Project description:Pleural infection is a severe and complicated disease with increasing incidence worldwide and is characterised by substantial associated morbidity and mortality.1,2 Although it is accepted that the disease is heterogeneous, and there is a validated clinical prediction score (RAPID)3,4, the biological endotypes of pleural infection remain elusive and pleural fluid specific criteria to assess the intrapleural response are not available. A better understanding of pleural infection subtypes could lead to improved treatment strategies and clinical outcomes. All patients with pleural infection follow the same clinical journey which focusses on hospital admission, pleural fluid drainage and administration of antibiotics however, their recovery progress and clinical outcomes differ significantly.1,2 A subgroup of patients exhibits ineffective or failed intrapleural fibrinolysis leading to the development of fibrous septations which further complicates treatment. Consequently, approximately 30% of patients do not respond to treatment and require invasive treatments including surgical drainage. Tandem mass spectrometry is a high-throughput proteomics assay which is a reliable, unbiased, and hypothesis-free analytical method for investigating the underlying biology of disease using clinical specimens.5 The pleural fluid proteome faithfully reflects the intrapleural environment and could be utilised to identify disease key mediators, biomarkers, and treatment targets. For instance, pleural fluid pH, glucose and lactate dehydrogenase are used as clinical biochemistry markers for diagnosing patients with pleural infection.1 Our study (The Oxford Pleural Infection Endotyping Study, TORPIDS 2) applied mass spectrometry to pleural fluid specimens (n=80) from the PILOT trial.4 Our primary aims were to discover endotypes in pleural infection, characterise the intrapleural immune response and investigate the association between patient endotypes and high-precision bacterial patterns. We assessed the association between pleural infection endotypes and important clinical outcomes (1-year survival and need for surgery)
2026-02-23 | PXD054108 | Pride
Project description:The bacteriology of pleural infection using next generation sequencing: The Oxford Pleural Infection Metagenomics Studies (TORPIDS)
Project description:Pleural fibrosis is defined as an excessive deposition of extracellular matrix (ECM) that results in destruction of the normal pleural tissue architecture and compromised function. However there is currently no effective medication for pleural fibrosis. Understanding the detailed mechanisms of pleural fibrosis is an important unmet need which could lead to the identification of new targets for treatment of this condition. microRNAs (miRNAs) play an important role in the posttranscriptional control of gene expression. In our study, cellular fractions from TBPE contained activities capable of promoting fibrosis-like behavior in pleural mesothelial cells (PMCs), the goal of this study is to compare the exosomal miRNA composition of TBPE and TPE. We isolated exosomes from transudative pleural effusion and tuberculous pleural effusions and performed miRNA sequencing. Our study represents the first detailed analysis of exosomal miRNA composition of TBPE and TPE with biologic replicates, generated by miRNA-Seq technology.
Project description:Next-generation proteomics of Vero E6 cells infected by Italy-INMI1 SARS-CoV-2 virus for defining relevant viral peptides for detection. Cells from Day4 post-infection at 0.01 multiplicity of infection. [Original project description]
Project description:The recent revolution in tissue-resident macrophage biology has resulted largely from murine studies performed in the C57BL/6 strain. Here, we provide a comprehensive analysis of immune cells in the pleural cavity using both C57BL/6 and BALB/c mice. Unlike C57BL/6 mice, naïve tissue-resident Large Cavity Macrophages (LCM) of BALB/c mice failed to fully implement the tissue residency programme. Following infection with a pleural-dwelling nematode these pre-existing differences were accentuated with LCM expansion occurring in C57BL/6 but not BALB/c mice. While infection drove monocyte recruitment in both strains, only in C57BL/6 mice were monocytes able to integrate into the resident pool. Monocyte to macrophage conversion required both T cells and IL-4Rα signalling. Host genetics are therefore a key influence on tissue resident macrophage biology, and during nematode infection Th2 cells control the differentiation pathway of tissue resident macrophages.
Project description:RATIONALE: Using BG00001 to insert the gene for interferon-beta into a person’s pleural cavity may improve the body’s ability to fight cancer.
PURPOSE: Phase I trial to study the effectiveness of intrapleural BG00001 in treating patients who have malignant pleural mesothelioma or malignant pleural effusions.
