Frontiers in Pharmacology最新文献

{"title":"Exploring the antidiabetic potential of <i>Octhochloa compressa</i>: a comprehensive study on chemical profiling, <i>in vitro</i>, <i>in vivo</i> and <i>in silico</i> pharmacological properties.","authors":"Jawaria Aslam, Mirza Imran Shahzad, Hanan Y Aati, Kashif-Ur-Rehman Khan, Maria Aslam, Athar Jamal, Umar Farooq, Bilal Ahmad Ghalloo","doi":"10.3389/fphar.2025.1541482","DOIUrl":"https://doi.org/10.3389/fphar.2025.1541482","url":null,"abstract":"<p><p>Diabetes can lead to various health complications but can be managed with medication, diet, lifestyle changes, and certain medicinal plants with antidiabetic properties. <i>Octhochloa compressa,</i> a plant native to arid regions with a history of medicinal use, is being comprehensively examined for the first time using <i>in vitro, in silico</i>, and <i>in vivo</i> approaches to evaluate its efficacy in combating diabetes. <i>In vitro</i> α-glucosidase inhibition assays were performed using aqueous, methanol, <i>n</i>-butanol, ethyl acetate, <i>n</i>-hexane, and dichloromethane extracts. The ethyl acetate (EtAc) and methanol (MetOH) extracts showed the strongest inhibition with IC₅₀ values of 190.6 ± 1.19 μg/mL and 281.0 ± 0.98 μg/mL, respectively. <i>In vivo</i>, the anti-diabetic activity of aqueous, MetOH, and EtAc extracts was assessed at 250, 500, and 750 mg/kg body weight in alloxan-induced hyperglycemic rabbits (blood glucose >250 mg/dL). A 30-day study revealed that EtAc extract at 500 mg/kg significantly reduced glucose levels from 328.38 ± 0.86 mg/dL to 121.61 ± 1.28 mg/dL (P < 0.001), along with notable improvements in serum bilirubin, lipid profile, creatinine, ALT, and AST levels compared to the negative control. Histopathological analysis showed no toxic effects on liver, kidney, or adrenal tissues. HPLC analysis of the potent EtAc extract identified bioactive compounds, and <i>in silico</i> docking revealed that tannins, gallic acid, coumarin, oxindole, and xanthone formed stable complexes with α-glucosidase (PDB ID: 3W37), with docking scores of -7.91, -6.59, -6.34, -6.33, and -6.07 kcal/mol, respectively. These findings suggest that <i>O. compressa</i> contains active compounds with significant anti-diabetic properties and minimal toxicity, making it a promising candidate for diabetes management and its complications. Future research should isolate and characterize key bioactive compounds and validate their mechanisms, safety, and clinical efficacy to advance <i>O. compressa</i> as a potential antidiabetic therapy.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1541482"},"PeriodicalIF":4.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215509","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":"Application of global trigger tool to determine the prevalence of adverse drug reactions in adult patients admitted to general and COVID-19 intensive care units.","authors":"Rafael Nogueira de Souza, Marília Berlofa Visacri, Fabiana Bragança Albanese Trotta, Deise de Souza Ventura, Mauricio Wesley Perroud, Patrícia Moriel","doi":"10.3389/fphar.2025.1514942","DOIUrl":"https://doi.org/10.3389/fphar.2025.1514942","url":null,"abstract":"<p><strong>Objective: </strong>The primary aim of this study was to determine the prevalence of adverse drug reactions (ADRs) in adult patients admitted to a general adult intensive care unit (G-ICU) and a COVID-19 adult intensive care unit (C19-ICU). The secondary aims were to characterize patients in both ICUs; identify factors associated with the occurrence of ADRs; assess the performance of triggers in detecting ADRs; describe ADRs in terms of severity, mechanism, causality, and suspected drugs; and compare the trigger tool methodology with spontaneous reporting.</p><p><strong>Methods: </strong>This was a descriptive and retrospective study involving the application of triggers adapted from the Global Trigger Tool to identify ADRs through the analysis of physical and electronic medical records, medical prescriptions, and laboratory test results of adult patients admitted to the G-ICU and C19-ICU of a tertiary hospital in Sumaré (HES), São Paulo, Brazil, from January 2020 to December 2020. The patients were characterized by sex, age, length of stay, clinical outcome (discharge or death), and sequential organ failure assessment (SOFA) scores. The performance of triggers in detecting ADRs was determined by calculating positive predictive value (PPV). ADRs were characterized by severity, mechanism, causality, and suspected drugs. The 2020 spontaneous reporting database at the HES was analyzed, and ADRs from the ICUs were identified.</p><p><strong>Results: </strong>The study evaluated 135 patients (56.3% from the G-ICU and 43.7% from the C19-ICU), with a predominance of males (54.8%) and a mean age of 61.0 ± 15.1 years. The mean hospital stay was 13.0 ± 11.0 days, the average SOFA score throughout hospitalization was 8.4 ± 3.8, and the ICU mortality rate was 69.6%. Of the 135 admitted patients, 55 (40.7%) presented with at least one ADR, of which 31 (52.5%) were admitted to the C19-ICU. The length of hospitalization was associated with the presence of ADR in both ICUs studied and age only in the C19-ICU. Additionally, patients admitted to the C19-ICU had a 2.4 times higher risk of developing ADRs. A total of 85 ADRs were identified, 65 (76.5%) of which occurred through triggers. The triggers with the best performance in detecting ADRs, with a PPV of 100%, were \"Partial Thromboplastin Time >50,\" \"Skin Rash,\" \"Protamine,\" and \"Hydroxyzine.\" Most ADRs were moderate (56.5%), Type A (96.5%), and classified as possible (64.7%). Insulin was the drug most frequently associated with ADRs, with 22 occurrences. Only five ADRs in ICU patients were spontaneously reported in 2020.</p><p><strong>Conclusion: </strong>Of all the patients, 40.7% experienced at least one ADR during hospitalization. The number of ADRs identified by the trigger tool was significantly higher than those reported spontaneously. This demonstrates that using triggers to investigate ADRs is an effective method to significantly enhance an institution's pharmacovigilance actions.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1514942"},"PeriodicalIF":4.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215493","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":"Longitudinal relationships between serum ferritin and prognosis among severe community-acquired pneumonia patients.","authors":"Jing Xu, Ming-Feng Han, Kai-Shu Ma, Ting Zhang, Rui-Rui Wang, Jing-Jing Zhang, Hui Zhao, Lin Fu","doi":"10.3389/fphar.2025.1556185","DOIUrl":"https://doi.org/10.3389/fphar.2025.1556185","url":null,"abstract":"<p><strong>Background: </strong>Ferritin is one of the major intracellular iron storage proteins and is implicated in the pathophysiological processes of many inflammatory diseases, but its function in community-acquired pneumonia (CAP) was unclear. The purpose of this study was to evaluate the expression of ferritin and analyze the relationship of serum ferritin with CAP.</p><p><strong>Methods: </strong>Severe CAP patients and age- and gender-matched healthy participants were recruited for the study. Serum ferritin was detected through ELISA. Physiological characteristics were recorded.</p><p><strong>Results: </strong>The serum ferritin level was significantly increased in severe CAP patients upon initial hospitalization compared to healthy participants, and it decreased after therapy. Correlative analyses hinted that there were obvious relationships of serum ferritin with the indicators of blood routine, liver function, and inflammation. Moreover, linear and logistic regression analyses confirmed that the serum ferritin level was positively related to the scores of CURB-65, CRB-65, and PSI. The poor prognosis including mechanical ventilation, vasoactive agent, ICU admission, death, and longer hospital stays were assessed in severe CAP cases during hospitalization. Multivariate logistic regression showed that higher serum ferritin levels were closely linked to the poor prognostic outcomes.</p><p><strong>Conclusion: </strong>There is significantly positive association between the serum ferritin level upon initial hospitalization with the severity and poor prognosis. Thus, serum ferritin could be an indicator for the determination of severity and prognosis among CAP cases.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1556185"},"PeriodicalIF":4.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215530","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":"Selinexor in acute myeloid leukemia: therapeutic applications and current challenges.","authors":"Ziyu Qie, Li Ma, Jie Tan, Xiaochun Peng","doi":"10.3389/fphar.2025.1602911","DOIUrl":"https://doi.org/10.3389/fphar.2025.1602911","url":null,"abstract":"<p><p>This article aims to review the current application status and research advancements of selinexor in the treatment of acute myeloid leukemia (AML). Selinexor, as the first oral selective inhibitor of nuclear export protein Exportin-1 (XPO1), inhibits the abnormal nuclear export of tumor suppressor proteins by blocking XPO1, thereby restoring their activity and exerting antitumor effects. Clinical studies have shown that selinexor monotherapy or combination therapy has demonstrated good anti-leukemia effects in AML, especially in patients with relapsed/refractory AML. In addition, the combination of selinexor with other drugs, such as demethylating agents and FLT3 inhibitors, has shown synergistic antitumor effects. Although selinexor has shown potential, its resistance and adverse reactions still need further research and control. Future research directions include exploring the best medication schemes, clarifying the appropriate population, and developing new combination treatment plans to improve treatment effects and overcome drug resistance issues.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1602911"},"PeriodicalIF":4.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The essential oil from the rhizomes of <i>Stahlianthus involucratus</i> attenuates the progression of vascular aging and atherosclerosis by regulating Nrf2-mediated mitochondrial quality.","authors":"Jianmei Li, Zaishang Wang, Yu Wang, Jiaxin Lin, Ning Tang, Chu Zheng, Qin Xu","doi":"10.3389/fphar.2025.1579333","DOIUrl":"https://doi.org/10.3389/fphar.2025.1579333","url":null,"abstract":"<p><strong>Introduction: </strong>Atherosclerosis (AS), characterized by chronic inflammation within the vasculature, is linked to endothelial dysfunction and oxidative stress. The senescence of vascular endothelial cells (VECs) serves as a pathological basis for AS. Stahlianthus involucratus (King ex Baker) Craib ex Loes is a folk medicinal plant commonly used in Guangxi has its rhizome as the active component. In traditional Chinese medicine, it is believed to promote blood circulation, remove blood stasis, stop bleeding, and disperse accumulated blood. Essential oil extracted from Stahlianthus involucratus rhizomes (EOSIR) is a key bioactive component. However, little research has been reported on the effects of EOSIR on cardiovascular disease.</p><p><strong>Methods: </strong>Validation techniques, including H&E staining and western blotting, were employed to assess the efficacy of EOSIR in both in vivo and in vitro models of AS.</p><p><strong>Results: </strong>In vivo experiments, EOSIR decreased plaque volume in atherosclerotic vessels of mice. Activation of the Nrf2 signaling pathway by EOSIR alleviated ox-LDL-induced injury in HUVECs, including a reduction in cellular senescence, apoptosis, ROS, and mitochondrial membrane potential, effects that were reversed by Nrf2 silencing. EOSIR also restored mitochondrial morphology in cells and enhanced Nrf2 expression as well as ATP levels in aortic tissue. Both in vivo and in vitro, EOSIR upregulated the Nrf2, NQO1, and HO-1 expression, downregulated Keap1 expression, and improved the mitochondrial-associated protein expression.</p><p><strong>Discussion: </strong>These findings suggest that EOSIR may prevent the onset of AS both in vivo and in vitro by modulating the mitochondrial quality control system through the Nrf2 signaling pathway.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1579333"},"PeriodicalIF":4.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215532","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":"Associated factors, emergency department visits, and hospitalization days of receiving adjunctive Chinese herbal medicine therapy for patients with non-small cell lung cancer: a nationwide cohort study in Taiwan.","authors":"Meng-Bin Tang, Wei-Yin Kuo, Pei-Tseng Kung, Wen-Chen Tsai","doi":"10.3389/fphar.2025.1435541","DOIUrl":"https://doi.org/10.3389/fphar.2025.1435541","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer prevention and treatment, particularly lung cancer, remain major healthcare challenges in Taiwan and globally. This study investigates factors and healthcare utilization patterns associated with adjunctive Chinese herbal medicine (CHM) therapy in non-small cell lung cancer (NSCLC) patients.</p><p><strong>Methods: </strong>Using Taiwan's National Health Insurance Research Database and the Taiwan Cancer Registry, we conducted a retrospective cohort study of non-small cell lung cancer patients diagnosed between 2007 and 2013. Descriptive analysis, propensity score matching, and regression models were employed to assess CHM therapy utilization and its impact on emergency department visits and hospitalization days.</p><p><strong>Results: </strong>Among 43,122 non-small cell lung cancer patients, 5.76% received adjunctive CHM therapy, with the majority at stage IV cancer. Factors such as cancer stage, age, gender, marital status, education level, monthly salary, degree of urbanization, severity of comorbidity, comorbid diseases, hospital ownership, experience of using Chinese medicine, chemotherapy status, and years of diagnosis are significantly associated with whether NSCLC patients receive adjunctive CHM therapy. Patients receiving adjunctive CHM therapy for 181-365 days reduced emergency department visits by 16% (OR = 0.84, 95%CI: 0.74-0.95) and shortened hospitalization days by 17% (Ratio = 0.83, 95%CI: 0.75-0.91).</p><p><strong>Conclusion: </strong>Prolonged adjunctive CHM therapy, particularly for 181-365 days, is associated with decreased healthcare utilization among non-small cell lung cancer patients. These findings suggest a potential role for extended CHM therapy in managing NSCLC and warrant consideration by clinical teams.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1435541"},"PeriodicalIF":4.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215504","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":"Enhancing medication appropriateness: Insights from the STOPP (Screening Tool of Older Persons' Prescriptions) criteria version 3 on prescribing practices among the older adults in Pakistan.","authors":"Halima Sadia, Safila Naveed, Hina Rehman, Shazia Jamshed, Huma Dilshad","doi":"10.3389/fphar.2025.1551819","DOIUrl":"https://doi.org/10.3389/fphar.2025.1551819","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of potentially inappropriate medications (PIMs) in older adults populations is a significant concern, often leading to adverse drug events and increased health-care utilization.</p><p><strong>Objective: </strong>In the present study, we aim to evaluate the prevalence of PIMs among hospitalized older adults patients in Pakistan using STOPP (Screening Tool of Older Persons' Prescriptions) criteria version 3.</p><p><strong>Methodology: </strong>A prospective observational study was conducted at a tertiary-care hospital in Karachi over 1 year from March 2023 to March 2024. Patients aged 60 years and above, prescribed at least one medication, were included. Data on demographics, comorbidities, and medications were collected and analyzed using the STOPP criteria to identify PIMs. Statistical analysis was performed using IBM SPSS Statistics version 21. To find the variables linked to PIM use, multivariable logistic regression analysis was used. The 95% CI and adjusted odds ratio (aOR) were used to measure the statistical association's strength. A p-value of less than 0.05 was deemed statistically significant.</p><p><strong>Results: </strong>Among 450 participants, the median age was 67 years, with a predominance of male patients (55.3%). The prevalence of PIM use was 56.6%, and a total of 388 instances of PIM use were identified according to STOPP criteria version 3. Acetylsalicylic acid (18%) and pheniramine (11%) were the most frequent inappropriately prescribed medications. The multivariable logistic regression analysis revealed that polypharmacy and the presence of one or more comorbidities primarily influence the PIM use.</p><p><strong>Conclusion: </strong>The findings highlight a critical need for improved prescribing practices in the older adults population in Pakistan. Utilizing screening tools like the STOPP criteria can significantly enhance medication safety and optimize pharmacotherapy in this vulnerable group.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1551819"},"PeriodicalIF":4.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The preventive effect of sodium-glucose co-transporter-2 inhibitors on atrial fibrillation and atrial flutter in patients with chronic kidney disease: a meta-analysis.","authors":"Qian Yang, Chen Wang, Wenjing Wang, Yanhong Li, Yi Dang","doi":"10.3389/fphar.2025.1585491","DOIUrl":"https://doi.org/10.3389/fphar.2025.1585491","url":null,"abstract":"<p><strong>Background: </strong>The presence of atrial fibrillation (AF) and atrial flutter (AFL) in patients with chronic kidney disease (CKD) can exacerbate renal dysfunction, which in turn increases the onset of AF or AFL. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have been proven to have cardiac and renal protective effects. The meta-analysis was performed to investigate whether SGLT2i can reduce the risk of AF/AFL in patients with CKD.</p><p><strong>Methods: </strong>PubMed, Embase, Cochrane Library, and Clinical Trials.gov were searched up to December 2024. Randomized controlled trials (RCTs) comparing of SGLT2i and placebo on AF/AFL in patients with CKD were included. Risk ratio (RR) with 95% confidence interval (CI) were calculated in the overall population and selected subgroups.</p><p><strong>Results: </strong>10 RCTs involving 28,712 patients were included. SGLT2i significantly reduced the risk of the composite events of AF and AFL in patients with CKD (0.65% vs. 0.91%; RR 0.73, 95% CI 0.56-0.95, <i>P</i> = 0.02) in overall population, but did not reduce the risk of AF (0.56% vs. 0.75%; RR 0.76, 95% CI 0.57-1.01, <i>P</i> = 0.06) or AFL (0.097% vs. 0.17%; RR 0.58, 95% CI 0.30-1.13, <i>P</i> = 0.11). Subgroup analysis based on sample size and follow-up duration showed that SGLT2i reduced the risk of AF in trials with sample size more than 1,000 and follow-up duration longer than 2 years (0.59% vs. 0.80%; RR 0.74, 95% CI 0.55-0.99, <i>P</i> = 0.04). Subgroup analysis based on different populations showed that SGLT2i reduced the risk of AF in patients with CKD (partial without diabetes) (0.48% vs. 0.90%; RR 0.53, 95% CI 0.33-0.85, <i>P</i> = 0.009), while had no effect on AF in patients with both diabetes and CKD. Subgroup analysis based on different types of SGLT2i showed that only empagliflozin reduced the risk of AF compared to placebo (0.51% vs. 0.94%; RR 0.55, 95% CI 0.31-0.96, <i>P</i> = 0.04).</p><p><strong>Conclusion: </strong>SGLT2i could reduce the risk of the composite events of AF and AFL in patients with CKD, and also could reduce the risk of AF in trials with large sample size and long follow-up duration.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/view/CRD420251053244.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1585491"},"PeriodicalIF":4.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Traditional Chinese Medicine targeting the TGF-β/Smad signaling pathway as a potential therapeutic strategy for renal fibrosis.","authors":"Hao Jiao, Meijuan Zhang, Lili Chen, Zhirui Zhang","doi":"10.3389/fphar.2025.1513329","DOIUrl":"https://doi.org/10.3389/fphar.2025.1513329","url":null,"abstract":"<p><p>Renal fibrosis (RF) is an inevitable outcome of nearly all progressive chronic kidney diseases (CKD). However, effective therapies that can halt or reverse the development of RF and CKD progression remain limited. Traditional Chinese Medicine (TCM) offers a unique therapeutic approach, demonstrating significant anti-fibrotic potential through its antioxidant and anti-inflammatory pharmacological properties. However, comprehensive reviews focusing on the role of TCM in targeting signaling pathways associated with RF are still scarce. In this review, the literature was screened according to the clarity of the relevance of TCM, including the types and mechanisms of TCM. We summarize the pivotal role of the TGF-β/Smad signaling pathway in RF and provide an overview of single Chinese botanical drug, their active ingredients, and TCM compounds that ameliorate RF by modulating this pathway, aiming to establish a solid foundation for future basic and clinical research in the field of RF. While TCM holds unique advantages in treating RF, its limitations need to be addressed through scientific research and technological innovation. Future studies will focus on elucidating mechanisms, improving quality control, validating clinical efficacy, and fostering international collaboration to promote the scientific and global application of TCM in modern medicine.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1513329"},"PeriodicalIF":4.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215534","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":"ARID1A deficiency attenuates the response to EGFR-TKI treatment in lung adenocarcinoma.","authors":"Fangfang Yang, Helei Hou, Guanqun Wang, Guangming Fu, Xingfa Huo, Xueqin Duan, Na Zhou, Xiaochun Zhang","doi":"10.3389/fphar.2025.1582005","DOIUrl":"https://doi.org/10.3389/fphar.2025.1582005","url":null,"abstract":"<p><strong>Background: </strong>Concurrent genetic alterations (e.g., TP53 comutations) significantly impair EGFR-TKI responsiveness and survival outcomes in EGFR-mutant lung adenocarcinoma (LUAD). AT-rich interactive domain 1A (ARID1A), which is a key subunit of SWI/SNF complexes, demonstrates critical regulatory functions as a tumour suppressor gene in cancer. The aim of this study is to determine the role of ARID1A deficiency in the therapeutic efficacy of EGFR-TKIs in LUAD.</p><p><strong>Methods: </strong>We identified the ARID1A mutation as a potential prognostic marker in EGFR-mutant LUAD by analysing data from cBioPortal. The expression of ARID1A was detected via immunohistochemical staining. A lentivirus was employed to construct the ARID1A knockdown model in PC9 cell. We further analyzed the biological roles of ARID1A knockdown through CCK8, flow cytometry analysis and transwell assay.</p><p><strong>Results: </strong>The ARID1A mutation was associated with poor OS in EGFR-mutant LUAD patients, and the prognostic influence was greater than that of concurrent EGFR mutations with TP53, KRAS, CDKN2A, PIK3CA, RB1 or PTEN. By analysing the clinical data of our centre, we revealed that patients with loss of ARID1A expression demonstrated poorer median progression-free survival (mPFS, 10.3 versus 30 months, <i>P</i> = 0.005) when they received EGFR-TKIs as the first-line treatment after postoperative progression (cohort A). A shorter median disease-free survival (mDFS, 29 versus NA months, <i>P</i> = 0.003) was also observed in the ARID1A low-expression cohort than in the ARID1A high-expression group in patients receiving postoperative adjuvant EGFR-TKI treatments (cohort B). We also found that ARID1A deficiency attenuated the efficacy of osimertinib by activating the EGFR/AKT/mTOR signalling axis in PC9 cell.</p><p><strong>Conclusion: </strong>ARID1A deficiency may be an independent prognostic factor and attenuates the response to EGFR-TKIs in patients with EGFR-mutant LUAD. In addition, loss of ARID1A expression confers resistance to EGFR-TKI by activating the EGFR/AKT/mTOR signalling axis.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1582005"},"PeriodicalIF":4.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215503","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}