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PURPOSE: Leukocyte adhesion to vascular and matrix Metalloproteinase-8 (MMP8) expression is increased in sepsis and associated with poor prognosis in sepsis patients. This study aimed to investigate the role of MMP8 in sepsis serum mediated leukocyte adhesion. METHODS: Bioinformatics analysis of GSE64457 and GSE65682 was performed to evaluate the role of MMP8 in the progression of sepsis. Expression of MMP8 in blood samples from patients with sepsis was detected by qRT-PCR and ELISA. Human umbilical vein endothelial cells (HUVECs) were treated with sepsis serum, control serum, and MMP8 inhibitor. Expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) were detected by qRT-PCR and ELISA, respectively. The protein expression of total p38, phosphorylated-p38, ERK1/2, and p-ERK1/2 was detected by Western blotting. Peripheral blood mononuclear cells (PBMCs) and polymorphonuclear neutrophils (PMNs) were incubated with the treated HUVECs to calculate leukocyte adhesion. RESULTS: Four hundred and twenty-nine differentially expressed genes (DEGs) and seven hub genes between sepsis patients and healthy controls were identified. GO function analysis of DEGs and hub genes indicated that the DEGs and hub genes were mainly enriched in neutrophil activation. MMP8 was selected as a key gene with an unfavorable prognosis in sepsis patients. The mRNA and protein expression of MMP8 in blood from sepsis patients were significantly higher than controls. Leukocyte adhesion and mRNA and protein expression of VCAM-1 and ICAM-1 were significantly increased in the sepsis serum group compared to that in the control group, as was the protein expression of p-p38 and p-ERK1/2. However, the MMP8 inhibitor suppressed the leukocyte adhesion promoted by sepsis serum by decreasing the expression of VCAM-1, ICAM-1, p-p38, and p-ERK1/2. CONCLUSION: Our study indicated that MMP8 acts as a key gene in the development of sepsis, and sepsis serum promotes leukocyte adhesion to HUVECs via MMP8, which suggest that MMP8 might be a potential therapeutic target for sepsis.
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BACKGROUND: Patients with severe burns continue to display a high mortality rate during the initial shock period. The precise molecular mechanism underlying the change in host response during severe burn shock remains unknown. This study aimed to identify key genes leading to the change in host response during burn shock. METHODS: The GSE77791 dataset, which was utilized in a previous study that compared hydrocortisone administration to placebo (NaCl 0.9%) in the inflammatory reaction of severe burn shock, was downloaded from the Gene Expression Omnibus (GEO) database and analyzed to identify the differentially expressed genes (DEGs). Functional enrichment analyses of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed. The protein-protein interaction (PPI) network of DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and then visualized in Cytoscape. In addition, important modules in this network were selected using the Molecular Complex Detection (MCODE) algorithm, and hub genes were identified in cytoHubba, a Cytoscape plugin. RESULTS: A total of 1059 DEGs (508 downregulated genes and 551 upregulated genes) were identified from the dataset. The DEGs enriched in GO terms and KEGG pathways were related to immune response. The PPI network contained 439 nodes and 2430 protein pairs. Finally, important modules and hub genes were identified using the different Cytoscape plugins. The key genes in burn shock were identified as arginase 1 (ARG1), cytoskeleton-associated protein (CKAP4), complement C3a receptor (C3AR1), neutrophil elastase (ELANE), gamma-glutamyl hydrolase (GGH), orosomucoid (ORM1), and quiescin sulfhydryl (QSOX1). CONCLUSION: The DEGs, functional terms and pathways, and hub genes identified in the present study can help shed light on the molecular mechanism underlying the changes in host response during burn shock and provide potential targets for early detection and treatment of burn shock.
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OBJECTIVE: Bone metastasis was common in patients with malignant tumors. The purpose of this study was to investigate the serum bone-specific alkaline phosphatase (B-ALP) as a biomarker in the diagnosis of osseous metastases in patients with cancers. METHODS: We searched the databases of Pubmed, Cochrane Library, Medline, CNKI and Wanfang to screen the relevant articles about the serum B-ALP detection in the diagnosis of osseous metastases in patients with malignant carcinomas. The pooled sensitivity, specificity, summary receiver operating characteristic (SROC) curve were calculated by STATA12.0 software. RESULTS: Nineteen trials with 3 268 subjects were finally included in this study. The mean level of serum B-ALP was 41.50 ± 26.61 µg/L (216.90 ± 139.00U/L) in patients with osseous metastases and 14.49 ± 5.52 µg/L (103.30 ± 39.44 U/L) in patients without osseous metastases. The serum level of B-ALP was significant higher in the osseous metastases group than that in the control group (P < 0.05); The pooled sensitivity and specificity for diagnosis of osseous metastases were 0.74 with its 95% confidence interval (95% CI) of 0.62-0.83 and 0.80 (95% CI: 0.67-0.89), respectively. The area under the SRCO was 0.86 (95% CI: 0.83-0.89). CONCLUSION: Serum B-ALP can be a promising biomarker for detection of osseous metastases in patients with cancers.
