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5型腺病毒 1

疫苗 1

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靶基因表达 1

预存免疫 1

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Serologic study on the outbreak of acute upper respiratory tract infections caused by adenovirus 3

JIANG Lufang, JU Liwen, LIN Yuzun, ZHOU Liandi, YU Shunzhang, JIANG Qingwu, JIANG Renjie

《医学前沿（英文）》 2007年 第1卷 第2期   页码 215-218 doi: 10.1007/s11684-007-0041-3

摘要： From April to June, 2004, an outbreak of acute upper respiratory tract infections (AURTI) occurred in the north area of Jiangsu Province, China. Twenty throat swabs were collected with 13 of them presenting an adenovirus (Ad)-like cytopathogenic effect on HEp-2. These were verified as Ad by the electron microscope, direct immunofluorescence assay and Ad primer-mediated PCR. Moreover, they were identified as adenovirus type 3 (Ad3) by type-specific PCR and sequencing of the amplification products. Subsequent serologic studies were carried out to finally diagnose and document the outbreak. The neutralization test of paired serum of six in nine cases show obviously increased antibodies titers. The positive rate of IgM, IgG and recovery phase neutralization antibodies of the cases were 3.7%, 44.4% and 59.5% respectively while those of the controls were 0%, 8.3% and 33.3% respectively. The values of Chi-Square were 0.510, 0.018 and 0.226 respectively. The concordance between IgG detected by ELISA and neutralization anti bodies detected by the neutralization test was 61.4% and the value of Kappa was 0.070. By the serologic study, we can definitively diagnose that this outbreak of acute respiratory infections was caused by Adenovirus 3.

关键词： Twenty     Adenovirus     cytopathogenic     type-specific     AURTI    

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Investigation of gene therapy of denovirus in immune suppression

XIA Xi, WANG Beibei, CAO Li, CHEN Gang, WU Peng, LU Yunping, ZHOU Jianfeng, MA Ding

《医学前沿（英文）》 2008年 第2卷 第4期   页码 386-390 doi: 10.1007/s11684-008-0074-2

摘要： The aim of this paper is to investigate the safety of reconstructed adenovirus in immunosuppressive therapeutics and to explore the role of ciclosporin A in antagonizing the elimination of the vector. Several rats were given retroperitoneal injection of purified ADV-TK in order to obtain models. After 14 days’ treatment of ciclosporin A, samples of different periods were obtained, then stained with hematoxylin-eosin (HE) to detect inflammation reactions. Immunohistochemistry was used to examine the expression of adenovirus in organs. The results are as follows: (1) In HE stained sections of the organs, some transitory and reversible inflammation was detected. (2) In immunohistochemistry assay, reconstructed adenovirus decreased gradually as time went by in the control group, while it did not happen in the experimental group in which the adenovirus showed a relative increase compared with their counterparts ( < 0.05). (3) The distributions of adenovirus in the liver, spleen and lung were higher than those in the other organs detected. Reconstructed adenovirus as a vector is definitely safe in immunosuppressive therapeutics, and ciclosporin A, to some extent, is able to consequently inhibit the immune response of the rats and prolong the existing period of adenovirus.

关键词： different     reversible inflammation     immunohistochemistry     reconstructed adenovirus     ciclosporin    

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Adenovirus-mediated antisense ERK2 gene therapy ameliorates chronic allograft nephropathy in a rat model

Zhao DING, Zhishui CHEN, Xilin CHEN, Ming CAI, Hui GUO, Nianqiao GONG

《医学前沿（英文）》 2009年 第3卷 第2期   页码 204-210 doi: 10.1007/s11684-009-0039-0

摘要： To investigate the effect and underlying mechanism of adenovirus-mediated antisense ERK2 (Adanti-ERK2) gene therapy upon chronic allograft nephropathy (CAN) of rats, male Lewis (LEW, RT11) rats received male Fisher (F344, RT11v1) renal allografts. The recipients were divided into three groups: (1) empty control group; (2) vector control group; (3) gene therapy group. All recipients were sacrificed for the grafts and serum analysis at the 24th week after transplantation. Morphometric analysis was used to determine the fibrosis of grafts. Immunohistochemistry was used to detect the expression of E-Cadherin, Vimentin, TβR I and the infiltration of CD4 T lymphocyte, CD8 T lymphocyte and ED-1 monocytes. Enzyme linked immunosorbent assay (ELISA) was used to detect TGF-β1 in serum. The grafts in the control group and vector control group showed CAN. There was less E-Cadherin in renal tubular epithelial cells in the empty control group but more Vimentin and TβR I. In the gene therapy group, the fibrosis was ameliorated and fewer T lymphocytes and ED-1 monocytes infiltrated in the interstitium. There was no significant difference in the expression of E-Cadherin between the gene therapy group and normal rats. Compared with the empty control group, the expression of TGF-β1 in the gene therapy group was down-regulated. Adanti-ERK2 gene therapy protects the renal allograft and attenuates graft fibrosis, which may be correlated with a decreased renal tubular epithelial mesenchymal transition, a decreased infiltration of CD4 T lymphocyte, CD8 T lymphocytes and ED-1 monocytes in renal interstitium, and the down-regulated TGF-β1 expression.

关键词： anti-ERK2     renal transplantation     epithelial mesenchymal transition     chronic allograft nephropathy    

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Expression and function of DMT1 without IRE in C6 cells mediated by recombinant adenovirus

Xixun DU*, Huamin XU*, Hong JIANG, Jun WANG, Lei WANG, Junxia XIE

《医学前沿（英文）》 2009年 第3卷 第1期   页码 67-71 doi: 10.1007/s11684-009-0010-0

摘要： Divalent metal transporter 1 (DMT1) is a ferrous iron import protein. The improper expression of DMT1 is involved in neurodegenerative diseases. In the present study, we constructed a recombinant adenovirus containing the gene of DMT1 without the iron response element (DMT1-IRE) and investigated its expression and function in the C6 glioma cell line. The DMT1-IRE gene, obtained by RT-PCR, was cloned into the shuttle plasmid pAdTrack-CMV containing green fluorescent protein (GFP) reporter gene. Linearized plasmid pAdTrack-CMV-DMT1-IRE was subsequently co-transformed into ( ) BJ5183 cells along with an adenoviral backbone plasmid pAdEasy-1 after digestion with I. I-digested pAdEasy1-DMT1-IRE was then transfected into E1-transformed human embryonic kidney cells (HEK293 cells) , in which recombinant adenoviruses were generated within 7 to 10 days. The results demonstrated that we obtained the DMT1-IRE gene. pAdEasy1-DMT1-IRE yielded a large fragment, plus a smaller fragment of 4.5 kb after digestion with I. PCR confirmed pAdEasy1-DMT1-IRE contained gene DMT1-IRE, indicating the successful construction of recombinant adenovirus plasmid containing DMT1-IRE. GFP fluorescence further confirmed the generation of adenovirus. AdDMT1-IRE could efficiently infect C6 glioma cells. And cell viability decreased in Ad-DMT1-IRE infected cells after iron overload compared to the control. These results suggest that the over expressed DMT1-IRE can aggravate the iron induced cell death due to its iron influx function.

关键词： divalent metal transporter 1     recombinant adenovirus     homologous recombination     iron    

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Adenovirus-mediated tissue inhibitor of metalloproteinase-3 gene transfection inhibits rabbit intervertebral

Xudong YU MM, Zengwu SHAO MD, Liming XIONG MD, Weiwei XU MM, Hezhong WANG MM, Huifa XU MM,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 415-420 doi: 10.1007/s11684-009-0072-z

摘要： The aim of this study was to investigate the inhibitory effects of recombinant adenovirus vector carrying tissue inhibitor of metalloproteinase-3 (RAdTIMP-3) against degeneration of rabbit intervertebral disc. Thirty Japanese white rabbits of 4 months old were randomly divided into 5 groups. Mild or moderate rabbit lumbar disc degeneration model was constructed with the controllable axial loading device by imposing 98N pressure at the discs for 2 weeks. Various doses of virus were injected into the degenerated discs as follows: 20μL of normal saline in group 1; 20μL of RAd66 (an empty adenovirus vector, 1.0×10OPU/mL) in group 2; and 20, 10, and 5μL of RAdTIMP-3 (1.0×10OPU/mL) in groups 3, 4, and 5, respectively. Two weeks after the injection, the discs were collected for investigations, including assessment of degeneration degrees according to the Thompson’s grading system, reverse-transcription polymerase chain reaction (RT-PCR) assay for TIMP-3 gene, Safranin O-Fast green staining, and immunohistochemical staining for TIMP-3 and type II collagen. According to Thompson’s criteria, the degeneration of groups 3, 4, and 5, especially group 3, was alleviated as compared with groups 1 and 2. RT-PCR revealed that the expression of TIMP-3 in groups 3, 4, and 5, especially in group 3, was significantly enhanced as compared with group 1 (<0.01). Both Safranin O-Fast green staining and type II collagen staining demonstrated better reserved integrity of disc matrix in groups 3, 4, and 5 than in groups 1 and 2. TIMP-3 staining exhibited an obvious increase of positive-staining rate in groups 3, 4, and 5 as compared with group 1. The positive-staining rate in group 3 (79.42%±1.35%) was about 3times that of group 1 (25.47%±5.46%, <0.01). RAdTIMP-3 can effectively protect the matrix of rabbit intervertebral disc against overloading-induced degeneration in a dose-dependent manner, resulting in the alleviation of disc degeneration.

关键词： tissue inhibitor of metalloproteinase-3     intervertebral disc     rabbit     gene therapy    

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纳米复合肺靶向递送突破Ad5预存免疫屏障 Article

杨益隆, 吴诗坡, 王玉东, 邵方泽, 吕鹏, 李汭桦, 赵晓帆, 张军, 张晓鹏, 李建民, 侯利华, 徐俊杰, 陈薇

《工程（英文）》 2023年 第27卷 第8期   页码 127-139 doi: 10.1016/j.eng.2022.12.007

摘要：

重组5型腺病毒载体（Ad5）已成功用于埃博拉病毒、新型肺炎冠状病毒等新发突发传染病防控，然而针对病毒载体的预存免疫会对疫苗的免疫原性造成一定影响。维持重组Ad5型疫苗的高免疫原性并减少预存免疫效应，已成为该领域的重要研究方向。基于生物相容性纳米颗粒，本研究尝试通过调控Ad5与宿主的相互作用应对上述挑战。制备出的正电人血清白蛋白纳米颗粒[(+)HSAnp]能够与Ad5自组装形成复合物，针对柯萨奇病毒-腺病毒受体（CAR）阳性和阴性细胞均能显著提高靶基因表达量。在小鼠模型中，滴鼻吸入Ad5/(+)HSAnp复合物实现了高效（高达227倍）和长期（长达60天）的肺靶向靶基因表达，且增强效应可通过表面电位和给药剂量进行调控。经纳米复合的5型腺病毒载体埃博拉疫苗和新冠疫苗，在Ad5预存免疫模型中显著增强了体液免疫和黏膜免疫应答。本研究表明通过纳米颗粒调控病毒载体的聚集状态和表面电位，能够用于设计增强型的疫苗和基因治疗载体。


 

关键词： 5型腺病毒     疫苗     预存免疫     纳米颗粒     靶基因表达    

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标题 作者 时间 类型 操作

Serologic study on the outbreak of acute upper respiratory tract infections caused by adenovirus 3

JIANG Lufang, JU Liwen, LIN Yuzun, ZHOU Liandi, YU Shunzhang, JIANG Qingwu, JIANG Renjie

期刊论文

Investigation of gene therapy of denovirus in immune suppression

XIA Xi, WANG Beibei, CAO Li, CHEN Gang, WU Peng, LU Yunping, ZHOU Jianfeng, MA Ding

期刊论文

Adenovirus-mediated antisense ERK2 gene therapy ameliorates chronic allograft nephropathy in a rat model

Zhao DING, Zhishui CHEN, Xilin CHEN, Ming CAI, Hui GUO, Nianqiao GONG

期刊论文

Expression and function of DMT1 without IRE in C6 cells mediated by recombinant adenovirus

Xixun DU*, Huamin XU*, Hong JIANG, Jun WANG, Lei WANG, Junxia XIE

期刊论文

Adenovirus-mediated tissue inhibitor of metalloproteinase-3 gene transfection inhibits rabbit intervertebral

Xudong YU MM, Zengwu SHAO MD, Liming XIONG MD, Weiwei XU MM, Hezhong WANG MM, Huifa XU MM,

期刊论文

纳米复合肺靶向递送突破Ad5预存免疫屏障

杨益隆, 吴诗坡, 王玉东, 邵方泽, 吕鹏, 李汭桦, 赵晓帆, 张军, 张晓鹏, 李建民, 侯利华, 徐俊杰, 陈薇

期刊论文