Iván O. Rosas
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View article: Inhibition of epithelial cell YAP-TEAD/LOX signaling attenuates pulmonary fibrosis in preclinical models
Inhibition of epithelial cell YAP-TEAD/LOX signaling attenuates pulmonary fibrosis in preclinical models Open
View article: Macropinocytosis inhibition attenuates pro-fibrotic responses in lung fibroblasts and pulmonary fibrosis
Macropinocytosis inhibition attenuates pro-fibrotic responses in lung fibroblasts and pulmonary fibrosis Open
Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disorder with limited treatment options. Macropinocytosis is one of the key cellular processes involved in nutrient consumption from the extracellular environment under stre…
View article: Single cell transcriptomics in a treatment-segregated cohort exposes a STAT3-regulated therapeutic gap in idiopathic pulmonary fibrosis
Single cell transcriptomics in a treatment-segregated cohort exposes a STAT3-regulated therapeutic gap in idiopathic pulmonary fibrosis Open
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic pulmonary disease with unknown etiology. Since approved idiopathic pulmonary fibrosis (IPF) drugs only slow disease progression, novel therapeutics are required that improve cli…
View article: A deep generative model for deciphering cellular dynamics and in silico drug discovery in complex diseases
A deep generative model for deciphering cellular dynamics and in silico drug discovery in complex diseases Open
Human diseases are characterized by intricate cellular dynamics. Single-cell transcriptomics provides critical insights, yet a persistent gap remains in computational tools for detailed disease progression analysis and targeted in silico d…
View article: Approach to the Evaluation and Management of Interstitial Lung Abnormalities: An Official American Thoracic Society Clinical Statement
Approach to the Evaluation and Management of Interstitial Lung Abnormalities: An Official American Thoracic Society Clinical Statement Open
Background: There is growing interest in identifying early stages of interstitial lung disease (ILD) to improve patient outcomes. This document reviews updated evidence on interstitial lung abnormalities (ILAs); provides suggestions…
View article: Alveolar epithelial cell plasticity and injury memory in human pulmonary fibrosis
Alveolar epithelial cell plasticity and injury memory in human pulmonary fibrosis Open
Acute and repetitive lung epithelial injury can lead to irreversible and even progressive pulmonary fibrosis; Idiopathic pulmonary fibrosis (IPF) is a fatal disease and quintessential example of this phenomenon. The composition of epitheli…
View article: Secreted Phosphoprotein 1 in Lung Diseases
Secreted Phosphoprotein 1 in Lung Diseases Open
Secreted phosphoprotein 1 (SPP1), also known as osteopontin (OPN) or early T lymphocyte activation protein 1 (ETA-1), is a multifunctional protein involved in numerous biological processes, including immune modulation, stress response, and…
View article: Long-Term Clinical Outcomes of Adults Hospitalized for COVID-19 Pneumonia
Long-Term Clinical Outcomes of Adults Hospitalized for COVID-19 Pneumonia Open
We conducted a multicenter, observational, 12-month follow-up study to identify the extended health burden of severe COVID-19 pneumonia by characterizing long-term sequelae of acute infection in participants previously enrolled in clinical…
View article: Let-7 restrains an epigenetic circuit in AT2 cells to prevent fibrogenic intermediates in pulmonary fibrosis
Let-7 restrains an epigenetic circuit in AT2 cells to prevent fibrogenic intermediates in pulmonary fibrosis Open
View article: Early nintedanib deployment in COVID-19 interstitial lung disease (ENDCOV-I): study protocol of a randomised, double-blind, placebo-controlled trial
Early nintedanib deployment in COVID-19 interstitial lung disease (ENDCOV-I): study protocol of a randomised, double-blind, placebo-controlled trial Open
Introduction In December 2019, the novel SARS-CoV-2 triggered a global pneumonia outbreak, leading to millions of deaths worldwide. A subset of survivors faces increased morbidity and mortality, particularly due to subacute lung injury evo…
View article: SINGLE-CELL ANALYSIS OF SOMATIC MUTATIONS IN HUMAN LUNG REVEALS ASSOCIATION WITH TRANSCRIPTIONAL CHANGES IN AGING
SINGLE-CELL ANALYSIS OF SOMATIC MUTATIONS IN HUMAN LUNG REVEALS ASSOCIATION WITH TRANSCRIPTIONAL CHANGES IN AGING Open
Age is a major risk factor for lung disease. Accumulation of somatic mutations has been implicated in both aging and cellular senescence. We analyzed somatic mutations called from single-cell RNAseq (scRNAseq) data. scRNAseq was performed …
View article: ASSOCIATION OF INSULIN RESISTANCE WITH RADIOGRAPHIC LUNG ABNORMALITIES AND INCIDENT LUNG DISEASE: THE FRAMINGHAM OFFSPRING STUDY
ASSOCIATION OF INSULIN RESISTANCE WITH RADIOGRAPHIC LUNG ABNORMALITIES AND INCIDENT LUNG DISEASE: THE FRAMINGHAM OFFSPRING STUDY Open
ObjectiveInsulin resistance (IR) may be a risk factor for lung disease, but objective evidence is limited. We sought to define the relationship of longitudinal IR to radiographic imaging outcomes and examiner-identified incident lung disea…
View article: ASSOCIATION OF INSULIN RESISTANCE WITH RADIOGRAPHIC LUNG ABNORMALITIES AND INCIDENT LUNG DISEASE: THE FRAMINGHAM OFFSPRING STUDY
ASSOCIATION OF INSULIN RESISTANCE WITH RADIOGRAPHIC LUNG ABNORMALITIES AND INCIDENT LUNG DISEASE: THE FRAMINGHAM OFFSPRING STUDY Open
ObjectiveInsulin resistance (IR) may be a risk factor for lung disease, but objective evidence is limited. We sought to define the relationship of longitudinal IR to radiographic imaging outcomes and examiner-identified incident lung disea…
View article: Precision-Cut Lung Slices: Emerging Tools for Preclinical and Translational Lung Research: An Official American Thoracic Society Workshop Report
Precision-Cut Lung Slices: Emerging Tools for Preclinical and Translational Lung Research: An Official American Thoracic Society Workshop Report Open
The urgent need for effective treatments for acute and chronic lung diseases underscores the significance of developing innovative preclinical human research tools. The 2023 ATS Workshop on Precision Cut Lung Slices (PCLS) brought together…
View article: QM107, a novel CD148 (RTP Type J) activating peptide therapy for treating neovascular age‐related macular degeneration
QM107, a novel CD148 (RTP Type J) activating peptide therapy for treating neovascular age‐related macular degeneration Open
Background and Purpose Angiogenesis is a pathological component of neovascular age‐related macular degeneration. Current therapies, although successful, are prone to high levels of patient non‐response and a loss of efficacy over time, ind…
View article: LAPTM4B Alleviates Pulmonary Fibrosis by Enhancing NEDD4L-Mediated TGF-β Signaling Suppression
LAPTM4B Alleviates Pulmonary Fibrosis by Enhancing NEDD4L-Mediated TGF-β Signaling Suppression Open
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with fatal outcome and a poorly understood pathogenesis. The lysosomal protein transmembrane 4 beta (LAPTM4B), a multi-transmembrane endo-lysosomal membrane prot…
View article: LAPTM4B Alleviates Pulmonary Fibrosis by Enhancing NEDD4L-Mediated TGF-β Signaling Suppression
LAPTM4B Alleviates Pulmonary Fibrosis by Enhancing NEDD4L-Mediated TGF-β Signaling Suppression Open
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with fatal outcome and a poorly understood pathogenesis. The lysosomal protein transmembrane 4 beta (LAPTM4B), a multi-transmembrane endo-lysosomal membrane prot…
View article: SDePER: a hybrid machine learning and regression method for cell-type deconvolution of spatial barcoding-based transcriptomic data
SDePER: a hybrid machine learning and regression method for cell-type deconvolution of spatial barcoding-based transcriptomic data Open
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 se…
View article: TRβ activation confers AT2-to-AT1 cell differentiation and anti-fibrosis during lung repair via KLF2 and CEBPA
TRβ activation confers AT2-to-AT1 cell differentiation and anti-fibrosis during lung repair via KLF2 and CEBPA Open
Aberrant repair underlies the pathogenesis of pulmonary fibrosis while effective strategies to convert fibrosis to normal regeneration are scarce. Here, we found that thyroid hormone is decreased in multiple models of lung injury but is es…
View article: Immune checkpoint dysregulation in COVID-19 pathogenesis and disease severity.
Immune checkpoint dysregulation in COVID-19 pathogenesis and disease severity. Open
Accumulating evidence suggests dysregulated immune checkpoint (IC) signaling can exacerbate COVID-19 severity, but the role of these molecules in the pathogenesis of fatal COVID-19-related diffuse alveolar damage (DAD) remains elusive. Und…
View article: Triiodothyronine acts on DAO to regulate pulmonary fibrosis progression by facilitating cell senescence through the p53/p21 signaling pathway
Triiodothyronine acts on DAO to regulate pulmonary fibrosis progression by facilitating cell senescence through the p53/p21 signaling pathway Open
Background Idiopathic pulmonary fibrosis (IPF) is the result of multiple cycles of epithelial cell injury and fibroblast activation; currently, there is no clear etiology. Increasing evidence suggests that protein metabolism and amino acid…
View article: PIK-III exerts anti-fibrotic effects in activated fibroblasts by regulating p38 activation
PIK-III exerts anti-fibrotic effects in activated fibroblasts by regulating p38 activation Open
Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune-driven connective tissue disorder that results in fibrosis of the skin and internal organs such as the lung. Fibroblasts are known as the main effector cells involved in…
View article: LAPTM4B Alleviates Pulmonary Fibrosis by Enhancing NEDD4L-Mediated TGF-β Signaling Suppression
LAPTM4B Alleviates Pulmonary Fibrosis by Enhancing NEDD4L-Mediated TGF-β Signaling Suppression Open
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with fatal outcome and a poorly understood pathogenesis. The lysosomal protein transmembrane 4 beta (LAPTM4B), a multi-transmembrane endo-lysosomal membrane prot…
View article: Retraction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3
Retraction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3 Open
Chitinase 1 (CHIT1) plays a role in the pathogenesis of pulmonary fibrosis by modulating canonical and noncanonical TGF-β signaling via interaction with TGFBRAP1 and FOXO3. These findings highlight the CHIT1/SMAD7 axis as a potential bioma…
View article: <i>Let-7</i> restrains an oncogenic circuit in AT2 cells to prevent fibrogenic cell intermediates in pulmonary fibrosis
<i>Let-7</i> restrains an oncogenic circuit in AT2 cells to prevent fibrogenic cell intermediates in pulmonary fibrosis Open
Analysis of lung alveolar type 2 (AT2) progenitor stem cells has highlighted fundamental mechanisms that direct their differentiation into alveolar type 1 cells (AT1s) in lung repair and disease. However, microRNA (miRNA) mediated post-tra…
View article: Pamrevlumab for Idiopathic Pulmonary Fibrosis
Pamrevlumab for Idiopathic Pulmonary Fibrosis Open
Importance Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal an…
View article: Genetics and Genomics of Pulmonary Fibrosis: Charting the Molecular Landscape and Shaping Precision Medicine
Genetics and Genomics of Pulmonary Fibrosis: Charting the Molecular Landscape and Shaping Precision Medicine Open
Recent genetic and genomic advancements have elucidated the complex etiology of idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases (ILDs), emphasizing the contribution of heritable factors. This s…
View article: Design of the STRIVE-IPF trial- study of therapeutic plasma exchange, rituximab, and intravenous immunoglobulin for acute exacerbations of idiopathic pulmonary fibrosis
Design of the STRIVE-IPF trial- study of therapeutic plasma exchange, rituximab, and intravenous immunoglobulin for acute exacerbations of idiopathic pulmonary fibrosis Open
Background Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) affect a significant proportion of patients with IPF. There are limited data to inform therapeutic strategies for AE-IPF, despite its high mortality. We discuss the r…
View article: Utility of peripheral protein biomarkers for the prediction of incident interstitial features: a multicentre retrospective cohort study
Utility of peripheral protein biomarkers for the prediction of incident interstitial features: a multicentre retrospective cohort study Open
Introduction/rationale Protein biomarkers may help enable the prediction of incident interstitial features on chest CT. Methods We identified which protein biomarkers in a cohort of smokers (COPDGene) differed between those with and withou…
View article: Design of the STRIVE-IPF Trial- Study of Therapeutic Plasma Exchange, Rituximab, and Intravenous Immunoglobulin for Acute Exacerbations of Idiopathic Pulmonary Fibrosis
Design of the STRIVE-IPF Trial- Study of Therapeutic Plasma Exchange, Rituximab, and Intravenous Immunoglobulin for Acute Exacerbations of Idiopathic Pulmonary Fibrosis Open
Background: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) affect a significant proportion of patients with IPF. There are limited data to inform therapeutic strategies for AE-IPF, despite its high mortality. We discuss the …