HSP70 decreases receptor-dependent phosphorylation of Smad2 and blocks TGF-β-induced epithelial-mesenchymal transition

Smad2 and Smad3,the intracellular mediators of transforming growth factor β(TGF-β)signaling,are directly phosphorylated by the activated type I receptor kinase,and then shuttle from the cytoplasm into the nucleus to regulate target gene expression.Here,we report that the 70-kDa heat-shock protein(HSP70)interacts with Smad2 and decreases TGF-β signal transduction.Ectopic expression of HSP70 prevents receptor-dependent phosphorylation and nuclear translocation of Smad2,and blocks TGF-β-induced epithelial-mesenchymal transition(EMT)in HaCat cells.Our findings reveal an essential role of HSP70 in TGF-β-induced epithelial-mesenchymal transition(EMT)by impeding Smad2phosphorylation.     

银杏叶提取物促进脑缺血半暗带神经元自噬提高神经保护作用

银杏叶提取物(ginkgo biloba extract-761,EGb-761)注射液在中国常作为辅助药物被用于治疗脑卒中,但是,其潜在的细胞和药理机制尚未完全了解.该研究旨在探讨EGb-761是否通过调节缺血性脑卒中半暗带神经元的自噬从而发挥保护作用.采用雄性SD大鼠大脑中动脉闭塞(middle cerebral ...     

气候变化与人类活动对青藏高原湿地的影响研究进展

青藏高原是中国湿地分布最多的区域,其独特的高寒湿地对区域生态环境安全有着不可或缺的作用。梳理了青藏高原湿地变化的时空特征,基于此,重点分析了气候变化与人类活动对不同类型湿地的影响和作用机制。研究发现：(1)主导不同类型湿地变化的气候因素有差异,影响存在区域异质性。湖泊湿地主要受降水量影响,湖泊湿地在北部扩张、南部缩小的趋势与降水量的空间差异存在较强的一致性;沼泽湿地主要受气温影响,气温升高导致水分蒸发、植被群落演替,沼泽湿地向草地转化,江河源区和若尔盖高原等主要分布区域呈现退化趋势;河流湿地主要受气温影响,气温升高加速河源冰川消融、同时也增大河流蒸散发量,共同作用下河流湿地呈现北部减少、南部增加的趋势。(2)过度放牧、泥炭开采、水利建设等是影响湿地变化的主要人类活动。若尔盖高原同时存在过度放牧、泥炭开采和沟渠建设多重人类活动影响,当地沼泽湿地退化明显;柴达木盆地的人工湿地由于盐业开采迅速扩张。(3)当前研究存在数据可对比性不足、大区域尺度和野外定点持续监测数据缺乏等问题,导致对气候变化与人类活动影响机制研究不够深入。未来应加强高寒湿地定期监测与风险评估,完善高寒湿地生态系统与环境变化和...     

miR-324-5p promotes adipocyte differentiation and lipid droplet accumulation by targeting Krueppel-like factor 3 (KLF3)

miRNAs, a kind of noncoding small RNA, play a significant role in adipose differentiation. In this study, we explored the effect of miR-324-5p in adipose differentiation, and found that miR-324-5p could promote adipocytes differentiation and increase body weight in mice. We overexpressed miR-324-5p during adipocytes differentiation, by oil red O and bodipy staining found that lipid accumulation was increased, and the expression level of adipogenic related genes were significantly increased. And the opposite experimental results were obtained after inhibiting miR-324-5p. In vivo, we injected miR-324-5p agomiR in obese mice and found that body weight, adipocyte area, and adipogenic-related gene expression level were significantly increased but lipolytic genes were decreased. To further explore the mechanism of miR-324-5p regulation in lipid accumulation, we constructed Krueppel-like factor 3 (KLF3) 3′-untranslated region luciferase reporter vector and KLF3 pcDNA 3.1 overexpression vector, and found that miR-324-5p was able to directly target KLF3. Overall, in this study we found that miR-324-5p could promote mice preadipoytes differentiation and increase mice fat accumulation by targeting KLF3.     

脱细胞神经移植物对骨髓间充质干细胞的诱导分化

目的探讨脱细胞神经移植物诱导大鼠骨髓间充质干细胞分化为施旺细胞样细胞的可行性。方法将分离纯化的SD大鼠骨髓间充质干细胞进行体外培养扩增,行表型鉴定后,取第5代细胞,诱导组采用脱细胞神经移植物匀浆进行诱导,非诱导组加入等量无血清培养基,倒置相差显微镜观察诱导后细胞形态变化,免疫细胞化学染色检测诱导后细胞S-100,神经胶质纤维酸性蛋白(glial fibrillary acidic protein GFAP)的表达情况。结果BMSCs表型鉴定为CD44+、CD54+、CD34-,免疫细胞化学染色GFAP、S-100的阳性表达率分别为为(42±4)%和(64±5)%。结果 脱细胞神经移植物可诱导骨髓间充质干细胞分化为施旺细胞样细胞。     

Nicotine prevents the apoptosis induced by menadione in human lung cancer cells

Approximately 50% of long-term cigarette smokers die prematurely from the adverse effects of smoking, including on lung cancer and other illnesses. Nicotine is a main component in tobacco and has been implicated as a potential factor in the pathogenesis of human lung cancer. However, the mechanism of nicotine action in the development of lung cancer remains largely unknown. In the present study, we designed a nicotine-apoptosis system, by pre-treatment of nicotine making lung cancer cell A549 to be in a physiological nicotine environment, and observed that nicotine promoted cell proliferation and prevented the menadione-induced apoptosis, and exerts its role of anti-apoptosis by shift of apoptotic stage induced by menadione from late apoptotic stage to early apoptotic stage, in which NF-kappaB was up-regulated. Interference analysis of NF-kappaB in A549 cells showed that knock down of NF-kappaB resulted in apoptosis promotion and counteracted the protective effect of nicotine. The findings suggest that nicotine has potential effect in lung cancer genesis, especially in patients with undetectable early tumor development and development of specific NF-kappaB inhibitors would represent a potentially exciting new pharmacotherapy for tobacco-related lung cancer.     

60Co-γ射线辐照种子对牛至形态与挥发性成分的影响

牛至精油中的主要成分香芹酚和百里香酚具有较强的抑菌活性和替代抗生素的良好潜力。为了筛选有价值的遗传变异, 构建了牛至(Origanum vulgare)的⁶⁰Co-γ射线育种体系, 利用固相微萃取联合气相色谱-质谱方法进行挥发性成分测定, 并通过主成分分析和层次聚类等多元分析法, 深入探讨⁶⁰Co-γ射线对牛至M₁代形态特征、腺毛密度和腺毛大小以及挥发性成分的影响。结果表明, 牛至种子的半致死剂量为16.39 Gy; 辐照M₁代植株的株高、茎粗、分枝数、叶长和叶宽均发生变化, 筛选到多株形态突变体; 同时, 腺毛密度和腺毛大小发生多种变化, 从163株存活株中筛选出25株腺毛密度与大小均显著增大的单株;⁶⁰Co-γ射线处理对牛至挥发性成分的种类影响相对较小, 主要影响挥发性成分的含量, 并可诱导5种化学型, 即香芹酚型、百里香酚型、γ-萜品烯型、β-石竹烯型和大根香叶烯型; 最终筛选获得6株香芹酚和百里香酚含量升高的突变单株。研究证实了⁶⁰Co-γ射线辐照可作为牛至育种的一种有效诱变手段, 适宜辐照剂量为20 Gy。研究为牛至优良种质资源的选育提供了基础数据和新途径。     

Tumor suppressor RASSF1A promoter: p53 binding and methylation

Oncogenes and tumor suppressors work in concert to regulate cell growth or death, which is a pair of antagonist factors for regulation of tumorigenesis. Here we show promoter characteristic of tumor suppressor RASSF1A, which revealed a p53 binding site in the distal and a GC-rich region in the proximal promoter region of RASSF1A, in despite of TATA box-less. The GC-rich region, which is ～300 bp upstream from the RASSF1A ATG, showed the strongest promoter activity in an assay of RASSF1A-driving GFP expression. Methylation analysis of the CpG island showed that 78.57% of the GC sties were methylated in testis tumor samples compared with methylation-less in normal testis. Hypermethylation of the GC-rich region is associated with RASSF1A silencing in human testis tumors. In addition, electrophoretic mobility shift assay indicated that p53 protein bound to the RASSF1A promoter. Further chromatin immunoprecipitation confirmed p53 binding to the RASSF1A. Moreover, p53 binding to the promoter down-regulated RASSF1A expression. These results suggest that p53 protein specifically binds to the RASSF1A promoter and inhibits its expression. Our results provide new insight into the mechanism of action of tumor suppressors and may be a starting point for development of new approaches to cancer treatment.