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Jin X.,Central Hospital of Minhang District | Jin X.,Shanghai JiaoTong University | Liu L.,Shanghai JiaoTong University | Zhou Z.,Central Hospital of Minhang District | And 4 more authors.
FEBS Journal | Year: 2016

Classically activated macrophages (M1) are associated with inflammation in diabetic patients. Inflammation is a known risk factor in diabetes. The present study tested the hypothesis that pioglitazone (PIO) alleviates inflammation in diabetic mice fed a high-fat diet by inhibiting advanced glycation end-product (AGE)-induced classical macrophage activation. It was found that AGE treatment promoted the transcription of pro-inflammatory molecules and M1 surface markers, whereas PIO increased the expression of anti-inflammatory genes and decreased the expression of pro-inflammatory mediators in bone marrow-derived macrophages (BMDMs) in a dose-dependent manner. Furthermore, pretreatment with PIO abrogated the effects of AGE on pro-inflammatory markers and partly inhibited AGE-induced nuclear factor-κB (NF-κB) activation. PIO treatment partly reduced the inflammatory phenotype in diabetic ApoE−/− mice, and significantly reduced NF-κB activation in plaques. Therefore, we conclude that PIO blocks classical activation of macrophages and attenuates inflammation in mouse models of diabetes. © 2016 Federation of European Biochemical Societies

Dai Y.-E.,Nanjing Medical University | Tang L.,Tongling Peoples Hospital | Healy J.,University of Montreal | Sinnett D.,University of Montreal
PLoS ONE | Year: 2014

Objective: Two common polymorphisms in the IKZF1 gene (rs4132601 and rs11978267 variants) have been reported to be associated with childhood acute leukemia (AL) risk, however the results were inconsistent. Here, we conducted a meta-analysis to generate large-scale evidence on whether IKZF1 variants are risk factors for childhood AL. Methods: The PubMed, Embase, EBSCO, and Web of Science were searched up to June 2, 2014 for studies on the association of IKZF1 polymorphisms with childhood AL risk. Data were extracted and the odd ratios (ORs) and95% confidence intervals (95% CIs) were calculated by a fixed-effects orrandom-effects model. Subgroup analysis by ethnicity and leukemia subtype, sensitivity and cumulative meta-analyses were performed. Moreover, publication bias was assessed by Begg's and Egger's tests. Results: In total, 33 case control studies were finally included in this meta-analysis. For rs4132601 polymorphism, significantly increased AL risk was observed in all genetic models (the association was still significant when the p value was Bonferroni adjusted to 0.025). In the subgroup analysis by tumor type, statistical association was observed in B-cell precursor ALL (BCP-ALL). Additionally, when stratified by ethnicity, significantly increased AL risk was only observed in European subgroup, but not among African or mixed population subgroups. Finally, similar results were found forrs11978267 polymorphism. Conclusion: In summary, this meta-analysis provides evidence that rs4132601 and rs11978267 polymorphisms in the IKZF1 gene mightcontribute to the occurrence of BCP-ALL, especially in European populations. Moreover, further studies with large sample size are required to clarify possibleroles of IKZF1 variants in other ethnic groups (e.g., Asians and Africans). © 2014 Dai et al.

Zhuang X.,Fudan University | Qiao T.,Fudan University | Yuan S.,Fudan University | Chen W.,Fudan University | And 2 more authors.
OncoTargets and Therapy | Year: 2013

Background: Cytosine-phosphate-guanine (CpG) oligodeoxyribonucleotides (ODNs), which induce signaling via Toll-like receptor 9, have recently been suggested to enhance sensitivity to traditional therapies, including chemotherapy, in certain cancer cell lines. This study aimed to define the dose-effect relationship for CpG ODN 1826 in increasing radiosensitivity and its impact on immune function in a mouse model of Lewis lung cancer. Methods: The tumor-bearing mouse model was induced by injecting Lewis lung cancer cells into the right anterior leg subcutaneously. Sixty-four C57BL/6 J mice were evenly randomized into eight groups, comprising: a control group; an irradiation group; a CpG ODN 0.15 group; a CpG ODN 0.3 group; a CpG ODN 0.45 group; a CpG 0.15 + irradiation group; a CpG 0.3 + irradiation group; and a CpG 0.45 + irradiation group. Tumor growth, serum tumor necrosis factor-alpha and interleukin-12 concentrations, spleen and thymus exponents, and effect of CpG on the secondary immune response were measured, and apoptosis of tumor cells was investigated using TdT-mediated dUTP nick end labeling (TUNEL) after treatment. Results: Tumor volumes in the treated groups were smaller than in the control group, with those of the CpG 0.45 + irradiation group being the smallest. TUNEL showed that the apoptosis rate in all the active treatment groups was higher than in the control group. CpG ODN apoptosis rate, serum tumor necrosis factor-alpha and interleukin-12 levels, and the spleen and thymus exponent showed greater improvement in the groups receiving combination therapy of CpG ODN and irradiation than the control group or the group receiving irradiation alone. With the increasing concentration of CpG ODN 1826, its effect became more and more significant, meanwhile, inoculation of Lewis lung cancer cells failed in those CpG ODN-cured mice. Conclusion: CpG ODNs dramatically increased the radiosensitivity of Lewis lung cancer and enhanced immune function in mice in a dose-related manner. © 2013 Zhuang et al, publisher and licensee Dove Medical Press Ltd.

Chen C.,Tongling Peoples Hospital | Xu X.-F.,Jiangsu University
Chinese Journal of Tissue Engineering Research | Year: 2013

BACKGROUND: The calcium sulfate is mostly used as carriers for antibiotics and osteogenic factors by now. OBJECTIVE: To observe the in vitro delivery effect of bone morphogenetic protein-2/injectable calcium sulfate cement slow-release system and the in vitro biocompatibility with bone marrow mesenchymal stem cells. METHODS: Bone morphogenetic protein-2/injectable calcium sulfate cement slow-release scaffold was prepared and its release properties were detected. Bone marrow mesenchymal stem cells obtained from Sprague-Dawley rats were induced, cultured and proliferated in vitro, and then, the cells were seeded onto the bone morphogenetic protein-2/injectable calcium sulfate cement scaffolds (experimental group) or single injectable calcium sulfate cement scaffolds (control group). RESULTS AND CONCLUSION: The release of bone morphogenetic protein-2 on the scaffolds of experimental group could last for 31 days. Rat bone marrow mesenchymal stem cells had a good biocompatibility with the bone morphogenetic protein-2/injectable calcium sulfate cement scaffolds. The adhesive rate, cell number and alkaline phosphatase activity at the same time point in the scaffolds of experimental group were significantly greater than those of the control group. Cells could be observed on each scaffold under a scanning electron microscope. In the experimental group, interconnected cell processes were fused, extracellular matrix was visible in the dense area, and the scaffold was surrounded by a large number of cells. The cells in experimental group grew better than the control group.

Sun J.,Huaian Matenal and Child Health Hospital | Zheng J.,Xuzhou Medical College | Tang L.,Tongling Peoples Hospital | Healy J.,University of Montreal | And 2 more authors.
PLoS ONE | Year: 2015

The CCAAT/enhancer binding proteins (CEBPs) have been involved in the etiology of acute leukemia (AL) and investigated in numerous genetic association studies, however, the results were inconclusive. The current meta-analysis was conducted to clarify the effect of CEBPE rs2239633 variant on childhood AL risk. Electronic literature search was performed on August 15, 2014, from databases of Medline, PubMed, Embase, and Web of Science. A total of 22 case-control studies were eligible for the pooled analysis. The results demonstrated that rs2239633 A allele was significantly associated with a decreased risk of childhood AL (A vs G: OR=0.87, 95%CI = 0.80, 0.94, p<0.001) but not in Asian and mixed populations. Moreover, the results of sensitivity and cumulative meta-analysis indicated the robustness of our results. Also, Begg's and Egger's tests did not indicate any evidence of obvious asymmetry. In summary, our study provided evidence that CEBPE rs2239633 variant is associated with decreased risk of childhood B-cell ALL in Europeans. © 2015, Public Library of Science. All rights reserved.

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