Experimental Lung Research最新文献

{"title":"Protective effect of liver X receptor on cigarette smoke and lipopolysaccharide induced airway inflammation and emphysema in mice.","authors":"Fenfang Yu, Lin Gao, Ke Xu, Xiaobing Yang, Junran Zhang, Yu Tang, Zhifei Ma, Wei Gu, Bining Wu, Ying Shi","doi":"10.1080/01902148.2024.2329436","DOIUrl":"10.1080/01902148.2024.2329436","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study is to assess the impact of Liver X receptors (LXRs) on airway inflammation, airway remodeling, and lipid deposition induced by cigarette smoke and lipopolysaccharide (LPS) exposure in the lung.</p><p><strong>Methods: </strong>Wild mice and LXR-deficient mice were exposed to cigarette smoke and LPS to induce airway inflammation and remodeling. In addition, some wild mice received intraperitoneal treatment with the LXR agonist GW3965 before exposure to cigarette smoke and LPS. Lung tissue and bronchoalveolar lavage fluid were collected to evaluate airway inflammation, airway remodeling and lipid deposition.</p><p><strong>Results: </strong>Exposure to cigarette smoke and LPS resulted in airway inflammation, emphysema and lipid accumulation in wild mice. These mice also exhibited downregulated LXRα and ABCA1 in the lung. Treatment with GW3965 mitigated inflammation, remodeling and lipid deposition, while the deletion of LXRs exacerbated these effects. Furthermore, GW3965 treatment following exposure to cigarette smoke and LPS increased LXRα and ABCA1 expression and attenuated MyD88 expression in wild mice.</p><p><strong>Conclusion: </strong>LXRs demonstrate the potential to mitigate cigarette smoke and LPS- induced airway inflammation, emphysema and lipid disposition in mice.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"50 1","pages":"53-64"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174159","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":"High oxygen exposure's impact on newborn mice: Temporal changes observed via micro-computed tomography.","authors":"Himeko Sato, Akie Kato, Hiroyuki Adachi, Kiichi Takahashi, Hirokazu Arai, Masato Ito, Fumihiko Namba, Tsutomu Takahashi","doi":"10.1080/01902148.2024.2375099","DOIUrl":"https://doi.org/10.1080/01902148.2024.2375099","url":null,"abstract":"<p><strong>Introduction: </strong>Bronchopulmonary dysplasia (BPD) impacts life expectancy and long-term quality of life. Currently, BPD mouse models exposed to high oxygen are frequently used, but to reevaluate their relevance to human BPD, we attempted an assessment using micro-computed tomography (µCT).</p><p><strong>Methods: </strong>Newborn wildtype male mice underwent either 21% or 95% oxygen exposure for 4 days, followed until 8 wk. Weekly µCT scans and lung histological evaluations were performed independently.</p><p><strong>Results: </strong>Neonatal hyperoxia for 4 days hindered lung development, causing alveolar expansion and simplification. Histologically, during the first postnatal week, the exposed group showed a longer mean linear intercept, enlarged alveolar area, and a decrease in alveolar number, diminishing by week 4. Weekly µCT scans supported these findings, revealing initially lower lung density in newborn mice, increasing with age. However, the high-oxygen group displayed higher lung density initially. This difference diminished over time, with no significant contrast to controls at 3 wk. Although no significant difference in total lung volume was observed at week 1, the high-oxygen group exhibited a decrease by week 2, persisting until 8 wk.</p><p><strong>Conclusion: </strong>This study highlights µCT-detected changes in mice exposed to high oxygen. BPD mouse models might follow a different recovery trajectory than humans, suggesting the need for further optimization.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"50 1","pages":"127-135"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554455","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":"Exosomal miR-223 promotes ARDS by targeting insulin-like growth factor 1 receptor: A cell communication study.","authors":"Miaomiao Li, Lilei Zhuang, Tao Jiang, Li Sun","doi":"10.1080/01902148.2024.2318561","DOIUrl":"10.1080/01902148.2024.2318561","url":null,"abstract":"<p><strong>Background: </strong>Acute respiratory distress syndrome (ARDS) is a respiratory failure syndrome characterized by hypoxemia and changes in the respiratory system. ARDS is the most common cause of death in COVID-19 deaths was ARDS. In this study, we explored the role of miR-223 in exosomes in ARDS.</p><p><strong>Methods: </strong>Exosomes were purified from the supernatants of macrophages. qPCR was used to detect relative mRNA levels. A luciferase reporter assay was performed to verify the miRNA target genes. Western blotting was used to detect the activation of inflammatory pathways. Flow cytometry was performed to assess apoptosis. An LPS-induced ARDS mouse model was used to assess the function of miR-223 in ARDS.</p><p><strong>Results: </strong>Exosomes secreted by macrophages promoted apoptosis in A549 cells. Macrophages and exosomes contain high levels of miR-223. Exogenous miR-223 can decrease the expression of insulin-like growth factor 1 receptor (IGF-1R) in A549 and promote the apoptosis of A549.Transfection of anti-miR223 antisense nucleotides effectively reduced the level of miR-223 in macrophages and exosomes and eliminated the pro-apoptotic effect of A549. <i>In vivo</i>, LPS stimulation increased inflammatory cell infiltration in the lungs of mice, whereas knockdown of miR-223 in mice resulted in significantly reduced eosinophil infiltration.</p><p><strong>Conclusions: </strong>Macrophages can secrete exosomes containing miR-223 and promote apoptosis by targeting the IGF-1R/Akt/mTOR signaling pathway in A549 cells and mouse models, suggesting that miR-223 is a potential target for treating COVID-19 induced ARDS.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"50 1","pages":"42-52"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995973","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":"Sulfotransferase homolog 2 receptors blockade on monocyte subsets along with their inflammatory cytokines for septic lung injury.","authors":"Peng Wang, Shuqi Yang, Changcheng Li, Baohua Ma, Mengqiu Yi, Xiaobo Chen, Min Yu","doi":"10.1080/01902148.2024.2398989","DOIUrl":"10.1080/01902148.2024.2398989","url":null,"abstract":"<p><strong>Purpose of the study: </strong>To observe the dynamic changes in monocyte subsets during septic lung injury and to assess the anti-inflammatory role of the sulfotransferase homolog 2 (ST2) receptor.</p><p><strong>Materials and methods: </strong>Dynamic changes of monocyte subsets from patients with septic lung injury and mice post-cecal ligation and puncture (CLP) were monitored. ST2 receptors on mice monocytes and concentrations of IL-33, IL-1β, IL-12, and IL-27 from peripheral blood or culture supernatant were detected.</p><p><strong>Results: </strong>CD14^lowCD16^- (Mo0) and CD14⁺⁺CD16⁺ (Mo2) monocyte subsets were significantly expanded in patients with sepsis-related acute respiratory distress syndrome. In sepsis model mice, monocyte counts, particularly of Ly6C^int and CDLy6C^int+hi monocytes, were significantly increased. The mean optical density value of TNF-α after CLP mainly increased after 24 h, whereas that of IL-6 was significantly increased at all time points assessed after CLP. The levels of IL-1β, IL-12, IL-27, and IL-33 increased to variable degrees at 6, 12, 24, and 48h after CLP, and ST2⁺ monocytes were significantly expanded in sepsis model mice compared to sham-operated mice. ST2 receptor blockade suppressed IL-1β and IL-12 production in cell culture.</p><p><strong>Conclusions: </strong>Changes in monocyte subsets expressing the ST2 receptor play an important role in septic lung injury by modulating inflammatory cytokine secretion.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"50 1","pages":"146-159"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145486","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":"Hsa_circ_0008833 promotes COPD progression via inducing pyroptosis in bronchial epithelial cells.","authors":"Tian Xie, Zehua Yang, Shaojing Xian, Qi Lin, Linhui Huang, Yipeng Ding","doi":"10.1080/01902148.2024.2303474","DOIUrl":"10.1080/01902148.2024.2303474","url":null,"abstract":"<p><p><b>Purpose:</b> Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder. Pyroptosis represents a distinctive form of inflammatory cell death that is mediated through the activation of Caspase-1 and inflammasomes. CircRNAs have emerged as a novel class of biomolecules with implications in various human diseases. This study aims to investigate the circRNAs profile of in COPD progression and identify pivotal circRNAs associated with the development of this disease. <b>Methods:</b> he expression profiles of circRNAs in peripheral blood mononuclear cells of COPD patients were assessed by circRNA microarray. Furthermore, flag-labeled vectors were constructed to assess the potential protein-coding capacity of has-circ-0008833. 16HBE cells were stably transfected with lentivirus approach, and cell proliferation and death were assessed to clarify the functional roles of has-circ-0008833 and its encoded protein circ-0008833aa. Additionally, western blot analysis was furthered performed to determine the level of Caspase-1, IL-18, IL-1β, NLRP3, ASC, and cleaved GSDMD regulated by has-circ-0008833 and circ-0008833-57aa. <b>Results:</b> Initially, we screened the expression profiles of human circRNAs in peripheral blood mononuclear cells of COPD patients, and found that has-circ-0008833 exhibited a significant increase in COPD mononuclear cells. Subsequently, we demonstrated that has-circ-0008833 carried an open reading frame (ORF), which encoded a functional protein, referred to as circ-0008833-57aa. By employing gain-of-function approaches, our results suggested that both circ-0008833 and circ-0008833-57aa inhibited proliferation, but accelerated the rate of 16HBE cell death. Finally, we discovered that circ-0008833 and circ-0008833-57aa promoted the expression of Caspase-1, IL-18, IL-1β, NLRP3, ASC, and cleaved GSDMD in 16HBE cells. <b>Conclusions:</b> Upregulation of circ-0008833 might promote COPD progression by inducing pyroptosis of bronchial epithelial cells through the encoding of a 57-amino acid peptide.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"50 1","pages":"1-14"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485256","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":"Animal models of infection-induced acute lung injury.","authors":"Wanying Tan, Lingjun Qi, Zhenghuai Tan","doi":"10.1080/01902148.2024.2428939","DOIUrl":"10.1080/01902148.2024.2428939","url":null,"abstract":"<p><p><b>Aim:</b> Acute lung injury (ALI) is characterized by severe hypoxemia, reduced lung elasticity, and notable pulmonary edema, often caused by infections and potentially progressing to ARDS. This article explores animal models of ALI and clarifies its main pathogenic mechanisms.</p><p><p><b>Materials and Methods:</b> we reviewed 20 years of ALI animal model advancements via PubMed, assessing clinical symptoms, histopathology, and reproducibility, and provided guidance on selecting models aligned with ALI pathogenesis.</p><p><p><b>Results:</b> key proinflammatory mediators and interleukins play a significant role in ALI development, though their interactions are not fully understood. Preclinical models are essential for investigating ALI causes and testing treatments. Animal models mimic ALI from sources such as infections, drugs, and I/R events, but differences between mouse and human lungs necessitate careful validation of these findings.</p><p><p><b>Conclusions:</b> A comprehensive strategy is essential to address clinical treatment and drug R&D challenges to prevent severe complications and reduce mortality rates.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"50 1","pages":"221-241"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667568","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":"Performance of newly developed add-on devices on aerosol delivery in noninvasive ventilated subjects.","authors":"Amal E Rashad, Yasmin M Madney, Ahmed M Abdelhaleem Ali, Mohammad F Mohammad, Fahad T Alsulami, Yousef Saeed Alqarni, Rania M Sarhan, Mohamed E A Abdelrahim","doi":"10.1080/01902148.2024.2418555","DOIUrl":"https://doi.org/10.1080/01902148.2024.2418555","url":null,"abstract":"<p><p><b>Background:</b> Several techniques had been developed to generate aerosolized medications during noninvasive ventilation (NIV) using variable inhalation methods. This study hypothesized that large spacers were more efficient significantly than small spacers and adapters during NIV. <b>Objective:</b> The main objective of this study was to compare the performance of newly developed spacers with standard T-piece in NIV chronic obstructive pulmonary disease (COPD) subjects. <b>Methods:</b> Sixty COPD subjects requiring NIV were included in this study. A dual-limb circuit was used, and the mode of ventilator was set in spontaneous volume-controlled mode. Dual-limb ventilation circuit, consists of inspiratory-limb and expiratory-limb, is pressure and volume controlled in response to subject expiration providing relatively high resistance to expiratory flow. Two experimental sets were evaluated: the first was introducing two preliminary pressurized metered-dose inhalers (pMDI) puffs before the nebulization of 1 ml of a respirable solution of salbutamol by vibrating mesh nebulizer (VMN) using Minimhal and Combihaler. The second was to only nebulize 1 ml of salbutamol respirable solution by VMN using Combihaler, Minimhal, and standard T-piece. Two urine samples were collected after aerosol delivery: urine sample after 30 min. (USAL0.5) as an indicator of lung deposition and all urine pooled 24 h (USAL24) post-inhalation as an indicator of systemic absorption. The amount of salbutamol extracted from urine samples was assayed by high-performance liquid chromatography. <b>Results:</b> Minimhal + pMDI + VMN delivered a higher percentage of salbutamol 30 min post-inhalation than Minimhal + VMN (<i>p</i> < 0.001). Also, Combihaler + pMDI + VMN delivered a higher percentage of salbutamol 30 min post-inhalation than Combihaler + VMN (<i>p</i> < 0.001). Combihaler + VMN delivered a higher percentage of salbutamol 30 min and 24 h post-inhalation than both Minimhal + VMN and T-piece + VMN (<i>p</i> < 0.001). Standard T-piece delivered the lowest aerosol amount delivered to the lung compared to both spacers (<i>p</i> < 0.05). <b>Conclusions:</b> Introducing two pMDI puffs significantly improved aerosol delivery by both spacers. Combihaler significantly improves aerosol delivery more than Minimhal.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"50 1","pages":"199-207"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497732","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":"Exploring the role of oral microbiome dysbiosis in cardiometabolic syndrome and smoking.","authors":"Layla I Mohammed, Zain Zaki Zakaria, Fatiha M Benslimane, Maha Al-Asmakh","doi":"10.1080/01902148.2024.2331185","DOIUrl":"10.1080/01902148.2024.2331185","url":null,"abstract":"<p><p>Oral microbiome research has gained significant interest in recent years due to its potential impact on overall health. Smoking has been identified as a significant modulator of the oral microbiome composition, leading to dysbiosis and possible health consequences. Research has primarily focused on the association between smoking and oral microbiome, as well as smoking's association with cardiometabolic syndrome (CMS). This narrative review presents an overview of the recent findings and current knowledge on the oral microbiome and its role in CMS, including the effects of smoking and ethnicity. We discussed the development and composition of the oral microbiome and the association of periodontitis with diabetes and cardiovascular diseases. Furthermore, we highlighted the correlations between oral microbiome and CMS factors, such as diabetes, hypertension, dyslipidemia, and obesity. There is a need for further research in this area to better understand the mechanisms underlying the impact of smoking on oral microbiome dysbiosis and the development of CMS. Interestingly, geographic location and ethnicity have been shown to impact the oral microbiome profiles across populations. This knowledge will help develop personalized disease prevention and treatment approaches considering individual differences in oral microbiome composition. Understanding the complex interplay between oral microbiome, smoking, and CMS is essential for developing effective prevention and treatment strategies for a wide range of diseases.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"50 1","pages":"65-84"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305361","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":"BCL6 attenuates hyperoxia-induced lung injury by inhibiting NLRP3-mediated inflammation in fetal mouse.","authors":"Dan Chen, Hui-Min Zhao, Xian-Hui Deng, Sheng-Peng Li, Mei-Hui Zhou, Ya-Xian Wu, Ying Tong, Ren-Qiang Yu, Qing-Feng Pang","doi":"10.1080/01902148.2024.2320665","DOIUrl":"10.1080/01902148.2024.2320665","url":null,"abstract":"<p><strong>Background: </strong>The transcriptional repressor B-cell lymphoma 6 (BCL6) has been reported to inhibit inflammation. So far, experimental evidence for the role of BCL6 in bronchopulmonary dysplasia (BPD) is lacking. Our study investigated the roles of BCL6 in the progression of BPD and its downstream mechanisms.</p><p><strong>Methods: </strong>Hyperoxia or lipopolysaccharide (LPS) was used to mimic the BPD mouse model. To investigate the effects of BCL6 on BPD, recombination adeno-associated virus serotype 9 expressing BCL6 (rAAV9-BCL6) and BCL6 inhibitor FX1 were administered in mice. The pulmonary pathological changes, inflammatory chemokines and NLRP3-related protein were observed. Meanwhile, BCL6 overexpression plasmid was used in human pulmonary microvascular endothelial cells (HPMECs). Cell proliferation, apoptosis, and NLRP3-related protein were detected.</p><p><strong>Results: </strong>Either hyperoxia or LPS suppressed pulmonary BCL6 mRNA expression. rAAV9-BCL6 administration significantly inhibited hyperoxia-induced NLRP3 upregulation and inflammation, attenuated alveolar simplification and dysregulated angiogenesis in BPD mice, which were characterized by decreased mean linear intercept, increased radical alveolar count and alveoli numbers, and the upregulated CD31 expression. Meanwhile, BCL6 overexpression promoted proliferation and angiogenesis, inhibited apoptosis and inflammation in hyperoxia-stimulated HPMECs. Moreover, administration of BCL6 inhibitor FX1 arrested growth and development. FX1-treated BPD mice exhibited exacerbation of alveolar pathological changes and pulmonary vessel permeability, with upregulated mRNA levels of pro-inflammatory cytokines and pro-fibrogenic factors. Furthermore, both rAAV9-BCL6 and FX1 administration exerted a long-lasting effect on hyperoxia-induced lung injury (≥4 wk).</p><p><strong>Conclusions: </strong>BCL6 inhibits NLRP3-mediated inflammation, attenuates alveolar simplification and dysregulated pulmonary vessel development in hyperoxia-induced BPD mice. Hence, BCL6 may be a target in treating BPD and neonatal diseases.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"50 1","pages":"25-41"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989704","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":"Stevioside attenuates bleomycin-induced pulmonary fibrosis by activating the Nrf2 pathway and inhibiting the NF-κB and TGF-β1/Smad2/3 pathways.","authors":"Wei Hao, Ting-Ting Yu, Dong-Ze Zuo, Heng-Zhao Hu, Ping-Ping Zhou","doi":"10.1080/01902148.2023.2286465","DOIUrl":"10.1080/01902148.2023.2286465","url":null,"abstract":"<p><p><b>Objective:</b> This study aimed to investigate the effects of stevioside (STE) on pulmonary fibrosis (PF) and the potential mechanisms. <b>Methods:</b> In this study, a mouse model of PF was established by a single intratracheal injection of bleomycin (BLM, 3 mg/kg). The experiment consisted of four groups: control group, BLM group, and STE treatment groups (STE 50 and 100 mg/kg). ELISA and biochemical tests were conducted to determine the levels of TNF-α, IL-1β, IL-6, NO, hydroxyproline (HYP), SOD, GSH, and MDA. Histopathological changes and collagen deposition in lung tissues were observed by HE and Masson staining. Immunohistochemistry was performed to determine the levels of collagen I-, collagen III-, TGF-β1- and p-Smad2/3-positive cells. Western blot analysis was used to measure the expression of epithelial-mesenchymal transition (EMT) markers, including α-SMA, vimentin, E-cadherin, and ZO-1, as well as proteins related to the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, nuclear transcription factor-κB (NF-κB) pathway, and TGF-β1/Smad2/3 pathway in lung tissues. <b>Results:</b> STE significantly alleviated BLM-induced body weight loss and lung injury in mice, decreased HYP levels, and reduced the levels of collagen I- and collagen III-positive cells, thereby decreasing extracellular matrix (ECM) deposition. Moreover, STE markedly improved oxidative stress (MDA levels were decreased, while SOD and GSH activity were enhanced), the inflammatory response (the levels of TNF-α, IL-1β, IL-6, and NO were reduced), and EMT (the expression of α-SMA and vimentin was downregulated, and the expression of E-cadherin and ZO-1 was upregulated). Further mechanistic analysis revealed that STE could activate the Nrf2 pathway and inhibit the NF-κB and TGF-β1/Smad2/3 pathways. <b>Conclusion:</b> STE may alleviate oxidative stress by activating the Nrf2 pathway, suppress the inflammatory response by downregulating the NF-κB pathway, and inhibit EMT progression by blocking the TGF-β1/Smad2/3 pathway, thereby improving BLM-induced PF.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"49 1","pages":"205-219"},"PeriodicalIF":1.7,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138477173","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}