Pharmacological Reports最新文献

{"title":"High BMI predicts poor cancer pain relief when rotating from oral opioids to transdermal Fentanyl: a two-center retrospective study.","authors":"Ya Chen, Songling Han, Xiaogang Hu, Xue Ma, Yue Qiu, Yuelu Tang, Xiaoxiao Wang, Lixian Li, Chao Li, Wanyi Chen","doi":"10.1007/s43440-025-00723-8","DOIUrl":"https://doi.org/10.1007/s43440-025-00723-8","url":null,"abstract":"<p><strong>Background: </strong>The analgesic effect of transdermal fentanyl (TDF) differs among cancer pain patients. This study aims to investigate the relationship between clinical factors and pain relief when using TDF in cancer pain patients who rotate from oral opioids to TDF.</p><p><strong>Methods: </strong>A two-center retrospective study was conducted in Chongqing University Cancer Hospital and Sichuan Cancer Hospital, including adult cancer pain patients who rotated from oral opioids to TDF between 2018 and 2022. Based on the clinical characteristics, logistic regressions and directed acyclic graphs (DAG) were employed to identify significant factors influencing the efficacy of TDF. The study adhered to STROBE guidelines.</p><p><strong>Results: </strong>This survey included 359 patients, among them, 254 patients (70.8%) attained good pain relief after rotating to TDF. 59.3% of patients utilized TDF at standard dosage, while 24.8% used underdose TDF, with only 52.8% achieving adequate pain relief, significantly lower than other groups (p < 0.001). Initial univariable analysis of 22 clinical factors among the standard dose group showed that a higher body mass index (BMI, median 23.2 kg/m² vs. 21.0 kg/m², OR = 0.83 [0.75-0.91], p < 0.001) and the presence of lung cancer (OR = 0.31 [0.11-0.89], p = 0.030) predicted potentially unsatisfactory pain control after TDF treatment. Subsequently, a multivariable regression analysis based on DAG-directed factor selection identified BMI (OR = 0.82 [0.74-0.92], adjusted p < 0.01) as the only independent factor influencing TDF effectiveness.</p><p><strong>Conclusions: </strong>Our study suggested that high BMI was a significant predictor of poor cancer pain relief when rotating from oral opioids to TDF, and provides a useful measurement of managing adult cancer pain when using TDF.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT06369961, registered on April 11, 2024; https://clinicaltrials.gov/study/NCT06369961 .</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":"77 3","pages":"789-799"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chalcone-9: a novel inhibitor of the JAK-STAT pathway with potent anti-cancer effects in triple-negative breast cancer cells.","authors":"Song-Hee Lee, Haeri Lee, Yong-Jin Kwon, Seul-Ki Kim, Eun-Bi Seo, Jie Ohn Sohn, Byung-Hak Kim, Jung-Youl Park, Sang-Kyu Ye","doi":"10.1007/s43440-025-00721-w","DOIUrl":"10.1007/s43440-025-00721-w","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer remains the leading cause of cancer incidence and mortality among women worldwide, with triple-negative breast cancer (TNBC) posing significant treatment challenges. The dysregulation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway contributes to tumor progression, making it a potential therapeutic target. Chalcones, known for their diverse biological activities, including anti-cancer effects, hold promise for drug development. This study explores the anti-cancer activity of (E)-4-(3-(2-(benzyloxy)-6-hydroxyphenyl)-3-oxoprop-1-en-1-yl)benzoic acid (chalcone-9), a novel chalcone derivative.</p><p><strong>Methods: </strong>The cytotoxic effects of chalcone-9 were evaluated in breast cancer cell lines, including TNBC lines MDA-MB-231 and MDA-MB-468. Western blotting and qRT-PCR were used to analyze the impact on JAK1, JAK2, STAT1, and STAT3 activation and their downstream gene expression. In silico molecular docking analysis was conducted to determine whether chalcone-9 can interact with JAK1 and JAK2. A wound healing assay was used to observe the effect of chalcone-9 on tumor cell migration, and flow cytometry was employed to analyze whether chalcone-9 inhibits tumor cell cycle progression and induces apoptosis. The expression of apoptosis markers was also assessed.</p><p><strong>Results: </strong>Chalcone-9 exhibited dose-dependent cytotoxicity in breast cancer cell lines, with TNBC cells showing higher sensitivity. Chalcone-9 effectively inhibited the activation of JAK1, JAK2, STAT1, and STAT3, outperforming conventional JAK/STAT inhibitors. The structure of chalcone-9 was confirmed to stably interact with JAK1 and JAK2 proteins. It also suppressed STAT1 and STAT3 target gene expression, reduced tumor cell migration, and induced apoptosis, as evidenced by PARP and caspase cleavage and decreased survivin levels.</p><p><strong>Conclusions: </strong>Chalcone-9 demonstrates significant anti-cancer activity, particularly against TNBC. By targeting the JAK/STAT pathway and promoting apoptosis, chalcone-9 emerges as a promising therapeutic candidate for aggressive breast cancers.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"761-774"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of magnolol on the liver antioxidant status in rats with diabetes.","authors":"Sławomir Dudek, Weronika Borymska, Maria Zych, Dżesika Chełminiak, Magdalena Kimsa-Dudek, Ilona Kaczmarczyk-Żebrowska","doi":"10.1007/s43440-025-00718-5","DOIUrl":"10.1007/s43440-025-00718-5","url":null,"abstract":"<p><strong>Background: </strong>Magnolol isolated from Magnolia (Magnolia sp.) flowers are used to support the treatment of diabetes. The aim of this study was to investigate the effects of magnolol on the liver antioxidant status in rats with type 2 diabetes and assess oxidative stress parameters at both biochemical and molecular levels.</p><p><strong>Methods: </strong>Mature male Wistar rats with high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetes were administered magnolol at doses of 5 or 25 mg/kg body weight po for 4 weeks. Then, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), the concentrations of advanced protein oxidation products (AOPPs) and malondialdehyde (MDA), the total antioxidant response (TAR), and the total oxidative status (TOS) were assessed using commercially available colorimetric kits according to the manufacturers' protocols. The mRNA levels of the cytochrome P450 family 1 subfamily A member 2 (CYP1A2), cytochrome P450 family 2 subfamily E member 1 (CYP2E1), nuclear factor erythroid 2-related factor 2 (NFE2L2), and Kelch like ECH-associated protein 1 (KEAP1) genes were determined using real-time quantitative reverse transcription-polymerase chain reaction (RT‒qPCR). All parameters were analyzed in liver samples.</p><p><strong>Results: </strong>Compared with 5 mg/kg magnolol, 25 mg/kg magnolol had a more beneficial effect on several indicators of oxidative stress in the liver observed as significant decreases in the activity of SOD and CAT, as well as decreased MDA concentrations. Further, significant increases in the concentrations of AOPPs and native thiols were observed. The gene encoding CYP2E1 was upregulated in diabetic rats compared with control rats. Moreover, compared with diabetic rats, diabetic rats treated with 25 mg/kg magnolol presented increased expression of the KEAP1 gene.</p><p><strong>Conclusions: </strong>The induction of diabetes is known to disturb redox homeostasis. The administration of magnolol at the higher dose used in this study, might counteract the changes in the liver antioxidant status at both the molecular and biochemical levels. Owing to the positive alterations in some oxidative stress parameters, after further in-depth study, magnolol may be considered a promising compound that could be used to complement diabetes treatment.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"716-728"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic liability for anxiety and treatment response to the monoamine stabilizer OSU6162 in alcohol dependence: a retrospective secondary analysis.","authors":"Mun-Gwan Hong, Lotfi Khemiri, Joar Guterstam, Johan Franck, Nitya Jayaram-Lindström, Philippe A Melas","doi":"10.1007/s43440-025-00707-8","DOIUrl":"10.1007/s43440-025-00707-8","url":null,"abstract":"<p><strong>Background: </strong>OSU6162, a monoamine stabilizer, has demonstrated efficacy in reducing alcohol and anxiety-related behaviors in preclinical settings. In a previous randomized, double-blind, placebo-controlled trial involving patients with alcohol dependence (AD), OSU6162 significantly reduced craving for alcohol but did not alter drinking behaviors. This retrospective secondary analysis explores whether genetic predispositions related to AD and associated traits might influence the response to OSU6162 treatment in original trial participants.</p><p><strong>Methods: </strong>Polygenic risk scores (PRSs) were calculated for 48 AD patients using PRSice-2 and genome-wide association study (GWAS) data for (i) alcohol use disorder and alcohol consumption, (ii) problematic alcohol use, (iii) drinks per week, (iv) major depression, and (v) anxiety (case-control comparisons and quantitative anxiety factor scores). Linear regression analyses, adjusted for population stratification, assessed interaction effects between PRSs and treatment type (OSU6162 or placebo) on various clinical outcomes.</p><p><strong>Results: </strong>Significant interactions were found between treatment type and anxiety factor score PRS at the genome-wide significance threshold. In the OSU6162-treated group, a higher anxiety PRS was associated with reductions in the number of drinks consumed (FDR = 0.0017), percentage of heavy drinking days (FDR = 0.0060), and percentage of drinking days (FDR = 0.0017), with a trend toward reduced blood phosphatidylethanol (PEth) levels (FDR = 0.068). These associations were absent in the placebo group.</p><p><strong>Conclusions: </strong>These preliminary findings suggest that anxiety PRS may help predict response to OSU6162 treatment in AD. Further research with larger cohorts and more comprehensive genetic data is needed to confirm these results and advance personalized medicine approaches for alcohol use disorder.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"840-849"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms underlying the effects of statins on bone metabolism: an evolving paradigm of statins delivery modalities for bone regeneration.","authors":"Randa Mohammed Zaki, Mohamed A M Ali, Mayada Said, Anis Ahmad Chaudhary, Fehmi Boufahja, Obaid Afzal, Abdelghafar M Abu-Elsaoud, Alyaa S Abdel Halim","doi":"10.1007/s43440-025-00716-7","DOIUrl":"10.1007/s43440-025-00716-7","url":null,"abstract":"<p><p>Statins, recognized for their lipid-lowering capabilities, have demonstrated osteoanabolic and anti-resorptive effects on bone metabolism. The effects encompass the overexpression of bone morphogenetic proteins, heightened osteoblast activity, and the control of inflammation. Nevertheless, conventional systemic administration of statins has difficulties, including restricted bone bioavailability and possible adverse effects. Recent improvements in targeted and localized drug delivery are revolutionizing the therapeutic landscape for statins in bone applications. This review consolidates existing knowledge regarding the molecular processes by which statins influence bone metabolism and describes novel drug delivery methods such as nano-carriers, biomaterial scaffolds, and controlled-release systems. It seeks to address current knowledge deficiencies and offer insights into how enhanced bioavailability and specificity can optimize the efficiency of statins in bone regeneration. The review integrates molecular insights with novel pharmacological strategies to inform future research and clinical applications, pinpointing critical areas for exploration, such as optimal dose, delivery safety, and clinical efficacy.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"624-644"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential drug-drug interactions analysis in Polish pediatric hemato-oncologic unit, including acute lymphoblastic leukemia patients.","authors":"Arkadiusz Adamiszak, Julia Drobińska, Izabela Niewiadomska-Wojnałowicz, Katarzyna Derwich, Edmund Grześkowiak, Agnieszka Bienert","doi":"10.1007/s43440-025-00719-4","DOIUrl":"10.1007/s43440-025-00719-4","url":null,"abstract":"<p><strong>Background: </strong>The lack of information on drug-drug interactions in the pediatric population significantly complicates making effective therapeutic decisions. Our study aimed to analyze the rate and risk factors as well as present potential drug-drug interactions (pDDIs) specifically for pediatric patients from the pediatric hemato-oncologic unit, including acute lymphoblastic leukemia (ALL) patients.</p><p><strong>Methods: </strong>We conducted a six-month prospective study in which clinical pharmacists examined medical records once a week to look for pDDIs using the Lexicomp^® Drug Interactions Checker. Spearman's rank coefficient, logistic regression, and the U-Mann-Whitney test were used to identify correlations, analyze risk factors for pDDIs, and compare ALL patients with non-ALL patients, respectively. Recommendations were provided for the D and X pDDIs categories.</p><p><strong>Results: </strong>We identified 507 pDDIs in 119 screened patients, 388 of which were clinically relevant. Nearly 68% of the patients were exposed to at least one significant interaction. The number of pDDIs was positively correlated with the number of medications (r_s=0.75, p < 0.001), off-label used drugs (r_s=0.42, p < 0.001), comorbidities (r_s=0.21, p = 0.019), and hospitalization length (r_s=0.48, p < 0.001). The multivariate analysis revealed that at least 7 administered medications (OR = 8.63; 95% CI = 2.92-25.47) and 13 days in the hospital (OR = 3.47; 95% CI = 1.31-9.19) were risk factors for pDDIs. Furthermore, patients treated for ALL represent an at-risk group with a statistically higher number of drugs taken and pDDIs identified.</p><p><strong>Conclusions: </strong>Limited data on drug-drug interactions in the pediatric population emphasizes the need for close collaboration between clinical pharmacists and clinicians to improve the safety and effectiveness of pharmacotherapy.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"751-760"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carvacrol in asthma management: a comprehensive review of its therapeutic potential and mechanisms of action.","authors":"Deepa Neopane, Poonam Kushwaha","doi":"10.1007/s43440-025-00709-6","DOIUrl":"10.1007/s43440-025-00709-6","url":null,"abstract":"<p><p>Asthma, a chronic inflammatory disorder of the airways, remains a significant global health concern. Current treatments focus on symptom management and inflammation control, but the search for more effective and safer therapies continues. Carvacrol, a naturally occurring monoterpenoid phenol found in essential oils of various plants, has emerged as a promising bioactive compound with potent anti-inflammatory, antioxidant, and bronchodilatory properties. This review explores the potential of carvacrol as a novel therapeutic agent for asthma management. We discuss its mechanisms of action, including modulation of inflammatory pathways, inhibition of oxidative stress, and relaxation of bronchial muscles. Additionally, preclinical and clinical studies evaluating the efficacy and safety of carvacrol in asthma treatment are analyzed. The integration of carvacrol into existing treatment regimens could offer a multifaceted approach to asthma management, enhancing therapeutic outcomes and improving patients' quality of life.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"610-623"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New pharmacological approaches in the treatment of schizophrenia.","authors":"Józef Muszyński, Agnieszka Bienert, Rasha Wafaie Elsorady, Filip Rybakowski","doi":"10.1007/s43440-025-00722-9","DOIUrl":"10.1007/s43440-025-00722-9","url":null,"abstract":"<p><p>Schizophrenia is a primary health concern, imposing a significant burden on both patients and healthcare systems globally. It is a disease with a complex etiology in which both genetic and environmental factors are involved. Despite numerous studies, the mechanism of its origin is still not fully understood. The hypotheses are synaptic, serotonergic, muscarinic, dopaminergic, microRNA-related, and neurodegenerative theories. Treatment to date is mainly based on antipsychotic drugs that act on the dopaminergic system. Although they are effective in reducing positive symptoms, their effect on negative and cognitive symptoms is limited, and their use is often associated with numerous side effects. A breakthrough in the treatment of schizophrenia came with the approval of the first drug with a non-dopaminergic mechanism of action, which opens up new therapeutic possibilities. As a result, there is intensive research into innovative substances that could increase the effectiveness of treatment and improve the quality of life of patients. In this review, we present the current state of knowledge about schizophrenia, its prevalence, risk factors, and its impact on patients' functioning. We pay special attention to new therapeutic directions, including drugs that affect systems other than the dopaminergic one, which could open up new prospects for treating the condition.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"561-575"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eribulin exerts multitarget antineoplastic activity in glioma cells.","authors":"Guilherme Augusto Sousa Alcântara, Mariane Cristina do Nascimento, Livia Bassani Lins de Miranda, Bruna Oliveira de Almeida, Keli Lima, Eduardo Magalhães Rego, Leticia Veras Costa-Lotufo, João Agostinho Machado-Neto","doi":"10.1007/s43440-025-00711-y","DOIUrl":"10.1007/s43440-025-00711-y","url":null,"abstract":"<p><strong>Background: </strong>Gliomas, particularly glioblastomas, are highly aggressive cancers with rapid proliferation and poor prognosis. Current treatments have limited efficacy, highlighting the need for new therapeutic strategies. Eribulin mesylate, a synthetic macrocyclic ketone, has shown potential as an anticancer agent in several malignancies. This study investigates the cellular and molecular effects of eribulin in glioma models, focusing on its impact on cell cycle progression, apoptosis, mitochondrial function, and migration.</p><p><strong>Methods: </strong>Glioma cell lines were treated with eribulin. Cell viability was measured by MTT assay, and the cell cycle was analyzed by flow cytometry. Apoptosis was assessed through morphological changes, PARP1 cleavage, and γH2AX expression. Mitochondrial integrity and reactive oxygen species levels were evaluated by flow cytometry. Cell migration was assessed using a spheroid-based assay, and protein expression changes were analyzed by Western blotting.</p><p><strong>Results: </strong>Eribulin reduced cell viability, with HOG cells exhibiting the highest sensitivity. Cell cycle analysis showed G₂/M phase arrest and morphological examination revealed polyploidy and apoptotic features. Mitochondrial dysfunction was observed, with decreased mitochondrial membrane potential and increased reactive oxygen species, particularly in HOG and T98G cells. Molecular analysis indicated activation of apoptotic pathways (PARP1 cleavage and γH2AX elevation) and reduced stathmin 1 expression. Eribulin also significantly reduced cell migration in HOG cells.</p><p><strong>Conclusion: </strong>Eribulin demonstrates potent anti-glioma effects through apoptosis, mitochondrial dysfunction, and cell cycle disruption. These findings support its potential as a therapeutic option for glioblastoma treatment, warranting further investigation into its mechanisms and clinical applicability.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"817-828"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The metabolism of big endothelin-1 axis and lipids affects carotid atherosclerotic plaque stability - the possible opposite effects of treatment with statins and aspirin.","authors":"Adam Płoński, Anna Krupa, Dariusz Pawlak, Katarzyna Sokołowska, Beata Sieklucka, Marcin Gabriel, Adam Filip Płoński, Jerzy Głowiński, Krystyna Pawlak","doi":"10.1007/s43440-025-00714-9","DOIUrl":"10.1007/s43440-025-00714-9","url":null,"abstract":"<p><strong>Background: </strong>The understanding of endothelin's role in carotid plaque instability is limited. We have studied the big endothelin-1 (ET-1) axis and its role in carotid plaque stability in patients undergoing carotid endarterectomy (CEA). The interactions of endothelins with known CVD risk factors were also evaluated.</p><p><strong>Methods: </strong>We studied 77 patients, who were divided into subgroups based on the optimal cut-off for grey-scale median (GSM), a marker of plaque instability. GSM values < 46.87 were designated as unstable carotid plaque, while GSM ≥ 46.87 were assigned to stable plaque. Twelve people without carotid atherosclerosis served as controls. Big ET-1, ET-1 and ET-1 (1-31) were measured and the endothelin-converting enzyme-1 (ECE-1) and chymase activity were calculated. Clinical and laboratory parameters were also evaluated.</p><p><strong>Results: </strong>ET-1 levels and ECE-1 activity were increased in all patient groups compared to controls (all P < 0.001) - and were higher in patients with unstable plaque than in those with stable plaque (P < 0.01). ET-1 (1-31) did not differ between the groups. ET-1 levels and ECE-1 activity inversely correlated with total cholesterol, LDL-cholesterol, and GSM values, whereas GSM was positively associated with total cholesterol and LDL fractions. Detailed analysis of patients according to the pharmacotherapy used revealed that statins favored ET-1 formation independently of cholesterol-lowering properties, whereas aspirin reduced this effect.</p><p><strong>Conclusions: </strong>ET-1 formation is the main pathway of big ET-1 metabolism in patients with carotid atherosclerosis, especially in those with plaque instability. Statins and aspirin appear to have opposing effects on ET-1 formation, suggesting the greater benefit related to plaque stability in patients taking both drugs concomitantly.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"739-750"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}