orthotopic-left-lung-transplantation-in-rats

Orthotopic Left Lung Transplantation in Rats

The rat left lung orthotopic transplantation model is an essential tool in lung transplant research. Although lung transplantation is a complex procedure, ...

The First Affiliated Hospital of Guangzhou Medical University

Effective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus . In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. In this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500 mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events. A total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose. Although randomized trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating the COVID-19 pandemic.

Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19.

Nebulized amphotericin B (NAB) is recommended for preventing invasive fungal diseases (IFDs) after lung transplantation. However, the optimal duration of NAB treatment is still unknown. This study aimed to compare the effectiveness of three different durations of antifungal prophylaxis with NAB after lung transplantation: a prolonged course beyond post-transplant 3 months, a medium course of 2 weeks to 3 months, and a short course of less than 2 weeks.

Efficacy of different durations of antifungal prophylaxis with nebulized amphotericin B after lung transplantation: a retrospective cohort study.

Increasing evidence revealed that lung microbiota dysbiosis was associated with pulmonary infection in lung transplant recipients (LTRs). Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungal pathogen that frequently causes lethal pneumonia in LTRs. However, the lung microbiota in LTRs with P. jirovecii pneumonia (PJP) remains unknow.

Alterations of lung microbiota in lung transplant recipients with pneumocystis jirovecii pneumonia.

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.

Overexpression of STX11 alleviates pulmonary fibrosis by inhibiting fibroblast activation via the PI3K/AKT/mTOR pathway.

The composition and characteristics of airway microbiota offer critical insights for clinical decision-making. Current research on chronic lung diseases shows differences in the composition and characteristics of upper and lower respiratory tract microbiota compared with healthy individuals. However, the temporal changes of these microbial communities in lung transplant recipients remain poorly characterized.

Article	Year
Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19. National science review\| PubMed ID: 34676087	2020
Efficacy of different durations of antifungal prophylaxis with nebulized amphotericin B after lung transplantation: a retrospective cohort study. Journal of thoracic disease\| PubMed ID: 37969308	2023
Alterations of lung microbiota in lung transplant recipients with pneumocystis jirovecii pneumonia. Respiratory research\| PubMed ID: 38486264	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
Characteristics of upper and lower respiratory tract microbiota after lung transplantation. Respiratory research\| PubMed ID: 40281571	2025

Xiaohua Wang

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