Experimental Lung Research最新文献

{"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}

{"title":"Intermittent hypoxia: Friend or foe on endothelial repair in mouse model.","authors":"Tao Song,&nbsp;Mo Chen,&nbsp;Xin Wang,&nbsp;Endong Zhu,&nbsp;Yanchao Xue,&nbsp;Juan Wang,&nbsp;Bei Sun,&nbsp;Jing Feng","doi":"10.1080/01902148.2021.1891355","DOIUrl":"https://doi.org/10.1080/01902148.2021.1891355","url":null,"abstract":"<p><p><b>Aim of the study:</b> Obstructive sleep apnea, which is characterized by intermittent hypoxia (IH), is a common respiratory disease. The aim of the present study was to explore the relationship between hypoxia and endothelial progenitor cell (EPC) function, and explain the role of IH in endothelial repair.<b>Materials and methods:</b> Peripheral blood mononuclear cells (PBMCs) were isolated from a mouse model of IH. The number of CD133⁺ kinase insert domain receptor (KDR)⁺, CD133⁺CD34⁺, CD34⁺KDR⁺ and ALDH^lowCD34⁺KDR⁺ EPCs was determined by flow cytometry. HIF-1α, stromal-derived factor-1 (SDF-1) α and VEGF were measured by ELISA. The proliferative ability of PBMCs was determined. EPC migration was assessed by Transwell assay and surface proteins by western blot analysis. EPCs were co-cultured with mouse brain endothelial cells and their angiogenic ability was analyzed.<b>Results:</b> The number of CD133⁺KDR⁺, CD133⁺CD34⁺ and CD34⁺KDR⁺ EPCs increased with IH ingravescence. The number of ALDH^lowCD34⁺KDR⁺ EPCs with mild IH stimulation was higher and gradually decreased in the moderate and severe IH groups. The release of HIF-1α, SDF-1α and VEGF in the serum increased with the increase in the degree of IH. In the mild IH treatment, the migration and angiogenesis of EPCs, as well as the expression of vascular endothelial growth factor receptor 2 and cysteine-X-cysteine receptor 4, were higher than those in the control group, but progressively decreased in the groups with moderate and severe IH.<b>Conclusion</b>: Increased levels of IH accelerated the increase in vasoactive factors in peripheral blood, thereby mobilizing a large number of EPCs. Increasing of IH diminished the mobilization, chemotactic and angiogenetic ability of EPCs.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 5","pages":"211-225"},"PeriodicalIF":1.7,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1891355","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25444443","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":"Comparison of properties of dust in alveolar of rats and the workplace.","authors":"Xu Zhang,&nbsp;Zheng Zhang,&nbsp;Peng Wang,&nbsp;Shuyu Xiao,&nbsp;Ke Han,&nbsp;Yali Tang,&nbsp;Heliang Liu,&nbsp;Yuping Bai,&nbsp;Yulan Jin,&nbsp;Jinlong Li,&nbsp;Xiaoming Li,&nbsp;Qingan Xia,&nbsp;Fuhai Shen","doi":"10.1080/01902148.2021.1916649","DOIUrl":"https://doi.org/10.1080/01902148.2021.1916649","url":null,"abstract":"<p><strong>Objectives: </strong>The purpose of this study was to analyze the α-SiO₂ content, composition, dispersion, morphology, and free radical content of dust between the alveolar and the workplace, to explore the possible changes in the properties (especially the pathogenicity) of dust after it enters the lung.</p><p><strong>Methods: </strong>We collected the dust in the workplace in HANDAN Coal mine. They were selected by a 400 mesh sieve and was made a suspension of 50 mg/ml, which would be used to perfuse into the trachea of rats. When one week, four weeks, eight weeks, fourteen weeks, twenty weeks after perfusing, we harvested dust in rats alveolar through lung lavage for further processing.</p><p><strong>Results: </strong>In the animal test, typical fibrous nodules appeared 20 weeks after dust exposure. No inflammatory reaction was observed in the saline group. The results of animal experiments showed that there was no significant difference in the content of α-SiO₂ between dust in the workplace and the lung lavage (<i>P</i> > 0.05). The content of the Fe element gradually increased with dust exposure time. The 12 elements of Al, Mg, Si, Pb, Mn, Ni, Zn, Cu, Cr, Sb, Cd, and AS were reduced in the experiment group compared with the workplace group. The shape of the dust in the workplace was mostly spherical. The shape of the dust extracted from the lung lavage fluid was mostly blocky and angular, and a few dust edges were sharp, and more than 80% of the particle size was smaller than 5 μm, while less than 1% of the particle size was larger than 10 μm. The amount of hydroxyl radical released by lung lavage dust in phosphate buffer was higher than that of the workplace dust.</p><p><strong>Conclusions: </strong>After the dust entered the alveoli, the content of α-SiO₂ in the dust did not change with dust exposure time, while the content of elements in the dust, the morphology, and dispersion of the dust changed. The ability of dust in alveoli to produce hydroxyl radicals in phosphate buffer was higher than that in the workplace.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 5","pages":"239-249"},"PeriodicalIF":1.7,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1916649","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38906345","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":"DLC1 inhibits lung adenocarcinoma cell proliferation, migration and invasion via regulating MAPK signaling pathway.","authors":"Niu Niu,&nbsp;Xingjie Ma,&nbsp;Haitao Liu,&nbsp;Junjie Zhao,&nbsp;Chao Lu,&nbsp;Fan Yang,&nbsp;Weibo Qi","doi":"10.1080/01902148.2021.1885524","DOIUrl":"https://doi.org/10.1080/01902148.2021.1885524","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD), one of the most common cancers, is a major threat to people's health due to its high mortality, and the survival of most patients suffering LUAD remains poor. This study aimed to explore the mechanism of Deleted in Liver Cancer 1 (DLC1) as a tumor suppressor underlying the occurrence and progression of LUAD. As revealed by bioinformatics analysis and qRT-PCR, DLC1 was significantly down-regulated in LUAD tumor tissue and cells. A series of cellular experiments including CCK-8, wound healing and Transwell assays were performed to detect the effect of DLC1 on the biological function of LUAD cells. It was found that overexpressing DLC1 significantly inhibited LUAD cell proliferative, migratory and invasive abilities, while knockdown of DLC1 promoted these abilities. Gene Set Enrichment Analysis (GSEA) and dual-luciferase assay were used to explore the downstream signaling pathway of DLC1, finding that DLC1 could remarkably inhibit the activity of mitogen-activated protein kinase (MAPK) signaling pathway. Western blot implemented for MAPK signaling pathway-related proteins further identified that DLC1 restrained the activation of MAPK/ERK signaling pathway. Furthermore, rescue experiments suggested that DLC1 inhibited LUAD cell proliferation and invasion by suppressing the MAPK/ERK signaling pathway. Overall, our study discussed the DLC1-dependent mechanism involved in LUAD. We found that the up-regulation of DLC1 may inhibit the malignant progression of LUAD by suppressing MAPK signaling pathway, which supports the view that DLC1 may serve as a molecular target for the targeted therapy of LUAD patients.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 4","pages":"173-182"},"PeriodicalIF":1.7,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1885524","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25444446","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":"Acute and chronic effects of intravitreal bevacizumab on lung biomarkers of angiogenesis in the rat exposed to neonatal intermittent hypoxia.","authors":"Thomas J Duggan,&nbsp;Charles L Cai,&nbsp;Jacob V Aranda,&nbsp;Kay D Beharry","doi":"10.1080/01902148.2020.1866712","DOIUrl":"https://doi.org/10.1080/01902148.2020.1866712","url":null,"abstract":"<p><strong>Purpose/aim: </strong>Intravitreal bevacizumab (Avastin) is an irreversible vascular endothelial growth factor (VEGF) inhibitor used to treat severe retinopathy of prematurity (ROP) in extremely low gestational age neonates (ELGANs). ELGANs who are at the highest risk for developing severe ROP often experience brief intermittent hypoxia (IH) episodes which may cause oxidative damage. We tested the hypothesis that intravitreal Avastin leaks into the systemic circulation during exposure to IH and has adverse effects on biomarkers of pulmonary microvascular maturation, thus leading to pulmonary hemorrhage and long-term pulmonary sequelae.</p><p><strong>Methods: </strong>Neonatal rats at postnatal day (PN) 0 (birth) were exposed to either: 1) hyperoxia (50% O₂) or 2) neonatal IH (50% O₂ with brief episodes of 12% O₂) from PN0 to PN14. Room air (RA) littermates served as controls. At PN14, the time of eye opening in rats, a single dose of Avastin (0.125 mg in 5 µL) was injected into the vitreous cavity of the left eyes. A control group received equivalent volume saline. At PN23 and PN45, blood gases, lung-to-body weight ratios, histology, immunofluorescence, and lung biomarkers of angiogenesis were examined.</p><p><strong>Results: </strong>At PN23, Avastin increased lung VEGF, nitric oxide derivatives (NOx), and hypoxia-inducible factor (HIF)_1a in the hyperoxia-exposed groups, but decreased soluble VEGFR-1 (sVEGFR-1). At PN45, lungs from animals exposed to neonatal IH and treated with Avastin were severely hemorrhagic with morphologic changes in lung architecture consistent with chronic lung disease. This was associated with higher VEGF and NOx levels, and lower insulin-like growth factor (IGF)-I and sVEGFR-1.</p><p><strong>Conclusions: </strong>These findings prove our hypothesis that intravitreal Avastin penetrates the blood-ocular barrier in IH and alters lung biomarkers of angiogenesis. Avastin targeting of VEGF could affect normal lung development which may be exaggerated under pathologic conditions such as IH, ultimately leading to vascular permeability, vessel rupture, and pulmonary hemorrhage.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 3","pages":"121-135"},"PeriodicalIF":1.7,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2020.1866712","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38764554","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 NEAT1 promotes airway smooth muscle cell inflammation by activating the JAK3/STAT5 pathway through targeting of miR-139.","authors":"Meng-Xia Zhu,&nbsp;Lin-Hui Huang,&nbsp;Yi-Ke Zhu,&nbsp;Xing-Jun Cai","doi":"10.1080/01902148.2021.1876792","DOIUrl":"https://doi.org/10.1080/01902148.2021.1876792","url":null,"abstract":"<p><p><b>Background</b> Asthma is a chronic inflammatory heterogeneous respiratory disease. Previous studies showed that the lncRNA NEAT1 (nuclear paraspeckle assembly transcript 1) might play an important role in the pathogenesis of asthma, but its potential mechanism in airway smooth muscle cell (ASMC) inflammation remains largely unknown and needs further investigation.<b>Methods</b> We performed cellular immunofluorescence to identify the features of ASMCs and detected the expression levels of lncRNA NEAT1, miR-139, TNF-α, IL-6, IL-8 and IL-1β by quantitative real-time PCR (Q-PCR) and ELISA. Western blotting (WB) was used to measure the protein expression of the related genes, and bioinformatics as well as dual luciferase assays were used to validate the interaction between lncRNA NEAT1 and miR-139 and the interaction between miR-139 and the 3'-UTR of JAK3.<b>Results</b> The expression of lncRNA NEAT1 was increased in the ASMCs of asthma patients, but miR-139 was decreased. Overexpression of lncRNA NEAT1 promoted the expression of the inflammatory cytokines such as TNF-α, IL-6, IL-8 and IL-1β in ASMCs. LncRNA NEAT1 was able to target miR-139 to activate the JAK3/STAT5 signaling pathway and induced the expression of these inflammatory cytokines in ASMCs. Overexpression of miR-139 or suppression of the JAK3/STAT5 signaling pathway reversed the inflammatory effect of lncRNA NEAT1.<b>Conclusion</b> LncRNA NEAT1 played a pivotal role in ASMC inflammation and exerted its function through the miR-139/JAK3/STAT5 signaling network.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 4","pages":"161-172"},"PeriodicalIF":1.7,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1876792","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25371351","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":"Circ_0000735 enhances the proliferation, metastasis and glycolysis of non-small cell lung cancer by regulating the miR-635/FAM83F axis.","authors":"Guigang Tai,&nbsp;Miao Zhang,&nbsp;Fang Liu","doi":"10.1080/01902148.2021.1881188","DOIUrl":"https://doi.org/10.1080/01902148.2021.1881188","url":null,"abstract":"<p><strong>Background: </strong>Circular RNA (circRNA) is considered to be an important regulator of cancer malignant progression, including non-small cell lung cancer (NSCLC). Circ_0000735 has been found to be associated with NSCLC progression. Therefore, its role and molecular mechanism in NSCLC deserve further exploration.</p><p><strong>Methods: </strong>Quantitative real-time PCR (qRT-PCR) was used to measure the expression of circ_0000735, microRNA (miR)-635 and family with sequence similarity 83 member F (FAM83F). Cell proliferation, migration, invasion and apoptosis were determined using cell counting kit 8 assay, colony formation assay, transwell assay and flow cytometry. Cell glycolysis were measured by detecting the glucose consumption and lactate production of cells. Western blot analysis was utilized to test the protein levels of glycolysis markers and FAM83F. The relationship between circ_0000735 and miR-635 or miR-635 and FAM83F was verified by dual-luciferase reporter assay. The effect of circ_0000735 on NSCLC tumor growth was evaluated by constructing xenograft models.</p><p><strong>Results: </strong>Circ_0000735 was a highly expressed circRNA in NSCLC. Silenced circ_0000735 could inhibit NSCLC cell proliferation, migration, invasion, glycolysis, and increase apoptosis. MiR-635 could be sponged by circ_0000735, and its inhibitor could reverse the regulation of circ_0000735 silencing on NSCLC progression. Moreover, FAM83F was a target of miR-635, and circ_0000735 positively regulated FAM83F by sponging miR-635. The inhibitory effect of miR-635 on NSCLC progression could also be reversed by FAM83F overexpression. Additionally, circ_0000735 knockdown reduced NSCLC tumor growth through regulating miR-635/FAM83F axis.</p><p><strong>Conclusion: </strong>Circ_0000735 promoted NSCLC progression by the miR-635/FAM83F axis, showing that circ_0000735 might be a promising biomarker for NSCLC. Highlights: Circ_0000735 knockdown represses NSCLC cell progression and tumor growth. Circ_0000735 functions as a miR-635 sponge. FAM83F is targeted by miR-635.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 3","pages":"136-148"},"PeriodicalIF":1.7,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1881188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25347816","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":"PDE3-inhibitor enoximone prevented mechanical ventilation in patients with SARS-CoV-2 pneumonia.","authors":"Jan Beute,&nbsp;Pieter Boermans,&nbsp;Bart Benraad,&nbsp;Jan Telman,&nbsp;Zuzana Diamant,&nbsp;Alex KleinJan","doi":"10.1080/01902148.2021.1881189","DOIUrl":"https://doi.org/10.1080/01902148.2021.1881189","url":null,"abstract":"<p><strong>Background: </strong>Standard care in severe SARS-CoV-2 pneumonia complicated by severe dyspnea and respiratory failure, consists of symptom reduction, ultimately supported by mechanical ventilation. Patients with severe SARS-CoV-2, a prominent feature of COVID-19, show several similar symptoms to Critical Asthma Syndrome (CAS) patients, such as pulmonary edema, mucus plugging of distal airways, decreased tissue oxygenation, (emergent) exhaustion due to severe dyspnea and respiratory failure. Prior application of elective phosphodiesterase (PDE)3-inhibitors milrinone and enoximone in patients with CAS yielded rapid symptomatic relief and reverted the need for mechanical ventilation, due to their bronchodilator and anti-inflammatory properties. Based on these observations, we hypothesized that enoximone may be beneficial in the treatment of patients with severe SARS-CoV-2 pneumonia and prominent CAS-features.</p><p><strong>Methods: </strong>In this case report enoximone was administered to four consecutive patients (1 M; 3 F; 46-70 y) with emergent respiratory failure due to SARS-CoV-2 pneumonia. Clinical outcome was compared with three controls who received standard care only.</p><p><strong>Results: </strong>After an intravenous bolus of enoximone 20 mg followed by 10 mg/h via perfusor, a rapid symptomatic relief was observed: two out of four patients recovered within a few hours, the other two (with comorbid COPD GOLD II/III) responded within 24-36 h. Compared to the controls, in the enoximone-treated patients respiratory failure and further COVID-19-related deterioration was reverted and mechanical ventilation was prevented, leading to reduced hospital/ICU time.</p><p><strong>Discussion: </strong>Our preliminary observations suggest that early intervention with the selective PDE3-inhibitor enoximone may help to revert respiratory failure as well as avert mechanical ventilation, and reduces ICU/hospital time in patients with severe SARS-CoV-2 pneumonia. Our findings warrant further research on the therapeutic potential of PDE3-inhibition, alone or in combination with other anti-COVID-19 strategies.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 3","pages":"149-160"},"PeriodicalIF":1.7,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01902148.2021.1881189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25336224","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":"Glycogen phosphorylase B promotes cell proliferation and migration through PI3K/AKT pathway in non-small cell lung cancer.","authors":"Yiyi Zhan,&nbsp;Ru Chen,&nbsp;Tianhai Wang,&nbsp;Shijun Shan,&nbsp;Hongge Zhu","doi":"10.1080/01902148.2020.1864065","DOIUrl":"https://doi.org/10.1080/01902148.2020.1864065","url":null,"abstract":"<p><strong>Objective: </strong>Glycogen phosphorylase B (PYGB), the rate-determining enzyme in glycogen degradation, plays a critical role in progression of various tumors. The present study focused on the potential molecular mechanism toward PYGB in non-small cell lung cancer (NSCLC) progression.</p><p><strong>Methods: </strong>Expression of PYGB in NSCLC tissues and cell lines was evaluated via quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry. Cell viability, proliferation and apoptosis were investigated using 3-(4,5-Dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay, 5-bromo-2-deoxyuridine (<i>BrdU</i>) and flow cytometry, respectively. Cell migration and invasion ability were detected by wound healing and transwell invasion assays, respectively. The <i>in vivo</i> effect of PYGB on NSCLC tumor growth was determined via subcutaneous xenotransplanted tumor model.</p><p><strong>Results: </strong>PYGB was upregulated in NSCLC tissues and cell lines, suggesting a poor prognosis in NSCLC patients. <i>In vitro</i> functional assays indicated that knockdown of PYGB suppressed cell viability, proliferation, migration and invasion, while promoted cell apoptosis in NSCLC. Mechanistically, we found that overexpression of PYGB could activate phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, while these effects were effectively reversed by knockdown of PYGB. <i>In vivo</i> tumorigenesis and PI3K/AKT signaling pathway were also inhibited by PYGB knockdown.</p><p><strong>Conclusions: </strong>Knockdown of PYGB suppressed NSCLC progression, suggesting PYGB as a novel biomarker and potential molecular therapeutic target for further investigation in NSCLC.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 3","pages":"111-120"},"PeriodicalIF":1.7,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38724665","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}