Experimental Lung Research最新文献

{"title":"Ser69 phosphorylation of TIMAP affects endothelial cell migration.","authors":"Nikolett Király,&nbsp;Csilla Csortos,&nbsp;Anita Boratkó","doi":"10.1080/01902148.2021.1960651","DOIUrl":"https://doi.org/10.1080/01902148.2021.1960651","url":null,"abstract":"<p><strong>Purpose/aim: </strong>TIMAP (TGF-β-inhibited membrane-associated protein) is a regulatory subunit of protein phosphatase 1 (PP1). The N-terminal region contains a binding motif for the catalytic subunit of PP1 (PP1c) and a nuclear localization signal (NLS). Phosphorylation of TIMAP on Ser331, Ser333 and Ser337 side chains was shown to regulate the activity of the TIMAP-PP1c complex. Several studies, however, reported an additional side chain of TIMAP. Ser69 is located near to the PP1c binding motif and NLS, therefore, we hypothesized that the phosphorylation of this side chain perhaps may regulate the interaction between TIMAP and PP1c, or may affect the nuclear transport of TIMAP. <b>Materials and Methods:</b> To study the significance of Ser69 phosphorylation, GST-tagged or c-myc-tagged wild type, phosphomimic S69D and phosphonull S69A recombinant TIMAP proteins were expressed in bacteria or endothelial cells, respectively. Protein-protein interactions of the wild type or mutant forms of TIMAP were studied by pull-down and Western blot. Localization of TIMAP S69 mutants in pulmonary artery endothelial cells was detected by immunofluorescent staining and expression and localization of the recombinants were investigated by subcellular fractionation and Western blot. <b>Results</b><i>:</i> Modifications of Ser69 of TIMAP had no effect on binding of PP1c, ERM or RACK1. However, S69D TIMAP showed enhanced membrane localization and an increased number of membrane protrusions were observed in the cells overexpressing this phosphomimic mutant. Furthermore, significantly faster wound healing and migration rate of the S69D mutant overexpressing cells were detected by endothelial barrier resistance measurements (ECIS). Specific interaction was shown between TIMAP and polo-like kinase 4 (PLK4), a potential kinase to phosphorylate Ser69. <b>Conclusions:</b> Altogether, our results indicate that Ser69 phosphorylation by PLK4 may evoke an enrichment of TIMAP in the plasma membrane region and may play an important role in endothelial cell migration without affecting the PP1c binding ability of TIMAP.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 7","pages":"334-343"},"PeriodicalIF":1.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1960651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39271164","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":"Pulmonary hypoxia and venous admixture correlate linearly to the kinetic energy from porcine high velocity projectile behind armor blunt trauma.","authors":"Ulf P Arborelius,&nbsp;David Rocksén,&nbsp;Jenny Gustavsson,&nbsp;Mattias Günther","doi":"10.1080/01902148.2021.1950869","DOIUrl":"https://doi.org/10.1080/01902148.2021.1950869","url":null,"abstract":"<p><p><b>Purpose.</b> Behind armor blunt trauma (BABT) is a non-penetrating injury caused by the rapid deformation of body armor, by a projectile, which may in extreme circumstances cause death. The understanding of the mechanisms is still low, in relation to what is needed for safety threshold levels. High velocity projectile BABT causes immediate and severe hypoxia by increased venous admixture (Q's/Q't), but it is not known whether the level of hypoxia correlates to the kinetic energy (E_k) of the projectile.<b>Materials and Methods.</b> We constructed a 65 mm BABT-simulator to measure the E_k absorbed by the thorax. The simulator was validated to 7.62 mm high velocity BABT (swine with removed organs) for 7.62 mm (n = 7) and 65 mm (n = 12). Physiological measurements during 60 minutes were performed in 40 anesthetized swine in groups control (n = 9), 7.62 mm (n = 7), 65 mm weight variation (n = 24), 65 mm speed variation (n = 12, included in the weight variation group). New calculations were done for a previously studied group of 7.62 mm with backing (n = 9).<b>Results.</b> 65 mm BABT simulation and 7.62 mm BABT had similar back-face signatures (24 mm), and maximum thoracic impression speed (24-34 m/s). Back-face signatures correlated linearly to E_k (R²=0.20). Rib fractures had a 50% likelihood at back-face signature 23.0 mm (95% CI 18.5 to 29.0 mm, area under ROC curve 0.93). E_k correlated linearly to pO₂ (R²=0.34, p = 0.0026) and venous admixture (R²=0.37, p = 0.0046). The extrapolated E_k at 5 minutes for pO₂=0 kPa was 587 J and for venous admixture = 100% 574 J.<b>Conclusions.</b> Hypoxia and venous admixture correlated linearly to E_k, allowing for a calculated predicted lethal E_k to ≥574 J, which should be verified in survival studies. Lethality predictions from lung physiology is an alternative to clay impressions and may facilitate the development of ballistic safety equipment and new BABT safety criteria.Supplemental data for this article is available online at https://doi.org/10.1080/01902148.2021.1950869 .</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 7","pages":"323-333"},"PeriodicalIF":1.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1950869","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39198228","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 role of circTMOD3 in regulating LPS-induced acute inflammation and injury in human lung fibroblast WI-38 cells.","authors":"Ke Ma,&nbsp;Wei Wang,&nbsp;Chunyan Gao,&nbsp;Jine He","doi":"10.1080/01902148.2021.1940376","DOIUrl":"https://doi.org/10.1080/01902148.2021.1940376","url":null,"abstract":"<p><strong>Background: </strong>Circular RNAs (circRNAs) have been implicated in the molecular etiology of pediatric pneumonia. Here, we investigated the precise action of circRNA tropomodulin 3 (circTMOD3, hsa_circ_0035292) in cell injury and inflammation induced by lipopolysaccharide (LPS). <b>Methods:</b> Cell viability was gauged by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis and cycle distribution were assessed by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to measure interleukin-6 (IL-6), IL-1β and tumor necrosis factor alpha (TNF-α) production. The levels of circTMOD3, microRNA (miR)-146b-3p, and C-X-C motif chemokine receptor 1 (CXCR1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Ribonuclease (RNase) R, Actinomycin D and subcellular localization assays were done to characterize circTMOD3. The direct relationship between miR-146b-3p and circTMOD3 or CXCR1 was confirmed by dual-luciferase reporter assays. <b>Results:</b> Our data showed that LPS induced the expression of circTMOD3 in WI-38 cells. CircTMOD3 was resistant to RNase R and was mainly present in the cytoplasm. Silencing endogenous circTMOD3 alleviated WI-38 cell injury and inflammation triggered by LPS. Mechanistically, circTMOD3 directly targeted miR-146b-3p, and CXCR1 was a direct and functional target of miR-146b-3p. CircTMOD3 regulated LPS-induced cell inflammation and injury by targeting miR-146b-3p, and miR-146b-3p-mediated suppression of CXCR1 impacted LPS-evoked cytotoxicity and inflammation. Furthermore, circTMOD3 functioned as a competing endogenous RNA (ceRNA) for miR-146b-3p to induce CXCR1 expression. <b>Conclusion:</b> Our findings demonstrated the regulation of circTMOD3 in LPS-induced cell injury and inflammation at least partially via miR-146b-3p-independent modulation of CXCR1.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 7","pages":"311-322"},"PeriodicalIF":1.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1940376","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39251239","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":"IL23R on myeloid cells is involved in murine pulmonary granuloma formation.","authors":"Tina Schreiber,&nbsp;Maren Falk-Paulsen,&nbsp;Jan Kuiper,&nbsp;Konrad Aden,&nbsp;Rainer Noth,&nbsp;Nicolas Gisch,&nbsp;Stefan Schreiber,&nbsp;Philip Rosenstiel,&nbsp;Burkhard Bewig","doi":"10.1080/01902148.2021.1962433","DOIUrl":"https://doi.org/10.1080/01902148.2021.1962433","url":null,"abstract":"<p><strong>Purpose of the study: </strong>The involvement of the IL-23/IL23R pathway is well known in the disease pathogenesis of sarcoidosis and other inflammatory diseases. To date, the pathogenic mechanism of IL-23 is most notably described on CD4⁺ Th17 lymphocytes. However, the function of the IL23R on myeloid cells in sarcoidosis is poorly understood. Thus, the aim of the study is to investigate the role of the IL23R on myeloid cell in pulmonary granuloma formation. <b>Methods:</b> We generated IL23RLysMCre mice lacking the IL23R gene in myeloid cells. The importance of IL23R in myeloid cells for the development of sarcoidosis was studied in a mouse model of inflammatory lung granuloma formation through embolization of PPD from <i>Mycobacterium bovis</i>-coated Sepharose beads into previously PPD-immunized mice. In addition the function of IL23R on myeloid cells was studied in LPS or IFNγ stimulated BMDMs and BMDCs. The mRNA and protein expression levels of relevant cytokines were analyzed by RT-PCR (TaqMan) and ELISA. The composition of immune cells in BALF was quantified by flow cytometry and alteration in granuloma sizes were observed by H&E stained lung sections. <b>Results:</b> Mycobacterium Ag-elicted pulmonary granulomas tend to be smaller in IL23RLysMCre mice and NF-κB dependent Th1 cytokines in the murine lungs are reduced compared to wildtype mice. In line, we observed that IL23R-deficient bone marrow-derived macrophages show a reduced production of Th1 cytokines after LPS stimulation. <b>Conclusion:</b> We here for the first time demonstrate a role for IL23R on myeloid cells in pulmonary inflammation and granuloma formation. Our findings provide essential insights in the pathogenesis of inflammatory lung diseases like sarcoidosis, which might be useful for the development of novel therapeutics targeting distinct immunological pathways like IL-23/IL23R.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 7","pages":"344-353"},"PeriodicalIF":1.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39321657","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":"Hydrogen regulates the M1/M2 polarization of alveolar macrophages in a rat model of chronic obstructive pulmonary disease.","authors":"Jing-Chao Su,&nbsp;Yi Zhang,&nbsp;Chen Cheng,&nbsp;Yi-Nan Zhu,&nbsp;Yu-Meng Ye,&nbsp;Yong-Kang Sun,&nbsp;Shui-Ying Xiang,&nbsp;Yuan Wang,&nbsp;Zi-Bing Liu,&nbsp;Xin-Fang Zhang","doi":"10.1080/01902148.2021.1919788","DOIUrl":"https://doi.org/10.1080/01902148.2021.1919788","url":null,"abstract":"<p><strong>Objective: </strong>Chronic obstructive pulmonary disease (COPD) is a respiratory disease with high morbidity and mortality worldwide, so far there is no ideal treatment method. Previous studies have shown that hydrogen (H₂) is involved in the treatment of COPD as an antioxidant. In this study, the effect of H₂ on M1/M2 polarization of alveolar macrophages in COPD rats was observed, and its anti-inflammatory mechanism was further elucidated. <b>Methods</b>: Twenty-four Sprague-Dawley rats were randomly divided into three groups including the control, COPD and H₂ group. A rat model of COPD was established by cigarette exposure combined with lipopolysaccharide (LPS) induction. H₂ therapy was administered 2 hours per day for 14 days. Lung function and pathology were assessed. The levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1 and IL-10 in bronchoalveolar lavage fluid (BALF) and lung tissue were measured by enzyme-linked immunosorbent assay. The mRNA, protein expression and immunoreactivity of inducible nitric oxide synthase (iNOS) and arginase (Arg)-1 in lung were observed by quantitative real-time PCR, western blot and immunohistochemistry. <b>Results</b>: Compared with the control rats, there were a significant decline in lung function, a marked inflammatory infiltration and pulmonary parenchymal remodeling and the increases of IL-6, TNF-α and TGF-β1 levels in BALF and lung tissue, but a lower expression of IL-10 in COPD rats. The iNOS mRNA and protein expression, as well as its optical density (OD), were increased significantly in lung tissue, while those of Arg-1 decreased significantly. H₂ treatment improved the lung function and the parenchymal inflammation, reversed the increased levels of IL-6, TNF-α and TGF-β1, and the lower IL-10. Meanwhile, H₂ also down-regulated the expression of iNOS, but up-regulated expression of Arg-1 in lung tissue. <b>Conclusion</b>: H₂ reduces inflammation in the lung of COPD, which may be related to its inhibition of M1 type polarization and activation of M2 type polarization of alveolar macrophage.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 7","pages":"301-310"},"PeriodicalIF":1.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1919788","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39201209","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":"Role of the Notch ligands Jagged1 and Delta4 in Th17/Treg immune imbalance in a mouse model of chronic asthma.","authors":"Zhen He,&nbsp;Jirong Wu,&nbsp;Xiaoli Zeng,&nbsp;Hairong Bao,&nbsp;Xiaoju Liu","doi":"10.1080/01902148.2021.1933653","DOIUrl":"10.1080/01902148.2021.1933653","url":null,"abstract":"<p><strong>Purpose: </strong>Asthma is associated with a T helper (Th)17/regulatory T (Treg) cells immune imbalance where the Notch signaling pathway contributes vitally. This study aimed to explore the role of Notch ligands Jagged1 and Delta4 in the Th17/Treg immune imbalance of chronic asthmatic mice.</p><p><strong>Methods: </strong>The experimental animals were randomly assigned to the Saline, ovalbumin (OVA), and OVA + γ-secretase inhibitor (GSI) groups. A mouse model of chronic asthma was induced by OVA sensitization and challenge. GSI was injected intraperitoneally before the OVA challenge in the OVA + GSI group. Lung function, lung histopathology and immunohistochemistry to assess airway inflammation, enzyme-linked immunosorbent assay to measure cytokines levels, flow cytometry to measure the proportions of Th17 (Th17%) and Treg% in CD4⁺T cells, quantitative real-time polymerase chain reaction and western blot to measure mRNA and protein levels of Jagged1 and Delta4 in lung tissue, and correlation analysis were performed.</p><p><strong>Results: </strong>Lung function and histopathology and IL-4, IL-13, and IFN-γ levels in the bronchoalveolar lavage fluid (BALF) of chronic asthmatic mice showed characteristic changes of asthma. The Th17%, Th17/Treg ratio, BALF and serum IL-17 levels, and IL-17/IL-10 ratio increased significantly in the OVA group, while the Treg% and IL-10 level significantly decreased. mRNA and protein expression levels of Jagged1 and Delta4 increased significantly. GSI could reduce the Th17%, Th17/Treg ratio, IL-17, IL-17/IL-10 ratio, and Jagged1 expression in chronic asthmatic mice. The mRNA and protein levels of Jagged1 and Delta4 were positively correlated with the Th17/Treg ratio in the OVA group, while only those of Jagged1 were positively correlated with the Th17/Treg ratio in the OVA + GSI group.</p><p><strong>Conclusions: </strong>In chronic asthmatic mice, the Th17/Treg ratio increased, and the Notch ligands Jagged1 and Delta4 were overactive and positively regulated the Th17/Treg imbalance. GSI partially inhibited Jagged1 and relieved the Th17/Treg imbalance.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 6","pages":"289-299"},"PeriodicalIF":1.7,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1933653","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39001697","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":"Extracellular sulfatases as potential blood-based biomarkers for early detection of lung cancer.","authors":"Yi-Wei Yang,&nbsp;David M Jablons,&nbsp;Hassan Lemjabbar-Alaoui","doi":"10.1080/01902148.2021.1885525","DOIUrl":"https://doi.org/10.1080/01902148.2021.1885525","url":null,"abstract":"<p><strong>Purpose: </strong>Non-small lung (NSCLC) is the deadliest cancer, with survival measured in months. Earlier diagnosis using a robust biomarker would likely improve survival. This study aims to determine whether blood levels of the extracellular sulfatases (SULF1 and SULF2) and their bio-activity can serve as novel biomarkers for NSCLC early detection.</p><p><strong>Materials and methods: </strong>Using human plasma specimens from NSCLC patients, nonmalignant COPD patients, and healthy individuals, we determined the association between plasma SULF levels and the presence of NSCLC. We assessed the plasma SULF levels as a function of sex and age. We also evaluated the plasma levels of heparin-binding factors potentially mobilized by the SULFs. To increase test specificity of blood SULF2 as a biomarker for the early diagnosis of NSCLC, we investigated the presence of a tumor-specific SULF2 isoform released in the blood, which could be used as a biomarker alone or in multiplex assays.</p><p><strong>Results: </strong>The median level of plasma SULF2 was significantly elevated in NSCLC patients than in healthy controls (∼2 fold). However, these data were confounded by age. Surprisingly, COPD patients also showed a dramatically increased SULF2 plasma level. We showed a significant increase in the median plasma levels of several HSPG-binding factors in early-stage NSCLC patients compared to controls. Furthermore, we revealed a significant positive correlation of the SULF2 protein level with the plasma levels of two HSPG-binding factors IL6 and IL8. We demonstrated that NSCLC cancer cells and tissues overexpress a SULF2 splice variant. We determined the presence of a SULF2 splice variant form in NSCLC plasma, which was not detectable in COPD and control plasmas.</p><p><strong>Conclusion: </strong>Our findings highlight the potential for the plasma levels of SULF2 protein and its bio-activity as novel blood biomarkers for early diagnosis of NSCLC.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 6","pages":"261-279"},"PeriodicalIF":1.7,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1885525","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38915138","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 different concentrations of mesenchymal stem cells treatment on LPS-induced acute respiratory distress syndrome rat model.","authors":"Guangyang Liu,&nbsp;Zhiquan Di,&nbsp;Chunhua Hao,&nbsp;Weiting Wang,&nbsp;Tianxian Pei,&nbsp;Libo Zheng,&nbsp;Haomiao Long,&nbsp;Hao Wang,&nbsp;Wenbin Liao,&nbsp;Wen Wang,&nbsp;Chenliang Zhang,&nbsp;Xin Li,&nbsp;Yi Mi,&nbsp;Fengying Yan,&nbsp;Yongjun Liu","doi":"10.1080/01902148.2021.1897191","DOIUrl":"10.1080/01902148.2021.1897191","url":null,"abstract":"<p><strong>Purpose: </strong>This study was prospectively designed to investigate the effects of different concentrations of mesenchymal stem cells treatment on respiratory mechanics, oxygenation, hemodynamics and inflammatory response in LPS-induced acute respiratory distress syndrome (ARDS) rat model. <b>Methods</b>: One hundred and twenty six LPS-induced ARDS model rats (weighted 200-220 g) were randomly divided into three groups: 1) Control group (N = 42); 2) low-dose hUC-MSC treatment group (MSC group 1, 1x10⁷ cell/kg, N = 42); 3) high-dose hUC-MSC treatment group (MSC group 2, 2x10⁷ cell/kg, N = 42), sham operation group as healthy group (N = 15). The rats were observed closely for 24 hours after hUC-MSC treatment, and the survival rate was calculated. At 24 hours, all rats were tested for hemodynamics, blood gas analysis, heart, lung, liver and kidney functions, inflammatory factors detection in blood samples and broncho-alveolar lavage fluid (BALF). The lung tissue of the rats was collected for HE staining analysis. <b>Results</b>: After LPS injection, ARDS was obvious in all LPS-infused rat groups, consistent with severe acute lung injury and high death rate. However, compared with the control group, a single intravenous injection hUC-MSC at dose of 1 × 10⁷ cells/kg (low dose group) and 2 × 10⁷ cells/kg (high dose group) reduced the mortality of rats with LPS-induced ARDS, as well as improving the lung function, increased the arterial oxygen pressure, improved the heart function, and reduced the levels of inflammatory factors including IL-1β, IL-6, and TNF-α. In addition, the high dose MSC group showed better lung injury therapeutic effects than the low dose MSC group. Data from this study demonstrated that injection of hUC-MSC had a significant therapeutic effect in treating the rat model of LPS-induced ARDS and multiple organ function injury.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 5","pages":"226-238"},"PeriodicalIF":1.7,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1897191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25513190","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":"Inhibitory effects of somatostatin analogue in bleomycin-induced pulmonary fibrosis.","authors":"Tatsuya Hosono,&nbsp;Masashi Bando,&nbsp;Yoshiko Mizushina,&nbsp;Masafumi Sata,&nbsp;Koichi Hagiwara,&nbsp;Yukihiko Sugiyama","doi":"10.1080/01902148.2021.1916650","DOIUrl":"10.1080/01902148.2021.1916650","url":null,"abstract":"<p><strong>Background and objectives: </strong>Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease. An increased expression of somatostatin receptor subtype 2 in patients with IPF was identified and lung fibroblasts expressed somatostatin receptors <i>in vitro</i>. In addition, somatostatin analogue inhibits the expression of transforming growth factor-β, insulin-like growth factor (IGF) -1, platelet-derived growth factor, and basic fibroblast growth factor. Therefore, we examined the effects of somatostatin analogue on bleomycin-induced pulmonary fibrosis in mice. In a similar model, it has been reported that administration of high-dose somatostatin analogs suppressed acute inflammation and subsequent pulmonary fibrosis. However, it was clarified that the same effect can be obtained even at the dose used in clinical practice.</p><p><strong>Methods: </strong>C57BL/6 mice received a single tracheal instillation of bleomycin. After randomly allocated, mice were treated with subcutaneous injection of either normal saline or somatostatin analogue.</p><p><strong>Results: </strong>Somatostatin analogue reduced the number of neutrophils and lymphocytes in bronchoalveolar lavage (BAL) and IGF-1 level in serum and BAL fluid and attenuated weight loss. The hydroxyproline content of the lung homogenates in somatostatin analogue treatment group was significantly lower than in that of normal saline treatment group.</p><p><strong>Conclusions: </strong>These results suggest that somatostatin analogue may attenuate pulmonary fibrosis after bleomycin treatment at the dose used in clinical practice.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 6","pages":"280-288"},"PeriodicalIF":1.7,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1916650","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38908482","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":"ACTL6A promotes the growth in non-small cell lung cancer by regulating Hippo/Yap pathway.","authors":"Ling Ma,&nbsp;Li Shan","doi":"10.1080/01902148.2021.1916651","DOIUrl":"https://doi.org/10.1080/01902148.2021.1916651","url":null,"abstract":"<p><p><b>Purpose:</b> To delve into the related molecular mechanism of ACTL6A on non-small cell lung cancer (NSCLC) cell growth and apoptosis.<b>Methods:</b> Quantitative real-time polymerase chain reaction, immunohistochemical staining, and western blot assays were employed to examine ACTL6A mRNA and protein expression in four NSCLC cell line (NCI-H2170, LTEP-s, NCI-H1703, and PC-9) and normal lung cell line (BEAS-2B). CCK-8 cell viability assays and clone formation assay were applied to verify the cell proliferation of NCI-H2170 cell line after knockdown of ACTL6A. Flow cytometry assays were applied to check the role of ACTL6A in the apoptosis of NSCLC cells. The western blot assays were employed to examine the protein expression of WWC1, YAP, TAZ, and CYR61 in NCI-H2170 after knockdown of ACTL6A. Finally, xenograft tumor was taken out and checked the tumor volumes and weight. Immunohistochemical staining and western blot assays were employed to examine cell proliferation and apoptosis of NSCLC <i>in vivo</i>.<b>Results:</b> In this study, the results showed that the mRNA and protein expression level of ACTL6A was higher in four NSCLC cell line than normal lung cell line, respectively. Suppression of ACTL6A inhibited the growth and promoted apoptosis of NSCLC cells. Meanwhile, ACTL6A promotes tumor growth and inhibits apoptosis of NSCLC <i>in vivo</i> via Hippo/YAP signaling pathway.<b>Conclusion:</b> ACTL6A promotes the proliferation in NSCLC by regulating Hippo/YAP pathway.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 5","pages":"250-259"},"PeriodicalIF":1.7,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1916651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38906275","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}