2.Protective effects of oxymatrine on adriamycin-induced cardiotoxicity in rabbits and its mechanism
Fei, MA ; Xiao-ping, LI ; Jian-chun, GU ; Li, ZHANG ; Lei-zheng, ZHENG
Journal of Shanghai Jiaotong University(Medical Science) 2009;29(6):685-688
Objective To establish the in vivo models of adriamycin(ADR)-induced cardiotoxicity in rabbits, investigate the protective effect of oxymatrine (OMT) on ADR-induced cardiotoxicity, and explore the possible mechanism. Methods Twenty-six rabbits were randomly divided into ADR group (n=8, 2 mg/kg ADR), OMT group (n=5, 10 mg/kg OMT), ADR + OMT group (n=8, 10 mg/kg OMT was injected 30 min before ADR injection) and saline group (n=5, same quantity of normal saline), and rabbits in each group were infused with medicine or normal saline through ear marginal vein once a week for 8 weeks. The apoptosis of myocardial cells was detected by TUNEL methods, and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) was determined. Results After treatment, the body weight of ADR group was significantly lower than that of the other groups(P < 0.05), the activity of SOD and GSH-Px significantly decreased and the apoptosis index (AI) was significantly higher than that of the other groups(P <0.01). There were similar while minor changes in ADR + OMT group. There was no significant adverse effects in OMT group. Conclusion OMT protects heart from adriamycin-induced injury in rabbits, which may relate to the decrease in level of antioxidant and apoptosis of myocardial cells.
3.Recent Progress on Plant Bioreactor Expressing Pharmaceutical Proteins
Xiao-Chun DU ; Zheng-Quan HE ; Lei CHEN ; Ye YANG ; Wei YAO ;
China Biotechnology 2006;0(09):-
Plant bioreactor called mocular farming has enormous potential to produce recombinant protein infinitely. Products expressed in plants has nature physico-chemical property and bioactivity. Plant bioreactor could be an safe, economic and convenient production system which has been widely applied in industries and agriculture, especially in the life science and pharmaceutical industry. The application of recombinant transgenic plant in the production of vaccines, antibodies and pharmaceutical proteins has become a hot point in the plant genetic engineering both at home and broad. However, there are some limiting factors of application such as yield, downstream processing and so on. The advantages and research progress for the mocular farming of pharmaceutical proteins recent three years was discussed, focusing on the existing problems and new strategies in this area.
4.Research progress in antisense drug mechanism and chemical modification strategies
Lei LI ; Yi-xuan ZHENG ; Chun-ying MA ; Wen-hua FENG
Acta Pharmaceutica Sinica 2022;57(9):2709-2719
Over the past three decades, more and more antisense drugs have been approved for marketing or clinical trails. Antisense technology has become the focus of pharmaceutical research due to its unique advantages in treating diseases and strong clinical development potential. There is a big difference from traditional small molecule chemical drugs, and macromolecular protein biological drugs. Antisense drugs are a very independent drug form. Antisense drugs were initially used to treat diseases with single gene mutations, but recently they have gradually begun to be used for the treatment of common diseases. Rational antisense drug design is crucial for disease treatment based on genetics. This paper reviews the latest progress in the field of action mechanism, chemical modification and delivery strategy of antisense drugs, and analyzes the current intractable problems. It is believed that with the resolution of these problems, the research of antisense drugs can reach a new level.
5.Phenotypic modulation of mesangial cells in diabetic rats and effect of tujian mixture.
De-hai YIN ; Xiao-chun LIANG ; Fa-lei ZHENG
Chinese Journal of Integrated Traditional and Western Medicine 2003;23(10):772-776
OBJECTIVETo explore whether there is phenotypic modulation of mesangial cells in streptozotocin (STZ) induced diabetic rats and study the effect of Tujian Mixture (TJM) on it.
METHODSSD rats were divided into the normal control group (NC group, n = 8), the unilateral nephrectomized control group (QC group, n = 8), the STZ induced diabetes mellitus with unilateral nephrectomy model group (DM group, n = 8), the Valsartan treated group (VT group, n = 8) and the TJM treated group (ZY group, n = 9), rats in the latter two groups were modeled as in the DM group and treated with Valsartan (20 mg/kg.d) and TJM (20 g/kg.d) respectively for 12 weeks. The expression of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta 1 (TGF-beta 1) in rats glomeruli were observed by immunohistochemistry assay, and the ratio of alpha-SMA and TGF-beta 1 positive area/total glomerule tuft area (SMA/GT and TGF/GT) were analyzed using computer-assisted image analysis software.
RESULTSIn the NC and the QC groups, only trace of alpha-SMA positive staining was found. But there was prominant alpha-SMA positive staining in glomeruli of the DM group, with SMA/GT and TGF/GT increased significantly (P < 0.01), and marked increase of 24 hrs proteinuria excretion (P < 0.01). As compared with the DM group, the three indexes were all significantly lower in the VT and ZY groups (P < 0.01), and the lowering of proteinuria was more significant in the ZY group than that in the VT group (P < 0.01).
CONCLUSIONThe expression of alpha-SMA in glomeruli in STZ induced diabetic rats with unilateral nephrectomy is pronounced, indicating that phenotypic modulation of mesangial cells involvement in the pathogenesis of diabetic nephropathy. TJM and Valsartan can reduce 24 hrs proteinuria excretion, inhibit the phenotypic modulation of mesangial cells and the expression of TGF-beta 1 in glomeruli of diabetic rats, and the effect of TJM is more potent than that of Valsartan in lowering urinary protein excretion.
Animals ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; Diabetic Nephropathies ; etiology ; metabolism ; pathology ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Glomerular Mesangium ; metabolism ; pathology ; Image Processing, Computer-Assisted ; Male ; Nephrectomy ; Phenotype ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta ; metabolism
7.Expressions of aspartic proteinase and cysteine proteinase in photoaged fibroblasts
Wei LAI ; Yue ZHENG ; Chun LU ; Miaojian WAN ; Shuxia XIE ; Qingfang XU ; Lei GUAN ; Zhangzhang YE ; Jinling YI
Chinese Journal of Dermatology 2010;43(3):192-195
Objective To investigate the expression changes of aspartic proteinase (cathepsin D) and cysteine proteinase (cathepsin K) in photoaged fibroblasts. Methods The senescence of human fibroblasts was induced via culture in the presence of 8-methoxypsralen (MOP) of 50 mg/L in darkness for 24 hours followed by irradiation with UVA of 80 kJ/m~2. Then, aged fibroblasts were confirmed by senescence-associated β-galactosidase (SA-β-gal) staining. Real-time RT-PCR and Western blot were carried out to detect the mRNA and protein expressions of cathepsin D and cathepsin K in photoaged and normal control fibroblasts, respectively. Results Western blot showed a significant difference between photoaged and control fibroblasts in the grey scale of cathepsin D and cathepsin K (3.25 ± 0.33 vs 14.18 ± 2.25, f = 30.61, P < 0.01; 2.39 ± 0.66 vs 29.38 ± 4.62, t = 12.63, P< 0.01). The △Ct values for cathepsin D and cathepsin K mRNA were 2.79 ± 0.17 and -0.92 ± 0.06, respectively, in photoaged fibroblasts, significantly lower than those in the control fibroblasts (4.54 ± 0.34, 2.57 ± 0.13, t = 20.78, 28.50, respectively, both P < 0.01). According to the value of 2~(-△△Ct), the expression of cathepsin D and cathepsin K mRNA decreased 0.24 ± 0.021 and 0.09 ± 0.005 folds, respectively, in photoaged fibroblasts compared with the control fibroblasts. Conclusion The expression of cathepsin D and cathepsin K is decreased in photoaged fibroblasts.
8.Study on the extracting method of salviae miltiorrhizae madix et rhizoma in Huoluo-Xiaoling granules
Chao WANG ; Yuanyan LIU ; Qing LI ; Lei XIA ; Zhiqian SONG ; Chun WANG ; Yuna CAO ; Zheng WEI ; Linyan ZENG ; Zhenli LIU
International Journal of Traditional Chinese Medicine 2011;33(7):605-608
Objective To optimize the extraction method of salviae miltiorrhizae madix et rhizoma in Huoluo-Xiaoling granules. Methods According to the contents of Salvianolic acid B and Tanshinone Ⅱ A, the extraction method was established by comparing different solvents (water and 70% ethanol)and extracting modes (compound extraction and single herb extraction). Then orthogonal design was used to determine the optimum extraction method. Results Considering the contents of salvianolic acid B and tanshinone Ⅱ A, 70% ethanol extract was better than water extract and compound extraction was better than single herb extraction.The optimum extraction condition was 70% ethanol in eight times of the herbs weight, extracted for 1h by 3times. Conclusion The extraction method was simple and stable.
9.Neuropeptide Y promotes TGF-beta1 production in RAW264.7 cells by activating PI3K pathway via Y1 receptor.
Jiang-Rui ZHOU ; Zheng XU ; Chun-Lei JIANG
Neuroscience Bulletin 2008;24(3):155-159
OBJECTIVETo examine the effect of neuropeptide Y (NPY) on TGF-beta1 production in RAW264.7 macrophages.
METHODSEnzyme linked immunosorbent assay (ELISA) was used to detect TGF-beta1 production. Cell counting kit 8 (CCK-8) was used to assay the viability of RAW264.7 cells. Western blot was used to detect the phosphorylation of PI3K p85.
RESULTSNPY treatment could promote TGF-beta1 production and rapid phosphorylation of PI3K p85 in RAW264.7 cells via Y1 receptor. The elevated TGF-beta1 production induced by NPY could be abolished by wortmannin pretreatment.
CONCLUSIONNPY may elicit TGF-beta1 production in RAW264.7 cells via Y1 receptor, and the activated PI3K pathway may account for this effect.
Androstadienes ; pharmacology ; Animals ; Blotting, Western ; Cell Count ; Cell Line ; Cell Survival ; drug effects ; immunology ; Enzyme Activation ; drug effects ; physiology ; Enzyme-Linked Immunosorbent Assay ; Immunosuppressive Agents ; pharmacology ; Macrophages ; drug effects ; immunology ; metabolism ; Mice ; Neuropeptide Y ; metabolism ; pharmacology ; Phosphatidylinositol 3-Kinases ; drug effects ; metabolism ; Phosphorylation ; drug effects ; Receptors, Neuropeptide Y ; agonists ; metabolism ; Signal Transduction ; drug effects ; immunology ; Transforming Growth Factor beta1 ; agonists ; metabolism ; Up-Regulation ; drug effects ; immunology
10.Characterization of BZLF1 gene and its promoter Zp of EBV strains in children with EBV-associated diseases in recent 5 years in Beijing area.
Ya-Li LIU ; Uun-Hong AI ; Jing YAN ; Xiao-Lei GUAN ; Chun-Yan LIU ; Zheng-De XIE
Chinese Journal of Virology 2014;30(1):6-12
This study aims to investigate the genetic characteristics of BZLF1 gene and its promoter Zp of the epidemic strains in children with primary Epstein-Barr virus (EBV)-associated diseases. Total DNA was extracted from the peripheral blood of 134 children with EBV-associated infectious mononucleosis (EBV-IM) and 32 children with EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) who were admitted to Beijing Children's Hospital from 2006 to 2011. The EBNA3C, BZLF1, and Zp genes were amplified by PCR assay. Typing of EBV was performed according to the size of the amplification product of EBNA3C gene; the amplification products of BZLF1 and Zp genes were subjected to direct sequencing, and sequence analysis was performed using BioEdit 7. 0. 9. The results were as follows: (1) EBV-1 was present in 140 samples (97.2%, 140/144) and EBV-II in 4 samples (2.8%, 4/144). (2) Three BZLF1 genotypes and their 12 subtypes (including 6 newly found subtypes) were detected in this study; there were no significant differences in the frequencies of BZLF1-A and BZLF1-B between the children with EBV-IM and EBV-HLH (P = 0.083); BZLF1-A1 was the dominant genotype in children with EBV-associated diseases; t BZLF1-A mostly had three 29-bp repeats in the first intron of BZLF1 gene, and BZLF1-B mostly had 30-bp repeats (P = 0.000), with the number of repeats varying from 1 to 13. (3) Four Zp genotypes were detected in this study, including Zp-P, Zp-V3, Zp-V4, and Zp-V1; there were no significant differences in the frequencies of these Zp genotypes between children with EBV-IM and EBV-HLH (P = 0.272, 0.252, 1.0, and 1.0, respectively). (4) The linkage analysis of BZLF1 gene and its promoter Zp showed that BZLF1-A1 was highly associated with Zp-V3 (P = 0.000), while BZLF1-B4 with Zp-P (P = 0.000); EBV-I + BZLF1 A1 was highly associated with Zp-V3 (P = 0.000), while EBV-I+BZLF1-B4 with Zp-P (P = 0.000). The conclusions are as follows: (1) BZLF1-A1 is the dominant genotype in children with EBV-associated diseases; there are mostly 29-bp repeats in the first intron of BZLF1 gene for BZLF1-A genotype and 30-bp repeats for BZLF1-B genotype. (2) Zp-P and Zp-V3 are dominant Zp genotypes of EBV in children, which shared similar detection rates. (3) BZLF1-A1 is highly associated with Zp-V3, while BZLF1-B4 with Zp-P; EBV-I+BZLF1-A1 is highly associated with Zp-V3, while EBV-I+BZLF1-B4 with Zp-P.
Child
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Child, Preschool
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China
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epidemiology
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Epstein-Barr Virus Infections
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epidemiology
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virology
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Female
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Genotype
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Herpesvirus 4, Human
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genetics
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physiology
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Humans
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Infant
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Infant, Newborn
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Introns
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genetics
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Male
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Promoter Regions, Genetic
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genetics
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Repetitive Sequences, Nucleic Acid
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genetics
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Trans-Activators
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genetics