Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA257455 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To evaluate whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple-organ dysfunction syndrome. The INntravenous CLArithromycin in Sepsis and multiple organ dysfunction Syndrome trial was a phase 3, randomized, double blind, placebo-controlled clinical study, conducted in 11 intensive care units and 2 Internal Medicine wards in 2 countries. Patients with sepsis, respiratory failure and total sequential organ failure assessment score of ≥7 were enrolled between December 2017 and September 2019. Follow-up lasted 90 days. Patients were randomized to receive 1 gr of intravenous clarithromycin or placebo once daily for 4 consecutive days.
2022-06-30 | GSE196117 | GEO
Project description:Sepsis is a complex syndrome characterized by organ dysfunction triggered by dysregulated host response to infection, and the kidney is the most commonly injured organ. To model septic-induced AKI in animal, a well-established mouse model induced by caecal ligation and puncture (CLP) was established.
2023-11-09 | GSE220812 | GEO
Project description:Sepsis is a complex syndrome characterized by organ dysfunction triggered by dysregulated host response to infection, and the kidney is the most commonly injured organ. To model septic-induced AKI in animal, a well-established mouse model induced by caecal ligation and puncture (CLP) was established.
2023-11-09 | GSE220782 | GEO
Project description:The temporal evolution of sepsis was monitored by transcriptional profiling of five critically ill children with meningococcal sepsis and sepsis-induced multiple organ failure. Blood was sampled at 6 time points during the first 48 hours of their admission to pediatric intensive care, where the children received standard clinical treatment including organ support and antimicrobial therapy. Striking transcript instability was observed over the 48 hours, with increasing numbers of regulated genes over time. Most notably, proposed biomarkers for sepsis risk stratification also showed expression instability, with varied expression levels over 48 hours. This study demonstrates the extent of the complexity of temporal changes in gene expression that occur during the evolution of sepsis-induced multiple organ failure. Importantly, stratification tools that propose expression of biomarkers must take into account the temporal changes, over the use of single snapshots that may be less informative.
2013-04-03 | E-MEXP-3850 | biostudies-arrayexpress
Project description:Sepsis-induced multiple organ dysfunction syndrome (MODS) is a major cause of morbidity and mortality in critically ill patients and remains impervious to most therapeutic interventions. We utilized a clinically relevant murine model of MODS induced by ventilator-associated pneumonia to systematically delineate pathways dysregulated in lung, liver, and kidney. We focused on processes commonly activated across injured organs and constructed a MODS-associated network based on connectivity among the gene members of these functionally coherent pathways. Our analyses led to the identification of several putative drivers of MODS whose expression was regulated by epidermal growth factor receptor. Our unbiased, integrative method is a promising approach to unravel mechanisms in system-wide disorders afflicting multiple compartments such as sepsis-induced MODS, and guide the discovery of novel putative therapeutic targets.
2014-12-31 | GSE60088 | GEO
Project description:Background: Pulmonary endothelial cell (EC) activation is a key factor in acute respiratory distress syndrome (ARDS). In sepsis, increased glycolysis leads to lactate buildup, which induces lysine lactylation (Kla) on histones and other proteins. However, the role of protein lactylation in EC dysfunction during sepsis-induced ARDS remains unclear. Methods: Integrative lactylome and proteome analysis was performed to identify the global lactylome profiling in lung tissues of septic mice. Cut&Tag analysis were used to identify the transcriptional targets of histone H3 lysine 14 lactylation (H3K14la) in ECs. Results: Septic mice exhibited elevated levels of lactate and H3K14la in lung tissues, particularly in pulmonary ECs. Suppressing glycolysis reduced both H3K14la and EC activation, suggesting a link between glycolysis and lactylation. Moreover, H3K14la was found to be enriched at promoter regions of ferroptosis-related genes such as transferrin receptor (TFRC) and solute carrier family 40 member 1 (SLC40A1), which contributed to EC activation and lung injury under septic conditions. Conclusions: We for the first time reported the role of lactate-dependent H3K14 lactylation in regulating EC ferroptosis to promote vascular dysfunction during sepsis-induced lung injury. Our findings suggest that manipulation of glycolysis/H3K14la/ferroptosis axis may provide novel therapeutic approaches for sepsis-associated ARDS.
2025-05-07 | PXD056805 | Pride
Project description:Sepsis is a life-threatening disease that often causes multiple organ dysfunctions. Long noncoding RNAs (lncRNAs) are involved in the pathogenesis and development of sepsis. However, there is little known about the function of lncRNAs in sepsis-induced myocardial dysfunction.To test the hypothesis that dysregulating lncRNAs may be involved in sepsis-induced myocardial dysfunction, we identified differentially expressed (DE) lncRNAs and mRNAs in cardiac tissue by high-throughput sequencing. We constructed coding and non-coding co-expression (CNC) and lncRNA-micro RNA (miRNA)-mRNA competing endogenous networks. The findings will provide useful information for exploring therapeutic candidate targets and new molecular biomarkers of septic myocardial injury.
2023-05-17 | GSE153086 | GEO
Project description:Sepsis is a life-threatening condition triggered by a dysregulated host response to microbial infection resulting in vascular dysfunction, organ failure and death. Here we provide a semi-quantitative atlas of the murine vascular cell-surface proteome at the organ level, and how it changes during sepsis. Using in-vivo chemical labeling, multi-dimensional liquid chromatography, and high-resolution mass spectrometry, we demonstrate the presence of a vascular proteome that is perfusable and shared across multiple organs. This proteome was enriched in membrane-anchored proteins, including multiple regulators of endothelial barrier functions and the innate immunity. Further, we automated our workflows and applied them to a murine model of methicillin-resistant Staphylococcus aureus sepsis to unravel changes during systemic inflammatory responses. We provide an organ-specific atlas of both systemic and local changes of the vascular proteome triggered by sepsis. The data indicates that upon a septic challenge, the different organ vasculatures undergo unique and extensive remodeling.
2019-04-15 | MSV000083690 | MassIVE
Project description:Background: Sepsis involves aberrant immune responses to infection, but the exact nature of this immune dysfunction remains poorly defined. Bacterial endotoxins like lipopolysaccharide (LPS) are potent inducers of inflammation, which has been associated with the pathophysiology of sepsis, but repeated exposure can also induce a suppressive effect known as endotoxin tolerance or cellular reprogramming. It has been proposed that endotoxin tolerance might be associated with the immunosuppressive state that was primarily observed during late-stage sepsis. However, this relationship remains poorly characterised. Here we clarify the underlying mechanisms and timing of immune dysfunction in sepsis. Methods: We defined a gene expression signature characteristic of endotoxin tolerance. Gene-set test approaches were used to correlate this signature with early sepsis, both newly and retrospectively analysing microarrays from 593 patients in 11 cohorts. Then we recruited a unique cohort of possible sepsis patients at first clinical presentation in an independent blinded controlled observational study to determine whether this signature was associated with the development of confirmed sepsis and organ dysfunction. Findings: All sepsis patients presented an expression profile strongly associated with the endotoxin tolerance signature (p < 0.01; AUC 96.1%). Importantly, this signature further differentiated between suspected sepsis patients who did, or did not, go on to develop confirmed sepsis, and predicted the development of organ dysfunction. Interpretation: Our data support an updated model of sepsis pathogenesis in which endotoxin tolerance-mediated immune dysfunction (cellular reprogramming) is present throughout the clinical course of disease and related to disease severity. Thus endotoxin tolerance might offer new insights guiding the development of new therapies and diagnostics for early sepsis. For the RNA-Seq study reported here, 73 patients were recruited with deferred consent at the time of first examination in an emergency ward based on the opinion of physicians that there was a potential for the patient's condition to develop into sepsis. These were retrospectively divided into groups based on clinical features and compared to 11 non-urgent surgical controls.
2014-11-14 | E-GEOD-63311 | biostudies-arrayexpress
Project description:Severely-afflicted COVID-19 patients can exhibit disease manifestations representative of sepsis, including acute respiratory distress syndrome and multiple organ failure. We hypothesized that diagnostic tools used in managing all-cause sepsis, such as clinical criteria, biomarkers, and gene expression signatures, should extend to COVID-19 patients. Here we analyzed the whole blood transcriptome of 124 early (1-5 days post-hospital admission) and late (6-20 days post-admission) sampled patients with confirmed COVID-19 infections from hospitals in Quebec, Canada. Mechanisms associated with COVID-19 severity were identified between severity groups (ranging from mild disease to the requirement for mechanical ventilation and mortality), and established sepsis signatures were assessed for dysregulation. Specifically, gene expression signatures representing pathophysiological events, namely cellular reprogramming, organ dysfunction, and mortality, were significantly enriched and predictive of severity and lethality in COVID-19 patients. Mechanistic endotypes reflective of distinct sepsis aetiologies and therapeutic opportunities were also identified in subsets of patients, enabling prediction of potentially-effective repurposed drugs. The expression of sepsis gene expression signatures in severely-afflicted COVID-19 patients indicates that these patients should be classified as having severe sepsis. Accordingly, in severe COVID-19 patients, these signatures should be strongly considered for the mechanistic characterization, diagnosis, and guidance of treatment using repurposed drugs.
2022-12-18 | GSE221234 | GEO