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The value of plasma fibronectin (pFN) in the diagnosis and prognosis of sepsis has not been fully established. Previous studies finding that pFN is significantly reduced in sepsis, however, whether reduced pFn affects the prognosis of sepsis has not been clarified. Here, we detected and analyzed pFN and other conventional inflammatory markers in advanced sepsis patients and performed correlation analysis with SOFA score. We also used Fn gene conditional knockout mice which were performed by cecum ligation and puncture (CLP) to investigate the effect of FN deficiency on sepsis prognosis. We found, compared with procalcitonin, c-reactive protein, and interleukin-6, pFN was more correlated with SOFA score in advanced sepsis patients (r -.720, p .001). In animal experiments, Fn gene knockout mice showed significantly greater mortality after CLP compared with the control group because of inhibited phagocytosis and bacterial clearance ability of macrophages, with double cytokine storm. Furthermore, FN can regulate macrophages through the integrin α5β1/Fak/Src signaling pathway. Overall, we found pFN can more accurately reflect the severity and prognosis of advanced sepsis. The absence of FN altered the cytokine storm and phagocytic function of macrophages, suggesting that FN could be a potential therapeutic target in sepsis.

This study performed the first microarray analysis of long-noncoding RNA (lncRNA) and mRNA expression profiles in human steroid-induced avascular necrosis of the femoral head (SAVNFH). Expression levels of lncRNAs and mRNAs in three human SAVNFH samples and three human femoral head fracture samples (controls) were detected using third-generation lncRNA microarrays (KangChen Biotech, Shanghai, China). The fold change, false discovery rate, and P value were utilized to filter genes with significant differential expression in the SAVNFH samples compared with the control samples. In total, there were 1179 upregulated and 3214 downregulated lncRNAs (P2. zerofold, P < 0.05). Meanwhile, 1092 upregulated and 565 downregulated mRNAs were found in the SAVNFH samples compared with the control samples. Then, quantitative real-time polymerase chain reaction was used to confirm the previous microarray results using 8 and 20 selected dysregulated lncRNAs and mRNAs, respectively, and the results generally confirmed the microarray findings. Finally, we used Gene Ontology (GO) and pathway analysis to investigate the functions of the altered mRNAs and their associated GO terms and biological pathways. The Immune system process term (GO:0002376) was the most significantly upregulated GO term, and the Regulation of blood coagulation term (GO:0030193) was the most significantly downregulated GO term in the biological process category for the SAVNFH samples. "Hematopoietic cell lineage - Homo sapiens (human) (Pathway ID: hsa04640)" and "Complement and coagulation cascades - Homo sapiens (human) (Pathway ID: hsa04610)" were the most significantly up- and downregulated pathways in the SAVNFH samples compared with the controls. In conclusion, the differential expression of lncRNAs and mRNAs may be correlated with the pathogenesis of SAVNFH, and these significantly dysregulated lncRNAs and mRNAs may function through networks or participate in several specific biological processes. Further research is needed to understand their exact functions and mechanisms in SAVNFH.

We used RNA-sequencing (RNA-Seq) technology and an old hematopoietic stem and progenitor cells (HSPCs) model in vitro to analyze differential expressions of mismatch repair (MMR)-related genes in aged HSPCs, so as to explore the mechanism of DNA MMR injury in hematopoietic stem cells (HSC) aging. In this study, by combining RNA-seq data and National Center for Biotechnology Information database, we focus on six widely reported MMR genes MSH2, MSH3, MSH6, MLH1, PMS1, PMS2, and five MMR genes with closer ties to HSC aging Pcna, Exo1, Rpa1, Rpa2, and Rpa3 according to the genes functional classification and the related signaling pathway. It is concluded that MMR is closely related to HSC aging. This study provides experimental evidence for future researching MMR in HSC aging.