Clinical Respiratory Journal最新文献_第2页

Prediction of Clinical Severity of COVID-19 Using a Combination of Heparin-Binding Protein, Interleukin-6, and C-Reactive Protein: A Retrospective Study 使用肝素结合蛋白、白细胞介素-6 和 C 反应蛋白组合预测 COVID-19 的临床严重程度：一项回顾性研究。

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-08-26 DOI: 10.1111/crj.70003

Yidan Gao, Ke Zhao, Jing Liu, Xiangbo Zhang, Ling Gong, Xiang Zhou, Gongying Chen

Background

Systemic inflammation stands as a pivotal factor tightly interwoven with the progression of COVID-19. This study endeavors to elucidate the significance of three key inflammatory molecules, that is, heparin-binding protein (HBP), interleukin-6 (IL-6), and C-reactive protein (CRP), in assessing the severity and prognostic implications of COVID-19.

Methods

The demographic, clinical, and laboratory data were retrospectively collected from a cohort of 214 adult patients diagnosed with COVID-19. Patients were divided into two groups: nonsevere (n = 93; 43.5%) and severe (n = 121; 56.5%). Additionally, based on their organ function, patients were categorized into nonorgan failure (n = 137) and organ failure (n = 77) groups. The levels of inflammation-related cytokines were then compared among these defined groups.

Results

The severe group was characterized by a higher proportion of males, older age, and longer hospital stays compared to nonsevere cases. Additionally, severe cases exhibited a higher prevalence of underlying diseases and organ failure. Statistical analysis revealed significantly elevated levels of HBP, IL-6, and CRP in the severe group. HBP, IL-6, and CRP were identified as independent risk factors for severe COVID-19. Furthermore, a combined assessment of these biomarkers demonstrated superior diagnostic sensitivity (85.10%) and specificity (95.70%) for predicting COVID-19 severity. A positive relationship between elevated HBP, IL-6, and CRP levels and impaired organ function was also observed. The predictive efficiency significantly increased (hazard ratio = 3.631, log-rank p = 0.003) when two or more of them were combinedly used. Notably, elevated levels of HBP, IL-6, and CRP were associated with an increased risk of mortality.

Conclusions

In conclusion, the combined assessment of HBP, IL-6, and CRP offers enhanced accuracy and specificity in predicting the severity, organ failure, and mortality risk associated with COVID-19.

背景：全身性炎症是与 COVID-19 的进展紧密交织在一起的关键因素。本研究试图阐明肝素结合蛋白（HBP）、白细胞介素-6（IL-6）和 C 反应蛋白（CRP）这三种关键炎症分子在评估 COVID-19 的严重程度和预后影响方面的意义：回顾性收集了 214 名确诊为 COVID-19 的成年患者的人口统计学、临床和实验室数据。患者分为两组：非重度（93 人；43.5%）和重度（121 人；56.5%）。此外，根据器官功能，患者被分为非器官衰竭组（n = 137）和器官衰竭组（n = 77）。然后比较这些组别中炎症相关细胞因子的水平：结果：与非重症病例相比，重症组男性比例更高、年龄更大、住院时间更长。此外，重症病例患有基础疾病和器官衰竭的比例更高。统计分析显示，重症组的 HBP、IL-6 和 CRP 水平明显升高。HBP、IL-6 和 CRP 被确定为严重 COVID-19 的独立危险因素。此外，对这些生物标志物的综合评估显示，预测 COVID-19 严重程度的诊断灵敏度（85.10%）和特异性（95.70%）都很高。此外，还观察到 HBP、IL-6 和 CRP 水平升高与器官功能受损之间存在正相关关系。当合并使用其中两种或两种以上时，预测效率明显提高（危险比 = 3.631，对数秩 P = 0.003）。值得注意的是，HBP、IL-6 和 CRP 水平升高与死亡风险增加有关：总之，联合评估 HBP、IL-6 和 CRP 可提高预测 COVID-19 的严重程度、器官衰竭和死亡风险的准确性和特异性。

{"title":"Prediction of Clinical Severity of COVID-19 Using a Combination of Heparin-Binding Protein, Interleukin-6, and C-Reactive Protein: A Retrospective Study","authors":"Yidan Gao, Ke Zhao, Jing Liu, Xiangbo Zhang, Ling Gong, Xiang Zhou, Gongying Chen","doi":"10.1111/crj.70003","DOIUrl":"10.1111/crj.70003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Systemic inflammation stands as a pivotal factor tightly interwoven with the progression of COVID-19. This study endeavors to elucidate the significance of three key inflammatory molecules, that is, heparin-binding protein (HBP), interleukin-6 (IL-6), and C-reactive protein (CRP), in assessing the severity and prognostic implications of COVID-19.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The demographic, clinical, and laboratory data were retrospectively collected from a cohort of 214 adult patients diagnosed with COVID-19. Patients were divided into two groups: nonsevere (<i>n</i> = 93; 43.5%) and severe (<i>n</i> = 121; 56.5%). Additionally, based on their organ function, patients were categorized into nonorgan failure (<i>n</i> = 137) and organ failure (<i>n</i> = 77) groups. The levels of inflammation-related cytokines were then compared among these defined groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The severe group was characterized by a higher proportion of males, older age, and longer hospital stays compared to nonsevere cases. Additionally, severe cases exhibited a higher prevalence of underlying diseases and organ failure. Statistical analysis revealed significantly elevated levels of HBP, IL-6, and CRP in the severe group. HBP, IL-6, and CRP were identified as independent risk factors for severe COVID-19. Furthermore, a combined assessment of these biomarkers demonstrated superior diagnostic sensitivity (85.10%) and specificity (95.70%) for predicting COVID-19 severity. A positive relationship between elevated HBP, IL-6, and CRP levels and impaired organ function was also observed. The predictive efficiency significantly increased (hazard ratio = 3.631, log-rank <i>p</i> = 0.003) when two or more of them were combinedly used. Notably, elevated levels of HBP, IL-6, and CRP were associated with an increased risk of mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In conclusion, the combined assessment of HBP, IL-6, and CRP offers enhanced accuracy and specificity in predicting the severity, organ failure, and mortality risk associated with COVID-19.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Comparative Efficacy and Safety of Immunotherapy on Non–Small Cell Lung Cancer Patients With Brain Metastases: A Systematic Review and Network Meta-Analysis 免疫疗法对非小细胞肺癌脑转移患者的疗效和安全性比较：系统综述与网络元分析》。

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-08-20 DOI: 10.1111/crj.13823

Tianyi Lyu, Bo Sun, Daowen Yang, Xirui Zhao, Ruoshui Wang, Xinyang Shu, Demin Li, Hong Chen

Background

Growing evidence suggests that immunotherapy has a positive effect on non–small cell lung cancer (NSCLC) patients with brain metastases (BMs). However, it remains unclear which type of immunotherapy is more efficient. The aim of this network meta-analysis (NMA) was to compare the efficacy and safety of different immunotherapy types and determine the optimal option.

Method

Four databases (PubMed, Cochrane Library databases, Embase, and Web of Science) and ClinicalTrial.gov were searched from inception until January 26, 2023. Randomized controlled trials (RCTs), prospective nonrandomized trials, or observational studies investigating NSCLC patients with BMs treated by immunotherapy were included. The quality of the included studies was evaluated using the Cochrane risk of bias (ROB) tool and the Newcastle-Ottawa Scale (NOS). The efficacy of immunotherapy on NSCLC patients with BMs was evaluated using frequentist random-effects NMA.

Result

Eleven studies from 1560 citations, encompassing 1437 participants, were included in this NMA. Statistical analysis showed that pembrolizumab (SMD = 4.35, 95% CI [2.21, 6.60]) and nivolumab+ipilimumab (SMD = 3.81, 95% CI [1.21, 6.40]) could improve overall survival (OS). Pembrolizumab (SMD = 3.32, 95% CI [2.75, 3.90]) demonstrated better effects in improving the overall response rate (ORR). No significant difference in adverse event (AE) was observed between immunotherapy and chemotherapy.

Conclusion

Our findings indicated that pembrolizumab was the most promising immunotherapy for NSCLC patients with BMs. Nivolumab+ipilimumab might be an alternative choice to improve OS.

Limitation

Inconsistency tests were not performed because of the scarcity of direct comparison. Besides, high heterogeneity was observed in our NMA.

背景：越来越多的证据表明，免疫疗法对患有脑转移（BMs）的非小细胞肺癌（NSCLC）患者有积极作用。然而，目前仍不清楚哪种免疫疗法更有效。本网络荟萃分析（NMA）旨在比较不同类型免疫疗法的疗效和安全性，并确定最佳方案：方法：对四个数据库（PubMed、Cochrane Library 数据库、Embase 和 Web of Science）和 ClinicalTrial.gov 进行了检索，检索时间从开始到 2023 年 1 月 26 日。纳入的研究包括随机对照试验（RCT）、前瞻性非随机试验或观察性研究，这些研究调查了接受免疫疗法治疗的NSCLC骨髓瘤患者。采用科克伦偏倚风险（ROB）工具和纽卡斯尔-渥太华量表（NOS）对纳入研究的质量进行了评估。使用频数随机效应NMA评估了免疫疗法对患有BMs的NSCLC患者的疗效：该NMA纳入了来自1560篇引用文献的11项研究，涉及1437名参与者。统计分析显示，pembrolizumab（SMD = 4.35，95% CI [2.21，6.60]）和 nivolumab+ipilimumab （SMD = 3.81，95% CI [1.21，6.40]）可改善总生存期（OS）。Pembrolizumab（SMD = 3.32，95% CI [2.75，3.90]）在提高总体应答率（ORR）方面表现出更好的效果。免疫疗法与化疗在不良反应（AE）方面无明显差异：我们的研究结果表明，pembrolizumab是治疗NSCLC骨髓瘤患者最有前景的免疫疗法。局限性：未进行一致性检验：局限性：由于缺乏直接比较，因此没有进行不一致性测试。此外，我们的NMA观察到了高度异质性。

{"title":"Comparative Efficacy and Safety of Immunotherapy on Non–Small Cell Lung Cancer Patients With Brain Metastases: A Systematic Review and Network Meta-Analysis","authors":"Tianyi Lyu, Bo Sun, Daowen Yang, Xirui Zhao, Ruoshui Wang, Xinyang Shu, Demin Li, Hong Chen","doi":"10.1111/crj.13823","DOIUrl":"10.1111/crj.13823","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Growing evidence suggests that immunotherapy has a positive effect on non–small cell lung cancer (NSCLC) patients with brain metastases (BMs). However, it remains unclear which type of immunotherapy is more efficient. The aim of this network meta-analysis (NMA) was to compare the efficacy and safety of different immunotherapy types and determine the optimal option.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Four databases (PubMed, Cochrane Library databases, Embase, and Web of Science) and ClinicalTrial.gov were searched from inception until January 26, 2023. Randomized controlled trials (RCTs), prospective nonrandomized trials, or observational studies investigating NSCLC patients with BMs treated by immunotherapy were included. The quality of the included studies was evaluated using the Cochrane risk of bias (ROB) tool and the Newcastle-Ottawa Scale (NOS). The efficacy of immunotherapy on NSCLC patients with BMs was evaluated using frequentist random-effects NMA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>Eleven studies from 1560 citations, encompassing 1437 participants, were included in this NMA. Statistical analysis showed that pembrolizumab (SMD = 4.35, 95% CI [2.21, 6.60]) and nivolumab+ipilimumab (SMD = 3.81, 95% CI [1.21, 6.40]) could improve overall survival (OS). Pembrolizumab (SMD = 3.32, 95% CI [2.75, 3.90]) demonstrated better effects in improving the overall response rate (ORR). No significant difference in adverse event (AE) was observed between immunotherapy and chemotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings indicated that pembrolizumab was the most promising immunotherapy for NSCLC patients with BMs. Nivolumab+ipilimumab might be an alternative choice to improve OS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Limitation</h3>\u0000 \u0000 <p>Inconsistency tests were not performed because of the scarcity of direct comparison. Besides, high heterogeneity was observed in our NMA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13823","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Respiratory Pathogens at Exacerbation in Chronic Bronchitis With Airway Bacterial Colonisation: A Cohort Study 气道细菌定植的慢性支气管炎恶化时的呼吸道病原体：队列研究

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-08-20 DOI: 10.1111/crj.13811

Thomas L. Jones, Claire Roberts, Scott Elliott, Sharon Glaysher, Ben Green, Janis K. Shute, Anoop J. Chauhan

Background and Objective

COPD and bronchiectasis are common causes of morbidity, particularly around exacerbation. Colonisation with respiratory pathogens can increase the frequency and severity of exacerbations. However, bacterial and viral presence at exacerbation in people with airway colonisation has not been well studied.

Methods

A 6-month cohort study of participants (n = 30) with chronic bronchitis due to bronchiectasis (n = 26) and/or COPD (n = 13) and colonisation with Pseudomonas aeruginosa or Haemophilus influenzae was proven on two sputum cultures at exacerbation in the previous 12 months. Participants were provided self-management education and collected sputum samples daily. Sputum samples at baseline (at least 14 days before or after an exacerbation) and at each exacerbation were examined for a panel of 34 respiratory pathogens using commercially available RT-PCR kits and compared to results obtained using culture methods for the detection of bacteria.

Results

Participants provided 29 baseline samples and 71 samples at exacerbation. In 17/29 baseline samples, RT-PCR analysis confirmed the organism demonstrated by culture, while 12 samples showed a discrepancy from culture results. Most exacerbations (57.7%) were not associated with acquiring new bacteria or viruses, while 19.8% showed new bacteria, 15.7% new viruses and 7% both new viruses and bacteria.

Conclusion

Over half of exacerbations were not associated with new organisms in this cohort of participants with chronic bronchitis and colonisation. However, 26.8% demonstrated a new bacterial species in sputum, which is relevant for antibiotic therapy. Baseline RT-PCR and culture results were discordant in one-third of participants.

背景和目的：慢性阻塞性肺病和支气管扩张是常见的发病原因，尤其是在病情加重时。呼吸道病原体定植会增加病情加重的频率和严重程度。然而，关于气道定植患者在病情加重时是否存在细菌和病毒的研究还不够深入：方法：对因支气管扩张（26 人）和/或慢性阻塞性肺病（13 人）而患有慢性支气管炎的参与者（30 人）进行为期 6 个月的队列研究，研究对象在过去 12 个月内病情加重时的两次痰培养均证明其存在铜绿假单胞菌或流感嗜血杆菌定植。参与者接受自我管理教育，并每天采集痰样。使用市售 RT-PCR 试剂盒对基线（病情恶化前后至少 14 天）和每次病情恶化时的痰液样本进行检测，以检测 34 种呼吸道病原体，并将检测结果与使用培养方法检测细菌的结果进行比较：参与者提供了 29 份基线样本和 71 份加重时的样本。在 17/29 份基线样本中，RT-PCR 分析证实了培养所显示的病原体，而 12 份样本与培养结果存在差异。大多数病情恶化（57.7%）与感染新的细菌或病毒无关，19.8%感染了新的细菌，15.7%感染了新的病毒，7%同时感染了新的病毒和细菌：结论：在这批患有慢性支气管炎并有定植的参与者中，超过半数的病情恶化与新生物无关。然而，26.8%的患者痰中出现了新的细菌种类，这与抗生素治疗有关。三分之一的参与者的基线 RT-PCR 和培养结果不一致。

{"title":"Respiratory Pathogens at Exacerbation in Chronic Bronchitis With Airway Bacterial Colonisation: A Cohort Study","authors":"Thomas L. Jones, Claire Roberts, Scott Elliott, Sharon Glaysher, Ben Green, Janis K. Shute, Anoop J. Chauhan","doi":"10.1111/crj.13811","DOIUrl":"10.1111/crj.13811","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objective</h3>\u0000 \u0000 <p>COPD and bronchiectasis are common causes of morbidity, particularly around exacerbation. Colonisation with respiratory pathogens can increase the frequency and severity of exacerbations. However, bacterial and viral presence at exacerbation in people with airway colonisation has not been well studied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A 6-month cohort study of participants (<i>n</i> = 30) with chronic bronchitis due to bronchiectasis (<i>n</i> = 26) and/or COPD (<i>n</i> = 13) and colonisation with <i>Pseudomonas aeruginosa</i> or <i>Haemophilus influenzae</i> was proven on two sputum cultures at exacerbation in the previous 12 months. Participants were provided self-management education and collected sputum samples daily. Sputum samples at baseline (at least 14 days before or after an exacerbation) and at each exacerbation were examined for a panel of 34 respiratory pathogens using commercially available RT-PCR kits and compared to results obtained using culture methods for the detection of bacteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants provided 29 baseline samples and 71 samples at exacerbation. In 17/29 baseline samples, RT-PCR analysis confirmed the organism demonstrated by culture, while 12 samples showed a discrepancy from culture results. Most exacerbations (57.7%) were not associated with acquiring new bacteria or viruses, while 19.8% showed new bacteria, 15.7% new viruses and 7% both new viruses and bacteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Over half of exacerbations were not associated with new organisms in this cohort of participants with chronic bronchitis and colonisation. However, 26.8% demonstrated a new bacterial species in sputum, which is relevant for antibiotic therapy. Baseline RT-PCR and culture results were discordant in one-third of participants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13811","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Safflower Alleviates Pulmonary Arterial Hypertension by Inactivating NLRP3: A Combined Approach of Network Pharmacology and Experimental Verification 红花通过激活 NLRP3 缓解肺动脉高压：网络药理学与实验验证相结合的方法

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-08-18 DOI: 10.1111/crj.13826

Shibiao Ding, Jinyu Cui, Luning Yan, Chuhui Ru, Fei He, Aifeng Chen

Introduction

Traditional Chinese medicinal plant, safflower, shows effective for treating pulmonary arterial hypertension (PAH), yet the underlying mechanisms remain largely unexplored. This study is aimed at exploring the potential molecular mechanisms of safflower in the treatment of PAH.

Methods

Network pharmacology approach and molecular docking were applied to identify the core active compounds, therapeutic targets, and potential signaling pathways of safflower against PAH. Meanwhile, high-performance liquid chromatography (HPLC) assay was performed to determine the core compounds from safflower. Further, the mechanism of action of safflower on PAH was verified by in vivo and in vitro experiments.

Results

A total of 15 active compounds and 177 targets were screened from safflower against PAH. Enrichment analysis indicated that these therapeutic targets were mainly involved in multiple key pathways, such as TNF signaling pathway and Th17 cell differentiation. Notably, molecular docking revealed that quercetin (core compound in safflower) displayed highest binding capacity with NLRP3. In vivo, safflower exerted therapeutic effects on PAH by inhibiting right ventricular hypertrophy, inflammatory factor release, and pulmonary vascular remodeling. Mechanistically, it significantly reduced the expression of proangiogenesis-related factors (MMP-2, MMP-9, Collagen 1, and Collagen 3) and NLRP3 inflammasome components (NLRP3, ASC, and Caspase-1) in PAH model. Similarly, these results were observed in vitro. Besides, we further confirmed that NLRP3 inhibitor had the same therapeutic effect as safflower in vitro.

Conclusion

Our findings suggest that safflower mitigates PAH primarily by inhibiting NLRP3 inflammasome activation. This provides novel insights into the potential use of safflower as an alternative therapeutic approach for PAH.

简介中国传统药用植物红花对治疗肺动脉高压（PAH）有显著疗效，但其潜在机制仍有待探索。本研究旨在探索红花治疗 PAH 的潜在分子机制：方法：采用网络药理学方法和分子对接法鉴定红花治疗 PAH 的核心活性化合物、治疗靶点和潜在信号通路。同时，采用高效液相色谱法（HPLC）测定了红花中的核心化合物。此外，还通过体内和体外实验验证了红花对 PAH 的作用机制：结果：共从红花中筛选出 15 种活性化合物和 177 个针对 PAH 的靶点。富集分析表明，这些治疗靶点主要涉及多个关键通路，如 TNF 信号通路和 Th17 细胞分化。值得注意的是，分子对接显示槲皮素（红花中的核心化合物）与 NLRP3 的结合能力最强。在体内，红花通过抑制右心室肥大、炎症因子释放和肺血管重塑，对 PAH 发挥了治疗作用。从机理上讲，红花能明显减少 PAH 模型中促血管生成相关因子（MMP-2、MMP-9、胶原蛋白 1 和胶原蛋白 3）和 NLRP3 炎性体成分（NLRP3、ASC 和 Caspase-1）的表达。同样，在体外也观察到了这些结果。此外，我们还进一步证实了 NLRP3 抑制剂在体外具有与红花相同的治疗效果：我们的研究结果表明，红花主要通过抑制 NLRP3 炎性体的激活来缓解 PAH。结论：我们的研究结果表明，红花主要通过抑制 NLRP3 炎性体的活化来缓解 PAH，这为红花作为 PAH 替代疗法的潜在用途提供了新的见解。

{"title":"Safflower Alleviates Pulmonary Arterial Hypertension by Inactivating NLRP3: A Combined Approach of Network Pharmacology and Experimental Verification","authors":"Shibiao Ding, Jinyu Cui, Luning Yan, Chuhui Ru, Fei He, Aifeng Chen","doi":"10.1111/crj.13826","DOIUrl":"10.1111/crj.13826","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Traditional Chinese medicinal plant, safflower, shows effective for treating pulmonary arterial hypertension (PAH), yet the underlying mechanisms remain largely unexplored. This study is aimed at exploring the potential molecular mechanisms of safflower in the treatment of PAH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Network pharmacology approach and molecular docking were applied to identify the core active compounds, therapeutic targets, and potential signaling pathways of safflower against PAH. Meanwhile, high-performance liquid chromatography (HPLC) assay was performed to determine the core compounds from safflower. Further, the mechanism of action of safflower on PAH was verified by in vivo and in vitro experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 15 active compounds and 177 targets were screened from safflower against PAH. Enrichment analysis indicated that these therapeutic targets were mainly involved in multiple key pathways, such as TNF signaling pathway and Th17 cell differentiation. Notably, molecular docking revealed that quercetin (core compound in safflower) displayed highest binding capacity with NLRP3. In vivo, safflower exerted therapeutic effects on PAH by inhibiting right ventricular hypertrophy, inflammatory factor release, and pulmonary vascular remodeling. Mechanistically, it significantly reduced the expression of proangiogenesis-related factors (MMP-2, MMP-9, Collagen 1, and Collagen 3) and NLRP3 inflammasome components (NLRP3, ASC, and Caspase-1) in PAH model. Similarly, these results were observed in vitro. Besides, we further confirmed that NLRP3 inhibitor had the same therapeutic effect as safflower in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that safflower mitigates PAH primarily by inhibiting NLRP3 inflammasome activation. This provides novel insights into the potential use of safflower as an alternative therapeutic approach for PAH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13826","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Bazedoxifene Inhibits Cell Viability, Colony-Forming Activity, and Cell Migration in Human Non–Small Cell Lung Cancer Cells and Improves the Treatment Efficacy of Paclitaxel and Gemcitabine 比达昔芬抑制人类非小细胞肺癌细胞的细胞活力、集落形成活性和细胞迁移，并提高紫杉醇和吉西他滨的治疗效果

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-08-17 DOI: 10.1111/crj.13822

Yaochen Huang, Jiayuh Lin, Xiangning Fu, Lequn Li, Shenging Fu

Background

Bazedoxifene is a third-generation selective estrogen receptor modulator that inhibits the IL6/IL6R/GP130 signaling pathway by inhibiting IL6-induced homodimerization of GP130. Considering that the IL6/IL6R/GP130 signaling pathway is important in tumorigenesis and metastasis, bazedoxifene is thought to have an antitumor effect, which has been proven preliminarily in breast cancer and pancreatic cancer but has not yet been studied in non–small cell lung cancer (NSCLC). This study is aimed at evaluating the antitumor effect of bazedoxifene in NSCLC.

Methods

A549 and H1299 NSCLC cell lines were employed and exposed to various concentrations of bazedoxifene, paclitaxel, gemcitabine, and their combinations for cell viability, colony formation, and wound healing assays to demonstrate the antitumor effect of bazedoxifene with or without paclitaxel or gemcitabine.

Results

MTT cell viability, colony formation, and wound healing assays showed that bazedoxifene was capable of inhibiting cell viability, colony formation, and cell migration in a dose-dependent manner. In addition, bazedoxifene was capable of working with paclitaxel or gemcitabine synergistically to inhibit cell viability, colony formation, and cell migration.

Conclusion

This study demonstrated the potential antitumor effect of bazedoxifene and its ability to improve the treatment efficacy of paclitaxel and gemcitabine.

背景巴唑昔芬是一种第三代选择性雌激素受体调节剂，它通过抑制 IL6 诱导的 GP130 同源二聚化来抑制 IL6/IL6R/GP130 信号通路。考虑到IL6/IL6R/GP130信号通路在肿瘤发生和转移中的重要作用，巴唑昔芬被认为具有抗肿瘤作用，这已在乳腺癌和胰腺癌中得到初步证实，但尚未在非小细胞肺癌（NSCLC）中进行研究。本研究旨在评估巴唑昔芬对 NSCLC 的抗肿瘤作用。方法采用 A549 和 H1299 NSCLC 细胞株，将其暴露于不同浓度的巴唑昔芬、紫杉醇、吉西他滨以及它们的复方制剂中，进行细胞活力、菌落形成和伤口愈合检测，以证明巴唑昔芬与紫杉醇或吉西他滨联合或不联合的抗肿瘤效果。结果 MTT 细胞活力、集落形成和伤口愈合试验表明，巴唑昔芬能以剂量依赖性方式抑制细胞活力、集落形成和细胞迁移。此外，巴唑昔芬还能与紫杉醇或吉西他滨协同抑制细胞活力、集落形成和细胞迁移。结论本研究证明了巴唑昔芬潜在的抗肿瘤作用及其改善紫杉醇和吉西他滨治疗效果的能力。

{"title":"Bazedoxifene Inhibits Cell Viability, Colony-Forming Activity, and Cell Migration in Human Non–Small Cell Lung Cancer Cells and Improves the Treatment Efficacy of Paclitaxel and Gemcitabine","authors":"Yaochen Huang, Jiayuh Lin, Xiangning Fu, Lequn Li, Shenging Fu","doi":"10.1111/crj.13822","DOIUrl":"https://doi.org/10.1111/crj.13822","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bazedoxifene is a third-generation selective estrogen receptor modulator that inhibits the IL6/IL6R/GP130 signaling pathway by inhibiting IL6-induced homodimerization of GP130. Considering that the IL6/IL6R/GP130 signaling pathway is important in tumorigenesis and metastasis, bazedoxifene is thought to have an antitumor effect, which has been proven preliminarily in breast cancer and pancreatic cancer but has not yet been studied in non–small cell lung cancer (NSCLC). This study is aimed at evaluating the antitumor effect of bazedoxifene in NSCLC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A549 and H1299 NSCLC cell lines were employed and exposed to various concentrations of bazedoxifene, paclitaxel, gemcitabine, and their combinations for cell viability, colony formation, and wound healing assays to demonstrate the antitumor effect of bazedoxifene with or without paclitaxel or gemcitabine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MTT cell viability, colony formation, and wound healing assays showed that bazedoxifene was capable of inhibiting cell viability, colony formation, and cell migration in a dose-dependent manner. In addition, bazedoxifene was capable of working with paclitaxel or gemcitabine synergistically to inhibit cell viability, colony formation, and cell migration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrated the potential antitumor effect of bazedoxifene and its ability to improve the treatment efficacy of paclitaxel and gemcitabine.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13822","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Predictive Value of Lymphocyte-to-Neutrophil Ratio and Platelet-to-Neutrophil Ratio on PD-L1 Expression in Lung Cancer 淋巴细胞与中性粒细胞比率和血小板与中性粒细胞比率对肺癌 PD-L1 表达的预测价值

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-08-14 DOI: 10.1111/crj.13821

Shun-Shun Cui, Ya Shen, Rui-Qing Yang

Objective

This study aimed to examine the predictive effect of the lymphocyte-to-neutrophil ratio (LNR) and the platelet-to-neutrophil ratio (PNR) on the expression of programmed death receptor ligand 1 (PD-L1) in patients diagnosed with lung cancer.

Methods

The clinical records of 86 patients diagnosed with lung cancer between January 2020 and February 2022 at Fu Yang People's Hospital were retrospectively analyzed. The records included information on age, gender, smoking history, hematological indices at the time of admission, staging of the lung malignancy, histopathological subtype, comorbidities, and the expression levels of PD-L1. Patients were stratified into two distinct cohorts based on their PD-L1 expression levels: Those with an expression level greater than or equal to 1% were classified into the PD-L1 positive expression group, while the remainder were categorized as the PD-L1 negative expression group. Univariate analysis and multivariate logistic regression analysis were used to identify the influencing factors of PD-L1, and the diagnostic efficacy was calculated using the receiver operating characteristic (ROC) curve.

Results

Upon analysis, the PD-L1 positive expression group manifested notably lower values as compared to their counterparts in the PD-L1 negative expression group (LNR: 0.262 ± 0.105 vs. 0.390 ± 0.201; PNR: 41.03 [29.64, 50.11] vs. 49.50 [37.38, 73.83]), and these differences were statistically significant. There was a notable disparity in PD-L1 expression based on gender, with males exhibiting a statistically significant higher positivity rate compared to females. Furthermore, patients in Stages I–III of the disease demonstrated a markedly elevated PD-L1 positivity rate compared to those in Stage IV (p < 0.05). Incorporating univariates with statistical differences into multivariate logistic regression analysis suggests that stage and LNR are independent risk factors for PD-L1 negative expression. ROC curve analyses revealed that the area under the ROC curve (AUC) for LNR as an indicator for PD-L1 positive expression stood at 0.706, while the AUC for PNR was calculated at 0.687.

Conclusion

PD-L1 expression is correlated with gender and lung cancer staging, and LNR and PNR have a predictive value for PD-L1 expression.

研究目的本研究旨在探讨淋巴细胞与中性粒细胞比值（LNR）和血小板与中性粒细胞比值（PNR）对肺癌患者程序性死亡受体配体1（PD-L1）表达的预测作用：回顾性分析阜阳市人民医院2020年1月至2022年2月期间确诊的86例肺癌患者的临床病历。这些病历包括患者的年龄、性别、吸烟史、入院时的血液学指标、肺部恶性肿瘤分期、组织病理学亚型、合并症以及 PD-L1 的表达水平。根据患者的 PD-L1 表达水平将其分为两个不同的组群：PD-L1表达水平大于或等于1%的患者被分为PD-L1阳性表达组，其余患者被分为PD-L1阴性表达组。采用单变量分析和多变量逻辑回归分析确定PD-L1的影响因素，并利用接收者操作特征曲线（ROC）计算诊断效果：经分析，PD-L1阳性表达组的数值明显低于PD-L1阴性表达组（LNR：0.262 ± 0.105 vs. 0.390 ± 0.201；PNR：41.03 [29.64, 50.11] vs. 49.50 [37.38, 73.83]），这些差异具有统计学意义。PD-L1的表达在性别上存在明显差异，男性的阳性率明显高于女性。此外，与 IV 期患者相比，I-III 期患者的 PD-L1 阳性率明显升高（p 结论：PD-L1 的表达与性别相关：PD-L1 的表达与性别和肺癌分期相关，LNR 和 PNR 对 PD-L1 的表达具有预测价值。

{"title":"Predictive Value of Lymphocyte-to-Neutrophil Ratio and Platelet-to-Neutrophil Ratio on PD-L1 Expression in Lung Cancer","authors":"Shun-Shun Cui, Ya Shen, Rui-Qing Yang","doi":"10.1111/crj.13821","DOIUrl":"10.1111/crj.13821","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to examine the predictive effect of the lymphocyte-to-neutrophil ratio (LNR) and the platelet-to-neutrophil ratio (PNR) on the expression of programmed death receptor ligand 1 (PD-L1) in patients diagnosed with lung cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The clinical records of 86 patients diagnosed with lung cancer between January 2020 and February 2022 at Fu Yang People's Hospital were retrospectively analyzed. The records included information on age, gender, smoking history, hematological indices at the time of admission, staging of the lung malignancy, histopathological subtype, comorbidities, and the expression levels of PD-L1. Patients were stratified into two distinct cohorts based on their PD-L1 expression levels: Those with an expression level greater than or equal to 1% were classified into the PD-L1 positive expression group, while the remainder were categorized as the PD-L1 negative expression group. Univariate analysis and multivariate logistic regression analysis were used to identify the influencing factors of PD-L1, and the diagnostic efficacy was calculated using the receiver operating characteristic (ROC) curve.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Upon analysis, the PD-L1 positive expression group manifested notably lower values as compared to their counterparts in the PD-L1 negative expression group (LNR: 0.262 ± 0.105 vs. 0.390 ± 0.201; PNR: 41.03 [29.64, 50.11] vs. 49.50 [37.38, 73.83]), and these differences were statistically significant. There was a notable disparity in PD-L1 expression based on gender, with males exhibiting a statistically significant higher positivity rate compared to females. Furthermore, patients in Stages I–III of the disease demonstrated a markedly elevated PD-L1 positivity rate compared to those in Stage IV (<i>p</i> < 0.05). Incorporating univariates with statistical differences into multivariate logistic regression analysis suggests that stage and LNR are independent risk factors for PD-L1 negative expression. ROC curve analyses revealed that the area under the ROC curve (AUC) for LNR as an indicator for PD-L1 positive expression stood at 0.706, while the AUC for PNR was calculated at 0.687.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PD-L1 expression is correlated with gender and lung cancer staging, and LNR and PNR have a predictive value for PD-L1 expression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13821","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

The Deubiquitinase USP22-Stabilized COL17A1 Promotes Lung Adenocarcinoma Progression 去泛素化酶 USP22 稳定的 COL17A1 促进肺腺癌的发展

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-08-14 DOI: 10.1111/crj.13824

Guangxi Chen, Dandan Du, Haihua Wang, Huifeng Li

Background

Lung adenocarcinoma (LUAD) is a highly aggressive and rapidly fatal malignancy worldwide. Collagen XVII (COL17A1) has been implicated in various protumorigenic processes. However, the functions and mechanisms of COL17A1 in LUAD progression still remain elusive.

Methods

COL17A1 and ubiquitin-specific protease 22 (USP22) mRNA analysis was performed by quantitative PCR, and their protein levels were detected by immunoblotting and immunohistochemistry. The functional influence was evaluated by determining cell viability, proliferation, apoptosis, invasion, migration, and ferroptosis in vitro, as well as xenograft growth in vivo. Co-immunoprecipitation (Co-IP) and IP experiments were used to examine the USP22/COL17A1 interaction and COL17A1 deubiquitination. Cycloheximide treatment was used to analyze COL17A1 protein stability.

Results

COL17A1 and USP22 were upregulated in human LUAD tissues and cell lines. Functionally, COL17A1 knockdown acted for the suppression of LUAD cell growth, invasion, and migration as well as promotion of cell apoptosis and ferroptosis in vitro. COL17A1 knockdown could diminish the tumorigenicity of LUAD cells in vivo. Mechanistically, USP22 stabilized and upregulated COL17A1 by enhancing the deubiquitination of COL17A1. Additionally, reexpression of COL17A1 could reverse USP22 silencing-induced phenotype changes of LUAD cells in vitro.

Conclusion

Our findings demonstrate that USP22-stabilized COL17A1 possesses oncogenic activity in LUAD. We propose that USP22 and COL17A1 would be potential targets for the establishment of therapeutic approaches against LUAD.

背景：肺腺癌（LUAD）是一种侵袭性极强的恶性肿瘤，在全球范围内迅速致命。胶原蛋白 XVII（COL17A1）与多种原发肿瘤过程有关。然而，COL17A1在LUAD进展过程中的功能和机制仍然扑朔迷离：方法：通过定量 PCR 分析 COL17A1 和泛素特异性蛋白酶 22 (USP22) 的 mRNA，并通过免疫印迹和免疫组化检测其蛋白水平。通过测定体外的细胞活力、增殖、凋亡、侵袭、迁移和铁变态反应以及体内的异种移植生长来评估其功能影响。共免疫沉淀（Co-IP）和 IP 实验用于检测 USP22/COL17A1 的相互作用和 COL17A1 的去泛素化。环己亚胺处理用于分析 COL17A1 蛋白的稳定性：结果：COL17A1和USP22在人类LUAD组织和细胞系中上调。从功能上讲，体外敲除 COL17A1 可抑制 LUAD 细胞的生长、侵袭和迁移，并促进细胞凋亡和铁凋亡。敲除 COL17A1 可降低 LUAD 细胞在体内的致瘤性。从机制上讲，USP22通过增强COL17A1的去泛素化来稳定和上调COL17A1。此外，在体外重新表达 COL17A1 可以逆转 USP22 沉默诱导的 LUAD 细胞表型变化：我们的研究结果表明，USP22 稳定的 COL17A1 在 LUAD 中具有致癌活性。我们认为，USP22 和 COL17A1 将成为治疗 LUAD 的潜在靶点。

{"title":"The Deubiquitinase USP22-Stabilized COL17A1 Promotes Lung Adenocarcinoma Progression","authors":"Guangxi Chen, Dandan Du, Haihua Wang, Huifeng Li","doi":"10.1111/crj.13824","DOIUrl":"10.1111/crj.13824","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lung adenocarcinoma (LUAD) is a highly aggressive and rapidly fatal malignancy worldwide. Collagen XVII (COL17A1) has been implicated in various protumorigenic processes. However, the functions and mechanisms of COL17A1 in LUAD progression still remain elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>COL17A1 and ubiquitin-specific protease 22 (USP22) mRNA analysis was performed by quantitative PCR, and their protein levels were detected by immunoblotting and immunohistochemistry. The functional influence was evaluated by determining cell viability, proliferation, apoptosis, invasion, migration, and ferroptosis in vitro, as well as xenograft growth in vivo. Co-immunoprecipitation (Co-IP) and IP experiments were used to examine the USP22/COL17A1 interaction and COL17A1 deubiquitination. Cycloheximide treatment was used to analyze COL17A1 protein stability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>COL17A1 and USP22 were upregulated in human LUAD tissues and cell lines. Functionally, COL17A1 knockdown acted for the suppression of LUAD cell growth, invasion, and migration as well as promotion of cell apoptosis and ferroptosis in vitro. COL17A1 knockdown could diminish the tumorigenicity of LUAD cells in vivo. Mechanistically, USP22 stabilized and upregulated COL17A1 by enhancing the deubiquitination of COL17A1. Additionally, reexpression of COL17A1 could reverse USP22 silencing-induced phenotype changes of LUAD cells in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings demonstrate that USP22-stabilized COL17A1 possesses oncogenic activity in LUAD. We propose that USP22 and COL17A1 would be potential targets for the establishment of therapeutic approaches against LUAD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13824","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

It Is Time to Get to Know the Neuroendocrine Cell Hyperplasia of Infancy 是时候了解婴儿神经内分泌细胞增生症了。

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-08-13 DOI: 10.1111/crj.13827

Long Jin, Wen Wei

In the two decades that have elapsed since the initial proposal of neuroendocrine cell hyperplasia of infancy (NEHI), several hundred cases have been reported and researched. However, a comprehensive analysis of research progress remains absent from the literature. The present article endeavors to evaluate the current progress of NEHI research and offer a reference for the clinical management of this condition.

自最初提出婴儿神经内分泌细胞增生症（NEHI）以来的二十年间，已有数百例病例被报道和研究。然而，文献中仍然缺乏对研究进展的全面分析。本文旨在评估目前 NEHI 的研究进展，并为该病的临床治疗提供参考。

引用次数: 0

Circular RNA NFIX Functions as an Oncogene in Non-Small Cell Lung Cancer by Modulating the miR-214-3p/TRIAP1 Axis 环状 RNA NFIX 通过调节 miR-214-3p/TRIAP1 轴在非小细胞肺癌中发挥癌基因的功能

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-08-12 DOI: 10.1111/crj.13801

Guohua Liu, Hanbing Shi, Hongyan Zheng, Weili Kong, Xinyue Cheng, Liling Deng

Background

circRNA NFIX has been shown to exist as an oncogene in glioma. But its expression and role in NSCLC (non-small cell lung cancer) are still unclear. This research aimed to discover the expression and function of circRNA NFIX in NSCLC.

Methods

In this research, qRT-PCR was utilized to investigate the expression levels of circRNA NFIX, miRNA-214-3p, and TRIAP1 in NSCLC tissues and cell lines. The binding sites between circRNA NFIX/TRIAP1 and miRNA-214-3p were predicted using the Starbase. These interactions were further validated using a double luciferase reporter assay. Cell proliferation and apoptosis were assessed through MTT and flow cytometry, respectively. The expression of apoptosis-related proteins was measured by western blot assay.

Results

miRNA-214-3p could link with circRNA NFIX. circRNA NFIX was upregulated, while miRNA-214-3p was downregulated in NSCLC cell lines and clinical samples. Besides, suppression of circRNA NFIX repressed cell proliferation and induced apoptosis in NSCLC cells by upregulating miRNA-214-3p expression. Besides, the data indicated that TRIAP1 was a target of miRNA-214-3p, and it was negatively regulated by miRNA-214-3p in NSCLC cells. The excessive expression of miRNA-214-3p suppressed NSCLC cell proliferation and increased apoptosis. In addition, overexpression of TRIAP1 significantly reversed the effects on NSCLC cells caused by miRNA-214-3p mimic.

Conclusion

circRNA NFIX silencing repressed the proliferation of NSCLC cells and induced cell apoptosis by regulating the miR-214-3p/TRIAP1 axis, which was a potential diagnostic and therapeutic target for NSCLC.

背景：circRNA NFIX 已被证明是胶质瘤的致癌基因。但它在 NSCLC（非小细胞肺癌）中的表达和作用仍不清楚。本研究旨在发现 circRNA NFIX 在 NSCLC 中的表达和功能：方法：本研究利用 qRT-PCR 技术检测了 circRNA NFIX、miRNA-214-3p 和 TRIAP1 在 NSCLC 组织和细胞系中的表达水平。利用Starbase预测了circRNA NFIX/TRIAP1与miRNA-214-3p之间的结合位点。使用双荧光素酶报告实验进一步验证了这些相互作用。细胞增殖和凋亡分别通过 MTT 和流式细胞术进行评估。结果表明：miRNA-214-3p 可与 circRNA NFIX 连接。在 NSCLC 细胞系和临床样本中，circRNA NFIX 上调，而 miRNA-214-3p 下调。此外，抑制 circRNA NFIX 可抑制细胞增殖，并通过上调 miRNA-214-3p 的表达诱导 NSCLC 细胞凋亡。此外，数据还表明，TRIAP1是miRNA-214-3p的靶标，它在NSCLC细胞中受到miRNA-214-3p的负调控。miRNA-214-3p的过度表达抑制了NSCLC细胞的增殖，增加了细胞的凋亡。结论：circRNA NFIX沉默通过调节miR-214-3p/TRIAP1轴抑制NSCLC细胞增殖并诱导细胞凋亡，是NSCLC的潜在诊断和治疗靶点。

{"title":"Circular RNA NFIX Functions as an Oncogene in Non-Small Cell Lung Cancer by Modulating the miR-214-3p/TRIAP1 Axis","authors":"Guohua Liu, Hanbing Shi, Hongyan Zheng, Weili Kong, Xinyue Cheng, Liling Deng","doi":"10.1111/crj.13801","DOIUrl":"10.1111/crj.13801","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>circRNA NFIX has been shown to exist as an oncogene in glioma. But its expression and role in NSCLC (non-small cell lung cancer) are still unclear. This research aimed to discover the expression and function of circRNA NFIX in NSCLC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this research, qRT-PCR was utilized to investigate the expression levels of circRNA NFIX, miRNA-214-3p, and TRIAP1 in NSCLC tissues and cell lines. The binding sites between circRNA NFIX/TRIAP1 and miRNA-214-3p were predicted using the Starbase. These interactions were further validated using a double luciferase reporter assay. Cell proliferation and apoptosis were assessed through MTT and flow cytometry, respectively. The expression of apoptosis-related proteins was measured by western blot assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>miRNA-214-3p could link with circRNA NFIX. circRNA NFIX was upregulated, while miRNA-214-3p was downregulated in NSCLC cell lines and clinical samples. Besides, suppression of circRNA NFIX repressed cell proliferation and induced apoptosis in NSCLC cells by upregulating miRNA-214-3p expression. Besides, the data indicated that TRIAP1 was a target of miRNA-214-3p, and it was negatively regulated by miRNA-214-3p in NSCLC cells. The excessive expression of miRNA-214-3p suppressed NSCLC cell proliferation and increased apoptosis. In addition, overexpression of TRIAP1 significantly reversed the effects on NSCLC cells caused by miRNA-214-3p mimic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>circRNA NFIX silencing repressed the proliferation of NSCLC cells and induced cell apoptosis by regulating the miR-214-3p/TRIAP1 axis, which was a potential diagnostic and therapeutic target for NSCLC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

FOXA2 Activates RND1 to Regulate Arachidonic Acid Metabolism Pathway and Suppress Cisplatin Resistance in Lung Squamous Cell Carcinoma FOXA2 激活 RND1 以调节花生四烯酸代谢途径并抑制肺鳞癌的顺铂抗性

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal

Pub Date : 2024-08-11 DOI: 10.1111/crj.13814

Yafu Zhou, Huiguo Chen, Jianhua Yan, Qi Yao, Chunchu Kong, You Peng, Shengying Xiao, Jinsong Yang

Background

The primary cause of cancer-related fatalities globally is lung cancer. Although the chemotherapy drug cisplatin (DDP) has brought certain benefits to patients, the rapid development of drug resistance has greatly hindered treatment success.

Methods

We used the lung squamous cell carcinoma (LUSC) mRNA data set to explore the differentially expressed gene (RND1) in LUSC and detected RND1 expression in LUSC cells and DDP-resistant cells by qRT-PCR. Meanwhile, we performed abnormal expression treatment on RND1 and conducted CCK8, colony formation, and flow cytometry to evaluate the impact of RND1 expression on cell proliferation, apoptosis, and DDP resistance. In addition, we analyzed metabolism pathways involving RND1 using GSEA. We also used online tools such as hTFtarget and JASPAR to screen for the upstream transcription factor FOXA2 of RND1 and verified their relationship through CHIP and dual luciferase experiments. Finally, we validated the role of FOXA2-RND1 in DDP resistance in LUSC through the above experiments.

Results

RND1 was downregulated in LUSC, and overexpression of RND1 repressed proliferation and DDP resistance of LUSC cells and facilitated cell apoptosis. RND1 modulated the arachidonic acid (AA) metabolism pathway, and FOXA2 positively manipulated RND1 expression. By activating FOXA2, stabilizing RND1, and regulating AA levels, the sensitivity of LUSC cells to DDP could be enhanced.

Conclusion

Our study suggested that FOXA2 positively modulated the RND1-AA pathway, which repressed the resistance of LUSC cells to DDP.

背景：肺癌是全球癌症致死的主要原因。尽管化疗药物顺铂（DDP）给患者带来了一定的益处，但耐药性的迅速发展极大地阻碍了治疗的成功：方法：我们利用肺鳞状细胞癌（LUSC）mRNA数据集探索肺鳞状细胞癌中的差异表达基因（RND1），并通过qRT-PCR检测RND1在肺鳞状细胞癌细胞和DDP耐药细胞中的表达。同时，我们对 RND1 进行了异常表达处理，并通过 CCK8、集落形成和流式细胞术评估了 RND1 表达对细胞增殖、凋亡和 DDP 抗性的影响。此外，我们还利用 GSEA 分析了涉及 RND1 的代谢通路。我们还利用 hTFtarget 和 JASPAR 等在线工具筛选了 RND1 的上游转录因子 FOXA2，并通过 CHIP 和双荧光素酶实验验证了它们之间的关系。最后，我们通过上述实验验证了 FOXA2-RND1 在 LUSC DDP 抗性中的作用：结果：RND1在LUSC中下调，过表达RND1抑制了LUSC细胞的增殖和DDP抗性，并促进了细胞凋亡。RND1调节花生四烯酸（AA）代谢途径，而FOXA2对RND1的表达有积极的调节作用。通过激活 FOXA2、稳定 RND1 和调节 AA 水平，可提高 LUSC 细胞对 DDP 的敏感性：我们的研究表明，FOXA2能积极调节RND1-AA通路，从而抑制LUSC细胞对DDP的抗性。

{"title":"FOXA2 Activates RND1 to Regulate Arachidonic Acid Metabolism Pathway and Suppress Cisplatin Resistance in Lung Squamous Cell Carcinoma","authors":"Yafu Zhou, Huiguo Chen, Jianhua Yan, Qi Yao, Chunchu Kong, You Peng, Shengying Xiao, Jinsong Yang","doi":"10.1111/crj.13814","DOIUrl":"10.1111/crj.13814","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The primary cause of cancer-related fatalities globally is lung cancer. Although the chemotherapy drug cisplatin (DDP) has brought certain benefits to patients, the rapid development of drug resistance has greatly hindered treatment success.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used the lung squamous cell carcinoma (LUSC) mRNA data set to explore the differentially expressed gene (RND1) in LUSC and detected RND1 expression in LUSC cells and DDP-resistant cells by qRT-PCR. Meanwhile, we performed abnormal expression treatment on RND1 and conducted CCK8, colony formation, and flow cytometry to evaluate the impact of RND1 expression on cell proliferation, apoptosis, and DDP resistance. In addition, we analyzed metabolism pathways involving RND1 using GSEA. We also used online tools such as hTFtarget and JASPAR to screen for the upstream transcription factor FOXA2 of RND1 and verified their relationship through CHIP and dual luciferase experiments. Finally, we validated the role of FOXA2-RND1 in DDP resistance in LUSC through the above experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>RND1 was downregulated in LUSC, and overexpression of RND1 repressed proliferation and DDP resistance of LUSC cells and facilitated cell apoptosis. RND1 modulated the arachidonic acid (AA) metabolism pathway, and FOXA2 positively manipulated RND1 expression. By activating FOXA2, stabilizing RND1, and regulating AA levels, the sensitivity of LUSC cells to DDP could be enhanced.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study suggested that FOXA2 positively modulated the RND1-AA pathway, which repressed the resistance of LUSC cells to DDP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13814","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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