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A novel molecular mechanism for nitrated α-synuclein-induced cell death

Journal of Molecular Cell Biology 2011年第4期3卷 239-249页

作者： yanying liu Min Qiang Yan Wei Rongqiao He State Key Laboratory of Brain and Cognitive Sciences Institute of BiophysicsChinese Academy of Sciences15 Datun RoadChaoyang DistrictBeijing 100101China Key Laboratory of Mental Health Institute of PsychologyChinese Academy of Sciences15 Datun RoadChaoyang DistrictBeijing 100101China

Although previous studies have demonstrated the involvement of nitrated a-synuclein in neurodegenerative disorders(synucleinopathies),the effects of nitrated α-synuclein and the molecular mechanisms underlying its toxicity are still *** the present study,nitrated α-synuclein with four 3-nitrotyrosines(Tyr^(39),Tyr^(125),Tyr^(133),and Tyr^(136))was obtained non-enzymatically by incubation with *** nitrated protein existed as a mixture of monomers,dimers,and polymers in *** nitrated a-synuclein could induce cell death in a time-and concentration-dependent manner when SH-SY5Y cells(a human neuroblastoma cell line)were incubated with the dimers and *** with anti-integrin α5β1 antibody partially rescued the SH-SY5Y cells from the cell *** blotting and immunoprecipitation revealed that the nitrated protein bound to integrin on the cell *** of nitric oxide(NO)and calcium-independent inducible NO synthase(iNOS)activity increased during the initial stages of the *** expression of phosphorylated focal adhesion kinase(FAK)decreased in the ***,an increase in caspase 3 activity was observed in SH-SY5Y *** results demonstrate that activation of iNOS and inhibition of FAK may both be responsible for the cell death induced by nitrated α-*** data suggest that the cytotoxicity of nitrated a-synuclein is mediated via an integrin-iNOS/-FAK signaling pathway,and that the nitration of α-synuclein plays a role in neuronal degeneration.

关键词： nitric oxide nitration neuronal death toxicity focal adhesion kinase calcium-independent inducible nitric oxide synthase

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Altered influenza virus haemagglutinin(HA)-derived peptide is potent therapy for CIA by inducing Th1 to Th2 shift

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Cellular & Molecular Immunology 2011年第4期8卷 348-358页

作者： Jian Sun Yuan Jia Ru Li Jianping Guo Xiaolin Sun yanying liu Yingni Li Haihong Yao Xia liu Jing Zhao Zhanguo Li Department of Rheumatology and Immunology Clinical Immunology CenterPeking University People’s HospitalBeijingChina

There has been an increase in interest in the use of altered peptides as antigen-specific therapeutic agents in autoimmune *** we investigated the inhibitory effect and possible mechanism of an altered influenza virus haemagglutinin(HA)-derived peptide in collagen-induced arthritis(CIA).CIA was induced in DBA/1 mice by immunisation with type II collagen(CII).Altered HA308-317,wild-type HA308-317 or irrelevant peptide was administered intranasally beginning from arthritis *** and histological scores were assessed,and cytokine levels in the serum or supernatants from splenocytes were *** percentages of Th1 and Th2 cells in response to different peptides were analysed by FACS both in vivo and in *** results showed that intranasal administration of altered HA308-317 peptide significantly ameliorated *** therapeutic effect of altered HA308-317 peptide was associated with a substantial decrease in production of interferon(IFN)-c,interleukin(IL)-6,monocyte chemoattractant protein(MCP)-1,anti-CII IgG,IgG1 and IgG2a antibodies,and an markedly increase in production of IL-10 and IL-4 in serum or supernatants from splenocytes treated with altered HA308-317 *** percentage of Th2(CD41IL-41)cells was upregulated significantly by altered HA308-317 peptide with a decreased percentage of Th1(T helper 1;CD41INF-c1)cells both in vivo and in *** findings suggest that altered HA308-317 peptide might be a promising candidate for rheumatoid arthritis(RA)treatment.

关键词： altered HA peptide collagen-induced arthritis Th1/Th2

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Marsdenia tenacissima injection induces the apoptosis of prostate cancer by regulating the AKT/GSK3β/STAT3 signaling axis

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Chinese Journal of Natural Medicines 2023年第2期21卷 113-126页

作者： LI Xiaolan HE Songhua LIANG Wei ZHANG Weiquan CHEN Xin LI Qiaofeng YANG Xin liu yanying ZHU Dan LI Li liu Buming SU Zhiheng CHEN Jie GUO Hongwei Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation&College of Pharmacy Guangxi Medical UniversityNanning 530021China Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education&Center for Translational Medicine Guangxi Medical UniversityNanning 530021China Guangxi Institute for Food and Drug Control Drug Administration of Zhuang Autonomous RegionNanning 530021China Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards Guangxi Institute of Chinese Medicine&Pharmaceutical ScienceNanning 530022China The Affiliated Tumor Hospital Guangxi Medical UniversityNanning 530021China

Marsdenia tenacissima injection,a standard Marsdenia tenacissima extract(MTE),has been approved as an adjuvant therapeutic agent for various *** previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer(PCa)***,the underlying mechanisms and active ingredients of MTE against PCa were not completely *** study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa *** addition,MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7,Cyt c,and *** vivo,DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor *** staining and Western blot confirmed the pro-apoptotic effects of *** pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets,and 709 PCa-associated targets were retrieved,from which 149 overlapped targets were screened *** enrichment analysis showed that the HIF-1,PI3K-AKT,and ErbB signaling pathways were closely related to tumor *** blot results confirmed that MTE increased the expression of p-AKT^(Ser473) and p-GSK3β^(Ser9),and decreased the expression of p-STAT3^(Tyr705) in vitro and in vivo.A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLCQTOF-MS/*** docking analysis indicated that six compounds may interact with AKT,GSK3β,and *** conclusion,MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis,resulting in inhibition of PCa growth in vitro and in vivo.

关键词： Marsdenia tenacissima injection Prostate cancer Apoptosis AKT/GSK3β/STAT3

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Role of alpha-synuclein in neuronal apoptosis induced by rotenone

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Neural Regeneration Research 2006年第1期1卷 32-35页

作者： yanying liu Hui Yang Beijing Institute for Neuroscience Capital University of Medical Sciences Beijing 100069 China

BACKGROUND： Aggregation of α-synuclein is the major component of Lewy bodies, which are the pathological hallmarks of Parkinson disease （PD）. Although the mechanism of this protein aggregates is unclear, previous study showed that environmental toxins such as rotenone could induce the expression and aggregation of α-synuclein. OBJECTIVE： To observe the role of α-synuclein in PD.DESIGN ： A randomized controlled trial.SETTING ： Beijing Institute for Neuroscience, Capital University of Medical Sciences.MATERIALS ： This study was performed from July 2005 to January 2006 at the Beijing Institute for Neuroscience, Capital University of Medical Sciences. Human dopaminergic neuroblastoma SH-SY5Y cells were provided by Beijing Institute for Neuroscience, Capital University of Medical Sciences. METHODS： Human dopaminergic neuroblastoma SH-SY5Y cells were treated to make α-synuclein over express. Rotenone was added into the medium of cultured both native SH-SY5Y cells and α-synuclein-overexpression SH-SY5Y cells. Lactate dehydrogenase （LDH） assay was used to detect with the cell viability. Flow cytometry and electrophoresis were adopted to measure the cell apoptosis. MAIN OUTCOME MEASURES ： Cell viability, DNA fragmentation, and the number of cell apoptosis.RESULTS： After being treated with rotenone, LDH activity of α-synuclein overexpressed SH-SY5Y cells was （76.625±6.34） μkat/L, which was significantly lower than that of control group （P 〈 0.05）. As compared with normal SH-SY5Y cell, α-synuclein over-expressed SH-SY5Y cells had less DNA fragments and apoptotic cells, α-synuclein might play a role in cell apoptosis induced by rotenone, which was also confirmed by using of antioxidant reagent. CONCLUSION： α-synuclein may partially protect against cell apoptosis induced by rotenone in SH-SY5Y cells.

关键词： Role of alpha-synuclein in neuronal apoptosis induced by rotenone

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PROCESS FOR SYNTHESIS OF 3-（N-ETHYL-N- METHOXYLONEMETHYL） AMINO-4-METHYL ACCETANILIDE

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精细石油化工 2010年第6期27卷 63-66页

作者： liu yanying Li Kunlan Wang Ximeng School of Chemistry Engineering ＆ Material Dalian Polytechnic University Dalian 116034 Liaoning China

以3-(N-乙基)氨基-4-甲氧基乙酰苯胺(I)和氯乙酸甲酯为原料、无水碳酸钠为缚酸剂、甲苯为溶剂, 合成3-(N-乙基-N_甲氧基羰基甲基)氨基-4-甲氧基乙酰苯胺. 经正交实验法, 考察了I和氯乙酸甲酯的摩尔投料比、反应温度、甲苯及碳酸钠用量... 详细信息

以3-(N-乙基)氨基-4-甲氧基乙酰苯胺(I)和氯乙酸甲酯为原料、无水碳酸钠为缚酸剂、甲苯为溶剂, 合成3-(N-乙基-N_甲氧基羰基甲基)氨基-4-甲氧基乙酰苯胺. 经正交实验法, 考察了I和氯乙酸甲酯的摩尔投料比、反应温度、甲苯及碳酸钠用量对收率的影响, 其最佳工艺条件为: n(I): n(氯乙酸酯)-1: 1.1, 反应温度为100℃, 溶剂甲苯用量为10.4 m1,n(I): n(碳酸钠)-1: 0.56, 收率96.8％

关键词：摘要编辑部编辑工作读者

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Transformative hyaluronic acid-based active targeting supramolecular nanoplatform improves long circulation and enhances cellular uptake in cancer therapy

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Acta Pharmaceutica Sinica B 2019年第2期9卷 397-409页

作者： Lu Zhong Lu Xu yanying liu Qingsong Li Dongyang Zhao Zhenbao Li Huicong Zhang Haotian Zhang Qiming Kan Yongjun Wang Jin Sun Zhonggui He Department of Pharmaceutics Wuya College of Innovation Shenyang Pharmaceutical University Department of Pharmacy Shenyang Pharmaceutical University

Hyaluronic acid(HA) is a natural ligand of tumor-targeted drug delivery systems(DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors(HARE and LYVE-1) are also overexpressing in the reticuloendothelial system(RES). Therefore,polyethylene glycol(PEG) modification of HA-based DDS is necessary to reduce RES ***, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement,significantly compromising the in vivo antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform(Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine *** in vitro and in vivo investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and in vivo nonspecific biodistribution.

关键词： Hyaluronic acid Benzoic imine linkage Active-targeting Cancer therapy Natural ligand Supramolecular nanoplatform Transformative nanoparticles PEG dilemma

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Mixed Quantum Classical Reaction Rates based on the Phase Space Formulation of the Hierarchical Equations of Motion

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Chinese Journal of Chemical Physics 2022年第5期35卷 727-737,I0011页

作者： Tao Xing Tianchu Li yanying liu Qiang Shi Beijing National Laboratory for Molecular Sciences State Key Laboratory for Structural Chemistry of Unstable and Stable SpeciesCAS Research/Education Center for Excellence in Molecular SciencesInstitute of ChemistryChinese Academy of SciencesZhongguancunBeijing 100190China University of Chinese Academy of SciencesBeijing 100049China

In a previous work[***.140,174105(2014)],we have shown that a mixed quantum classical(MQC)rate theory can be derived to investigate the quantum tunneling effects in the proton transfer ***,the method is based on the high temperature approximation of the hierarchical equation of motion(HEOM)with the Debye-Drude spectral density,and results in a multistate Zusman type of *** now extend this theory to include quantum effects of the bath degrees of *** writing the full HEOM into a multidimensional partial differential equation in phase space,we can define a new reaction coordinate,and the previous method can be generalized to the full quantum *** validity of the new method is demonstrated by using numerical examples,including the spin-Boson model,and the double well model for proton transfer *** new method is found to resolve some key problems of the previous theory based on high temperature approximation,including possible numerical instability in long time simulation and wrong rate constant at low temperatures.

关键词： Hierarchical equation of motion Reaction rate theory Proton transfer Electron transfer

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Exploring the relationship of hyaluronic acid molecular weight and active targeting efficiency for designing hyaluronic acid-modified nanoparticles

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Asian Journal of Pharmaceutical Sciences 2019年第5期14卷 521-530页

作者： Lu Zhong yanying liu Lu Xu Qingsong Li Dongyang Zhao Zhenbao Li Huicong Zhang Haotian Zhang Qiming Kan Jin Sun Zhonggui He Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang110016China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang110016China

Although it is reported that the targeting ability of hyaluronic acid(HA)-based nanoparticles(NPs) is molecular weight(MW) dependent,the influence of HA MW on targeting efficiency of HA-functionalized NPs and the underlying mechanism remain elusive. In this study,we constituted three HA-functionalized Dox-loaded NPs(Dox/HCVs) different HA MWs(7,63,and 102 k Da) and attempted to illustrate the effects of HA MW on the targeting *** three Dox/HCVs had similar physiochemical and pharmaceutical characteristics,but showed different affinity to CD44 receptor. Furthermore,Dox/HCV-63 exerted the best targeting effect and the highest cytotoxicity compared with Dox/HCV-7 and Dox/HCV-102. It was interesting to found that both the HA-CD44 binding affinity and induced CD44 clustering by HA-based NPs were HA MW-dependent,the two of which determine the apparent targeting efficacy of Dox/HCV NPs in the conflicting directions. Those results laid a good foundation for rationally designing HA-based NPs in cancer therapy.

关键词： Hyaluronic acid Molecular weight Active targeting efficiency CD44 receptor Potential mechanism

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Degradation of petroleum contaminants in oil

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Chinese Journal Of Geochemistry 2006年第B8期25卷 126-127页

作者： yanying SUN Fei liu Honghan CHEN Wei HE Beijing Key Laboratory of Water Resources and Environmental Engineering China University of Geosciences Beijing 100083 China

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Efficacy and safety of low-dose interleukin-2 in combination with methotrexate in patients with active rheumatoid arthritis:a randomized,double-blind,placebo-controlled phase 2 trial

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Signal Transduction and Targeted Therapy 2022年第4期7卷 1194-1201页

作者： Xiaoying Zhang Miao Miao Ruijun Zhang Xu liu Xiaozhen Zhao Miao Shao Tian liu Yuebo Jin Jiali Chen Huixin liu Xia Zhang Yun Li Yunshan Zhou Yue Yang Ru Li Haihong Yao yanying liu Chun Li Yuhui Li Limin Ren Yin Su Xiaolin Sun Jing He Zhanguo Li Department of Rheumatology and Immunology Peking University People’s Hospital100044 BeijingChina Department of Rheumatology and Immunology The First Affiliated Hospital of Wannan Medical College241000 WuhuAnhuiChina Department of Clinical Epidemiology and Biostatistics Peking University People’s Hospital100044 BeijingChina Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis(BZ0135) BeijingChina Peking-Tsinghua Center for Life Sciences BeijingChina State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijingChina

Rheumatoid arthritis(RA)is an aggressive autoimmune arthritis,and current therapies remain unsatisfactory due to low remission rate and substantially adverse ***-dose interleukin-2(Ld-IL2)is potentially a therapeutic approach to further improve the *** randomized,double-blind,placebo-controlled trial was undertaken to evaluate the efficacy and safety of Ld-IL2 in patients with active *** were randomly assigned(1:1)to receive Ld-IL2,defined as a dose of 1 million IU,or placebo in a 12-week trial with a 12-week *** cycles of Ld-IL2 or placebo were administered subcutaneously every other day for 2 weeks(a total of 7 doses),followed by a 2-week *** patients received a stable dose of methotrexate(MTX).The primary outcomes were the proportion of patients achieving the ACR20,DAS28-ESR<2.6,and the change from baseline in CDAI or SDAI at week *** endpoints included other clinical responses and *** primary outcomes were achieved in the perprotocol *** improvements from baseline in CDAI and SDAI were significantly greater across time points for the LdIL2+MTX group(n=17)than for the placebo+MTX group(n=23)(P=0.018 and P=0.015,respectively).More patients achieved ACR20 response in the Ld-IL2+MTX group than those in the placebo+MTX group at week 12(70.6%vs 43.5%)and at week 24(76.5%vs 56.5%)(P=0.014).In addition,low Treg and high IL-21 were associated with good responses to ***-IL-2 treatment was well-tolerated in this *** results suggested that Ld-IL2 was effective and safe in *** number:NCT 02467504.

关键词： patients placebo methotrexate

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