Wilms tumor (WT) is the most prevalent urologic malignancy in childhood. Nonetheless, the genetic factors underlying WT remain largely unknown. The miR-423 rs6505162 C>A polymorphism is associated with the susceptibility to numerous cancers; however, no investigations have been conducted on its association with WT. To evaluate the correlation between the miR-423 rs6505162 C>A polymorphism and WT risk in Chinese children, we genotyped this polymorphism using the Taqman method in 145 cases and 531 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the association. The results showed that the rs6505162 CA genotype was associated with decreased susceptibility to WT (CA versus CC: adjusted OR=3D0.65, 95% CI=3D0.42-0.99, P=3D0.047). In the stratified analysis, we found that CA/AA genotypes conferred a significantly decreased overall risk of WT in children younger than 18 months (adjusted OR=3D0.30, 95% CI=3D0.14-0.63, P=3D0.002) and those with clinical stage I+II WT (adjusted OR=3D0.42, 95% CI=3D0.20-0.85, P=3D0.017) when compared with CC genotype. In summary, the miR-423 rs6505162 C>A polymorphism may negatively modify WT susceptibility in Chinese children. Our findings should be validated in larger studies involving other ethnicities.
Zhang, Tiesong
Ma, Jing
Li, Chao
Lin, Ken
Lou, Fan
Jiang, Hongchao
Gao, Yingqin
Yang, Yanli
Ming, Cheng
Ruan, Biao
Pediatric head and neck cancers account for overall 12% of all pediatric cancers. Despite recent advances in therapeutic modalities, children with tumor metastasis have poor prognosis. Therefore, there is an unmet need for new and effective treatment modalities for pediatric head and neck cancers. The present study describes a simple and efficient method for fabrication of cationic lipid-polymer hybrid nanoparticles (CLPNs) for co-delivery of cisplatin (CDDP) and DNA (CDDP/DNA CLPNs) for the therapy of childhood head and neck cancers. CDDP/DNA CLPNs were prepared by the modified double emulsion solvent evaporation method with self-assembly. CDDP-loaded CLPNs (CDDP CLPNs), CDDP-loaded polymeric nanoparticles (PNPs) (CDDP PNPs), and DNA-loaded Lipofectamine 2000 (DNA LIPO) were also prepared for comparison. The results illustrated that the concentration of the cationic lipid has influence on the characteristics of CLPNs. In vitro anticancer effect, in vitro transfection efficiency, in vivo antitumor and gene delivery efficacy of CDDP/DNA CLPNs have advantages over other formulations tested. In conclusion, outstanding delivery ability of CLPNs for both CDDP and DNA could combine the therapeutic efficiency of both drug and gene for the treatment of pediatric rhabdomyosarcoma (RMS).
Hyperoxia therapy for acute lung injury (ALI) may unexpectedly lead to reactive oxygen species (ROS) production and cause additional ALI. Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide that regulates inflammasome activation. However, the role of CGRP in DNA damage during hyperoxia is unclear. Therefore, the aim of the present study was to investigate the effects of CGRP on DNA damage and the cell death of alveolar epithelial type II cells (AEC II) exposed to 60% oxygen. AEC II were isolated from 19-20 gestational day fetal rat lungs and were exposed to air or to 60% oxygen during treatment with CGRP or the specific CGRP receptor antagonist CGRP(8-37). The cells were evaluated using immunofluorescence to examine surfactant protein-C and ROS levels were measured by probing with 2,7-dichlorofluorescin diacetate. The apoptosis rate and cell cycle of AEC II were analyzed by flow cytometry, and apoptosis was determined by western blotting analysis of activated caspase 3. The DNA damage was confirmed with immunofluorescence of H2AX via high-content analysis. The ROS levels, apoptotic cell number and the expression of H2AX were markedly increased in the hyperoxia group compared with those in the air group. Concordantly, ROS levels, apoptotic cell number and the expression of H2AX were significantly lower with a significant arrest of S and G2/M phases in the CGRP/O-2 group than in the hyperoxia or CGRP(8-37)/O-2 groups. CGRP was concluded to protect lung epithelium cells against hyperoxic insult, and upregulation of CGRP may be a possible novel therapeutic target to treat hyperoxic lung injury.
Summary Objective: Interaction between advanced glycation end-products (AGEs) and receptor for AGEs (RAGE) in cells could affect both extracellular and intracellular structure and function, which plays a pivotal role in diabetic microvascular complications. The results from previous epidemiological studies on the association between RAGE gene -374T/A polymorphism and diabetic retinopathy (DR) risk were inconsistent. Thus, we conducted this meta-analysis to summarize the possible association between RAGE -374T/A polymorphism and DR risk. Method: We searched all relevant articles on the association between RAGE -374T/A polymorphism and DR risk from PubMed, Cochrane Library, ScienceDirect, Wanfang, VIP and Chinese National Knowledge Infrastructure (CNKI) web databases up to August 2016. Odds ratio (OR) with 95% confidence interval (CI) were calculated to assess those associations. All analyses were performed using the Review Manager software. Results: Nine case-control studies, including 1,705 DR cases and 2,236 controls were enrolled, and the results showed that the A allele of RAGE -374T/A polymorphism was significantly associated with increased DR risk in dominant model (TA/AA vs. TT: OR=3D1.22, 95CI 1.05-1.41, p=3D0.006) and heterozygote model (TA vs. TT: OR=3D1.26, 95CI 1.07-1.47, p=3D0.005). The subgroup analysis by ethnicity showed that significantly increased DR risk was found in both Asian and Caucasian populations. Conclusion: This meta-analysis reveals that the A allele of RAGE -374T/A polymorphism probably increase DR risk.=09
Qiu, Lijuan
Wang, Lin
Tan, Li
Li, Ming
Wu, Chengqing
Li, Li
Zhang, Zhen
Jiang, Hongchao
Sun, Qiangming
Zhang, Tiesong
Mycoplasma pneumoniae (MP) is particularly prevalent in low-immunity school-age children. Few data have been reported on MP prevalence in Yunnan, China. This study was designed to investigate the prevalence and characterize genomic DNA of MP in a small outbreak in 2016, Southwest China. RepMP4 and RepMP2/3 genes of MP positive samples were amplified for molecular typing through sequence alignment and PCR-RFLP assay. Phylogenetic trees were constructed by MEGA5.0. The results showed that two distinct P1 types (type I and type II) were prevalent in this MP outbreak. Type I was the most prevalent type, and clustered in the same evolutionary branch of C26 (China, 2012). Only 1 MP isolate belonged to type II, and clustered in the branch of KCH405 (Japan, 2016). Fifty-nine nucleotide mutations were observed in P1 genes of type I isolates (51 in RepMP4, 8 in RepMP2/3). Ninety-five nucleotide mutations were observed in P1 genes of the type II isolates (33 in RepMP4, 62 in RepMP2/3). It is noteworthy that 31 mutation sites were clustered in an 84-bp fragment in the RepMP4 gene of type II isolates. One new fragment that appeared in two of the type I strains was not found in NCBI. Nucleotide diversity analyze results showed that RepMP4 was more likely to be genetically diverse than RepMP2/3. Two-tailed Z-test result of RepMP4 suggested positive selection between 6 P1 type I isolates and M29 (China, 2005). According to secondary structure prediction, 36 new possible protein binding sites were found and another 9 sites were lost, 2 helices were missed and 1 new helix appeared in type I isolates. As for type II isolates, 16 protein binding regions were gained and 31 were lost. This study may help to understand the intrinsic geographical relatedness and contributes further to the research of MP.