Expression and significance of ASPP2 in squamous carcinoma of esophagus

To study the significance of apoptosis stimulating protein of P53 2 (ASPP2) expression in esophageal squamous cell carcinoma (ESCC), immunohistochemistry S-P method was used to examine the expression of ASPP2 in 136 cases of ESCC, 35 cases of high grade intraepithelial neoplasia (HGIN), 29 cases of low grade intraepithelial neoplasia (LGIN) and 37 cases of normal esophageal epithelium (NEE). The associations of ASPP2 expression with clinicopathological data and overall survival (OS) were also analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate ASPP2 expression in a total of 20 matched human ESCC tumor tissues and normal adjacent tissues (NAT). In addition, EC109 cells were treated with cisplatin (CDDP) in vitro for 24 h (the intervention group) and the control group was set up at the same time. Western blot was used to examine the expression of ASPP2 protein between the two groups. The expression of ASPP2 decreased progressively from NEE to LGIN, to HGIN, and to ESCC, and it was related to TNM stage, histological differentiation and lymph node metastasis in ESCC (P < 0.05). ASPP2 was a protective factor of patients with ESCC (P = 0.008). The relative expression of ASPP2 mRNA was markedly downregulated in ESCC compared with the paired NAT (P < 0.01). Western blot results showed that cells in the intervention group could express ASPP2 while there was no expression of ASPP2 in the control group. Taken together, these results indicate that the abnormal expression of ASPP2 may play an important role for development and metastasis in ESCC.     

Comparison of maternal omentin-1 levels and genetic variability between spontaneous term and preterm births

Objective: To determine maternal omentin-1 levels and genetic variability in the omentin-1 gene in women with spontaneous term and preterm births (PTBs).

Materials and methods: Maternal serum omentin-1 levels and the role of the omentin-1 Val109Asp (rs2274907) polymorphism were evaluated in 32 women with spontaneous term birth (sTB) and 30 women with spontaneous preterm birth (sPTB) including women with (n?=?16) and without (n?=?14) preterm premature rupture of membranes (PPROM).

Results: Maternal omentin-1 levels were significantly lower in women with sPTBs compared to term births during the hospitalization period (p?=?.015). However, maternal omentin-1 levels were similar in women with sPTBs with and without PPROM (p?=?.990). Furthermore, the omentin-1 Val109Asp polymorphism was found to have no significant effect on omentin-1 serum levels. In addition, no significant differences in genotype distributions and allelic frequencies between sTB and sPTB were established.

Conclusions: High omentin-1 levels in normal sTBs compared to PTBs without significant differences between cases with and without PPROM suggest that omentin-1 plays a potential role in the pathophysiology of PTB but not in the PPROM mechanism itself.     

香加皮三萜类化合物抑制食管癌Eca109细胞裸鼠成瘤及其机制

目的： 研究香加皮三萜类化合物（triterpenes compound extracted from cortex periplocae,TCCP）对荧光素酶（luciferase）标记的人食管鳞癌细胞株Eca109（Eca109-luc细胞）在裸鼠体内成瘤的作用及其机制。 方法： Eca109-luc细胞经皮下接种裸鼠,构建Eca109-luc细胞裸鼠移植瘤模型,观察TCPP治疗后移植瘤体积和质量的变化,应用活体成像系统观察移植瘤生长情况,H-E染色观察移植瘤组织形态学变化,流式细胞仪检测移植瘤细胞的凋亡,Western blotting检测移植瘤组织中survivin的表达。 结果： TCPP在体内能明显抑制裸鼠Eca109-luc移植瘤的生长,移植瘤体积和质量明显减少,抑瘤率为40.7%。TCPP 治疗组小鼠移植瘤组织出现明显炎性细胞浸润及肿瘤细胞坏死,移植瘤细胞的凋亡率明显高于大豆油对照组（P<005）,移植瘤组织中survivin蛋白表达水平明显下降（P<0.05）。 结论： TCCP在体内能抑制人食管癌Eca109细胞的生长,其作用机制可能与下调survivin的表达诱导肿瘤细胞凋亡有关。     

ｐ２７Ｋｉｐ１基因Ｖ１０９Ｇ多态性与乳腺癌易感性的Ｍｅｔａ分析

目的　探讨ｐ２７^Ｋｉｐ１（ＣＤＫＮ１Ｂ,以下简称ｐ２７）基因Ｖ１０９Ｇ多态性与乳腺癌易感性的关系。方法　检索Ｍｅｄｌｉｎｅ、Ｐｕｂｍｅｄ、ＷｅｂｏｆＳｃｉｅｎｃｅ和ＣＮＫＩ数据库,获取ｐ２７基因Ｖ１０９Ｇ多态性与乳腺癌易感性的相关研究,以病例组和对照组ｐ２７基因Ｖ１０９Ｇ基因型分布的比值比（ＯＲ）为效应指标,确定纳入标准,对文献进行评价筛选和异质性检验,用Ｍｅｔａ分析软件对各研究原始结果进行统计处理,计算合并ＯＲ值及９５％可信区间。结果　按照纳入标准共入选３篇文献,累计病例１８５３例,对照病例１５１６例,Ｍｅｔａ分析结果显示合并ＯＲ值为０.９５（９５％可信区间：０.８２～１.１２,Ｚ值为０.５８）。结论　以目前相关研究结果的Ｍｅｔａ分析显示,ｐ２７基因Ｖ１０９Ｇ基因多态性与乳腺癌易感性之间不存在相关性,即ｐ２７基因Ｖ１０９Ｇ多态性不影响个体患乳腺癌的风险。     

顺铂下调铜离子转运蛋白1诱导人食管鳞癌细胞EC109耐药

摘要：目的研究人食管鳞癌细胞顺铂耐药性产生的机制。方法MTT法检测顺铂对耐药细胞EC109/CDDP及其亲代细
胞EC109的细胞毒作用。电感耦合等离子体质谱检测细胞内顺铂的蓄积和Pt-DNA加合物的形成。Western blotting检
测人多聚腺苷二磷酸核糖聚合酶（poly-ADP-ribose polymerase, PARP）的剪切和铜离子转运蛋白1（copper transporter 1,
CTR1）的蛋白表达。结果顺铂耐药细胞株EC109/CDDP较其亲代细胞EC109对顺铂引起的细胞毒作用和凋亡敏感性
下降,细胞内顺铂蓄积和Pt-DNA加合物的形成减少,并且CTR1蛋白表达水平降低。结论顺铂通过降低细胞CTR1蛋白
表达抑制顺铂进入细胞,导致细胞耐药性的产生。     

芝麻酚通过AMPK/SIRT1/NF-κB信号通路调控食管鳞状细胞癌Eca109细胞的自噬和凋亡

目的：探讨芝麻酚（SEM）通过腺苷酸活化蛋白激酶（AMPK）/沉默信息调节因子1(SIRT1)/核因子κB(NF-κB)通路影响食管鳞状细胞癌（ESCC）Eca109细胞自噬和凋亡的机制。方法:用不同浓度的SEM(0、1.562 5、3.125、6.25、12.5、25、50、100、200、400μmol/L)分别处理Eca109细胞、人食管上皮细胞HEEpiC 48 h,CCK-8法检测细胞增殖率，筛选适宜的SEM浓度用于后续实验。将Eca109细胞分为对照组（CK组，0μmol/L）、低剂量SEM组（SEM-L组，25μmol/L）、中剂量SEM组（SEM-M组，50μmol/L）、高剂量SEM组（SEM-H组，100μmol/L）、高剂量SEM+Compound C(AMPK抑制剂)组（SEM-H+Compound C组，100μmol/L+10μmol/L），所有各组Eca109细胞在对应的药物浓度下处理48 h后，CCK-8法检测Eca109细胞增殖，流式细胞术检测细胞凋亡，透射电镜观察Eca109细胞内自噬小体，WB法检测Eca109细胞中微管相关蛋白1轻链3(LC3)-...     

GPR109A expressed on medullary thymic epithelial cells affects thymic Treg development

Regulatory T cells (Treg) maintain immune homeostasis due to their anti-inflammatory functions. They can be generated either centrally in the thymus or in peripheral organs. Metabolites such as short-chain fatty acids produced by intestinal microbiota can induce peripheral Treg differentiation, by activating G-protein-coupled-receptors like GPR109A. In this study, we identified a novel role for GPR109A in thymic Treg development. We found that Gpr109a^−/− mice had increased Treg under basal conditions in multiple organs compared with WT mice. GPR109A was not expressed on T cells but on medullary thymic epithelial cells (mTECs), as revealed by single-cell RNA sequencing in both mice and humans and confirmed by flow cytometry in mice. mTECs isolated from Gpr109a^−/− mice had higher expression of autoimmune regulator (AIRE), the key regulator of Treg development, while the subset of mTECs that did not express Gpr109a in the WT displayed increased Aire expression and also enhanced signaling related to mTEC functionality. Increased thymic Treg in Gpr109a^−/− mice was associated with protection from experimental autoimmune encephalomyelitis, with ameliorated clinical signs and reduced inflammation. This work identifies a novel role for GPR109A and possibly the gut microbiota, on thymic Treg development via its regulation of mTECs.