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Abnormal methylation of secreted frizzled-related proteins (SFRPs) has been observed in various human cancer types. The loss of SFRP gene expression induces the activation of the Wnt pathway and is a vital mechanism for tumorigenesis and development. The aim of the present systematic review was to assess the association between SFRP methylation and cancer risk. A meta-analysis was systematically conducted to assess the clinicopathological significance of SFRP methylation in cancer risk. The Cochrane Library, PubMed and Web of Science databases were comprehensively searched, and 83 publications with a total of 21,612 samples were selected for the meta-analysis. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to evaluate the degree of associations between SFRP promoter methylation and cancer risk. Subgroup analysis, meta regression and sensitivity analysis were used to identify the potential sources of heterogeneity. SFRP1, SFRP2, SFRP4 and SFRP5 hypermethylation was significantly associated with cancer risk, with ORs of 8.48 (95% CI, 6.26–11.49), 8.21 (95% CI, 6.20–10.88), 11.41 (95% CI, 6.42–20.30) and 6.34 (95% CI, 3.86–10.42), respectively. SFRP2 methylation was significantly associated with differentiation in colorectal cancer (OR, 2.16; 95% CI, 1.02–4.56). The results of the present study demonstrated that SFRP methylation may contribute to carcinogenesis, especially in certain cancer types, including hepatocellular carcinoma and colorectal cancer.

Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy. Inflammatory cell infiltration, imbalance of inflammatory cytokines, and oxidative damage were reported to be involved during RILI pathogenesis, especially in the early phase of RILI. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidative cascades, and regulates life span of mice after administration of thoracic irradiation. We investigated the effects of Nrf2 on RILI and inflammation using Nrf2-knockout, Nrf2-overexpression and wild-type mice with or without 15 Gy ionizing radiation to thorax. Our results showed that Nrf2 deficiency aggravated radiation-induced histopathological changes, macrophage and neutrophil infiltration, serum levels of pro-inflammatory cytokines (IL-6, MCP-1, IFN-γ, TNF, and IL-12p70), and the levels of peroxidation products in the mouse lung. Moreover, loss of Nrf2 reduced radiation-induced serum levels of anti-inflammatory cytokine, IL-10, and antioxidative proteins. Nrf2 overexpression significantly alleviated radiation-induced histopathological changes, macrophages and neutrophils infiltration, serum levels of pro-inflammatory cytokines, and the levels of peroxidation products in lung tissues. Nrf2 overexpression also increased the serum levels of IL-10 and antioxidative proteins. These results indicated that Nrf2 had a protective role against radiation-induced acute lung injury and inflammation, and that antioxidative therapy might be a promising treatment for RILI.

ObjectiveVaricose veins are a common problem worldwide and can cause significant impairments in health-related quality of life, but the etiology and pathogenesis remain not well defined. This study aims to elucidate transcriptomic regulations of varicose veins by detecting differentially expressed genes, pathways and regulator genes.MethodsWe harvested great saphenous veins (GSV) from patients who underwent coronary artery bypass grafting (CABG) and varicose veins from conventional stripping surgery. RNA-Sequencing (RNA-Seq) technique was used to obtain the complete transcriptomic data of both GSVs from CABG patients and varicose veins. Weighted Gene Co-expression network analysis (WGCNA) and further analyses were then carried out with the aim to elucidate transcriptomic regulations of varicose veins by detecting differentially expressed genes, pathways and regulator genes.ResultsFrom January 2015 to December 2016, 7 GSVs from CABG patients and 13 varicose veins were obtained. WGCNA identified 4 modules. In the brown module, gene ontology (GO) analysis showed that the biological processes were focused on response to stimulus, immune response and inflammatory response, etc. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that the biological processes were focused on cytokine-cytokine receptor interaction and TNF signaling pathway, etc. In the gray module, GO analysis showed that the biological processes were skeletal myofibril assembly related. The immunohistochemistry staining showed that the expression of ASC, Caspase-1 and NLRP3 were increased in GSVs from CABG patients compared with varicose veins. Histopathological analysis showed that in the varicose veins group, the thickness of vascular wall, tunica intima, tunica media and collagen/smooth muscle ratio were significantly increased, and that the elastic fiber/internal elastic lamina ratio was decreased.ConclusionThis study shows that there are clear differences in transcriptomic information between varicose veins and GSVs from CABG patients. Some inflammatory RNAs are down-regulated in varicose veins compared with GSVs from CABG patients. Skeletal myofibril assembly pathway may play a crucial role in the pathogenesis of varicose veins. Characterization of these RNAs may provide new targets for understanding varicose veins diagnosis, progression, and treatment.