PTEN基因通过调控ROS抑制结肠癌细胞增殖

为了探讨PTEN基因在结肠癌中的作用以及其机制研究,MTT法检测结肠癌细胞细胞增殖;蛋白免疫印迹检测结肠癌细胞中Ki67蛋白的表达;DCFDA染色流式细胞仪检测结肠癌细胞中ROS水平。结果表明PTEN基因能明显抑制结肠癌细胞细胞增殖;PTEN基因能显著降低结肠癌细胞中Ki67蛋白的表达;细胞内ROS水平在PTEN基因处理组中明显高于空质粒结肠癌细胞组;NAC预处理可明显抑制PTEN基因抑制的细胞增殖;NAC预处理可显著抑制PTEN基因对结肠癌细胞Ki67蛋白的降低作用。PTEN基因能够抑制结肠癌细胞增殖并上调结肠癌细胞内ROS水平。     

Molecular engineering of respiratory syncytial virus immunogen for rational redesign of prophylactic peptide vaccines against pediatric viral pneumonia

The immunogen FFL_001 of respiratory syncytial virus (RSV), a widely spread virus that infects the lungs and breathing passages, is a three-helix bundle protein of 115 amino acids long that consists of three helical arms H1, H2 and H3. Here, we attempted to perform molecular engineering of the immunogen, aiming to considerably reduce the protein scaffold of FFL_001 with only moderate activity loss. Structural analysis and molecular dynamics (MD) simulations revealed that two helices H2 and H3 of the FFL_001 three-helix bundle can directly interact with its cognate monoclonal antibody Motavizumab, while the remaining helix H1 plays a crucial role in stabilisation of the three-helix bundle conformation. Binding of the two split peptide segments separately representing FFL_001 two-helix bundle H2-H3 and Motavizumab-binding site to the antibody would incur considerable entropy penalty as compared to binding of the intact FFL_001, suggesting that peptide segments are highly flexible that exhibit a strong intrinsic disorder in solution. In this respect, a scheme was proposed to rationally redesign the immunogen protein scaffold by truncation and cyclisation of the three-helix bundle. The cyclisation was conducted on the spatially vicinal residue pairs in H2 and H3 helical arms by mutating the residue to cysteine and introducing a disulphide bond across them. Consequently, we obtained three cyclic peptides that were theoretically predicted to have strong binding potency towards Motavizumab. In order to substantiate the computational finding, binding affinity of the designed cyclic peptide and its linear counterpart was determined. Consistently, no binding can be found between the linear peptide and Motavizumab (K_d = n.d.), while a moderately high affinity was observed for cyclic peptide (K_d = 16.2 nM).     

Cholesterol homeostasis regulated by ABCA1 is critical for retinal ganglion cell survival

Science China Life Sciences - Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1. ABCA1 is a key regulator of cholesterol efflux and...