Inhibition of Matrix Metalloproteinase-8 Protects Against Sepsis Serum Mediated Leukocyte Adhesion

Xiao, Fang; Duan, Shu-Fang; Hu, Zhiyuan; Wang, Junjie; Qiu, Le; Wang, Fei; Chen, Xulin

doi:10.3389/fmed.2022.814890

Cited by 6 publications

(5 citation statements)

References 48 publications

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“…In the process of sepsis, bacterial products and pro-inflammatory cytokines stimulate the expression of β-integrin on the surface of neutrophils, promoting adhesion between white blood cells and vascular endothelial cells [24]. However, excessive adhesion of white blood cells is also detrimental to the survival of sepsis patients [25]. Th17 cells take a key part in immune homeostasis and infection [26].…”

Section: Discussionmentioning

confidence: 99%

Prediction of Prognosis in Patients with Sepsis Based on Platelet-Related Genes

Jiang,

Zhang,

Wang

et al. 2024

Horm Metab Res

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The study aimed to develop a risk prognostic model using platelet-related genes (PRGs) to predict sepsis patient outcomes. Sepsis patient data from the Gene Expression Omnibus (GEO) database and PRGs from the Molecular Signatures Database (MSigDB) were analyzed. Differential analysis identified 1139 differentially expressed genes (DEGs) between sepsis and control groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed enrichment in functions related to immune cell regulation and pathways associated with immune response and infectious diseases. A risk prognostic model was established using LASSO and Cox regression analyses, incorporating 10 PRGs selected based on their association with sepsis prognosis. The model demonstrated good stratification and prognostic effects, confirmed by survival and receiver operating characteristic (ROC) curve analyses. It served as an independent prognostic factor in sepsis patients. Further analysis using the CIBERSORT algorithm showed higher infiltration of activated natural killer (NK) cells and lower infiltration of CD8 T cells and CD4 T cells naïve in the high-risk group compared to the low-risk group. Additionally, expression levels of human leukocyte antigen (HLA) genes were significantly lower in the high-risk group. In conclusion, the 10-gene risk model based on PRGs accurately predicted sepsis patient prognosis and immune infiltration levels. This study provides valuable insights into the role of platelets in sepsis prognosis and diagnosis, offering potential implications for personalized treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Prediction of Prognosis in Patients with Sepsis Based on Platelet-Related Genes

Jiang,

Zhang,

Wang

et al. 2024

Horm Metab Res

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“…Therefore, the activation and dysfunction of vascular endothelial cells are the central link in the progression and deterioration of sepsis. HUVECs, which could (in theory) be passed on indefinitely, has been widely used in investigating apoptosis in sepsis ( Lee et al, 2014 ; van der Slikke et al, 2021 ; Fang et al, 2022 ). In our study, we applied LPS-induced HUVECs as the septic endothelial cell model to verify our results of network pharmacology.…”

Section: Discussmentioning

confidence: 99%

Reduning Attenuates LPS-Induced Human Unmilical Vein Endothelial Cells (HUVECs) Apoptosis Through PI3K-AKT Signaling Pathway

Wang

Guo

et al. 2022

Front. Pharmacol.

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The molecular mechanism of Reduning (RDN) in the treatment of sepsis was analyzed based on network pharmacology. The system pharmacology method was administered to search the active ingredients and targets of RDN, identify the sepsis-related genes, and determine the targets of RDN in the treatment of sepsis. Cytoscape was used to build a “drug component-target” network to screen key compounds. A protein-protein interaction (PPI) network was constructed using STRING, and core targets were revealed through topological analysis. 404 shared targets of RDN and sepsis were introduced into DAVID Bioinformatics Resources 6.8 for GO and KEGG enrichment analysis to predict their possible signaling pathways and explore their molecular mechanisms. GO enrichment analysis highlighted that they were largely related to protein phosphorylation, inflammatory reaction, and positive regulation of mitogen-activated protein kinase (MAPK) cascade. KEGG enrichment analysis outlined that they were enriched in PI3K-AKT signaling pathway, calcium signaling pathway, rhoptry-associated protein 1 (Rap1) signaling pathway, and advanced glycation end products and receptors for advanced glycation end products (AGE-RAGE) signaling pathway. Molecular biological validation results exposed that RDN could significantly improve the protein expression of p-AKT and p-PI3K, alleviate apoptosis-related proteins expression level and decrease apoptosis rate in LPS-induced HUVECs. In conclusion, it was illustrated that RDN could considerably constrain LPS-induced apoptosis by activating the PI3K-AKT signaling pathway, which advocated a basis for fundamental mechanism research and clinical application of RDN in the treatment of sepsis.

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“…0.607 (95% CI = 0.524-0.685) [75,76,104,105] Inter-alpha inhibitor proteins IαIp Serine protease, it is prominent among the histone-precipitated proteins. IαIP is composed to light and heavy chains (HC).…”

Section: Biomarkers For Neonatal Sepsis: Focus On Endothelial Glycocalyxmentioning

confidence: 99%

The Endothelial Glycocalyx and Neonatal Sepsis

Fatmi

Saadi

Beltrán-García

et al. 2022

IJMS

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Sepsis carries a substantial risk of morbidity and mortality in newborns, especially preterm-born neonates. Endothelial glycocalyx (eGC) is a carbohydrate-rich layer lining the vascular endothelium, with important vascular barrier function and cell adhesion properties, serving also as a mechano-sensor for blood flow. eGC shedding is recognized as a fundamental pathophysiological process generating microvascular dysfunction, which in turn contributes to multiple organ failure and death in sepsis. Although the disruption of eGC and its consequences have been investigated intensively in the adult population, its composition, development, and potential mechanisms of action are still poorly studied during the neonatal period, and more specifically, in neonatal sepsis. Further knowledge on this topic may provide a better understanding of the molecular mechanisms that guide the sepsis pathology during the neonatal period, and would increase the usefulness of endothelial glycocalyx dysfunction as a diagnostic and prognostic biomarker. We reviewed several components of the eGC that help to deeply understand the mechanisms involved in the eGC disruption during the neonatal period. In addition, we evaluated the potential of eGC components as biomarkers and future targets to develop therapeutic strategies for neonatal sepsis.

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Inhibition of Matrix Metalloproteinase-8 Protects Against Sepsis Serum Mediated Leukocyte Adhesion

Cited by 6 publications

References 48 publications

Prediction of Prognosis in Patients with Sepsis Based on Platelet-Related Genes

Prediction of Prognosis in Patients with Sepsis Based on Platelet-Related Genes

Reduning Attenuates LPS-Induced Human Unmilical Vein Endothelial Cells (HUVECs) Apoptosis Through PI3K-AKT Signaling Pathway

The Endothelial Glycocalyx and Neonatal Sepsis

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