2.Dynamic change of collagen typeⅠand fibronectin in posterior sclera of form-deprivation myopia after TIMP-2 gene transfect in guinea pig
Lu-qin, WAN ; Gui-xiang, LIU ; Ling, WANG ; Ai-hua, SUI ; Qiang-qiang, GUO ; Yong-zi, LI ; Rui-feng, LI
Chinese Journal of Experimental Ophthalmology 2011;29(7):646-650
Background The domestic and international researches discovered that many proteins and enzymes of the extracellular matrix (ECM) participate in the sclera remodeling by affecting the collagen typeⅠand fibronectin.Objective This study was to investigate the effect of matrixmetalloproteinase-2 (TIMP-2) on expression of collagen typeⅠand fibronectin of ECM in the posterior sclera by injecting liposomes containing tissue inhibitor of TIMP-2 gene into suprachoroidal space of the form-deprivation myopia in guinea pig.Methods Form-deprivation myopia was induced by translucent goggles in 36 clean guinea pig for 2 weeks.Then the animals were randomly assigned to TIMP-2 group,empty plasmid group,saline group and 12 for each group.Liposomes of 5μl containing TIMP-2 gene,empty plasmid and saline were suprachoroidally injected in the right eye respectively,and the left eyes without any treatment were used as self-control group.Other 12 matched guinea pigs only covered the right eyes through out the experimental duration as model control group.The guinea pigs were sacrificed and the posterior sclera tissue of the eyeballs were collected at 2,7 and 14 days after injection of drug.The expressions of collagen typeⅠmRNA and fibronectin mRNA were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).This study followed the Regulation for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results The expression level of collagen type Ⅰ mRNA in the posterior sclera of guinea pig was lower but that of fibronectin mRNA was higher in TIMP-2 group than self-control group,showing significant differences between them (P<0.05).The expression level of collagen type Ⅰ mRNA in the posterior scleral tissue began to increase from the 2nd day after drug injection and was obviously elevated at the 7th day and then gradually decreased at the 14th day.However,the expression level of fibronectin mRNA in the posterior scleral tissue showed the opposite pattern.The expression levels of collagen typeⅠmRNA and fibronectin mRNA at the 7th after drug injection were significantly lower than that at the 2nd day or 14th day (P<0.01).Conclusion Suprachoroidal injection of TIMP-2 in form-deprivation myopia could up-regulate the expression of collagen typeⅠmRNA and down-regulate the expression of fibronectin mRNA in the posterior scleral tissue.It may slow down the sclera remodeling of form-deprivation myopia in guinea pig in the early stage.
3.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
4.Dynamic predictive modeling of extraction process for red ginseng using near-infrared spectroscopy.
Jie-Qiang ZHU ; Wan-Fang PAN ; Yi ZHONG ; Xiao-Hui FAN ; Li-Yuan KANG ; Zheng LI
China Journal of Chinese Materia Medica 2014;39(14):2660-2664
It is the objective of this study to develop dynamic predictive model for the extraction process of red Ginseng using NIR spectroscopy. NIR spectroscopy was collected online and PLSR models were developed for total quantity of ginsenosides. The performance of NIR prediction model achieved R, RMSEC, RMSEP of 0.996 09, 0.018 9, 0.016 8, respectively. A first order dynamic mass transfer model was combined with NIR prediction of the quality indicator to predict the trajectory of the extraction process based upon the initial 3 or 4 data points. The results showed good agreement with actual measurements indicating reasonable accuracy of the predictive model. It could potentially be used for advanced predictive control of the extraction process.
Chemical Fractionation
;
methods
;
Ginsenosides
;
chemistry
;
isolation & purification
;
Models, Theoretical
;
Panax
;
chemistry
;
Spectroscopy, Near-Infrared
5.Relationship of circadian distribution of acute myocardial infarction with AMI location and ST segment changes in elderly patients
Hua CUI ; Ping YE ; Qiang SUN ; Xiaoying LI ; Li FAN ; Luyue GAI ; Shiwen WAN
Chinese Journal of Geriatrics 2008;27(11):805-807
ObjectiveTo explore the relationship of circadian distribution of acute myocardial infarction with AMI location and ST segment changes in elderly patients.MethodsThe time of infarction, its anatomic location, changes of ST segment, and coronary angiography were studied in 909 elderly patients with acute myocardial infarction (AMI) ( 412 with anterior AMI and 423 with inferior AMI) admitted to our coronary care units from January 1996 to January 2006.ResultsThe onset of inferior myocardial infarction were more frequent between midnight and 6AM than other periods of the day (n=138/423,32.6% of all inferior myocardial infarction patients, P<0.01). The onset of anterior myocardial infarction were more frequent between 6AM and noon than other periods of the day (n=156/412, 37.9% of all anterior myocardial infarction patients, P<0.01). Coronary angiography was performed in 789 patients (86.8%, 516/909).118 cases of them with inferior infarction occured between midnight and 6AM, including 85.6% of them were due to right coronary artery occlusion and 14.0%(17/118) of them were due to left coronary artery occlusion (P<0.01).275 cases of them with inferior infarction oecured between 6AM and midnight, including 52.2% (149/275) of them were due to right coronary artery occlusion and 45.8% of them were due to left coronary artery occlusion (P>0. 05). The onset of inferior myocardial infarction between 6AM and noon was the most frenquent in patients with ST segment elevation (44.0%, 263/644), while the onset of inferior myocardial infarction between midnight and 6 AM was the most frenquent in patients with non-ST segment elevation (36.6%,96/265). ConclusionsThe frequency of AMI at night is higher in elderly patients with ST segment elevation than in elderly patients with non-ST segment elevation.AMI at night is usually due to right coronary artery occlusion, which suggests that a protective role of sleep may be limited to left coronary artery -related events and AMI of non-ST segment.
6.Design, synthesis and antitumor activities of novel E-substituted 2,3-diaryl propenoic acyloxy phosphonate derivatives.
Jia-qiang YANG ; Si-lan LIU ; Wan-li CHE ; Mao-sheng ZHANG ; Wan XIAO-QIANG ; Hong-lu JIAN ; Yong-zheng CHEN
Acta Pharmaceutica Sinica 2015;50(4):464-468
According to the super-position principle of the reinforcement of biological activities, a series of novel E-substituted 2, 3-diaryl propenoic acyloxy phosphonate derivatives were designed and synthesized. And the structures of the target compounds were confirmed by IR, 1H NMR, 13C NMR and elemental analysis. Furthermore, the cytotoxicities of all compounds on A-549, SGC-7901 and EC-109 in vitro were evaluated by MTT assay, and some of them showed good antitumor activity. Among the active compounds, especially, the IC50 value of compound 3e was (12.7 ± 1.9) μmol x L(-1) against A-549 cells, similar to cisplatin [IC50 = (8.0 ± 1.5) μmol x L(-1)], compounds 3g and 3k had better inhibition effect on EC-109 cells growth, with the IC50 values of (9.5 ± 1.8) μmol x L(-1) and (11.5 ± 0.9) μmol x L(-1) respectively, and compounds 3i and 3k exhibited good cytotoxic property on A-549, SGC-7901 and EC-109, which were worth further investigation.
Antineoplastic Agents
;
chemical synthesis
;
pharmacology
;
Cell Line, Tumor
;
Cell Proliferation
;
Drug Design
;
Humans
;
Organophosphonates
;
chemical synthesis
;
pharmacology
10.Study of the uptake of chitosan oligosaccharide nanoparticles by A549 cells.
Li-qing WAN ; Fu-qiang HU ; Hong YUAN
Acta Pharmaceutica Sinica 2004;39(3):227-231
AIMTo study the cellular uptake of chitosan oligosaccharide nanoparticles by A549 cells and evaluate the possibility of chitosan oligosaccharide nanoparticles used as a potential drug carrier.
METHODSChitosan oligosaccharide (CSO) was obtained by ultrafiltration separation after regulation of the condition of chitosanase degradation. The molecular weight of CSO was determined by gel permeation chromatography (GPC). Chitosan oligosaccharide nanoparticles (CSO-NPs) were prepared by a novel solvent diffusion method in an oil system after the carrier material grafted fluorescein isothiocyanate (FITC) and the particle size distribution and zeta potential were determined by light scattering and electrophoretic mobility. The cytotoxicity and uptake of FITC-labeled CSO-NPs in A549 cells following various incubation periods were studied by the MTT method and fluorescence microscopy, flow cytometric analysis, respectively.
RESULTSThe molecular weight (MW) of CSO was 18,678 u and the particles sizes of CSO-NPs were 133.3 nm (number average) and 368.2 nm (volume average), respectively. The IC50 of CSO and CSO-NPs were 944.36 and 643.16 mg x L(-1), respectively, and the result showed low cytotoxicity. Cellular uptake of CSO and CSO-NPs were relative to the concentration and the incubation time. Internalization of CSO-NPs increased 0.49 - 13.9 times more than that of the CSO with the same incubation time.
CONCLUSIONCSO and CSO-NPs have low cytotoxicity. CSO-NPs can significantly improved the uptake of CSO-NPs by A549 cells compared to the same molecular weight of CSO.
Adenocarcinoma ; pathology ; Chitin ; analogs & derivatives ; metabolism ; toxicity ; Chitosan ; Dose-Response Relationship, Drug ; Drug Carriers ; metabolism ; toxicity ; Epithelial Cells ; drug effects ; metabolism ; Humans ; Lung Neoplasms ; pathology ; Nanotechnology ; Oligosaccharides ; metabolism ; toxicity ; Particle Size ; Time Factors ; Tumor Cells, Cultured