Project description:Sepsis is a severe clinical syndrome related to an exaggerated host immune response to infection as well as systematic inflammation and serious tissue damage. Sepsis-associated acute kidney injury (SA-AKI) is one of the most frequent and serious complications of sepsis. This study aimed to identify new mechanisms in SA-AKI through transcriptome profiling (RNA-seq).
Project description:The activation of pulmonary endothelial cells (ECs) triggers the occurrence of lung injury and is a hallmark of sepsis-associated acute respiratory distress syndrome(ARDS). Aberrant metabolism favoring glycolysis plays a pivotal role in the pathogenesis of sepsis-induced EC activation. Herein we demonstrate that glycolysis-related histone lactylation, represented by H3K14 lactylation (H3K14la), drives sepsis-associated EC activation and lung injury. Accordingly, H3K14la level is elevated in injured lung tissue and activated ECs. Inhibition of lactate production suppresses both H3K14la levels and EC activation in response to lipopolysaccharide (LPS). We also show that lactate-dependent H3K14la is enriched at the promoters of ferroptosis-related genes, thereby inducing ferroptosis in ECs, and inhibiting ferroptosis effectively ameliorates EC activation. Taken together, elevated lactate in sepsis modulates EC activation and lung injury via histone lactylation and manipulation of glycolysis/H3K14la/ferroptosis axis may provide novel therapeutic approaches for the treatment of sepsis-associated ARDS.
2023-01-01 | GSE212087 | GEO
Project description:Gut microbiota predictors of sepsis-associated acute kidney injury
Project description:The goal of this observational study is to compare anesthetic modalities (intravenous propofol anesthesia with sevoflurane gas anesthesia) in patients who underwent colorectal cancer resection surgery regarding the outcome of acute kidney injury.
The main questions it aims to answer are:
* is there a difference in acute kidney injury incidence in the two anesthetic modalities?
* is there a difference in plasma creatinine between the two anesthetic modalities?
* are there any patient characteristics or intraoperative factors that effect the incidence of acute kidney injury in either anesthetic modality?
The study will analyze data from the CAN clinical trial database. (Cancer and Anesthesia: Survival After Radical Surgery - a Comparison Between Propofol or Sevoflurane Anesthesia, NCT01975064)
Project description:Sepsis-induced acute kidney injury (AKI) is the most common form of AKI with poor outcomes. Renal proteomic analysis after bacterial lipopolysaccharide (LPS) administration revealed that the local renal acute phase reaction (APR) is one of the strongest responses of the kidney during septic AKI in mice. Evaluation of mRNA expression confirmed that most acute phase proteins were produced in the kidney. Our study also provides missing information on the time course of septic renal APR. Proteomic analysis of LPS-induced AKI demonstrated a marked upregulation of local renal acute phase response (APR) that commenced a few hours post injection and peaked at 24 h. Much more APPs were involved in the renal APR than previously identified.
Project description:Sepsis-associated acute kidney injury (SA-AKI) is a severe and life-threatening condi-tion with high morbidity and mortality among emergency patients, and it poses a sig-nificant risk of chronic renal failure. Clinical treatments for SA-AKI remain reactive and non-specific, lacking effective diagnostic biomarkers or treatment targets. In this study, we established an SA-AKI mouse model using LPS and performed proteomics and metabolomics analyses. A variety of bioinformatic analyses, including Gene Set En-richment Analysis (GSEA), Weighted Gene Co-expression Network Analysis (WGCNA), protein and protein interactions (PPI), and MetaboAnalyst analysis, were conducted to investigate the key molecules of SA-AKI. Proteomics and metabolomics analyses re-vealed that sepsis led to impaired renal mitochondrial function and metabolic disorders. Immune-related pathways were found to be activated in kidneys upon septic infection. The catabolic products of polyamines accumulated in septic kidneys. Overall, our study provides a more comprehensive understanding of SA-AKI and identifies potential pathways for this condition.
Project description:Sepsis is a complex, life-threatening clinical syndrome that can cause other related diseases, such as acute kidney injury (AKI). Circular RNA (circRNA) is a type of non-coding RNA with a diverse range of functions, and it plays essential roles in miRNA sponge. CircRNA plays a huge part in the development of various diseases. CircRNA and the competing endogenous RNA (ceRNA) regulatory network are unknown factors in the onset and progression of septic AKI (SAKI). This study aimed to clarify the complex circRNA-associated regulatory mechanism of circRNAs in SAKI.
Project description:This study delves into the pathophysiological underpinnings of sepsis-associated acute kidney injury (SA-AKI), a critical and often fatal complication arising from the systemic inflammatory response and immune dysregulation triggered by sepsis. By employing the cecal ligation and puncture (CLP) method to simulate sepsis-induced AKI in mice, we conducted comprehensive transcriptome profiling using RNA sequencing (RNA-seq) to explore the molecular dynamics and identify potential new mechanisms underlying SA-AKI. The comparative analysis between the CLP-induced AKI model and control subjects aims to unravel the complex interplay of genes and signaling pathways involved in kidney damage and failure during sepsis. Through this approach, our research seeks to contribute to the broader understanding of SA-AKI's molecular basis.
Project description:Sepsis induced acute kidney injury (AKI) is associated with a rapid decline of kidney function, leading to unacceptably high morbidity and mortality rate as well as progression to chronic kidney disease (CKD). We have recently developed a septic AKI mouse model. By quantitatively assessing the kidney proteome and phosphoproteome changes upon bacterial infection, we accurately quantified over 2,200 kidney proteins with high confidence, which provided us the first global overview of the extensively remodeled kidney proteome and revealed widespread metabolic and oxidation-reduction processes undergone in septic kidney. This data will give us unprecedented insight into how renal cells response to microbe invasion, and will likely serve as a reference dataset of systems biology.