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Systems biomedicine:It's your turn—Recent progress in systems biomedicine

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Quantitative Biology 2013年第2期1卷 140-155页

作者： zhuqin zhang Zhiguo Zhao Bing Liu Dongguo Li Dandan zhang Houzao Chen Depei Liu State Key Laboratory of Medical Molecular Biology Department of Biochemistry and Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences & Peking Union Medical College

The concept of “systems biology” is raised by Hood in 1999. It means studying all components with a systematic view. Systems biomedicine is the application of systems biology in medicine. It studies all components in a whole system and aims to reveal the patho-physiologic mechanisms of disease. In recent years,with the development of both theory and technology,systems biomedicine has become feasible and popular. In this review,we will talk about applications of some methods of omics in systems biomedicine,including genomics,metabolomics(proteomics,lipidomics,glycomics),and *** will particularly talk about microbiomics and omics for common diseases,two felds which are developed rapidly recently. We also give some bioinformatics related methods and databases which are used in the feld of systems biomedicine. At last,some examples that illustrate the whole biological system will be given,and development for systems biomedicine in China and the prospect for systems biomedicine will be talked about.

关键词： Fetal Hemoglobin Level Kabuki Syndrome National Human Genome Research Institute Ovarian Cancer Association Consortium Wellcome Trust Case Control Consortium

SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells

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Science China(Life Sciences) 2013年第1期56卷 19-25页

作者： JIA YuYan GAO Peng CHEN HouZao WAN YanZhen zhang Ran zhang zhuqin YANG RuiFeng WANG Xu XU Jing LIU DePei State Key Laboratory of Medical Molecular Biology Department of Biochemistry and Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences & Peking Union Medical College

Intercellular adhesion molecule-1 （ICAM-1） plays an important role in the recruitment of leukocytes to the endothelium, which causes inflammation and initiation of atherosclerosis. We have previously shown that endothelium-specific over-expression of class III deacetylase SIRT1 decreases atherosclerosis. We therefore addressed the hypothesis that SIRT1 suppresses ICAM-1 expression in the endothelial cells. Here, we found that expression of SIRT1 and ICAM-1 was significantly induced by PMA and ionomycin （PMA/Io） in human umbilical vein endothelial cells （HUVECs）. Adenovirus-mediated over-expression of SIRT1 significantly inhibited PMA/Io-induced ICAM-1 expression （RNAi） resulted in increased expression of ICAM-1 in HUVECs in HUVECs. Knockdown of SIRT1 by RNA interference Luciferase report assay showed that over-expression of SIRT1 suppressed ICAM-1 promoter activity both in basic and in PMA/Io-induced conditions. We further found that SIRT1 was involved in transcription complex binding on the ICAM-1 promoter by chromatin immunoprecipitation （CHIP） assays. Furthermore, SIRT1 RNAi increased NF-~：B p65 binding ability to the ICAM-1 promoter by ChIP assays. Overall, these data suggests that SIRT1 inhibits ICAM-1 expression in endothelial cells, which may contribute to its anti-atherosclerosis effect.

关键词： SIRT1 ICAM-1 PMA and ionomycin

Endothelium-specific SIRT1 overexpression inhibits hyperglycemia-induced upregulation of vascular cell senescence

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Science China(Life Sciences) 2012年第6期55卷 467-473页

作者： CHEN HouZao WAN YanZhen ZHOU Shuang LU YunBiao zhang zhuqin zhang Ran CHEN Feng HAO DeLong ZHAO Xiang GUO ZhiChen LIU DePei LIANG ChihChuan National Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Department of Rheumatology and Immunology Peking Union Medical College HospitalBeijing 100005China

The rapidly increasing prevalence of diabetes mellitus worldwide is one of the most serious and challenging health problems in the 21st century. Mammalian sirtuin 1 （SIRT1） has been shown to decrease high-glucose-induced endothelial cell senescence in vitro and prevent hyperglycemia-induced vascular dysfunction. However, a role for SIRTI in prevention of hyperglyce- mia-induced vascular cell senescence in vivo remains unclear. We used endothelium-specific SIRT1 transgenic （SIRT1-Tg） mice and wild-type （WT） mice to construct a 40-week streptozotocin （STZ）-induced diabetic mouse model. In this mode, 42.9% of wild-type （WT） mice and 38.5% of SIRT1-Tg mice were successfully established as diabetic. Forty weeks of hyper- glycemia induced significant vascular cell senescence in aortas of mice, as indicated by upregulation of expression of senes- cence-associated markers including p53, p21 and plasminogen activator inhibitor-1 （PAI-1）. However, SIRT1-Tg diabetic mice displayed dramatically decreased expression of p53, p21 and PAI-I compared with diabetic WT mice. Moreover, man- ganese superoxide dismutase expression （MnSOD） was significantly downregulated in the aortas of diabetic WT mice, but was preserved in diabetic SIRT1-Tg mice. Furthermore, expression of the oxidative stress adaptor p66Shc was significantly de- creased in aortas of SIRT1-Tg diabetic mice compared with WT diabetic mice. Overall, these findings suggest that SIRT 1-mediated inhibition of hyperglycemia-induced vascular cell senescence is mediated at least partly through the reduction of oxidative stress.

关键词： SIRT1 hyperglycemia vascular cell senescence

Mouse macrophage specific knockout of SIRT1 influences macrophage polarization and promotes angiotensin Ⅱ-induced abdominal aortic aneurysm formation

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Journal of Genetics and Genomics 2018年第1期45卷 25-32页

作者： zhuqin zhang Jing Xu Yue Liu Tingting Wang Jianfei Pei Liqin Cheng Delong Hao Xiang Zhao Hou-Zao Chen De-Pei Liu State Key Laboratory of Medical Molecular Biology Department of Biochemistry and Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Peking Union Medical College No.5 Dong Dan San Tiao Beijing 100005 China

Abdominal aortic aneurysm （AAA） is a vascular degenerative disease. Macrophage polarization and the balance between classically activated macrophages （M1） and alternatively activated macrophages （M2） are crucial for AAA pathogenesis. The present study aims to investigate the roles of macrophage SIRTI in AAA formation and macrophage polarization. We found that in mouse peritoneal macrophages, SIRT1 expression was decreased after M1 stimulation, but was enhanced after M2 stimulation. Results from SIRT1flox/flox mice and macrophage specific SIRT1 knockout mice with treatment of angiotensin II （Ang 11） for 4 weeks showed that macropbage specific deficiency of SIRT1 increased the incidence of AAA and exacerbated the severity, including more severe aneurysm types, enlarged diameter of the aneurysm and increased degradation of elastin. In mouse aortas, SIRT1 deficiency increased the pro- inflammatory M1 molecule inducible nitric oxide synthase （iNOS）, and decreased M2 molecules such as arginase 1 （Argl） and mannose receptor （MR）. Furthermore, in peritoneal macrophages, SIRT1 deficiency increased the expression of M1 inflammatory molecules, but decreased the expression of M2 molecules. Overexpression of SIRT1 had the opposite effects. Thus, macrophage specific knockout of SIRT1 influences macrophage polarization and accelerates Ang II-induced AAA formation.

关键词： SIRT1 Inflammation Macrophage polarization Abdominal aortic aneurysm

Systems biomedicine： It＇s your turn --Recent progress in systems biomedicine

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Frontiers of Electrical and Electronic Engineering in China 2013年第2期8卷 140-155页

作者： zhuqin zhang Zhiguo Zhao Bing Liu Dongguo Li Dandan zhang Houzao Chen Depei Liu State Key Laboratory of Medical Molecular Biology Department of Biochemistry and Molecular Biology Institute of Basic MedicalSciences Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100005 China

The concept of ＂systems biology＂ is raised by Hood in 1999. It means studying all components with a systematic view. Systems biomedicine is the application of systems biology in medicine. It studies all components in a whole system and aims to reveal the patho-physiologic mechanisms of disease. In recent years, with the development of both theory and technology, systems biomedicine has become feasible and popular. In this review, we will talk about applications of some methods of omics in systems biomedicine, including genomics, metabolomics （proteomics, lipidomics, glycomics）, and epigenomics. We will particularly talk about microbiomics and omics for common diseases, two fields which are developed rapidly recently. We also give some bioinformatics related methods and databases which are used in the field of systems biomedicine. At last, some examples that illustrate the whole biological system will be given, and development for systems biomedicine in China and the prospect for systems biomedicine will be talked about.

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Vascular Transcriptome Profiling Reveals Aging-Related Genes in Angiotensin Ji-Induced Hypertensive Mouse Aortas

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Chinese Medical Sciences Journal 2020年第1期35卷 43-53页

作者： Shuangjie Lv Yangnan Ding Xiaoya Pei Xiang Zhao Delong Hao zhuqin zhang Houzao Chen Depei Liu State Key Laboratory of Medical Molecular Biology Department of Biochemistry and Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences&School of Basic Medicine Peking Union Medical CollegeBeijing 100005China

Objective AngiotensinⅡ(AngⅡ)-induced vascular damage is a major risk of ***,the underlying molecular mechanism of AngⅡ-induced vascular damage is still *** this study,we explored the novel mechanism associated with Ang Il-induced *** We treated 8-to 12-week-old C57BL/6J male mice with saline and AngⅡ(0.72 mg/kg-d)for 28 days,*** the RNA of the media from the collected mice aortas was extracted for transcriptome *** component analysis was applied to show a clear separation of different samples and the distribution of differentially expressed genes was manifested by Volcano *** annotations including Gene Ontology(GO)and Koto Encyclopedia of Genes and Genomes(KEGG)pathway were performed to reveal the molecular mechanism of AngⅡ-induced ***,the differentially expressed genes were validated by using quantitative real-time *** The result revealed that a total of 773 genes,including 599 up-regulated genes and 174 down-regulated genes,were differentially expressed in the aorta of AngⅡ-induced hypertension mice *** analysis of differentially expressed genes manifested that various cellular processes may be involved in the AngⅡ-induced hypertension,including some pathways associated with hypertension such as extracellular matrix,inflammation and immune ***,we also found that the differentially expressed genes were enriched in vascular aging pathway,and further validated that the expression levels of insulin-like growth factor 1 and adiponectin were significantly increased(P<0.05).Conclusion We identify that vascular aging is involved in AngⅡ-induced hypertension,and insulin-like growth factor 1 and adiponectin may be important candidate genes leading to vascular aging.

关键词： hypertension vascular aging angiotensin II transcriptome sequencing

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国外重大慢性非传染性疾病防治对策研究

中国工程科学 2017年第2期19卷 112-116页

作者：张祝琴刘德培中国医学科学院基础医学研究所北京100005

重大慢性非传染性疾病包括心脑血管疾病、癌症、呼吸系统疾病、糖尿病等,其流行给全球居民健康造成了重大威胁。为进一步对慢性病进行有效预防控制,促进健康、推动经济和社会发展,2014年中国工程院立项并开展了"重大慢性非传染性疾病防... 详细信息

重大慢性非传染性疾病包括心脑血管疾病、癌症、呼吸系统疾病、糖尿病等,其流行给全球居民健康造成了重大威胁。为进一步对慢性病进行有效预防控制,促进健康、推动经济和社会发展,2014年中国工程院立项并开展了"重大慢性非传染性疾病防治的国际对比研究"项目,对国内外慢性病预防控制情况以及可供我们借鉴的经验进行了详细分析。本文从慢性病发病概况入手,分析了各种疾病的预防控制措施,并对不同国家的慢性病预防控制体系进行比较,凝练有益经验和方法,提出了增强我国慢性病预防控制的措施和建议。

关键词：慢性病心脑血管疾病癌症呼吸系统疾病糖尿病疾病预防控制体系

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SZ110VF双螺杆空压机流场噪声分析

机械管理开发 2024年第4期39卷 66-68页

作者：张波山西宏厦第一建设有限责任公司山西阳泉045000

以SZ110VF双螺杆空压机为研究对象,介绍一种双螺杆空压机流场噪声分析方法.UG软件利用空压机材料特征、流场特点等参数构建出空压机流场三维模型,通过适当转换后,将模型导入FLUENT软件内,将模型划分出大量网格,之后以此为基础,分别对空... 详细信息

以SZ110VF双螺杆空压机为研究对象,介绍一种双螺杆空压机流场噪声分析方法.UG软件利用空压机材料特征、流场特点等参数构建出空压机流场三维模型,通过适当转换后,将模型导入FLUENT软件内,将模型划分出大量网格,之后以此为基础,分别对空压机宽频噪声分布情况及声功率级分布的影响因素进行分析,寻找出空压机流场噪声最小的方案,即齿顶间隙为0.2 mm,双螺杆中心距为81.2 mm,且双螺杆转速处于相对较低的水平.

关键词：双螺杆空压机流场噪声宽频噪声

基于异常载荷工况下的煤矿刮板输送机运动性能分析

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机械管理开发 2024年第4期39卷 62-63,68页

作者：张竹勤晋能控股煤业集团寺河煤矿山西晋城048205

基于刮板输送机基本结构,介绍一种基于ADAMS的刮板输送机异常载荷动力学特性仿真分析方法.此方法采用ADAMS软件构建刮板输送机虚拟样机,可实现刮板输送机卡、断链等异常载荷工况下动力学特性分析.为验证异常载荷动力学特性仿真分析方法... 详细信息

基于刮板输送机基本结构,介绍一种基于ADAMS的刮板输送机异常载荷动力学特性仿真分析方法.此方法采用ADAMS软件构建刮板输送机虚拟样机,可实现刮板输送机卡、断链等异常载荷工况下动力学特性分析.为验证异常载荷动力学特性仿真分析方法的应用价值,将仿真分析方法应用于工程实践,同现场实验法匹配对比后,检验仿真分析方法的分析精度.

关键词：刮板输送机异常载荷动力学特性 ADAMS