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检索条件"任意字段=中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议"

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Antioxidant Peptide Purified from Enzymatic Hydrolysates of Isochrysis Zhanjiangensis and its Protective Effect against Ethanol Induced Oxidative Stress of HepG2 Cells

Antioxidant Peptide Purified from Enzymatic Hydrolysates of ...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Mei-Fang Chen Yuanyuan Zhang Mei-Di He Cheng-Yong Li Chun-Xia Zhou Peng-Zhi Hong Zhong-Ji Qian College of Food Science and Technology Guangdong Ocean University College of Chemistry and Environment Guangdong Ocean University Shenzhen Institute of Guangdong Ocean University

Marine microalgae have been widely applied in cosmaceuticals,nutraceuticals,and functional *** the present study,we first investigated the hepatoprotective effects of peptide purified from microalgae,Isochrysis zhanjiangensis on HepG2 cells alcoholic *** was hydrolyzed utilizing chymotrypsin,trypsin,pepsin,and by in vitro gastrointestinal *** hydrolysates,the gastrointestinal hydrolysate showed relatively high free radical scavenging ability preliminarily and was purified with following sequential chromatography *** amino acid sequence and molecular mass of the purified peptide from ***(PIZ) was identified as Asn-Asp-Ala-Glu-Tyr-Gly-Ile-Cys-Gly-Phe(NDAEYGICGF;MW,1088.16 Da) via Q-TOF ESI/***,PIZ attenuated ethanol-induced cytotoxicity and inhibited the production of intracellular reactive oxygen species(ROS) by DFCH-DA *** blot results showed that superoxide dismutase(SOD) and glutathione(GSH) levels up-regulated with PIZ treatment before alcohol exposure while gamma-glutamyltransferase(GGT) protein expression *** results provide an opportunity to discover new highly active peptide(PIZ) against alcohol toxicity in HepG2 cells.

关键词： Isochrysis zhanjiangensis Peptide Enzymatic hydrolysates Free radical scavenging Oxidative stress

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SAE1 promotes human glioma progression through activating AKT SUMOylation and AKT signaling pathways

SAE1 promotes human glioma progression through activating AK...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Yanfang Yang Ziwei Liang Xixi Wang Zenghua Sheng Shufang Liang State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan Universityand Collaborative Innovation Center for Biotherapy

The SUMO-activating enzyme SAE1 involves in progression of several human ***,its biological roles of SAE1 in glioma are unknown in previous *** this study,we systematically investigate SAE1 associations with glioma progression in vitro and in ***1 is identified to increase in glioma tissues by a quantitative proteomic dissection,and SAE1 upregulation indicates a high level of tumor malignancy grade and a poor overall survival for glioma ***1 overexpression induces increase of the SUMOylation and Ser473 phosphorylation of AKT and promotes glioma cell growth in vitro and in nude mouse tumor *** the contrary,SAE1 silence induces an obvious suppression of the SUMOylation and Ser473 phosphorylation of Akt,which finally inhibit glioma cell proliferation and the nude mouse tumor growth through inducing cell cycle arrest at G2 phase and cell apoptosis due to serial biochemical molecular events,including CDK2,Cyclin D1,Bcl-2 significantly decreased,and p21,active Caspase-3,Bax ***,SAE1 promotes glioma cancer progression via enhancing Akt SUMOylation-mediated signaling pathways,and SAE1 is a promising prognostic marker and therapeutic target for human glioma.

关键词： Glioma SAE1 SUMOylation Phosphorylation Akt signaling pathway

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Modeling and predicting the activities of trans-acting splicing factors with machining learning

Modeling and predicting the activities of trans-acting splic...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Miaowei Mao Yue Hu Yun Yang Yajie Qian Huanhuan Wei Wei Fan Yi Yang Xiaoling Li Zefeng Wang CAS Key Laboratory of Computational Biology CAS-MPG Partner Institute for Computational BiologyShanghai Institute of Nutrition and HealthShanghai Institutes for Biological SciencesUniversity of Chinese Academy of SciencesCAS Center for Excellence in Molecular Cell ScienceChinese Academy of Sciences Synthetic Biology and Biotechnology Laboratory State Key Laboratory of Bioreactor EngineeringSchool of PharmacyEast China University of Science and Technology Signal Transduction Laboratory National Institute of Environmental Health Sciences

Alternative splicing(AS) is generally regulated by trans-splicing factors that specifically bind to cis-elements in *** genome encodes ～1500 RNA binding proteins(RBPs) that potentially regulate AS,yet their function remain largely *** explore their potential activities,we fused the putative functional domains of RBPs to a sequence-specific RNAbinding domain,and systemically analyzed how these engineered factors affect *** discovered that ～80% of low complexity domains in endogenous RBPs displayed distinct context-dependent activities in regulating splicing,indicating that AS is under more extensive regulation than previously *** developed a machine learning approach classify and predict the activities of RBPs based on their sequence compositions,and further validated this model using endogenous RBPs and synthetic *** results represent a systematic inspection,modeling,prediction and validation of how RBP sequences affect their activities in controlling splicing,paving the way for de novo engineering of artificial splicing factors.

关键词： Alternative splicing Splicing factors Machine learning RNA binding domains Protein engineering Protein activity prediction

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MRPL35 is upregulated in colorectal cancer and regulates colorectal cancer cell growth and apoptosis

MRPL35 is upregulated in colorectal cancer and regulates col...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Litao Zhang Peifen Lu Lihong Yan Lijun Yang Yutao Wang Junjun Chen Jie Dai Yahui Li Zhiming Kang Tao Yang Department of Biochemistry & Molecular Biology Shanxi Medical University Department of Pharmacology Shanxi Medical University

Mitochondrial ribosome proteins(MRPs),which are encoded by the nuclear genomic DNA,are important for mitochondrialencoded protein synthesis and mitochondrial *** evidence suggests that several MRPs also exhibit important extra-mitochondrial functions,such as involvement in apoptosis,protein biosynthesis and signal *** this study,we demonstrate a significant role of mitochondrial ribosomal protein L35 in colorectal cancer(CRC).The expression of MRPL35 was higher in CRC tissues than in matched cancer-adjacent tissues and higher in CRC cells than in normal mucosal epithelial *** MRPL35 expression in CRC tissue correlated with shorter overall survival for CRC *** of MRPL35 led to increased production of reactive oxygen species(ROS) together with DNA damage,loss of cell proliferation,G2/M arrest,a decrease in mitochondrial membrane potential,apoptosis and autophagy ***35 knockdown inhibited tumor proliferation in a CRC xenograft nude mouse ***,overexpression of MRPL35 or treatment of cells with the ROS scavenger,N-acetyl cysteine(NAC),abrogated ROS production,cell cycle arrest and *** findings suggest that MRPL35 plays an essential role in the development of CRC and may be a potential therapeutic target for CRC.

关键词： Mitochondrial ribosomal protein L35 colorectal cancer proliferation apoptosis

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Regulation of Cytochrome P450 Enzymes by Reversible Oxidation of Thiols to Sulfenic Acids

Regulation of Cytochrome P450 Enzymes by Reversible Oxidatio...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： F.Peter Guengerich Matthew E.Albertolle Department of Biochemistry Vanderbilt University School of Medicine

Cytochrome P450(P450) enzymes are the major catalysts involved in the metabolism of drugs,steroids,chemical carcinogens,and fat-soluble *** they are involved in >95% of oxidation/reduction reactions of *** signature spectroscopic properties and the catalytic activities are related to a conserved cysteine thiolate ligand binding to the proximal side of the heme *** found that the activity of one human P450 enzyme,P450 4 A11,was stimulated by the addition of mild reducing agents,***,and attenuated by H2 *** analyzed the enzyme and did not find disulfides but did find that the cysteine sulfur was oxidized to a sulfenic acid(-SOH),a reversible *** then found numerous drug metabolizing enzymes that contained sulfenic acids,including several mouse and human P450 s with the heme-cysteinyl sulfenic *** sulfenic acid was found in mouse and human liver and kidney samples in situ,suggesting physiological *** dynamics simulations suggest roles for specific amino acids in modulating the oxidation of the *** part of our continuing efforts in characterization of these systems in cells,we have synthesized new heavy isotope-labeled reagents with much faster kinetics than dimedone and iodoacetamide,which can be used to label sulfenic acids and disulfides,using liquid chromatography-mass *** phenomenon represents a potential new means of post-transcriptionally regulating the activities of P450 enzymes,although more in vivo evidence is in order.

关键词： Cytochrome P450 redox control sulfenic acid drug metabolism steroidogenesis heme ligands

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Phosphorylation of the RON tyrosine kinase is required for the OPN-promoted malignant properties of the non-small-cell lung cancer cells

Phosphorylation of the RON tyrosine kinase is required for t...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Siyuan Chang Jing Huang Shan Cheng Department of Biochemistry and Molecular Biology School of Basic Medical SciencesCapitalMedical University Beijing Key Laboratory of Cancer & Metastasis Research Capital Medical University

Osteopontin(OPN) has been identified as a biomarker for tumor progression in many human tumor *** non-small-cell lung cancer(NSCLC),the tumorigenic functions of OPN are not well *** current study sought to investigate the clinical implications of OPN expression in NSCLC and the impact of OPN on the functions of lung cancer cells through its regulation on the phosphorylation of the macrophage-stimulating protein receptor(RON) tyrosine kinase *** level of OPN and RON transcripts were the independent prognostic indicators of survival in NSCLC(p=0.001).Significantly higher levels of OPN,RON and p-RON proteins were also confirmed in tumor tissues(n=20,p<0.01 *** tissues).Knockdown of OPN suppressed in-vitro migration and invasion properties in the A549 lung cancer cell line which endogenously expresses *** small-molecule inhibition of RON or the siRNA silencing of RON significantly reduced OPN overexpression induced migration and invasion of lung cancer cells and had an inhibitory effect on the OPNinduced cell epithelial–mesenchymal transition(EMT).Our study suggests that the aberrant expression of OPN could be considered as an independent survival indicator and is associated with disease *** plays crucial roles in promoting the migration and invasion capacity of lung cancer cells through its activation of the RON signaling pathway,implying its potential clinical application as a therapeutic target for the treatment of the NSCLC.

关键词： OPN RON NSCLC migration invasion EMT

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Interleukin-22 promotes autophagy and inhibits apoptosis in rheumatoid arthritis through targeting the STAT3 pathway in synovial fibroblasts

Interleukin-22 promotes autophagy and inhibits apoptosis in ...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Bo Wang Weikun Hou Center for Translational Medicine the First Affiliated Hospital of Xi'an Jiaotong University Osteonecrosis and joint Reconstruction Ward Joint SurgeryXi'an Honghui Hospital

Rheumatoid arthritis(RA) is a common chronic autoimmune inflammatory *** role of autophagy and apoptosis in the pathogenesis of RA is ***-22(IL-22) as a cytokine of Th22 plays a significant and complicated role in inflammatory and autoimmune rheumatic *** propose that IL-22 regulates activation of autophagy and exerts inhibition of apoptosis in synovial fibroblasts,and is thereby essential for development of *** results showed that the concentration of IL-22 in RA was significantly higher than in HC and *** synovial fibroblasts and chondrocytes treated with rhIL-22,the apoptosis was significantly decreased in synovial fibroblasts,but not in *** protein expression of Bcl-2 was increased in a dose-dependent manner,and cleaved Caspase-3 was ***-22 triggered autophagic flux in synovial fibroblasts,which led to autophagy-related proteins Beclin 1 and LC3(8)were significantly *** induced autophagy and inhibited apoptosis were associated with STAT3 phosphorylation though expression of Bcl-2 and Beclin *** and inhibiting STAT3 by inhibitor or by siRNA led to synovial fibroblasts abrogated the effects of *** importantly,the STAT3 pathway could regulate the balance of apoptosis and autophagy in RA synovial *** conclude that IL-22 inhibited apoptosis and promoted autophagy,and this balance was regulated though STAT3 pathway leading to upreglation of Bcl-2 and Beclin 1 in RA synovial *** pathogenic mechanism suggest a strategy for using anti-STAT3 approach to RA treatment.

关键词： Interleukin-22 Apoptosis Autophagy STAT3 Rheumatoid arthritis

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Development of a Deep Learning Model for Binding Affinity Prediction and Fragment-based de novo Drug Design

Development of a Deep Learning Model for Binding Affinity Pr...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Shiwei Wang Jianfeng Pei Luhua Lai PTN Joint Graduate Program Academy for Advanced Interdisciplinary StudiesPeking University Center for Quantitative Biology Academy for Advanced Interdisciplinary StudiesPeking University BNLMS State Key Laboratory for Structural Chemistry of Unstable and Stable Speciesand Peking-Tsinghua Center for Life Sciences at College of Chemistry and Molecular EngineeringPeking University

The traditional drug design and discovery methods were time-consuming and expensive,which largely reduced the efficiency of drug design ***-based de novo drug design was applied to accelerate the procedure of drug *** a complementary of high-throughput screening technology,de novo drug design method is confronted with a virtually infinite search *** drug-like molecules can be discovered by exploring the chemical space with specific combinational search strategies,which provides a new approach to find novel ***,challenges including combinatorial explosion,scoring function and so on hinder the development and application of de novo drug *** this work,we hope to construct a reinforcement-learning model by combing Monto Carlo Tree Search method and deep neural network to solve the combinatorial explosion *** order to achieve our goals,we updated our Pocket program to extract more accurate pharmacophore models,which can help to extract features of 3 D structure information of protein-ligand ***,we developed a new scoring function to predict binding affinity of protein-ligand complex based on the 3 D structure *** further improving and optimizing,the new scoring function could be applied to binding affinity prediction and will be integrated to our fragment-based de novo drug design method.

关键词： scoring function Representation of binding pocket de novo drug design Reinforcement learning

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Discovery of Human STING Allosteric Inhibitors

Discovery of Human STING Allosteric Inhibitors

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Xiaobing Deng Xiaoyu Yu Sheng Bi Ying Liu Zhengfan Jiang Luhua Lai Peking-Tsinghua Center for Life Sciences Peking University College of Chemistry and Molecular Engineering Peking University School of Life Sciences Peking University

Stimulation of innate immune processes represents an attractive strategy to achieve multiple therapeutic outcomes including inhibition of virus replication,boosting antitumor immunity,enhancing vaccine immunogenicity,and improving *** recently discovered cGAS–STING pathway plays a crucial role in the production of type I IFNs caused by *** is the central signalling ***,if STING is a good target for autoimmune diseases treatment is an open question.1 It is challenging to design inhibitors for such an adaptor *** applied Computer Aided Drug Design(CADD) to discover STING allosteric *** first computationally identified a potential allosteric site in STING threedimensional *** then carried our virtual screening targeting this site and obtained a weak STING inhibitor *** optimization,compound 13100 showed enhanced inhibition of STING with an IC50 value of 20 M.13100 bound to hSTING with a dissociation constant of 17 M measured by *** used whole cell thermal shift assay to verify that 13100 binds to hSTING in *** of the key interacting residues of hSTING abolishes its inhibition response to *** study suggests that 13100 disrupts the interactions between STING and *** the best of our knowledge,our compounds are the first non-covalent STING inhibitors,which serve as useful probes to study cGAS-STING *** 13100 as a chemical probe,we proposed an auto-inhibition mechanism of STING,which was verified by mutation study and molecular dynamics simulations.

关键词： STING Allosteric Regulation Auto-inhibition

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Cell-surface Translocation of Annexin A2 contributes to bleomycin-induced pulmonary fibrosis by mediating inflammatory response in mice

Cell-surface Translocation of Annexin A2 contributes to bleo...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Yunlong Lei Department of Biochemistry and Molecular Biology Molecular Medicine and Cancer Research CenterChongqing Medical University

Bleomycin,a widely used cancer drug,may give rise to a serious side effect,pulmonary fibrosis which is associated with significant morbidity and *** the intensive efforts,the precise pathogenic mechanisms still remain to be *** previous study showed that bleomycin bound directly to annexin A2(ANXA2,p36),leading to development of pulmonary fibrosis by impeding TFEB-induced autophagic ***,we demonstrated that ANXA2 also played a critical role in bleomycin-induced inflammation,which represents another major cause of bleomycin-induced pulmonary *** found that bleomycin could induce the cell surface translocation of ANXA2 in lung epithelial cells through exosomes secretion associated with enhanced interaction between ANXA2 and *** of ANXA2 or blocking membrane ANXA2 by small peptide TM601 mitigated bleomycin-induced activation of NF-κB pathway and production of proinflammatory cytokine IL-6 in lung epithelial ***2-deficient(ANXA2-/-) mice treated with bleomycin exhibit reduced pulmonary fibrosis along with decreased cytokine production compared with bleomycin-challenged wild-type ***,the surface ANXA2 inhibitor TM601,could ameliorate fibrotic and inflammatory response in bleomycin-treated *** together,our results indicated that,in addition to disturb autophagic flux,ANXA2 can contribute to bleomycininduced pulmonary fibrosis by mediating inflammatory response.

关键词： Bleomycin annexin A2 pulmonary fibrosis inflammation IL-6

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