Experimental Lung Research最新文献

{"title":"Silencing of long noncoding RNA H19 alleviates pulmonary injury, inflammation, and fibrosis of acute respiratory distress syndrome through regulating the microRNA-423-5p/FOXA1 axis.","authors":"Xianyu Mu,&nbsp;Hongrong Wang,&nbsp;Haiyong Li","doi":"10.1080/01902148.2021.1887967","DOIUrl":"https://doi.org/10.1080/01902148.2021.1887967","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to explore the regulatory effects and mechanisms of long noncoding RNA H19 (H19) on pulmonary injury, inflammation, and fibrosis of acute respiratory distress syndrome (ARDS).</p><p><strong>Materials and methods: </strong>A rat model of ARDS was established by intratracheal instillation of 2 mg/kg lipopolysaccharide (LPS). qRT-PCR was performed to detect the expression of H19, miR-423-5p, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP)-1, and vascular endothelial growth factor (VEGF). Histology score was assessed by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of proinflammatory cytokines and the content of VEGF in bronchoalveolar lavage fluid (BALF). The lung fibrosis was evaluated using western blot and Masson's trichrome staining. Dual-luciferase reporter gene assay was used for confirming the relationship between miR-423-5p and H19/FOXA1 in alveolar macrophage cells (MH-S) and alveolar epithelial cells (MLE-12). The regulatory effects of H19/miR-423-5p/FOXA1 axis on the inflammation and fibrosis were further analyzed in LPS-induced MH-S cells.</p><p><strong>Results: </strong>The expression of H19 and FOXA1 was significantly up-regulated, while the expression of miR-423-5p was down-regulated in LPS-induced ARDS rats. Silencing of H19 decreased the mRNA expression of TNF-α, IL-1β, IL-6, MCP-1, and VEGF, the contents of TNF-α, IL-1β, IL-6, and VEGF in BALF, and histology score in LPS-induced ARDS rats. H19 knockdown also reduced the fibrosis scores and the protein expression of vimentin and α-SMA, and elevated the protein expression of E-cadherin in LPS-induced ARDS rats. Furthermore, silencing of miR-423-5p and overexpression of FOXA1 reversed the inhibitory effects of si-H19 on the inflammation and fibrosis of LPS-induced MH-S cells.</p><p><strong>Conclusions: </strong>Silencing of H19 relieved the pulmonary injury, inflammation and fibrosis of LPS-induced ARDS in rats. Silencing of H19 also alleviated the inflammation and fibrosis of LPS-induced MH-S cells through regulating the miR-423-5p/FOXA1 axis.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 4","pages":"183-197"},"PeriodicalIF":1.7,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1887967","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25404243","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}

{"title":"LncRNA CHRF promotes TGF-β1 induced EMT in alveolar epithelial cells by inhibiting miR-146a up-regulating L1CAM expression.","authors":"Ju Li,&nbsp;Zhen-Zhu Jiang,&nbsp;You-You Li,&nbsp;Wen-Ting Tang,&nbsp;Jing Yin,&nbsp;Xiao-Ping Long","doi":"10.1080/01902148.2021.1891354","DOIUrl":"https://doi.org/10.1080/01902148.2021.1891354","url":null,"abstract":"<p><strong>Purpose: </strong>Idiopathic pulmonary fibrosis (IPF) is a type of progressive lung fibrosis disease. The survival time of diagnosed IPF patients is often only 2 years. Currently much evidence showed that the epithelial-mesenchymal transition (EMT) process is the main cause of the occurrence and development of IPF. LncRNA cardiac hypertrophy related factor (CHRF) was reported to be related with IPF development. Here we explored the functions and regulatory mechanisms of CHRF on EMT in IPF.</p><p><strong>Materials and methods: </strong>A549 cells were treated with transforming growth factor-β1 (TGF-β1) for 48 h to construct IPF cell model. CHRF and miR-146a expression were quantified using qPCR. The expression of L1 cell adhesion molecule (L1CAM) and EMT related indicators (E-cadherin, Vimentin, Slug and N-cadherin) were detected by qPCR and western blot. Dual luciferase reporter experiment was conducted to prove the molecular interaction of miR-146a and L1CAM, as well as CHRF and miR-146a.</p><p><strong>Results: </strong>CHRF and L1CAM expression were significantly upregulated and promoted the EMT process in A549 after treatment of TGF-β1. MiR-146a was obviously down-regulated, and knockdown of CHRF inhibited the EMT process by up-regulating miR-146a, in A549 after treatment of TGF-β1. Meanwhile, overexpression of miR-146a inhibited EMT process via targeting L1CAM. In addition, L1CAM overexpression eliminated the inhibitory effect of sh-CHRF on the EMT process.</p><p><strong>Conclusions: </strong>These results provided evidence that CHRF promoted EMT process in A549 after treatment of TGF-β1, which proposed a new insight for depth understanding the pathological mechanisms of IPF.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 4","pages":"198-209"},"PeriodicalIF":1.7,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1891354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25519861","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}

{"title":"Ketogenic diet induces autophagy to alleviate bleomycin-induced pulmonary fibrosis in murine models.","authors":"En Mu,&nbsp;Jinli Wang,&nbsp;Liang Chen,&nbsp;Shuirong Lin,&nbsp;Jieming Chen,&nbsp;Xiaoming Huang","doi":"10.1080/01902148.2020.1840667","DOIUrl":"https://doi.org/10.1080/01902148.2020.1840667","url":null,"abstract":"<p><strong>Aim of the study: </strong>Ketogenic diet (KD) has been identified as an effective strategy in treating multiple diseases. KD is capable of inducing autophagy which is an important therapeutic target for pulmonary fibrosis (PF). This study aimed to investigate the effect of KD treatment on PF progression. <b>Materials and Methods:</b> Intratracheal instillation of bleomycin (BLM, 5 mg/kg) to establish PF model in male Kunming mice fed either KD or standard diet. The survival of mice was recorded every day for 3 weeks. The pulmonary tissues were weighed on day 21 and the pulmonary index was calculated. The histopathological changes of pulmonary tissues were analyzed by hematoxylin and eosin staining and Masson staining, and the collagen deposition by hydroxyproline assay. Then the content of proinflammatory factors in pulmonary tissues was measured using enzyme-linked immunosorbent assay, and the expression of profibrogenic cytokines, autophagy markers and PI3K/AKT/mTOR pathway-related proteins in pulmonary tissues using western blotting or immunohistochemistry. <b>Results:</b> KD treatment significantly restored the BLM-induced increase of pulmonary index and had a tendency to increase the survival rate of PF mice. Furthermore, KD treatment restored the BLM-induced damage of alveolar structure, infiltration of inflammatory cells and collagen deposition and decreased hydroxyproline content. In addition, the BLM-induced secretion of tumor necrosis factor-alpha, interleukin-6 and interleukin-1β and expression of transforming growth factor β1, phospho-Smad2/3, connective tissue growth factor, α-smooth muscle actin and collagen type III alpha 1 chain were inhibited by KD. KD treatment also up-regulated the expression of light chain 3 II/I and Beclin1 and down-regulated the expression of p62, phospho-AKT, phospho-mTOR and phospho-p70S6K, suggesting that KD induced autophagy and suppressed the BLM-induced activation of PI3K/AKT/mTOR signaling pathway. <b>Conclusions:</b> These findings indicate that KD can alleviate PF <i>in vivo</i> by regulating autophagy and PI3K/AKT/mTOR signaling pathway, which provides a novel therapeutic strategy for PF.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 1","pages":"26-36"},"PeriodicalIF":1.7,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2020.1840667","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38546459","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}

{"title":"The inflammatory biomarker YKL-40 is elevated in the serum, but not the sputum, of E-cigarette users.","authors":"Mario F Perez, Nkiruka C Atuegwu, Eric M Mortensen, Cheryl Oncken","doi":"10.1080/01902148.2020.1847216","DOIUrl":"10.1080/01902148.2020.1847216","url":null,"abstract":"<p><strong>Methods: </strong>We conducted a cross-sectional study of adults between 18 and 55 years old. Inclusion criteria were: exclusive e-cigarette use or cigarette smoking for ≥ 1 year or no history of tobacco use. Participants with a history of pulmonary illness, atopy, medications (except birth control pills), marijuana, and illegal substance use were excluded. Custom Multiplex ELISA was used to measure YKL-40 and other biomarker levels in the serum and induced sputum of the participants. Multivariable linear regression was used to compare the levels of YLK-40 in healthy participants, e-cigarette, and cigarette users after adjusting for age, sex, and BMI.</p><p><strong>Results: </strong>We recruited 20 healthy controls, 23 cigarette smokers, and 22 exclusive e-cigarette users. Serum YKL-40 (ng/ml) was significantly higher in e-cigarette users (Median 21.2 [IQR 12.1-24.0] ng/ml) when compared to controls (12.2 [IQR 8.7-18.1] ng/ml, p = 0.016) but comparable to cigarette smokers (21.6 [IQR 11.62-51.7] ng/ml, p = 0.31). No significant differences were found in the serum or sputum of the other biomarkers tested.</p><p><strong>Conclusion: </strong>The inflammatory biomarker, YKL-40 is elevated in the serum but not the sputum of e-cigarette users with no reported pulmonary disease. Further research is necessary to characterize this association.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 2","pages":"55-66"},"PeriodicalIF":1.7,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2020.1847216","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38706440","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}

{"title":"Investigating the effect of pretreatment with azithromycin on inflammatory mediators in bronchial epithelial cells exposed to cigarette smoke.","authors":"Nafiseh Naderi,&nbsp;Raquel Farias,&nbsp;Mira Abou Rjeili,&nbsp;Seyed-Mohammad-Yousof Mostafavi-Pour-Manshadi,&nbsp;Suurya Krishnan,&nbsp;Pei Zhi Li,&nbsp;Carolyn J Baglole,&nbsp;Jean Bourbeau","doi":"10.1080/01902148.2020.1857470","DOIUrl":"https://doi.org/10.1080/01902148.2020.1857470","url":null,"abstract":"<p><p><b>Purpose of the study:</b> Macrolide therapy is effective in reducing chronic obstructive pulmonary disease (COPD) exacerbations. Our recent study has shown the effectiveness of taking azithromycin in COPD patients, not only ex-smokers but also current smokers. Beyond their anti-microbial effects, macrolides have anti-inflammatory and immunomodulatory properties. The aim of this study was to determine if pretreatment with azithromycin modulates cigarette smoke-induced inflammation in airway epithelial cells. We hypothesized that pretreatment with azithromycin decreases exacerbation frequency by modulating inflammation in human airway epithelial cells exposed to cigarette smoke. <b>Materials and methods:</b> BEAS-2B bronchial epithelial cells were incubated with 5% cigarette smoke extract (CSE) for 3 h, 6 h, and 24 h. Then, airway epithelial cells were pretreated with azithromycin and exposed to 5% CSE. In each stage, the expression and release of IL-6 and IL-8 mRNA were analyzed by quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. <b>Results:</b> There was a significant increase of IL-6 and IL-8 mRNA, as well as an increase in extracellular IL-8 protein following exposure to 5% CSE. When cells were pretreated with azithromycin and exposed to 5% CSE for 3 h, there was a significant dose-dependent decrease in the expression of IL-6 mRNA. A final concentration of 9 µg/mL of azithromycin was sufficient to decrease IL-6, IL-8 mRNA, and extracellular IL-8 levels. <b>Conclusion:</b> Pretreatment with azithromycin decreased the expression of IL-6 and IL-8 mRNA and the release of IL-8 in bronchial epithelial cells exposed to cigarette smoke. These results demonstrate the direct effect of azithromycin on inflammatory mediators in bronchial epithelial cells exposed to cigarette smoke.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 2","pages":"98-109"},"PeriodicalIF":1.7,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2020.1857470","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38727575","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}

{"title":"Effects of cigarette smoke on the administration of isoniazid and rifampicin to macrophages infected with <i>Mycobacterium tuberculosis</i>.","authors":"Pablo Rodríguez-Fernández,&nbsp;Andromeda-Celeste Gómez,&nbsp;Isidre Gibert,&nbsp;Cristina Prat-Aymerich,&nbsp;Jose Domínguez","doi":"10.1080/01902148.2020.1854371","DOIUrl":"https://doi.org/10.1080/01902148.2020.1854371","url":null,"abstract":"<p><strong>Background: </strong>Smoking is a cause behind many diseases, including tuberculosis, and it is a risk factor for tuberculosis infection and mortality. Moreover, smoking is associated with a poor tuberculosis treatment outcome.</p><p><strong>Objectives: </strong>In this study, we focus on the effects of cigarette smoke on an infected cell culture treated with anti-tuberculosis drugs.</p><p><strong>Materials and methods: </strong>Cytotoxicity on THP-1, J774A.1 and MH-S cell lines and growth of <i>Mycobacterium tuberculosis</i> exposed to a reference or a commercial cigarette was evaluated. THP-1 cell line was exposed to cigarette smoke, infected with <i>Mycobacterium tuberculosis</i> and treated with anti-tuberculosis drugs. Apoptosis and death cell were also tested on <i>M. bovis</i> BCG infected cells. Minimal inhibitory concentrations of anti-tuberculosis drugs were analyzed.</p><p><strong>Results: </strong>All cells lines showed viability values higher than 80% when exposed to cigarette smoke extract. However, THP-1 cell line infected with <i>M. bovis</i> BCG and exposed to Marlboro cigarette smoke showed up to a 54% reduction of apoptotic cells than cells unexposed to smoke. <i>M. tuberculosis</i> exposed to Marlboro cigarette smoke for 11 days had an optical density 16% lower than unexposed bacteria. When cells were infected with <i>M. tuberculosis</i>, the intracellular recovery of CFUs showed up to a 0.66 log reduction in cells exposed to cigarette smoke extract because of a potential impairment in the phagocytosis. Macrophages treated with drugs showed up to a 2.55 log reduction in the intracellular load burden compared with non-treated ones. Despite poor treatment outcome on TB smoker patients, minimal inhibitory concentration of rifampicin increased only 2-fold in <i>M. tuberculosis</i> exposed to cigarette smoke.</p><p><strong>Conclusion: </strong>Smoking interferes with tuberculosis treatment impairing the immunity of the host.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 2","pages":"87-97"},"PeriodicalIF":1.7,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2020.1854371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38699593","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}

{"title":"STAT1 participates in the induction of substance P expression in airway epithelial cells by respiratory syncytial virus.","authors":"Yu-Long Luo,&nbsp;Sheng Wang,&nbsp;Zhi-Xin Fang,&nbsp;Yi-Chu Nie,&nbsp;Li-Ting Zhang,&nbsp;Chu-Qin Huang,&nbsp;Li Long,&nbsp;Ke-Fang Lai","doi":"10.1080/01902148.2020.1850922","DOIUrl":"https://doi.org/10.1080/01902148.2020.1850922","url":null,"abstract":"<p><strong>Purpose: </strong>The regulation effect and mechanism of respiratory syncytial virus (RSV) infection on the expression of tachykinin substance P (SP) in airway epithelial cells was investigated.</p><p><strong>Methods: </strong>The regulation of SP expression by RSV was investigated in the BEAS-2B airway epithelial cell line. RT-qPCR, immunofluorescence, and ELISA assay were used to examine the expression of the SP encoding gene <i>TAC1</i>, the intracellular SP protein expression, and the extracellular SP secretion.</p><p><strong>Results: </strong>The mRNA expression of <i>TAC1</i> and the intracellular SP protein level in BEAS-2B cells were significantly enhanced by RSV infection with multiplicity of infection (MOI) values of both 1 and 0.1 at 48 hours post infection. Heat-inactivated and UV-inactivated RSV, but not live RSV, significantly induced SP secretion in both control BEAS-2B cells and CX3CR1 receptor knockout cells without affecting the <i>TAC1</i> gene expression or cell viability. RSV G protein (2-10 μg/ml) and fractalkine (10-50 ng/ml), both CX3CR1 receptor ligands, did not affect SP secretion in BEAS-2B cells. Inhibition of STAT1 phosphorylation by fludarabine (1 μM) markedly reduced the RSV-induced <i>TAC1</i> gene expression and antagonized the inhibition of RSV replication by interferon-α in BEAS-2B cells.</p><p><strong>Conclusions: </strong>STAT1 participates in RSV infection-induced SP expression in airway epithelial cells.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 2","pages":"78-86"},"PeriodicalIF":1.7,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2020.1850922","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38642939","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}

{"title":"Ceramide synthases: insights into the expression and prognosis of lung cancer.","authors":"Huijiang Qian,&nbsp;Jingjing Deng,&nbsp;Chao Lu,&nbsp;Gouxin Hou,&nbsp;Hualiang Zhang,&nbsp;Ming Zhang,&nbsp;Zhixian Fang,&nbsp;Xiao-Dong Lv","doi":"10.1080/01902148.2020.1844345","DOIUrl":"https://doi.org/10.1080/01902148.2020.1844345","url":null,"abstract":"<p><p>CerSs (ceramide synthases), a group of enzymes that catalyze the formation of ceramides from sphingoid base and acyl-CoA substrates. As far, six types of CerSs (CerS1-CerS6) have been found in mammals. Each of these enzymes have unique characteristics, but maybe more noteworthy is the ability of individual CerS isoform to produce a ceramide with a characteristic acyl chain distribution. As key regulators of sphingolipid metabolism, CerSs highlight their unique characteristics and have emerging roles in regulating programmed cell death, cancer and many other aspects of biology. However, the role of CerSs in lung cancer has not been fully elucidated. In this study, there was no significant change in the sequence or copy number of CerSs gene, which could explain the stability of malignant tumor development through COSMIC database. In addition, gene expression in lung cancer was examined using the Oncomine^TM database, and the prognostic value of each gene in non-small cell lung cancer (NSCLC) was analyzed by Kaplan-Meier analysis. The results showed that high mRNA expression levels of CerS2, CerS3, CerS4 and CerS5 in all NSCLC patients were associated with improved prognosis. Among them, CerS2 and CerS5 are also highly expressed in adenocarcinoma (Ade), but not in squamous cell carcinoma (SCC). In contrast, high or low expression of CerS1 and CerS6 no difference was observed in patients with NSCLC, Ade and SCC. Integrated the data of this study suggested that these CerSs may be a potential tumor markers or drug target of new research direction.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 1","pages":"37-53"},"PeriodicalIF":1.7,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2020.1844345","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38597360","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}

{"title":"Ponatinib is a potential therapeutic approach for malignant pleural mesothelioma.","authors":"Yi-Wei Yang,&nbsp;Angelica Marrufo,&nbsp;Jillian Chase,&nbsp;Gavitt A Woodard,&nbsp;David M Jablons,&nbsp;Hassan Lemjabbar-Alaoui","doi":"10.1080/01902148.2020.1836691","DOIUrl":"https://doi.org/10.1080/01902148.2020.1836691","url":null,"abstract":"<p><strong>Purpose: </strong>Malignant pleural mesothelioma (MPM) is a rare and deadly malignancy. Current MPM therapies remain inadequate, and outcomes are often disappointing. New meaningful therapeutic approaches are urgently needed. Accumulating evidence indicates that the cAbl pathway promotes various tumor-stimulating processes in MPM. In this study, we sought to determine ponatinib's potential utility, a clinically approved and potent cAbl inhibitor, in MPM treatment.</p><p><strong>Material and methods: </strong>Four MPM lines (MSTO211H, H28, H2452, H2052) were treated with ponatinib <i>in vitro</i>, and their growth was assessed. Scratch wound assay was used to investigate the ponatinib effect on cell migration. The expression levels of pAbl and its downstream effectors pCrkL, pAKT, and pSTAT5 were characterized. The in vivo ponatinib effect was evaluated in human MPM cells derived tumor model.</p><p><strong>Results: </strong>In all four MPM lines, significant expression levels of phosphorylated cAbl/Arg and pCrkl were observed. Differentially but strongly, ponatinib inhibited the in vitro cell growth and migration of all four MPM line. Western blot analysis showed that the activation of Abl signaling was blocked in the ponatinib-treated MMP lines. In keeping, the cellular levels of pAbl and its downstream effector pCrkL, pAKT, and pSTAT5 were markedly decrease following ponatinib treatment. Moreover, ponatinib treatment amplified the levels of γH2AX in cells denoting increased double-strand DNA breaks levels. Notably, ponatinib treatment reduced in vivo tumor growth and reduced pCrkl and pSTAT5 levels in tumor samples.</p><p><strong>Conclusion: </strong>Ponatinib may offer a new therapeutic strategy for MPM patients based on cAbl signaling pathway inhibition.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 1","pages":"9-25"},"PeriodicalIF":1.7,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2020.1836691","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38534189","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}

{"title":"Impact of capsaicin concentration evoking coughs on clinical variables in patients with asthma.","authors":"Kyung-Hun Park,&nbsp;Byeong-Gon Kim,&nbsp;Preun-Haneul Lee,&nbsp;Jisu Hong,&nbsp;Junehyuck Lee,&nbsp;Sung-Woo Park,&nbsp;Do-Jin Kim,&nbsp;An-Soo Jang","doi":"10.1080/01902148.2020.1834016","DOIUrl":"https://doi.org/10.1080/01902148.2020.1834016","url":null,"abstract":"<p><strong>Background: </strong>Inhaled capsaicin (8-methyl-<i>N</i>-vanillyl-6-nonenamide) has been used to induce cough in a safe and dose-dependent manner. Chronic cough is associated with an increased sensitivity to inhaled capsaicin in patients with asthma. The aim of this study was to evaluate clinical impact of capsaicin provocation test for chronic cough, and to find relationship between capsaicin concentration producing coughs and clinical variables in patients with asthma. <b>Methods:</b> 385 patients with chronic cough [capsaicin provocation test (+, n = 152)] vs. [capsaicin provocation test (-, n = 233)] who has done with capsaicin provocation test recruited and evaluated by asthma diagnosis and clinical variables. Asthma diagnoses were based on the Global Initiative for Asthma guidelines. <b>Results:</b> Capsaicin positivity was more prevalent in patient with asthma diagnosis than in patients without asthma diagnosis (129/304 vs. 24/81, p = 0.037). Capsaicin positivity was more prevalent in female patients than in male patients (123/271 = 45.4% vs. 30/114 = 26.3%, p = 0.001). Capsaicin concentration producing coughs correlated with smoke amount (r = 0.126, p = 0.014). Capsaicin positivity was more prevalent in nonsmoker patients than in smoker patients (133/295 = 45.1% vs. 20/90 = 22.2%, p = 0.001). Capsaicin concentration producing coughs negatively correlated with methacholine PC20 (4 mg mL^-1, p = 0.037), (16 mg mL^-1, p = 0.069) and (20 mg mL^-1, p = 0.045). Capsaicin concentration producing coughs correlated with BMI (r = 0.120, p = 0.019). Capsaicin concentration producing coughs negatively correlated with FEV₁/FVC % pred. (r = -0.137, p = 0.007). There was no relationship between capsaicin concentration producing coughs and age, IgE, and atopy. <b>Conclusions:</b> Capsaicin test for asthma diagnosis should be considered for variable clinical factors. Key message Cough in asthmatic patients is not only common and troublesome but also predicts disease severity and poor prognosis. The capsaicin cough challenge test is a simple and reproducible provocation method for assessing cough susceptibility in patients with cough. Capsaicin test for asthma diagnosis should be considered for variable clinical factors.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 1","pages":"1-8"},"PeriodicalIF":1.7,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2020.1834016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38505449","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}