3.Development of a novel screening assay for inhibitors targeting HIF-1alpha and P300 interaction.
Fang-Fang LAI ; Fei NIU ; Han-Ze YANG ; Wan-Qi ZHOU ; Xiao-Guang CHEN
Acta Pharmaceutica Sinica 2014;49(6):849-853
Hypoxia is a general characteristic of most solid malignancies and intimately related to cancer progression. Homeostatic response to hypoxia is primarily mediated by hypoxia inducible factor-1alpha (HIF-1alpha) that elicits transcriptional activity through recruitment P300 coactivator. Targeting the interaction of HIF- alpha and P300 would thus constitute a novel approach for cancer treatment by suppressing tumor angiogenesis and metastasis. Here, a screening assay was developed for inhibitors targeting the interaction between HIF-1alpha and P300. The nucleotide sequence of human HIF-1alpha and P300 were cloned into pBIND and pACT vectors, named pBIND-HIF1alpha and pACT-P300. The interaction of HIF-1alpha and P300 was identified in HEK293 cell using mammalian two-hybrid system. And compound chetomin decreased their interaction in this mammalian two-hybrid system. We further verified HIF-1 inhibition effect of chetomin in U251-HRE cells. Therefore, we established a screening assay combined HIF-1alpha and P300 mammalian two-hybrid system and U251-HRE reporter assay for HIF-1 selective inhibitors.
Cell Hypoxia
;
Disulfides
;
pharmacology
;
Drug Screening Assays, Antitumor
;
E1A-Associated p300 Protein
;
antagonists & inhibitors
;
HEK293 Cells
;
Humans
;
Hypoxia-Inducible Factor 1, alpha Subunit
;
antagonists & inhibitors
;
Indole Alkaloids
;
pharmacology
;
Two-Hybrid System Techniques
4.The anti-tumor activity and molecular mechanisms of an Aurora kinase inhibitor ZLJ213 in suppressing colon cancer growth.
Wan-qi ZHOU ; Li-jing ZHANG ; Han-ze YANG ; Zhi-qiang FENG ; Yan LI
Acta Pharmaceutica Sinica 2015;50(7):854-860
The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.
Animals
;
Apoptosis
;
Aurora Kinase A
;
antagonists & inhibitors
;
Cell Cycle Checkpoints
;
Cell Line, Tumor
;
drug effects
;
Cell Proliferation
;
Colonic Neoplasms
;
pathology
;
Humans
;
Protein Kinase Inhibitors
;
pharmacology
;
Receptors, Vascular Endothelial Growth Factor
;
metabolism
;
Xenograft Model Antitumor Assays
5.Comparative study of intravenous thrombolysis treatment of cardiogenic cerebral infarction and noncardiac cerbral infarction
Weihua DENG ; Yong YANG ; Xiaoping PAN ; Ze LI ; Jin ZHOU ; Hui HUANG ; Haobo CHEN
The Journal of Practical Medicine 2015;(11):1781-1783
Objective To compare the efficacy and safety of intravenous thrombolysis on cardiogenic cerebral infarction and noncardiac infarction by recombinant tissue plasminogen activator (rt-PA). Methods Comparations of NIHSS, mRS and adverse events before and after treatment were made between the cardiogenic group and the noncardiac group. Results No significant differences in the NIHSS and mRS were found between the two groups. The incidence of brain hernia and dermatorrhagia in the cardiogenic group was higher than that in the noncardiac group. Conclusion Rt-PA therapy in cardiogenic cerebral infarction was effective and safe in spite of higher incidence of hemorrhage and brain hernia.
6.Association between rs1512268 single nucleotide polymorphism of NKX3.1 gene and the risk of prostate cancer: a preliminary study
Xiaohong SHI ; Jianye WANG ; Ming LIU ; Dong WEI ; Changhu ZHOU ; Yaoguang ZHANG ; Ze YANG
Chinese Journal of Geriatrics 2012;31(1):29-32
ObjectiveTo investigate the association between the common variant rs1512268 single nucleotide polymorphism(SNP) of NKX3.1 gene and the risk of prostate cancer,and to explore its interaction with related risk factors.MethodsTotally 122 patients with prostate cancer and 105 age matched male people (prostatic specific antigen < 4 μg/L,without family history of prostate cancer) as control group were enrolled.Polymerase chain reaction - high resolution melting curve(PCR - HRM) combined with gene sequencing methods were used to determine the distribution of allele and genotype frequencies of the rs1512268 SNP.ResultsThe distributions of GG,AG,AA genotypes were 42 cases(33.4%),66 cases(54.1%),14 cases(11.5%) in patients with prostate cancer,and 45 cases(42.9%),51 cases(48.6%),9 cases(8.6%) in healthy control,respectively.There were no significant differences in the distribution of genotype(x2 =1.70,0.69,0.52) and allele frequency (x2 =1.575) between the two groups(P> 0.05).The different genotypes of rs1512268 of NKX3.1 gene were not associated with age,Gleason score,PSA levels and clinical stage of prostate cancer (P>0.05). Conclusions rs1512268 SNP of NKX3.1 gene is not obviously associated with prostate cancer and may be not the genetic risk factor in Chinese.
7.Preparation of corn polysaccharide-Fe(Ⅲ) complex and assay of Fe(Ⅲ)
xiao-lei, DENG ; jian-hua, ZHANG ; jin-e, ZHOU ; ze-nai, CHEN ; yang, LU
Journal of Shanghai Jiaotong University(Medical Science) 2006;0(11):-
11.0 for the pH of reaction solution,65℃~75℃for the reaction temperature,and 1:1.7 for the mass ratio of corn(dry weight)to FeCl_3?6H_2O.The corn polysaccharide-Fe(Ⅲ)complex synthesized with the optimized process was stable,with good solubility in water.The assay of Fe(Ⅲ)was 39.86%,40.20%and 40.17%,respectively for three batches of products.The RSD was
8.PRELIMINARY STUDY ON AN ANTIBIOTIC-PRODUCING BACTERIUM
Xi-Qian LAN ; Jun-Hua HU ; Hong-Xiu WEN ; Jia-Lian CHEN ; Ze-Yang ZHOU ;
Microbiology 1992;0(05):-
An antibiotic-producing bacterium, which was numbered as 20 #-5, was separated from the soil in Chongqing. It was identified as the member of pseudomonas. Gram positive bacteria are badly suppressed by it. The antibiotic secreted by 20 #-5 can endure 100℃ for half an hour, and it can also go through the ultrafiltration membrane with pores of 0.22?m.
9.The correlation of obesity with gut Akkermansia and its features in the elderly population
Qi ZHOU ; Fei DONG ; Wanxi LI ; Chen CHEN ; Nan ZHANG ; Zhu WU ; Ze YANG ; Liang SUN
Chinese Journal of Geriatrics 2021;40(4):450-453
Objective:To investigate the impact of aging on the correlation between the intestinal microorganism Akkermansia and obesity, and to analyze the features of the correlation in the elderly population. Methods:This was a cross-sectional study.A total of 6896 cases were collected from the Guangdong intestinal microbiome in 2018, aged 18-94 years old, including 3806 females, 1641 cases with abdominal obesity(23.7%)and 707 cases with systemic obesity(10.3%). The 16S rRNA sequencing data were from individuals of Cantonese descent.The abundance of Akkermansia was calculated after data cleaning, clustering and annotation.The type of abdominal obesity or systemic obesity was diagnosed based on the standards of the Working Group on Obesity in China(2002). According to the five quintiles of the abundance of Akkermansia, subjects were divided into Q1~Q5(Q1-Q4: n=1379, Q5: n=1380). Logistic regression was used to study the relationship between Akkermansia and obesity after adjusting for common confoundors such as gender.Subjects were subgrouped into two types of age groups: the <65 group(n=5467)and the ≥65 group(n=1519); the <70 group(n=6136)and the ≥70 group(n=850). Age windows were used to analyze changes in characteristics of this relationship with increasing age. Results:There were significant differences in age and gender among different Akkermansia groups( t/ χ2=3.51, -5.03, P<0.01). Logistic regression analysis showed that after adjusting for two main confounding factors, age and gender, the risk of systemic obesity and abdominal obesity gradually decreased from Q2 to Q5 group, compared with Q1 group( P<0.001). The correlation between Akkermansia and obesity decreased with age.The protective effect of Akkermansia on obesity was weaker in the ≥65 and ≥70 groups, respectively, than in the <65 and <70 groups. Conclusions:Akkermansia is a protective factor for obesity, but the protective effect is affected by aging and weakened in the elderly.
10.The development and consideration of a framework for a Chinese elderly health standards system
Bi ZHANG ; Miao MIAO ; Qiang GAO ; Baiyu ZHOU ; Ze YANG ; Pengjun ZHANG
Chinese Journal of Geriatrics 2021;40(5):654-658
Objective:To develop a framework for a national system of elderly health standards in response to population aging in China and to meet the need for health service standards for elderly care, thus providing a roadmap for the development of elderly health standards.Methods:Preliminary indicators for a framework of a Chinese elderly health standards system were established by literature review and expert consultations.Using the Delphi method, we invited 23 experts to form a consultation panel.After two rounds of expert consultations, the preliminary framework was updated and the weight of each indicator was calculated by using the analytic hierarchy process.Results:A framework of the Chinese elderly health standards system was established after two rounds of expert consultations.The expert authority coefficient was 0.847.The framework proposed four primary indicators, including basic health standards, medical service standards, public health standards and social support standards, for the elderly, with a weight of 0.204, 0.346, 0.260 and 0.189 for each indicator.There were 22 secondary indicators, including standardized terminologies, medical services, health education, geriatrics personnel training, etc., for elderly care.Conclusions:Our research has generated a preliminary framework of an elderly health standards system that incorporates China's specific issues, takes into consideration of the needs of various parties and covers many relevant aspects.It will provide the basis for decision-making in the elderly health standardization process in China and safeguard the implementation of the Healthy China strategy.