1.Effect of downregulation the expression of HDAC1 on cells differentiation of HL-60 cells.
Shanliang LU ; Yiqun HUANG ; Xudong MA
Acta Pharmaceutica Sinica 2013;48(5):668-74
This study is to investigate the effect of downregulation histone deacetylases 1 (HDAC1) gene by the technology of RNA interference on the differentiation of HL-60 cells line. The optimal segment targeting HDAC1 gene was designed and transfected into HL-60 cells by Lipofectamine 2000. The HDAC1 mRNA and protein level were detected by RT-PCR and Western blotting. The morphologic change of HL-60 cells was detected by an optical microscope with Wright-Giemsa. Cell differentiation was tested by NBT reduction assay. Expression of CD13, CD33 and CD14 was measured by flow cytometry. The results indicated that HDAC1 mRNA and protein were markedly suppressed by the siRNA targeting HDAC1 in a concentration-dependent manner. HDAC1 siRNA promoted cell differentiation. HL-60 cells became more mature in morphology after transfected to HDAC1 siRNA at a concentration of 30-60 nmol x L(-1) for 24 h. NBT reduction ability of HDAC1 siRNA with 30 nmol x L(-1) was 0.31 +/- 0.09, compared with negative control (0.20 +/- 0.02) (t = -3.1, P < 0.01), and with 60 nmol x L(-1) was 0.25 +/- 0.02 in comparison with negative control (0.21 +/- 0.04) (t = -2.12, P < 0.05). But it has no change in HDAC1 siRNA > or = 120 nmol x L(-1). After transfection with 60 nmol x L(-1) HDAC1 siRNA to HL-60 cells, the expression of CD13 was (96.50 +/- 0.70)% in compared to siRNA-NC (3.39 +/- 0.68) % (t = 164.9, P < 0.000 5), CD33 was (66.73 +/- 0.50) % in compared to siRNA-NC (96.80 +/- 1.70) % (t = 43.4, P < 0.000 5). CD14 was (0.53 +/- 0.00) % by comparison with siRNA-NC (0.49 +/- 0.02) % (t = -0.97, P > 0.1). HDAC1 siRNA promoted cell differentiation in indicated concentration. HDAC1 might be one of the targets of gene therapy for leukemia.
2.Targeting the substrate binding domain of polo-like kinase 1: advances in the study of PBD1 inhibitors.
Liang ZHANG ; Yanhua CAO ; Shuai LU ; Shanliang SUN ; Haichun LIU ; Tao LU
Acta Pharmaceutica Sinica 2013;48(3):315-24
Polo-box domain 1 (PBD1) is a characteristic domain of polo-like kinase 1 (PLK1), which locates in C-terminal and can influence the catalytic activity and specific subcellular locations of PLK1. At present, most PLK1 inhibitors are developed to occupy the ATP pocket or its close sites. However, this kind of PLK1 inhibitors is difficult to pursue target selectivity and may encounter cross drug resistance with other kinase inhibitors due to the conserved sequence of ATP pocket. Recently, PBD1, with aberrant specificity in sequence and structure, has attracted enormous interests as the alternative target to the discovery of corresponding inhibitors for anti-tumor drugs. The structure and function of PBD1 as well as the advances of its inhibitors are reviewed in this paper.
3.Reproducibility and Risk Factors of Aortic Distensibility Quantification in Abdominal Aortic Aneurysm Using Multi-slice Spiral CT
Shanliang HAN ; Liang LI ; Yuan LIN ; Jiao WANG ; Xuesong LU ; Wei GONG ; Dong XING ; Yunfei ZHA
Chinese Journal of Medical Imaging 2017;25(10):767-771
Purpose To investigate the reproducibility and risk factors of aortic distensibility quantification in patients with abdominal aortic aneurysm using multi-slice spiral CT.Materials and Methods The abdominal aortic computed tomography angiography data of 54 patients with infrarenal abdominal aortic aneurysm were prospectively studied.64-muti detector spiral CT,retrospective ECG-gating and segment data collecting scanning were all carried out.The aortic distensibility,D value,and pulse wave velocity at renal artery level and infrarenal artery level were calculated using semiautomatic segmentation software.The difference of aortic distensibility at different levels was compared,and consistency test was performed.Results The D value at renal artery level and infrarenal artery level of abdominal aortic aneurysm was (1.05 ±0.22)×10-5/Pa and (0.49± 0.18)× 10-5/Pa,respectively;and the corresponding pulse wave velocity was (9.68± 1.09) m/s and (14.96 ±4.01) m/s,respectively.The intraclass correlation coefficient of intra-and interobserver at renal level was 0.92 and 0.79,while it was 0.85 and 0.79 at inffa level.The Bland-Altman graph showed that the vast majority of points were within the 95% CI,the difference of intraobserver between the two positions was 0.017×105/pa and 0.010×10-5/Pa,and the difference of interobserver was 0.013×105/Pa and 0.018×10-5/Pa.Multivariate analysis of all these variables showed aortic distensibility to be independently correlated to body mass index,pulse pressure,diastolic pressure and abdominal aortic aneurysm diameter (R2=0.68).Conclusion The quantification of aortic distensibility using multi-slice spiral in patients with abdominal aortic aneurysm shows high stability.Taking into consideration of the relationship between different risk factors and the incidence of abdominal aortic aneurysm can lead to a better clinical approach.