DNA and cell biology
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DNA and cell biology · Jan 2020
Fusobacterium nucleatum Caused DNA Damage and Promoted Cell Proliferation by the Ku70/p53 Pathway in Oral Cancer Cells.
Bacterial infection influences genomic stability and integrity by causing DNA damage, which increases the possibility of tumor initiation and development. We aimed to investigate whether Fusobacterium nucleatum, one of the periodontal pathogens, promoted oral squamous cell carcinoma (OSCC) by causing DNA double-strand break (DSB). Tca8113 tongue squamous cell carcinoma cells were infected with F. nucleatum. ⋯ Meanwhile, the expression of Ku70 and wild p53 was downregulated. When Ku70 was overexpressed, the expression of wild p53 in response to F. nucleatum infection was upregulated and cell proliferation was accordingly inhibited. We concluded that F. nucleatum infection promoted the proliferation ability of Tca8113 by causing DNA damage via the Ku70/p53 pathway.
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DNA and cell biology · Dec 2019
Anti-Inflammatory Activity of Adenosine 5'-Trisphosphate in Lipopolysaccharide-Stimulated Human Umbilical Vein Endothelial Cells Through Negative Regulation of Toll-Like Receptor MyD88 Signaling.
Activation of TLR4-MyD88-NF-κB signaling by lipopolysaccharide (LPS) evokes a proinflammatory immune response, and plays a pivotal role in initiation and progression of atherosclerosis (AS). ATP (adenosine 5'-trisphosphate), a powerful extracellular signal transduction molecule, functions to regulate immune inflammatory responses depending on the type of P2 receptors and cell lines. In this study, we first performed RT-PCR to detect the mRNA expression of monocyte chemoattractant protein-1 (MCP-1), IL-8, and IL-1β induced by different concentrations of LPS in human umbilical vein endothelial cells (HUVECs). ⋯ ATP at low concentrations also downregulated the mRNA expression of TLR4, CD14, and MyD88 and inhibited LPS-induced phosphorylation of p65. Furthermore, Suramin, a nonspecific P2Y receptor antagonist, did not attenuate the inhibition of ATP on LPS-induced IL-1β and MCP-1 expression. Taking this together, low concentration ATP inhibited LPS-induced inflammation in HUVECs by negatively regulating TLR4-MyD88 signaling, and P2Y receptors were not involved in this process, which might provide new ideas for prevention and treatment of inflammatory diseases such as AS.
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DNA and cell biology · Dec 2019
Identification of DDX58 and CXCL10 as Potential Biomarkers in Acute Respiratory Distress Syndrome.
Acute respiratory distress syndrome (ARDS) is a devastating condition of acute inflammatory lung injury and causes high morbidity and mortality. Therefore, investigations on the effective biomarkers will be significant for the understanding of ARDS. In our research, the gene expression profiles of 27 samples from ARDS patients (n = 18) and healthy controls (n = 9) were analyzed and eight gene co-expression modules were identified by constructing weighted gene co-expression network. The correlation analysis of modules with phenotypes showed that genes in the yellow and black modules, which were significantly enriched in the ARDS-related pathways, such as TNF signaling pathway, Toll-like receptor signaling pathway, and NF-kappa B signaling pathway, were associated with the phenotype "time postinfection." Genes DDX58 and CXCL10, which were highly expressed after infection and significantly enriched in ARDS-related pathways, presented high score in protein-protein interaction analysis, indicating that they may be associated with ARDS and providing novel biomarkers for its diagnosis, treatment, and surveillance.
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DNA and cell biology · Nov 2018
A Novel Variant of Desmoplakin Is Potentially Associated with Silicosis Risk.
Two genome-wide association studies and one sequencing study have coincidently reported significant associations of single nucleotide polymorphisms (SNPs) in the desmoplakin (DSP) gene with the risk of pulmonary fibrosis (mainly idiopathic pulmonary fibrosis). However, these findings have not been well generalized to occupational pulmonary fibrosis (e.g., silica-related silicosis). We systematically genotyped 8 potentially functional SNPs and the previously reported rs2076295 and rs2744371 in DSP gene region and evaluated the associations between these 10 SNPs and silicosis risk in a case-control study that included 177 silicosis cases and 204 controls with similar numbers of silica dust exposure years as the cases from a Chinese population. ⋯ Further functional annotation indicated that the rs2076304 might influence the binding of RHOXF1. The rs2076304 in DSP gene is associated with a significantly increased risk of silicosis in a Han Chinese population. Further studies are warranted to validate and extend our findings, especially the biological mechanisms of rs2076304 in silicosis susceptibility.