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Reveal the pharmacodynamic substances and mechanism of an edible medicinal plant Rhodiola crenulate in DSS-induced colitis through plasma pharmacochemistry and metabolomics

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Food Science and Human Wellness 2024年第4期13卷 2116-2131页

作者： Yu Peng Xiaoao Xiao Tingting Ji Xinyuan Wang Yixuan Xu Jianbo Xiao Hui Cao Zhiyong Chen Huifan Liu yuanqing gao Hongxun Tao Key Laboratory of Cardiovascular and Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjing 211166China School of Food and Biological Engineering Jiangsu UniversityZhenjiang 212013China Department of Analytical Chemistry and Food Science Faculty of ScienceUniversity of VigoVigo 36310Spain CISPAC Fontan BuildingCity of CultureSantiago de Compostela 15707Spain Shaanxi Academy of Traditional Chinese Medicine Xi'an 710003China Guangdong Key Laboratory of Science and Technology of Lingnan Specialty Food Zhongkai University of Agriculture and EngineeringGuangzhou 510550China State Key Laboratory of Southwestern Chinese Medicine Resources Chengdu 610075China

Rhodiola crenulate is the edible medicinal herbal medicine widely used for altitude sickness in ***,our previous work has found that *** extract(RCE)could significantly improve the pathology associated with dextran sulfate sodium-induced ***,the current research aims to reveal the pharmacodynamic material basis of RCE,as well as its mechanism against *** chemical characterization of RCE was performed by UHPLC-HR-MS,through which a total of 88 constituents were ***,our results also found 29 constituents absorbed into blood and 8 metabolized absorbable *** decreased flavonoids prototype and the elevated sulfated products of phenols were observed under pathophysiological conditions of *** metabolomics study revealed that colitis caused the alternation of fatty acid metabolism,steroid hormone biosynthesis and bile acid ***,RCE could prevent colitis by improving fatty acid metabolism and secondary bile acid metabolism.

关键词： Rhodiola crenulate Colitis Chemical characterization Plasma pharmacochemistry Metabolomics

Autophagy enhanced by curcumin ameliorates inflammation in atherogenesis via the TFEB-P300-BRD4 axis

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2280-2299页

作者： Xuesong Li Ruigong Zhu Hong Jiang Quanwen Yin Jiaming Gu Jiajing Chen Xian Ji Xuan Wu Haiping Fu Hui Wang Xin Tang yuanqing gao Bingjian Wang Yong Ji Hongshan Chen Key Laboratory of Cardiovascular and Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjing 211166China Key Laboratory of Targeted Intervention of Cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjing 211166China Department of Cardiothoracic Surgery the Second Affiliated Hospital of Nanjing Medical UniversityNanjing 211166China Department of Cardiology Huai’an First People’s Hospital Affiliated with Nanjing Medical UniversityHuai’an 223399China

Disturbance of macrophage-associated lipid metabolism plays a key role in *** between autophagy deficiency and inflammation response in foam cells(FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized lowdensity lipoprotein(ox-LDL) leads to abnormal crosstalk between autophagy and inflammation,thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4(BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation(LLPS) on the regulatory regions of inflammatory genes. Curcumin(Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.

关键词： Macrophage Autophagy TFEB P300 BRD4 Inflammation Atherosclerosis Curcumin

Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

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Neural Regeneration Research 2025年第1期20卷 242-252页

作者： Daiyu Hu yuanqing Cao Chenglin Cai Guangming Wang Min Zhou Luying Peng Yantao Fan Qiong Lai Zhengliang gao Fundamental Research Center Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)School of MedicineTongji UniversityShanghaiChina Institute of Geriatrics(Shanghai University) Affiliated Nantong Hospital of Shanghai University(The Sixth People’s Hospital of Nantong)Shanghai University School of MedicineNantongJiangsu ProvinceChina Shanghai Engineering Research Center of Organ Repair Shanghai University School of MedicineShanghaiChina Key Laboratory of Arrhythmias Ministry of EducationShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Human brain development is a complex process,and animal models often have significant *** address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and *** enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid *** involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid *** cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology *** a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental *** organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature *** exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic *** convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

关键词： cadmium cell death cell proliferation cortical development environmental toxins neural progenitor cells neurogenesis neurotoxicology organoids stem cells

Non-canonical STING-PERK pathway dependent epigenetic regulation of vascular endothelial dysfunction via integrating IRF3 and NF-κB in inflammatory response

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Acta Pharmaceutica Sinica B 2023年第12期13卷 4765-4784页

作者： Xuesong Li Xiang Chen Longbin Zheng Minghong Chen Yunjia Zhang Ruigong Zhu Jiajing Chen Jiaming Gu Quanwen Yin Hong Jiang Xuan Wu Xian Ji Xin Tang Mengdie Dong Qingguo Li yuanqing gao Hongshan Chen Key Laboratory of Cardiovascular and Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjing 211166China Department of Anesthesiology Sir Run Run HospitalNanjing Medical UniversityNanjing 211166China Department of Pharmacy Huashan HospitalFudan UniversityShanghai 200040China Department of Cardiothoracic Surgery the Second Affliated Hospital of Nanjing Medical UniversityNanjing 211166China Key Laboratory of Targeted Intervention of Cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjing 211166China Department of Cardiology Huai'an First People's Hospital Affliated with Nanjing Medical UniversityHuai'an 223399China

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis,while the underlying mechanism remains ***,we report that the non-canonical stimulator of interferon genes(STING)-PKR-like ER kinase(PERK)pathway was significantly activated in both human and mice atherosclerotic ***,STING activation leads to the activation of interferon regulatory factor 3(IRF3)and nuclear factor-kappa B(NF-κB)/p65,thereby facilitating IFN signals and *** contrast,our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4(BRD4)expression,which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines,thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation ***-specific STING and BRD4 deficiency significantly decreased the plaque area and ***,this pathway is triggered by leaked mitochondrial DNA(mtDNA)via mitochondrial permeability transition pore(mPTP),formed by voltage-dependent anion channel 1(VDAC1)oligomer interaction with oxidized mtDNA upon cholesterol oxidation ***,compared to macrophages,endothelial STING activation plays a more pronounced role in *** propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3,NF-κB and BRD4 in inflammatory responses,which provides emerging therapeutic modalities for vascular endothelial dysfunction.

关键词： Endothelial dysfunction Infiammation Mitochondrial DNA STING ROS PERK BRD4 Atherosclerosis

Prader-Willi综合征下丘脑功能障碍的遗传机制研究进展

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遗传 2022年第10期44卷 899-912页

作者：王心缘孙睿高原青南京医科大学药学院江苏省心脑血管药物重点实验室南京211166

Prader-Willi综合征(Prader-Willi syndrome,PWS)是一种罕见的先天发育性疾病,主要由父系15号染色体长臂15q11~q13区域基因缺失或沉默引起。PWS临床表型复杂,主要包括无法满足的饥饿、病态的肥胖、智力发育迟缓、性腺发育不良等,多数症... 详细信息

Prader-Willi综合征(Prader-Willi syndrome,PWS)是一种罕见的先天发育性疾病,主要由父系15号染色体长臂15q11~q13区域基因缺失或沉默引起。PWS临床表型复杂,主要包括无法满足的饥饿、病态的肥胖、智力发育迟缓、性腺发育不良等,多数症状提示与下丘脑的功能障碍相关。然而到目前为止,PWS的分子遗传机制尚不明确,尤其是基因和临床表现之间的对应关系和详细机制有待进一步研究。本文以PWS“基因型–下丘脑功能障碍表型”之间的关联为重点,综述了15q11~q13区域基因(NIPA1、NIPA2、TUBGCP5、CYFIP1、MAGEL2、NDN、MKRN3和SNORD116等)与PWS患者过度摄食和肥胖、性腺发育不良、睡眠呼吸障碍、生长发育迟缓等表型相关的研究进展,旨在加深对PWS遗传机制的理解,探讨潜在的PWS药物靶点的可能性。

关键词： Prader-Willi综合征下丘脑遗传机制

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一种电能量计量计费容灾系统的设计

电力系统自动化 2008年第16期32卷 52-55页

作者：陈琪高源晴李捷王军郭艳敏国电南瑞科技股份有限公司江苏省南京市210003

为满足电能量计量计费系统领域日益增长的安全可靠性需求,提出了一种电能量计量计费容灾系统的结构模型,阐述了该方案下容灾平台的软件结构模型及各功能模块的实现。介绍了基于该容灾平台的数据库访问机制、主备系统延时同步进程以及手... 详细信息

为满足电能量计量计费系统领域日益增长的安全可靠性需求,提出了一种电能量计量计费容灾系统的结构模型,阐述了该方案下容灾平台的软件结构模型及各功能模块的实现。介绍了基于该容灾平台的数据库访问机制、主备系统延时同步进程以及手工同步界面的功能,并简单说明了在该容灾平台下应用服务器端的典型操作流程。该容灾系统已经在国调电能量计量计费系统工程中投入现场运行。

关键词：容灾系统电能量计量计费系统结构设计

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《伤寒杂病论》中大黄配伍应用探讨

中国当代医药 2013年第6期20卷 129-130页

作者：高元庆云南省楚雄州人民医院药剂科云南楚雄675000

通过查阅古籍、文献、分析总结《伤寒杂病论》中大黄的应用,探讨大黄配伍规律的辨证特点和临床使用。《伤寒杂病论》中大黄配伍严谨,应用灵活,值得深入发掘和探讨,并且认真继承,充分应用于临床。

关键词：《伤寒杂病论》大黄配伍辨证应用

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构建政府现代信用机制

桂海论丛 2002年第6期18卷 43-45页

作者：高元庆苏州市委党校江苏苏州215011

构建适应市场经济要求的政府信用机制是建设社会信用制度的关键。政府信用机制包括 :规范政策机制、规范权力运作机制、承诺机制、政务公正公开机制、责任机制。还包括政府对社会信用建设的推动与管理机制 :对社会信用环境的综合治理、... 详细信息

构建适应市场经济要求的政府信用机制是建设社会信用制度的关键。政府信用机制包括 :规范政策机制、规范权力运作机制、承诺机制、政务公正公开机制、责任机制。还包括政府对社会信用建设的推动与管理机制 :对社会信用环境的综合治理、推动社会信用体系建设、促进民间信用中介机构建设、建立诚信惩戒制度、推动社会信用文化建设。

关键词：政府信用信用机制管理机制

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培养公民的现代民主意识

中共南京市委党校学报 2003年第2期 36-40页

作者：高元庆苏州市委党校法政教研室江苏苏州215011

社会主义政治文明的本质是人民当家作主 ,这就要求亿万人民群众树立起现代的民主意识 ,这对社会主义政治文明建设具有特殊的意义 ,这是一项宏大的基础工程。公民的民主意识包括 :主权在民的意识、法治主体的意识、民主价值观念等。公民... 详细信息

社会主义政治文明的本质是人民当家作主 ,这就要求亿万人民群众树立起现代的民主意识 ,这对社会主义政治文明建设具有特殊的意义 ,这是一项宏大的基础工程。公民的民主意识包括 :主权在民的意识、法治主体的意识、民主价值观念等。公民现代民主意识的培养还需要有一个良好的民主环境 ,包括经济、政治。

关键词：公民民主意识民主价值民主环境