Respiratory Research最新文献

{"title":"Intranasal delivery of R8-modified circNFXL1 liposomes ameliorates Su5416-induced pulmonary arterial hypertension in C57BL/6 mice.","authors":"Shan-Shan Li, Miao Guo, Ying Zhao, Feifei Fan, Shaoyuan Huang, Houzhi Yang, Xu Chen, Xin Jin","doi":"10.1186/s12931-025-03203-y","DOIUrl":"10.1186/s12931-025-03203-y","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary arterial hypertension (PAH) is a progressive, life-threatening condition characterized by increased pulmonary vascular resistance and right ventricular hypertrophy (RVH). Current treatments primarily alleviate symptoms but do not effectively target the underlying molecular mechanisms driving the disease. This study aimed to evaluate the therapeutic potential of R8-modified liposomal delivery of circNFXL1, a circular RNA, in a mouse model of PAH.</p><p><strong>Methods: </strong>R8-circNFXL1 liposomes were synthesized and characterized for their physicochemical properties, including encapsulation efficiency. PAH was induced in C57BL/6 mice using a combination of subcutaneous Su5416 administration and hypoxic exposure. Intranasal delivery of R8-circNFXL1 was performed, and therapeutic effects were assessed using echocardiography and hemodynamic measurements. Molecular mechanisms were explored through analysis of the miR-29b/Kcnb1 axis, a regulatory pathway in PAH.</p><p><strong>Results: </strong>The R8-circNFXL1 liposomes demonstrated optimal physicochemical properties, including high encapsulation efficiency. Treatment with R8-circNFXL1 significantly reduced RVH, improved cardiac function, and mitigated pulmonary vascular remodeling compared to untreated PAH controls. Molecular analysis revealed that R8-circNFXL1 modulated the miR-29b/Kcnb1 axis, providing insights into its mechanism of action.</p><p><strong>Conclusions: </strong>R8-circNFXL1 liposomes offer a promising, targeted therapeutic strategy for PAH by addressing underlying molecular mechanisms. This approach has potential implications for developing alternative treatments to improve disease management and outcomes in PAH.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"127"},"PeriodicalIF":5.8,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heme-induced lung injury in human precision cut lung slices: a new model for acute lung injury.","authors":"Namrata Kewalramani, Carlos Machahua, Thomas Michael Marti, Cas Zandbergen, Savvina Chortarea, Jessica Beretta-Piccoli, Christophe von Garnier, Patrick Dorn, Kleanthis Fytianos, Manuela Funke-Chambour","doi":"10.1186/s12931-025-03191-z","DOIUrl":"10.1186/s12931-025-03191-z","url":null,"abstract":"<p><strong>Background: </strong>Acute respiratory distress syndrome (ARDS) causes high mortality and has no specific pharmacological treatment. Scarcity of drugs against ARDS is in part due to the lack of models for ARDS. As raised serum heme levels are associated with higher mortality in patients with ARDS, we hypothesised that circulating heme contributes to ARDS pathology and can induce lung injury resembling human disease. We aimed to develop a new model for acute lung injury and ARDS research with heme-induced injury in human precision cut lung slices (PCLS).</p><p><strong>Methods: </strong>We analysed heme and its degrading enzymes along with inflammatory cytokines in patients with coronavirus disease 2019 (COVID-19) and ARDS compared to healthy adult subjects. In PCLS, we studied effects of heme on cell survival, membrane integrity, the transcriptome by gene expression and the proteome by protein expression analysis or ELISA. We also tested synergistical effects with lipopolysaccharide (LPS) on cell survival in addition to heme to simulate bacterial infection.</p><p><strong>Results: </strong>Patients with COVID-19 and ARDS had increased serum levels of heme and heme oxygenase 1 (HO-1) compared to controls. In PCLS, heme induced cell death in a dose-dependent manner, stimulated pro-inflammatory and injury signals and triggered changes to the extracellular matrix (ECM). Comparative analyses of the lung transcriptomic and proteomic signatures revealed 27 common markers (log2 fold change greater than 1, at adjusted (adj) p-value < 0.05 significant), most of which were inflammatory. Similar inflammatory cytokines were raised in blood from patients with COVID-19 and ARDS compared to controls. LPS did not increase cytotoxicity in addition to heme.</p><p><strong>Conclusion: </strong>Heme induced inflammatory cytokine release and cell death in human PCLS, resembling the patterns observed in blood samples from patients with COVID-19 and ARDS. Thus, heme-stimulated PCLS represent a novel ex vivo model for mechanistic studies for acute lung injury and ARDS.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"124"},"PeriodicalIF":5.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MARCKS protein is a potential target in a naturally occurring equine model of neutrophilic asthma.","authors":"Haleigh E Conley, Kaori Uchiumi Davis, Kenneth B Adler, Jean-Pierre Lavoie, M Katie Sheats","doi":"10.1186/s12931-025-03194-w","DOIUrl":"10.1186/s12931-025-03194-w","url":null,"abstract":"<p><strong>Background: </strong>Asthma is a chronic inflammatory airway disease that affects millions of people worldwide. Horses develop asthma spontaneously and serve as a relevant model for multiple phenotypes and endotypes of human asthma. In horses with equine asthma (EA), environmental organic dust triggers increased inflammatory cytokines, excess airway mucus, reversible bronchoconstriction, and airway inflammation. In horses with severe EA (sEA), lower airway inflammation is invariably neutrophilic, making sEA a potential model for severe neutrophilic asthma in humans. Alveolar macrophages (AM) and airway neutrophils contribute to lower airway inflammation and tissue damage through the release of cytokines and toxic mediators including reactive oxygen species. Previous work shows that the Myristoylated Alanine Rich C Kinase Substrate (MARCKS) protein is increased in activated macrophages and neutrophils and is an essential regulator of inflammatory functions in these cell types. We hypothesized that MARCKS protein would be increased in bronchoalveolar lavage (BAL) cells from horses with EA, and that in vitro inhibition of MARCKS with a specific inhibitor peptide known as MyristoylAted N-terminal Sequence (MANS), would diminish cytokine production and respiratory burst.</p><p><strong>Methods: </strong>BAL cells from two populations of healthy and asthmatic horses were evaluated for cytology and MARCKS protein analysis. Isolated alveolar macrophages and peripheral blood neutrophils were stimulated with zymosan to evaluate MARCKS inhibition in cytokine secretion and respiratory burst.</p><p><strong>Results: </strong>We found increased levels of normalized MARCKS protein in total BAL cells from horses with asthma compared to normal horses. MARCKS inhibition with the MANS peptide had no effect on zymosan-stimulated release of tumor necrosis factor alpha (TNFα) or interleukin-8 (IL-8) from alveolar macrophages but did attenuate zymosan-stimulated respiratory burst in both alveolar macrophages and peripheral blood neutrophils.</p><p><strong>Conclusions: </strong>These findings point to a possible role for MARCKS in the pathophysiology of neutrophilic equine asthma and support further investigation of MARCKS as a novel anti-inflammatory target for severe neutrophilic asthma.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"126"},"PeriodicalIF":5.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body composition, maximal fitness, and submaximal exercise function in people with interstitial lung disease.","authors":"Owen W Tomlinson, Anna Duckworth, Laura Markham, Rebecca L Wollerton, Michael Gibbons, Chris J Scotton, Craig A Williams","doi":"10.1186/s12931-025-03195-9","DOIUrl":"10.1186/s12931-025-03195-9","url":null,"abstract":"<p><strong>Background: </strong>Cardiopulmonary exercise testing (CPET) is feasible, valid, reliable, and clinically useful in interstitial lung disease (ILD). However, maximal CPET values are often presented relative to body mass, whereas fat-free mass (FFM) may better reflect metabolically active muscle during exercise. Moreover, despite the value of maximal parameters, people with ILD do not always exercise maximally and therefore clinically relevant submaximal parameters must be identified. Therefore, this study assessed peak oxygen uptake (VO_2peak) relative to FFM, identifying the validity of common scaling techniques; as well as characterising the oxygen uptake efficiency slope (OUES) and plateau (OUEP) as possible submaximal parameters.</p><p><strong>Methods: </strong>Participants with ILD underwent assessment of body composition and CPET via cycle ergometry during a single study visit. To determined effectiveness of scaling for body size, both body mass and FFM were scaled using ratio-standard (X/Y) and allometric (X/Y^b) techniques. Pearsons's correlations determined agreement between OUES, OUEP, and parameters of lung function. Cohens kappa (κ) assessed agreement between OUES, OUEP and VO_2peak.</p><p><strong>Results: </strong>A total of 24 participants (7 female; 69.8 ± 7.5 years; 17 with idiopathic pulmonary fibrosis) with ILD completed the study. Maximal exercise parameters did not require allometric scaling, and when scaled to FFM, it was shown that women have a significantly higher VO_2peak than men (p = 0.044). Results also indicated that OUEP was significantly and positively correlated with DL_CO (r = 0.719, p < 0.001), and held moderate agreement with VO_2peak (κ = 0.50, p < 0.01).</p><p><strong>Conclusion: </strong>This study identified that ratio-standard scaling is sufficient in removing residual effects of body size from VO_2peak, and that VO_2peak is higher in women when FFM is considered. Encouragingly, this study also identified OUEP as a possible alternative submaximal marker in people with ILD, and thus warrants further examination.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"123"},"PeriodicalIF":5.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burden of non-COVID-19 lower respiratory infections in China (1990-2021): a global burden of disease study analysis.","authors":"Manyu Li, Zeyu Song, Wenjun Wan, Haiwei Zhou","doi":"10.1186/s12931-025-03197-7","DOIUrl":"10.1186/s12931-025-03197-7","url":null,"abstract":"<p><strong>Background: </strong>The assessment of lower respiratory infection (LRI) mortality, incidence, and responsible pathogens in China provides a scientific basis for the prevention and management of LRI, especially for evaluating the impact of coronavirus disease 2019 (COVID-19). We provide a national estimate of the non-COVID-19 LRI burden and trends on people from 1990 to 2021 based on Global Burden of Disease (GBD) study 2021.</p><p><strong>Methods: </strong>We estimated China's mortality, incidence, disability-adjusted life years (DALYs), risk factors and aetiology attribution for LRI without including COVID-19 by using the estimated data of GBD study 2021. Mortality, incidence, DALYs, risk factors and aetiology were stratified by sex and age. Trends were evaluated using estimated annual percentage change.</p><p><strong>Results: </strong>In 2021, it is estimated that there were 206930.22 deaths (95% uncertainty interval [UI]: 171260.88-251990.47), with all-age mortality rate of 14.54 deaths (95% UI: 12.04-17.71) per 100,000 population. Compared to 2019, the all-age mortality rate had a 3.60% increase. Analyzing risk factors from 1990 to 2021, we found that the percentage of DALYs attributed to tobacco increased from 7.44% (95% UI: 1.26-15.72%) to 22.14% (95% UI: 3.28-38.41%), and that attributable to ambient particulate matter pollution increased from 19.84% (95% UI: 8.79-30.20%) to 32.72% (95% UI: 22.78-41.77%). The leading cause of mortality from LRIs remains Streptococcus pneumoniae from 1990 to 2021. However, the proportions of viral infections decreased. Compared to 2019, the proportion of deaths in 2021 caused by Influenza decreased from 13.03 to 2.70%, and the proportion of deaths due to RSV decreased from 2.21 to 0.41%.</p><p><strong>Conclusions: </strong>In China, substantial progress has been made in reducing LRI mortality, yet LRIs have remained a threat in China from 1990 to 2021. During the COVID-19 pandemic, the mortality attributable to Influenza and RSV declined. Effective vaccines and treatments targeted at the main pathogens of LRI are important.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"125"},"PeriodicalIF":5.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of a post-bronchodilator FEV₁/FVC < 0.7 on COPD diagnosis and treatment: a regression discontinuity design.","authors":"Alexander T Moffett, Scott D Halpern, Gary E Weissman","doi":"10.1186/s12931-025-03198-6","DOIUrl":"10.1186/s12931-025-03198-6","url":null,"abstract":"<p><strong>Background: </strong>Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend the diagnosis of chronic obstructive pulmonary disease (COPD) only in patients with a post-bronchodilator forced expiratory volume in 1 s to forced vital capacity ratio (FEV₁/FVC) less than 0.7. However the impact of this recommendation on clinical practice is unknown.</p><p><strong>Objective: </strong>To estimate the effect of a documented post-bronchodilator FEV₁/FVC < 0.7 on the diagnosis and treatment of COPD.</p><p><strong>Design: </strong>We used a regression discontinuity design to measure the effect of a post-bronchodilator FEV₁/FVC < 0.7 on COPD diagnosis and treatment.</p><p><strong>Participants: </strong>Patients included in a national electronic health record database who were 18 years of age and older and had a clinical encounter between 2007 and 2022 in which a post-bronchodilator FEV₁/FVC value was documented.</p><p><strong>Main measures: </strong>An encounter was associated with a COPD diagnosis if an international classification of disease code for COPD was assigned, and was associated with COPD treatment if a prescription for a medication commonly used to treat COPD was filled within 90 days.</p><p><strong>Results: </strong>Among 27,817 clinical encounters, involving 18,991 patients, a post-bronchodilator FEV₁/FVC < 0.7 was present in 14,876 (53.4%). The presence of a documented post-bronchodilator FEV₁/FVC < 0.7 increased the probability of a COPD diagnosis by 6.0% (95% confidence interval [CI] 1.1-10.9%) from 38.0% just above the 0.7 cutoff to 44.0% just below this cutoff. The presence of a documented post-bronchodilator FEV₁/FVC < 0.7 had no effect on the probability of COPD treatment (-2.1%, 95% CI -7.2 to 3.0%).</p><p><strong>Conclusions: </strong>The presence of a documented post-bronchodilator FEV₁/FVC < 0.7 had only a small effect on the diagnosis of COPD and no effect on corresponding treatment decisions.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"122"},"PeriodicalIF":5.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Describing the burden of moderate exacerbations in patients with asthma from the Extended Salford Lung Study (Ext-SLS): a retrospective cohort study.","authors":"Emma Goodall, Kieran J Rothnie, Beade Numbere, Shiyuan Zhang, Chris Compton, Robert Wood, Theo Tritton, Rosie Wild, Mark Small, Jørgen Vestbo, Ashley Woodcock","doi":"10.1186/s12931-025-03199-5","DOIUrl":"10.1186/s12931-025-03199-5","url":null,"abstract":"<p><strong>Background: </strong>There is a need for real-world data describing the frequency and impact of moderate asthma exacerbations in patients receiving inhaled corticosteroids/long-acting β₂-agonists (ICS/LABA). The Salford Lung Study (SLS) and associated extension study (Ext-SLS) evaluated ICS/LABA versus existing maintenance therapy in adults with asthma. This analysis assessed the impact of moderate exacerbations in patients from the Ext-SLS.</p><p><strong>Methods: </strong>This retrospective cohort study analysed linked primary and secondary care and patient questionnaire data from patients enrolled in the Ext-SLS (indexed April 2018-May 2019). Primary outcome was number of self-reported moderate asthma exacerbations 12 months pre-index, overall, by maintenance treatment class and asthma control status at index, using the Asthma Control Test (ACT; poor [< 16], somewhat controlled [16-18], and controlled [> 19]) and 6-item Asthma Control Questionnaire (ACQ-6; uncontrolled [≥ 1.50], partially controlled [> 0.75-<1.50], and controlled [≤ 0.75]). Secondary outcomes included index ACT and ACQ-6 score, healthcare resource utilisation (HCRU) and direct costs 12 months pre- and post-index, stratified by self-reported moderate exacerbation frequency pre-index.</p><p><strong>Results: </strong>Of 485 patients with ≥ 12 months' pre-index data, 86.6% (n = 420) self-reported moderate exacerbations, with similar frequency irrespective of maintenance treatment class (66.7-100.0%; ICS/LABA: 85.4%). Numerically greater proportions of patients self-reported a moderate exacerbation in the 12 months pre-index in ACT poor-control (n = 110/115 [95.7%]) and ACQ-6-uncontrolled (n = 200/210 [95.3%]) versus ACT- and ACQ-6-controlled (n = 205/260 [78.8%], n = 105/145 [72.4%]) groups. Symptom control worsened with increasing exacerbation frequency: mean (SD) ACT scores were 21.8 (3.3) and 15.7 (4.4) for patients with 0 or ≥ 7 events, respectively; mean (SD) ACQ-6 scores followed the same trend. Direct costs and HCRU increased with pre-index exacerbation frequency; mean (SD) all-cause and asthma-related total costs were £1509 (£2384) and £717 (£1459) for patients with no moderate exacerbations 12 months pre-index and £2002 (£2058) and £1086 (£1538) for patients with ≥ 7 exacerbations; similar trends occurred over 12 months post-index.</p><p><strong>Conclusions: </strong>Patients with asthma experience frequent moderate exacerbations, which are associated with poor asthma control, increased HCRU and costs, emphasising the poor quality of life patients experience. Tackling poor adherence, risk behaviour, and comorbidities as well as holistic management and medication review are needed.</p><p><strong>Clinical trial details: </strong>Registered on clinicaltrials.gov: NCT03152669, 12 May 2017.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"121"},"PeriodicalIF":5.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hidden in plain sight: the impact of human rhinovirus infection in adults.","authors":"Tommaso Morelli, Anna Freeman, Karl J Staples, Tom M A Wilkinson","doi":"10.1186/s12931-025-03178-w","DOIUrl":"https://doi.org/10.1186/s12931-025-03178-w","url":null,"abstract":"<p><strong>Background: </strong>Human rhinovirus (HRV), a non-enveloped RNA virus, was first identified more than 70 years ago. It is highly infectious and easily transmitted through aerosols and direct contact. The advent of multiplex PCR has enhanced the detection of a diverse range of respiratory viruses, and HRV consistently ranks among the most prevalent respiratory pathogens globally. Circulation occurs throughout the year, with peak incidence in autumn and spring in temperate climates. Remarkably, during the SARS-CoV-2 pandemic, HRV transmission persisted, demonstrating its resistance to stringent public health measures aimed at curbing viral transmission.</p><p><strong>Main body: </strong>HRV is characterised by its extensive genetic diversity, comprising three species and more than 170 genotypes. This diversity and substantial number of concurrently circulating strains allows HRVs to frequently escape the adaptive immune system and poses formidable challenges for the development of effective vaccines and antiviral therapies. There is currently a lack of specific treatments. Historically, HRV has been associated with self-limiting upper respiratory infection. However, there is now extensive evidence highlighting its significant role in severe lower respiratory disease in adults, including exacerbations of chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), as well as pneumonia. These severe manifestations can occur even in immunocompetent individuals, broadening the clinical impact of this ubiquitous virus. Consequently, the burden of rhinovirus infections extends across various healthcare settings, from primary care to general hospital wards and intensive care units. The impact of HRV in adults, in terms of morbidity and healthcare utilisation, rivals that of the other major respiratory viruses, including influenza and respiratory syncytial virus. Recognition of this substantial burden underscores the critical need for novel treatment strategies and effective management protocols to mitigate the impact of HRV infections on public health.</p><p><strong>Conclusion: </strong>This review examines the epidemiology, clinical manifestations, and risk factors associated with severe HRV infection in adults. By drawing on contemporary literature, we aim to provide a comprehensive overview of the virus's significant health implications. Understanding the scope of this impact is essential for developing new, targeted interventions and improving patient outcomes in the face of this persistent and adaptable pathogen.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"120"},"PeriodicalIF":5.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harmine alleviates LPS-induced acute lung injury by inhibiting CSF3-mediated MAPK/NF-κB signaling pathway.","authors":"Yihui Zhai, Kejie Chen, Zichuang Xu, Xiaojian Chen, Jiaying Tong, Yeying He, Chaoyue Chen, Meiqing Ding, Guang Liang, Xiaohui Zheng","doi":"10.1186/s12931-025-03196-8","DOIUrl":"https://doi.org/10.1186/s12931-025-03196-8","url":null,"abstract":"<p><strong>Background: </strong>Acute lung injury (ALI) is a life-threatening inflammatory lung disease that lacks safe and effective treatment strategies. Harmine, an alkaloid derived from Peganum harmala L plants, exhibits anti-inflammatory activity. However, the protective effect of harmine against ALI and its underlying mechanism remain unknown. This study aimed to elucidate the therapeutic effects and molecular mechanisms of harmine against ALI.</p><p><strong>Methods: </strong>The therapeutic effects of harmine were assessed in LPS-induced ALI mice. Serum, bronchoalveolar lavage fluid (BALF), lung tissues were routinely analyzed to evaluated disease severity. The anti-inflammatory mechanism was elucidated in LPS-simulated RAW264.7 cells using a series assays, including RNA-seq, gene silencing, immunofluorescence, western blotting, co-immunoprecipitation and bioinformatic analysis. The biological safety of harmine was determined both in vitro and in vivo through cytotoxicity test, long-term cell proliferation test, acute toxicity test in mice, and assessments of liver and kidney function and structural changes.</p><p><strong>Results: </strong>The results showed that harmine inhibited the expression and secretion of LPS-induced inflammatory factors (IL-6, IL-1β and TNF-α) and reduced inflammatory cell infiltration in the lungs, resulting in alleviated LPS-induced histopathological changes and injury in mice. Mechanically, the findings revealed that harmine does not disrupt the TLR4-MD2 interaction but instead attenuates inflammation by suppressing CSF3 transcription and expression, leading to the inhibition of the MAPK/NF-κB signaling pathway activation induced by LPS stimulation. Additionally, both in vitro and in vivo studies demonstrated that harmine administration does not exhibit obvious cytotoxicity or long-term cell proliferation inhibition, nor does it cause functional or organic lesions the liver and kidney in mice, or other acute toxic effects.</p><p><strong>Conclusions: </strong>These findings elucidated that the anti-inflammatory activity of harmine was achieved through the CSF3-mediated inactivation of the MAPK/NF-κB signaling pathway, suggesting that harmine could serve as a promising therapeutic drug for ALI and other inflammatory diseases.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"119"},"PeriodicalIF":5.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of urban airborne particulate matter exposure on the human upper respiratory tract microbiome: a systematic review.","authors":"Sonia Arca-Lafuente, Beatriz Nuñez-Corcuera, Rebeca Ramis, Spyros Karakitsios, Denis Sarigiannis, Saúl García Dos Santos, Amanda Fernández-Rodríguez, Verónica Briz","doi":"10.1186/s12931-025-03179-9","DOIUrl":"https://doi.org/10.1186/s12931-025-03179-9","url":null,"abstract":"<p><p>Exposure to air pollutants has a direct impact on human health, resulting in increased mortality rates. Airborne particulate matter (PM) has major adverse effects on health and can be classified as high-risk respiratory particles (fine/PM_2.5, aerodynamic diameter < 2.5 µm) or thoracic particles (coarse/PM₁₀, aerodynamic diameter < 10 µm). In addition, airborne PM can carry microbial communities that alter the commensal microbiota and lead to dysbiosis. Our aim was to synthesize the current research evidence describing the association between air pollution exposure and the microbiome composition of the upper respiratory tract (URT) of the adult population. In this work, a systematic search of the PubMed, EMBASE and Scopus databases was conducted. A total of 9 studies published from 2018 to 2023 were included. 66.5% of the participants were exposed to PM_2.5 concentrations higher than 40 µg/m³, and data showed that PM_2.5 atmospheric levels were positively correlated with PM₁₀ (r_s = 0.95, p < 0.001). All the reviewed studies performed 16S rRNA sequencing of the V3-V4 region from URT samples, using different methods. Overall, evidence of URT microbiome alterations after high PM exposure was observed, with seasonal and geographical influence. Discordant findings were found about bacterial diversity, with a predominant decrease after exposure to high PM levels. Regarding microbiome composition, the relative abundance of the Actinobacteria phylum declined following exposure to high levels of PM, but that of Bacteroidetes and Fusobacteria increased. The studies showed a low-middle risk of bias due to heterogeneity regarding sample processing, sequencing methods, and confounder control. To confirm the observed evidence of an association between PM levels and alterations in the URT microbiome, we strongly recommend that future research work be conducted in accordance with standard guidelines for reporting microbiome studies. In summary, the entry of fine and coarse particles into the URT is associated with microbial dysbiosis, increasing the risk of developing respiratory diseases and allergies.Prospero registration: This systematic review was registered on PROSPERO (#CRD42023416230).</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"118"},"PeriodicalIF":5.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}