At present, the angiotensin-converting enzyme (ACE) I/D polymorphism was considered to be associated to the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the association between it and the risk of COPD in different ethnic groups is still unclear. The purpose of this study is to conduct an updated meta-analysis of the association between them; collect literatures published before 10 February 2023 by searching PubMed, Embase, MEDLINE, CBM, CNKI, Wanfang, and VIP Chinese scientific databases; and display the analysis results by drawing forest plots. At the same time, publication bias, sensitivity analysis, and trial sequential analysis (TSA) were performed to evaluate the stability and reliability of the results. In the overall population, the result of the DD versus II model showed the association with the risk of COPD ([OR] = 1.30, 95% CI [1.08, 1.56]), and there were no associations in other genetic models (p > 0.05). In Caucasians, the results of all genetic models showed no associations (p > 0.05). In Asians, the results of D versus I, DD versus II, and DD versus II + ID models showed the associations with the risk of COPD (D vs. I: [OR] = 1.48, 95% CI [1.14, 1.93]; DD vs. II: [OR] = 2.04, 95% CI [1.53, 2.72]; DD vs. II + ID: [OR] = 2.19, 95% CI [1.45, 3.29]), while the results of ID versus II and DD + ID versus II models showed no associations (p > 0.05). Therefore, the D allele and “DD” genotype variation of the ACE I/D gene polymorphism are associated with susceptibility to COPD in Asians but not in Caucasians.
目前，血管紧张素转换酶（ACE）I/D 多态性被认为与慢性阻塞性肺病（COPD）的发病机制有关。然而，该多态性与不同种族人群罹患慢性阻塞性肺病的风险之间的关系仍不明确。本研究旨在通过检索PubMed、Embase、MEDLINE、CBM、CNKI、万方和VIP中文科学数据库，收集2023年2月10日之前发表的文献，并通过绘制森林图显示分析结果，从而对二者之间的相关性进行最新的荟萃分析。同时，还进行了发表偏倚、敏感性分析和试验序列分析（TSA），以评估结果的稳定性和可靠性。在总体人群中，DD 与 II 模型的结果显示与慢性阻塞性肺病的风险有关（[OR] = 1.30，95% CI [1.08，1.56]），其他遗传模型中没有相关性（P > 0.05）。在白种人中，所有遗传模型的结果都显示没有关联（P > 0.05）。在亚洲人中，D 与 I、DD 与 II 和 DD 与 II + ID 模型的结果显示与慢性阻塞性肺病的风险有关（D 与 I：[OR] = 1.48，95% CI [1.14，1.93]；DD 与 II：[OR] = 2.04，95% CI [1.53，2.72]；DD vs. II + ID：[OR] = 2.19，95% CI [1.45，3.29]），而 ID vs. II 和 DD + ID vs. II 模型的结果显示没有关联（P > 0.05）。因此，ACE I/D 基因多态性的 D 等位基因和 "DD "基因型变异与亚洲人的慢性阻塞性肺病易感性有关，但与白种人无关。
{"title":"Increased Frequency of Angiotensin-Converting Enzyme D Allele in Asian Patients With Chronic Obstructive Pulmonary Disease: An Updated Meta-Analysis","authors":"Xiaozheng Wu, Wen Li, Zhenliang Luo, Yunzhi Chen","doi":"10.1111/crj.70002","DOIUrl":"10.1111/crj.70002","url":null,"abstract":"<p>At present, the angiotensin-converting enzyme (ACE) I/D polymorphism was considered to be associated to the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the association between it and the risk of COPD in different ethnic groups is still unclear. The purpose of this study is to conduct an updated meta-analysis of the association between them; collect literatures published before 10 February 2023 by searching PubMed, Embase, MEDLINE, CBM, CNKI, Wanfang, and VIP Chinese scientific databases; and display the analysis results by drawing forest plots. At the same time, publication bias, sensitivity analysis, and trial sequential analysis (TSA) were performed to evaluate the stability and reliability of the results. In the overall population, the result of the DD versus II model showed the association with the risk of COPD ([OR] = 1.30, 95% CI [1.08, 1.56]), and there were no associations in other genetic models (<i>p</i> > 0.05). In Caucasians, the results of all genetic models showed no associations (<i>p</i> > 0.05). In Asians, the results of D versus I, DD versus II, and DD versus II + ID models showed the associations with the risk of COPD (D vs. I: [OR] = 1.48, 95% CI [1.14, 1.93]; DD vs. II: [OR] = 2.04, 95% CI [1.53, 2.72]; DD vs. II + ID: [OR] = 2.19, 95% CI [1.45, 3.29]), while the results of ID versus II and DD + ID versus II models showed no associations (<i>p</i> > 0.05). Therefore, the D allele and “DD” genotype variation of the ACE I/D gene polymorphism are associated with susceptibility to COPD in Asians but not in Caucasians.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074605","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}
<div> <section> <h3> Introduction</h3> <p>Lung adenocarcinoma (LUAD) is one of the major histopathological types of non-small cell lung cancer (NSCLC), including solid, acinar, lepidic, papillary and micropapillary subtypes. Increasing evidence has shown that micropapillary LUAD is positively associated with a higher percentage of driver gene mutations, a higher incidence of metastasis and a poorer prognosis, while lepidic LUAD has a relatively better prognosis. However, the novel genetic change and its underlying mechanism in the progression of micropapillary LUAD have not been exactly determined.</p> </section> <section> <h3> Methods</h3> <p>A total of 181 patients with LUAD who underwent surgery at the First Affiliated Hospital of Huzhou University from January 2020 to December 2022 were enrolled. Three predominant lepidic and three predominant micropapillary LUAD tissue samples were carried out using whole-exome sequencing. Comprehensive analysis of genomic variations and the difference between lepidic and micropapillary LUAD was performed. In addition, the <i>TMEM229A</i> Q200del mutation was verified using our cohort and TCGA-LUAD datasets. The correlations between the <i>TMEM229A</i> Q200del mutation and the clinicopathological characteristics of patients with LUAD were further analyzed. The functions and mechanisms of <i>TMEM229A</i> Q200del on NSCLC cell proliferation and migration were also determined.</p> </section> <section> <h3> Results</h3> <p>The frequency of genomic changes in patients with micropapillary LUAD was higher than that in patients with lepidic LUAD. Mutations in <i>EGFR</i>, <i>ATXN2</i>, <i>C14orf180</i>, <i>MUC12</i>, <i>NOTCH1</i>, and <i>PKD1L2</i> were concomitantly detected in three predominant micropapillary and three predominant lepidic LUAD cases. The <i>TMEM229A</i> Q200del mutation was only mutated in lepidic LUAD. Additionally, the <i>TMEM229A</i> Q200del mutation had occurred in 16 (8.8%) patients, and not found <i>TMEM229A</i> R76H and M346T mutations in our cohort, while <i>TMEM229A</i> mutations (R76H, M346T, and Q200del) occurred only in 1.0% of the TCGA-LUAD cohort. Further correlation analysis between the <i>TMEM229A</i> Q200del mutation and clinicopathological characteristics suggested that a lower frequency of the Q200del mutation was significantly associated with positive lymph node metastasis, advanced TNM stage, positive cancer thrombus, and pathological features. Finally, overexpression of <i>TMEM229A</i> Q200del suppressed NSCLC cell proliferation and migration in vitro. Mechanistically, overexpression of TMEM229A and TMEM229A Q200del both reduced the expression level of phosphorylated (p)-ERK a
{"title":"Whole-Exome Sequencing and Experimental Validation Unveil the Roles of TMEM229A Q200del Mutation in Lung Adenocarcinoma","authors":"Yi-Xian Liang, Yan-Ping Xie, Huan-Ming Yu, Wen-Juan Zhu, Cheng-Yi Yin, Zhao-Hui Dong, Xi-Lin Zhang","doi":"10.1111/crj.70006","DOIUrl":"10.1111/crj.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Lung adenocarcinoma (LUAD) is one of the major histopathological types of non-small cell lung cancer (NSCLC), including solid, acinar, lepidic, papillary and micropapillary subtypes. Increasing evidence has shown that micropapillary LUAD is positively associated with a higher percentage of driver gene mutations, a higher incidence of metastasis and a poorer prognosis, while lepidic LUAD has a relatively better prognosis. However, the novel genetic change and its underlying mechanism in the progression of micropapillary LUAD have not been exactly determined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 181 patients with LUAD who underwent surgery at the First Affiliated Hospital of Huzhou University from January 2020 to December 2022 were enrolled. Three predominant lepidic and three predominant micropapillary LUAD tissue samples were carried out using whole-exome sequencing. Comprehensive analysis of genomic variations and the difference between lepidic and micropapillary LUAD was performed. In addition, the <i>TMEM229A</i> Q200del mutation was verified using our cohort and TCGA-LUAD datasets. The correlations between the <i>TMEM229A</i> Q200del mutation and the clinicopathological characteristics of patients with LUAD were further analyzed. The functions and mechanisms of <i>TMEM229A</i> Q200del on NSCLC cell proliferation and migration were also determined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The frequency of genomic changes in patients with micropapillary LUAD was higher than that in patients with lepidic LUAD. Mutations in <i>EGFR</i>, <i>ATXN2</i>, <i>C14orf180</i>, <i>MUC12</i>, <i>NOTCH1</i>, and <i>PKD1L2</i> were concomitantly detected in three predominant micropapillary and three predominant lepidic LUAD cases. The <i>TMEM229A</i> Q200del mutation was only mutated in lepidic LUAD. Additionally, the <i>TMEM229A</i> Q200del mutation had occurred in 16 (8.8%) patients, and not found <i>TMEM229A</i> R76H and M346T mutations in our cohort, while <i>TMEM229A</i> mutations (R76H, M346T, and Q200del) occurred only in 1.0% of the TCGA-LUAD cohort. Further correlation analysis between the <i>TMEM229A</i> Q200del mutation and clinicopathological characteristics suggested that a lower frequency of the Q200del mutation was significantly associated with positive lymph node metastasis, advanced TNM stage, positive cancer thrombus, and pathological features. Finally, overexpression of <i>TMEM229A</i> Q200del suppressed NSCLC cell proliferation and migration in vitro. Mechanistically, overexpression of TMEM229A and TMEM229A Q200del both reduced the expression level of phosphorylated (p)-ERK a","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074608","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}
<p>With the rapid development of socio-economic technology, artificial intelligence (AI) is increasingly applied in daily life. When discussing AI, it is inevitable to mention ChatGPT, a language model based on AI technology. Pretrained on extensive language data, ChatGPT can perform various natural language processing tasks, including dialog generation. In addition, similar large language models include the intelligent assistant Kimi launched by Beijing Lunar Tech and the chatbot ERNIE developed by Baidu, among others.</p><p><i>Mycoplasma pneumoniae</i> pneumonia, caused by infection with <i>Mycoplasma pneumoniae</i>, refers to inflammation of the lungs that can affect the bronchi, bronchioles, alveoli, and interstitial tissue. It can occur at any age but is more common in children aged 5 and above, as well as in immunocompromised individuals (such as the elderly, immunodeficient individuals, or patients undergoing immunosuppressive therapy). The course of <i>Mycoplasma pneumoniae</i> pneumonia is generally 1–2 weeks, with a favorable prognosis and no sequelae in most cases. However, a small number of cases can develop into severe conditions, primarily presenting with symptoms of respiratory distress and respiratory failure. These severe cases are often associated with acute respiratory distress syndrome, plastic bronchitis affecting the large airways, diffuse bronchiolitis, and severe pulmonary embolism. In rare instances, severe extrapulmonary complications may be the main manifestations. Given the prevalence of <i>Mycoplasma pneumoniae</i> infection in China, we sought to understand whether ChatGPT could contribute to a better understanding of <i>Mycoplasma pneumoniae</i> pneumonia. We selected 13 questions that are most commonly asked by patients in clinical practice and posed them to ChatGPT-3.5, ChatGPT-4.0, Kimi, and ERNIE. Each question was run five times. Then we invited nine experts with extensive clinical experience and knowledge of Mycoplasma pneumonia to rate the accuracy of the answers. Among them, there were four respiratory specialists and five pediatric specialists, with five from our hospital and four from other hospitals. The scoring criteria were as follows: score = 0: completely incorrect; score < 6: inaccurate; 6 ≤ score < 8: mostly accurate; 8 ≤ score < 10: very accurate; score = 10: completely accurate. The final results were ChatGPT 3.5 8.46 ± 0.80, ChatGPT 4.0 7.05 ± 1.16, Kimi 8.62 ± 0.68, and ERNIE 9.33 ± 0.30. In descending order of accuracy, they were ERNIE, Kimi, ChatGPT 3.5, and ChatGPT 4.0.</p><p>We compared the answers provided by ChatGPT versions 3.5 and 4.0, ERNIE, and Kimi regarding Mycoplasma pneumonia and found that their accuracy ranked from the highest to the lowest as ERNIE, Kimi, ChatGPT 3.5, and ChatGPT 4.0, with ERNIE achieving the highest accuracy. Although ERNIE performed the best among the four AI models with more comprehensive answers, it still exhibited some answers with noticeable error
{"title":"An Accuracy Assessment: Responses to Mycoplasma Pneumoniae Pneumonia-Related Questions by Different Artificial Intelligence Tools","authors":"Shuang Li","doi":"10.1111/crj.70005","DOIUrl":"10.1111/crj.70005","url":null,"abstract":"<p>With the rapid development of socio-economic technology, artificial intelligence (AI) is increasingly applied in daily life. When discussing AI, it is inevitable to mention ChatGPT, a language model based on AI technology. Pretrained on extensive language data, ChatGPT can perform various natural language processing tasks, including dialog generation. In addition, similar large language models include the intelligent assistant Kimi launched by Beijing Lunar Tech and the chatbot ERNIE developed by Baidu, among others.</p><p><i>Mycoplasma pneumoniae</i> pneumonia, caused by infection with <i>Mycoplasma pneumoniae</i>, refers to inflammation of the lungs that can affect the bronchi, bronchioles, alveoli, and interstitial tissue. It can occur at any age but is more common in children aged 5 and above, as well as in immunocompromised individuals (such as the elderly, immunodeficient individuals, or patients undergoing immunosuppressive therapy). The course of <i>Mycoplasma pneumoniae</i> pneumonia is generally 1–2 weeks, with a favorable prognosis and no sequelae in most cases. However, a small number of cases can develop into severe conditions, primarily presenting with symptoms of respiratory distress and respiratory failure. These severe cases are often associated with acute respiratory distress syndrome, plastic bronchitis affecting the large airways, diffuse bronchiolitis, and severe pulmonary embolism. In rare instances, severe extrapulmonary complications may be the main manifestations. Given the prevalence of <i>Mycoplasma pneumoniae</i> infection in China, we sought to understand whether ChatGPT could contribute to a better understanding of <i>Mycoplasma pneumoniae</i> pneumonia. We selected 13 questions that are most commonly asked by patients in clinical practice and posed them to ChatGPT-3.5, ChatGPT-4.0, Kimi, and ERNIE. Each question was run five times. Then we invited nine experts with extensive clinical experience and knowledge of Mycoplasma pneumonia to rate the accuracy of the answers. Among them, there were four respiratory specialists and five pediatric specialists, with five from our hospital and four from other hospitals. The scoring criteria were as follows: score = 0: completely incorrect; score < 6: inaccurate; 6 ≤ score < 8: mostly accurate; 8 ≤ score < 10: very accurate; score = 10: completely accurate. The final results were ChatGPT 3.5 8.46 ± 0.80, ChatGPT 4.0 7.05 ± 1.16, Kimi 8.62 ± 0.68, and ERNIE 9.33 ± 0.30. In descending order of accuracy, they were ERNIE, Kimi, ChatGPT 3.5, and ChatGPT 4.0.</p><p>We compared the answers provided by ChatGPT versions 3.5 and 4.0, ERNIE, and Kimi regarding Mycoplasma pneumonia and found that their accuracy ranked from the highest to the lowest as ERNIE, Kimi, ChatGPT 3.5, and ChatGPT 4.0, with ERNIE achieving the highest accuracy. Although ERNIE performed the best among the four AI models with more comprehensive answers, it still exhibited some answers with noticeable error","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074603","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}
Tao Zeng, Wangsheng Ren, Hang Zeng, Dachun Wang, Xianyu Wu, Guo Xu
Background
Lung adenocarcinoma (LUAD) is a fatal disease with metabolic abnormalities. The dysregulation of S100 calcium-binding protein A2 (S100A2), a member of the S100 protein family, is connected to the development of various cancers. The impact of S100A2 on the LUAD occurrence and metastasis, however, has not yet been reported. The functional mechanism of S100A2 on LUAD cell metastasis was examined in this article.
Methods
The expression of TFAP2A and S100A2 in LUAD tissues and cells was analyzed by bioinformatics and qRT-PCR, respectively. The enrichment pathway analysis was performed on S100A2. Bioinformatics analysis determined the binding relationship between TFAP2A and S100A2, and their interaction was validated through dual-luciferase and chromatin immunoprecipitation experiments. Cell viability was determined using cell counting kit-8 (CCK-8). A transwell assay was performed to analyze the invasion and migration of cells. Immunofluorescence was conducted to obtain vimentin and E-cadherin expression, and a western blot was used to detect the expression of MMP-2, MMP-9, GLS, and GLUD1. The kits measured the NADPH/NADP ratio, glutathione (GSH)/glutathione disulfide (GSSG) levels, and the contents of glutamine, α-KG, and glutamate.
Results
S100A2 was upregulated in LUAD tissues and cells, and S100A2 mediated glutamine metabolism to induce LUAD metastasis. Additionally, the transcriptional regulator TFAP2A was discovered upstream of S100A2, and TFAP2A expression was upregulated in LUAD, which indicated that TFAP2A promoted the S100A2 expression. The rescue experiment found that upregulation of S100A2 could reverse the inhibitory effects of silencing TFAP2A on glutamine metabolism and cell metastasis.
Conclusion
In conclusion, by regulating glutamine metabolism, the TFAP2A/S100A2 axis facilitated LUAD metastasis. This suggested that targeting S100A2 could be beneficial for LUAD treatment.
{"title":"TFAP2A Activates S100A2 to Mediate Glutamine Metabolism and Promote Lung Adenocarcinoma Metastasis","authors":"Tao Zeng, Wangsheng Ren, Hang Zeng, Dachun Wang, Xianyu Wu, Guo Xu","doi":"10.1111/crj.13825","DOIUrl":"10.1111/crj.13825","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lung adenocarcinoma (LUAD) is a fatal disease with metabolic abnormalities. The dysregulation of S100 calcium-binding protein A2 (S100A2), a member of the S100 protein family, is connected to the development of various cancers. The impact of S100A2 on the LUAD occurrence and metastasis, however, has not yet been reported. The functional mechanism of S100A2 on LUAD cell metastasis was examined in this article.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The expression of TFAP2A and S100A2 in LUAD tissues and cells was analyzed by bioinformatics and qRT-PCR, respectively. The enrichment pathway analysis was performed on S100A2. Bioinformatics analysis determined the binding relationship between TFAP2A and S100A2, and their interaction was validated through dual-luciferase and chromatin immunoprecipitation experiments. Cell viability was determined using cell counting kit-8 (CCK-8). A transwell assay was performed to analyze the invasion and migration of cells. Immunofluorescence was conducted to obtain vimentin and E-cadherin expression, and a western blot was used to detect the expression of MMP-2, MMP-9, GLS, and GLUD1. The kits measured the NADPH/NADP ratio, glutathione (GSH)/glutathione disulfide (GSSG) levels, and the contents of glutamine, α-KG, and glutamate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>S100A2 was upregulated in LUAD tissues and cells, and S100A2 mediated glutamine metabolism to induce LUAD metastasis. Additionally, the transcriptional regulator TFAP2A was discovered upstream of S100A2, and TFAP2A expression was upregulated in LUAD, which indicated that TFAP2A promoted the S100A2 expression. The rescue experiment found that upregulation of S100A2 could reverse the inhibitory effects of silencing TFAP2A on glutamine metabolism and cell metastasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, by regulating glutamine metabolism, the TFAP2A/S100A2 axis facilitated LUAD metastasis. This suggested that targeting S100A2 could be beneficial for LUAD treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuxin Gong, Fawang Du, Yu Yao, Hanchao Wang, Xiaochuan Wang, Wei Xiong, Qin Wang, Gaoyan He, Linlin Chen, Heng Du, Juan Yang, Brent A. Bauer, Zhongruo Wang, Huojin Deng, Tao Zhu
Introduction
Low body weight in patients with COPD is associated with a poor prognosis and more comorbidities. However, the impact of increased body weight in patients with COPD remains controversial. The aim of this study was to explore the clinical features of overweight patients with AECOPD.
Methods
In this multicenter cross-sectional study, a total of 647 AECOPD patients were recruited. Finally, 269 normal weight and 162 overweight patients were included. Baseline characteristics and clinical and laboratory data were collected. The least absolute shrinkage and selection operator (LASSO) regression was performed to determine potential features, which were substituted into binary logistic regression to reveal overweight-associated clinical features. The nomogram and its associated curves were established to visualize and verify the logistic regression model.
Results
Six potential overweight-associated variables were selected by LASSO regression. Subsequently, a binary logistic regression model identified that the rates of type 2 diabetes (T2DM) and hypertension and levels of lymphocytes (LYM)%, and alanine aminotransferase (ALT) were independent variables of overweight in AECOPD patients. The C-index and AUC of the ROC curve of the nomogram were 0.671 and 0.666, respectively. The DCA curve revealed that the nomogram had more clinical benefits if the threshold was at a range of 0.22~0.78.
Conclusions
Collectively, we revealed that T2DM and hypertension were more common, and LYM% and ALT were higher in AECOPD patients with overweight than those with normal weight. The result suggests that AECOPD patients with overweight are at risk for additional comorbidities, potentially leading to worse outcomes.
{"title":"Clinical Characteristics of Overweight Patients With Acute Exacerbation Chronic Obstructive Pulmonary Disease (AECOPD)","authors":"Yuxin Gong, Fawang Du, Yu Yao, Hanchao Wang, Xiaochuan Wang, Wei Xiong, Qin Wang, Gaoyan He, Linlin Chen, Heng Du, Juan Yang, Brent A. Bauer, Zhongruo Wang, Huojin Deng, Tao Zhu","doi":"10.1111/crj.70001","DOIUrl":"10.1111/crj.70001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Low body weight in patients with COPD is associated with a poor prognosis and more comorbidities. However, the impact of increased body weight in patients with COPD remains controversial. The aim of this study was to explore the clinical features of overweight patients with AECOPD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this multicenter cross-sectional study, a total of 647 AECOPD patients were recruited. Finally, 269 normal weight and 162 overweight patients were included. Baseline characteristics and clinical and laboratory data were collected. The least absolute shrinkage and selection operator (LASSO) regression was performed to determine potential features, which were substituted into binary logistic regression to reveal overweight-associated clinical features. The nomogram and its associated curves were established to visualize and verify the logistic regression model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Six potential overweight-associated variables were selected by LASSO regression. Subsequently, a binary logistic regression model identified that the rates of type 2 diabetes (T2DM) and hypertension and levels of lymphocytes (LYM)%, and alanine aminotransferase (ALT) were independent variables of overweight in AECOPD patients. The C-index and AUC of the ROC curve of the nomogram were 0.671 and 0.666, respectively. The DCA curve revealed that the nomogram had more clinical benefits if the threshold was at a range of 0.22~0.78.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Collectively, we revealed that T2DM and hypertension were more common, and LYM% and ALT were higher in AECOPD patients with overweight than those with normal weight. The result suggests that AECOPD patients with overweight are at risk for additional comorbidities, potentially leading to worse outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":"18 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074604","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}
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.
{"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":"18 8","pages":""},"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}
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":"18 8","pages":""},"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}
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.
{"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":"18 8","pages":""},"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}
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.
{"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":"18 8","pages":""},"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}
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.
{"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":"18 8","pages":""},"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}
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