Deleted in malignant brain tumors 1 protein is a potential biomarker of acute respiratory distress syndrome induced by pneumonia

2016 ◽  
Vol 478 (3) ◽  
pp. 1344-1349 ◽  
Author(s):  
Shan Ren ◽  
Xia Chen ◽  
Li Jiang ◽  
Bo Zhu ◽  
Qi Jiang ◽  
...  
2021 ◽  
Author(s):  
Rahul Y Mahida ◽  
Joshua Price ◽  
Sebastian T. Lugg ◽  
Hui Li ◽  
Dhruv Parekh ◽  
...  

Recent studies have indicated that extracellular vesicles (EV) may play a role in the pathogenesis of Acute Respiratory Distress Syndrome (ARDS). EV have been identified as potential biomarkers of disease severity and prognosis in other pulmonary diseases. We sought to characterize the EV phenotype within ARDS patient broncho-alveolar lavage fluid (BAL), and to determine whether BAL EV could be utilized as a potential biomarker in ARDS. EV from the BAL of sepsis patients with ARDS, sepsis patients without ARDS, and post-operative control patients were characterized with regards to size, number and cell of origin. ARDS patients had significantly higher numbers of CD14+/CD81+ monocyte-derived BAL EV than sepsis patients without ARDS (p=0.022). CD14+/CD81+ BAL EV numbers were significantly higher in those ARDS patients who died during the 30 days following ICU admission (p=0.027). Also, across all sepsis patients there was an association between CD66b+/CD63+ neutrophil-derived BAL EV and increased BAL IL-8 concentration, increased alveolar neutrophil apoptosis and decreased alveolar macrophage efferocytosis. Thus, CD14+/CD81+ BAL EV are a potential biomarker for disease severity and mortality in ARDS. These findings provide the impetus to further elucidate the contribution of these EV to ARDS pathogenesis.


2021 ◽  
Author(s):  
Yang Xia ◽  
Lei Gao ◽  
Lili Guo ◽  
Hao Li ◽  
Min Shao ◽  
...  

Abstract BackgroundAcute respiratory distress syndrome (ARDS) is a life-threatening condition leading to severe pulmonary injuries, and proteomic analysis of bronchoalveolar lavage fluid (BALF) might elucidate potential biomarkers for diagnosis and targets for treatment of ARDS. MethodsThrough iTRAQ analysis, we investigated paired BALF samples from three ARDS patients in the acute and recovery phases. The proteins sharing the same expression patterns between the two ARDS phases among different patients were determined as co-upregulated and co-downregulated proteins (CUDPs), and differentially expressed proteins (DEPs), whose fold change > 1.2 and P value < 0.05, were selected from CUDPs. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied to determine the enriched functions and pathways of the CUDPs. Protein-protein interaction (PPI) network was generated at STRING database, and hub genes were identified by the Cytoscape software. A549 cells were treated by lipopolysaccharide (LPS) to simulate alveolar epithelial cells in ARDS.ResultsWe identified 374 CUDPs and 53 DEPs. The GO analysis indicated that the most significantly enriched function was neutrophil mediated immunity response, and the KEGG analysis revealed that the 374 CUDPs were most significantly enriched in Coronavirus disease COVID-19 interaction. RPSA was discovered as the most top hub gene among DEPs, and was downregulated at protein levels during ARDS recovery. Moreover, we further confirmed that both RNA and protein level of RPSA increased upon inflammatory stimulation in vitro.ConclusionOur results proposed RPSA as a candidate for biomarker and therapeutic target of ARDS.


2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Lin Liao ◽  
Pinhu Liao

Abstract Background: Acute respiratory distress syndrome (ARDS) is caused by uncontrolled inflammation, and the activation of alveolar macrophages (AM) is involved in pathophysiologic procedures. The present study aimed to identify key AM genes and pathways and try to provide potential targets for prognosis and early intervention in ARDS. Methods: The mRNA expression profile of GSE89953 was obtained from the Gene Expression Omnibus database. The LIMMA package in R software was used to identify differentially expressed genes (DEGs), and the clusterProfiler package was used for functional enrichment and pathway analyses. A protein–protein interaction network of DEGs was constructed to identify hub genes via the STRING database and Cytoscape software. Hub gene expression was validated using differentially expressed proteins (DEPs) obtained from the ProteomeXchange datasets to screen potential biomarkers. Results: A total of 166 DEGs (101 up-regulated and 65 down-regulated) were identified. The up-regulated DEGs were mainly enriched in regulation of the ERK1 and ERK2 cascade, response to interferon-gamma, cell chemotaxis, and migration in biological processes. In the KEGG pathway analysis, up-regulated DEGs were mainly involved in rheumatoid arthritis, cytokine–cytokine receptor interactions, phagosome, and the chemokine signaling pathway. The 12 hub genes identified included GZMA, MPO, PRF1, CXCL8, ELANE, GZMB, SELL, APOE, SPP1, JUN, CD247, and CCL2. Conclusion: SPP1 was consistently differentially expressed in both DEGs and DEPs. SPP1 could be a potential biomarker for ARDS.


2019 ◽  
Vol 8 (8) ◽  
pp. 1148 ◽  
Author(s):  
Kim ◽  
Hong ◽  
Lim ◽  
Koh ◽  
Jang ◽  
...  

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening condition caused by pulmonary and extrapulmonary insults. Exosomes are considered a major cell-to-cell communicator and immune modulator. However, their role in ARDS remains unclear. In this study, we investigated whether exosomes could be a potential biomarker of ARDS. Methods: We isolated exosomes from bronchoalveolar lavage (BAL) of patients with ARDS. The correlation between the level of exosomes with clinical data, including etiology, oxygenation, and 28-day mortality was analyzed. Enzyme-linked immune sorbent assays and western blotting were carried out to characterize BAL exosomes. Immune modulating response of exosomes was investigated by in vitro examination. Results: From 158 patients, we isolated mean 1568.9 µg/mL BAL exosomes, which presented a negative correlation with the PaO2/FiO2 ratio. The level of exosomes did not correlate with 28-day mortality but was elevated in the infectious etiology of ARDS. The exosomes have cargo proteins associated with apoptosis, necroptosis, and autophagy. An in vitro stimulation study revealed that BAL exosomes could induce the production of proinflammatory cytokines and chemokines, but those from patients with ARDS suppressed the production of vascular endothelial growth factor. Conclusions: In ARDS, exosomes are released in alveolar space, and the level is correlated with the etiology of ARDS. BAL exosomes could play an immune-modulating role by controlling the production of cytokines.


2020 ◽  
Vol 49 (10) ◽  
pp. 418-421
Author(s):  
Christopher Werlein ◽  
Peter Braubach ◽  
Vincent Schmidt ◽  
Nicolas J. Dickgreber ◽  
Bruno Märkl ◽  
...  

ZUSAMMENFASSUNGDie aktuelle COVID-19-Pandemie verzeichnet mittlerweile über 18 Millionen Erkrankte und 680 000 Todesfälle weltweit. Für die hohe Variabilität sowohl der Schweregrade des klinischen Verlaufs als auch der Organmanifestationen fanden sich zunächst keine pathophysiologisch zufriedenstellenden Erklärungen. Bei schweren Krankheitsverläufen steht in der Regel eine pulmonale Symptomatik im Vordergrund, meist unter dem Bild eines „acute respiratory distress syndrome“ (ARDS). Darüber hinaus zeigen sich jedoch in unterschiedlicher Häufigkeit Organmanifestationen in Haut, Herz, Nieren, Gehirn und anderen viszeralen Organen, die v. a. durch eine Perfusionsstörung durch direkte oder indirekte Gefäßwandschädigung zu erklären sind. Daher wird COVID-19 als vaskuläre Multisystemerkrankung aufgefasst. Vor dem Hintergrund der multiplen Organmanifestationen sind klinisch-pathologische Obduktionen eine wichtige Grundlage der Entschlüsselung der Pathomechanismen von COVID-19 und auch ein Instrument zur Generierung und Hinterfragung innovativer Therapieansätze.


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