SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation

The family of mammalian Sirtuin proteins comprises seven members homologous to yeast Sir2. Here we show that SIRT2, a cytoplasmic sirtuin, is the most abundant sirtuin in adipocytes. Sirt2 expression is downregulated during preadipocyte differentiation in 3T3-L1 cells. Overexpression of SIRT2 inhibits differentiation, whereas reducing SIRT2 expression promotes adipogenesis. Both effects are accompanied by corresponding changes in the expression of PPARgamma, C/EBPalpha, and genes marking terminal adipocyte differentiation, including Glut4, aP2, and fatty acid synthase. The mechanism underlying the effects of reduced SIRT2 in 3T3-L1 adipocytes includes increased acetylation of FOXO1, with direct interaction between SIRT2 and FOXO1. This interaction enhances insulin-stimulated phosphorylation of FOXO1, which in turn regulates FOXO1 nuclear and cytosolic localization. Thus, Sirt2 acts as an important regulator of adipocyte differentiation through modulation of FOXO1 acetylation/phosphorylation and activity and may play a role in controlling adipose tissue mass and function.     

PCR survey of hox genes in the goldfish Carassius auratus auratus

A tetraploidization event took place in the cyprinid lineage leading to goldfishes about 15 million years ago. A PCR survey for Hox genes in the goldfish Carassius auratus auratus (Actinopterygii: Cyprinidae) was performed to assess the consequences of this genome duplication. Not surprisingly, the genomic organization of the Hox gene clusters of goldfish is similar to that of the closely related zebrafish (Danio rerio). However, the goldfish exhibits a much larger number of recent pseudogenes, which are characterized by indels. These findings are consistent with the hypothesis that dosage effects cause selection pressure to rapidly silence crucial developmental regulators after a tetraploidization event.     

慢病毒介导的RNA干涉对乳腺癌SKBR3细胞HER2受体的下调及生长抑制

大约30％的乳腺癌中有表皮生长因子受体家族蛋白HER2的过表达,此类癌症的预后差,恶性程度高。RNA干涉（RNAi）是最近发展起来能特异性抑制哺乳动物细胞中基因表达的新技术。本文在以往获得的能够产生良好基因沉默效应的小干涉RNA（siRNA）的基础上,构建了U6和H1双启动子siRNA表达载体,并转染HER2高表达乳腺癌SKBR3细胞定量测定了其HER2下调效应。随后,siRNA表达盒经LR重组反应被克隆入慢病毒载体中,在成功包装成病毒后,感染SKBR3并经荧光定量PCR、蛋白印迹杂交和流式细胞仪一系列实验证明慢病毒介导的RNAi确实能有效地下调肿瘤抗原HER2的表达。细胞长期增殖实验表明经慢病毒处理后细胞生长得到抑制。我们的研究为进一步阐明HER2与癌症恶化的关系以及发展新的基因治疗药物提供了工具和可能。     

Associations between daytime and nighttime plasma orexin A levels and cognitive function in patients with obstructive sleep apnea

Sleep and Biological Rhythms - The relationship between plasma orexin A (OXA) levels and cognitive function in patients with obstructive sleep apnea (OSA) remains unclear. This study aimed to...     

microRNA-140-5p from human umbilical cord mesenchymal stem cells–released exosomes suppresses preeclampsia development

Functional & Integrative Genomics - This work unraveled the action of human umbilical cord mesenchymal stem cells–released exosomes (huc-MSCs-EXO) transfer of miR-140-5p in preeclampsia...     

G蛋白偶联胆汁酸受体1促进胃癌细胞的增殖、迁移和侵袭的实验研究

目的:探讨G蛋白偶联胆汁酸受体1(G-protein coupled bile acid receptor 1,GPBAR1/TGR5)对胃癌细胞增殖、迁移和侵袭的影响。方法:免疫组织化学染色方法(Immunohistochemistry,IHC)检测胃癌及癌旁组织芯片中TGR5表达情况;qRT-PCR及Western blot检测胃癌细胞系中TGR5表达水平;小干扰RNA处理AGS、MKN-45胃癌细胞后构建TGR5敲减细胞系,慢病毒载体转染胃癌SGC-7901细胞构建TGR5过表达细胞系;CCK-8实验、平板克隆形成实验、裸鼠皮下移植瘤实验检测TGR5对细胞增殖的影响;流式细胞仪检测TGR5对细胞周期及凋亡的影响;Tanswell实验检测TGR5对胃癌细胞迁移及侵袭的影响;Western blot检测上皮间充质转化(Epithelial-mesenchymal transition,EMT)相关分子β-连环蛋白(β-catenin)、锌脂蛋白转录因子(Snail)、E盒结合锌指蛋白(Zinc finger E-box binding homeobox 1,ZEB)1在AGS、MKN-45及SGC-7901胃癌细胞中的表达。结果:TGR5在胃癌及癌旁组织中均有表达,胃癌组织TGR5高表达率(41.0%)显著高于癌旁组织(9.5%),伴肠化生癌旁组织TGR5高表达率(50%)显著高于不伴肠化生的癌旁组织(0%),胃癌组织TGR5表达与肿瘤大小相关。TGR5在正常人胃上皮永生化细胞株GES-1及各胃癌细胞系中均有表达。TGR5表达敲低的AGS和MKN-45细胞增殖能力减弱、凋亡率显著升高、侵袭和迁移能力显著降低。过表达TGR5的SGC-7901细胞增殖能力增强、克隆形成能力提高、凋亡率明显减低、侵袭和迁移能力显著升高。此外,TGR5过表达显著上调了间质细胞标志物β-catenin、Snail、ZEB1的表达水平。结论:TGR5能够增强胃癌细胞增殖及迁移能力,并抑制细胞凋亡。TGR5可能通过EMT途径介导胃癌细胞转移。     

组织工程支架制备中超临界CO2技术的应用*

作为组织工程研究中三大要素之一,组织工程支架可为细胞的附着、迁移和增殖提供理想的环境。传统的组织工程支架制备方法,如粒子沥滤法、相分离法及静电纺丝法等在理论和技术上已较为成熟,但由于大多需要有机溶剂的参与,在制备过程中仍存在有机溶剂难以去除,以及支架孔洞难以控制、连通性较差等问题。超临界二氧化碳(supercritical carbon dioxide,SC-CO₂)密度近似液体,黏度和扩散系数近似气体,具有流动性强、溶解能力大、传热效率高等特殊的理化性质,与传统工艺相结合,可在绿色温和的反应体系中有效规避上述问题,在组织工程支架制备及药物负载方面具有广阔前景。