15 results on '"He, Pei-Lan"'
Search Results
2. High-throughput screening using pseudotyped lentiviral particles: A strategy for the identification of HIV-1 inhibitors in a cell-based assay
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Garcia, Jean-Michel, Gao, Anhui, He, Pei-Lan, Choi, Joyce, Tang, Wei, Bruzzone, Roberto, Schwartz, Olivier, Naya, Hugo, Nan, Fa-Jun, Li, Jia, Altmeyer, Ralf, and Zuo, Jian-Ping
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DIMETHYL sulfoxide , *GREEN fluorescent protein , *IATROGENIC diseases , *FLUORESCENT polymers - Abstract
Abstract: Two decades after its discovery the human immunodeficiency virus (HIV) is still spreading worldwide and killing millions. There are 25 drugs formally approved for HIV currently on the market, but side effects as well as the emergence of HIV strains showing single or multiple resistances to current drug-therapy are causes for concern. Furthermore, these drugs target only 4 steps of the viral cycle, hence the urgent need for new drugs and also new targets. In order to tackle this problem, we have devised a cell-based assay using lentiviral particles to look for post-entry inhibitors of HIV-1. We report here the assay development, validation as well as confirmation of the hits using both wild-type and drug-resistant HIV-1 viruses. The screening was performed on an original library, rich in natural compounds and pure molecules from Traditional Chinese Medicine pharmacopoeia, which had never been screened for anti-HIV activity. The identified hits belong to four chemical sub-families that appear to be all non-nucleoside reverse transcriptase inhibitors (NNRTIs). Secondary tests with live viruses showed that there was good agreement with pseudotyped particles, confirming the validity of this approach for high-throughput drug screens. This assay will be a useful tool that can be easily adapted to screen for inhibitors of viral entry. [Copyright &y& Elsevier]
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- 2009
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3. (5R)-5-hydroxytriptolide inhibits the immune response of human peripheral blood mononuclear cells
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Zhou, Ru, Tang, Wei, He, Pei-Lan, Yang, Yi-Fu, Li, Yuan-Chao, and Zuo, Jian-Ping
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IMMUNE response , *GENE expression , *IMMUNOSUPPRESSIVE agents , *WESTERN immunoblotting , *POLYMERASE chain reaction , *CELL proliferation , *THYMIDINE , *MITOGEN-activated protein kinases - Abstract
Abstract: Aim: (5R)-5-hydroxytriptolide (LLDT-8) displayed immunosuppressive activities both in vitro and in autoimmune disease models. Here, we aim to further clarify the effect of LLDT-8 on the immune responses of human peripheral blood mononuclear cells (PBMC). Method: Cell proliferation of human PBMC from healthy donors was evaluated by [3H]-thymidine uptake. NK cell cytotoxicity was assayed using K562 cells in a [3H] lysis assay. Cytokine production was determined by enzyme-linked immunosorbent assay. The expression of cell surface molecules was detected with flow cytometry. The mRNA expression and the protein phosphorylation levels were detected by RT-PCR and Western immunoblot assay. Results: LLDT-8 at 25 and 50 nM significantly inhibited the PHA- and recall antigens-induced T cell proliferation, and suppressed mixed lymphocyte reaction. LLDT-8 reduced cytokines production (IFN-γ, IL-2, TNF-α) in PHA- and Sac-activated PBMC. LLDT-8 did not alter the increased expression of MHC class I/II and B7.1, but reduced B7.2 by approximately 30%. No effect of LLDT-8 was observed for the expression of T cell activation markers (CD69, CD154). However, LLDT-8 significantly reduced IFN-γ-expressing T cell percentages and IFN-γ mRNA transcription in PHA-activated T cells. It also inhibited the phosphorylation levels of JNK and p38. LLDT-8 did not affect NK cytotoxic activity against K562 cells. Conclusion: LLDT-8 was a promising immunosuppressant for human immune-related diseases. [Copyright &y& Elsevier]
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- 2009
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4. (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide analog mediates immunosuppressive effects in vitro and in vivo
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Zhou, Ru, Zhang, Fan, He, Pei-Lan, Zhou, Wen-Liang, Wu, Qing-Li, Xu, Jian-Yi, Zhou, Yu, Tang, Wei, Li, Xiao-Yu, Yang, Yi-Fu, Li, Yuan-Chao, and Zuo, Jian-Ping
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IMMUNOSUPPRESSIVE agents , *IMMUNOSUPPRESSION , *CYTOKINES , *IMMUNE response , *THERAPEUTICS - Abstract
Abstract: A series of triptolide analogs have been successfully synthesized. In the present study we demonstrated one of them, (5R)-5-hydroxytriptolide (LLDT-8), showed low cytotoxicity and relative high immunosuppressive activities as compared with its parent compound triptolide in vitro. The CC50 values of triptolide and LLDT-8 were 2.1±0.3 and 256.6±73.8 nM, respectively. LLDT-8 significantly inhibited the proliferation of splenocytes induced by concanavalin A (ConA), lipopolysaccharide (LPS), or mixed lymphocyte reaction (MLR), and the IC50 values were 131.7±32.4, 171.5±17.3, and 38.8±5.1 nM, respectively. LLDT-8 (25, 50, 100 nM) dose-dependently reduced the production of Th1 type cytokines (IFN-γ, IL-2) and inflammatory cytokines (TNF-α, IL-6) in vitro. Administration of LLDT-8 (at the low dose of 0.4 μg/kg, i.p.; 40 μg/kg, p.o.) intensively suppressed 2,4-dinitrofluorobenzene (DNFB)-induced delayed type hypersensitivity (DTH) reactions. Treatment with LLDT-8 (40 μg/kg, i.p. and p.o.) also markedly inhibited the sheep red blood cell (SRBC)-induced antibody production in BLAB/c mice. Most importantly, comparing with triptolide, LLDT-8 significantly reduced toxicity, with a 122-fold lower cytotoxicity in vitro and 10-fold lower acute toxicity in vivo. The results suggested that LLDT-8 had immunosuppressive activities in both cellular and humoral immune responses. LLDT-8 might be a potential therapeutic agent for immune-related diseases. [Copyright &y& Elsevier]
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- 2005
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5. Effect of a hepatitis B virus inhibitor, NZ-4, on capsid formation.
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Yang, Li, Wang, Ya-Juan, Chen, Hai-Jun, Shi, Li-Ping, Tong, Xian-Kun, Zhang, Yang-Ming, Wang, Gui-Feng, Wang, Wen-Long, Feng, Chun-Lan, He, Pei-Lan, Xu, Yi-Bin, Lu, Meng-Ji, Tang, Wei, Nan, Fa-Jun, and Zuo, Jian-Ping
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HEPATITIS B treatment , *VIRUS inhibitors , *CAPSIDS , *DNA replication , *NUCLEOCAPSIDS - Abstract
During the hepatitis B virus (HBV) life cycle, nucleocapsid assembly is essential for HBV replication. Both RNA reverse transcription and DNA replication occur within the HBV nucleocapsid. HBV nucleocapsid is consisted of core protein (HBcAg), whose carboxy-terminal domain (CTD) contains an Arg-rich domain (ARD). The ARD of HBcAg does contribute to the encapsidation of pregenomic RNA (pgRNA). Previously, we reported a small-molecule, NZ-4, which dramatically reduced the HBV DNA level in an in vitro cell setting. Here, we explore the possible mechanisms by which NZ-4 inhibits HBV function. As an HBV inhibitor, NZ-4 leads to the formation of genome-free capsids, including a new population of capsid that runs faster on agarose gels. NZ-4's activity was dependent on the presence of the ARD I, containing at least one positively charged amino acid. NZ-4 might provide a new option for further development of HBV therapeutics for the treatment of chronic hepatitis B. [ABSTRACT FROM AUTHOR]
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- 2016
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6. Benzimidazole derivative, BM601, a novel inhibitor of hepatitis B virus and HBsAg secretion.
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Xu, Yi-Bin, Yang, Li, Wang, Gui-Feng, Tong, Xian-Kun, Wang, Ya-Juan, Yu, Ye, Jing, Jing-Feng, Feng, Chun-Lan, He, Pei-Lan, Lu, Wei, Tang, Wei, and Zuo, Jian-Ping
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BENZIMIDAZOLE derivatives , *HEPATITIS B virus , *ANTIGENS , *VIRAL proteins , *GOLGI apparatus , *BIOLOGICAL aggregation - Abstract
Highlights: [•] BM601 is the first benzimidazole derivative reported as HBV secretion inhibitor. [•] BM601 interferes surface protein aggregation in trans Golgi apparatus. [•] BM601 may help researchers to unveil novel aspects of HBV budding and secretion. [•] This work may throw lights on further anti-HBV studies of benzimidazole derivatives. [Copyright &y& Elsevier]
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- 2014
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7. Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities
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Ye, Deju, Shin, Woo-Jin, Li, Ning, Tang, Wei, Feng, Enguang, Li, Jian, He, Pei-Lan, Zuo, Jian-Ping, Kim, Hanjo, Nam, Ky-Youb, Zhu, Weiliang, Seong, Baik-Lin, Tai No, Kyoung, Jiang, Hualiang, and Liu, Hong
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NEURAMINIDASE , *ENZYME inhibitors , *DRUG activation , *DRUG development , *ANTIVIRAL agents , *DRUG administration - Abstract
Abstract: With the introduction of bioisosteres of the guanidinium group together with scaffold hopping, 35 zanamivir analogs with C-4-modification were synthesized, and their inhibitory activities against both group-1 and group-2 neuraminidase (H5N1 and H3N2) were determined. Compound D26 exerts the most potency, with IC50 values of 0.58 and 2.72 μM against N2 and N1, respectively. Further preliminary anti-avian influenza virus (AIV, H5N1) activities against infected MDCK cells were evaluated, and D5 exerts ∼58% protective against AIV infection, which was comparable to zanamivir (∼67%). In a rat pharmacokinetic study, compound D5 showed an increased plasma half-life (t 1/2) compared to zanamivir following either intravenous or oral administration. This study may represent a new start point for the future development of improved anti-AIV agents. [Copyright &y& Elsevier]
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- 2012
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8. Discovery and Optimization of 2,4-Diaminoquinazoline Derivatives as a New Class of Potent Dengue Virus Inhibitors.
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Chao, Bo, Tong, Xian-Kun, Tang, Wei, Li, De-Wen, He, Pei-Lan, Garcia, Jean-Michel, Zeng, Li-Min, Gao, An-Hui, Yang, Li, Li, Jia, Nan, Fa-Jun, Jacobs, Michael, Altmeyer, Ralf, Zuo, Jian-Ping, and Hu, You-Hong
- Abstract
The results of a high-throughput screening assay using the DENV-2 replicon showed that the 2,4-diaminoquinazoline derivative 4a has a high dengue virus inhibitory activity (EC50 = 0.15 μM). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure–antidengue activity relationship studies. Among the series of 2,4-diaminoquinazoline derivative probed, 4o was observed to display both the highest antiviral potency (EC50 = 2.8 nM, SI > 1000) and an excellent pharmacokinetic profile. [ABSTRACT FROM AUTHOR]
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- 2012
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9. Oral administration of artemisinin analog SM934 ameliorates lupus syndromes in MRL/ lpr mice by inhibiting Th1 and Th17 cell responses.
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Hou, Li-Fei, He, Shi-Jun, Li, Xin, Yang, Yang, He, Pei-Lan, Zhou, Yu, Zhu, Feng-Hua, Yang, Yi-Fu, Li, Ying, Tang, Wei, and Zuo, Jian-Ping
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ANIMAL experimentation , *BIOLOGICAL models , *MICE , *RESEARCH funding , *SYSTEMIC lupus erythematosus , *T cells - Abstract
Objective SM934, an artemisinin derivative, possesses potent antiproliferative and antiinflammatory properties. The aim of this study was to examine the effects and explore the mechanisms of SM934 to treat autoimmune disease in lupus-prone female MRL/ lpr mice. Methods In vitro, the effects of SM934 on the activation of polyclonal CD4+ T cells and the differentiation of naive CD4+ T cells were examined. In vivo, the preventative or therapeutic effects of SM934 in MRL/ lpr mice were investigated. Ex vivo, the mechanisms of treatment were explored according to the immunologic correlates of disease. Results In vitro, SM934 inhibited interferon-γ (IFNγ) and interleukin-17 (IL-17) production from polyclonal CD4+ T cells activated by T cell receptor engagement and the differentiation of naive CD4+ T cells into Th1 and Th17 cells, but not Treg cells. In vivo, 12-week-old MRL/ lpr mice treated with SM934 for 4 weeks showed significantly ameliorated proteinuria and renal lesion severity; decreased levels of blood urea nitrogen, serum IFNγ, and serum anti-double-stranded DNA antibodies; decreased spleen size; and a lower percentage of CD3+B220+CD4−CD8− T cells; 16-week-old MRL/ lpr mice treated with SM934 for 8 weeks avoided severe proteinuria and survived longer. Ex vivo, SM934 treatment elevated the percentage of Treg cells, inhibited the development of Th1 and Th17 cells, and impeded the comprehensive activation of STAT-1, STAT-3, and STAT-5 proteins in splenocytes. Conclusion Taken together, the results of this study demonstrated that the artemisinin analog SM934 had therapeutic effects in lupus-prone female MRL /lpr mice by inhibiting both Th1 cell and Th17 cell responses. Moreover, this study indicated that both IFNγ and IL-17 are required for the elicitation and development of murine lupus. [ABSTRACT FROM AUTHOR]
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- 2011
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10. SM934, a water-soluble derivative of arteminisin, exerts immunosuppressive functions in vitro and in vivo
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Hou, Li-Fei, He, Shi-Jun, Wang, Jun-Xia, Yang, Yang, Zhu, Feng-Hua, Zhou, Yu, He, Pei-Lan, Zhang, Yu, Yang, Yi-Fu, Li, Ying, Tang, Wei, and Zuo, Jian-Ping
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ANTIMALARIALS , *DRUG solubility , *IMMUNOSUPPRESSIVE agents , *CELL physiology , *LYMPHOCYTES , *APOPTOSIS , *INTERLEUKIN-2 , *POLYSACCHARIDES - Abstract
Abstract: In the present study, we investigated the immunosuppressive effects and underlying mechanisms of β-aminoarteether maleate (SM934), a derivative of artemisinin, against T cell activation in vitro and in vivo. In vitro, SM934 significantly inhibited the proliferation of splenocytes induced by concanavalin A (Con A), lipopolysaccharide (LPS), mixed lymphocyte reaction (MLR), and anti-CD3 plus anti-CD28 (anti-CD3/28). SM934 significantly inhibited interferon (IFN)-γ production and CD4+ T cell division stimulated by anti-CD3/28. SM934 also promoted apoptosis of CD69+ population in CD4+ T cells stimulated by anti-CD3/28. Furthermore, SM934 inhibited interleukin (IL)-2 mediated proliferation and survival through blocking Akt phosphorylation in activated T cells. In ovalbumin (OVA)-immunized mice, oral administration of SM934 suppressed OVA-specific T cell proliferation and IFN-γ production. SM934 treatment also significantly inhibited the sheep red blood cell (SRBC)-induced delayed type hypersensitivity (DTH) reactions in mice. Taken together, SM934 showed potent immunosuppressive activities in vitro and in vivo. Our results demonstrated that SM934 might be a potential therapeutic agent for immune-related diseases. [Copyright &y& Elsevier]
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- 2009
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11. Anti-hepatitis B virus activity of chlorogenic acid, quinic acid and caffeic acid in vivo and in vitro
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Wang, Gui-Feng, Shi, Li-Ping, Ren, Yu-Dan, Liu, Qun-Fang, Liu, Hou-Fu, Zhang, Ru-Jun, Li, Zhuang, Zhu, Feng-Hua, He, Pei-Lan, Tang, Wei, Tao, Pei-Zhen, Li, Chuan, Zhao, Wei-Min, and Zuo, Jian-Ping
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ANTIVIRAL agents , *HEPATITIS B virus , *CHLOROGENIC acid , *PLANT polyphenols , *BIOLOGICAL models , *VIRUS inhibitors , *VIRAL replication , *DUCKS , *COFFEE , *PLANT extracts , *DISEASES , *PREVENTION - Abstract
Abstract: Chlorogenic acid and its related compounds are abundant plant polyphenols that have a diverse antiviral activity. In this study, HepG2.2.15 cells and duck hepatitis B virus infection model were used as in vitro and in vivo models to evaluate their anti-HBV activity. In the cell model, all the three compounds inhibited HBV-DNA replication as well as HBsAg production. Chlorogenic acid and caffeic acid also reduced serum DHBV level in DHBV-infected duckling model. Moreover, the anti-HBV activity of crude extracts of coffee beans, which have a high content of chlorogenic acid, was studied. Both the extracts of regular coffee and that of decaffeinated coffee showed inhibitory effect on HBV replication. [Copyright &y& Elsevier]
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- 2009
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12. Suppressive effect of a novel water-soluble artemisinin derivative SM905 on T cell activation and proliferation in vitro and in vivo
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Wang, Jun-Xia, Tang, Wei, Yang, Zhong-Shun, Wan, Jin, Shi, Li-Ping, Zhang, Yu, Zhou, Ru, Ni, Jia, Hou, Li-Fei, Zhou, Yu, He, Pei-Lan, Yang, Yi-Fu, Li, Ying, and Zuo, Jian-Ping
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T cells , *ANTINEOPLASTIC agents , *ANTIVIRAL agents , *CELL proliferation - Abstract
Abstract: Artemisinin and its derivatives exhibit potent immunosuppressive activity. The aim of this study was to investigate the suppressive effects of SM905, a new water-soluble artemisinin derivative, on T lymphocytes both in vitro and in vivo, and explore its potential mode of action. The results showed that SM905 had a high inhibitory activity in Concanavalin A (ConA)-induced splenocyte proliferation and mixed lymphocyte reaction, and a relatively low cytotoxicity in vitro. In ovalbumin-immunized mice, oral administration of SM905 dose-dependently suppressed T cell proliferative response to ovalbumin, and inhibited anti-ovalbumin interleukin-2 (IL-2) and interferon-γ (IFN-γ) production by T cells. Further studies showed that SM905 inhibited TCR (T cell receptor)/CD3 plus CD28-mediated primary T cell proliferation and cytokine production (IL-2 and IFN-γ), and exerted an inhibitory action on the phosphorylation of mitogen-activated protein (MAP) kinases including extracellular signal-regulated kinase (ERK), p38 and Jun N-terminal kinase (JNK), and the activation of Ras. The results of this study provided experimental evidence that the new artemisinin derivative SM905 had immunosuppressive effects both in vitro and in vivo. SM905 suppressed T cell activation, which was associated with the inhibition of MAP kinases and Ras activation. Our results suggested a potential of SM905 to be developed as a new type agent for treating T cell-mediated immune disorder. [Copyright &y& Elsevier]
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- 2007
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13. Syntheses of triazole-modified zanamivir analogues via click chemistry and anti-AIV activities
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Li, Jian, Zheng, Mingyue, Tang, Wei, He, Pei-Lan, Zhu, Weiliang, Li, Tianxian, Zuo, Jian-Ping, Liu, Hong, and Jiang, Hualiang
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AVIAN influenza , *RESPIRATORY infections , *VIRUS diseases , *NEURAMINIDASE - Abstract
Abstract: Sixteen novel 4-triazole-modified zanamivir (1) analogues were synthesized using the click reactions, and their inhibitory activities against avian influenza virus (AIV, H5N1) were determined. Compound 3b exerts promising inhibitory activity with EC50 of 6.4μM, which is very close to that of zanamivir (EC50 =2.8μM). Molecular modeling provided the information about the binding model between inhibitors and neuraminidase, which are in good agreement with inhibitory activities. [Copyright &y& Elsevier]
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- 2006
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14. (5R)-5-Hydroxytriptolide (LLDT-8), a novel triptolide derivative, prevents experimental autoimmune encephalomyelitis via inhibiting T cell activation
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Fu, Yun-Feng, Zhu, Yi-Na, Ni, Jia, Zhong, Xiang-Gen, Tang, Wei, Zhou, Ru, Zhou, Yu, Dong, Jia-Rong, He, Pei-Lan, Wan, Hua, Li, Yuan-Chao, Yang, Yi-Fu, and Zuo, Jian-Ping
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T cells , *MULTIPLE sclerosis , *CELL proliferation , *LYMPHOCYTES - Abstract
Abstract: A novel triptolide derivative (5R)-5-hydroxytriptolide (LLDT-8) has been shown to have potent immunosuppressive activities. Here LLDT-8 was evaluated in experimental autoimmune encephalomyelitis (EAE), the model of multiple sclerosis (MS). LLDT-8 reduced the incidence and severity of EAE, which was associated with the inhibition of the MOG 35–55 lymphocyte recall response, anti-MOG 35–55 T cell responses, interleukin (IL)-2 and interferon (IFN)-γ production. In vitro, LLDT-8 inhibited primary T cells proliferation, division, IL-2 and IFN-γ production stimulated with anti-CD3/28. These findings highlight the fact that LLDT-8 prevents EAE by suppressing T cell proliferation and activation, with a potential for treatment of MS. [Copyright &y& Elsevier]
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- 2006
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15. Preventive effects of (5R)-5-hydroxytriptolide on concanavalin A-induced hepatitis
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Zhou, Ru, Tang, Wei, Ren, Yong-Xin, He, Pei-Lan, Yang, Yi-Fu, Li, Yuan-Chao, and Zuo, Jian-Ping
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CYTOKINES , *IMMUNOSUPPRESSIVE agents , *LIVER diseases , *BILIARY tract - Abstract
Abstract: (5R)-5-hydroxytriptolide (LLDT-8) exhibits strong immunosuppressive activities in vitro and in vivo. Here, we investigated the effects of LLDT-8 on concanavalin A-induced hepatitis. Liver damage was evaluated by serum alanine transaminase (ALT) level and liver histology. The effects of LLDT-8 were determined by measurement of serum cytokines, lymphocyte proliferation assay, flow cytometry analysis of splenic T cell percentage and apoptosis, reverse-transcription polymerase chain reaction (RT-PCR) analysis for gene transcriptions. In LLDT-8-treated mice, serum ALT level and histological damage were markedly attenuated. The beneficial effect of LLDT-8 was closely associated with (i) reduction of serum tumor necrosis factor-α, interferon-γ (IFN-γ), interleukin-2, interleukin-12, and interleukin-6 levels; (ii) elimination of activated T cells by increasing proapoptotic genes signal transducer and activator of transcription 1 (STAT1) and interferon regulatory factor-1 (IRF-1) expression in spleens; (iii) blockade of mRNA expressions for chemokines (monokine induced by IFN-γ, Mig; IFN-γ-inducible protein-10, IP-10; IFN-inducible T cell-α chemoattractant, I-TAC), vascular adhesion molecule-1 (VCAM-1), and chemokine receptors (C-C chemokine receptor 1, CCR1; C-C chemokine receptor 5, CCR5; C-X-C chemokine receptor 3, CXCR3) in livers. These results suggested the therapeutic potential of LLDT-8 in IFN-γ/STAT1/IRF-1 signaling- and inflammatory cytokines-mediated immune disorders. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
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