Similar Datasets
Project description:Pulmonary fibrosis (PF) is a progressive disease with a poor prognosis and lack of effective treatments. Therefore, identifying effective therapeutic modalities is required to improve outcome. However, the lack of predictive progressive disease biomarkers in the clinic causes a significant gap in the preclinical to clinical translational process. Here, we assessed and identified progressive alterations in pulmonary function, transcriptomics, and metabolomics in mice lungs at 7, 14, 21, and 28 days after a single dose of oropharyngeal bleomycin. By integrating multi-omics data, we identified two central gene subnetworks associated with multiple critical pathological changes in transcriptomics and metabolomics as well as pulmonary function. We presented a multi-omics-based framework to establish a translational link between the bleomycin-induced PF model in mice and human idiopathic pulmonary fibrosis to identify druggable targets and test therapeutic candidates. Our study also indicated peripheral CB1R antagonism as a rational therapeutic target for clinical translation in PF.
2023-04-11 | GSE213709 | GEO
Project description:Pulmonary fibrosis (PF) is a progressive disease with a poor prognosis and lack of effective treatments. Therefore, identifying effective therapeutic modalities is required to improve outcome. However, the lack of predictive progressive disease biomarkers in the clinic causes a significant gap in the preclinical to clinical translational process. Here, we assessed and identified progressive alterations in pulmonary function, transcriptomics, and metabolomics in mice lungs at 7, 14, 21, and 28 days after a single dose of oropharyngeal bleomycin. By integrating multi-omics data, we identified two central gene subnetworks associated with multiple critical pathological changes in transcriptomics and metabolomics as well as pulmonary function. We presented a multi-omics-based framework to establish a translational link between the bleomycin-induced PF model in mice and human idiopathic pulmonary fibrosis to identify druggable targets and test therapeutic candidates. Our study also indicated peripheral CB1R antagonism as a rational therapeutic target for clinical translation in PF.
2023-04-11 | GSE217814 | GEO
Project description:There is a tremendous current interest in measuring multiple types of omics features (e.g., DNA sequences, RNA expressions, methylation profiles, metabolic profiles, protein expressions) on a large number of subjects. Although genotypes are typically available for all study subjects, other data types may be measured only on a subset of subjects due to cost or other constraints. In addition, quantitative omics measurements, such as metabolite levels and protein expressions, are subject to detection limits in that the measurements below (or above) certain thresholds are not detectable. In this article, we propose a rigorous and powerful approach to handle missing values and detection limits in integrative analysis of multiomics data. We relate quantitative omics variables to genetic variants and other variables through linear regression models and relate phenotypes to quantitative omics variables and other variables through generalized linear models. We derive the joint-likelihood for the two sets of models by allowing arbitrary patterns of missing values and detection limits for quantitative omics variables. We carry out maximum-likelihood estimation through computationally fast and stable algorithms. The resulting estimators are approximately unbiased and statistically efficient. An application to a major study on chronic obstructive lung disease yielded new biological insights.
| S-EPMC7951090 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic disease of the lung that is marked by progressive decline in pulmonary function and ultimately respiratory failure. Genetic and environmental risk factors have been identified that indicate injury to, and dysfunction of the lung epithelium is central to initiating the pathogenic process. Following injury to the lung epithelium, growth factors, matrikines and extracellular matrix driven signaling together activate a variety of repair pathways that lead to inflammatory cell recruitment, fibroblast proliferation and expansion of the extracellular matrix, culminating in tissue fibrosis. This tissue fibrosis then leads to changes in the biochemical and biomechanical properties of the extracellular matrix, which potentiate profibrotic mechanisms through a "feed-forward cycle." This review provides an overview of the interactions of the pathogenic mechanisms of IPF with a focus on epithelial-mesenchymal crosstalk and the extracellular matrix as a therapeutic target for idiopathic pulmonary fibrosis.
| S-EPMC6146058 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2012-11-27 | GSE34941 | GEO
Project description:Pulmonary oedema (PO) is a common manifestation of acute heart failure (AHF) and is associated with a high-acuity presentation and with poor in-hospital outcomes. The clinical picture of PO is dominated by signs of pulmonary congestion, and its pathogenesis has been attributed predominantly to an imbalance in Starling forces across the alveolar-capillary barrier. However, recent studies have demonstrated that PO formation and resolution is critically regulated by active endothelial and alveolar signalling. PO represents a medical emergency and treatment should be individually tailored to the urgency of the presentation and acute haemodynamic characteristics. Although, the majority of patients admitted with PO rapidly improve as result of conventional intravenous (IV) therapies, treatment of PO remains largely opinion based as there is a general lack of good evidence to guide therapy. Furthermore, none of these therapies showed simultaneous benefit for symptomatic relief, haemodynamic improvement, increased survival and end-organ protection. Future research is required to develop innovative pharmacotherapies capable of relieving congestion while simultaneously preventing end-organ damage.
| S-EPMC5491006 | biostudies-other
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-06-09 | GSE173357 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-06-26 | GSE105067 | GEO
Project description:Dissecting the molecular landscape of fibrotic disease, a major unmet need, will inform the development of novel treatment strategies to target disease progression and identify desperately needed therapeutic targets. Here, we provide a detailed single-cell analysis of the immune landscape in Dupuytren's disease, a localized fibrotic condition of the hand, and identify a pathogenic signaling circuit between stromal and immune cells. We demonstrate M2 macrophages and mast cells as key cellular sources of tumor necrosis factor (TNF) that promotes myofibroblast development. TNF acts via the inducible TNFR2 receptor and stimulates interleukin-33 (IL-33) secretion by myofibroblasts. In turn, stromal cell IL-33 acts as a potent stimulus for TNF production from immune cells. Targeting this reciprocal signaling pathway represents a novel therapeutic strategy to inhibit the low-grade inflammation in fibrosis and the mechanism that drives chronicity.
| S-EPMC6892635 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-06-21 | E-GEOD-32539 | biostudies-arrayexpress