Curcumin ameliorates hepatic chronic inflammation induced by bile duct obstruction in mice through the activation of heme oxygenase-1

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MEMRI and tumors: a method for the evaluation of the contribution of Mn(II) ions in the extracellular compartment

The purpose of the work was to set‐up a simple method to evaluate the contribution of Mn²⁺ ions in the intra‐ and extracellular tumor compartments in a MEMRI experiment. This task has been tackled by “silencing” the relaxation enhancement arising from Mn²⁺ ions in the extracellular space. In vitro relaxometric measurements allowed assessment of the sequestering activity of DO2A (1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid) towards Mn²⁺ ions, as the addition of Ca‐DO2A to a solution of MnCl₂ causes a drop of relaxivity upon the formation of the highly stable and low‐relaxivity Mn‐DO2A. It has been proved that the sequestering ability of DO2A towards Mn²⁺ ions is also fully effective in the presence of serum albumin. Moreover, it has been shown that Mn‐DO2A does not enter cell membranes, nor does the presence of Ca‐DO2A in the extracellular space prompt migration of Mn ions from the intracellular compartment. On this basis the in vivo, instantaneous, drop in SE% (percent signal enhancement) in T₁‐weighted images is taken as evidence of the sequestration of extracellular Mn²⁺ ions upon addition of Ca‐DO2A. By applying the method to B16F10 tumor bearing mice, T₁ decrease is readily detected in the tumor region, whereas a negligible change in SE% is observed in kidneys, liver and muscle. The relaxometric MRI results have been validated by ICP‐MS measurements. Copyright © 2015 John Wiley & Sons, Ltd.     

MOB1A regulates glucose deprivation-induced autophagy via IL6-STAT3 pathway in gallbladder carcinoma

MOB kinase activator 1A (MOB1A) plays an important role in many diseases and cancers. Here, we observed that MOB1A was substantially overexpressed in gallbladder carcinoma (GBC) tissues compared with nontumor tissues. The high expression of MOB1A was closely associated with poor survival in patients with GBC at advanced TNM stages. Furthermore, our study indicated that MOB1A promoted autophagy by activating the IL6/STAT3 signaling pathway and regulating the chemosensitivity to gemcitabine under glucose deprivation conditions both in vitro and in vivo. In conclusion, these findings suggested that MOB1A is critical for the development of GBC via the MOB1A-IL6/STAT3-autophagy axis.     

m6A结合蛋白IGF2BP1在肝细胞癌中的基因调控网络分析

目的 分析m6A阅读器胰岛素样生长因子2-mRNA结合蛋白1（insulin-like growth factor 2 mRNA-binding protein 1，IGF2BP1）在肝细胞癌（hepatocellular carcinoma，HCC）中的表达水平及其对HCC患者预后的影响，并探讨IGF2BP1在HCC发生发展中的作用及其潜在机制。方法 基于5对HCC癌及相应癌旁组织mRNA-seq数据和TCGA数据库LIHC的mRNA-seq数据综合分析IGF2BP1在HCC中的表达情况，同时利用TCGA数据库中343例HCC患者的临床随访资料分析IGF2BP1表达水平对HCC患者总生存期的影响。基于TCGA数据库筛选IGF2BP1的共表达mRNA，并利用m6Avar在线网站预测mRNA的m6A位点及其RNA结合蛋白等信息，最终构建IGF2BP1的基因调控网络。结果 IGF2BP1基因在HCC中表达上调（log2FC HCC转录组数据=10.684，P<0.001；log2FC TCGA-LIHC数据集=7.032，P<0.001）。生存分析显示IGF2BP1低表达的HCC患者中位生存时间为5.84年，IGF2BP1高表达患者为4.44年，高表达患者总生存期缩短（P=0.011）。22个差异表达的mRNA与IGF2BP1存在靶向结合关系，并与其表达水平呈正相关。其中，HMGA2等15个高表达mRNA的HCC患者总生存期缩短。HMGA2、PEG10、CEP55、RHO、CDC6和KIF23基因中的潜在m6A甲基化位点位于mRNA 3'UTR端的miRNA结合区域。结论 IGF2BP1在HCC中高表达且导致患者总生存期缩短。IGF2BP1可能通过m6A甲基化及miRNA抑制作用的方式上调mRNA的表达，促进HCC发生并导致不良预后。     

Effects of Bisphenol A on expression of genes related to amino acid transporters,insulin- like growth factor,aquaporin and amino acid release by porcine trophectoderm cells

The peri-implantation period of pregnancy is critical for conceptus development, implantation, and signaling for establishment of pregnancy. This study evaluated the effects of bisphenol A (BPA) on proliferation, adhesion, and migration of porcine trophectoderm (pTr2) cells, expression of transporters of arginine and synthesis of amino acids. All concentrations of BPA decreased proliferation and adhesion of pTr2 cells after 96 h compared to the control group. Lower concentrations of BPA (1 × 10⁻⁹, 1 × 10^-8, 10^-7M) increased (P < 0.05), but higher concentrations of BPA (1 × 10^-5, 1 × 10^-4 M) decreased migration of pTr2 cells. BPA increased expression of SLC7A1 mRNA at lower concentrations (1 × 10⁻⁹ to 1 × 10^-6M) and SL7A6, another cationic acid transporter, at higher concentrations (1 × 10^-5, 1 × 10^-4 M). BPA also down-regulated the expression of IGF1 and IGF1 receptor at concentrations of 1 × 10^-7 to 1 × 10^-4 M compared to the control group. The expression of mRNAs for aquaporins (AQP) 3 and 4 were reduced at all concentrations of BPA, but at lower concentrations of BPA, (1 × 10⁻⁹ to 1 × 10^-8M) expression of AQP9 mRNA increased and the expression of AQP11 was not affected by BPA (P > 0.05). There was an inhibitory effect of BPA on the release of synthesis of asparagine, threonine, taurine, tryptophan, and ornithine into the culture medium by pTr2 cells. Collectively, BPA adversely affected the expression of transporters for cationic amino acids like arginine, as well as AQPs, IGF1, and IGF1R associated with proliferation, migration, and adhesion of pTr2 cells. Those adverse effects would likely increase pregnancy losses during the peri-implantation period of pregnancy.