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Wikstroelide M potently inhibits HIV replication by targeting reverse transcriptase and integrase nuclear translocation

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Chinese Journal of Natural Medicines 2014年第3期12卷 186-193页

作者： ZHANG Xuan HUANG Sheng-Zhuo GU Wan-Gang YANG Liu-Meng CHEN Huan zheng Chang-Bo ZHAO You-Xing WAN David Chi-Cheong zheng yong-tang Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences&Yunnan Province KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research of Common DiseasesKunming Institute of ZoologyChinese Academy of Sciences School of Pharmaceutical Science&Yunnan Key Laboratory of Pharmacology for Natural Products Kunming Medical University Institute of Tropical Bioscience and Biotechnology Chinese Academy of Tropical Agricultural Sciences School of Biomedical Sciences KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research of Common DiseasesFaculty of MedicineThe Chinese University of Hong Kong School of Pharmacy China Pharmaceutical University

AIM： To evaluate the anti-HIV activity and mechanism of action of wikstroelide M, a daphnane diterpene from Daphne acutiloba Rehder （Thymelaeaceae）. METHOD： The anti-HIV activities of wikstroelide M against different HIV strains were evaluated by cytopathic effect assay and p24 quantification assay with ELISA. The inhibitory effect of wikstroelide M on HIV reverse transcription was analyzed by real-time PCR and ELISA. The effect of wikstroelide M on HIV-1 integrase nuclear translocation was observed with a cell-based imaging assay. The effect of wikstroelide M on LEDGF/p75-IN interaction was assayed by molecular docking. RESULTS： Wikstroelide M potently inhibited different HIV-1 strains, including HIV-lmn, HIV-1AI7, and HIV-19495, induced a cytopathic effect, with ECs0 values ranging from 3.81 to 15.65 ***-I. Wikstroelide M also had high inhibitory activities against HIV-2noD and HIV-2cBL_20-induced cytopathic effects with ECs0 values of 18.88 and 31.90 *** 1. The inhibitory activities of wikstroelide M on the three HIV-1 strains were further confirmed by p24 quantification assay, with ECs0 values ranging from 15.16 to 35.57 ***-1. Wikstroelide M also potently inhibited HIV-lnm induced cytolysis in MT-4 cells, with an ECs0 value of 9.60 *** ~. The mechanistic assay showed that wikstroelide M targeted HIV-I reverse transcriptase and nuclear translocation of integrase through disrupting the interaction between integrase and LEDGF/p75. CONCLUSION： Wikslroelide M may be a potent HIV-1 and HIV-2 inhibitor, the mechanisms of action may include inhibition of reverse trascriptase activity and inhibition of integrase nuclear Iranslocation through dismpting the interaction between integrase and LEDGF/p75.

关键词： Wikstroelide M Daphnane diterpene Daphne acutiloba Rehder HIV Reverse trascriptase integrase Nucleartranslocation Lens epithelium-derived growth factor (LEDGF/p75) Molecular docking

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Comparison between MSM and TGW in HIV Status,Risk behavior,Substance Utility: A Systemic Review and Meta Analysis

Comparison between MSM and TGW in HIV Status,Risk behavior,S...

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第十一届全国免疫学学术大会

作者： Song Tian-Zhang zheng yong-tang Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences& Yunnan Province Kunming Institute of ZoologyChinese Academy of Sciences

Objective: Both as the key population groups in WHO guild-line, transgender women(TGW) shared the same boringsex and anal sexual practices with men who have sex with men(MSM). The differences in HIV events between the two groups are still unclear. The main Objective of this article is to provide a systematic overview of the situation regarding HIV/AIDS among TGW compared with ***: We comprehensively searched the major databases Pub Med, Embase, and the Cochrane Library. After extracted data from the including studies, HIV status, condoms use, high risk behavior, sexual transmitted diseases and basic characters of cases were compared between TGW and MSM using random effects ***: A total of 24 studies including 37521 cases were identified. There were no significant differences between TGW and MSM on HIV Status(OR 0.99, 95% CI 0.71 to 1.39, p=0.97) and condoms use, including frequency of using condom(OR 1.24, 95% CI 0.69 to 2.20, p=0.47) and condomless sexual behavior(OR 0.73, 95% CI 0.37 to 1.43, p=0.36). However, TGW had the higher proportion of high risk behavior, including exchange sex(OR 0.22, 95% CI 0.07 to 0.75, p=0.02), forced sex(OR 0.50, 95% CI 0.34 to 0.72, p=0.003), receptive sexual behavior(OR 0.07, 95% CI 0.05 to 0.1, p< 0.00001), sexual work experience(OR 0.29, 95% CI 0.15 to 0.54, p=0.0001). Moreover, most curable sexual transmitted diseases, including STD+(OR 0.64, 95 % CI 0.42 to 0.96, p=0.03), gonorrhea anal(OR 0.63, 95% CI 0.43 to 0.91, p=0.02), HSV-2(OR 0.36, 95% CI 0.26 to 0.50, p < 0.00001), syphilis(OR 0.44, 95% CI 0.35 to 0.55, p < 0.00001), were higher in TGW group compared with ***: Although TGW showed higher proportion in high risk behavior and sexual transmitted disease infection, the HIV status was same with MSM. The reason may be concentrated in the same proportions of condom use in the two group or the differences in genome or mentality between these two crowds.

关键词： HIV AIDS transgender women sex with men meta analysis

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An Improved Minimum Distance Method Based on Artificial Neural Networks

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Journal of University of Science and Technology Beijing 2002年第1期9卷 74-77页

作者： Qing Li, Deling zheng, Wenbo Meng yong tang Information Engineering School, University of Science and Technology Beijing, Beijing 100083, China E-mail: Li_Qing_2001@*** Univ Sci & Technol Beijing Informat Engn Sch Beijing 100083 Peoples R China

MDM (minimum distance method) is a very popular algorithm in staterecognition. But it has a presupposition, that is, the distance within one class must be shorterenough than the distance between classes. When this presupposition is not satisfied, the method isno longer valid. In order to overcome the shortcomings of MDM, an improved minimum distance method(IMDM) based on ANN (artificial neural networks) is presented. The simulation results demonstratethat IMDM has two advantages, that is, the rate of recognition is faster and the accuracy ofrecognition is higher compared with MDM.

关键词： state recognition minimum distance method artificial neural networks

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Characterization of classical major histocompatibility complex (MHC) class Ⅱ gene in northern pig-tailed macaques (Macaca leonina)

Characterization of classical major histocompatibility compl...

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第十二届全国免疫学学术大会

作者： Lian Xiao-Dong Zhang Xi-He Dai zheng-Xi zheng yong-tang Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province Kunming Institute of ZoologyChinese Academy of Sciences University of Chinese Academy of Sciences Kunming Primate Research Center Kunming Institute of ZoologyChinese Academy of Sciences

The northern pig-tailed macaque(Macaca leonina) has been identified as an independent species from the pig-tailed macaque *** species is a promising animal model in HIV/AIDS pathogenesis and vaccine studies due to susceptibility to ***,the major histocompatibility complex(MHC) genetics in northern pig-tailed macaques remains poorly *** have previously studied the MHC class Ⅰ genes in northern pig-tailed macaques and identified 39 novel ***,we describe the MHC class Ⅱ alleles in all six classical loci(DPA,DPB,DQA,DQB,DRA,and DRB) from northern pig-tailed macaques using a sequence-based typing method for the first time.A total of 60 MHCII alleles were identified of which 27 were shared by other macaque ***,northern pig-tailed macaques expressed a single DRA and multiple DRB genes similar to the expression in humans and other macaque *** and positive selection were detected,and phylogenetic analysis suggested the presence of a common ancestor in human and northern pig-tailed macaque MHC class Ⅱ allelic lineages at the DQA,DQB and DRB *** characterization of full-length MHC class Ⅱ alleles in this study significantly improves understanding of the immunogenetics of northern pig-tailed macaques and provides the groundwork for future animal model studies.

关键词： northern pig-tailed macaque MHC class-Ⅱ

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非人灵长类动物:免疫学基础研究到临床应用的桥梁

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中国免疫学杂志 2018年第8期34卷 1121-1130页

作者：郑宏毅郑永唐中国科学院昆明动物研究所昆明650223

非人灵长类动物的免疫学特征与人高度相似,能够解决啮齿类动物模型面临的医学转化困境,在免疫学研究中具有独特优势。常用的非人灵长类动物(如猕猴、平顶猴、食蟹猴、普通狨猴等)在感染免疫、免疫应答、免疫衰老、自身免疫性疾病等研究... 详细信息

非人灵长类动物的免疫学特征与人高度相似,能够解决啮齿类动物模型面临的医学转化困境,在免疫学研究中具有独特优势。常用的非人灵长类动物(如猕猴、平顶猴、食蟹猴、普通狨猴等)在感染免疫、免疫应答、免疫衰老、自身免疫性疾病等研究领域发挥着举足轻重的作用,是连接基础研究与临床应用之间的桥梁。现今非人灵长类动物应用于免疫学研究依然存在诸多问题,但在国内外学者不断的开发过程中被解决,其应用将更加标准化、规模化,更有利于免疫学发展。作为国家战略需求,我们应当抓住这个机会,加大力度支持非人灵长类的免疫学研究,实现中国免疫学的重大突破。

关键词：非人灵长类动物动物模型免疫学传染病免疫应答

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Transcriptome Analysis Reveal that the Violent Interferon Response and Impaired Immune Control Accelerates SIV Disease Progression of Aged Chinese Rhesus Macaques

Transcriptome Analysis Reveal that the Violent Interferon Re...

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第十二届全国免疫学学术大会

作者： zheng Hong-Yi Shao yong Chen Min Wang Xue-Hui Pang Wei Wu Dong-Dong zheng yong-tang Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences &Yunnan Province Kunming Institute of ZoologyChinese Academy of Sciences State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of Sciences

Background Despite successful viral suppression by anti-retroviral therapy(ART),elderly HIV patients still have a slower rate of immune reconstitution and a higher risk of mortality and AIDS progression than adult ***,the underlying reasons still not fully ***:We constructed the aged Chinese rhesus macaque(ChRM) AIDS models to find the characteristics and explore the mechanisms of elderly *** We intensively compared the immunological,virological and transcriptome dynamics between 6 young(mean age = 7) and 12 old(mean age =18) ChRM throughout the 1 year of SIVmac239 *** After 42 days post infection,5 old ChRM gradually died of AIDS *** ChRM showed a faster AIDS development than young macaques as their rapidly elevated plasma viral load,fast loss of CD4 T cells and serious inversion of CD4/CD8 *** further profiled the transcriptome of PBMC samples from d0,d10,d30,d90 and d360 days post *** with the phenotypic results,SIV infection triggered a dramatical upregulation of genes linked to interferon signaling and viral RNA transcription and replication in both young and old ***,young macaques showed a specific downregulation of some gene sets involved in immune activation,like JNK-MAPK,cytokine(IL-1,IL-12,IL-22 and IL-23) and p53 signaling *** the CD28 and TCR signaling pathway and the negative regulation of apoptosis and immune system progress are reduced especially in old *** of differential expression genes revealed that old macaques display a stronger activation of genes involved in virus response and defense and young macaques have a special ability to relieve the activation of lymphocytes and protein *** Overall,we demonstrated that the rapid disease progression of elderly HV patients may be induced by uncontrollable immune response,especially type Ⅰ interferon response.

关键词： aged animal AIDS model Chinese rhesus macaque interferon response transcriptome SIV infection

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Relation between eardrum flap area and healing outcome of traumatic eardrum perforation

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Chinese Journal of Traumatology 2011年第5期14卷 264-268页

作者： LOU zheng-cai tang yong-mei WU Xiao-hong CHEN Jia-hai Department of Otorhinolaryngology Yiwu Central Hospital Yiwu 322000 Zhejiang Province China

Objective： To retrospectively study the clinical effects of eardrum flap area on the healing outcome following traumatic ***： Totally 291 traumatic eardrum perforations with in-/everted edges were included in this study. They were randomly divided into three groups and received conservative treatment, epidermal growth factor （EGF） via Gelfoam patching, or edge-approximation plus Gelfoam patching respectively. Patients in each group were further divided into two subgroups according to the eardrum flap area ≤ 1/2 or 〉1/2 of the perforation size. The healing rate and mean closure time after tympanic membrane perforation were evaluated at three ***： Of the total 291 participants, 281 were included in the final statistical analysis. The area of curled edge did not affect the healing outcome significantly in any groups （P〉0.05）. The healing rate varied slightly： 90.7% vs 92.3% in spontaneous healing group, 98.2% vs 97.4% in EGF via Gelfoam patching group, and 96.5% vs 100% in edge-approximation plus Gelfoam patching group. In addition, in all groups the area of curled edge did not affect the mean closure time significantly （P〉0.05）. The closure time was （32.3±2.4） d vs （30.6±3.1） d in sponaneous healing group, （13.4±2.5） d vs （13.1± 1.9） d in EGF via Gelfoam patching group, and （11.9±3.1） d vs （12.2±2.1） d in edge-approximation plus Gelfoam patching ***： The eardrum flap area of traumatic eardrum perforation does not significantly affect the clinical outcomes.

关键词： Tympanic membraneperforation Wounds and injuries Surgical flaps Gelatin sponge, absorbable

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α3-Deletion Isoform of HLA-A11 Modulate Cytotoxicity of Natural Killer Cells:Correlations with HIV-1 infection of cells

α3-Deletion Isoform of HLA-A11 Modulate Cytotoxicity of Nat...

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第十二届全国免疫学学术大会

作者： Zhang Xi-He Lian Xiao-Dong Dai zheng-Xi zheng Hong-Yi Chen Xin zheng yong-tang Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences& Yunnan Province/Key Laboratory of Bioactive Peptides of Yunnan Province Kunming Institute of ZoologyChinese Academy of Sciences Kunming College of Life Science University of Chinese Academy of Sciences School of Life Sciences University of Science and Technology of China

Alternative splicing is ubiquitous in many genes,especially those involved in ***,although many immunologically-relevant genes have been observed that undergo alternative splicing,nothing is certain concerning the function of these *** human leukocyte antigen(HLA) I molecules expressed on almost all nucleated cells and play a pivotal role in both innate and adaptive *** splice variants of HLA I genes have been reported,there is currently no deeper research dedicated to the function of these *** this report,we clarify the characteristics,expression,and function of a novel splice variant of HLA-A11 named HLA-A11 *** report that HLA-A11 svE4 locate on the cell surface without p2-microglobulin(β2 m).Additionally,HLA-A11 svE4 not only homodimerized,but formed a heterodimer with HLA-A open conformers(OCs) instead of combining with β2 ***,HLA-A11 svE4 inhibited activation of natural killer(NK) cells to protect target *** with β2 m and HLA-A11,the heterodimer of HLA-A11 svE4 and HLA-A11 protected target cells from lysis by NK cells more ***,HLA-AsvE4 was upregulated by HIV-1 in vivo and by herpes simplex virus,cytomegalovirus and hepatitis B virus in *** addition,our findings indicated that HLA-A11 svE4 molecules were functional in activating CD8 T cells through antigen *** together,these results indicated that HLA-A11 svE4 can homodimerize and form a novel heterodimeric complex with HLA-A11 ***,the data are consistent with HLA-A11 svE4 playing a role in immune escape of HIV-1.

关键词： HLA-I Alternative splicing open conformers Nature Killer cells HIV-1

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蛋白激酶C在H IV复制中的作用与药物发现

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中国药理学通报 2005年第9期21卷 1025-1029页

作者：张高红唐宏郑永唐中国科学院昆明动物研究所云南昆明中国科学院微生物研究所北京100080

蛋白激酶C(PKC)是一类磷脂依赖的丝氨酸/苏氨酸蛋白激酶,PKC在中枢神经系统疾病及心血管紊乱等多种人类疾病中都发挥了重要作用。研究发现,PKC可以通过多种途径刺激H IV病毒的活化,并磷酸化病毒复制周期中的多种蛋白,如P17gag、Nef、Rev... 详细信息

蛋白激酶C(PKC)是一类磷脂依赖的丝氨酸/苏氨酸蛋白激酶,PKC在中枢神经系统疾病及心血管紊乱等多种人类疾病中都发挥了重要作用。研究发现,PKC可以通过多种途径刺激H IV病毒的活化,并磷酸化病毒复制周期中的多种蛋白,如P17gag、Nef、Rev和V if等,这些蛋白的磷酸化在病毒复制周期中起到了不可忽视的作用。了解PKC与H IV及细胞间的复杂关系,开发抑制PKC蛋白激酶的药物从而达到抑制H IV复制的目的,或激活PKC从而减少或消除体内潜伏的H IV病毒库是对PKC在抗H IV研究中应用提出的两个主要方向,对于开发新型抗H IV药物有重要意义。

关键词：蛋白激酶C HIV 信号转导磷酸化

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Synergistic effect of bonding heterogeneity and phonon localization in introducing excellent thermoelectric properties in layered heteroanionic NdZnSbO material

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Journal of Energy Chemistry 2025年第1期100卷 259-272页

作者： Da Wan Shuwei tang Shulin Bai Xiaodong Li Peng Ai Wanrong Guo Tuo zheng College of Materials Science and Engineering Liaoning Technical University Faculty of Chemistry Northeast Normal University

Layered rare-earth metal oxides, harnessing the dual properties of oxides and two-dimensional layered materials, exhibit remarkable thermal stability and quantum confinement effects. Therefore, this work adopts the first-principles calculation combined with the Boltzmann transport theory to predict the thermoelectric properties of NdZnSbO compound. The coexistence of weak interlayer van der Waals interactions, robust intralayer ionic bonding, and partial covalent bonding leads to remarkable bonding heterogeneity, which engenders pronounced phonon scattering and imposes constraints on thermal transport along the out-of-plane direction. The weakened chemical bonds induced by the antibonding states, together with the rattling-like behavior of the Zn atom, culminate in the profound anharmonicity in the layered NdZnSbO compound. The weakening bond and heavy element contribute to the softness of phonon modes, which significantly diminishes the phonon group velocity. The redistribution-dominated four-phonon scattering process spans a large optical gap, which effectively reduces the lattice thermal conductivity. The NdZnSbO compound exhibits direct semiconductor characteristic with a bandgap of 0.73 e V by adopting the Heyd-Scuseria-Ernzerhof(HSE06) functional in combination with spin–orbit coupling(SOC) effect. The multi-valley feature of NdZnSbO compound augur favorably for band degeneracy, thus amplifying the power factor. Consequently, an optimal figure-of-merit(ZT) of 3.40 at 900 K is achieved for the n-type NdZnSbO compound. The present study delves deeply insights into the origins for the low thermal conductivity of NdZnSbO compound and proposes an optimization scheme to enhance overall thermoelectric performance.

关键词： Bond strength (chemical)

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