Seeking for endometrial carcinoma-related genes and their bioinformatics analysis

Objective:Screening and excavating genes and biological information related to endometrial carcinoma(EC),to provide novel means for clinical diagnosis and treatment.Methods:The gene chip data of EC was obtained from the Gene Expression Omnibus(GEO)database,we integrated gene discrepantly expressive gene analysis,enrichment of genic function and pathway analysis,protein-protein interaction(PPI)network and literature mining to predict genes and pathways of EC.Results:Functional enrichment analysis identified 976differential expression genes were participated in cell cycle regulation,proliferation,biosynthesis,protein phosphorylation and fission biological process,etc.We found eight significantly up-regulated pathways in the microarray datasets,including the MAPK signaling pathway and mTOR pathway,and six down-regulated pathways,including the P53signaling pathway and cell cycle.Gene protein related interaction network analysis was further performed,and we found twelve distinct genes,including the PCNA and CCND1,these genes were located in key position of EC related network,which may be related to the pathogenesis and progression of EC.Furthermore,there was a high correlation between PCNA and CCND1with EC by consulting the related literature and data,however,the functional mechanism was uncleared.Conclusion:The pathogenesis and progression of EC may involve in several different pathways and genes,the genes PCNA,CCND1and MAPK signaling pathway may be valuable.

Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns(With video)

Background:Burn shock caused by vascular leakage is one of the main causes of high mortality in severe burn injury.However,the pathophysiological mechanism of vascular leakage is still unclear.The purpose of this study was to explore the molecular mechanism of vascular leakage in the early stage of severe burn and provide a new target for the treatment of severe burns.Methods:Neutrophils were isolated from human peripheral blood by magnetic beads sorting.ELISA was used to detect neutrophil-derived granule proteins and glycocalyx injury products in plasma.The vascular leakage and neutrophil movement were assessed by in vivo laser confocal imaging in mice,and high-quality video were provided.Adhesion-related molecules were investigated by qRT-PCR.The damage to glycocalyx of mice vascular endothelial cellswas observed by transmission electron microscope and scanning electron microscope.Proteomic analysis,flow cytometry and immunofluorescence were used to further study the relationship between human peripheral blood neutrophil-derived hypochlorite(HOCl)and CD44 of human vascular endothelial cells.Results:In this study,we found that rapidly increasing activated neutrophils secrete heparin binding protein(HBP)andmyeloperoxidase(MPO)after severe burn injury.Increased HBP triggers vascular leakage with synergy of MPO,results in systemic edema and burn shock.Furthermore,we found that the MPO catalytic product HOCl but not MPO triggers CD44 extracellular domain shedding from vascular endothelial cells to damage the glycocalyx.Damage to the glycocalyx results in firm adhesion of neutrophils and increases vascular leakage.However,MPO inhibitors partially protect the glycocalyx of vascular endothelial cells.The combination of HBP and MPO inhibitors markedly reduces vascular leakage and systemic edema in the early stage of severe burns.Conclusions:Taken together,these data reveal that neutrophil-derived HBP and MPO play an important synergies role in triggering vascular leakage at the early stage of severe burns.Targeted intervention in these two biomolecules may introduce new strategies for helping to reduce large amount of fluid loss and subsequent burn shock.