{"title":"Inonotus obliquus (chaga) ameliorates folic acid-induced renal fibrosis in mice: the crosstalk analysis among PT cells, macrophages and T cells based on single-cell sequencing.","authors":"Yueling Peng, Yaling Zhang, Rui Wang, Xinyu Wang, Xingwei Liu, Hui Liao, Rongshan Li","doi":"10.3389/fphar.2025.1556739","DOIUrl":"10.3389/fphar.2025.1556739","url":null,"abstract":"<p><strong>Background: </strong>Renal fibrosis, characterized by the abnormal accumulation of extracellular matrix in renal tissue and progressive loss of kidney function, is posing a significant challenge in clinical treatment. While several therapeutic options exist, effective treatments remain limited. Inonotus obliquus (Chaga), a traditional medicinal mushroom, has shown promising effects in chronic kidney disease (CKD), yet its cellular and molecular mechanisms remain largely unexplored.</p><p><strong>Methods: </strong>We analysed the chemical composition of Chaga using UPLC-MS and predicted its biological targets using PubChem and Swiss Target Prediction. We used single-cell RNA sequencing to study cellular responses in a mouse model of folic acid-induced renal fibrosis, complemented by spatial transcriptomics to map cellular location patterns. Histological assessment was performed using H&E and Masson trichrome staining.</p><p><strong>Results: </strong>For the first time, we employed single-cell RNA sequencing technology to investigate Chaga treatment in renal fibrosis. Histological analysis revealed that Chaga treatment significantly reduced renal tubular damage scores [from 5.00 (5.00, 5.00) to 2.00 (2.00, 2.00), p < 0.05] and decreased collagen deposition area (from 11.40% ± 3.01% to 4.06% ± 0.45%, p < 0.05) at day 14. Through analysis of 82,496 kidney cells, we identified 30 distinct cell clusters classified into eight cell types. Key findings include the downregulation of pro-inflammatory M1 macrophages and upregulation of anti-inflammatory M2 macrophages, alongside decreased T cell responses. Single-cell sequencing revealed differential gene expression in proximal tubular subpopulations associated with reduced fibrosis. Pathway and network pharmacology analyses of 60 identified compounds in Chaga and their 675 predicted targets suggested potential effects on immune and fibrotic pathways, particularly affecting Tregs and NKT cells. Cell-to-cell communication analyses revealed potential interactions between proximal tubular cells, macrophages, and T Cells, providing insights into possible mechanisms by which Chaga may ameliorate renal fibrosis.</p><p><strong>Conclusion: </strong>Our study provided new insights into the potential therapeutic effects of Chaga in renal fibrosis through single-cell sequencing analysis. Our findings suggest that Chaga may represent a promising candidate for renal fibrosis treatment, though further experimental validation is needed to establish its clinical application.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1556739"},"PeriodicalIF":4.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752191","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}
Frontiers in PharmacologyPub Date : 2025-03-14eCollection Date: 2025-01-01DOI: 10.3389/fphar.2025.1530371
Longping He, Zhuqing Luo, Lichun Zhang, Xingping Deng, Lincui Zhong, Qingwei Lin, Qingbo Zeng, Ye Zhou, Jingchun Song
{"title":"Preventive administration of shengmaiyin: a novel approach to counteract heatstroke-induced coagulopathy in rats.","authors":"Longping He, Zhuqing Luo, Lichun Zhang, Xingping Deng, Lincui Zhong, Qingwei Lin, Qingbo Zeng, Ye Zhou, Jingchun Song","doi":"10.3389/fphar.2025.1530371","DOIUrl":"10.3389/fphar.2025.1530371","url":null,"abstract":"<p><strong>Background: </strong>Coagulation disorders play a pivotal role in the elevated mortality rates associated with exertional heatstroke (EHS).</p><p><strong>Purpose: </strong>To investigate the impact of Shengmai Yin Oral Liquid (SMY) on heatstroke-induced coagulopathy (HIC) in rats with EHS and to elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>A cohort of eighteen male SPF-grade SD rats, each implanted with a telemetric temperature capsule, were randomly allocated to three groups: a normal control (NC) group, an EHS group, and an SMY group (n = 6 per group). The SMY group received SMY orally at a dosage of 20g/(Kg·day) for a period of five consecutive days. Both the EHS and SMY groups were subjected to exercise in a climate-controlled chamber maintained at 40°C with 70% relative humidity until signs of exhaustion and a core body temperature of 42°C were reached, with the duration and distance of their exercise being meticulously documented. Histopathological assessments were performed on the liver, kidney, lung, duodenum, and heart of the rats. Blood samples were collected to measure prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count, and levels of lactic acid (Lac), thrombomodulin (TM), thrombospondin-1 (TSP-1), von Willebrand factor (vWF), and plasminogen activator inhibitor-1 (PAI-1). Plasma samples were subjected to data-independent acquisition (DIA)-based quantitative proteomics analysis, and differentially expressed proteins identified were further authenticated using parallel reaction monitoring (PRM) and Enzyme-Linked Immunosorbent Assay (ELISA).</p><p><strong>Results: </strong>The SMY group exhibited a significantly extended running distance and time before reaching a core temperature of 42°C compared to the EHS group. Histopathological examination revealed thrombosis in the liver, kidney, lung, duodenum, and heart of rats in the EHS group, whereas no significant thrombosis was observed in the SMY group. The EHS group showed significantly prolonged PT and APTT, increased Lac, decreased platelet count, and elevated plasma levels of TM, vWF, TSP-1, and PAI-1 compared to the NC group (<i>P</i> < 0.05). In contrast, the SMY group demonstrated a significant reduction in APTT, an increase in platelet count, and decreased plasma levels of TM, vWF, PAI-1, and TSP-1 compared to the EHS group (<i>P</i> < 0.05). Among the 1,189 proteins identified, 56 differentially expressed proteins (DEPs) were associated with SMY's protective effects against HIC, primarily involved in the upregulation of the relaxin signaling pathway, protein digestion and absorption, platelet activation, and ECM-receptor interaction signaling pathways, as well as the downregulation of the spliceosome and ribosome signaling pathways. PRM quantitative analysis indicated that SMY may upregulate the expression of Nucleobindin-1 (Nucb1), Procollagen C-endopeptidase enhancer 1 (Pcolce), and lectin galactoside-binding sol","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1530371"},"PeriodicalIF":4.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752027","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}
Frontiers in PharmacologyPub Date : 2025-03-14eCollection Date: 2025-01-01DOI: 10.3389/fphar.2025.1552707
Qianxue Wu, Jiawei Xu, Xin Tang, Jin Yu, Benhua Li, Jun Yang, Xiang Zhang
{"title":"SB218078 inhibits angiogenesis and epithelial-mesenchymal transition in breast cancer.","authors":"Qianxue Wu, Jiawei Xu, Xin Tang, Jin Yu, Benhua Li, Jun Yang, Xiang Zhang","doi":"10.3389/fphar.2025.1552707","DOIUrl":"10.3389/fphar.2025.1552707","url":null,"abstract":"<p><strong>Purpose: </strong>Small-molecule inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2) face clinical limitations due to adverse effects. This study aimed to evaluate the novel compound SB218078 as a dual-targeting agent against both tumor angiogenesis and epithelial-mesenchymal transition (EMT) in breast cancer, while exploring its mechanisms of action.</p><p><strong>Methods: </strong>The anti-angiogenic effects of SB218078 were investigated using <i>in vitro</i> models of endothelial cell migration, invasion, and tube formation, alongside <i>in vivo</i> zebrafish developmental angiogenesis assays. Breast cancer progression was assessed through cellular proliferation, migration, invasion tests, and mouse xenograft models. Mechanistic studies focused on the Chk1/ZEB1 signaling axis, validated through genetic interventions.</p><p><strong>Results: </strong>SB218078 effectively suppressed angiogenesis by inhibiting endothelial cell functions and disrupting developmental vascular networks in zebrafish. It also impeded breast cancer cell aggressiveness and tumor growth <i>in vivo</i>. Mechanistically, SB218078 selectively targeted ZEB1-an EMT transcription factor-via Chk1 inhibition, with ZEB1 knockdown mimicking its anti-angiogenic effects, while ZEB1 overexpression reversed this activity.</p><p><strong>Conclusion: </strong>SB218078 emerges as a promising dual-action therapeutic candidate for breast cancer, simultaneously blocking angiogenesis and EMT through the Chk1-ZEB1 axis. Its specificity for ZEB1, distinct from other EMT regulators, offers a novel strategy to overcome the limitations of traditional VEGFR2 inhibitors, warranting further preclinical development.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1552707"},"PeriodicalIF":4.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752030","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 protective role of cannabidiol in stress-induced liver injury: modulating oxidative stress and mitochondrial damage.","authors":"Chengyu Huang, Huichao Liang, Xiaohua Liang, Yueyi Liu, Jiaoling Wang, Haoran Jiang, Xinhui Kou, Jun Chen, Lili Huang","doi":"10.3389/fphar.2025.1567210","DOIUrl":"10.3389/fphar.2025.1567210","url":null,"abstract":"<p><strong>Background: </strong>Stress-induced liver injury, resulting from acute or chronic stress, is associated with oxidative stress and inflammation. The endocannabinoid system, particularly cannabinoid receptor 2 (CB<sub>2</sub>R), plays a crucial role in liver damage. However, there are currently no clinical drugs targeting CB<sub>2</sub>R for liver diseases. Cannabidiol (CBD), a CB2R agonist, possesses anti-inflammatory and antioxidant properties. This study aims to investigate the pharmacological effects of CBD in a mouse model of stress-induced liver injury.</p><p><strong>Methods: </strong>We employed a mouse model of stress-induced liver injury to evaluate the protective effects of CBD. Assessments included histopathological analysis, cytokine detection via ELISA, protein expression analysis using immunohistochemistry and Western blot, and gene transcription differential analysis. Transmission electron microscopy was utilized to observe mitochondrial morphology. Additionally, we examined the expression levels of CB<sub>2</sub>R, SLC7A11, α-SMA, and ACSL4 proteins to elucidate the mechanisms underlying CBD's effects.</p><p><strong>Results: </strong>CBD exhibited significant protective effects against stress-induced liver injury in mice. Decreases in liver function indicators (including Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)) and inflammatory cytokines (such as IL-1β and Tumor Necrosis Factor-alpha (TNF-α)) were observed. CBD enhanced CB<sub>2</sub>R expression and reduced α-SMA levels, mitigating liver fibrosis. It also decreased ACSL4 levels, increased SOD and GSH-Px activities, and upregulated SLC7A11 protein expression. Furthermore, CBD improved mitochondrial morphology, indicating a reduction in oxidative cell death.</p><p><strong>Conclusion: </strong>CBD activates the CB<sub>2</sub>R/α-SMA pathway to modulate liver inflammation and fibrosis. Through the SLC7A11/ACSL4 signaling pathway, CBD alleviates oxidative stress in stress-induced liver injury, enhances mitochondrial morphology, and reduces liver damage. These findings provide a theoretical basis for the potential application of CBD in the prevention and treatment of stress-induced liver injury.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1567210"},"PeriodicalIF":4.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752050","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}
Frontiers in PharmacologyPub Date : 2025-03-14eCollection Date: 2025-01-01DOI: 10.3389/fphar.2025.1542015
Ning Cao, Zhangxuan Shou, Mimi Wang, You Wu, Xuefeng Wang
{"title":"The potential role and mechanism of Rhizoma Coptidis in prevention of diabetic encephalopathy: targeting sodium ion and channels.","authors":"Ning Cao, Zhangxuan Shou, Mimi Wang, You Wu, Xuefeng Wang","doi":"10.3389/fphar.2025.1542015","DOIUrl":"10.3389/fphar.2025.1542015","url":null,"abstract":"<p><strong>Introduction: </strong>Rhizoma Coptidis (RC) is an edible and medicinal herb with anti-hyperglycemia, which has potential application in the prevention of diabetic encephalopathy (DE). However, its efficacy and underlying mechanism in DE prevention have not been elucidated yet. The objective of the current study is to investigate the preventive effect of RC on DE, thereby focusing on the target through the method of network pharmacology and molecular docking.</p><p><strong>Methods: </strong>Sixty 4-week-old, male C57BL/6 mice were randomly allocated to six groups: control, model, metformin (200 mg/kg), RCL (0.75 g/kg), RCM (1.5 g/kg), and RCH (3 g/kg). The DE-model mice were induced by streptozocin combined with a high-fat diet. In addition, the neuroprotective effect of RC was determined both <i>in vivo</i> and <i>in vitro</i>. Network pharmacology analysis was used to screen the potential mechanism of RC. Thereafter, the underlying mechanism of action of RC was explored by molecular docking prediction and Western blot analysis. An analysis of patients with DE was performed to validate it from another perspective.</p><p><strong>Results: </strong>The results showed that the cognitive state of DE model mice was improved and neuronal injury was ameliorated after RC administration. Active compounds in RC, berberine and coptisine, were found to ameliorate HT22 injury induced by high glucose. Network pharmacology results suggest that voltage-gated sodium channel subtypes (Nav1.1, Nav1.2, and Nav1.6) may be the targets for RC prevention of DE. Furthermore, the Western blot analysis revealed that RC significantly upregulated Nav1.1 and Nav1.2, while Nav1.6 could not. In addition, serum sodium was related to the cognitive status of DE patients, which can be used as a diagnostic index for mild and moderate-severe DE.</p><p><strong>Discussion: </strong>RC has the potential to be a functional food or adjuvant drug for DE prevention, and Nav1.1 and Nav1.2 are promising DE intervention targets.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1542015"},"PeriodicalIF":4.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752046","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}
Frontiers in PharmacologyPub Date : 2025-03-14eCollection Date: 2025-01-01DOI: 10.3389/fphar.2025.1551451
Eunjung Choi, Gyeongseon Shin, SeungJin Bae
{"title":"Unaware and unpowered: evaluating patient perceptions and preferences of biosimilars in South Korea.","authors":"Eunjung Choi, Gyeongseon Shin, SeungJin Bae","doi":"10.3389/fphar.2025.1551451","DOIUrl":"10.3389/fphar.2025.1551451","url":null,"abstract":"<p><strong>Objectives: </strong>Biosimilars offer a promising solution to challenges related to healthcare budget sustainability. However, limited patient awareness and understanding often hinder their timely adoption. This cross-sectional survey evaluates the perceptions, preferences, and experiences of South Korean patients regarding biosimilars.</p><p><strong>Methods: </strong>An anonymous, self-administered, web-based survey comprising up to 26 questions was conducted. Participants were recruited from Ewha Womans University Medical Centers from November 2023 to August 2024. The analysis focused on respondents with medical conditions typically treated with biologics, such as solid tumors, blood cancers, and autoimmune diseases.</p><p><strong>Results: </strong>Out of 133 responses, 100 were analyzed after excluding 33 individuals with irrelevant medical conditions. Among these, 66% had heard of biosimilars, primarily through the internet (28.8%, 19 out of 66). However, 55% were unfamiliar with the definition of biosimilars, and 61% did not understand the difference between generics and biosimilars. While most respondents considered biosimilars comparable to originators in terms of safety (45%) and efficacy (41%), the primary concerns were a lack of confidence in their safety (50%) and efficacy (50%). Among patients who exclusively used either originators or biosimilars, 91.7% and 95%, respectively, cited their doctors' recommendations as the main reason for choosing their treatment.</p><p><strong>Conclusion: </strong>Patients primarily rely on doctors' recommendations, yet their awareness and understanding of biosimilars remain limited. To enhance positive perceptions of biosimilars among patients, implementing diverse educational programs and actively involving a multidisciplinary health team is essential. Such initiatives will not only increase patient access to these treatments but also contribute to the long-term sustainability of healthcare systems by encouraging the broader adoption of biosimilars.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1551451"},"PeriodicalIF":4.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752064","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}
Frontiers in PharmacologyPub Date : 2025-03-14eCollection Date: 2025-01-01DOI: 10.3389/fphar.2025.1584190
Patricia Carrilho, Sidharth Chopra, Mallikarjuna Rao Pichika, Robert E Fleming, Nermi L Parrow
{"title":"Editorial: The potential of transferrin as a drug target and drug delivery system.","authors":"Patricia Carrilho, Sidharth Chopra, Mallikarjuna Rao Pichika, Robert E Fleming, Nermi L Parrow","doi":"10.3389/fphar.2025.1584190","DOIUrl":"10.3389/fphar.2025.1584190","url":null,"abstract":"","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1584190"},"PeriodicalIF":4.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752188","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}
Frontiers in PharmacologyPub Date : 2025-03-14eCollection Date: 2025-01-01DOI: 10.3389/fphar.2025.1537720
Gilvânia A Cordeiro, Jessica A Faria, Leticia Pavan, Israel J P Garcia, Eduarda P F I Neves, Gustavo Fernando de Frazao Lima, Hericles M Campos, Pâmela Y Ferreira, Paulo C Ghedini, Elisa M Kawamoto, Maira C Lima, José A F P Villar, Ana Maria M Orellana, Leandro A Barbosa, Cristoforo Scavone, Jacqueline A Leite, Hérica L Santos
{"title":"Evaluation of the neuroprotective potential of benzylidene digoxin 15 against oxidative stress in a neuroinflammation models induced by lipopolysaccharide and on neuronal differentiation of hippocampal neural precursor cells.","authors":"Gilvânia A Cordeiro, Jessica A Faria, Leticia Pavan, Israel J P Garcia, Eduarda P F I Neves, Gustavo Fernando de Frazao Lima, Hericles M Campos, Pâmela Y Ferreira, Paulo C Ghedini, Elisa M Kawamoto, Maira C Lima, José A F P Villar, Ana Maria M Orellana, Leandro A Barbosa, Cristoforo Scavone, Jacqueline A Leite, Hérica L Santos","doi":"10.3389/fphar.2025.1537720","DOIUrl":"10.3389/fphar.2025.1537720","url":null,"abstract":"<p><p>Neuroinflammation, often driven by the overproduction of reactive oxygen species (ROS), plays a crucial role in the pathogenesis of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. The susceptibility of the brain to oxidative stress is attributed to its high metabolic activity and limited antioxidant defense. This study aimed to evaluate the neuroprotective potential of Benzylidene Digoxin 15 (BD-15) following treatment and pretreatment in a lipopolysaccharide (LPS)-induced neuroinflammation model. Additionally, we examined whether BD-15 enhances the generation of neurons from neural progenitor cells (NPCs).Male Wistar rats were used for acute treatment studies and divided into four groups: control (saline), BD-15 (100 μg/kg), LPS (250 μg/kg), and LPS + BD-15 (250 μg/kg + 100 μg/kg). Swiss albino mice were used for chronic pretreatment studies and divided into the following groups: control (saline), BD-15 (0.56 mg/kg), LPS (1 mg/kg), and LPS + BD-15 (1 mg/kg + 0.56 mg/kg). Behavioral changes were assessed using the open field test, and brain tissues were analyzed for oxidative stress markers, including malondialdehyde (MDA), reduced glutathione (GSH), protein carbonylation, catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST). To assess neurogenesis, primary NPC cultures derived from the hippocampus of newborn Wistar rats were used, which led to reduced locomotor activity and increased oxidative stress, particularly in the cortex, as indicated by elevated MDA levels and reduced GSH levels. BD-15 treatment reversed these effects, notably by restoring GSH levels and reducing protein carbonylation in the cerebellum. Chronic BD-15 treatment in Swiss mice improved oxidative stress markers including MDA, SOD, CAT, and GST. Furthermore, BD-15 exhibits neuroprotective properties by alleviating oxidative stress and motor dysfunction, suggesting its potential as a therapeutic agent for neuroinflammatory disorders. However, BD-15 did not affect NPC cell proliferation, indicating that this cardiotonic steroid did not alter the cell cycle of these progenitor cells.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1537720"},"PeriodicalIF":4.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752189","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}
Frontiers in PharmacologyPub Date : 2025-03-14eCollection Date: 2025-01-01DOI: 10.3389/fphar.2025.1534552
Xianlin Li, Xiunan Yue, Lan Zhang, Xiaojun Zheng, Nan Shang
{"title":"Pharmacist-led surgical medicines prescription optimization and prediction service improves patient outcomes - a machine learning based study.","authors":"Xianlin Li, Xiunan Yue, Lan Zhang, Xiaojun Zheng, Nan Shang","doi":"10.3389/fphar.2025.1534552","DOIUrl":"10.3389/fphar.2025.1534552","url":null,"abstract":"<p><strong>Background: </strong>Optimizing prescription practices for surgical patients is crucial due to the complexity and sensitivity of their medication regimens. To enhance medication safety and improve patient outcomes by introducing a machine learning (ML)-based warning model integrated into a pharmacist-led Surgical Medicines Prescription Optimization and Prediction (SMPOP) service.</p><p><strong>Method: </strong>A retrospective cohort design with a prospective implementation phase was used in a tertiary hospital. The study was divided into three phases: (1) Data analysis and ML model development (1 April 2019 to 31 March 2022), (2) Establishment of a pharmacist-led management model (1 April 2022 to 31 March 2023), and (3) Outcome evaluation (1 April 2023 to 31 March 2024). Key variables, including gender, age, number of comorbidities, type of surgery, surgery complexity, days from hospitalization to surgery, type of prescription, type of medication, route of administration, and prescriber's seniority were collected. The data set was divided into training set and test set in the form of 8:2. The effectiveness of the SMPOP service was evaluated based on prescription appropriateness, adverse drug reactions (ADRs), length of hospital stay, total hospitalization costs, and medication expenses.</p><p><strong>Results: </strong>In Phase 1, 6,983 prescriptions were identified as potential prescription errors (PPEs) for ML model development, with 43.9% of them accepted by prescribers. The Random Forest (RF) model performed the best (AUC = 0.893) and retained high accuracy with 12 features (AUC = 0.886). External validation showed an AUC of 0.786. In Phase 2, SMPOP services were implemented, which effectively promoted effective communication between pharmacists and physicians and ensured the successful implementation of intervention measures. The SMPOP service was fully implemented. In Phase 3, the acceptance rate of pharmacist recommendations rose to 71.3%, while the length of stay, total hospitalization costs, and medication costs significantly decreased (<i>p</i> < 0.05), indicating overall improvement compared to Phase 1.</p><p><strong>Conclusion: </strong>SMPOP service enhances prescription appropriateness, reduces ADRs, shortens stays, and lowers costs, underscoring the need for continuous innovation in healthcare.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1534552"},"PeriodicalIF":4.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752022","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}