assessment of the accuracy of the blind docking methods and calls for the correct use of docking methods to make the results of network analysis and experiments more convincing.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1566772"},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803017","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":"Mechanisms mediating effects of cardiotonic steroids in mammalian blood cells.","authors":"Yuri M Poluektov, Olga D Lopina, Maria A Strelkova, Iuliia D Kuleshova, Alexander A Makarov, Irina Yu Petrushanko","doi":"10.3389/fphar.2025.1520927","DOIUrl":"10.3389/fphar.2025.1520927","url":null,"abstract":"<p><p>Cardiotonic steroids (CTSs) were known as steroidal plant compounds that exert cellular effects by the binding to Na,K-ATPase. Earlier, plant (exogenous) CTSs were used to treat chronic heart failure. By now, endogenous CTS have been identified in mammals, and their concentrations in the blood, normally in a subnanomolar range, are altered in numerous pathologies. This indicates their role as endogenous regulators of physiological processes. CTS transport occurs primarily in the blood, yet the CTS effects on blood cells remain poorly understood. This review summarizes the CTS effects on blood cells of animals and humans under normal and pathological conditions, and analyzes their action based on known mechanisms of action in mammalian cells. At high concentrations (greater than 10^-9 M), CTS binding to Na,K-ATPase inhibits the enzyme, whereas lower concentrations of CTSs induce signaling cascades or activate the enzyme. All these mechanisms are shown to be present in blood cells. The particular CTS effect is determined by the CTS type, its concentration, the isoform composition of the catalytic α-subunit of Na,K-ATPase in the cell, and other cell features. It has been demonstrated that all blood cell types (erythrocytes, leukocytes, and platelets) expressed both ubiquitously distributed α1-isoform and tissue-specific α3-subunit, which exhibits a different ion and CTS affinity compared to α1. This results in a wide spectrum of blood cell responses to fluctuations in CTS levels in the blood. In particular, an increase in the level of endogenous CTSs by a more twofold is sufficient to induce a decline in the activity of erythrocyte Na,K-ATPase. The administration of exogenous CTSs is able to modulate the proinflammatory activity of leukocytes, which is attributed to the activation of signaling cascades, and to exert an influence on platelet activation. Hence, alterations of CTS levels in bloodstream significantly affect the functionality of blood cells, contributing to the organism's adaptive response. On top of this, a comparison of the effects of CTSs on human leukocytes and rodent leukocytes carrying the CTS-resistant α1-isoform often reveals opposite effects, thus indicating that rodents are an unsuitable model for studying CTS effects on these cells.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1520927"},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803076","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":"Identifying acute myeloid leukemia subtypes based on pathway enrichment.","authors":"Ling Zhong, Jiangti Luo, Junze Dong, Xiang Yang, Xiaosheng Wang","doi":"10.3389/fphar.2025.1557112","DOIUrl":"10.3389/fphar.2025.1557112","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and the second most common in children. Despite the introduction of targeted therapies, AML survival rates have shown limited improvement, particularly among older patients. This study explored personalized treatment strategies for AML by proposing a novel subtyping method. Through unsupervised clustering based on the enrichment scores of 14 pathways related to metabolism, immunity, DNA repair, and oncogenic signaling, we identified three AML subtypes: DNA repair (DR), immune-enriched (ImE), and immune-deprived (ImD), consistent in four independent datasets. DR is marked by high expression of DNA repair and metabolic pathways, high stemness and proliferation potential, as well as high sensitivity to chemotherapy. ImD is characterized by low expression of immune and oncogenic pathways, favorable survival prognosis, low mutation rates of <i>RUNX1</i> and <i>TP53</i>, high homeostasis, and low migration potential. ImE exhibits high enrichment of immune and oncogenic pathways, low stemness and proliferation capacity, low homeostasis, high migration potential, and low sensitivity to chemotherapy. Our pathway enrichment-based subtyping approach would offer a promising framework for understanding the molecular heterogeneity of AML and guiding personalized treatment of this disease.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1557112"},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795186","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":"Chinese herbal medicine (Guben Qushi Huayu formula) combined with Ixekizumab in reducing psoriasis vulgaris relapse: Protocol for a mixed-methods research study.","authors":"Ziqing Li, Kewen Guan, Hao Deng, Shuyan Ye, Jingwen Deng, Danni Yao, Yuhong Yan, Haiming Chen, Chuanjian Lu, Jingjie Yu","doi":"10.3389/fphar.2025.1551001","DOIUrl":"10.3389/fphar.2025.1551001","url":null,"abstract":"<p><strong>Introduction: </strong>Psoriasis vulgaris (PV) is an inflammatory, chronically relapsing dermatological disease associated with significant comorbidities. Ixekizumab is recommended as the first-line therapy for severe PV, but encounters persistent challenges with relapse after treatment discontinuation. In clinical practice, Chinese herbal medicine (CHM) including Guben Qushi Huayu formula (GQHF) has been demonstrated effective in reducing PV relapse. However, there remains a scarcity of high-level evidence-based study in this respect. Therefore, this study aims to preliminarily evaluate the feasibility and acceptability of Ixekizumab combined with GQHF in reducing PV relapse.</p><p><strong>Methods and analysis: </strong>This study employs a mixed-method research (MMR) design, encompassing both quantitative and qualitative studies. The quantitative study consists of a randomized controlled trial involving 50 participants with severe PV, who will be randomly allocated to the intervention group (Ixekizumab plus GQHF) and the control group (Ixekizumab plus GQHF placebo) in a 1:1 ratio. Relapse rate is the primary endpoint. The qualitative study involves semi-structured interviews to concurrently explore the acceptability of the application of Ixekizumab combined with GQHF among the enrolled participants.</p><p><strong>Discussion: </strong>This pilot study utilizes MMR to investigate the effect of Ixekizumab combined with GQHF in reducing PV relapse. The findings are expected to provide valuable clinical evidence and a novel therapeutic option for PV. Moreover, it is our intention to conduct a larger MMR trial to further strengthen the clinical evidence and broaden the application of Ixekizumab in combination with GQHF.</p><p><strong>Clinical trial registration: </strong>https://www.chictr.org.cn/index.html, identifier ChiCTR2100054950.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1551001"},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794726","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":"Cell death in acute lung injury: caspase-regulated apoptosis, pyroptosis, necroptosis, and PANoptosis.","authors":"Jun Xiao, Lichuan Wang, Bohan Zhang, Ana Hou","doi":"10.3389/fphar.2025.1559659","DOIUrl":"10.3389/fphar.2025.1559659","url":null,"abstract":"<p><p>There has been abundant research on the variety of programmed cell death pathways. Apoptosis, pyroptosis, and necroptosis under the action of the caspase family are essential for the innate immune response. Caspases are classified into inflammatory caspase-1/4/5/11, apoptotic caspase-3/6/7, and caspase-2/8/9/10. Although necroptosis is not caspase-dependent to transmit cell death signals, it can cross-link with pyroptosis and apoptosis signals under the regulation of caspase-8. An increasing number of studies have reiterated the involvement of the caspase family in acute lung injuries caused by bacterial and viral infections, blood transfusion, and ventilation, which is influenced by noxious stimuli that activate or inhibit caspase engagement pathways, leading to subsequent lung injury. This article reviews the role of caspases implicated in diverse programmed cell death mechanisms in acute lung injury and the status of research on relevant inhibitors against essential target proteins of the described cell death mechanisms. The findings of this review may help in delineating novel therapeutic targets for acute lung injury.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1559659"},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794791","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":"Editorial: Targeting mitochondria in aging and disease.","authors":"Cara B Gonzales, John M Seubert, Antonio Marcus Paes","doi":"10.3389/fphar.2025.1589728","DOIUrl":"10.3389/fphar.2025.1589728","url":null,"abstract":"","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1589728"},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795019","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":"Comprehensive assessment of antioxidant, antidiabetic, and anti-glycation properties of aqueous and methanolic extracts from <i>Pistacia lentiscus</i> L. leaves: a potential natural source for managing oxidative stress and diabetes-related complications.","authors":"Hasnae El Allaoui, Khadija Haboubi, Kawthar El Ahmadi, Mohamed Bouhrim, Aouatif ElAbdouni, Bruno Eto, Abdelaaty A Shahat, Rashed N Herqash, Mohmed El Bestrioui, Zakia Zouaoui, Mohamed Nhiri","doi":"10.3389/fphar.2025.1551841","DOIUrl":"10.3389/fphar.2025.1551841","url":null,"abstract":"<p><p>This study evaluates the phenolic and flavonoid contents, as well as the antioxidant, antidiabetic, and anti-glycation properties of aqueous and methanolic extracts from <i>Pistacia lentiscus</i> L. leaves. The antioxidant activity was assessed using DPPH, ABTS, FRAP, and iron-chelation assays, revealing superior activity in the aqueous extract. Both extracts exhibited potent antidiabetic effects by inhibiting the digestive enzyme alpha-amylase, with IC50 values of 2,291 ± 0.002 μg/mL (aqueous) and 2,889 ± 0.002 μg/mL (methanolic). Additionally, the extracts demonstrated significant anti-glycation activity, reducing advanced glycation end-product (AGE) formation, inhibiting fructosamine levels, and protecting thiol groups, with the aqueous extract providing greater protection. These findings underscore the potential of <i>P. lentiscus</i> L. as a natural source of bioactive compounds for managing oxidative stress and diabetes-related complications.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1551841"},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795081","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}