Experimental Lung Research最新文献

{"title":"Transglutaminase 2 mediates lung inflammation and remodeling by transforming growth factor beta 1 <i>via</i> alveolar macrophage modulation.","authors":"Young Chan Kim,&nbsp;Jeonghyeon Kim,&nbsp;Subin Kim,&nbsp;Boram Bae,&nbsp;Ruth Lee Kim,&nbsp;Eui-Man Jeong,&nbsp;Sang-Heon Cho,&nbsp;Hye-Ryun Kang","doi":"10.1080/01902148.2021.1998733","DOIUrl":"https://doi.org/10.1080/01902148.2021.1998733","url":null,"abstract":"<p><p>Transforming growth factor beta 1 (TGF-β1) induces pulmonary fibrosis by enhancing epithelial apoptosis and affects the enzymatic activity of transglutaminase 2 (TG2). The aim of this study was to determine the role of TG2 in TGF-β1-induced lung remodeling and alveolar macrophage modulation. We characterized the <i>in viv</i>o effects of TGF-β1 and TG2 on lung inflammation, fibrosis, and macrophage activity using transgenic C57BL/6 mice with wild and null TG2 loci. The effect of TG2 inhibition on <i>in vitro</i> TGF-β1-stimulated alveolar macrophages was assessed through mRNA analysis. TG2 was remarkably upregulated in the lungs of TGF-β1 transgenic (TGF-β1 Tg) mice, especially in alveolar macrophages and epithelial cells. In the absence of TG2, TGF-β1-induced inflammation was suppressed, decreasing the number of macrophages in the bronchoalveolar lavage fluid. In addition, the alveolar destruction and peribronchial fibrosis induced by TGF-β1 overexpression were significantly reduced, which correlated with decreases in the expression of fibroblast growth factor and matrix metallopeptidase 12, respectively. However, TG2 deficiency did not compromise the phagocytic activity of alveolar macrophages in TGF-β1 Tg mice. At the same time, TG2 contributed to the regulation of TGF-β1-induced macrophage activation. Inhibition of TG2 did not affect the TGF-β1-induced expression of CD86, an M1 marker, in macrophages, but it did reverse the TGF-β1-induced expression of CD206. This result suggests that TG2 mediates TGF-β1-induced M2-like polarization but does not contribute to TGF-β1-induced M1 polarization. In conclusion, TG2 regulates macrophage modulation and plays an important role in TGF-β1-induced lung inflammation, destruction, and fibrosis.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 10","pages":"465-475"},"PeriodicalIF":1.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39922699","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":"Protective effect of oxytocin through its anti-inflammatory and antioxidant role in a model of sepsis-induced acute lung injury: Demonstrated by CT and histological findings.","authors":"I H Sever,&nbsp;B Ozkul,&nbsp;D Erisik Tanriover,&nbsp;O Ozkul,&nbsp;C S Elgormus,&nbsp;S G Gur,&nbsp;I Sogut,&nbsp;Y Uyanikgil,&nbsp;E O Cetin,&nbsp;O Erbas","doi":"10.1080/01902148.2021.1992808","DOIUrl":"https://doi.org/10.1080/01902148.2021.1992808","url":null,"abstract":"<p><p>Although several studies demonstrate the anti-inflammatory effect of oxytocin in different pathophysiological processes, there are limited data describing the impact of oxytocin on acute respiratory distress syndrome (ARDS). We aimed to elucidate the protective effect of oxytocin in ARDS with histopathological evaluation and radiological imaging in addition to biochemical markers.</p><p><p>Fecal intraperitoneal injection procedure (FIP) was performed on 24 of 32 rats included in the study for creating a sepsis model. Rats were randomly assigned into four groups: control group (no procedure was applied, n = 8), untreated septic group [was operated (FIP) and received no treatment, n = 8], placebo group (FIP, treated with 10 ml/kg of saline at once, n = 8), and treated group (FIP, treated with 0.1 mg/kg of oxytocin at once, n = 8). Chest CT was performed for all rats 20 hours after the procedure and density of the lungs were measured manually by using HU. All animals were sacrificed for histopathological examination of lung damage and blood samples were collected for biochemical analysis.</p><p><p>Plasma malondialdehyde (MDA), lactic acid (LA), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL 1-β) levels were significantly increased in the placebo (FIP + saline) and the untreated (FIP) groups, and plasma levels of all biomarkers were reversed by oxytocin. Further, the density of the lung parenchyma (Hounsfield unit) on CT images and the histopathological lung damage score values were closer to the control group in the oxytocin-treated group compared to the placebo group.</p><p><p>Our findings suggested that oxytocin could exert anti-inflammatory, antioxidant and protective effects in FIP-induced ARDS.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 9","pages":"426-435"},"PeriodicalIF":1.7,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39556200","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":"In vitro optimization of miniature bronchoscope lentiviral vector delivery for the small animal lung.","authors":"Nathan Rout-Pitt,&nbsp;Martin Donnelley,&nbsp;David Parsons","doi":"10.1080/01902148.2021.1989523","DOIUrl":"https://doi.org/10.1080/01902148.2021.1989523","url":null,"abstract":"<p><p>Current gene therapy delivery protocols for small animal lungs typically utilize indirect dose delivery via the nasal airways, or bolus delivery directly into the trachea. Both methods can result in variable transduction throughout the lung, as well as between animals, and cannot be applied in a targeted manner. To minimize variability and improve lung coverage we previously developed and validated a method to visualize and dose gene vectors into pre-selected lobes of rat lungs using a mini-bronchoscope. Lentiviral (LV) vectors are known to be fragile and can be inactivated easily by temperature or the application of shear stresses. There are several ways that the bronchoscope could be configured to deliver the LV vector, and these could result in different amounts of functional LV vector being delivered to the lung. This study evaluated several methods of LV vector delivery through the bronchoscope, and how flow rates and LV vector stabilizing diluents impact LV vector delivery. NIH-3T3 cells were exposed to LV vector containing the green fluorescent protein (GFP) reporter gene using various bronchoscopic delivery techniques and the number of GFP-positive cells produced by each was quantified by flow cytometry. The results showed that directly drawing the LV vector into the bronchoscope tip resulted in 80-90% recovery of viable vector, and was also the simplest method of delivery. The fluid delivery rate and the use of stabilizing serum in the vector diluent had no effect on the viability of the LV vector delivered. These findings can be used to optimize LV vector dose delivery into individual lung lobes of small animal models.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 9","pages":"417-425"},"PeriodicalIF":1.7,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39507293","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":"House dust mite-derived allergens effect on matrix metalloproteases in airway epithelial cells.","authors":"Dilara Karaguzel,&nbsp;Basak Ezgi Sarac,&nbsp;Hayriye Akel Bilgic,&nbsp;Gokce Yagmur Summak,&nbsp;Mehmet Altay Unal,&nbsp;Omer Kalayci,&nbsp;Cagatay Karaaslan","doi":"10.1080/01902148.2021.1998734","DOIUrl":"https://doi.org/10.1080/01902148.2021.1998734","url":null,"abstract":"<p><p><b>Aim of the Study</b>: Many allergens have protease activities. Although the immunomodulatory effects of these antigens are well known, the effects attributed to their protease activities are not thoroughly investigated. We set out to determine the effects of house dust mite (HDM) allergens with varying protease activities on bronchial epithelial cell functions. <b>Materials and methods:</b> BEAS-2B cells were maintained in ALI-culture and stimulated with Der p1 (cysteine protease), Der p6 (serine protease), and Der p2 (non-protease) with and without specific protease inhibitors or heat denaturation. Cell viability and epithelial permeability were measured with MTT and paracellular flux assay, respectively. The effect of heat denaturation on allergen structure was examined using <i>in silico</i> models. Matrix metalloproteinases (MMPs) were investigated at the transcription (qPCR), protein (ELISA), and functional (zymography) levels. <b>Results:</b> Epithelial permeability increased only after Der p6 but not after Der p1 or Der p2 stimulation. Der p2 increased both MMP-2 and MMP-9 expression, while Der p1 increased only MMP-9 expression. The heat-denatured form of Der p1 unexpectedly increased MMP-9 gene expression, which, through the use of <i>in silico</i> models, was attributed to its ability to change receptor connections by the formation of new electrostatic and hydrogen bonds. IL-8 and GM-CSF production were increased after Der p1 and Der p2 but decreased after Der p6 stimulation. IL-6 decreased after Der p1 but increased following stimulation with Der p6 and heat-denatured Der p2. <b>Conclusion:</b> Allergens in house dust mites are capable of inducing various changes in the epithelial cell functions by virtue of their protease activities.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 9","pages":"436-450"},"PeriodicalIF":1.7,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39593579","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":"A RAS inhibitor reduces allergic airway remodeling via regulating IL-33-derived type 2 innate lymphoid cells.","authors":"Toshifumi Tezuka,&nbsp;Masahiko Azuma,&nbsp;Hirohisa Ogawa,&nbsp;Mayo Kondo,&nbsp;Hisanori Uehara,&nbsp;Yoshinori Aono,&nbsp;Masaki Hanibuchi,&nbsp;Yasuhiko Nishioka","doi":"10.1080/01902148.2021.1999536","DOIUrl":"https://doi.org/10.1080/01902148.2021.1999536","url":null,"abstract":"<p><p><b>Purpose:</b> IL-33 is known to induce corticosteroid-resistant eosinophilic inflammation and airway remodeling by activating type 2 innate lymphoid cells (ILC2s). Although the RAS signal pathway plays an important role in IL-33-induced ILC2s activation and airway remodeling, it is not known if RAS inhibitors are effective against refractory asthma. We examined the effects of the RAS inhibitor XRP44X in refractory asthma. <b>Methods:</b> RAS activity were examined by BAL fluid and T-cells isolated from spleen cells in <i>Dermatophagoides pteronyssinus</i> (Dp)-sensitized/challenged acute allergic airway inflammation model. A chronic allergic airway inflammation mouse model was generated by challenged with Dp. XRP44X and/or fluticasone were administrated nasally to different experimental groups. The effects of nasal simultaneous administration of XRP44X or fluticasone were assessed in mice administrated with IL-33 or Dp. <b>Results:</b> RAS activity in CD4⁺ T cells stimulated by Dp were suppressed by XRP44X. Although fluticasone and XRP44X only improved allergic airway inflammation in mice, XRP44X in combination with fluticasone produced further improvement in not only eosinophilic inflammation but also bronchial subepithelial thickness. XRP44X suppressed IL-5 and IL-13 production from ILC2s, although this effect was not suppressed by fluticasone. IL-33-induced airway inflammation resistant to fluticasone was ameliorated by XRP44X via regulating the accumulation of lung ILC2s. <b>Conclusion:</b> The RAS signal pathway plays a crucial role in allergen-induced airway remodeling associated with ILC2s. XRP44X may have therapeutic potential for refractory asthma.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 9","pages":"451-463"},"PeriodicalIF":1.7,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39593548","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":"TMT-Based proteomics analysis of LPS-induced acute lung injury.","authors":"Shengsong Chen,&nbsp;Yi Zhang,&nbsp;Qingyuan Zhan","doi":"10.1080/01902148.2021.1981494","DOIUrl":"https://doi.org/10.1080/01902148.2021.1981494","url":null,"abstract":"<p><strong>Purpose: </strong>The proteome during lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice is unclear.</p><p><strong>Materials and methods: </strong>In this study, eight-week-old male C57BL/6 mice were intraperitoneally injected with LPS and sacrificed 18 hours after LPS administration to identify protein expression levels in lung tissue using tandem mass tag (TMT) analysis for relative quantification. Hematoxylin-eosin (HE) staining was used to evaluate lung injury in mice. Immunohistochemical staining was used to calculate the production of myeloperoxidase (MPO) and TUNEL staining was performed to detect apoptosis. GO functional clustering and KEGG pathway enrichment analyses were performed to determine functions of differentially expressed proteins (DEPs) and transduction pathways. Domain annotation and subcellular localization analysis of the DEPs were also performed. Furthermore, parallel reaction monitoring (PRM) analysis was used to verify the top 30 DEPs.</p><p><strong>Results: </strong>A total of 5188 proteins were found to be expressed in lung tissues from LPS- and saline-treated mice. Among these proteins, 293 were differentially expressed between the two groups; 255 proteins were upregulated in the LPS-treated ALI mice, while 38 were downregulated. GO analysis showed that the DEPs are mainly extracellular, and KEGG analysis suggested that the DEPs are mainly enriched in the NOD-like receptor signaling pathway, complement and coagulation cascades and natural killer cell-mediated cytotoxicity. Enrichment of the DEPs is mainly peptidase S1A, serine proteases, peptidase S1, and the serpin domain. 26.6% of the DEPs are in the nucleus, 24.6% are in the cytosol, 19.1% are in the extracellular space, and 18.8% are in the plasma membrane. PRM validation showed that the trend of 30 DEPs was same with TMT analysis. Among these, Cytochrome b-245 heavy chain (Cybb), Monocyte differentiation antigen CD14 (Cd14) and Neutrophil gelatinase-associated lipocalin (NGAL) were the most obvious change.</p><p><strong>Conclusions: </strong>Our results may help to identify markers and therapeutic targets for LPS-induced ALI.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 8","pages":"402-415"},"PeriodicalIF":1.7,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39471943","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":"Cysteinyl leukotriene induces eosinophil extracellular trap formation via cysteinyl leukotriene 1 receptor in a murine model of asthma.","authors":"Aline Andrea da Cunha,&nbsp;Josiane Silva Silveira,&nbsp;Géssica Luana Antunes,&nbsp;Keila Abreu da Silveira,&nbsp;Rodrigo Benedetti Gassen,&nbsp;Ricardo Vaz Breda,&nbsp;Paulo Márcio Pitrez","doi":"10.1080/01902148.2021.1923864","DOIUrl":"https://doi.org/10.1080/01902148.2021.1923864","url":null,"abstract":"<p><strong>Purpose: </strong>Eosinophils are one of the main cells responsible to the inflammatory response in asthma by the release of inflammatory molecules such as cytokines, reactive oxygen species (ROS), cytotoxic granule, eosinophil extracellular trap (EET), and lipid mediators as cysteinyl leukotriene (cysLT). The interconnections between these molecules are not fully understood. Here, we attempted to investigate the cysLT participation in the mechanisms of EET formation in an asthma model of OVA challenge.</p><p><strong>Materials and methods: </strong>Before intranasal challenge with OVA, BALB/cJ mice were treated with a 5-lipoxygenase-activating protein (FLAP) inhibitor (MK-886), or with a cysLT1 receptor antagonist (MK-571) and the lung and bronchoalveolar lavage fluid (BALF) were analyzed.</p><p><strong>Results: </strong>We showed that OVA-challenged mice treated with MK-886 or MK-571 had a decrease in inflammatory cells, goblet cells hyperplasia, and eosinophil peroxidase (EPO) activity in the airway. However, only OVA-challenged mice treated with MK-571 had an improvement in lung function. Also, treatments with MK-886 or MK-571 decreased Th2 cytokines levels in the airway. Moreover, we observed that OVA-challenged mice treated with MK-886 or MK-571 had a decrease in EET formation in BALF. We also verified that EET release was not due to cell death because the cell viability remained the same among the groups.</p><p><strong>Conclusion: </strong>We revealed that the decrease in cysLT production or cysLT1 receptor inhibition by MK-886 or/and MK-571 treatments, respectively reduced EET formation in BALF, showing that cysLT regulates the activation process of EET release in asthma.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 8","pages":"355-367"},"PeriodicalIF":1.7,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39375847","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":"Identification of circular RNA circVPS33A as a modulator in house dust mite-induced injury in human bronchial epithelial cells.","authors":"Yinghao Su,&nbsp;Limei Geng,&nbsp;Yunlei Ma,&nbsp;Xiangyan Yu,&nbsp;Ziyi Kang,&nbsp;Zenglu Kang","doi":"10.1080/01902148.2021.1974125","DOIUrl":"https://doi.org/10.1080/01902148.2021.1974125","url":null,"abstract":"<p><strong>Background: </strong>House dust mite has been well documented as a major source of allergen in asthma. Circular RNAs (circRNAs) vacuolar protein sorting 33A (circVPS33A, circ_0000455) is overexpressed in a murine asthma model. Herein, we sought to identify its critical action in <i>Dermatophagoides pteronyssinus</i> peptidase 1 (Der p1)-induced dysfunction of BEAS-2B cells.</p><p><strong>Methods: </strong>The levels of circVPS33A, microRNA (miR)-192-5p, and high-mobility group box 1 (HMGB1) were assessed by quantitative real-time PCR (qRT-PCR) or western blot. Actinomycin D treatment and Ribonuclease R (RNase R) assay were used to characterize circVPS33A. Cell viability, proliferation, apoptosis, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and transwell assays, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to quantify interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6. Direct relationship between miR-192-5p and circVPS33A or HMGB1 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assay.</p><p><strong>Results: </strong>CircVPS33A was highly expressed in asthma plasma and Der p1-treated BEAS-2B cells. Knocking down circVPS33A suppressed Der p1-induced injury in BEAS-2B cells. CircVPS33A targeted miR-192-5p. MiR-192-5p directly targeted HMGB1, and miR-192-5p-mediated repression of HMGB1 alleviated Der p1-driven cell injury. Furthermore, circVPS33A modulated HMGB1 expression through miR-192-5p.</p><p><strong>Conclusion: </strong>Our findings demonstrated that circVPS33A regulated house dust mite-induced injury in human bronchial epithelial cells at least partially depending on the modulation of the miR-192-5p/HMGB1 axis.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 8","pages":"368-381"},"PeriodicalIF":1.7,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39408378","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":"Riociguat can ameliorate bronchopulmonary dysplasia in the SU5416 induced rat experimental model.","authors":"Shinichi Katsuragi,&nbsp;Hidekazu Ishida,&nbsp;Hidehiro Suginobe,&nbsp;Hirofumi Tsuru,&nbsp;Renjie Wang,&nbsp;Chika Yoshihara,&nbsp;Atsuko Ueyama,&nbsp;Jun Narita,&nbsp;Ryo Ishii,&nbsp;Shigetoyo Kogaki,&nbsp;Keiichi Ozono","doi":"10.1080/01902148.2021.1976311","DOIUrl":"https://doi.org/10.1080/01902148.2021.1976311","url":null,"abstract":"<p><strong>Background: </strong>Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature neonates. Classical BPD is caused by hyperoxia and high-pressure mechanical ventilation, whereas BPD in recent era is caused by impaired pulmonary angiogenesis and alveolarization in extreme prematurity. Although sildenafil was reported to be effective in a hyperoxia-induced rat BPD model, several clinical trials could not demonstrate any significant improvement in the respiratory statuses of BPD infants. Riociguat is a soluble guanylate cyclase stimulator that increases cyclic guanosine monophosphate activity in a nitric oxide independent manner. However, a beneficial effect in BPD has not been established yet.</p><p><strong>Methods and results: </strong>We established BPD model in rats by injection of SU5416 on day 1 followed by maintenance under normoxia, which resulted in oversimplified alveoli, sparse pulmonary capillary vessels, severe pulmonary hypertension, and growth retardation, which mimicked the features observed in recent clinical management of BPD. We administered riociguat from day 10, when BPD rats exhibited growth retardation. Histological analyses demonstrated that riociguat treatment significantly but partially ameliorated lung alveolarization, vascularization, and pulmonary hypertension. However, the survival rate was not significantly improved by riociguat treatment.</p><p><strong>Conclusions: </strong>Riociguat could ameliorate pulmonary alveolarization, vascularization, and hypertension in the SU5416 induced BPD rat model, but could not improve the overall survival.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 8","pages":"382-389"},"PeriodicalIF":1.7,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39420986","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":"Double-chamber plethysmography <i>versus</i> oscillometry to detect baseline airflow obstruction in a model of asthma in two mouse strains.","authors":"Magali Boucher,&nbsp;Cyndi Henry,&nbsp;Fatemeh Khadangi,&nbsp;Alexis Dufour-Mailhot,&nbsp;Ynuk Bossé","doi":"10.1080/01902148.2021.1979693","DOIUrl":"https://doi.org/10.1080/01902148.2021.1979693","url":null,"abstract":"<p><strong>Aim of the study: </strong>The current gold standard to assess respiratory mechanics in mice is oscillometry, a technique from which several readouts of the respiratory system can be deduced, such as resistance and elastance. However, these readouts are often not altered in mouse models of asthma. This is in stark contrast with humans, where asthma is generally associated with alterations when assessed by either oscillometry or other techniques. In the present study, we have used double-chamber plethysmography (DCP) to evaluate the breathing pattern and the degree of airflow obstruction in a mouse model of asthma.</p><p><strong>Materials and methods: </strong>Female C57BL/6 and BALB/c mice were studied at day 1 using DCP, as well as at day 11 using both DCP and oscillometry following a once-daily exposure to either house-dust mite (HDM) or saline for 10 consecutive days.</p><p><strong>Results: </strong>All DCP readouts used to describe either the breathing pattern (e.g., tidal volume and breathing frequency) or the degree of airflow obstruction (e.g., specific airway resistance) were different between mouse strains at day 1. Most of these strain differences persisted at day 11. Most oscillometric readouts (e.g., respiratory system resistance and elastance) were also different between strains. Changes caused by HDM were obvious with DCP, including decreases in tidal volume, minute ventilation, inspiratory time and mid-tidal expiratory flow and an increase in specific airway resistance. HDM also caused some strain specific alterations in breathing pattern, including increases in expiratory time and end inspiratory pause, which were only observed in C57BL/6 mice. Oscillometry also detected a small but significant increase in tissue elastance in HDM <i>versus</i> saline-exposed mice.</p><p><strong>Conclusions: </strong>DCP successfully identified differences between C57BL/6 and BALB/c mice, as well as alterations in mice from both strains exposed to HDM. We conclude that, depending on the study purpose, DCP may sometimes outweigh oscillometry.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 8","pages":"390-401"},"PeriodicalIF":1.7,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39434402","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}