CircRNAs in BALF exosomes and plasma as diagnostic biomarkers in patients with acute respiratory distress syndrome caused by severe pneumonia
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE217763 | GEO | 2022/11/11
REPOSITORIES: GEO
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Project description:The acute respiratory distress syndrome (ARDS) results from overwhelming pulmonary inflammation. We used single cell RNA sequencing to probe ARDS at a higher resolution for insights into ARDS pathogenesis. Peripheral blood mononuclear cells of patients with pneumonia and sepsis with early ARDS were compared to that of sepsis patients who did not develop ARDS. Monocyte clusters from ARDS patients revealed multiple distinguishing characteristics in comparison to monocytes from patients without ARDS including down-regulation of SOCS3 expression accompanied by a pro-inflammatory signature with up-regulation of multiple type I IFN-induced genes, especially in CD16+ cells. These data show that monocytes of ARDS patients up-regulate expression of genes not just restricted to those associated with inflammation. Together, our findings identify molecules that are likely involved in ARDS pathogenesis that may inform biomarker and therapeutic development.
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Project description:Acute respiratory distress syndrome (ARDS) remains a significant hazard to human health and is clinically challenging because there are no prognostic biomarkers and no effective pharmacotherapy. The lung compartment metabolome may detail the status of the local environment that could be useful in ARDS biomarker discovery and the identification of drug target opportunities. However, neither the utility of bronchoalveolar lavage fluid (BALF) as a biofluid for metabolomics nor the optimal analytical platform for metabolite identification are established. To address this, we undertook a study to compare metabolites in BALF samples from patients with ARDS and healthy controls using a newly developed liquid chromatography (LC)-mass spectroscopy (MS) platform for untargeted metabolomics. Following initial testing of three different high performance liquid chromatography (HPLC) columns, we determined that reversed phase (RP)-LC and hydrophilic interaction chromatography (HILIC), were the most informative chromatographic methods because they yielded the most and highest quality data. Following confirmation of metabolite identification, statistical analysis resulted in 37 differentiating metabolites in the BALF of ARDS compared with health across both analytical platforms. Pathway analysis revealed networks associated with amino acid metabolism, glycolysis and gluconeogenesis, fatty acid biosynthesis, phospholipids and purine metabolism in the ARDS BALF. The complementary analytical platforms of RPLC and HILIC-LC generated informative, insightful metabolomics data of the ARDS lung environment.
Research is published:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068805/
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Project description:Rat model of ARDS was induced by saline lavage and mechanical ventilation. miRNA from rat lungs were used for dual color DNA microarray hybridization with 3DNA 50 kit version 2. Two-condition experiment, CON vs. ARDS lung tissues. replicates: 6 control, 6 ARDS. One replicate per array.
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Project description:Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging threat to human health throughout the world. Rodent MRSA pneumonia models mainly focus on the early innate immune responses to MRSA infection. However, the molecular pattern and mechanisms of recovery from MRSA lung infection are largely unknown. In this study, a nonlethal mouse MRSA pneumonia model was employed to investigate events during lung recovery from MRSA infection. We compared lung bacterial clearance, bronchoalveolar lavage fluid (BALF) characterization, lung histology, and gene expression profiling between Day 1 and Day 3 post-MRSA infection. Compared to Day 1 post-infection, bacterial colony counts and both BALF total cell number and protein concentration significantly decreased at Day 3 post-infection. Lung cDNA microarray analysis identified 47 significantly up-regulated and 35 down-regulated genes (p<0.01, 1.5-fold change [up and down]). Changes in eight genes were confirmed by real-time PCR. The pattern of gene expression suggests lung recovery is characterized by enhanced cell division, vascularization, and wound healing and by adjustment in host adaptive immune responses. Collectively, this data helps elucidate the molecular mechanisms of lung recovery after MRSA infection. RNA expression analysis was performed using the Illumina MouseRef-8 v2.0 BeadChip (Illumina, San Diego, CA), which provides coverage of approximately 25,700 genes and expressed sequence tags. Four independent mouse lung tissue samples at Day 1 and Day 3 post-MRSA infection were used in this study.
2013-11-12 | E-GEOD-36587 | biostudies-arrayexpress
Project description:Rationale: Serial measurements of genome-wide transcriptional changes in alveolar macrophages (AM) and peripheral blood monocytes (PBM) from patients with acute respiratory distress (ARDS) could clarify the biologic programs activated in ARDS and the relationship of these changes to clinical outcomes. Objectives: To identify transcriptional programs activated in purified AM and PBM over the course of ARDS, and determine the relationship of these programs with patient outcomes. Methods: We performed transcriptional profiling of total RNA isolated from AMs and PBMs purified from bronchoalveolar lavage fluid (BALF) and peripheral blood respectively, collected from patients (n = 26) with ARDS previously enrolled in a phase-II clinical trial. Cells were obtained at baseline (day 0) after enrollment. Measurements and Main Results: Using an unbiased gene set enrichment analysis (GSEA), we found highly divergent patterns of gene expression in AMs and PBMs. Notably, immuno-inflammatory gene sets were enriched in AMs isolated on day 0 in those who survived and had more ventilator-free days (VFD); however, this association between inflammatory and immune gene sets and good outcomes was not seen in PBMs. Conclusion: Transcriptional responses during ARDS are remarkably different between AMs and PBMs. Rationale: Serial measurements of genome-wide transcriptional changes in alveolar macrophages (AM) and peripheral blood monocytes (PBM) from patients with acute respiratory distress (ARDS) could clarify the biologic programs activated in ARDS and the relationship of these changes to clinical outcomes. Objectives: To identify transcriptional programs activated in purified AM and PBM over the course of ARDS, and determine the relationship of these programs with patient outcomes. Methods: We performed transcriptional profiling of total RNA isolated from AMs and PBMs purified from bronchoalveolar lavage fluid and peripheral blood respectively, collected from patients (n = 26) with ARDS previously enrolled in a phase-II clinical trial. Cells were obtained at baseline (day 0) after enrollment. Measurements and Main Results: Using an unbiased gene set enrichment analysis (GSEA), we found highly divergent patterns of gene expression in AMs and PBMs. Notably, immuno-inflammatory gene sets were enriched in AM isolated on day 0 in those who survived and had more ventilator-free days (VFD); however, this association between inflammatory and immune gene sets and good outcomes was not seen in PBMs. Conclusion: Transcriptional responses during ARDS are remarkably different between AM and PBM.
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Project description:Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging threat to human health throughout the world. Rodent MRSA pneumonia models mainly focus on the early innate immune responses to MRSA infection. However, the molecular pattern and mechanisms of recovery from MRSA lung infection are largely unknown. In this study, a nonlethal mouse MRSA pneumonia model was employed to investigate events during lung recovery from MRSA infection. We compared lung bacterial clearance, bronchoalveolar lavage fluid (BALF) characterization, lung histology, and gene expression profiling between Day 1 and Day 3 post-MRSA infection. Compared to Day 1 post-infection, bacterial colony counts and both BALF total cell number and protein concentration significantly decreased at Day 3 post-infection. Lung cDNA microarray analysis identified 47 significantly up-regulated and 35 down-regulated genes (p<0.01, 1.5-fold change [up and down]). Changes in eight genes were confirmed by real-time PCR. The pattern of gene expression suggests lung recovery is characterized by enhanced cell division, vascularization, and wound healing and by adjustment in host adaptive immune responses. Collectively, this data helps elucidate the molecular mechanisms of lung recovery after MRSA infection.
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