Frontiers in Pharmacology最新文献_第8页

Case report: Epilepsy during the use of recombinant human growth hormone: a report on two cases and a literature review 病例报告：使用重组人生长激素期间的癫痫：两例病例报告和文献综述

IF 5.6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Frontiers in Pharmacology

Pub Date : 2024-09-12 DOI: 10.3389/fphar.2024.1458487

Yuan Zhou, Ruofan Jia, Zhuangjian Xu, Yaping Ma

BackgroundEpilepsy during recombinant human growth hormone (rhGH) therapy is rare in children. The potential association between rhGH treatment and epilepsy remains unclear.MethodsWe retrospectively analyzed the clinical data of two Chinese boys who experienced epilepsy during the use of rhGH and reviewed the relevant literature.Results:Case 1, an 8-year and 2-month-old boy, was diagnosed with short stature, malnutrition, and congenital hypothyroidism. He was on levothyroxine sodium tablets for a long time. Recurrent febrile convulsions were present at 6–7 years. Electroencephalogram and magnetic resonance imaging (MRI) showed no abnormality, and no treatment was given. He was diagnosed with complex febrile convulsions. The boy started rhGH treatment (approximately 0.15 IU/kg/day, sc, qd) at 8 years and 4 months. Epilepsy occurred three times during the 6 months of rhGH treatment. Electroencephalography confirmed a definitive diagnosis of epilepsy. Then, he discontinued rhGH treatment at 8 years and 11 months and started taking levetiracetam (0.25 g, po, bid) for antiepileptic therapy. Epilepsy was well-controlled 4 months later. He continued rhGH treatment at 10 years and 3 months and has been on rhGH treatment until now, with no recurrence of epilepsy. He has been taking levetiracetam to date. Case 2, a 9-year and 1-month-old boy, was diagnosed with central precocious puberty, predicted short final height, and overweight. He started treatment with triptorelin (3.75 mg, im, q4w) and rhGH (approximately 0.15 IU/kg/day, sc, qd) at 9 years and 3 months. He tended to fall repeatedly when he was approximately 10 years old. Electroencephalography showed a few medium- to high-amplitude sharp waves and sporadic sharp slow waves in the left middle temporal region, sometimes involving the left posterior temporal region. He was diagnosed with epilepsy. Triptorelin discontinuance provided no symptom relief, which worsened further. Subsequently, he withdrew from rhGH treatment, and the symptoms occurred occasionally within a week and stopped after 15 days. The electroencephalogram returned to normal. No further seizures occurred during follow-up to date.ConclusionDuring the use of rhGH in short-stature children with complex febrile convulsions or underlying lesions related to neurological impairment or those being treated with antiepileptic drugs, epilepsy may be induced.

背景重组人生长激素（rhGH）治疗期间的癫痫在儿童中很少见。结果：病例1是一名8岁零2个月大的男孩，被诊断为身材矮小、营养不良和先天性甲状腺功能减退症。他长期服用左甲状腺素钠片。6-7 岁时出现反复发热抽搐。脑电图和磁共振成像（MRI）均未显示异常，也未给予治疗。他被诊断为复杂性热性惊厥。男孩在8岁零4个月时开始接受rhGH治疗（约0.15 IU/kg/天，皮质，每天一次）。在接受rhGH治疗的6个月期间，癫痫发作了3次。脑电图确诊为癫痫。随后，他在8岁11个月时停止了rhGH治疗，开始服用左乙拉西坦（0.25克，po，bid）进行抗癫痫治疗。4 个月后，癫痫得到了很好的控制。10 岁零 3 个月时，他继续接受 rhGH 治疗，至今癫痫未复发。迄今为止，他一直在服用左乙拉西坦。病例 2 是一名 9 岁零 1 个月大的男孩，被诊断为中枢性性早熟、预测身高偏矮和超重。他在 9 岁零 3 个月时开始接受曲普瑞林（3.75 毫克，im，q4w）和 rhGH（约 0.15 IU/kg/天，sc，qd）治疗。他在大约 10 岁时有反复跌倒的倾向。脑电图显示，左侧中颞区有一些中到高波幅的尖波和零星的尖慢波，有时涉及左侧后颞区。他被诊断为癫痫。停用曲普瑞林后症状没有缓解，反而进一步恶化。随后，他停止了rhGH治疗，症状在一周内偶尔出现，15天后停止。脑电图恢复正常。结论对于患有复杂热性惊厥或神经系统损伤相关潜在病变的矮身材儿童，或正在接受抗癫痫药物治疗的儿童，在使用rhGH期间可能会诱发癫痫。

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引用次数: 0

Corrigendum: Effects of Bifidobacterium bifidum tetragonum tablets and Jin Gui Ren Qi Pill on intestinal flora and metabolism in patients with diabetic kidney disease. 更正：双歧杆菌四联活菌片和金匮肾气丸对糖尿病肾病患者肠道菌群和代谢的影响。

IF 4.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

Frontiers in Pharmacology

Pub Date : 2024-09-12 eCollection Date: 2024-01-01 DOI: 10.3389/fphar.2024.1480859

Cheng-Yu Zhang, Dong-Jie Yue, Di Wang, Fei-Fei Wu

[This corrects the article DOI: 10.3389/fphar.2024.1346168.].

引用次数: 0

Wuwei Kushen Changrong capsule alleviates DSS-induced colitis in mice via inhibition of NLRP3 inflammasome and STAT3 pathway. 武威苦参长荣胶囊通过抑制NLRP3炎性体和STAT3通路缓解DSS诱导的小鼠结肠炎

IF 4.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

Frontiers in Pharmacology

Pub Date : 2024-09-12 eCollection Date: 2024-01-01 DOI: 10.3389/fphar.2024.1423012

Mingjun Chen, Yang Feng, Dan Luo, Chen Zhang, Jing Zhou, Hengheng Dai, Mingxiong Lin, ZhanQi Tong

Purpose: Wuwei Kushen Changrong capsule (Composite Sophora Colon-soluble Capsule, CSCC) is a Chinese patent medicine developed to treat ulcerative colitis. Studies highlight CSCC potential efficacy for ulcerative colitis (UC) but unclear mechanism limits its widely treatment for patients. We aimed to investigate the anti-colitis efficacy of CSCC and explore the mechanism by which GPR43 inhibits the NLRP3/STAT3 signaling pathway, thereby mediating the protective effects of CSCC on the intestinal barrier.

Methods: The protective effects of CSCC were evaluated in a murine ulcerative colitis model induced by 3% DSS. Assessments included body weight, Disease Activity Index (DAI) score, colon length, and histopathological score. Colon tissue, cell function, and immune-inflammatory status were evaluated using immunohistochemistry, immunofluorescence, ELISA, and real-time fluorescence quantitative PCR (RT-PCR). Protein expression levels of relevant pathways and receptors were measured using Western blot. All experiments were repeated.

Results: CSCC protected mice from DSS-induced colitis by upregulating Gpr43, promoting the expression of ZO-1 and Occludin tight junction proteins. Mechanistically, CSCC inhibits the MEK4/JNK1/STAT3 activation pathway, consequently suppressing the STAT3/NLRP3/IL-1β pathway and inhibiting the production of inflammatory factors such as IL-17A.

Conclusion: The mechanisms through which CSCC protects against DSS-induced colitis may include upregulating Gpr43, inhibiting the STAT3/NLRP3 pathway, and suppressing inflammation factors like IL-17A. These findings highlight the mechanisms underlying CSCC's anti-colitis effects and suggest its potential as a therapeutic candidate for managing the progression of UC.

目的：无为苦参长荣胶囊（复方槐花结肠溶胶囊，CSCC）是一种用于治疗溃疡性结肠炎的中成药。研究表明，长荣胶囊对溃疡性结肠炎（UC）具有潜在疗效，但由于机制不清，其治疗范围有限。我们旨在研究CSCC的抗结肠炎功效，并探索GPR43抑制NLRP3/STAT3信号通路，从而介导CSCC对肠屏障保护作用的机制：方法：在 3% DSS 诱导的小鼠溃疡性结肠炎模型中评估 CSCC 的保护作用。评估包括体重、疾病活动指数（DAI）评分、结肠长度和组织病理学评分。使用免疫组化、免疫荧光、酶联免疫吸附和实时荧光定量 PCR（RT-PCR）对结肠组织、细胞功能和免疫炎症状态进行了评估。采用 Western 印迹法测定了相关通路和受体的蛋白表达水平。所有实验均重复进行：结果：CSCC通过上调Gpr43、促进ZO-1和Occludin紧密连接蛋白的表达，保护小鼠免受DSS诱导的结肠炎的影响。从机制上讲，CSCC抑制了MEK4/JNK1/STAT3活化途径，从而抑制了STAT3/NLRP3/IL-1β途径，抑制了IL-17A等炎症因子的产生：结论：CSCC保护DSS诱导的结肠炎的机制可能包括上调Gpr43、抑制STAT3/NLRP3通路和抑制IL-17A等炎症因子。这些发现强调了 CSCC 抗结肠炎作用的机制，并表明 CSCC 有可能成为控制 UC 病程进展的候选疗法。

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引用次数: 0

Adjuvant and neoadjuvant therapy with or without CDK4/6 inhibitors in HR+/HER2- early breast cancer: a systematic review and meta-analysis 使用或不使用CDK4/6抑制剂对HR+/HER2-早期乳腺癌进行辅助治疗和新辅助治疗：系统综述和荟萃分析

IF 5.6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Frontiers in Pharmacology

Pub Date : 2024-09-12 DOI: 10.3389/fphar.2024.1438288

Zhihao Zhang, Xin Zhao, Jie Chen

BackgroundThe combination of cyclin-dependent kinases 4/6 (CDK4/6) inhibitors and endocrine therapy is the standard treatment for patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) advanced breast cancer. However, the role of CDK4/6 inhibitors in early breast cancer remains controversial.MethodsThis study aimed to evaluate the efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy versus endocrine therapy alone in patients with HR+, HER2- early breast cancer. A systematic review of Cochrane, PubMed and EMBASE databases was conducted. The efficacy endpoints of adjuvant therapy were invasive disease-free survival (IDFS), overall survival (OS) and distant relapse-free survival (DRFS). The efficacy endpoint included complete cell cycle arrest (CCCA) and complete pathologic response (PCR) with neoadjuvant therapy. Grade 3/4 adverse events (AEs) were assessed as safety outcomes.ResultsEight randomized controlled trials (RCTs) were included in the study. CDK4/6 inhibitors combined with endocrine therapy showed a significant improvement in IDFS (hazard ratio (HR) = 0.81, 95% confidence interval (CI) = 0.68–0.97, P = 0.024), but not DRFS (HR = 0.84, 95% CI = 0.56–1.29, P = 0.106) or OS (HR = 0.96, 95% CI = 0.77–1.19, P = 0.692) in adjuvant therapy. In the neoadjuvant therapy setting, CDK4/6 inhibitors improved CCCA compared with the control group (RR = 2.08, 95% CI = 1.33–3.26, P = 0.001). The risk of 3/4 grade AEs increased significantly with the addition of CDK4/6 inhibitors to endocrine therapy.ConclusionThe addition of CDK4/6 inhibitors in HR+/HER2- early breast cancer patients significantly improved IDFS in adjuvant therapy and CCCA in neoadjuvant. However, CDK4/6 inhibitors also showed significant toxicities during therapy.Systematic Review Registration:Identifier CRD42024530704.

背景细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂与内分泌治疗的联合应用是激素受体阳性（HR+）/HER2阴性（HER2-）晚期乳腺癌患者的标准治疗方法。本研究旨在评估 CDK4/6 抑制剂联合内分泌治疗与单纯内分泌治疗对 HR+、HER2- 早期乳腺癌患者的疗效和安全性。研究人员对 Cochrane、PubMed 和 EMBASE 数据库进行了系统回顾。辅助治疗的疗效终点为无侵袭性疾病生存期（IDFS）、总生存期（OS）和无远处复发生存期（DRFS）。疗效终点包括新辅助治疗的完全细胞周期停滞（CCCA）和完全病理反应（PCR）。3/4级不良事件（AEs）被评估为安全性结果。在辅助治疗中，CDK4/6抑制剂联合内分泌治疗可显著改善IDFS（危险比（HR）=0.81，95%置信区间（CI）=0.68-0.97，P=0.024），但不能改善DRFS（HR=0.84，95% CI=0.56-1.29，P=0.106）或OS（HR=0.96，95% CI=0.77-1.19，P=0.692）。在新辅助治疗中，与对照组相比，CDK4/6抑制剂可改善CCCA（RR = 2.08，95% CI = 1.33-3.26，P = 0.001）。结论在HR+/HER2-早期乳腺癌患者中添加CDK4/6抑制剂可显著改善辅助治疗中的IDFS和新辅助治疗中的CCCA。然而，CDK4/6抑制剂在治疗过程中也表现出明显的毒性。

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引用次数: 0

Overcoming drug resistance of cancer cells by targeting the FGF1/FGFR1 axis with honokiol or FGF ligand trap. 利用霍诺克醇或 FGF 配体陷阱靶向 FGF1/FGFR1 轴，克服癌细胞的耐药性。

IF 4.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

Frontiers in Pharmacology

Pub Date : 2024-09-12 eCollection Date: 2024-01-01 DOI: 10.3389/fphar.2024.1459820

Jakub Szymczyk, Martyna Sochacka, Martyna Biadun, Katarzyna Dominika Sluzalska, Danuta Witkowska, Malgorzata Zakrzewska

Background: Chemoresistance of cancer cells, resulting from various mechanisms, is a significant obstacle to the effectiveness of modern cancer therapies. Targeting fibroblast growth factors (FGFs) and their receptors (FGFRs) is becoming crucial, as their high activity significantly contributes to cancer development and progression by driving cell proliferation and activating signaling pathways that enhance drug resistance.

Methods: We investigated the potential of honokiol and FGF ligand trap in blocking the FGF1/FGFR1 axis to counteract drug resistance. Using PEAQ-ITC, we verified direct interaction of honokiol with the FGFR1 kinase domain. We then demonstrated the effect of FGF1/FGFR1 inhibition on taltobulin resistance in cells expressing FGFR1. Finally, we generated drug-resistant clones by prolonged exposure of cells with negligible FGFR levels to taltobulin alone, taltobulin and honokiol, or taltobulin and FGF ligand trap.

Results: We demonstrated for the first time a direct interaction of honokiol with the FGFR1 kinase domain, resulting in inhibition of downstream signaling pathways. We revealed that both honokiol and FGF ligand trap prevent FGF1-dependent protection against taltobulin in cancer cells expressing FGFR1. In addition, we showed that cells obtained by long-term exposure to taltobulin are resistant to both taltobulin and other microtubule-targeting drugs, and exhibit elevated levels of FGFR1 and cyclin D. We also found that the presence of FGF-ligand trap prevents the development of long-term resistance to taltobulin.

Conclusion: Our results shed light on how blocking the FGF1/FGFR1 axis by honokiol and FGF ligand trap could help develop more effective cancer therapies, potentially preventing the emergence of drug-resistant relapses.

背景：各种机制导致的癌细胞耐药性是现代癌症疗法有效性的一大障碍。靶向成纤维细胞生长因子（FGFs）及其受体（FGFRs）正变得至关重要，因为它们的高活性通过驱动细胞增殖和激活增强耐药性的信号通路，极大地促进了癌症的发生和发展：我们研究了霍诺克醇和 FGF 配体陷阱在阻断 FGF1/FGFR1 轴以对抗耐药性方面的潜力。我们使用 PEAQ-ITC 验证了霍诺基奥与 FGFR1 激酶结构域的直接相互作用。然后，我们证明了抑制 FGF1/FGFR1 对表达 FGFR1 的细胞产生滑脱素耐药性的影响。最后，我们将 FGFR 含量可忽略不计的细胞长期暴露于taltobulin 单药、taltobulin 和 honokiol 或 taltobulin 和 FGF 配体陷阱中，从而产生了耐药克隆：结果：我们首次证明了honokiol与表皮生长因子受体1激酶结构域的直接相互作用，从而抑制了下游信号通路。我们发现，在表达 FGFR1 的癌细胞中，honokiol 和 FGF 配体捕获剂都能阻止 FGF1 依赖性保护作用。此外，我们还发现，长期暴露于taltobulin的细胞会对taltobulin和其他微管靶向药物产生耐药性，并表现出FGFR1和细胞周期蛋白D水平的升高：我们的研究结果揭示了通过霍诺克醇和表皮生长因子配体诱捕剂阻断表皮生长因子1/表皮生长因子1轴如何有助于开发更有效的癌症疗法，并有可能防止耐药性复发的出现。

{"title":"Overcoming drug resistance of cancer cells by targeting the FGF1/FGFR1 axis with honokiol or FGF ligand trap.","authors":"Jakub Szymczyk, Martyna Sochacka, Martyna Biadun, Katarzyna Dominika Sluzalska, Danuta Witkowska, Malgorzata Zakrzewska","doi":"10.3389/fphar.2024.1459820","DOIUrl":"https://doi.org/10.3389/fphar.2024.1459820","url":null,"abstract":"Background: Chemoresistance of cancer cells, resulting from various mechanisms, is a significant obstacle to the effectiveness of modern cancer therapies. Targeting fibroblast growth factors (FGFs) and their receptors (FGFRs) is becoming crucial, as their high activity significantly contributes to cancer development and progression by driving cell proliferation and activating signaling pathways that enhance drug resistance.Methods: We investigated the potential of honokiol and FGF ligand trap in blocking the FGF1/FGFR1 axis to counteract drug resistance. Using PEAQ-ITC, we verified direct interaction of honokiol with the FGFR1 kinase domain. We then demonstrated the effect of FGF1/FGFR1 inhibition on taltobulin resistance in cells expressing FGFR1. Finally, we generated drug-resistant clones by prolonged exposure of cells with negligible FGFR levels to taltobulin alone, taltobulin and honokiol, or taltobulin and FGF ligand trap.Results: We demonstrated for the first time a direct interaction of honokiol with the FGFR1 kinase domain, resulting in inhibition of downstream signaling pathways. We revealed that both honokiol and FGF ligand trap prevent FGF1-dependent protection against taltobulin in cancer cells expressing FGFR1. In addition, we showed that cells obtained by long-term exposure to taltobulin are resistant to both taltobulin and other microtubule-targeting drugs, and exhibit elevated levels of FGFR1 and cyclin D. We also found that the presence of FGF-ligand trap prevents the development of long-term resistance to taltobulin.Conclusion: Our results shed light on how blocking the FGF1/FGFR1 axis by honokiol and FGF ligand trap could help develop more effective cancer therapies, potentially preventing the emergence of drug-resistant relapses.","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344720","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}

引用次数: 0

Inhibition of the RIP3/MLKL/TRPM7 necroptotic pathway ameliorates diabetes mellitus-induced erectile dysfunction by reducing cell death, fibrosis, and inflammation 通过减少细胞死亡、纤维化和炎症，抑制 RIP3/MLKL/TRPM7 坏死途径可改善糖尿病诱发的勃起功能障碍

IF 5.6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Frontiers in Pharmacology

Pub Date : 2024-09-12 DOI: 10.3389/fphar.2024.1436013

Lipan Niu, Pei Yang, Bingbing Zhu, Xiufang Jin, Chengxia Yang, Xijia Zhang, Yulian Liu, Rui Zhang, Fengxia Liu

Diabetes mellitus-induced erectile dysfunction (DMED) is a common complication in patients with diabetes mellitus. Necroptosis is regarded as a form of cell death that is intimately associated with the inflammatory response, which is not only initiated by inflammatory factors such as TNF-α, but also triggers the inflammatory cascade through the rupture of the dying cell. There is no definitive study on the role of necroptosis in the pathological process of DMED. In light of the pathological features of high inflammation levels in DMED patients, we assessed whether the necroptosis plays an important role in the course of DMED. Our study revealed that penile tissues of DMED rats showed high levels of key necroptosis factors such as receptor-interacting protein kinase 3 (RIP3), mixed-lineage kinase domain-like protein (MLKL), and transient receptor potential melatonin 7 (TRPM7). Furthermore, the inhibition of necroptosis with a receptor-interacting protein kinase 3 (RIP3) inhibitor or Yimusake (a common herbal remedy for ED) effectively rescued damage to corpus cavernosum smooth muscle cells (CCSMC) under high glucose conditions. Our findings suggest that inhibition of the RIP3/MLKL/TRPM7 necroptotic pathway could effectively ameliorate CCSMCs fibrosis and death induced by high glucose and inhibited the inflammatory response.

糖尿病诱发的勃起功能障碍（DMED）是糖尿病患者常见的并发症。坏死被认为是一种与炎症反应密切相关的细胞死亡形式，它不仅由 TNF-α 等炎症因子引发，还通过濒死细胞的破裂触发炎症级联反应。关于坏死细胞在 DMED 病理过程中的作用，目前还没有明确的研究。鉴于DMED患者炎症水平较高的病理特征，我们评估了坏死细胞在DMED病程中是否扮演重要角色。我们的研究发现，DMED大鼠的阴茎组织显示出高水平的关键坏死因子，如受体相互作用蛋白激酶3（RIP3）、混合系激酶结构域样蛋白（MLKL）和瞬时受体电位褪黑激素7（TRPM7）。此外，在高糖条件下，用受体相互作用蛋白激酶3（RIP3）抑制剂或Yimusake（一种治疗ED的常用中药）抑制坏死突变可有效挽救海绵体平滑肌细胞（CCSMC）的损伤。我们的研究结果表明，抑制RIP3/MLKL/TRPM7坏死通路可有效改善高糖诱导的海绵体平滑肌细胞纤维化和死亡，并抑制炎症反应。

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引用次数: 0

Bibliometric and visual analysis of membranous nephropathy literature from 2010 to 2023 2010 年至 2023 年膜性肾病文献的文献计量和视觉分析

IF 5.6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Frontiers in Pharmacology

Pub Date : 2024-09-12 DOI: 10.3389/fphar.2024.1426897

Yirui Chen, Chen Liu, Hongnan Shen, Pingping Su, Liang Pang, Congcong Zeng, Jinguo Cheng

BackgroundMembranous glomerulonephritis, also known as membranous nephropathy (MN), is a common cause of nephrotic syndrome in adults. Despite extensive research on MN, bibliometric studies on the subject are scarce. Therefore, this study aimed to provide a visual analysis of global trends in membranous nephropathy research over the past 13 years.MethodsThis study conducted a bibliometric and visual analysis of global trends in MN research from 2010 to 2023. Articles related to MN were retrieved from the Web of Science Core Collection (WoSCC) database. Tools such as CiteSpace and VOSviewer were utilized to analyze publications, countries, institutions, authors, publishing journals, co-cited references, and keywords to identify the current state and future trends in MN research.ResultsThe analysis encompassed 1,624 publications, showing an annual increase from 2010 to 2023. The People’s Republic of China emerged as the most active country in this field, while France’s Sorbonne Universite and Institut National de la Sante et de la Recherche Medicale (Inserm) led in publication volume among academic institutions. Debiec Hanna stood out as the most prolific author. BMC Nephrology had the highest number of publications, making it the most favored journal in the field. The article with the greatest co-citation intensity was “Primary Membranous Nephropathy,” a review published in 2017.ConclusionThis study shows that there has been increasing interest in membranous nephropathy over the past 13 years. The most frequently encountered keywords were “membranous nephropathy” “nephrotic syndrome,” and “glomerulonephritis.” Analysis of emerging terms indicated that “a2 receptor antibody,” “domain containing 7a,” and “t cell” may remain prominent subjects of research in the forthcoming years. The findings highlight key research trends and areas of interest that can inform researchers, clinicians, and policymakers about the current state of MN research and help guide future research directions and clinical practice.

背景膜性肾小球肾炎又称膜性肾病（MN），是成人肾病综合征的常见病因。尽管对膜性肾小球肾炎进行了广泛的研究，但有关这一主题的文献计量学研究却很少。因此，本研究旨在对过去13年间膜性肾病研究的全球趋势进行直观分析。方法本研究对2010年至2023年MN研究的全球趋势进行了文献计量和直观分析。与膜性肾病相关的文章均从科学网核心数据库（Web of Science Core Collection，WoSCC）中检索。利用 CiteSpace 和 VOSviewer 等工具对出版物、国家、机构、作者、出版期刊、共被引用文献和关键词进行分析，以确定 MN 研究的现状和未来趋势。中华人民共和国是该领域最活跃的国家，而法国索邦大学和国立卫生与医学研究院（Inserm）的论文数量在学术机构中遥遥领先。Debiec Hanna是最多产的作者。BMC 肾脏病学》发表的论文数量最多，是该领域最受青睐的期刊。联合引用强度最大的文章是《原发性膜性肾病》，这是一篇发表于2017年的综述。最常出现的关键词是 "膜性肾病""肾病综合征 "和 "肾小球肾炎"。对新兴术语的分析表明，"a2 受体抗体"、"含 7a 的结构域 "和 "t 细胞 "在未来几年可能仍是研究的主要课题。研究结果突出了主要的研究趋势和关注领域，可为研究人员、临床医生和决策者提供有关 MN 研究现状的信息，并有助于指导未来的研究方向和临床实践。

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引用次数: 0

Mapping and visualization of global research progress on deubiquitinases in ovarian cancer: a bibliometric analysis 卵巢癌中的去泛素酶全球研究进展图谱与可视化：文献计量分析

IF 5.6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Frontiers in Pharmacology

Pub Date : 2024-09-12 DOI: 10.3389/fphar.2024.1445037

Fang Qiu, Yuntong Li, Lile Zhou, Yingli Wu, Yunzhao Wu, Zhilei Fan, Yingying Wang, Dongjun Qin, Chaoqun Li

BackgroundOvarian cancer is a highly aggressive malignancy with limited therapeutic options and a poor prognosis. Deubiquitinating enzymes (DUBs) have emerged as critical regulators of protein ubiquitination and proteasomal degradation, influencing various cellular processes relevant to cancer pathogenesis. In this study, the research progress between ovarian cancer and DUBs was mapped and visualized using bibliometrics, and the expression patterns and biological roles of DUBs in ovarian cancer were summarized.MethodsStudies related to DUBs in ovarian cancer were extracted from the Web of Science Core Collection (WoSCC) database. VOSviewer 1.6.20, CiteSpace 6.3.R1, and R4.3.3 were used for bibliometric analysis and visualization.ResultsFor analysis 243 articles were included in this study. The number of publications on DUBs in ovarian cancer has gradually increased each year. China, the United States, and the United Kingdom are at the center of this field of research. The Johns Hopkins University, Genentech, and Roche Holding are the main research institutions. David Komander, Zhihua Liu, and Richard Roden are the top authors in this field. The top five journals with the largest publication volumes in this field are Biochemical and Biophysical Research Communications, Journal of Biological Chemistry, PLOS One, Nature Communications, and Oncotarget. Keyword burst analysis identified five research areas: “deubiquitinating enzyme,” “expression,” “activation,” “degradation,” and “ubiquitin.” In addition, we summarized the expression profiles and biological roles of DUBs in ovarian cancer, highlighting their roles in tumor initiation, growth, chemoresistance, and metastasis.ConclusionAn overview of the research progress is provided in this study on DUBs in ovarian cancer over the last three decades. It offers insight into the most cited papers and authors, core journals, and identified new trends.

背景卵巢癌是一种侵袭性很强的恶性肿瘤，治疗方案有限，预后很差。去泛素化酶（DUBs）已成为蛋白质泛素化和蛋白酶体降解的关键调控因子，影响着与癌症发病机制相关的各种细胞过程。本研究利用文献计量学方法对卵巢癌与DUBs之间的研究进展进行了映射和可视化，并总结了DUBs在卵巢癌中的表达模式和生物学作用。方法从Web of Science Core Collection（WoSCC）数据库中提取卵巢癌中DUBs的相关研究。使用 VOSviewer 1.6.20、CiteSpace 6.3.R1 和 R4.3.3 进行文献计量分析和可视化。有关卵巢癌中DUBs的论文数量逐年增加。中国、美国和英国是这一研究领域的中心。约翰霍普金斯大学、基因泰克公司和罗氏控股公司是主要的研究机构。大卫-科曼德、刘志华和理查德-罗登是该领域的顶级作者。该领域发表量最大的前五名期刊是《生物化学与生物物理研究通讯》、《生物化学杂志》、《PLOS One》、《自然通讯》和《Oncotarget》。关键词突发分析确定了五个研究领域："去泛素化酶"、"表达"、"激活"、"降解 "和 "泛素"。此外，我们还总结了 DUBs 在卵巢癌中的表达谱和生物学作用，强调了它们在肿瘤发生、生长、化疗抗性和转移中的作用。本研究概述了过去三十年来卵巢癌中 DUBs 的研究进展，深入分析了被引用次数最多的论文和作者、核心期刊以及已发现的新趋势。

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引用次数: 0

Inhibitory effects of calcium channel blockers nisoldipine and nimodipine on ivacaftor metabolism and their underlying mechanism 钙通道阻滞剂尼索地平和尼莫地平对伊伐卡夫多代谢的抑制作用及其内在机制

IF 5.6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Frontiers in Pharmacology

Pub Date : 2024-09-12 DOI: 10.3389/fphar.2024.1403649

Hailun Xia, Xinhao Xu, Jie Chen, Hualu Wu, Yuxin Shen, Xiaohai Chen, Ren-ai Xu, Wenzhi Wu

Ivacaftor is the first potentiator of the cystic fibrosis transmembrane conductance regulator (CFTR) protein approved for use alone in the treatment of cystic fibrosis (CF). Ivacaftor is primarily metabolized by CYP3A4 and therefore may interact with drugs that are CYP3A4 substrates, resulting in changes in plasma exposure to ivacaftor. The study determined the levels of ivacaftor and its active metabolite M1 by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). We screened 79 drugs and 19 severely inhibited ivacaftor metabolism, particularly two cardiovascular drugs (nisoldipine and nimodipine). In rat liver microsomes (RLM) and human liver microsomes (HLM), the half-maximal inhibitory concentrations (IC50) of nisoldipine on ivacaftor metabolism were 6.55 μM and 9.10 μM, respectively, and the inhibitory mechanism of nisoldipine on ivacaftor metabolism was mixed inhibition; the IC50 of nimodipine on ivacaftor metabolism in RLM and HLM were 4.57 μM and 7.15 μM, respectively, and the inhibitory mechanism of nimodipine on ivacaftor was competitive inhibition. In pharmacokinetic experiments in rats, it was observed that both nisoldipine and nimodipine significantly altered the pharmacokinetic parameters of ivacaftor, such as AUC(0-t) and CLz/F. However, this difference may not be clinically relevant. In conclusion, this paper presented the results of studies investigating the interaction between these drugs and ivacaftor in vitro and in vivo. The objective is to provide a rationale for the safety of ivacaftor in combination with other drugs.

伊伐卡夫托是首个获准单独用于治疗囊性纤维化（CF）的囊性纤维化跨膜传导调节因子（CFTR）蛋白增效剂。伊伐卡夫托主要通过CYP3A4代谢，因此可能与CYP3A4底物药物发生相互作用，导致伊伐卡夫托的血浆暴露量发生变化。本研究通过超高效液相色谱串联质谱法（UPLC-MS/MS）测定了伊伐卡夫多及其活性代谢物M1的水平。我们筛选了 79 种药物，其中 19 种严重抑制了伊伐卡夫多的代谢，尤其是两种心血管药物（尼索地平和尼莫地平）。在大鼠肝微粒体（RLM）和人肝微粒体（HLM）中，尼索地平对伊伐卡夫多代谢的半最大抑制浓度（IC50）分别为 6.55 μM 和 9.10 μM，尼索地平对伊伐卡夫托代谢的抑制机制为混合抑制；尼莫地平在RLM和HLM中对伊伐卡夫托代谢的IC50分别为4.57 μM和7.15 μM，尼莫地平对伊伐卡夫托的抑制机制为竞争抑制。在大鼠药代动力学实验中观察到，尼索地平和尼莫地平都会显著改变伊伐卡夫托的药代动力学参数，如 AUC(0-t) 和 CLz/F。然而，这种差异可能与临床无关。总之，本文介绍了这些药物与伊伐卡夫托在体外和体内相互作用的研究结果。目的是为伊伐卡夫多与其他药物联用的安全性提供依据。

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引用次数: 0

Safety assessment of sulfasalazine: a pharmacovigilance study based on FAERS database 磺胺沙拉嗪的安全性评估：基于 FAERS 数据库的药物警戒研究

IF 5.6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Frontiers in Pharmacology

Pub Date : 2024-09-12 DOI: 10.3389/fphar.2024.1452300

Wangyu Ye, Yuan Ding, Meng Li, Zhihua Tian, Shaoli Wang, Zhen Liu

BackgroundSulfasalazine is a widely used anti-inflammatory medication for treating autoimmune disorders such as ulcerative colitis (UC), Crohn’s disease, and rheumatoid arthritis. However, its safety profile has not been systematically evaluated in real-world settings. By analyzing the FDA Adverse Event Reporting System (FAERS) database, we identified risk signals associated with adverse reactions to sulfasalazine, offering valuable insights for clinical decision-making and risk management.MethodsReports of adverse events (AEs) associated with sulfasalazine, covering the period from Q1 2004 to Q4 2023, were extracted from the FAERS database. Detailed case information was aggregated to assess demographic characteristics. The associations between sulfasalazine and adverse events were evaluated using the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM).ResultsWe extracted 7,156 adverse event reports from the FAERS database where sulfasalazine was identified as the “Primary Suspect (PS)” drug. Using disproportionality analysis, we identified 101 preferred terms (PT) related to sulfasalazine across 24 organ systems. Notable adverse reactions consistent with the drug’s labeling were observed, including Stevens-Johnson syndrome, agranulocytosis, eosinophilic pneumonia, and crystalluria. Additionally, novel positive signals not previously documented in the drug label were identified, including acute febrile neutrophilic dermatosis, aseptic meningitis, glomerulonephritis, and hepatosplenic T-cell lymphoma.ConclusionMost of the adverse reaction findings in this study are consistent with previous clinical research, and we have also identified new potential AEs associated with sulfasalazine. These findings provide valuable insights for the safety monitoring and clinical application of sulfasalazine.

背景磺胺嘧啶是一种广泛用于治疗溃疡性结肠炎（UC）、克罗恩病和类风湿性关节炎等自身免疫性疾病的抗炎药物。然而，该药的安全性尚未在真实世界中得到系统评估。通过分析美国食品药品管理局不良事件报告系统（FAERS）数据库，我们确定了与柳氮磺胺吡啶不良反应相关的风险信号，为临床决策和风险管理提供了有价值的见解。方法从FAERS数据库中提取了与柳氮磺胺吡啶相关的不良事件（AEs）报告，时间跨度为2004年第一季度至2023年第四季度。对病例的详细信息进行汇总，以评估人口统计学特征。结果我们从FAERS数据库中提取了7156份不良事件报告，其中磺胺吡啶被确定为 "主要可疑（PS）"药物。通过比例失调分析，我们在 24 个器官系统中确定了 101 个与柳氮磺胺吡啶相关的首选术语 (PT)。观察到了与药物标签一致的显著不良反应，包括史蒂文斯-约翰逊综合征、粒细胞减少症、嗜酸性粒细胞肺炎和结晶尿。此外，我们还发现了药物标签中以前未记录的新的阳性信号，包括急性发热性嗜中性粒细胞皮炎、无菌性脑膜炎、肾小球肾炎和肝脾T细胞淋巴瘤。这些发现为磺胺沙拉嗪的安全性监测和临床应用提供了有价值的见解。

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引用次数: 0