Molecular mechanisms and functions of pyroptosis in sepsis and sepsis-associated organ dysfunction

Wen, Ri; Liu, Yongping; Tong, Xiao-Xu; Zhang, Tie-Ning; Yang, Ni

doi:10.3389/fcimb.2022.962139

Cited by 29 publications

(21 citation statements)

References 181 publications

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“…This results in various organ dysfunctions including cardiovascular, liver, pulmonary renal and brain impairments ( 2 ). As the latest sepsis guidelines suggest the impact of multiple organ dysfunction on the host, therefore, different types of cell death, including apoptosis ( 3 ), pyroptosis ( 4 ), and necroptosis ( 5 ) might be involved in sepsis.…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis of single-cell RNA-seq and chipset data unravels PANoptosis-related genes in sepsis

Dai,

Zheng,

et al. 2024

Front. Immunol.

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

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Section: Introductionmentioning

confidence: 99%

Integrated analysis of single-cell RNA-seq and chipset data unravels PANoptosis-related genes in sepsis

Dai,

Zheng,

et al. 2024

Front. Immunol.

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“…Cysteine-requiring aspartate protease (caspase) is a protease family that plays an important role in programmed cell death (including apoptosis) [32]. The activity of caspase family members in caspase in the system will increase significantly in the course of apoptosis [33].…”

Section: Discussionmentioning

confidence: 99%

Costimulatory Molecules CD80/86 Trigger Non-Specific Cytotoxic Cell of Nile tilapia (Oreochromis niloticus) to Kill CIK Cells

Huang

Chen

Xie

et al. 2022

Fishes

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The teleost non-specific cytotoxic cell (NCC), as the evolutionary precursors of NK cells, is an important cytotoxic cell population in the innate immune system of teleost. We have recently realized that costimulatory CD80/86 have conservation in structural and interactional features with its ligand CD28 in Nile tilapia (Oreochromis niloticus). However, the ability of CD80/86 to regulate NCC activity has not been fully investigated. In the present study, we first obtained the recombinant fusion CD80/86 protein from O. niloticus (rOn-CD80/86). Then, NCC incubation with rOn-CD80/86 resulted in a significant production of NCC effector cytokines, including tumor necrosis factor-alpha, cellular apoptosis susceptibility and NK-lysin. Furthermore, NCC treatment with rOn-CD80/86 could significantly improve the ability to kill kidney cells of Grass carp (CIK) and up-regulate the activities of caspase-1 and caspase-3 in CIKs. The yeast, two-hybrid assay showed that On-CD80/86 cannot directly interact with non-specific cytotoxic cell receptor protein-1 of O. niloticus (On-NCCRP-1). The single-cell RNA-Seq data of Nile tilapia head kidney lymphocytes analysis found On-CD28 did not exhibit expression on NCCs subsets. The above results suggest that costimulatory molecules On-CD80/86 is independent of On-NCCRP-1 and On-CD28 receptor in modulating NCC killing activity in vitro of Nile tilapia. The results also provide more insights into the mechanism of NCC activity regulation.

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“…[4]Despite extensive research efforts, the precise mechanisms driving sepsis pathophysiology remain incompletely understood, hindering the development of effective therapeutic strategies. [5] Neutrophil Extracellular Traps (NETs), formed through a process known as NETosis, have emerged as key players in the pathophysiology of sepsis. [6-8] NETs are web-like structures composed of chromatin bers and antimicrobial proteins released by neutrophils to ensnare and neutralize invading pathogens.…”

Section: Introductionmentioning

confidence: 99%

Dissecting the Role of NETosis-Related Biomarkers in Sepsis: An Integrated Multi-Dataset Analysis for Diagnostic and Prognostic Applications

方

2024

Preprint

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1.Abstract: Sepsis, a systemic and life-threatening response to infection, presents complex challenges in clinical management and prognosis due to its intricate pathophysiology. The formation of Neutrophil Extracellular Traps (NETs) through a process known as NETosis has been identified as a significant contributor to the development of sepsis. This study aimed to dissect the roles of NETosis-related genes, particularly Myeloperoxidase (MPO) and Proteinase 3 (PRTN3), in sepsis progression. By integrating and analyzing multiple Gene Expression Omnibus (GEO) datasets, we conducted a comprehensive gene expression profiling that revealed consistent downregulation of MPO and PRTN3, among others, in sepsis patients. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, we characterized the biological functions and pathways associated with these genes, emphasizing their relevance to immune responses in sepsis. A prediction model utilizing these biomarkers was constructed using a Random Forest classifier, which demonstrated robust predictive capability, as reflected by an AUROC of 0.77 for training and 0.68 for validation datasets. Survival analysis further underscored the prognostic value of demographic factors, particularly gender and age. The model highlighted gender-specific survival rates and revealed a significant decline in survival probability in patients over 40 years of age. These findings illuminate the diagnostic and prognostic potential of MPO and PRTN3 in sepsis, offering novel insights into the molecular dynamics of the disease and suggesting a direction for future therapeutic strategies. The study's integrated approach and novel findings advocate for personalized management of sepsis, tailoring interventions to individual patient profiles to improve outcomes.

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Molecular mechanisms and functions of pyroptosis in sepsis and sepsis-associated organ dysfunction

Cited by 29 publications

References 181 publications

Integrated analysis of single-cell RNA-seq and chipset data unravels PANoptosis-related genes in sepsis

Integrated analysis of single-cell RNA-seq and chipset data unravels PANoptosis-related genes in sepsis

Costimulatory Molecules CD80/86 Trigger Non-Specific Cytotoxic Cell of Nile tilapia (Oreochromis niloticus) to Kill CIK Cells

Dissecting the Role of NETosis-Related Biomarkers in Sepsis: An Integrated Multi-Dataset Analysis for Diagnostic and Prognostic Applications

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