Estrogen receptor subtype mediated anti-inflammation and vasorelaxation via genomic and nongenomic actions in septic mice DOI Creative Commons
Luyun Zhang, Hanxing Wan, Mengting Zhang

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: May 17, 2023

Sepsis is a life-threatening disease with high mortality worldwide. Septic females have lower severity and than the males, suggesting estrogen exerts protective action, but nothing known about role of vascular endothelial receptor subtypes in this process. In present study, we aimed to study receptors on mesenteric arterioles normal sepsis mice elucidate underlying mechanisms. was induced by intraperitoneal injection LPS. The changes expression release serum cell supernatant proinflammatory cytokines, including TNF-α, IL-1β IL-6, were measured qPCR ELISA, functions multiple organs analyzed. functional activities mouse determined Mulvany-style wire myograph. phospholipase C (PLC) inositol 1,4,5-trisphosphate (IP3R) cells examined Western blot their characterized Ca2+ imaging. female had higher survival rate male mice, pretreatment E2 for 5 days significantly improved inhibited cytokines septic mice. ameliorated pulmonary, intestinal, hepatic renal organ injuries mice; ER via PLC/IP3R/Ca2+ pathway. E2/ER immediately endothelial-derived hyperpolarization (EDH)-mediated vasorelaxation pathway, which more impaired could rescue acetylcholine (ACh)-induced EDH-mediated through mediates anti-inflammation genomic nongenomic actions sepsis. Mechanistically, activation reduces induces leading amelioration sepsis-induced injury rate.

Language: Английский

The role of neutrophil extracellular traps in sepsis and sepsis-related acute lung injury DOI

Shujing Zou,

Hongyu Jie, Xinai Han

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 124, P. 110436 - 110436

Published: Sept. 7, 2023

Language: Английский

Citations

33
The double sides of NLRP3 inflammasome activation in sepsis DOI
Clara Vigneron, Bénédicte F. Py, Guillaume Monneret

et al.

Clinical Science, Journal Year: 2023, Volume and Issue: 137(5), P. 333 - 351

Published: March 1, 2023

Abstract Sepsis is defined as a life-threatening organ dysfunction induced by dysregulated host immune response to infection. Immune sepsis complex and dynamic. It schematically described an early systemic inflammatory leading failures deaths, followed the development of persistent alterations affecting both innate adaptive responses associated with increased risk secondary infections, viral reactivations, late mortality. In this review, we will focus on role NACHT, leucin-rich repeat pyrin-containing protein 3 (NLRP3) inflammasome in pathophysiology sepsis. NLRP3 multiproteic intracellular activated infectious pathogens through two-step process resulting release pro-inflammatory cytokines IL-1β IL-18 formation membrane pores gasdermin D, inducing form cell death called pyroptosis. The can be ambivalent. Indeed, although it might protect against when moderately after initial infection, excessive activation induce inflammation multiple failure during acute phase disease. Moreover, become exhausted contribute post-septic immunosuppression, driving impaired functions cells. Targeting could thus attractive option either antagonists or inhibition pathway downstream components. Available treatments results first clinical trials discussed.

Language: Английский

Citations

19
Dysregulated dendritic cells in sepsis: functional impairment and regulated cell death DOI Creative Commons

Liyu Zheng,

Yu Duan,

Peng-yi He

et al.

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: May 30, 2024

Abstract Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Studies have indicated that immune plays central role in the pathogenesis of sepsis. Dendritic cells (DCs) play crucial emergence The major manifestations DCs septic state are abnormal functions and depletion numbers, which linked higher mortality vulnerability secondary infections Apoptosis most widely studied pathway number reduction DCs. In past few years, there has been surge studies focusing on regulated cell death (RCD). This emerging field encompasses various forms death, such necroptosis, pyroptosis, ferroptosis, autophagy-dependent (ADCD). Regulation DC’s RCD can serve possible therapeutic focus for treatment Throughout time, numerous tactics devised effectively implemented improve during sepsis progression, including modifying inhibiting DC death. this review, we provide an overview functional impairment states. Also, highlight recent advances targeting regulate following challenge. Graphical

Language: Английский

Citations

8
Integrated analysis of single-cell RNA-seq and chipset data unravels PANoptosis-related genes in sepsis DOI Creative Commons
Wei Dai, Ping Zheng, Jian Wu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 3, 2024

Background The poor prognosis of sepsis warrants the investigation biomarkers for predicting outcome. Several studies have indicated that PANoptosis exerts a critical role in tumor initiation and development. Nevertheless, has not been fully elucidated. Methods We obtained Sepsis samples scRNA-seq data from GEO database. PANoptosis-related genes were subjected to consensus clustering functional enrichment analysis, followed by identification differentially expressed calculation score. A PANoptosis-based prognostic model was developed. In vitro experiments performed verify distinct genes. An external dataset used cellular localization. Results Unsupervised analysis using 16 identified three subtypes sepsis. Kaplan-Meier showed significant differences patient survival among subtypes, with different immune infiltration levels. Differential 48 DEGs. Boruta algorithm PCA DEGs as signature developed PANscore based on these genes, which can distinguish clinical characteristics may serve potential biomarker. Single-cell sequencing six cell types, high relatively B cells, low CD16+ CD14+ monocytes Megakaryocyte progenitors. ZBP1, XAF1, IFI44L, SOCS1, PARP14 higher cells PANscore. Conclusion machine learning profiling related subgroups features

Language: Английский

Citations

7
Exploring ncRNA-mediated pathways in sepsis-induced pyroptosis DOI
Asif Ahmad Bhat, Yassine Riadi, Muhammad Afzal

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 256, P. 155224 - 155224

Published: Feb. 23, 2024

Language: Английский

Citations

6
Elucidating cuproptosis in metabolic dysfunction-associated steatotic liver disease DOI Open Access

Yamei Li,

Ping Qi, Siyuan Song

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116585 - 116585

Published: April 13, 2024

Emerging research into metabolic dysfunction-associated steatotic liver disease (MASLD) up until January 2024 has highlighted the critical role of cuproptosis, a unique cell death mechanism triggered by copper overload, in disease's development. This connection offers new insights MASLD's complex pathogenesis, pointing to accumulation as key factor that disrupts lipid metabolism and insulin sensitivity. The identification cuproptosis significant contributor MASLD underscores potential for targeting copper-mediated pathways novel therapeutic approaches. promising avenue suggests managing levels could mitigate progression, offering fresh perspective on treatment strategies. Further investigations how influences are essential unraveling detailed mechanisms at play identifying effective interventions. focus copper's health opens possibility developing targeted therapies address underlying causes MASLD, moving beyond symptomatic tackle root problem. exploration context exemplifies importance understanding metal homeostasis diseases represents step forward quest more treatments. direction lights path innovative management reversal.

Language: Английский

Citations

5
Caspase-3/GSDME mediated pyroptosis: A potential pathway for sepsis DOI

Chaoze Jiao,

Haidan Zhang,

Hongyao Li

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 124, P. 111022 - 111022

Published: Oct. 12, 2023

Language: Английский

Citations

13
ADAR1 protects pulmonary macrophages from sepsis-induced pyroptosis and lung injury through miR-21/A20 signaling DOI Creative Commons
Xiaojun Zhao, Jiangang Xie,

Chujun Duan

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 20(2), P. 464 - 485

Published: Dec. 5, 2023

Acute lung injury is a serious complication of sepsis with high morbidity and mortality. Pyroptosis proinflammatory form programmed cell death that leads to immune dysregulation organ dysfunction during sepsis. We previously found adenosine deaminase acting on double-stranded RNA 1 (ADAR1) plays regulatory roles in the pathology sepsis, but mechanism ADAR1 sepsis-induced pyroptosis remains unclear. Here, we mainly investigated effects underlying pulmonary macrophages through sequencing clinical samples, caecal ligation puncture (CLP)-induced septic mouse models, vitro cellular experiments using RAW264.7 cells lipopolysaccharide (LPS) stimulation. The results showed was activated peripheral blood mononuclear (PBMCs) from patients In CLP-induced model, macrophages. LPS-stimulated significantly increased activation NLRP3 inflammasome. downregulated PMBCs overexpression alleviated inflammasome activation. Mechanistically, macrophage were mediated by miR-21/A20/NLRP3 signalling cascade. attenuated hindered axis. Our study highlights role protecting against suggests targeting ADAR1/miR-21 as therapeutic opportunity sepsis-related injury.

Language: Английский

Citations

12
Unlocking the Potential: Quercetin and Its Natural Derivatives as Promising Therapeutics for Sepsis DOI Creative Commons

Tian Wang,

Linxi Lv, Hui Feng

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(2), P. 444 - 444

Published: Feb. 16, 2024

Sepsis is a syndrome of organ dysfunction caused by an uncontrolled inflammatory response, which can seriously endanger life. Currently, there still shortage specific therapeutic drugs. Quercetin and its natural derivatives have received lot attention recently for their potential in treating sepsis. Here, we provide comprehensive summary the recent research progress on quercetin derivatives, with focus mechanisms antioxidation anti-inflammation. To obtain necessary information, conducted search PubMed, Web Science, EBSCO, Cochrane library databases using keywords sepsis, anti-inflammatory, antioxidant, anti-infection, quercetin, to identify relevant from 6315 articles published last five years. At present, 11 been intensively studied. They primarily exert anti-inflammation effects through PI3K/AKT/NF-κB, Nrf2/ARE, MAPK pathways. The feasibility these compounds experimental models clinical application were also discussed. In conclusion, good treatment

Language: Английский

Citations

4
Boarding pyroptosis onto nanotechnology for cancer therapy DOI

Weiyue Ban,

Zhichao Chen,

Tao Zhang

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 370, P. 653 - 676

Published: May 15, 2024

Language: Английский

Citations

4