Sepsis is an aggressive and life-threatening organ dysfunction induced by infection. Excessive inflammation and coagulation contribute to the negative outcomes for sepsis, resulting in high morbidity and mortality. In this study, we explored whether Eupatilin could alleviate lung injury, reduce inflammation and coagulation during sepsis. Methods: We constructed an in vitro sepsis model by stimulating RAW264.7 cells with 1 μg/mL lipopolysaccharide (LPS) for 6 hours. The cells were divided into control group, LPS group, LPS+ Eupatilin (Eup) group, and Eup group to detect their cell activity and inflammatory cytokines and coagulation factor levels. Cells in LPS+Eup and Eup group were pretreated with Eupatilin (10μM) for 2 hours. In vivo, mice were divided into sham operation group, cecal ligation and puncture (CLP) group and Eup group. Mice in the CLP and Eup groups were pretreated with Eupatilin (10mg/kg) for 2 hours by gavage. Lung tissue and plasma were collected and inflammatory cytokines, coagulation factors and signaling were measured. Results: In vitro, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and tissue factor (TF) expression in LPS-stimulated RAW264.7 cells was downregulated by Eupatilin (10μM). Furthermore, Eupatilin inhibited phosphorylation of the JAK2/STAT3 signaling pathway and suppressed p-STAT3 nuclear translocation. In vivo, Eupatilin increased the survival rate of the mice. In septic mice, plasma concentrations of TNF-α, IL-1β and IL-6, as well as TF, plasminogen activator inhibitor 1 (PAI-1), D-dimer, thrombinantithrombin complex (TAT) and fibrinogen were improved by Eupatilin. Moreover, Eupatilin alleviated lung injury by improving the expression of inflammatory cytokines and TF, fibrin deposition and macrophage infiltration in lung tissue. Conclusion:Our results revealed that Eupatilin may modulate inflammation and coagulation indicators as well as improve lung injury in sepsis via the JAK2/STAT3 signaling pathway.

Abstract Gastric carcinoma (GC) remains high incidence and mortality both in developed and developing countries. SPARC is extracellular non-structural matrix glycoprotein. Previous studies were closely associated with bone disease. However, the role of SPARC in GC remains largely unclear. In our study, we explored the diagnosis, prognosis and pathway enrichments value of SPARC in GC. Here, with the data from The Cancer Genome Atlas (TCGA), we used receiver operating characteristic (ROC) curve analysis to estimate the diagnosis value of the SPARC expression, Univariate and multivariate analysis to the prognosis, Gene set enrichment analysis (GSEA) to the signal pathway enrichments. As a result, SPARC expression was significantly higher in the GC tissue samples. Those with high SPARC expression of GC patients were worse prognosis. GSEA shows the gene sets related signal pathways including transforming growth factor (TGF) beta signaling pathway, pathways in cancer, Wnt signaling pathway, Mitogen-activated protein kinase (MAPK) signaling pathway etc. In brief, those results suggest that SPARC can serve as a potential biomarker for GC in diagnosis and prognosis.

Objective. Sepsis is a life-threatening condition, and the mechanism of coagulation dysfunction in sepsis remains unknown. We aimed to investigate the mechanism of coagulation dysfunction in sepsis.Methods. Standard methods were used to establish the sepsis models and generate gene expression profiles. Bioinformatics analysis was carried out by GO and KEGG enrichment analysis, construction of PPIs and screening of seed genes. Finally, seed genes were used to rebuild the disease-related pathways.Results. Our experiments revealed an inflammatory response and coagulation dysfunction in both animal and cell models. After determining the DEGs, GO and KEGG functional analysis showed that there is a significant correlation between the inflammatory response and DNA damage. PPI network analysis screened 9 seed genes related to cell mitosis and platelet-derived growth factor receptor signaling pathways. Some of the seed genes were relevant to COVID-19.Conclusions. This study explored the molecular mechanism of coagulation dysfunction in sepsis models by bioinformatics analysis. This may have guiding significance in reducing the risk of complications in patients with sepsis and improving the effectiveness of treatment.

Gastric carcinoma (GC) remains high incidence and mortality both in developed and developing countries. SPARC is extracellular non-structural matrix glycoprotein. Previous studies were closely associated with bone disease. However, the role of SPARC in GC remains largely unclear. In our study, we explored the diagnosis, prognosis and pathway enrichments value of SPARC in GC. Here, with the data from The Cancer Genome Atlas (TCGA), we used receiver operating characteristic (ROC) curve analysis to estimate the diagnosis value of the SPARC expression, Univariate and multivariate analysis to the prognosis, Gene set enrichment analysis (GSEA) to the signal pathway enrichments. As a result, SPARC expression was significantly higher in the GC tissue samples. Those with high SPARC expression of GC patients were worse prognosis. GSEA shows the gene sets related signal pathways including transforming growth factor (TGF) beta signaling pathway, pathways in cancer, Wnt signaling pathway, Mitogen-activated protein kinase (MAPK) signaling pathway etc. In brief, those results suggest that SPARC can serve as a potential biomarker for GC in diagnosis and prognosis.