Mitochondrial ribosomal protein L35 (MRPL35) has been reported to contribute to the growth of non–small cell lung cancer (NSCLC) cells. However, the functions and mechanisms of MRPL35 on glutamine metabolism in NSCLC remain unclear.
Methods
The detection of mRNA and protein of MRPL35, ubiquitin-specific protease 39 (USP39), and solute carrier family 7 member 5 (SLC7A5) was conducted using qRT-PCR and western blotting. Cell proliferation, apoptosis, and invasion were evaluated using the MTT assay, EdU assay, flow cytometry, and transwell assay, respectively. Glutamine metabolism was analyzed by detecting glutamine consumption, α-ketoglutarate level, and glutamate production. Cellular ubiquitination analyzed the deubiquitination effect of USP39 on MRPL35. An animal experiment was conducted for in vivo analysis.
Results
MRPL35 was highly expressed in NSCLC tissues and cell lines, and high MRPL35 expression predicted poor outcome in NSCLC patients. In vitro analyses suggested that MRPL35 knockdown suppressed NSCLC cell proliferation, invasion, and glutamine metabolism. Moreover, MRPL35 silencing hindered tumor growth in vivo. Mechanistically, USP39 stabilized MRPL35 expression by deubiquitination and then promoted NSCLC cell proliferation, invasion, and glutamine metabolism. In addition, MRPL35 positively affected SLC7A5 expression in NSCLC cells in vitro and in vivo. Moreover, the anticancer effects of MRPL35 silencing could be rescued by SLC7A5 overexpression in NSCLC cells.
Conclusion
MRPL35 expression was stabilized by USP39-induced deubiquitination in NSCLC cells, and knockdown of MRPL35 suppressed NSCLC cell proliferation, invasion, and glutamine metabolism in vitro and impeded tumor growth in vivo by upregulating SLC7A5, providing a promising therapeutic target for NSCLC.
{"title":"MRPL35 Induces Proliferation, Invasion, and Glutamine Metabolism in NSCLC Cells by Upregulating SLC7A5 Expression","authors":"Wei Hou, Juan Chen, Yaoyuan Wang","doi":"10.1111/crj.13799","DOIUrl":"10.1111/crj.13799","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mitochondrial ribosomal protein L35 (MRPL35) has been reported to contribute to the growth of non–small cell lung cancer (NSCLC) cells. However, the functions and mechanisms of MRPL35 on glutamine metabolism in NSCLC remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The detection of mRNA and protein of MRPL35, ubiquitin-specific protease 39 (USP39), and solute carrier family 7 member 5 (SLC7A5) was conducted using qRT-PCR and western blotting. Cell proliferation, apoptosis, and invasion were evaluated using the MTT assay, EdU assay, flow cytometry, and transwell assay, respectively. Glutamine metabolism was analyzed by detecting glutamine consumption, α-ketoglutarate level, and glutamate production. Cellular ubiquitination analyzed the deubiquitination effect of USP39 on MRPL35. An animal experiment was conducted for in vivo analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MRPL35 was highly expressed in NSCLC tissues and cell lines, and high MRPL35 expression predicted poor outcome in NSCLC patients. In vitro analyses suggested that MRPL35 knockdown suppressed NSCLC cell proliferation, invasion, and glutamine metabolism. Moreover, MRPL35 silencing hindered tumor growth in vivo. Mechanistically, USP39 stabilized MRPL35 expression by deubiquitination and then promoted NSCLC cell proliferation, invasion, and glutamine metabolism. In addition, MRPL35 positively affected SLC7A5 expression in NSCLC cells in vitro and in vivo. Moreover, the anticancer effects of MRPL35 silencing could be rescued by SLC7A5 overexpression in NSCLC cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MRPL35 expression was stabilized by USP39-induced deubiquitination in NSCLC cells, and knockdown of MRPL35 suppressed NSCLC cell proliferation, invasion, and glutamine metabolism in vitro and impeded tumor growth in vivo by upregulating SLC7A5, providing a promising therapeutic target for NSCLC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13799","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581585","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}
Zhiqiang He, Jing Wu, Xiao ming Fu, Xiao ran Li, Hai Xu, Yu-Chen Chen
Renal angiomyolipoma has two histological variants: classical and epithelioid. Epithelioid angiomyolipoma is considered as a potential malignant tumor, often leading to recurrence and metastasis, with rapid progression in most of the cases. The lung is one of the most commonly reported sites of metastasis, and pulmonary metastasis of renal angiomyolipoma is usually diagnostic by computed tomography (CT) scans. Here, we report for the first time renal angiomyolipoma with lung metastasis by combining CT and magnetic resonance imaging (MRI).
{"title":"CT and MRI Findings of Renal Angiomyolipoma With Lung Metastasis: A Case Report and Literature Review","authors":"Zhiqiang He, Jing Wu, Xiao ming Fu, Xiao ran Li, Hai Xu, Yu-Chen Chen","doi":"10.1111/crj.13796","DOIUrl":"10.1111/crj.13796","url":null,"abstract":"<p>Renal angiomyolipoma has two histological variants: classical and epithelioid. Epithelioid angiomyolipoma is considered as a potential malignant tumor, often leading to recurrence and metastasis, with rapid progression in most of the cases. The lung is one of the most commonly reported sites of metastasis, and pulmonary metastasis of renal angiomyolipoma is usually diagnostic by computed tomography (CT) scans. Here, we report for the first time renal angiomyolipoma with lung metastasis by combining CT and magnetic resonance imaging (MRI).</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565166","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}
One hundred eighty pairs of tissues of esophageal squamous cell carcinoma (ESCC) were tested by the transcriptome sequencing in order to explore etiology factors. The chi-square test and correlation analysis demonstrated that the relative expression levels of keratin 17 (KRT17) and collagen type I α1 chain (COL1A1) were significantly higher in EC with diabetes. Expression of KRT17 was correlated with blood glucose (r = 0.204, p = 0.001) and tumor size (r = −0.177, p = 0.038) in patients. COL1A1 correlated with age (r = −0.170, p = 0.029) and blood glucose levels (r = 0.190, p = 0.015). Experimental results of qRT-PCR: KRT17 and COL1A1 genes were highly expressed in ESCC (p < 0.05). When the two genes were used as a combination test, the positive detection rate of EC was 90.6%, and the ROC curve had greater power. The KRT17 and COL1A1 genes had the potential to be biomarkers for the diagnosis of ESCC.
{"title":"Keratin 17 and Collagen type 1 genes: Esophageal cancer molecular marker discovery and evaluation","authors":"Huiwen Pan, Jie Hong, Aizhong Shao, Zhiguo Zhao, Guowen Ding, Zhijie Fang, Keping Chen, Jingfeng Zhu","doi":"10.1111/crj.13793","DOIUrl":"10.1111/crj.13793","url":null,"abstract":"<p>One hundred eighty pairs of tissues of esophageal squamous cell carcinoma (ESCC) were tested by the transcriptome sequencing in order to explore etiology factors. The chi-square test and correlation analysis demonstrated that the relative expression levels of keratin 17 (KRT17) and collagen type I α1 chain (COL1A1) were significantly higher in EC with diabetes. Expression of KRT17 was correlated with blood glucose (<i>r</i> = 0.204, <i>p</i> = 0.001) and tumor size (<i>r</i> = −0.177, <i>p</i> = 0.038) in patients. COL1A1 correlated with age (<i>r</i> = −0.170, <i>p</i> = 0.029) and blood glucose levels (<i>r</i> = 0.190, <i>p</i> = 0.015). Experimental results of qRT-PCR: KRT17 and COL1A1 genes were highly expressed in ESCC (<i>p</i> < 0.05). When the two genes were used as a combination test, the positive detection rate of EC was 90.6%, and the ROC curve had greater power. The KRT17 and COL1A1 genes had the potential to be biomarkers for the diagnosis of ESCC.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560425","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}
Idiopathic pulmonary fibrosis (IPF) is a progressive disease and has a high mortality rates [1]. While the overall prognosis of IPF is poor, the decline in pulmonary function tests and progression to death varies widely [2]. Identification of patients with slow progression or rapid progression would be valuable for subsequent studies, including genetic analyses and investigation of IPF clinical phenotypes. Additionally, it could influence treatment decisions, including the timing of transplantation. We congratulate Doubkova and colleagues for their study aiming to establish the impact of demographic parameters, pulmonary function parameters and high-resolution computed tomography scores [1]. It was revealed that diffusing lung carbon monoxide (DLCO) decline seems to be superior to forced vital capacity (FVC) decline in predicting mortality. After a thorough review of their article, we offer the following comments to enrich the understanding of their study.
FVC is the most common outcome used in investigating the course of patients with IPF and change in FVC percentage predicted over time is a well-known predictor of mortality [3]. The primary endpoint as FVC decline in INPULSIS [4], ASCEND [5], CAPACITY [6] and TOMORROW [7] studies. However, DLCO decline was found to be an independent predictor of mortality after multivariate analysis instead of FVC decline in this study [1]. Statistically, only more clinically significant parameters should be included in the multivariate analysis among those showing high correlation. In line with this, it should be noted that both FVC and DLCO decline, which are expected to have a high correlation, were included in the multivariate analysis. This may lead to a multicollinearity problem and impact the accuracy of the results. To address this issue, it may be beneficial to create two separate models [Model 1: FVC model (not including DLCO) and Model 2: DLCO model (not including FVC)].
Regarding baseline characteristics, there were significant differences in the extent of lung involvement, FVC (%) and DLCO (%) found between alive and deceased patients. Deceased patients were more likely to have higher alveolar and interstitial scores, as well as lower DLCO (%) and FVC (%). Since baseline FVC (%) and DLCO (%) were not included in the univariate Cox analysis, we cannot determine the independent effect of decline in FVC (%) and DLCO (%). This is important because patients with more severe baseline conditions are more likely to deteriorate and experience mortality.
As authors indicated, pulmonary hypertension has not been assessed. However, this may affect the prognostic role of DLCO (%), which is the primary conclusion of this study, because DLCO is expected to be significantly low in patients with pulmonary hypertension. Indeed, given the highly variable clinical course of IPF, the
{"title":"A Commentary on the Role of Pulmonary Function Parameters in Idiopathic Pulmonary Fibrosis Follow-Up","authors":"Guliz Degirmenci, Celal Satici","doi":"10.1111/crj.13797","DOIUrl":"10.1111/crj.13797","url":null,"abstract":"<p>Idiopathic pulmonary fibrosis (IPF) is a progressive disease and has a high mortality rates [<span>1</span>]. While the overall prognosis of IPF is poor, the decline in pulmonary function tests and progression to death varies widely [<span>2</span>]. Identification of patients with slow progression or rapid progression would be valuable for subsequent studies, including genetic analyses and investigation of IPF clinical phenotypes. Additionally, it could influence treatment decisions, including the timing of transplantation. We congratulate Doubkova and colleagues for their study aiming to establish the impact of demographic parameters, pulmonary function parameters and high-resolution computed tomography scores [<span>1</span>]. It was revealed that diffusing lung carbon monoxide (DLCO) decline seems to be superior to forced vital capacity (FVC) decline in predicting mortality. After a thorough review of their article, we offer the following comments to enrich the understanding of their study.</p><p>FVC is the most common outcome used in investigating the course of patients with IPF and change in FVC percentage predicted over time is a well-known predictor of mortality [<span>3</span>]. The primary endpoint as FVC decline in INPULSIS [<span>4</span>], ASCEND [<span>5</span>], CAPACITY [<span>6</span>] and TOMORROW [<span>7</span>] studies. However, DLCO decline was found to be an independent predictor of mortality after multivariate analysis instead of FVC decline in this study [<span>1</span>]. Statistically, only more clinically significant parameters should be included in the multivariate analysis among those showing high correlation. In line with this, it should be noted that both FVC and DLCO decline, which are expected to have a high correlation, were included in the multivariate analysis. This may lead to a multicollinearity problem and impact the accuracy of the results. To address this issue, it may be beneficial to create two separate models [Model 1: FVC model (not including DLCO) and Model 2: DLCO model (not including FVC)].</p><p>Regarding baseline characteristics, there were significant differences in the extent of lung involvement, FVC (%) and DLCO (%) found between alive and deceased patients. Deceased patients were more likely to have higher alveolar and interstitial scores, as well as lower DLCO (%) and FVC (%). Since baseline FVC (%) and DLCO (%) were not included in the univariate Cox analysis, we cannot determine the independent effect of decline in FVC (%) and DLCO (%). This is important because patients with more severe baseline conditions are more likely to deteriorate and experience mortality.</p><p>As authors indicated, pulmonary hypertension has not been assessed. However, this may affect the prognostic role of DLCO (%), which is the primary conclusion of this study, because DLCO is expected to be significantly low in patients with pulmonary hypertension. Indeed, given the highly variable clinical course of IPF, the","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460899","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}
One of the most crucial and essential methods for the prevention and management of respiratory infections is for healthcare professionals to take precautions for their own safety. Using Protection Motivation Theory (PMT), the current study looked into effective elements influencing the staff at Kazeroon's Valiasr Hospital's preventive actions against respiratory diseases.
Methods
One hundred ninety-two male and 108 female employees of the Valiasr Hospital in Kazeroon, Iran, participated in this cross-sectional study, in May 2022. Census data were used as the sample technique. A questionnaire based on the PMT and a questionnaire collecting demographic data served as the data collection method. The study's content validity was confirmed by 10 health education experts, and its reliability was assessed using internal consistency techniques, resulting in a Cronbach's alpha coefficient of 0.87.The statistical program SPSS 24 was used to examine the data using the independent t test, logistic regression, and Pearson correlation.
Results
The average age was 34.11 ± 8.91 for men and 32.77 ± 6.09 for women. The majority of participants were married (73.3%), had university education (76.7%), and earned a monthly income between 10 and 15 million Tomans (75%). Notably, 97.7% of participants had received the COVID-19 vaccine, and 77.7% had undergone training related to respiratory infections. The most common preventive practices included avoiding touching the eyes, noses, or mouths, wearing appropriate protective gear, and maintaining a safe distance of 1–2 m from others. Analysis of PMT constructs showed that participants had a generally positive perception toward preventive behaviors. Perceived vulnerability (P = 0.02), perceived cost (P = 0.03), and motivation (P = 0.001) were the three analyzed components that had the greatest impact on respiratory infection preventative behavior. Logistic regression revealed that perceived susceptibility, cost, and motivation significantly predicted the prevention of respiratory infections, with a predictive power of 45%. These findings highlight the importance of understanding the factors influencing preventive behaviors among hospital staff, from respiratory infections like COVID-19.
Conclusion
According to the findings, the personnel at Kazeroon's Valiasr Hospital wore gloves, goggles, and other appropriate personal protective equipment. The
{"title":"Preventive behaviors of respiratory infections in staff of hospital in Kazeroon, Fars, Iran: An application of protection motivation theory","authors":"Tayebeh Rakhshani, Zohreh Shafiei, Samira Taravatmanesh, Seyyed Mansour Kashfi, Pooyan Afzali Harsini, Amirhossein Kamyab, Ali Khani Jeihooni","doi":"10.1111/crj.13791","DOIUrl":"10.1111/crj.13791","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>One of the most crucial and essential methods for the prevention and management of respiratory infections is for healthcare professionals to take precautions for their own safety. Using Protection Motivation Theory (PMT), the current study looked into effective elements influencing the staff at Kazeroon's Valiasr Hospital's preventive actions against respiratory diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>One hundred ninety-two male and 108 female employees of the Valiasr Hospital in Kazeroon, Iran, participated in this cross-sectional study, in May 2022. Census data were used as the sample technique. A questionnaire based on the PMT and a questionnaire collecting demographic data served as the data collection method. The study's content validity was confirmed by 10 health education experts, and its reliability was assessed using internal consistency techniques, resulting in a Cronbach's alpha coefficient of 0.87.The statistical program SPSS 24 was used to examine the data using the independent <i>t</i> test, logistic regression, and Pearson correlation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The average age was 34.11 ± 8.91 for men and 32.77 ± 6.09 for women. The majority of participants were married (73.3%), had university education (76.7%), and earned a monthly income between 10 and 15 million Tomans (75%). Notably, 97.7% of participants had received the COVID-19 vaccine, and 77.7% had undergone training related to respiratory infections. The most common preventive practices included avoiding touching the eyes, noses, or mouths, wearing appropriate protective gear, and maintaining a safe distance of 1–2 m from others. Analysis of PMT constructs showed that participants had a generally positive perception toward preventive behaviors. Perceived vulnerability (<i>P</i> = 0.02), perceived cost (<i>P</i> = 0.03), and motivation (<i>P</i> = 0.001) were the three analyzed components that had the greatest impact on respiratory infection preventative behavior. Logistic regression revealed that perceived susceptibility, cost, and motivation significantly predicted the prevention of respiratory infections, with a predictive power of 45%. These findings highlight the importance of understanding the factors influencing preventive behaviors among hospital staff, from respiratory infections like COVID-19.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>According to the findings, the personnel at Kazeroon's Valiasr Hospital wore gloves, goggles, and other appropriate personal protective equipment. The ","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421947","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}
Wanjun Wang, Mo Xian, Yongxia Lei, Juhua Yang, Lulu Wu
To the Editor:
Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder caused by hypersensitivity to Aspergillus, which colonizes the airways of patients with asthma [1]. Previous studies have shown that fungal colonization in Aspergillus-allergic diseases could lead to more rapid airway obstruction [2], but they lack a direct link to clinical relevance and outcome. Therefore, we aimed to identify Aspergillus fumigatus colonization in ABPA patients and compare their profile without colonization.
We retrospectively analyzed the clinical data of 116 patients at the Department of Allergy and Clinical Immunology, the First Affiliated Hospital of Guangzhou Medical University, from January 2014 to October 2020, of which 96 cases were diagnosed with ABPA according to the criteria described previously [3]. Twenty patients with the diagnosis of refractory asthma, according to the Global Institute for Asthma (GINA), were enrolled as controls. The definition of ABPA exacerbation was worsening of clinical status, obstructive deterioration of lung function, rising total IgE levels by > 50%, and the appearance of new shallow infiltrates on radiology. All patients underwent a trans-bronchoscopy and bronchial mucosa biopsy. We utilized metagenomic next-generation sequencing for the detection of the A. fumigatus genome from the samples. Details about the methods are in Appendix S1.
Our study showed that the basic demographic features were similar in subjects with or without tissue colonization, except for the expectoration of mucus plugs. Eosinophil counts; blood A. fumigatus-sIgE, IgG, and total IgE levels; and the rate of Pseudomonas aeruginosa colonization were all higher in ABPA than in severe asthma. In subjects with colonization, an average of 690 ± 530 bp A. fumigatus nucleotide reads were detected, but only 3.9% had a positive sputum culture. The FEV1, FVC, and FEV1/FVC values were significantly lower in subjects with colonization. Higher bronchiectasis CT values (59.5 ± 7.1 vs. 34 ± 8, p < 0.05) and more numbers of involved lobes and segments were observed in subjects with colonization (4.8 ± 0.6 vs. 3.3 ± 1.2 and 16.2 ± 4.6 vs. 9.6 ± 4.9, both p < 0.05). The presence of HAM was seen in 76.4% of subjects with colonization. The duration of follow-up among the three groups was nearly identical. The ABPA subjects received a higher dosage of ICS and a longer period of oral corticosteroids. More than half of the subjects with colonization (54.9%) were treated with itraconazole. A significantly larger proportion, 24/51 (47.1% vs. 24.4%), of subjects with colonization experienced ABPA exacerbations (Table 1). Twenty-two of these 24 subjects experienced their first exacerbation after 12 months of the initial diagnosis (Appendix S2). The incidence rate of exacerbation was also signi
{"title":"Allergic Bronchopulmonary Aspergillosis (ABPA) With Colonized Aspergillus fumigatus Detected by Metagenomic Next-Generation Sequencing on Tissue Samples: A Distinct Subset of ABPA With a Higher Risk of Exacerbation","authors":"Wanjun Wang, Mo Xian, Yongxia Lei, Juhua Yang, Lulu Wu","doi":"10.1111/crj.13794","DOIUrl":"10.1111/crj.13794","url":null,"abstract":"<p>To the Editor:</p><p>Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder caused by hypersensitivity to <i>Aspergillus</i>, which colonizes the airways of patients with asthma [<span>1</span>]. Previous studies have shown that fungal colonization in <i>Aspergillus</i>-allergic diseases could lead to more rapid airway obstruction [<span>2</span>], but they lack a direct link to clinical relevance and outcome. Therefore, we aimed to identify <i>Aspergillus fumigatus</i> colonization in ABPA patients and compare their profile without colonization.</p><p>We retrospectively analyzed the clinical data of 116 patients at the Department of Allergy and Clinical Immunology, the First Affiliated Hospital of Guangzhou Medical University, from January 2014 to October 2020, of which 96 cases were diagnosed with ABPA according to the criteria described previously [<span>3</span>]. Twenty patients with the diagnosis of refractory asthma, according to the Global Institute for Asthma (GINA), were enrolled as controls. The definition of ABPA exacerbation was worsening of clinical status, obstructive deterioration of lung function, rising total IgE levels by > 50%, and the appearance of new shallow infiltrates on radiology. All patients underwent a trans-bronchoscopy and bronchial mucosa biopsy. We utilized metagenomic next-generation sequencing for the detection of the <i>A. fumigatus</i> genome from the samples. Details about the methods are in Appendix S1.</p><p>Our study showed that the basic demographic features were similar in subjects with or without tissue colonization, except for the expectoration of mucus plugs. Eosinophil counts; blood <i>A. fumigatus</i>-sIgE, IgG, and total IgE levels; and the rate of <i>Pseudomonas aeruginosa</i> colonization were all higher in ABPA than in severe asthma. In subjects with colonization, an average of 690 ± 530 bp <i>A. fumigatus</i> nucleotide reads were detected, but only 3.9% had a positive sputum culture. The FEV<sub>1</sub>, FVC, and FEV<sub>1</sub>/FVC values were significantly lower in subjects with colonization. Higher bronchiectasis CT values (59.5 ± 7.1 vs. 34 ± 8, <i>p</i> < 0.05) and more numbers of involved lobes and segments were observed in subjects with colonization (4.8 ± 0.6 vs. 3.3 ± 1.2 and 16.2 ± 4.6 vs. 9.6 ± 4.9, both <i>p</i> < 0.05). The presence of HAM was seen in 76.4% of subjects with colonization. The duration of follow-up among the three groups was nearly identical. The ABPA subjects received a higher dosage of ICS and a longer period of oral corticosteroids. More than half of the subjects with colonization (54.9%) were treated with itraconazole. A significantly larger proportion, 24/51 (47.1% vs. 24.4%), of subjects with colonization experienced ABPA exacerbations (Table 1). Twenty-two of these 24 subjects experienced their first exacerbation after 12 months of the initial diagnosis (Appendix S2). The incidence rate of exacerbation was also signi","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421946","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}
Pulmonary heart disease (PHD) involves altered structure and function of the right ventricle caused by an abnormal respiratory system that causes pulmonary hypertension. However, the association between changes in plasma proteomics and PHD remains unclear. Hence, we aimed to identify causal associations between genetically predicted plasma protein levels and PHD. Mendelian randomization was performed to test the target proteins associated with PHD. Summary statistics for the human plasma proteome and pulmonary heart disease were acquired from the UK Biobank (6038 cases and 426 977 controls) and the FinnGen study (6753 cases and 302 401 controls). Publicly available pQTLs datasets for human plasma proteins were obtained from a largescale genome-wide association study in the INTERVAL study. The results were validated using a case–control cohort. We first enrolled 3622 plasma proteins with conditionally independent genetic variants; three proteins (histo-blood group ABO system transferase, activating signal cointegration 1 complex subunit 1, and calcium/calmodulin-dependent protein kinase I [CAMK1]) were significantly associated with the risk of pulmonary heart disease in the UK Biobank cohort. Only CAMK1 was successfully replicated (odds ratio: 1.1056, 95% confidence interval: 1.019–1.095, p = 0.0029) in the FinnGen population. In addition, the level of CAMK1 in 40 patients with PHD was significantly higher (p = 0.023) than that in the control group. This work proposes that CAMK1 is associated with PHD, underscoring the importance of the calcium signaling pathway in the pathophysiology to improve therapies for PHD.
{"title":"Association between plasma proteome and pulmonary heart disease: A two-stage Mendelian randomization analysis","authors":"Shiyang Li, Haifeng Ding, Qi Li, Xiaobin Zeng, Yanyu Zhang, Chengyi Lai, Xiaoshuang Xie, Yongjiang Tang, Jianjun Lan","doi":"10.1111/crj.13775","DOIUrl":"10.1111/crj.13775","url":null,"abstract":"<p>Pulmonary heart disease (PHD) involves altered structure and function of the right ventricle caused by an abnormal respiratory system that causes pulmonary hypertension. However, the association between changes in plasma proteomics and PHD remains unclear. Hence, we aimed to identify causal associations between genetically predicted plasma protein levels and PHD. Mendelian randomization was performed to test the target proteins associated with PHD. Summary statistics for the human plasma proteome and pulmonary heart disease were acquired from the UK Biobank (6038 cases and 426 977 controls) and the FinnGen study (6753 cases and 302 401 controls). Publicly available pQTLs datasets for human plasma proteins were obtained from a largescale genome-wide association study in the INTERVAL study. The results were validated using a case–control cohort. We first enrolled 3622 plasma proteins with conditionally independent genetic variants; three proteins (histo-blood group ABO system transferase, activating signal cointegration 1 complex subunit 1, and calcium/calmodulin-dependent protein kinase I [CAMK1]) were significantly associated with the risk of pulmonary heart disease in the UK Biobank cohort. Only CAMK1 was successfully replicated (odds ratio: 1.1056, 95% confidence interval: 1.019–1.095, <i>p</i> = 0.0029) in the FinnGen population. In addition, the level of CAMK1 in 40 patients with PHD was significantly higher (<i>p</i> = 0.023) than that in the control group. This work proposes that CAMK1 is associated with PHD, underscoring the importance of the calcium signaling pathway in the pathophysiology to improve therapies for PHD.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13775","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237412","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}
Xueli Bai, Yanan Niu, Shuang Wei, Zhifan Zhu, Min Xu, Hu Liu, Xiansheng Liu, Ruiying Wang
Background
The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent Omicron variant has raised concerns for chronic obstructive pulmonary disease (COPD) patients due to the potential risk of disruptions to healthcare services and unknown comorbidities between COPD and Omicron.
Method
In this study, we conducted a follow-up investigation of 315 COPD patients during the Omicron outbreak at Shanxi Bethune Hospital to understand the impact of the pandemic on this vulnerable population. Among all patients, 228 were infected with Omicron, of which 82 needed hospitalizations.
Result
We found that COPD patients with high blood eosinophil (EOS) counts exhibited lower susceptibility to Omicron infection and were more likely to have milder symptoms that did not require hospitalization. Conversely, patients with low EOS counts showed higher rates of infection and hospitalization. Moreover, EOS count was positively correlated with T lymphocyte counts in hospitalized patients after Omicron infection, suggesting potential associations between EOS and specific immune responses in COPD patients during viral infections. Correlation analysis revealed a positive correlation between EOS count and lymphocyte and T-cells, and a negative correlation between EOS count and age, neutrophil, and C-reactive protein.
Conclusion
Overall, our study contributes to the knowledge of COPD management during the COVID-19 Omicron outbreak and emphasizes the importance of considering individual immune profiles to improve care for COPD patients in the face of the ongoing global health crisis.
{"title":"COPD patients with high blood eosinophil counts exhibit a lower rate of omicron infection and milder post-infection symptoms","authors":"Xueli Bai, Yanan Niu, Shuang Wei, Zhifan Zhu, Min Xu, Hu Liu, Xiansheng Liu, Ruiying Wang","doi":"10.1111/crj.13790","DOIUrl":"10.1111/crj.13790","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent Omicron variant has raised concerns for chronic obstructive pulmonary disease (COPD) patients due to the potential risk of disruptions to healthcare services and unknown comorbidities between COPD and Omicron.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>In this study, we conducted a follow-up investigation of 315 COPD patients during the Omicron outbreak at Shanxi Bethune Hospital to understand the impact of the pandemic on this vulnerable population. Among all patients, 228 were infected with Omicron, of which 82 needed hospitalizations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>We found that COPD patients with high blood eosinophil (EOS) counts exhibited lower susceptibility to Omicron infection and were more likely to have milder symptoms that did not require hospitalization. Conversely, patients with low EOS counts showed higher rates of infection and hospitalization. Moreover, EOS count was positively correlated with T lymphocyte counts in hospitalized patients after Omicron infection, suggesting potential associations between EOS and specific immune responses in COPD patients during viral infections. Correlation analysis revealed a positive correlation between EOS count and lymphocyte and T-cells, and a negative correlation between EOS count and age, neutrophil, and C-reactive protein.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, our study contributes to the knowledge of COPD management during the COVID-19 Omicron outbreak and emphasizes the importance of considering individual immune profiles to improve care for COPD patients in the face of the ongoing global health crisis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13790","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180771","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}
Nianxi Tan, Junyi Tang, Guang Chen, Weilin Jiang, Zhiqin Liu
Objective
This study aimed to explore the role and regulatory mechanism of lncRNA ZEB1-AS1 in lung cancer.
Methods
The expression of ZEB1-AS1 and miR-320b was determined by qRT-PCR. Cell viability, proliferation migration, and invasion were assessed using the CCK-8, colony-forming, and Transwell assay. EMT markers were quantified using western blot. The growth of subcutaneous tumor growth and metastatic bone tumors was evaluated in mouse model of lung cancer. Additionally, metastatic bone tumors were examined using H&E staining.
Results
ZEB1-AS1 expression was upregulated, while miR-320b levels were downregulated in lung cancer. Knockdown of ZEB1-AS1 resulted in a significant suppression of cell viability, proliferation, migration, invasion, and EMT in A549 cells. Furthermore, we confirmed the targeting relationship between ZEB1-AS1 and miR-320b, as well as between miR-320b and BMPR1A. Our findings suggested that ZEB1-AS1 regulated cell viability, proliferation, migration, and invasion, as well as EMT, in lung cancer cells by targeting the miR-320b/BMPR1A axis. Moreover, our in vivo experiments confirmed that ZEB1-AS1 mediated bone metastasis through targeting miR-320b/BMPR1A axis in mice with lung cancer.
Conclusion
ZEB1-AS1 mediated bone metastasis through targeting miR-320b/BMPR1A axis in lung cancer.
{"title":"ZEB1-AS1 mediates bone metastasis through targeting miR-320b/BMPR1A axis in lung cancer","authors":"Nianxi Tan, Junyi Tang, Guang Chen, Weilin Jiang, Zhiqin Liu","doi":"10.1111/crj.13770","DOIUrl":"10.1111/crj.13770","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to explore the role and regulatory mechanism of lncRNA ZEB1-AS1 in lung cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The expression of ZEB1-AS1 and miR-320b was determined by qRT-PCR. Cell viability, proliferation migration, and invasion were assessed using the CCK-8, colony-forming, and Transwell assay. EMT markers were quantified using western blot. The growth of subcutaneous tumor growth and metastatic bone tumors was evaluated in mouse model of lung cancer. Additionally, metastatic bone tumors were examined using H&E staining.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ZEB1-AS1 expression was upregulated, while miR-320b levels were downregulated in lung cancer. Knockdown of ZEB1-AS1 resulted in a significant suppression of cell viability, proliferation, migration, invasion, and EMT in A549 cells. Furthermore, we confirmed the targeting relationship between ZEB1-AS1 and miR-320b, as well as between miR-320b and BMPR1A. Our findings suggested that ZEB1-AS1 regulated cell viability, proliferation, migration, and invasion, as well as EMT, in lung cancer cells by targeting the miR-320b/BMPR1A axis. Moreover, our in vivo experiments confirmed that ZEB1-AS1 mediated bone metastasis through targeting miR-320b/BMPR1A axis in mice with lung cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ZEB1-AS1 mediated bone metastasis through targeting miR-320b/BMPR1A axis in lung cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13770","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089456","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}
Long COVID, or post-acute sequelae of COVID-19 (PASC), represents a complex condition with persistent symptoms following SARS-Cov-2 infection. The symptoms include fatigue, dyspnoea, cognitive impairment, decreased quality of life in variable levels of severity. Potential mechanisms behind long COVID include vascular damage, immune dysregulation and viral persistence. Diagnosing long COVID involves medical evaluation by multidisciplinary team and assessment of persistent symptoms with scoring systems in development. Treatment strategies are symptom-focused, encompassing multidisciplinary care, rehabilitation and tailored exercise programmes. Pulmonary rehabilitation, an effective and critical component of long COVID management, has shown promise, particularly for patients with respiratory symptoms such as dyspnoea. These programmes, which combine exercise, breathing techniques, education and psychological support, improve symptoms, quality of life and overall recovery. Innovative technologies, such as telemedicine, wearable devices, telerehabilitation, are transforming long COVID management. Telemedicine facilitates consultations and interventions, eliminating healthcare access barriers. Wearable devices enable remote and continuous monitoring of patients during their rehabilitation activities. Telerehabilitation has proven to be safe and feasible and to have high potential for COVID-19 recovery. This review provides a concise overview of long COVID, encompassing its definition, prevalence, mechanisms, clinical manifestations, diagnosis and management approaches. It emphasizes the significance of multidisciplinary approach in diagnosis and treatment of long COVID, with focus on pulmonary rehabilitation and innovative technology advances to effectively address the management of long COVID.
{"title":"Emerging trends in management of long COVID with a focus on pulmonary rehabilitation: A review","authors":"Allison Y. Li, Willis X. Li, Jinghong Li","doi":"10.1111/crj.13777","DOIUrl":"10.1111/crj.13777","url":null,"abstract":"<p>Long COVID, or post-acute sequelae of COVID-19 (PASC), represents a complex condition with persistent symptoms following SARS-Cov-2 infection. The symptoms include fatigue, dyspnoea, cognitive impairment, decreased quality of life in variable levels of severity. Potential mechanisms behind long COVID include vascular damage, immune dysregulation and viral persistence. Diagnosing long COVID involves medical evaluation by multidisciplinary team and assessment of persistent symptoms with scoring systems in development. Treatment strategies are symptom-focused, encompassing multidisciplinary care, rehabilitation and tailored exercise programmes. Pulmonary rehabilitation, an effective and critical component of long COVID management, has shown promise, particularly for patients with respiratory symptoms such as dyspnoea. These programmes, which combine exercise, breathing techniques, education and psychological support, improve symptoms, quality of life and overall recovery. Innovative technologies, such as telemedicine, wearable devices, telerehabilitation, are transforming long COVID management. Telemedicine facilitates consultations and interventions, eliminating healthcare access barriers. Wearable devices enable remote and continuous monitoring of patients during their rehabilitation activities. Telerehabilitation has proven to be safe and feasible and to have high potential for COVID-19 recovery. This review provides a concise overview of long COVID, encompassing its definition, prevalence, mechanisms, clinical manifestations, diagnosis and management approaches. It emphasizes the significance of multidisciplinary approach in diagnosis and treatment of long COVID, with focus on pulmonary rehabilitation and innovative technology advances to effectively address the management of long COVID.</p>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13777","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077011","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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