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Journal of Cystic Fibrosis最新文献

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Insights into epithelial-mesenchymal transition from cystic fibrosis rat models. 从囊性纤维化大鼠模型中了解上皮-间质转化。
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM
Journal of Cystic Fibrosis
Pub Date : 2024-09-11 DOI: 10.1016/j.jcf.2024.09.003
Nathan Rout-Pitt, Bernadette Boog, Alexandra McCarron, Nicole Reyne, David Parsons, Martin Donnelley

Background: Molecular pathways contributing to Cystic Fibrosis pathogenesis remain poorly understood. Epithelial-mesenchymal transition (EMT) has been recently observed in CF lungs and certain CFTR mutation classes may be more susceptible than others. No investigations of EMT processes in CF animal models have been reported.

Aim: The aim of this study was to assess the expression of EMT-related markers in Phe508del and knockout (CFTR-KO) rat lung tissue and tracheal-derived basal epithelial stem cells, to determine whether CFTR dysfunction can produce an EMT state.

Method: The expression of EMT-related markers in lung tissue and cultured tracheal basal epithelial stem cells from wildtype (WT), Phe508del, and CFTR-KO rats were assessed using qPCR and Western blots. Cell responses were evaluated in the presence of Rho-associated protein kinase (ROCK) inhibitor Y27632, which blocks EMT-pathways, or after treatment with TGFβ1 to stimulate EMT.

Results: Different gene expression profiles were observed between Phe508del and CFTR-KO rat models compared to wild type. There was lower expression of type 1 collagen in KO lungs and primary cell cultures, while Phe508del lungs and cells had higher expression, particularly when treated with TGFβ1. The addition of Y27632 rescued changes in EMT related genes in Phe508del cells but not in KO cells.

Conclusion: Our findings show the first evidence of upregulated EMT pathways in the lungs and airway cells of any CF animal model. Differences in the regulation of the EMT genes and proteins in the Phe508del and CFTR-KO cells suggest that the signalling pathways underlying EMT are CFTR mutation dependent.

背景：导致囊性纤维化发病机制的分子途径仍然鲜为人知。最近在 CF 肺中观察到上皮-间质转化（EMT），某些 CFTR 突变类别可能比其他类别更易受影响。目的：本研究旨在评估 Phe508del 和基因敲除（CFTR-KO）大鼠肺组织和气管源性基底上皮干细胞中 EMT 相关标记物的表达，以确定 CFTR 功能障碍是否会产生 EMT 状态：方法：使用 qPCR 和 Western 印迹法评估野生型（WT）、Phe508del 和 CFTR-KO 大鼠肺组织和培养的气管基底上皮干细胞中 EMT 相关标记物的表达。在有阻断 EMT 通路的 Rho- 相关蛋白激酶（ROCK）抑制剂 Y27632 存在的情况下，或用刺激 EMT 的 TGFβ1 处理后，对细胞反应进行了评估：与野生型相比，Phe508del 和 CFTR-KO 大鼠模型的基因表达谱不同。在 KO 肺和原代细胞培养物中，1 型胶原的表达量较低，而 Phe508del 肺和细胞的表达量较高，尤其是在用 TGFβ1 处理时。加入 Y27632 后，Phe508del 细胞中 EMT 相关基因的变化得到了缓解，而 KO 细胞中的变化则没有缓解：我们的研究结果首次证明了在任何 CF 动物模型的肺和气道细胞中 EMT 通路的上调。Phe508del细胞和CFTR-KO细胞中EMT基因和蛋白的调控差异表明，EMT的信号通路依赖于CFTR突变。
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引用次数: 0
Letter to the Editor. 致编辑的信
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM
Journal of Cystic Fibrosis
Pub Date : 2024-09-06 DOI: 10.1016/j.jcf.2024.08.006
Atefeh Khajeh, Yakup Kilic, Rushabh Shah, Simon Pg Padley, Carole A Ridge
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引用次数: 0
Are demographic findings really possible from reports in a spontaneous reporting system? 自发报告系统中的报告真的能得出人口统计结果吗？
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM
Journal of Cystic Fibrosis
Pub Date : 2024-09-01 DOI: 10.1016/j.jcf.2024.07.007
Yoshihiro Noguchi, Tomoaki Yoshimura
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引用次数: 0
Impact of interruption of CFTR modulator therapies CFTR 调节器疗法中断的影响。
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM
Journal of Cystic Fibrosis
Pub Date : 2024-09-01 DOI: 10.1016/j.jcf.2024.05.006

Novel drug therapy targeting the defective cystic fibrosis transmembrane conductance regulator protein has the potential to significantly enhance the quality of life for numerous patients with cystic fibrosis. However, in some countries social insurance does not pay for modulators because these drugs are extremely expensive. This study sought to understand the impact on the health of children whose modulator treatments were interrupted because of legal procedures and delivery processes. Our study identified that the significant increase in percent-predicted forced expiratory volume levels (FEV1) and BMI z-score values associated with modulator therapies decreased sharply with their discontinuation. Significant worsening in FEV1, BMI z-scores, and BW z-scores were detected in the first follow-up visit after therapy discontinuation within 1 month. Eight patients had a reduction of FEV1 of more than 10%. The findings suggest that modulatory treatment continuation is important, and it is crucial that treatment is not interrupted.

针对囊性纤维化跨膜传导调节蛋白缺陷的新型药物疗法有可能显著提高众多囊性纤维化患者的生活质量。然而，在一些国家，社会保险并不支付调节剂的费用，因为这些药物非常昂贵。本研究旨在了解因法律程序和交付过程而中断调节剂治疗的儿童的健康状况。我们的研究发现，与调节剂疗法相关的预测用力呼气容积百分比（FEV1）和体重指数（BMI）z-score 值的显著增加随着调节剂疗法的中断而急剧下降。在停药 1 个月后的首次随访中，发现 FEV1、BMI z 分数和体重 z 分数显著恶化。有 8 名患者的 FEV1 下降了 10%以上。研究结果表明，继续进行调节性治疗非常重要，关键是不能中断治疗。
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引用次数: 0
42 BOS-318 attenuates Pseudomonas aeruginosa lung infection in mouse models 42 BOS-318 可减轻小鼠模型中铜绿假单胞菌的肺部感染
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM
Journal of Cystic Fibrosis
Pub Date : 2024-09-01 DOI: 10.1016/S1569-1993(24)00885-3
O. Bernard, M. Kwon, M. Magnen, M. Yu
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引用次数: 0
32 Pseudomonas aeruginosa detects fungal toxins using a novel regulatory cascade 32 铜绿假单胞菌利用新型调控级联检测真菌毒素
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM
Journal of Cystic Fibrosis
Pub Date : 2024-09-01 DOI: 10.1016/S1569-1993(24)00875-0
J. Aycock, S. Dolan
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引用次数: 0
49 Differential effects of cationic antimicrobials on intrinsic antibiotic resistance in Pseudomonas aeruginosa 49 阳离子抗菌剂对铜绿假单胞菌内在抗生素耐药性的不同影响
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM
Journal of Cystic Fibrosis
Pub Date : 2024-09-01 DOI: 10.1016/S1569-1993(24)00892-0
J. Albin, D. Vithanage, C. Johnson, B. Pentelute
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引用次数: 0
73 Treatment outcomes in nontuberculous mycobacterial infection in people with cystic fibrosis in Denmark, 2012–2022 73 2012-2022 年丹麦囊性纤维化患者非结核分枝杆菌感染的治疗结果
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM
Journal of Cystic Fibrosis
Pub Date : 2024-09-01 DOI: 10.1016/S1569-1993(24)00916-0
C. Leo-Hansen, T. Bryrup, M. Jeppesen, M. Kolpen, P. Jensen, T. Pressler, H. Johansen, D. Faurholt-Jepsen, M. Olsen, T. Qvist
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引用次数: 0
58 CbrA mediates Pseudomonas aeruginosa antagonism of Candida albicans 58 CbrA 介导铜绿假单胞菌对白色念珠菌的拮抗作用
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM
Journal of Cystic Fibrosis
Pub Date : 2024-09-01 DOI: 10.1016/S1569-1993(24)00901-9
A. Conaway, I. Todorovic, D. Mould, D. Hogan
{"title":"58 CbrA mediates Pseudomonas aeruginosa antagonism of Candida albicans","authors":"A. Conaway,&nbsp;I. Todorovic,&nbsp;D. Mould,&nbsp;D. Hogan","doi":"10.1016/S1569-1993(24)00901-9","DOIUrl":"10.1016/S1569-1993(24)00901-9","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"23 ","pages":"Page S32"},"PeriodicalIF":5.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
60 Pyochelin-mediated cefiderocol sensitization depends on the FptA transporter 60 Pyochelin 介导的头孢哌酮致敏作用取决于 FptA 转运体
IF 5.4 2区 医学 Q1 RESPIRATORY SYSTEM
Journal of Cystic Fibrosis
Pub Date : 2024-09-01 DOI: 10.1016/S1569-1993(24)00903-2
A. Milesi Galdino, P. Jorth
{"title":"60 Pyochelin-mediated cefiderocol sensitization depends on the FptA transporter","authors":"A. Milesi Galdino,&nbsp;P. Jorth","doi":"10.1016/S1569-1993(24)00903-2","DOIUrl":"10.1016/S1569-1993(24)00903-2","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"23 ","pages":"Page S33"},"PeriodicalIF":5.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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