unilateral-lung-volume-analysis-using-micro-ct-for-enhanced

Unilateral Lung Volume Analysis Using Micro-CT for Enhanced Assessment of Pulmonary Fibrosis in Preclinical Models

Pulmonary fibrosis (PF) is a progressive and irreversible interstitial lung disease characterized by poor prognosis and limited treatment options. The ...

The First Affiliated Hospital of Guangzhou Medical University

To investigate CTX-M genotypes among extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) isolated from patients with community-onset and hospital-onset infections in China, their clonality and the distribution of CTX-M variants in different specimens of community-onset and hospital-onset infections.

Dominance of CTX-M-type extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolated from patients with community-onset and hospital-onset infection in China.

Factors attributable to the level of fraction of exhaled nitric oxide (FeNO) in different age groups of asthmatic children are still lack of report.

Factors associated with exhaled nitric oxide in children with asthma and allergic rhinitis.

Reported data on the disease spectrum of interstitial lung diseases (ILDs) of China are sparse and varied. We aimed to investigate the spectrum of ILDs and the distribution of diagnostic methods under a uniform diagnosis.

The interstitial lung disease spectrum under a uniform diagnostic algorithm: a retrospective study of 1,945 individuals.

To evaluate the efficacy and safety of ultra-low dose (100 mg) rituximab (RTX) administration in anti-melanoma differentiation-associated gene 5 (MDA5) positive patients with polymyositis/dermatomyositis (PM/DM) associated interstitial lung disease.

Ultra-low dose rituximab as add-on therapy in anti-MDA5-positive patients with polymyositis /dermatomyositis associated ILD.

The application of transbronchial lung cryobiopsy (TBLC) and uniportal and tubeless video-assisted thoracic surgery (UT-VATS) in the multidisciplinary diagnosis of interstitial lung disease (ILD) has not been demonstrated in real-world clinical practice. This prospective study included 137 patients with no definitive diagnosis who were the subject of two multidisciplinary discussion (MDD) sessions. As indicated in the first MDD, 67 patients underwent UT-VATS and 70 underwent TBLC. The specificity of biopsy information and its contribution to final MDD diagnosis were evaluated in the second MDD. The post-operative complications and hospitalization costs associated with the two biopsy methods were compared. UT-VATS was favored for patients initially diagnosed with idiopathic pulmonary fibrosis (IPF), bronchiolitis-associated interstitial lung disease (RB-ILD)/desquamative interstitial pneumonia (DIP) and undefined idiopathic interstitial pneumonia (UIIP), while TBLC was preferred for pulmonary lymphangioleiomyomatosis (PLAM) and pulmonary alveolar proteinosis (PAP). The spirometry parameters were better in patients who underwent UT-VATS than those who underwent TBLC. UT-VATS provided more specific pathological results than TBLC (85.7 vs 73.7%,  = 0.06). In patients initially diagnosed with UIIP, pathological information from UT-VATS was more clinically useful than that obtained from TBLC, although both tests contributed similarly to cases initially diagnosed as interstitial pneumonia with auto-immune features (IPAF)/connective tissue disease-related ILD (CTD-ILD). The safety of UT-VATS was comparable with TBLC although TBLC was cheaper during hospitalization (US$4,855.7 vs US$3,590.9,  < 0.001). multidisciplinary discussion decisions about biopsies were driven by current knowledge of sampling and diagnosis capacity as well as potential risks of different biopsy methods. The current MDD considered UT-VATS more informative than TBLC in cases initially diagnosed as UIIP although they were equally valuable in patients initially diagnosed with IPAF/CTD-ILD.

The Application of Transbronchial Lung Cryobiopsy and Uniportal and Tubeless Video-Assisted Thoracic Surgery in the Multidisciplinary Diagnosis of Interstitial Lung disease-A Real-World Prospective Study.

Idiopathic pulmonary fibrosis (IPF) mainly occurs in elderly people over the age of sixty. IPF pathogenesis is associated with alveolar epithelial cells (AECs) senescence. Activation of PI3K/AKT signaling induced by insulin-like growth factor 1 (IGF1) participates in AEC senescence and IPF by releasing CTGF, TGF-β1, and MMP9. Our previous study demonstrated that core fucosylation (CF) modification, catalyzed by a specific core fucosyltransferase (FUT8) can regulate the activation of multiple signaling pathways, and inhibiting CF can alleviate pulmonary fibrosis in mice induced by bleomycin. However, whether CF is involved in IGF1-mediated AEC senescence in IPF remains unclear. In this study, we found that the IGF1/PI3K/AKT signaling pathway was activated in IPF lung tissue. Meanwhile, CF was present in senescent AECs. We also showed that IGF1 could induce AECs senescence with enhanced CF  and . Inhibiting CF alleviated AECs senescence and pulmonary fibrosis induced by IGF1. In addition, activation of IGF1/PI3K/AKT signaling depends on CF. In conclusion, this study confirmed that CF is an important target regulating the IGF1 signaling pathway in AEC senescence and IPF, which might be a candidate target to treat IPF in the future.

Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation.

Allergen nasal challenge can induce increase of eosinophils in sputum, but report about eosinophilic inflammation in upper airway after allergen bronchial challenge in Chinese asthmatics was rare. The article aims to evaluate response of upper and lower airways to house dust mite (HDM) allergen bronchial challenge.

Response of upper and lower airway inflammation to bronchial challenge with house dust mite in Chinese asthmatics: a pilot study.

Alveolar epithelial cell senescence is a core event in the development of pulmonary fibrosis. Endoplasmic reticulum stress accelerates cellular senescence significantly; however, whether this stress promotes alveolar epithelial cell senescence in pulmonary fibrosis and its mechanisms are unclear. As a common intersection of endoplasmic reticulum stress signaling pathways, CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) activates the oxidative stress pathway, which in turn accelerates cellular senescence. Therefore, we speculated CHOP pathway activation would affect endoplasmic reticulum stress-induced alveolar epithelial cell senescence in pulmonary fibrosis. In this study, we observed that alveolar epithelial cell senescence was accompanied by CHOP overexpression in idiopathic pulmonary fibrosis lung tissues. Bleomycin and tunicamycin combination models in vivo and in vitro showed that CHOP downregulation rescued alveolar epithelial cell senescence, reduced fibroblast activation mediated by the senescence-associated secretory phenotype, and improved pulmonary fibrosis pathology. Mechanistic studies showed that CHOP accelerated alveolar epithelial cell senescence by promoting reactive oxygen species generation, which activated the nuclear factor-kappa B pathway. Our study suggested that CHOP activates the downstream nuclear factor-kappa B pathway, thus contributing to endoplasmic reticulum stress-induced alveolar epithelial cell senescence and pulmonary fibrosis.

CCAAT/enhancer-binding protein (C/EBP) homologous protein promotes alveolar epithelial cell senescence via the nuclear factor-kappa B pathway in pulmonary fibrosis.

 Idiopathic pulmonary fibrosis (IPF) is an aggressive fibrotic pulmonary disease with spatially and temporally heterogeneous alveolar lesions. There are no early diagnostic biomarkers, limiting our understanding of IPF pathogenesis.  Lung tissue from surgical lung biopsy of patients with early-stage IPF ( = 7), transplant-stage IPF ( = 2), and healthy controls ( = 6) were subjected to mRNA sequencing and verified by real-time quantitative PCR (RT-qPCR), immunohistochemistry, Western blot, and single-cell RNA sequencing (scRNA-Seq).  Three hundred eighty differentially expressed transcripts (DETs) were identified in IPF that were principally involved in extracellular matrix (ECM) remodeling, lipid metabolism, and immune effect. Of these DETs, 21 (DMD, MMP7, POSTN, ECM2, MMP13, FASN, FADS1, SDR16C5, ACAT2, ACSL1, CYP1A1, UGT1A6, CXCL13, CXCL5, CXCL14, IL5RA, TNFRSF19, CSF3R, S100A9, S100A8, and S100A12) were selected and verified by RT-qPCR. Differences in DMD, FASN, and MMP7 were also confirmed at a protein level. Analysis of scRNA-Seq was used to trace their cellular origin to determine which lung cells regulated them. The principal cell sources of DMD were ciliated cells, alveolar type I/II epithelial cells (AT cells), club cells, and alveolar macrophages (AMs); MMP7 derives from AT cells, club cells, and AMs, while FASN originates from AT cells, ciliated cells, and AMs.  Our data revealed a comprehensive transcriptional mRNA profile of IPF and demonstrated that ECM remodeling, lipid metabolism, and immune effect were collaboratively involved in the early development of IPF.

Complex Involvement of the Extracellular Matrix, Immune Effect, and Lipid Metabolism in the Development of Idiopathic Pulmonary Fibrosis.

Lung resident mesenchymal stem cells (LR-MSCs) play an important role in idiopathic pulmonary fibrosis (IPF) by transforming into myofibroblasts, thereby losing their repair ability. Evidence suggests that key proteins of multiple signaling pathways are involved in myofibroblast differentiation of LR-MSCs, such as β-Catenin and GLI family zinc finger 1 (GLI1). These proteins are regulated by SUMO (small ubiquitin-like modifier) modification, which is a post-translational modification that promotes protein degradation, while Sumo specific protein 1 (SENP1)-mediated deSUMOylation produces the opposite biological effects. Therefore, we speculated that SENP1 might be a potential target for treating pulmonary fibrosis by preventing the myofibroblast differentiation of LR-MSCs.

SENP1 regulates the transformation of lung resident mesenchymal stem cells and is associated with idiopathic pulmonary fibrosis progression.

To explore whether cytokines could be potential biomarkers to predict the occurrence of the progressive fibrosis (PF) phenotype among patients with interstitial pneumonia with autoimmune features (IPAF).

Characterizing the lavage and serum cytokine profiles of interstitial pneumonia with autoimmune features and their implications for progressive fibrosis.

Fibroblast activation plays an important role in the occurrence and development of idiopathic pulmonary fibrosis (IPF), which is a progressive, incurable, and fibrotic lung disease. However, the underlying mechanism of fibroblast activation in IPF remains elusive. Here, we showed that the expression levels of STX11 and SNAP25 were downregulated in the lung tissues from patients with IPF and mice with bleomycin (BLM)-induced lung fibrosis as well as in the activated fibroblasts. Upregulation of STX11 or SNAP25 suppressed TGF-β1-induced activation of human lung fibroblasts (HLFs) via promoting autophagy. However, they failed to suppress fibroblast actviation when autophagy was blocked with the use of chloroquine (CQ). In addition, STX11 or SNAP25 could inhibit TGF-β1-induced fibroblast proliferation and migration. In vivo, overexpression of STX11 exerted its protective role in the mice with BLM-induced lung fibrosis. STX11 and SNAP25 mutually promoted expression of each other. Co-IP assay indicated that STX11 has an interaction with SNAP25. Mechanistically, STX11-SNAP25 interaction activated fibroblast autophagy and further inhibited fibroblast activation via blocking the PI3K/AKT/mTOR pathway. Overall, the results suggested that STX11-SNAP25 interaction significantly inhibited lung fibrosis by promoting fibroblast autophagy and suppressing fibroblast activation via blocking the PI3K/ATK/mTOR signaling pathway. Therefore, STX11 serves as a promising therapeutic target in IPF.

Article	Year
Dominance of CTX-M-type extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolated from patients with community-onset and hospital-onset infection in China. PloS one\| PubMed ID: 24983621	2014
Factors associated with exhaled nitric oxide in children with asthma and allergic rhinitis. The clinical respiratory journal\| PubMed ID: 31602812	2020
The interstitial lung disease spectrum under a uniform diagnostic algorithm: a retrospective study of 1,945 individuals. Journal of thoracic disease\| PubMed ID: 32802448	2020
Ultra-low dose rituximab as add-on therapy in anti-MDA5-positive patients with polymyositis /dermatomyositis associated ILD. Respiratory medicine\| PubMed ID: 33032789	2020
The Application of Transbronchial Lung Cryobiopsy and Uniportal and Tubeless Video-Assisted Thoracic Surgery in the Multidisciplinary Diagnosis of Interstitial Lung disease-A Real-World Pros... Frontiers in molecular biosciences\| PubMed ID: 34222336	2021
Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation. Aging\| PubMed ID: 34329195	2021
Response of upper and lower airway inflammation to bronchial challenge with house dust mite in Chinese asthmatics: a pilot study. Journal of thoracic disease\| PubMed ID: 34527337	2021
CCAAT/enhancer-binding protein (C/EBP) homologous protein promotes alveolar epithelial cell senescence via the nuclear factor-kappa B pathway in pulmonary fibrosis. The international journal of biochemistry & cell biology\| PubMed ID: 34954323	2022
Complex Involvement of the Extracellular Matrix, Immune Effect, and Lipid Metabolism in the Development of Idiopathic Pulmonary Fibrosis. Frontiers in molecular biosciences\| PubMed ID: 35174208	2021
SENP1 regulates the transformation of lung resident mesenchymal stem cells and is associated with idiopathic pulmonary fibrosis progression. Cell communication and signaling : CCS\| PubMed ID: 35836260	2022
Characterizing the lavage and serum cytokine profiles of interstitial pneumonia with autoimmune features and their implications for progressive fibrosis. Rheumatology (Oxford, England)\| PubMed ID: 37606981	2024
Overexpression of STX11 alleviates pulmonary fibrosis by inhibiting fibroblast activation via the PI3K/AKT/mTOR pathway. Signal transduction and targeted therapy\| PubMed ID: 39523374	2024

Shu Xia

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