FGF21 Signaling Exerts Anti-Fibrotic Properties During Pulmonary Fibrosis.

Rationale: Idiopathic Pulmonary Fibrosis (IPF) is a lethal disease with limited therapeutic options. FGF21, an endocrine fibroblast growth factor that acts through the FGFR1/KLB pathway, mitigates liver fibrosis.

Objectives: We hypothesized that FGF21 could exert anti-fibrotic properties in the lung.

SDePER: a hybrid machine learning and regression method for cell-type deconvolution of spatial barcoding-based transcriptomic data.

Spatial barcoding-based transcriptomic (ST) data require deconvolution for cellular-level downstream analysis. Here we present SDePER, a hybrid machine learning and regression method to deconvolve ST data using reference single-cell RNA sequencing (scRNA-seq) data. SDePER tackles platform effects between ST and scRNA-seq data, ensuring a linear relationship between them while addressing sparsity and spatial correlations in cell types across capture spots.

Identification of FGFR4 as a regulator of myofibroblast differentiation in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with limited therapeutic options. Fibroblast growth factor receptor-4 (FGFR4) is a known receptor for several paracrine fibroblast growth factors (FGFs). FGFR4 is also the main receptor for FGF19, an endocrine FGF that was demonstrated by our group to have antifibrotic properties in the lung.

Similarities and differences of interstitial lung disease associated with pathogenic variants in SFTPC and ABCA3 in adults.

Background And Objective: Variants in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults, with few studies in adults.

Methods: We conducted a multicentre retrospective study of all consecutive adult patients diagnosed with ILD associated with variants in SFTPC or ABCA3 in the French rare pulmonary diseases network, OrphaLung. Variants and chest computed tomography (CT) features were centrally reviewed.

Unagi: Deep Generative Model for Deciphering Cellular Dynamics and In-Silico Drug Discovery in Complex Diseases.

Human diseases are characterized by intricate cellular dynamics. Single-cell sequencing provides critical insights, yet a persistent gap remains in computational tools for detailed disease progression analysis and targeted in-silico drug interventions. Here, we introduce UNAGI, a deep generative neural network tailored to analyze time-series single-cell transcriptomic data.

Comparison between computerised lung SPECT-CT and noncontrast thoracic HRCT for quantitative analysis of post-acute COVID-19 pulmonary vascular pruning.

https://bit.ly/3qAQZDW.

Peripheral Blood Single-Cell Sequencing Uncovers Common and Specific Immune Aberrations in Fibrotic Lung Diseases.

Rationale And Objectives: The extent and commonality of peripheral blood immune aberrations in fibrotic interstitial lung diseases are not well characterized. In this study, we aimed to identify common and distinct immune aberrations in patients with idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (FHP) using cutting-edge single-cell profiling technologies.

Methods: Single-cell RNA sequencing was performed on patients and healthy controls' peripheral blood and bronchoalveolar lavage samples using 10X Genomics 5' gene expression and V(D)J profiling.

A hybrid machine learning and regression method for cell type deconvolution of spatial barcoding-based transcriptomic data.

Spatial barcoding-based transcriptomic (ST) data require cell type deconvolution for cellular-level downstream analysis. Here we present SDePER, a hybrid machine learning and regression method, to deconvolve ST data using reference single-cell RNA sequencing (scRNA-seq) data. SDePER uses a machine learning approach to remove the systematic difference between ST and scRNA-seq data (platform effects) explicitly and efficiently to ensure the linear relationship between ST data and cell type-specific expression profile.

Identification of Paired-related Homeobox Protein 1 as a key mesenchymal transcription factor in pulmonary fibrosis.

Matrix remodeling is a salient feature of idiopathic pulmonary fibrosis (IPF). Targeting cells driving matrix remodeling could be a promising avenue for IPF treatment. Analysis of transcriptomic database identified the mesenchymal transcription factor PRRX1 as upregulated in IPF.

Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal disorder. Two U.S.

From COVID to fibrosis: lessons from single-cell analyses of the human lung.

The increased resolution of single-cell RNA-sequencing technologies has led to major breakthroughs and improved our understanding of the normal and pathologic conditions of multiple tissues and organs. In the study of parenchymal lung disease, single-cell RNA-sequencing has better delineated known cell populations and identified novel cells and changes in cellular phenotypes and gene expression patterns associated with disease. In this review, we aim to highlight the advances and insights that have been made possible by applying these technologies to two seemingly very different lung diseases: fibrotic interstitial lung diseases, a group of relentlessly progressive lung diseases leading to pulmonary fibrosis, and COVID-19 pneumonia, an acute viral disease with life-threatening complications, including pulmonary fibrosis.

FGF19 Is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits Lung Fibrosis in Mice.

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with limited therapeutic possibilities. FGF19 (fibroblast growth factor 19), an endocrine FGF, was recently shown to decrease liver fibrosis. To ask whether FGF19 had antifibrotic properties in the lung and decipher its effects on common features associated with lung fibrogenesis, we assessed, by ELISA, FGF19 concentrations in plasma and BAL fluids obtained from control subjects and patients with IPF.

Lesson of the month: management for aspiration of a silver nitrate pencil tip during tracheostomy care.

We present the cases of two laryngectomised patients who were treated for granulomas of the tracheostomy orifice with a silver nitrate pencil. During tracheostomy care, the tip broke off, was aspirated and fell into the bronchial tree. Necrotising ulcerative injuries of the right bronchial tree with clear delineation were found without lesions in the subsegmental division.

Chaotic activation of developmental signalling pathways drives idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterised by an important remodelling of lung parenchyma. Current evidence indicates that the disease is triggered by alveolar epithelium activation following chronic lung injury, resulting in alveolar epithelial type 2 cell hyperplasia and bronchiolisation of alveoli. Signals are then delivered to fibroblasts that undergo differentiation into myofibroblasts.

ERS International Congress 2019: highlights from Best Abstract awardees.

http://bit.ly/2XWlD7Y.

Anti-parietal cell autoimmunity is associated with an accelerated decline of lung function in IPF patients.

Background: Autoantibodies against lung epithelial antigens are often detected in patients with Idiopathic Pulmonary Fibrosis (IPF). Anti-Parietal Cell Antibodies (APCA) target the H+/K+ATPase (proton pump). APCA prevalence and lung H+/K+ATPase expression was never studied in IPF patients.

Human airway trypsin-like protease exerts potent, antifibrotic action in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by the deposition of excessive extracellular matrix and the destruction of lung parenchyma, resulting from an aberrant wound-healing response. Although IPF is often associated with an imbalance in protease activity, the mechanisms underlying the sustained repair mechanisms are not fully understood. Here, we addressed the role of the recently identified, membrane-anchored serine protease human airway trypsin-like protease (HAT).