Sepsis-Induced Endothelial Dysfunction: Permeability and Regulated Cell Death DOI Creative Commons

Wei Zhang,

Luofeng Jiang, Xirui Tong

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 9953 - 9973

Published: Nov. 1, 2024

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. Endothelial cells (ECs) are an important cell type typically affected in sepsis, resulting compromised barrier function and various forms of regulated death (RCD). However, the precise mechanisms underlying sepsis-induced EC damage remain unclear. This review summarizes recent research progress on factors that may affect permeability RCD ECs under septic conditions, including glycocalyx, damage-associated molecular patterns, ECs, such as apoptosis, pyroptosis, ferroptosis, autophagy. offers insights into endothelial aiming contribute developing small-molecule targeted clinical therapies.

Language: Английский

Exploring the Anti-PANoptosis Mechanism of Dachaihu Decoction Against Sepsis-Induced Acute Lung Injury: Network Pharmacology, Bioinformatics, and Experimental Validation DOI Creative Commons
Zhen Yang,

Xingyu Kao,

Lin Zhang

et al.

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 349 - 368

Published: Jan. 1, 2025

Dachaihu decoction (DCHD) is a common Chinese medicine formula against sepsis-induced acute lung injury (SALI). PANoptosis novel type of programmed cell death. Nevertheless, The mechanisms DCHD SALI via anti-PANoptosis remains unknown. First, we identified the intersecting targets among DCHD, SALI, and using relevant databases published literature. Then, protein-protein interaction (PPI) network, molecular docking, functional enrichment analysis were conducted. In vivo, cecal ligation puncture (CLP) was used to construct sepsis mouse model, therapeutic effects on evaluated hematoxylin eosin (H&E) staining, quantitative real-time PCR (qRT-PCR), ELISA. Finally, qRT-PCR, immunofluorescence Western blotting verify effect DCHD-containing serum (DCHD-DS) LPS-induced RAW 264.7 macrophages in vitro. 82 by mapping PANoptosis. Enrichment showed that modulating tumor necrosis factor (TNF), AGE-RAGE, phosphoinositide 3-kinase (PI3K)-AKT, Toll-like receptor signaling pathways targeting Casp3, cellular antigen p53 (TP53), B-cell lymphoma 2 (Bcl2), toll-like receptor-4 (TLR4), STAT3, STAT1, RELA, NF-κB1, myeloid leukemia-1 (MCL1), JUN, IL-1β, HSP90AA1, Casp9, Casp8, Bcl2l1. Molecular docking revealed key components have high binding affinity core targets. improved histopathological injury, reduced inflammatory expression, alleviated oxidative stress tissues. vitro, DCHD-DS morphology changes, release pro-inflammatory factors, p65 nucleus aggregation. Furthermore, verified inhibited downregulating PI3K/AKT/NF-κB signalling pathway. attenuates inhibiting control Our study provides solid foundation for investigating its clinical application treatment SALI.

Language: Английский

Citations

0
Recent Advances in Pathogenesis and Anticoagulation Treatment of Sepsis-Induced Coagulopathy DOI Creative Commons

Cheng Man,

Yuan An,

Guoxin Wang

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 737 - 750

Published: Jan. 1, 2025

Coagulopathy in sepsis is common and associated with high mortality. Although immunothrombosis necessary for infection control, excessive thrombus formation can trigger a systemic thrombo-inflammatory response. Immunothrombosis plays core role sepsis-induced coagulopathy, research has revealed complex interplay between inflammation coagulation. Different mechanisms underlying sepsis-related coagulopathy are discussed, including factors contributing to the imbalance of pro- anticoagulation relevant endothelial cells. The potential therapeutic implications anticoagulants on these discussed. This review contributes our understanding pathogenesis patients sepsis. Recent studies suggest that cells play an important immunoregulation hemostasis. Meanwhile, non-anticoagulation effects anticoagulants, especially heparin, which act septic patients, have been partially revealed. We believe further insights into will help physicians evaluate patient conditions effectively, leading advanced early recognition better decision-making treatment

Language: Английский

Citations

0
Emodin protects against severe acute pancreatitis-associated acute lung injury by activating Nrf2/HO-1/GPX4 signal and inhibiting ferroptosis in vivo and in vitro DOI Creative Commons
Gang Shen, Haiyun Wen, Huijuan Li

et al.

BMC Gastroenterology, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 5, 2025

Severe acute pancreatitis (SAP) has high morbidity, a complicated and dangerous course, many complications, including severe pulmonary complications. SAP-associated lung injury (SAP-ALI) is still significant challenge for surgeons because of its mortality. Therefore, more effective treatment methods are urgently needed. Emodin (EMO) shown tremendous potential in treating refractory diseases. However, protection mechanism SAP-ALI needs to be further clarified. This study was undertaken investigate the protective effects EMO against SAP rats alveolar epithelial cells, with particular focus on classical ferroptosis pathway. In an vivo study, forty SD were evenly split into five groups: sham operation (SO) group, biliopancreatic duct retrogradely injected 5% sodium taurocholate (STC) create + group administered via gavage following modeling, ML385 (a given inhibitor nuclear factor erythroid 2-related 2 (Nrf2)), group. vitro A549 cell lines exposed lipopolysaccharide (LPS) treated EMO. also used inhibit expression Nrf2. Pancreatic tissue damage evaluated using histological examination molecular experiments. Enzyme-linked immunosorbent assays (ELISA) assess levels pro-inflammatory cytokines, Fe2+, associated oxidative stress indicators serum supernatant. Real-time polymerase chain reaction (PCR), Western blot (WB), immunofluorescence find expressions related mRNAs proteins or cells. The findings demonstrated that suppressing Nrf2 exacerbated inflammatory response brought by pathological alterations SAP-ALI. reversed this change activating Nrf2/Heme Oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4) signal path. Moreover, these results showed EMO, contrary ML385, suppressed response, which manifested as up-regulated glutathione (GSH) GPX4 down-regulated malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS) levels. Our effectively inhibited both vitro, while modulating Nrf2/HO-1/GPX4 signaling pathway provide

Language: Английский

Citations

0
Focus on the role of calcium signaling in ferroptosis: a potential therapeutic strategy for sepsis-induced acute lung injury DOI Creative Commons
Yifei Xu,

Xintian Qu,

Minghao Liang

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Sept. 17, 2024

By engaging in redox processes, ferroptosis plays a crucial role sepsis-induced acute lung injury (ALI). Although iron stimulates calcium signaling through the stimulation of redox-sensitive pathways, function signals physiological process septic ALI remains unidentified. Iron homeostasis disequilibrium is frequently accompanied by aberrant signaling. Intracellular overflow can be symptom dysregulation cellular state, which characterized overload during early phase ferroptosis. This lead to disruptions and The mechanisms controlling are reviewed here, along with their significance injury, potential these processes clarified. We propose that development combined involving bidirectional interaction between Our goal raise awareness about pathophysiology investigate relationship also aimed develop calcium-antagonistic therapies target improve quality survival for patients suffering from injury.

Language: Английский

Citations

1
Targeting ferroptosis offers therapy choice in sepsis-associated acute lung injury DOI
Yu Wang, Weixue Wang, Yi Zhang

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 283, P. 117152 - 117152

Published: Dec. 8, 2024

Language: Английский

Citations

1
Toosendanin Alleviates Acute Lung Injury by Reducing Pulmonary Vascular Barrier Dysfunction Mediated by Endoplasmic Reticulum Stress Through mTOR DOI

Xiaocheng Mao,

Cheng Wang, Hong Tang

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 136, P. 156277 - 156277

Published: Nov. 24, 2024

Language: Английский

Citations

0
Sepsis-Induced Endothelial Dysfunction: Permeability and Regulated Cell Death DOI Creative Commons

Wei Zhang,

Luofeng Jiang, Xirui Tong

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 9953 - 9973

Published: Nov. 1, 2024

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. Endothelial cells (ECs) are an important cell type typically affected in sepsis, resulting compromised barrier function and various forms of regulated death (RCD). However, the precise mechanisms underlying sepsis-induced EC damage remain unclear. This review summarizes recent research progress on factors that may affect permeability RCD ECs under septic conditions, including glycocalyx, damage-associated molecular patterns, ECs, such as apoptosis, pyroptosis, ferroptosis, autophagy. offers insights into endothelial aiming contribute developing small-molecule targeted clinical therapies.

Language: Английский

Citations

0