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Regulation of exogenous bFGF gene mediated by recombinant adeno-associated virus

Ke SONG, Nianjing RAO, Meiling CHEN, Yingguang CAO

《医学前沿（英文）》 2009年 第3卷 第2期   页码 158-163 doi: 10.1007/s11684-009-0042-5

摘要： The regulatory effect of basic fibroblast growth factor (bFGF) mediated by recombinant adeno-associated virus (AAV) was investigated. Recombinant plasmid pAAV-S3-bFGF, and pSVneo were co-transfected into BHK-21 cells, then the recombinant AAV genome was replicated and packaged with the helper virus HSV1-rc/ΔUL2. The titer of the recombinant rAAV2-tet-off-bFGF was determined by dot-blot assay. MC3T3-E1 cells were infected with rAAV2-tet-off-bFGF. Regulatory effects of Doxycycline (Dox) on bFGF and osteogenic factors were assayed quantitatively by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The physical particle titer of rAAV2-tet-off-bFGF successfully constructed was 1.8×10 vector genomes/mL, and the virus could infect MC3T3-E1 cells effectively. In MC3T3-E1 cells treated with Dox, the expression levels of exogenous bFGF and osteogenic factors declined to varying degrees. It was concluded that rAAV2-tet-off-bFGF could infect MC3T3 cells efficiently, and this recombinant system could be regulated successfully by Dox .

关键词： tetracycline regulatory system     adeno-associated virus     basic fibroblast growth factor     gene regulation    

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Long-term correction of hemorrhagic diathesis in hemophilia A mice by an AAV-delivered hybrid FVIII composed of the human heavy chain and the rat light chain

《医学前沿（英文）》 2022年 第16卷 第4期   页码 584-595 doi: 10.1007/s11684-021-0844-7

摘要： Conventional therapies for hemophilia A (HA) are prophylactic or on-demand intravenous FVIII infusions. However, they are expensive and inconvenient to perform. Thus, better strategies for HA treatment must be developed. In this study, a recombinant FVIII cDNA encoding a human/rat hybrid FVIII with an enhanced procoagulant potential for adeno-associated virus (AAV)-delivered gene therapy was developed. Plasmids containing human FVIII heavy chain (hHC), human light chain (hLC), and rat light chain (rLC) were transfected into cells and hydrodynamically injected into HA mice. Purified AAV viruses were intravenously injected into HA mice at two doses. Results showed that the hHC+ rLC protein had a higher activity than the hHC+ hLC protein at comparable expression levels. The specific activity of hHC+ rLC was about 4- to 8-fold higher than that of their counterparts. Hydrodynamic injection experiments obtained consistent results. Notably, the HA mice undergoing the AAV-delivered hHC+ rLC treatment exhibited a visibly higher activity than those treated with hHC+ hLC, and the therapeutic effects lasted for up to 40 weeks. In conclusion, the application of the hybrid FVIII (hHC+ rLC) via an AAV-delivered gene therapy substantially improved the hemorrhagic diathesis of the HA mice. These data might be of help to the development of optimized FVIII expression cassette for HA gene therapy.

关键词： hemophilia A     adeno-associated virus (AAV)     human/rat hybrid factor VIII     gene therapy     dual chain strategy    

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延长腺相关病毒递送药物的半衰期提高治疗效果 Article

吴会芳, 胡丹, 李泉晓, 王春雨, 朱晓艺, 李威, 陈宾凡, 季萍, 黄可可, 黄爱玲, 黄竞荷, Dimiter S. Dimitrov, 吴艳玲, 应天雷

《工程（英文）》 2023年 第21卷 第2期   页码 203-213 doi: 10.1016/j.eng.2022.02.009

摘要： 在这项腺相关病毒（adeno-associated virus, AAV）基因治疗研究中，通过与免疫球蛋白G1（immunoglobulin G 1, IgG1）可溶性单体Fc 区（soluble monomeric

关键词： 基因治疗     腺相关病毒     半衰期     成纤维细胞生长因子21     2型糖尿病    

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Overexpression of netrin-1 improves neurological outcomes in mice following transient middle cerebral artery occlusion

null

《医学前沿（英文）》 2011年 第5卷 第1期   页码 86-93 doi: 10.1007/s11684-011-0118-x

摘要：

Netrin-1 (NT-1) is one of the axon-guiding molecules that are critical for neuronal development. Because of its structural homology to the endothelial mitogens, NT-1 may have similar effects on vascular network formation. NT-1 was shown to be able to stimulate the proliferation and migration of human cerebral endothelial cells in vitro and also promote focal neovascularization in adult brain in vivo. In the present study, we reported the delivery of NT-1 using an adeno-associated virus (AAV) vector (AAV-NT-1) into mouse brain followed by transient middle cerebral artery occlusion (tMCAO). We found that AAV vectors did not elicit a detectable inflammatory response, cell loss or neuronal damage after brain transduction. The level of NT-1 was increased in the AAV-NT-1-transduced tMCAO mice compared with the control mice. Furthermore, the neurobehavioral outcomes were significantly improved in AAV-NT-1-transduced mice compared with the control animals (P<0.05) 7 days after tMCAO. Our data suggests that NT-1 plays a neuronal function recovery role in ischemic brain and that NT-1 gene transfer might present a valuable approach to treat brain ischemic disorders.

关键词： adeno-associated virus     angiogenesis     gene transfer     ischemia     middle cerebral artery occlusion     netrin-1    

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Cyclooxygenase-2 gene-1195G/A genotype is associated with the risk of HBV-induced HCC: A case-control

Li-Feng LIU MD, PhD, Qiong CHEN MD, PhD, Ying CHANG MD, PhD, Ju-Sheng LIN MD, PhD, Jin-Liang ZHANG MM,

《医学前沿（英文）》 2010年 第4卷 第1期   页码 90-95 doi: 10.1007/s11684-010-0021-x

摘要： This study aimed to identify functional single nucleotide polymorphisms in the cyclooxygenase-2 gene promoter and evaluate their effects on the risk of primary hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infection. We conducted a population-based, case-control study enrolling 630 Han Chinese people in Hubei province. Subjects included primary HCC patients with HBV infection (=210), chronic hepatitis B cases (=210) and healthy Han Chinese (=210). -1195G/A polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing analysis. We found-1195A allele carriers had a higher risk of HCC with HBV infection (OR, 0.72; 95% CI, 0.548–0.946). The-1195A allele might be used as a marker in screening individuals at high risk of HCC with HBV infection.

关键词： cyclooxygenase-2 gene     single nucleotide polymorphisms     susceptibility     primary hepatocellular carcinoma     hepatitis B virus infection    

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Removal of virus aerosols by the combination of filtration and UV-C irradiation

《环境科学与工程前沿（英文）》 2023年 第17卷 第3期 doi: 10.1007/s11783-023-1627-y

摘要：

● The removal of virus aerosols by filtration and UV-C irradiation was proposed.

关键词： Filtration system     UV-C irradiation     Virus aerosol     Public health     COVID-19    

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Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

《农业科学与工程前沿（英文）》 2017年 第4卷 第3期   页码 260-267 doi: 10.15302/J-FASE-2016116

摘要： The innate immune response is the first line of defense against viral invasion and pro-inflammatory chemokines and cytokines have a critical function in the innate immune responses against virus infections. The ability of a rabies virus (RABV) to induce the expression of chemokines and cytokines can lead to viral clearance from the central nervous system (CNS), whereas the ability to evade such expression and activation contributes to virulence and pathogenicity. In this review, the crucial contribution of chemokines/cytokines to clearing RABV from the CNS is discussed, including recruiting leukocytes into the CNS, enhancement of blood brain barrier permeability and activation of various immune cells that are essential for viral clearance. In addition, recombinant RABV expressing cytokines and chemokines can induce elevated innate and adaptive immune responses which result in clearing an established wild-type RABV infection in the CNS.

关键词： antiviral     blood brain barrier     chemokines and cytokines     innate immunity     rabies virus    

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Crk-associated substrate, vascular smooth muscle and hypertension

TANG Dale

《医学前沿（英文）》 2008年 第2卷 第4期   页码 323-331 doi: 10.1007/s11684-008-0062-6

摘要： Hypertension is characterized by vascular smooth muscle constriction and vascular remodeling involving cell migration, hypertrophy and growth. Crk-associated substrate (CAS), the first discovered member of the adapter protein CAS family, has been shown to be a critical cellular component that regulates various smooth muscle functions. In this review, the molecular structure and protein interactions of the CAS family members are summarized. Evidence for the role of CAS in the regulation of vascular smooth muscle contractility is presented. Contraction stimulation induces CAS phosphorylation on Tyr-410 in arterial smooth muscle, creating the binding site for the Src homology (SH) 2/SH3 protein CrkII, which activates neuronal Wiskott-Aldrich syndrome protein (N-WASP)-mediated actin assembly and force development. The functions of CAS in cell migration, hypertrophy and growth are also summarized. Abelson tyrosine kinase (Abl), c-Src, focal adhesion kinase (FAK), proline-rich tyrosine kinase 2 (PYK2), protein tyrosine phosphatase-proline, glutamate, serine and threonine sequence protein (PTP-PEST) and SHP-2 have been documented to coordinate the phosphorylation and dephosphorylation of CAS. The downstream signaling partners of CAS in the context of cell motility, hypertrophy, survival and growth are also discussed. These new findings establish the important role of CAS in the modulation of vascular smooth muscle functions. Furthermore, the upstream regulators of CAS may be new biologic targets for the development of more effective and specific treatment of cardiovascular diseases such as hypertension.

关键词： Contraction stimulation     phosphatase-proline     molecular structure     discovered     hypertension    

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Immunological and virological characteristics of human immunodeficiency virus type 1 superinfection:

null

《医学前沿（英文）》 2017年 第11卷 第4期   页码 480-489 doi: 10.1007/s11684-017-0594-8

摘要：

Superinfection is frequently detected among individuals infected by human immunodeficiency virus type I (HIV-1). Superinfection occurs at similar frequencies at acute and chronic infection stages but less frequently than primary infection. This observation indicates that the immune responses elicited by natural HIV-1 infection may play a role in curb of superinfection; however, these responses are not sufficiently strong to completely prevent superinfection. Thus, a successful HIV-1 vaccine likely needs to induce more potent and broader immune responses than those elicited by primary infection. On the other hand, potent and broad neutralization responses are more often detected after superinfection than during monoinfection. This suggests that broadly neutralizing antibodies are more likely induced by sequential immunization of multiple different immunogens than with only one form of envelope glycoprotein immunogens. Understanding why the protection from superinfection by immunity induced by primary infection is insufficient and if superinfection can lead to cross-reactive immune responses will be highly informative for HIV-1 vaccine design.

关键词： human immunodeficiency virus type I     superinfection     incidence     immune response    

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Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies

《医学前沿（英文）》 2022年 第16卷 第3期   页码 459-466 doi: 10.1007/s11684-021-0841-x

摘要： Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.

关键词： Fanconi anemia     aplastic anemia     hematologic malignancy     germline predisposition    

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New definition of metabolic dysfunction-associated fatty liver disease with elevated brachial-ankle pulse

《医学前沿（英文）》 2022年 第16卷 第5期   页码 714-722 doi: 10.1007/s11684-021-0888-8

摘要： A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01–1.55) and 1.35 (95% CI 1.07–1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07–2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.

关键词： metabolic dysfunction-associated fatty liver disease     non-alcoholic fatty liver disease     fibrosis score     brachial-ankle pulse wave velocity     albuminuria    

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Advances in newly developing therapy for chronic hepatitis C virus infection

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 166-174 doi: 10.1007/s11684-014-0334-2

摘要：

Chronic hepatitis C virus (HCV) infection afflicts a reported 170 million people worldwide and is often complicated by cirrhosis and hepatocellular carcinoma. Morbidity and mortality are decreased with the successful treatment of chronic HCV infection. Increased understanding of the HCV has allowed further development of new direct-acting antiviral (DAA) agents against the HCV and has also allowed the development of IFN-free oral treatment regimens. In late 2013 the first nucleotide polymerase inhibitor regimen with RBV alone for genotypes 2/3 and in combination with a 12-week regimen of PEG-IFN+RBV for genotypes 1, 4 was approved for use in the US. A number of promising new DAA regimens which are IFN-free are in phase 3 development and the first will likely be approved for use in the US in 2014. The currently approved regimens are discussed in detail and currently available data on future regimens are reviewed herein.

关键词： direct-acting antiviral (DAA)     nucleotide polymerase inhibitors     protease inhibitors    

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Universal influenza virus vaccines: what can we learn from the human immune response following exposure

null

《医学前沿（英文）》 2017年 第11卷 第4期   页码 471-479 doi: 10.1007/s11684-017-0602-z

摘要：

Several universal influenza virus vaccine candidates based on eliciting antibodies against the hemagglutinin stalk domain are in development. Typically, these vaccines induce responses that target group 1 or group 2 hemagglutinins with little to no cross-group reactivity and protection. Similarly, the majority of human anti-stalk monoclonal antibodies that have been isolated are directed against group 1 or group 2 hemagglutinins with very few that bind to hemagglutinins of both groups. Here we review what is known about the human humoral immune response to vaccination and infection with H7 subtype influenza viruses on a polyclonal and monoclonal level. It seems that unlike vaccination with H5 hemagglutinin, which induces antibody responses mostly restricted to the group 1 stalk domain, H7 exposure induces both group 2 and cross-group antibody responses. A better understanding of this phenomenon and the underlying mechanisms might help to develop future universal influenza virus vaccine candidates.

关键词： universal influenza virus vaccine     hemagglutinin stalk     H7N9    

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Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection

Weibao Song, Hongjuan Zhang, Yu Zhang, Rui Li, Yanxing Han, Yuan Lin, Jiandong Jiang

《医学前沿（英文）》 2021年 第15卷 第3期   页码 404-415 doi: 10.1007/s11684-021-0834-9

摘要： Zika virus (ZIKV) is an emerging pathogen associated with neurological complications, such as Guillain–Barré syndrome in adults and microcephaly in fetuses and newborns. This mosquito-borne flavivirus causes important social and sanitary problems owing to its rapid dissemination. However, the development of antivirals against ZIKV is lagging. Although various strategies have been used to study anti-ZIKV agents, approved drugs or vaccines for the treatment (or prevention) of ZIKV infections are currently unavailable. Repurposing clinically approved drugs could be an effective approach to quickly respond to an emergency outbreak of ZIKV infections. The well-established safety profiles and optimal dosage of these clinically approved drugs could provide an economical, safe, and efficacious approach to address ZIKV infections. This review focuses on the recent research and development of agents against ZIKV infection by repurposing clinical drugs. Their characteristics, targets, and potential use in anti-ZIKV therapy are presented. This review provides an update and some successful strategies in the search for anti-ZIKV agents are given.

关键词： Zika virus     clinical drugs     ZIKV inhibitors     antivirals     repurposing    

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Dynamics of foot-and-mouth disease virus replication in cells at different phases of the cell-division

Claudia DOEL,Zhidong ZHANG,Lise MAZELET,Ryan WATERS,John BASHIRUDDIN

《农业科学与工程前沿（英文）》 2014年 第1卷 第3期   页码 250-257 doi: 10.15302/J-FASE-2014031

摘要： Foot-and-mouth-disease virus (FMDV) replicates in epithelial cells. The restriction of FMDV RNA to the basal cell layer of epithelia suggests a possible link between FMDV replication and the cell status. This paper describes studies in which FMDV infection was investigated in cells that were held at various cell division phases using cell cycle inhibitors. The results suggest that when cells were arrested at the G or G /S phase, high levels of viral RNA were detected by quantitative real-time reverse transcription PCR and viral protein synthesis was observed by specific labeling techniques. In contrast, when cells were arrested at the G /M phase, reduced or no viral RNA synthesis was detected.

关键词： foot-and-mouth disease virus     cell cycle     replication    

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标题 作者 时间 类型 操作

Regulation of exogenous bFGF gene mediated by recombinant adeno-associated virus

Ke SONG, Nianjing RAO, Meiling CHEN, Yingguang CAO

期刊论文

Long-term correction of hemorrhagic diathesis in hemophilia A mice by an AAV-delivered hybrid FVIII composed of the human heavy chain and the rat light chain

期刊论文

延长腺相关病毒递送药物的半衰期提高治疗效果

吴会芳, 胡丹, 李泉晓, 王春雨, 朱晓艺, 李威, 陈宾凡, 季萍, 黄可可, 黄爱玲, 黄竞荷, Dimiter S. Dimitrov, 吴艳玲, 应天雷

期刊论文

Overexpression of netrin-1 improves neurological outcomes in mice following transient middle cerebral artery occlusion

null

期刊论文

Cyclooxygenase-2 gene-1195G/A genotype is associated with the risk of HBV-induced HCC: A case-control

Li-Feng LIU MD, PhD, Qiong CHEN MD, PhD, Ying CHANG MD, PhD, Ju-Sheng LIN MD, PhD, Jin-Liang ZHANG MM,

期刊论文

Removal of virus aerosols by the combination of filtration and UV-C irradiation

期刊论文

Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

期刊论文

Crk-associated substrate, vascular smooth muscle and hypertension

TANG Dale

期刊论文

Immunological and virological characteristics of human immunodeficiency virus type 1 superinfection:

null

期刊论文

Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies

期刊论文

New definition of metabolic dysfunction-associated fatty liver disease with elevated brachial-ankle pulse

期刊论文

Advances in newly developing therapy for chronic hepatitis C virus infection

null

期刊论文

Universal influenza virus vaccines: what can we learn from the human immune response following exposure

null

期刊论文

Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection

Weibao Song, Hongjuan Zhang, Yu Zhang, Rui Li, Yanxing Han, Yuan Lin, Jiandong Jiang

期刊论文

Dynamics of foot-and-mouth disease virus replication in cells at different phases of the cell-division

Claudia DOEL,Zhidong ZHANG,Lise MAZELET,Ryan WATERS,John BASHIRUDDIN

期刊论文