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Temporal and Tight Hepatitis C Virus Gene Activation in Cultured Human Hepatoma Cells Mediated by a Cell-Permeable Cre Recombinase

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Acta Biochimica et Biophysica Sinica 2004年第10期36卷 687-694页

作者： Dong XIAO*, Kang XU1, Ying YUE, Zhong-Min GUO, Bing HUANG, Xin-Yan DENG, Huan TANG2, and Xi-Gu CHEN* Center of Experimental Animals, Zhongshan university, guangzhou 510080, china 1The first affiliated hospital of sun yat-sen university, Zhongshan university, guangzhou 510080, china 2The Third Military Medical university, Chongqing 400010, china Center of Experimental Animals Zhongshan University The first affiliated hospital of sun yat-sen university Zhongshan University The Third Military Medical university

Conditional gene expression has greatly facilitated the examination of the functions of particular gene products. Using the Cre/lox P switching expression system, we plan to develop efficient conditional transgeneactivation of hepatitis C virus core protein (HCV-C) cDNA (nucleotide 342–914) in the transgenic mice to overcome “immune tolerance” formed during the embryonic period and “immune escape” against hepatitis virus antigen in our project. To use this system in vivo, the dormant transgenic construct, i.e., pApoE-SCS-EGFP-HCV-C, was generated using techniques of standard molecular biology. The liver- specific human apoE promoter was here used to target expression of genes of interest (EGFP and HCV-C) to murine liver. Prior to generating the transgenic mice, the availability of Cre/lox P system and construct functionality were successfully verified by a cell-free recombination system and via checking the expression of EGFP and HCV-C in the human hepatoma cells at the mRNA and protein levels. These results suggest that the Cre/lox P system could tightly control expression of EGFP and HCV-C in vitro, which laid a solid foundation to conditionally activate expression of target gene(s) in transgenic mice by Cre-mediated site-specific recombination.

关键词： hepatitis C virus Cre/lox P switching expression system cell-free and intracellular recombination systems cell-permeable Cre recombinase EGFP human hepatoma cells

Bacterial Phosphoproteomic Analysis Reveals the Correlation Between Protein Phosphorylation and Bacterial Pathogenicity

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Genomics,Proteomics & Bioinformatics 2011年第Z2期 119-127页

作者： Ruiguang Ge and Weiran Shan Laboratory of Integrative Biosciences, College of Life Sciences, sun yat-sen university, guangzhou 510275, china

Increasing evidence shows that protein phosphorylation on serine, threonine and tyrosine residues is a major regulatory post-translational modification in the bacteria. This review focuses on the implications of bacterial phosphoproteome in bacterial pathogenicity and highlights recent development of methods in phosphoproteomics and the connectivity of the phosphorylation networks. Recent technical developments in the high accuracy mass spectrometry have dramatically transformed proteomics and made it possible the characterization of a few exhaus- tive site-specific bacterial phosphoproteomes. The high abundance of tyrosine phosphorylations in a few bacterial phosphoproteomes suggests their roles in the pathogenicity, especially in the case of pathogen-host interactions; the high abundance of multi-phosphorylation sites in bacterial phosphoprotein is a compensation of the relatively small phosphorylation size and an indicator of the delicate regulation of protein functions.

关键词： protein phosphorylation bacterium pathogenicity phosphoproteomics

Blindness as A Challenging Medical and Social Problem in china

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Eye Science 2002年第1X期18卷 4-8页

作者： Shixing HuZhongshan Ophthalmic Center, sun yat-sen university, guangzhou 510060, china Zhongshan Ophthalmic Center Sun Yat-sen University Guangzhou 510060 China

china, a country with about one fifth of the world' s population, has been gaining a rapideconomic growth since 1980s. This country has around 5 million blind people, accountingfor 18% of the blind in the world. The major causes of blindness include cataract,corneal diseases, trachoma, glaucoma, vitreoretinopathy and a number of factorscontributing to blindness in children. The principal cause of blindness in china was nolonger trachoma but cataracts. Vitamin A deficiency remains a public health problem inthe under-developed ***-related conditions in china, such as vision loss due tocataract and retinal disorders, will increase accordingly if no preventive meaunes aretaken. Glaucoma and diabetic retinopathy appear to be predominant induction of thedevastating blind. In this fast developing country blindness is not only a medical orhealth, but also a social problem. Developed strategies have been adopted simultaneouslyby national efforts under the leadership of the government, international agencies,nongovernmental organizations, as well as private sectors in their every-day work toprevent and treat blindness.

关键词：预防盲中国健康保健

Antiangiogenic therapy:a novel approach to overcome tumor hypoxia

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Chinese Journal of Cancer 2010年第8期29卷 715-720页

作者： Fang Peng1,2, Ming Chen1,2 1 State Key Laboratory of Oncology in South china, guangzhou, Guangdong 510060, P. R. china 2 department of Radiation Oncology, sun yat-sen university Cancer Center, guangzhou, Guangdong 510060, P. R. china department of Radiation Oncology Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China Guangdong Guangzhou 510060

Hypoxia is a common phenomenon in solid tumors. Resistance of hypoxic tumor cells to radiation is a significant reason of failure in the local control of tumors. The growth and metastasis of solid tumors rely on blood vessels. Antiangiogenic agents mainly target tumor blood vessels, and radiation therapy mainly targets tumor cells. Combination of antiangiogenic treatment and radiation exhibits synergistic effect, which improves the response of tumors to radiation therapy. The mechanisms of interaction between antiangiogenic agents and ionizing radiation are complex and involve interactions between tumor cells and tumor microenvironment, including tumor oxygenation, stroma, and vasculature. The original mechanism of antiangiogenesis is to induce ischemia and hypoxia in tumors, thereby, "starve" the tumors. However, recently, emerging data suggest that antiangiogenic agents could reduce the proportion of hypoxic cells through normalizing tumor vasculature, decreasing oxygen consumption, and other mechanisms. The use of antiangiogenic agents provides a new approach to overcome the hypoxia problem, and ultimately improves the efficacy of radiation therapy. In this review, we discuss tumor hypoxia, tumor angiogenesis and its regulation, mechanisms of antiangiogenic therapy combined with radiation therapy, and how antiangiogenic therapy overcomes tumor hypoxia.

关键词：抗血管生成肿瘤细胞抗缺氧疗法放射治疗电离辐射肿瘤血管生成相互作用

Synthesis and Characterization of a Novel pH-sensitive Complex for Drug Release

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Journal of Wuhan university of Technology(Materials Science) 2010年第1期25卷 24-27页

作者：许东颖李光吉 department of Polymer Science and Engineering South China University of Technology

A novel pH-sensitive complex was prepared by using oxidized konjac glucomannan and 4-aminosalicylic acid （4-ASA） through glutaraldehyde as a cross-linking agent. The product was characterized by FTIR and 13C NMR spectra, and the thermogravimetric analysis was also studied. The drug release studies in vitro showed that the amount of 4-ASA released from the complex was about 4%, 56% and 17% after 12 h at pH 1.2, 6.8 and 7.4, respectively. The data demonstrate that the rate of the drug release of the complex can be more effectively controlled by pH value. The results showed that the novel pH-sensitive complex could be potentially useful for colon-targeting drug delivery system.

关键词： konjac glucomannan pH-sensitivity drug release

ON SETS OF ZEROES OF CLIFFORD ALGEBRA-VALUED POLYNOMIALS

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Acta Mathematica Scientia 2010年第3期30卷 1004-1012页

作者：杨燕钱涛 School of mathematics and Computational Science Sun Yat-Sen University department of mathematics Faculty of Science and Technology University of Macao

In this note, we study zeroes of Clifford algebra-valued polynomials. We prove that if such a polynomial has only real coefficients, then it has two types of zeroes： the real isolated zeroes and the spherical conjugate ones. The total number of zeroes does not exceed the degree of the polynomial. We also present a technique for computing the zeroes.

关键词： Clifford algebra zeroes of polynomials

Promoter polymorphism of MRP1 associated with reduced survival in hepatocellular carcinoma

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World Journal of Gastroenterology 2010年第48期16卷 6104-6110页

作者： Jing Zhao,Bing-Yun Yu,Jin-E Yang,Key Laboratory of Gene Engineering of the Ministry of Education,School of Life Sciences,sun yat-sen (Zhongshan) university,guangzhou 510275,Guangdong Province,china Dao-Yuan Wang,department of Medical Oncology,The First Affiliated Hospital of guangzhou Medical College,guangzhou 510120,Guangdong Province,china Key Laboratory of Gene Engineering of the Ministry of Education School of Life Sciences Sun Yat-sen (Zhongshan) University Xin Gang Xi Road 135# Guangzhou 510275 Guangdong Province China. lssyje@***

AIM:To investigate the effect of the G-1666A polymorphism in the multidrug resistance related protein-1 (MRP1) on outcome of hepatocellular carcinoma (HCC). METHODS:A cohort of 162 patients with surgically resected HCC who received no postsurgical treatment until relapse was studied. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. Electrophoretic mobility shift assay (EMSA) was used to evaluate the influence of the G-1666A polymorphism on the binding affinity of the MRP1 promoter with its putative transcription factors. RESULTS:Kaplan-Meier analysis showed that patients with GG homologues had a reduced 4-year disease-free survival compared with those carrying at least one A allele (P = 0.011). Multivariate Cox regression analysis indicated that the-1666GG genotype represented an independent predictor of poorer disease-free survival [hazard ratio (HR) = 3.067,95% confidence interval (CI):1.587-5.952,P = 0.001],and this trend became worse in men (HR = 3.154,95% CI:1.604-6.201,P = 0.001). A similar association was also observed between 4-year overall survival and the polymorphism in men (HR = 3.342,95% CI:1.474-7.576,P = 0.004). Moreover,EMSA suggested that the G allele had a stronger binding affinity to nuclear proteins. CONCLUSION:The MRP1-1666GG genotype predicted a worse outcome and was an independent predictor of poor survival in patients with HCC from Southeast china.

关键词： Multidrug resistance related protein-1 Single nucleotide polymorphism Hepatocellular carcinoma Prognosis

Vortex genesis over the Bay of Bengal in spring and its role in the onset of the Asian Summer Monsoon

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Science china Earth Sciences 2011年第1期54卷 1-9页

作者： WU GuoXiong1, GUAN Yue1,2, WANG TongMei3, LIU YiMin1, YAN JingHui4 & MAO JiangYu1 1 State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics (LASG), Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing 100029, china 2Graduate university of Chinese Academy of Sciences, Beijing 100049, china 3department of Atmospheric Science, sun yat-sen university, guangzhou 510275, china 4National Climate Center, china Meteorological Administration, Beijing 100080, china 1. State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics (LASG) Institute of Atmospheric Physics Chinese Academy of Sciences Beijing 100029 China2. Graduate University of Chinese Academy of Sciences Beijing 100049 China3. Department of Atmospheric Science Sun Yat-Sen University Guangzhou 510275 China4. National Climate Center China Meteorological Administration Beijing 100080 China

Physical processes associated with onset of the 1998 Asian summer monsoon were examined in detail using multi-source datasets. We demonstrated that strong ocean-atmosphere-land interaction in the northern Indian Ocean and tropical Asian area during spring is a fundamental factor that induces the genesis and development of a monsoon onset vortex over the Bay of Bengal (BOB), with the vortex in turn triggering onset of the Asian summer monsoon. In spring, strong surface sensible heating over India and the Indochina Peninsula is transferred to the atmosphere, forming prominent in situ cyclonic circulation, with anticyclonic circulations over the Arabian Sea and northern BOB where the ocean receives abundant solar radiation. The corresponding surface winds along the North Indian Ocean coastal areas cause the ocean to produce the in situ offshore currents and upwelling, resulting in sea surface temperature (SST) cooling. With precipitation on the Indochina Peninsula increasing from late April to early May, the offshore current disappears in the eastern BOB or develops into an onshore current, leading to SST increasing. A southwest-northeast oriented spring BOB warm pool with SST >31°C forms in a band from the southeastern Arabian Sea to the eastern BOB. In early May, the Somali cross-equatorial flow forms due to the meridional SST gradient between the two hemispheres, and surface sensible heat over the African land surface. The Somali flow overlaps in phase with the anticyclone over the northern Arabian Sea in the course of its inertial fluctuation along the equator. The convergent cold northerlies on the eastern side of the anticyclone cause the westerly in the inertial trough to increase rapidly, so that enhanced sensible heat is released from the sea surface into the atmosphere. The cyclonic vorticity forced by such sensible heating is superimposed on the inertial trough, leading to its further increase in vorticity strength. Since atmospheric inertial motion is destr

关键词： air-sea interaction spring BOB warm pool monsoon onset vortex inertial oscillation Asian summer monsoon onset

Purification and partial characterizations of coagulant protein Fla from Daboia russelli siamensis (Myanmar) venom

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Acta Pharmacologica Sinica 2007年第10期28卷 1580-1584页

作者： Huan-huan sun~(1,3),Qi CHEN~(2,3),Xi LIN~1,Jia-shu CHEN~(1,4),Peng-xin QIU~1,Guang-mei YAN~~1 department of Pharmacology,Zhongshan Medical College,sun yat-sen university guangzhou 510080,china ~2 Guangdong Institute forDrug Control,guangzhou 510000,china department of Pharmacology Zhongshan Medical College Sun Yat-Sen University Guangzhou China Guangdong Institute for Drug Control Guangzhou China

Aim:To purify and characterize the coagulant protein FIa from Daboia russellisiamensis (Myanmar) ***:FIa was purified from Daboia russellisiamensis (Myanmar) venom by ion-exchange chromatography on CM-SephadexC-50,and gel filtration on Sephadex G-75 and a Superdex 75 *** hemo-static activity of FIa was determined by the method of Williams and *** chromogenic substrates were used respectively to determine the activa-tion of factor X and *** fibrinogen-clotting activity of FIa wasdetermined by the method of Gao et *** saline was used as a negativecontrol while factor Xa and thrombin were used as positive controls,***:FIa,a coagulant protein,was achieved by ion-exchange chromatogra-phy and gel filtration with a molecular weight of 34 479 and an isoelectric point *** was shown to have strong hemostatic *** hemostatic activity of0.5 mg FIa was equal to that of 1.5625 u *** primarily activated factor X,however,had no influence on prothrombin,nor did it cleave or clot ***:FIa is a factor X-activating enzyme,which could activate factor X tofactor Xa,but has no effect on prothrombin and fibrinogen.

关键词： snake venoms Daboia russelli siamensis factor X blood coagulation