Identification of the ferroptosis-related genes in Sepsis- Associated Encephalopathy by multiple transcriptional datasets analysis DOI Creative Commons

Zhefan Xie,

Wei Zhang, Lingfeng Li

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Abstract Sepsis associated encephalopathy (SAE), a severe sepsis complication, remains challenging to treat due limited effective options. Current therapies focus on symptomatic relief and managing complications, without addressing the underlying causes, highlighting need for further research. The condition's complex pathophysiology involves inflammation, blood-brain barrier disruption, neuronal damage, necessitating comprehensive understanding of its mechanisms through multi-dataset We used RNA sequencing, Mendelian randomization, bioinformatics study gene changes in SAE. Our analysis identified 1,259 differentially expressed genes related inflammatory bacterial responses. randomization revealed 20 key genes, including ITPA IL18R1, with risk. GSVA GSEA analyses validated their roles signaling pathways. Single-cell showed expression across cell types co-expression ferroptosis-related genes. also constructed regulatory miRNA networks, identifying several transcription factors miRNAs involved regulation. multi-omics approach offers new insights into molecular SAE identifies potential therapeutic targets this condition.

Language: Английский

Glial vascular Unit as a bridge between Blood-Brain Barrier and glymphatic System: Roles in sepsis-associated encephalopathy DOI
Jiyun Hu, Shucai Xie, Tao Chen

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: 570, P. 68 - 71

Published: Feb. 19, 2025

Language: Английский

Citations

0
LCN2 induces neuronal loss and facilitates sepsis-associated cognitive impairments DOI Creative Commons
Cuiping Guo, Wensheng Li, Yi Liu

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 1, 2025

Abstract Sepsis-associated encephalopathy (SAE) is a severe neurological syndrome marked by widespread brain dysfunctions due to sepsis. Despite increasing data supporting the hypothesis of neuronal damage, exact mechanism sepsis-related cognitive disorders and therapeutic strategies remain unclear need further investigation. In this study, sepsis model was established in C57 mice using lipopolysaccharide (LPS). The findings demonstrated that LPS exposure induced loss, synaptic deficits accompanied mitochondrial damage. Bioinformatics western blot analyses significant increase Lipocalin-2 (LCN2) during as key hub gene involved immune inflammation. Interestingly, recombinant LCN2 protein exhibited similar effects on dysfunction mice. Conversely, downregulating effectively nullified impact LPS, leading amelioration deficits, reactive oxygen species (ROS)-associated These suggest novel etiopathogenic SAE, which initiated increased LCN2, loss deficit. Inhibition could be therapeutically beneficial treating sepsis-induced impairments.

Language: Английский

Citations

0
Annexin A3 Represses Endothelial Permeability and Inflammation During Sepsis via Actin Cytoskeleton Modulation DOI Creative Commons
Manyu Xing, Shuang Liang,

Wei Cao

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Abstract Increased endothelial permeability and a dysregulated inflammatory response play key roles in organ damage sepsis. The role of annexin A3 (ANXA3) regulating inflammation during sepsis is explored using ANXA3 knockout mice primary human umbilical vein cells (HUVECs). absence exacerbated outcomes, including increased mortality, lung injury, leukocyte infiltration, vascular permeability. highly expressed its loss results the formation cytoskeletal stress fibers decrease expression junction proteins zonula occludens (Zo)‐1, (VE)‐cadherin, claudin 5, leading to increase knockdown also upregulates E‐selectin (CD62E) through phosphorylation activating transcription factor 2 (ATF2), which increases monocyte adhesion HUVECs after LPS stimulation. Inhibiting actin polymerization reverse these effects. Thus, stabilizes cytoskeleton, playing protective dysfunction

Language: Английский

Citations

0
Remimazolam attenuates lipopolysaccharide-induced neuroinflammation and cognitive dysfunction DOI Creative Commons

Leguang Zhou,

Mengzhe Xiao,

Hongzhao Shi

et al.

Behavioural Brain Research, Journal Year: 2024, Volume and Issue: unknown, P. 115268 - 115268

Published: Sept. 1, 2024

Language: Английский

Citations

1
A novel method for clustering cellular data to improve classification DOI Creative Commons
Diek W. Wheeler, Giorgio A. Ascoli

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(9), P. 2697 - 2705

Published: Sept. 24, 2024

Many fields, such as neuroscience, are experiencing the vast proliferation of cellular data, underscoring need for organizing and interpreting large datasets. A popular approach partitions data into manageable subsets via hierarchical clustering, but objective methods to determine appropriate classification granularity missing. We recently introduced a technique systematically identify when stop subdividing clusters based on fundamental principle that cells must differ more between than within clusters. Here we present corresponding protocol classify datasets by combining data-driven unsupervised clustering with statistical testing. These general-purpose functions applicable any dataset can be organized two-dimensional matrices numerical values, including molecular, physiological, anatomical demonstrate using from Janelia MouseLight project characterize morphological aspects neurons.

Language: Английский

Citations

0
Serum mitochondrial-encoded NADH dehydrogenase 6 and Annexin A1 as novel biomarkers for mortality prediction in critically ill patients with sepsis DOI Creative Commons
Fan Zhou, Meiling Chen, Yilin Liu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 14, 2024

Objectives Formyl peptide receptor 1 (FPR1) is a member of G protein-coupled (GPCR) family that detects potentially danger signals characterized by the appearance N-formylated peptides which originate from either bacteria or host mitochondria during organ injury, including sepsis. Mitochondrial-encoded NADH dehydrogenase 6 (MT-ND6) and Annexin A1 (ANXA1), as mitochondrial damage-associated molecular patterns (mtDAMPs) agonist endogenous FPR1 respectively, interact with regulating polymorphonuclear leukocytes (PMNs) function inflammatory response However, there no direct evidence MT-ND6 ANXA1 in circulation patients sepsis their potential role clinical significance, diagnosis mortality prediction Methods A prospective cohort study was conducted ICU within large academic hospital. We measured serum (n=180) non-sepsis (n=60) Enzyme-linked immunosorbent assays (ELISA). The ROC curve Kaplan Meier analysis used to evaluate diagnostic prognostic ability two biomarkers for Results concentration were significantly elevated sepsis, values (0.789) second only SOFA scores (AUC = 0.870). Higher concentrations (>1.41 ng/ml) lower (< 8.09 ng/mL) closely related higher predictive 0.705 0.694, respectively. When classified based on four pro-inflammation anti-inflammation cytokines, it shown combination obviously improved septic mixed hyperinflammation immunosuppression phenotypes. Conclusion Our findings provide valuable models testing patient risk strengthen agonists FPR1, ANXA1, novel biomarker selection therapeutic agents target mtDAMPs regulator GPCRs

Language: Английский

Citations

0
Identification of the ferroptosis-related genes in Sepsis- Associated Encephalopathy by multiple transcriptional datasets analysis DOI Creative Commons

Zhefan Xie,

Wei Zhang, Lingfeng Li

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Abstract Sepsis associated encephalopathy (SAE), a severe sepsis complication, remains challenging to treat due limited effective options. Current therapies focus on symptomatic relief and managing complications, without addressing the underlying causes, highlighting need for further research. The condition's complex pathophysiology involves inflammation, blood-brain barrier disruption, neuronal damage, necessitating comprehensive understanding of its mechanisms through multi-dataset We used RNA sequencing, Mendelian randomization, bioinformatics study gene changes in SAE. Our analysis identified 1,259 differentially expressed genes related inflammatory bacterial responses. randomization revealed 20 key genes, including ITPA IL18R1, with risk. GSVA GSEA analyses validated their roles signaling pathways. Single-cell showed expression across cell types co-expression ferroptosis-related genes. also constructed regulatory miRNA networks, identifying several transcription factors miRNAs involved regulation. multi-omics approach offers new insights into molecular SAE identifies potential therapeutic targets this condition.

Language: Английский

Citations

0