BMC Pharmacology & Toxicology最新文献

{"title":"Bisacurone ameliorates myocardial ischemia/reperfusion injury in rats: regulation of inflammatory and apoptosis pathways via CHOP/GRP78 proteins.","authors":"Xueyan Liao, Qi Wang, Xiaoming Yang, Yuan Yao, Dezhi Zhu, Jing Feng, Kechun Wang","doi":"10.1186/s40360-025-00949-5","DOIUrl":"10.1186/s40360-025-00949-5","url":null,"abstract":"<p><strong>Background: </strong>Myocardial infarction is caused by persistent ischemia with or without reperfusion. Bisacurone, a terpenoid present in turmeric, possesses cardioprotective properties that alleviate heart hypertrophy and diabetic cardiomyopathy. However, its effect on myocardial ischemia-reperfusion damage (MIRI) has yet to be evaluated. Thus, the present study aimed to evaluate the underlying cardioprotective mechanism of bisacurone against MIRI in experimental rats.</p><p><strong>Materials and methods: </strong>Male Sprague-Dawley rats (200-220 g) were administered either vehicle, diltiazem (10 mg/kg), or bisacurone (25, 50, and 100 µg/kg) for 14 days, followed by induction of MIRI by partial ligation of the left anterior descending artery and subsequent reperfusion injury.</p><p><strong>Results: </strong>Bisacurone (50 and 100 µg/kg) significantly (p < 0.05) attenuated IRI-induced cardiac damage, as evidenced by improvements in electrocardiographic, hemodynamic, and left ventricular function tests. Furthermore, cardiac mitochondrial enzyme levels and HO-1 and Bcl-2 mRNA expression were substantially (p < 0.05) upregulated, whereas cardiac oxido-nitrosative stress, ANP, BNP, cTn-I, TNF-α, IL-1, TGF-β, Bax, and caspase-3 mRNA levels were effectively (p < 0.05) downregulated compared to the IRI control. It markedly (p < 0.05) reduced the number of apoptotic cells in cardiac tissue, as determined by flow cytometric analysis. Western blot analysis revealed that bisacurone therapy reduced IRI-induced myocardial apoptosis, as evidenced by a significant (p < 0.05) decrease in CHOP and GRP78-protein expression. Bisacurone also improved IRI-induced histological and ultrastructural aberrations in cardiac tissue.</p><p><strong>Conclusions: </strong>The findings of this study suggest that bisacurone exerts its cardioprotective effects by inhibiting oxido-nitrosative stress, inflammatory release (TNF-α, IL-1β, and TGF-β), apoptosis (Bax and Caspase-3), and by regulating the expression of CHOP and GRP78.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"115"},"PeriodicalIF":2.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207590","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":"Protective role of coenzyme Q10 against trihexyphenidyl-induced pulmonary toxicity in Wistar rats.","authors":"Joseph Gbenga Omole, Lydia Oluwatoyin Ajayi, Itunuoluwa Rachael Ajewole, Teniola Osholonge, Oyedayo Phillips Akano, Ayodeji Folorunsho Ajayi","doi":"10.1186/s40360-025-00955-7","DOIUrl":"10.1186/s40360-025-00955-7","url":null,"abstract":"<p><strong>Background: </strong>Trihexyphenidyl (THP), an anticholinergic drug used to manage Parkinson's disease and dystonia, has been associated with oxidative stress and metabolic disturbances, particularly affecting pulmonary function. Long-term exposure to THP may induce lung toxicity through increased oxidative stress, mitochondrial dysfunction, and apoptosis. Coenzyme Q10 (CoQ10), a lipid-soluble antioxidant and mitochondrial cofactor, has been shown to protect against oxidative damage and apoptosis in various models of toxicity. However, its role in mitigating THP-induced pulmonary toxicity remains unexplored. This study investigated the protective effects of CoQ10 against THP-induced pulmonary toxicity in male Wistar rats.</p><p><strong>Methods: </strong>Thirty-two adult male Wistar rats (180-200 g) were randomly assigned to four groups (n = 8 per group): (i) Control (vehicle-treated), (ii) THP (1.5 mg/kg), (iii) CoQ10 (10 mg/kg), and (iv) THP + CoQ10. Treatments were administered orally once daily for 21 days. Body weight was recorded at baseline and endpoint. At the end of treatment, rats were euthanized, and lungs were excised, weighed, and processed for biochemical and histological analyses. Oxidative stress markers were assessed, including catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA). Metabolic enzymes such as lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) were measured. Angiotensin-converting enzyme (ACE) activity was evaluated to assess vascular function, while caspase-3 levels were determined as an apoptotic marker. Histopathological examination of lung tissues was performed using hematoxylin and eosin staining.</p><p><strong>Results: </strong>THP administration resulted in significant weight loss, increased lung weight, oxidative stress (decreased CAT, GPx, SOD, and GSH; increased MDA), and metabolic alterations (elevated LDH, PDH, lactate, and pyruvate). ACE activity was reduced, and caspase-3 was elevated, indicating apoptosis. CoQ10 co-administration mitigated these effects, restoring antioxidant enzyme activity, metabolic balance, and ACE levels while reducing MDA and caspase-3 expression. Histological analysis confirmed that CoQ10 ameliorated THP-induced pulmonary damage.</p><p><strong>Conclusion: </strong>CoQ10 demonstrated significant protective effects against THP-induced oxidative stress, metabolic disturbances, and apoptosis, likely due to its antioxidant and anti-inflammatory properties. These findings suggest CoQ10 as a potential therapeutic agent for THP-induced pulmonary toxicity, warranting further research.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"114"},"PeriodicalIF":2.8,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191442","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":"Exploration of the optimal concentration of quercetin liposome nanoparticles for the treatment of liver damage.","authors":"Nana Yin, Jian Pang, Xiangyan Liu","doi":"10.1186/s40360-025-00951-x","DOIUrl":"10.1186/s40360-025-00951-x","url":null,"abstract":"<p><strong>Background: </strong>Hepatic injury is a common pathological process for a wide spectrum of liver diseases. Quercetin has been found to counteract this process by scavenging free radicals, but its therapeutic effect is limited due to poor water-solubility. Thus, the question of how to deliver quercetin to a target organ effectively with minimal side effects has remained a clinical challenge. Our previous research findings indicate that when quercetin is delivered in the form of liposomal nanoparticles, its targeting efficiency to the liver is significantly enhanced. Although quercetin liposomal nanoparticles have been shown to improve the therapeutic effect on liver damage compared to traditional quercetin treatment, the optimal dosage of liposomal quercetin still warrants further exploration. The aim of this study was therefore to ascertain whether there are differences in the therapeutic effects on liver damage at different dosages of quercetin liposomes and to determine the optimal dosage.</p><p><strong>Methods: </strong>62 rats modeled with liver injury were enrolled and distributed into 4 groups, where they were treated with quercetin liposome nanoparticles, blank liposome nanoparticles, simple quercetin, and normal saline accordingly. Serum samples were measured for liver function indicators, and tissue samples were analyzed by pathohistological examination. Statistical analysis was performed to quantify the difference between the experimental and control groups.</p><p><strong>Results: </strong>Both liver function and histopathological examinations demonstrated enhanced therapeutic effects as the concentration of quercetin liposome drugs increased. Moreover, compared to traditional quercetin treatments, liposomal quercetin nanoparticles of varying concentrations uniformly provide better liver protection, with the highest dose group showing the best therapeutic effect. In addition, low concentration carrier liposome nanoparticles also showed a certain protective effect on the liver damage in rats.</p><p><strong>Conclusion: </strong>Liposomal quercetin nanoparticles exhibit superior efficacy in liver protection and repair compared to pure quercetin, with the highest dose group showing the best therapeutic effect.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"112"},"PeriodicalIF":2.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172112","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":"The assessment of the relationship between anticholinergic burden and short-term blood pressure variability.","authors":"Cevdet Furkan Köşker, Reşit Emre Alparğan, Muhammed Ali Coşkuner, Gökhan Köker, Bilgin Bahadır Başgöz","doi":"10.1186/s40360-025-00952-w","DOIUrl":"10.1186/s40360-025-00952-w","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the relationship between short-term blood pressure variability (BPV) and anticholinergic burden (ACB) in adults with hypertension.</p><p><strong>Methods: </strong>This study included 238 hypertensive patients aged 50 and older who underwent ambulatory blood pressure monitoring. The medications used by the patients were recorded, and the ACB of each medication was calculated using the ACB Scale. The BPV was assessed based on 24-hour ambulatory blood pressure measurements using three methods: standard deviation (SD), coefficient of variation of the standard deviation (SD-CoV), and weighted standard deviation (wSD), with evaluations conducted for both day-time and night-time periods.</p><p><strong>Results: </strong>A total of 139 patients (58.40%) had no ACB score, 64 (26.89%) had an ACB score of 1, and 35 (14.71%) had an ACB score of 2 or higher. ACB scores were significantly higher among patients with heart disease, and ACB tended to increase with age. However, no statistically significant relationship was found between ACB and mean blood pressure, nocturnal blood pressure dips, or any parameters of short-term BPV including Sd, SD-CoV and wSD.</p><p><strong>Conclusion: </strong>No significant association was found between ACB and short-term BPV. To the best of our knowledge, this is the first study to investigate this relationship, which may inspire further research.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"113"},"PeriodicalIF":2.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172114","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":"Ranolazine as a therapeutic agent for diabetic cardiomyopathy: reducing endoplasmic reticulum stress and inflammation in type 2 diabetic rat model.","authors":"Matin Mohyadini, Aghele Fahimi, S Zahra Bathaie, Hamid Yaghooti","doi":"10.1186/s40360-025-00945-9","DOIUrl":"10.1186/s40360-025-00945-9","url":null,"abstract":"<p><strong>Background: </strong>Diabetic cardiomyopathy (DCM) is a significant cardiovascular complication of diabetes, characterized by structural and functional heart muscle dysfunction. Oxidative stress, endoplasmic reticulum (ER) stress, and inflammation are pivotal in the pathogenesis of DCM. Ranolazine, primarily used for angina, has demonstrated potential cardioprotective effects. This study investigates the effects of ranolazine on oxidative stress, ER stress, and inflammation in the heart tissue of type 2 diabetic rats.</p><p><strong>Methods: </strong>Diabetes was induced in male Wistar rats using Nicotinamide (110 mg/kg) and Streptozotocin (60 mg/kg). The rats were then divided into control and diabetic groups, with further subdivision into ranolazine-treated and untreated subgroups. Ranolazine was administered via gavage for eight weeks. Various parameters, including body weight, heart weight, serum glucose, troponin-I levels, oxidative stress markers, ER stress markers, and inflammatory markers, were assessed.</p><p><strong>Results: </strong>Diabetic rats showed increased heart weight and decreased body weight over eight weeks. Ranolazine treatment improved body weight but didn't affect serum glucose levels. The treatment significantly lowered serum troponin-I and oxidative stress markers, increased superoxide dismutase (SOD) and glutathione (GSH) levels, and decreased malondialdehyde (MDA) concentrations. Additionally, ranolazine reduced the expression of stress-related genes (GRP78, XBP1, and NLRP3) and lowered serum IL1β levels.</p><p><strong>Conclusions: </strong>The results indicate that ranolazine protects against DCM by attenuating oxidative stress, ER stress, and inflammation. Its potential as a therapeutic agent for DCM warrants further investigation.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"111"},"PeriodicalIF":2.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156884","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":"Safety evaluation of baloxavir marboxil: analysis and discussion utilizing real adverse events from the FAERS database.","authors":"Xiaolong Lai, Liuyin Jin, Yixia Zhou, Yang Li, Lindan Sheng, Guomin Xie, Jianjiang Fang","doi":"10.1186/s40360-025-00940-0","DOIUrl":"10.1186/s40360-025-00940-0","url":null,"abstract":"<p><strong>Background: </strong>As a novel anti-influenza agent, baloxavir marboxil lacks real-world safety data in large populations. Therefore, this study aimed to investigate adverse drug events (ADEs) associated with baloxavir marboxil by analyzing the Food and Drug Administration Adverse Event Reporting System (FAERS) database.</p><p><strong>Methods: </strong>Adverse event reports involving baloxavir marboxil were extracted from the FAERS database spanning the fourth quarter of 2018 to the third quarter of 2023. Demographic characteristics and reporter profiles were analyzed to characterize the exposed population. A disproportionality analysis was performed using four validated pharmacovigilance algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). These complementary approaches were employed to detect, prioritize, and validate potential safety signals.</p><p><strong>Results: </strong>Analysis of 8,824,675 ADE reports from the FAERS database identified 1,654 cases (0.19%) associated with baloxavir marboxil. Pediatric patients (< 18 years) exhibited the highest ADE reporting rate. Geospatial analysis revealed marked clustering, with 98.97% of reports originating from the United States (63.2%) and Japan (35.77%). We detected 47 significant safety signals spanning 27 System Organ Classes (SOCs), including established reactions such as pneumonia (n = 90) and vomiting (n = 77). Novel signals emerging from the analysis comprised hemorrhagic diathesis (n = 3), rhabdomyolysis (n = 25), hepatic dysfunction (n = 13), and cardiorespiratory arrest (n = 7). Notably, bleeding-related events (e.g., ischemic colitis, IC025 = 5.03) and neurological complications (e.g., febrile delirium, IC025 = 9.12) demonstrated statistically significant associations.</p><p><strong>Conclusion: </strong>This pharmacovigilance study identifies previously undercharacterized safety signals associated with baloxavir marboxil, including hemorrhagic complications, liver dysfunction, rhabdomyolysis, and life-threatening cardiorespiratory events. Pediatric populations and patients on anticoagulants may require heightened monitoring. While these findings provide critical pharmacovigilance insights, our study is inherently constrained by the spontaneous reporting system, which introduces potential underreporting, reporting biases, and confounding factors. Future research could employ more rigorous prospective study designs, integrating clinical trials and epidemiological studies, to more accurately assess the safety risks of baloxavir marboxil.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"110"},"PeriodicalIF":2.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149108","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":"Effect of probiotics on prognosis in patients with hepatectomy: a systematic review and meta-analysis of randomized controlled trial.","authors":"Qinghu Jiang, Hua Zou, Furui Zhong, Jian Ma","doi":"10.1186/s40360-025-00944-w","DOIUrl":"10.1186/s40360-025-00944-w","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effect of perioperative probiotics on prognosis in patients with hepatectomy.</p><p><strong>Method: </strong>By conducting a computer-based search of electronic databases to collect randomized controlled trials (RCTs) on the use of probiotics in the perioperative period for patients undergoing liver resection. Two researchers independently screened the literature, extracted data, assessed bias risk, and performed a meta-analysis using RevMan 5.4 software.</p><p><strong>Result: </strong>A total of 988 patients were enrolled across 14 studies. The results of the meta-analysis revealed that the probiotics group had lower rates of postoperative infectious complications (OR = 0.49; 95%CI 0.49 to 0.60; P < 0.01), serum endotoxin levels (SMD= -0.69; 95%CI -1.27 to -0.11; P = 0.02), white blood cell counts (SMD= -0.37; 95%CI -0.67 to -0.061.47; P = 0.02), hospital stays (SMD= -0.85; 95%CI -1.53 to -0.18; P = 0.01), and first postoperative exhaust times (SMD= -0.85; 95%CI -1.53 to -0.18; P = 0.01) compared to the control group. No significant differences in liver function indices (alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBiL) and international normalized ratio (INR)) or postoperative inflammatory markers (C-reactive protein (CRP), procalcitonin, interleukin-6 (IL-6)) were found between the two groups (all P > 0.05).</p><p><strong>Conclusions: </strong>Probiotics used perioperatively can lower postoperative infection risk and shorten hospital stays for hepatectomy patients, but they do not appear to aid in liver function restoration or inflammation reduction.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"109"},"PeriodicalIF":2.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149106","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":"Medication errors in malaria management in children: insights from pharmacovigilance data in the Democratic Republic of Congo.","authors":"Mireille Ngale Amba, Erick Kamangu Ntambwe, Aline Engo Biongo, Nsengi Ntamabyaliro, Gauthier Mesia Kahunu, Joseph Bodi Mabiala, Celestin Nsibu Ndosimao, Gaston Tona Lutete, Ghada Miremont-Salamé, Annie Fourrier-Réglat","doi":"10.1186/s40360-025-00941-z","DOIUrl":"10.1186/s40360-025-00941-z","url":null,"abstract":"<p><strong>Introduction: </strong>Since 2012, DRC adopted WHO recommendations for the malaria treatment with artemisinin-based drugs. Medication errors are defined as \"a failure in the treatment process that results in, or has the potential to result in, harm to the patient\". Medication errors are a major public health problem and one of the leading causes of death in the United States. The impact of medical errors can have severe consequences on children due to physiological features of children.</p><p><strong>Objectives: </strong>To identify, describe, and propose actionable strategies to address medication errors during malaria treatment in children with adverse effects in the DRC.</p><p><strong>Methods: </strong>This is a cross-sectional study of the ADR reports of children (< 18 years old) in the DRC recorded in VigiBase^®, the WHO pharmacovigilance database, from 2010 to February 2018. Five treatment process criteria (choice of treatment, dosage, duration, timing and route of administration) were selected to identify medication errors.</p><p><strong>Results: </strong>Medication errors accounted for 65,9% of the 851 cases retrieved from VigiBase^®. Children aged 2-11 years represented 55.2% of the study population. The choice of treatment, duration and dosage were the main prescription criteria for deviations.</p><p><strong>Discussion: </strong>The availability of alternative formulations, self-medication and inadequate dosage forms are factors contributing to medication errors. The information available in VigiBase^® did not allow us to evaluate the overall process of malaria management. Pharmacovigilance must be consolidated to raise awareness among consumers and providers and to ensure more effective monitoring.</p><p><strong>Conclusion: </strong>Non-compliance with national guidelines for the management of malaria is important in DRC. Our study amply demonstrates the need to strengthen the four pillars of the WHO's third global challenge, \"Medication without harm\", to reduce medication errors. This study advocates a significant mobilisation of resources for the training of health professionals and the strengthening of pharmacovigilance. Field studies on the management of malaria in children should be conducted to quantify drug errors.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"108"},"PeriodicalIF":2.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126286","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":"Safety, pharmacokinetics, preliminary efficacy, pharmacodynamics, and immunogenicity of QX002N, an anti-IL-17A monoclonal antibody, after short-term treatment of active ankylosing spondylitis.","authors":"Min Wu, Qianqian Li, Min Fang, Hong Zhang, Yanhua Ding","doi":"10.1186/s40360-025-00885-4","DOIUrl":"10.1186/s40360-025-00885-4","url":null,"abstract":"<p><strong>Background: </strong>To investigate the safety, pharmacokinetics, preliminary efficacy, pharmacodynamics, and immunogenicity of QX002N, an interleukin-17 A monoclonal antibody, in Chinese patients with active ankylosing spondylitis (AS).</p><p><strong>Methods: </strong>In this phase 1b, double-blind, placebo-controlled, multiple ascending dose study, eligible patients with active AS were randomized into three dose (40, 80, or 160 mg) cohorts, with a 4:1 ratio in each cohort to subcutaneously receive either QX002N or a placebo once every 2 weeks with six doses in total. All patients were followed for 14 weeks (98 days) after the last dose. The primary endpoints were the safety and pharmacokinetics of QX002N, and the secondary endpoints included its preliminary efficacy, pharmacodynamics, and immunogenicity.</p><p><strong>Results: </strong>Thirty patients (n = 10 in each cohort) were included, with 24 receiving QX002N and 6 receiving a placebo. A total of 85 adverse drug reactions, predominantly Grade 1-2, were identified in 20 out of 24 patients (83.3%) who took QX002N. The exposure to QX002N increased proportionally with the dose escalating from 40 mg to 160 mg. Patients taking 160 mg QX002N achieved higher response rates (ASAS20: 87.6% at Week 8 [Day 56]); ASAS40: 50.0% at Week 12 [Day 78]), than those taking 40-mg or 80-mg QX002N. An increase in interleukin-17 A and a decrease in interleukin-6 levels in the serum, with decreases in the erythrocyte sedimentation rate and high-sensitivity C-reactive protein levels, were observed. Anti-drug antibodies were detected in only one of 24 patients taking QX002N.</p><p><strong>Conclusions: </strong>Subcutaneous administration of QX002N demonstrates a favorable safety profile, with linear pharmacokinetic characteristics. Promising clinical responses in pharmacodynamics and preliminary efficacy have been observed. Immunogenicity does not appear to be a concern.</p><p><strong>Trial registration: </strong>This study was registered with Chinadrugtrials.org.cn (CTR20201277), the data of registration was in 20 Jul, 2020.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"107"},"PeriodicalIF":2.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101256","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":"Immunomodulatory effects of detoxification agents on dendritic cell populations in methamphetamine addiction.","authors":"Ghasem Mosayebi, Seyed Mohammad Moazzeni, Hadiseh Farahani, Hassan Solhi, Mohammad Rafiei, Ali Ghazavi","doi":"10.1186/s40360-025-00943-x","DOIUrl":"10.1186/s40360-025-00943-x","url":null,"abstract":"<p><strong>Background and aim: </strong>Drug abuse can impact the function of immune cells, leading to a compromised immune system response. This study aimed to investigate the immunomodulatory effects of Methamphetamine and its detoxification agents on peripheral blood dendritic cells.</p><p><strong>Methods: </strong>A total of 60 participants were enrolled, including 30 individuals with Methamphetamine addiction and 30 matched healthy controls. Participants were assessed at three time points: at the beginning of detoxification, at the end of detoxification, and one-month post-detoxification. Flow cytometry was employed to analyze dendritic cell subsets (CD11c + myeloid dendritic cells and CD123 + plasmacytoid dendritic cells) and surface marker expression (HLA-DR, CD11c, CD123).</p><p><strong>Results: </strong>The percentages of both CD11c + and CD123 + dendritic cells in peripheral blood were significantly lower in Methamphetamine addicts compared to the control group. Detoxification with Risperidone corrected this reduction, while the combination of Risperidone and Methylphenidate failed to produce any change in the percentage of dendritic cells. The expression of HLA-DR, CD11c, and CD123 markers was downregulated in the dendritic cells of Methamphetamine addicts. Treatment with Risperidone restored these markers, whereas the combination therapy further exacerbated the downregulation of these markers.</p><p><strong>Conclusion: </strong>The findings suggest that detoxification with Risperidone may help ameliorate the immunological disorders associated with Methamphetamine use.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"106"},"PeriodicalIF":2.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101339","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}