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Single-cell transcriptomics reveals the ameliorative effect of rosmarinic acid on diabetic nephropathy-induced kidney injury by modulating oxidative stress and inflammation

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1661-1676页

作者： Junhui chen Qian Zhang Jinan Guo Di Gu Jing Liu Piao Luo Yunmeng Bai jiayun chen Xinzhou Zhang Sheng Nie Chunbo chen Yulin Feng Jigang Wang National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine Jiangxi University of Chinese MedicineNanchang 330006China Department of Pulmonary and Critical Care Medicine Shenzhen Institute of Respiratory Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalFirst Affiliated Hospital of Southern University of Science and TechnologySecond Clinical Medical College of Jinan UniversityShenzhen 518020China School of Traditional Chinese Medicine and School of Pharmaceutical Sciences Southern Medical UniversityGuangzhou 510515China Department of Urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Urology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Nephrology Nanfang Hospitalthe First Affiliated Hospital of Southern Medical UniversityGuangzhou 510515China Department of Critical Care Medicine Shenzhen People's Hospital(the Second Clinical Medical CollegeJinan Universitythe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020China State Key Laboratory for Quality Esurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Department of Oncology the Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China

Diabetic nephropathy(DN)is a severe complication of diabetes,characterized by changes in kidney structure and *** natural product rosmarinic acid(RA)has demonstrated therapeutic effects,including anti-inflammation and anti-oxidative-stress,in renal damage or *** this study,we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell *** results demonstrated that RA significantly alleviated renal tubular epithelial injury,particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes,while attenuating the inflammatory response of macrophages,oxidative stress,and cytotox-icity of natural killer *** findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage,oxidative stress,and inflammation,offering valuable guidance for the clinical application of RA in the treatment of DN.

关键词： Rosmarinic acid Diabetic nephropathy scRNA sequencing Injury Oxidative stress Infiammation Proteomics

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IL-33、TIMP-1及MMP-2在慢性乙型肝炎肝硬化中的诊断效能分析

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现代实用医学 2024年第5期36卷 599-602页

作者：郑霄顾佳萍陈佳云浙江大学医学院附属第二医院临平院区杭州311100

目的分析白介素-33 (IL-33)、基质金属蛋白酶组织抑制剂-1(TIMP-1)、基质金属蛋白酶-2(MMP-2)在慢性乙型肝炎肝硬化(HBC)中的诊断效能。方法选取2021年7月至2022年6月浙江大学医学院附属第二医院临平院区收治的HBC患者184例(HBC组),... 详细信息

目的分析白介素-33 (IL-33)、基质金属蛋白酶组织抑制剂-1(TIMP-1)、基质金属蛋白酶-2(MMP-2)在慢性乙型肝炎肝硬化(HBC)中的诊断效能。方法选取2021年7月至2022年6月浙江大学医学院附属第二医院临平院区收治的HBC患者184例(HBC组),另选取同期于本院体检的健康人群182例设为对照组。比较HBC组、对照组血清IL-33、TIMP-1及MMP-2水平。HBC组根据疾病分期分为代偿组、失代偿组。HBC患者出院后随访至2023年12月,采用Cox风险比例回归模型分析HBC预后的影响因素;绘制受试者工作特征曲线(ROC)分析血清IL-33、TIMP-1联合MMP-2对HBC预后的预测价值。结果与对照组比较,HBC组血清IL-33、TIMP-1、MMP-2水平升高(P <0.05);与代偿组比较,失代偿组血清IL-33、TIMP-1及MMP-2水平升高(P <0.05)。分析显示,年龄、饮酒、Child Pugh分级、自发性腹膜炎、IL-33、TIMP-1及MMP-2均是HBC预后的影响因素(均P<0.05);与IL-33、TIMP-1、MMP-2单独检测比较,三者联合检测的ROC曲线下面积升高(均P <0.05)。结论IL-33、TIMP-1、MMP-2在HBC中表达升高,且与疾病分期有关,三者联合检测对HBC预后具有较高的诊断效能。

关键词：慢性乙型肝炎肝硬化白介素-33 基质金属蛋白酶组织抑制剂-1 基质金属蛋白酶-2

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新型融合BEV/BPV信息的高分辨率快速磁共振成像方法

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原子核物理评论 2024年第1期41卷 504-509页

作者：陈佳赟王小奇覃仕瑞魏然陈德启张可曹莹戴建荣唐源国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院放疗科北京100021 飞燕四海医疗科技有限公司北京100800

建立了一种新型融合Beam Eye View(BEV)/Beam Path View(BPV)信息的高分辨率快速磁共振成像方法。选取3例肝转移磁共振引导放疗(MRgRT)患者,采集同一患者使用腹部加压带限制腹部运动(RAM组)的运动管理模式下和自由呼吸(FB组)模式下图像... 详细信息

建立了一种新型融合Beam Eye View(BEV)/Beam Path View(BPV)信息的高分辨率快速磁共振成像方法。选取3例肝转移磁共振引导放疗(MRgRT)患者,采集同一患者使用腹部加压带限制腹部运动(RAM组)的运动管理模式下和自由呼吸(FB组)模式下图像,共计31 200帧。采用邻近肿瘤具有明确边界的血管进行肿瘤位置跟踪,计算其在95%置信区间下的径向矢量运动幅度差异△R95。在BEV/BPV平面上RAM组和FB组在所有分次中的△R95的差异分别为:患者1均小于0.58 mm;患者2高达2.57 mm以上;患者3分别为0.71 mm/1.05 mm。结果表明,腹部压迫方案可以有效地减小肿瘤的运动幅度,另外肿瘤运动幅度△R95变化具有完全的个体相关性。该方法也可作为MRgRT技术中肿瘤放疗外放边界缩小的影像基础。

关键词：高分辨率快速MRI成像 BEV/BPV信息融合运动幅度比较肝转移患者磁共振引导放疗

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肿瘤病人静脉通路选择决策的证据审查

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循证护理 2024年第16期10卷 2857-2862页

作者：唐淑慧钱火红曹洁陈佳云周茹珍海军军医大学第一附属医院上海200433

目的:基于循证方法制定肿瘤病人静脉通路置管前评估与选择的审查指标,并进行临床审查,进一步分析障碍因素及促进因素,为规范管理临床静脉通路选择提供参考。方法:基于循证方法形成最佳证据,并制定审查指标,在我院164例肿瘤病人及168名... 详细信息

目的:基于循证方法制定肿瘤病人静脉通路置管前评估与选择的审查指标,并进行临床审查,进一步分析障碍因素及促进因素,为规范管理临床静脉通路选择提供参考。方法:基于循证方法形成最佳证据,并制定审查指标,在我院164例肿瘤病人及168名医护人员中进行审查,采用行为促进(i-PARIHS)框架分析障碍因素及促进因素,并拟定相应对策。结果:本研究共汇总形成了26条最佳证据,制定了16条审查指标,经对164例肿瘤病人进行证据的审查,共有7项指标依从性<60%;62.20%的病人存在决策冲突,46.34%病人决策存在延迟状态。结论:临床上应增加静脉通路的评估和选择相关的培训,优化静脉通路选择流程,细化评估和选择要素,增加静脉通路选择环节质量控制和监督;优化病人随访系统,搭建决策辅助信息化系统,促进证据的临床转化。

关键词：肿瘤血管通路评估循证护理临床实践障碍因素促进因素证据审查

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血脂水平对胆总管取石术及胆囊切除术后复发性胆总管结石的影响

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江苏医药 2024年第7期50卷 729-732页

作者：邱艳陈佳云刘士花左溶王路路庄颖海军军医大学第一附属医院消化内科上海200433

目的探讨血脂水平对胆总管取石术及胆囊切除术后复发性胆总管结石的影响。方法 303例胆总管结石患者行内镜逆行胰胆管造影(ERCP)胆总管取石术及胆囊切除术,中位随访时间66个月。61例患者发生复发性胆总管结石(复发组),242例患者未发生... 详细信息

目的探讨血脂水平对胆总管取石术及胆囊切除术后复发性胆总管结石的影响。方法 303例胆总管结石患者行内镜逆行胰胆管造影(ERCP)胆总管取石术及胆囊切除术,中位随访时间66个月。61例患者发生复发性胆总管结石(复发组),242例患者未发生复发性胆总管结石(未复发组)。收集相关资料,采用Cox回归分析复发性胆总管结石的影响因素。结果与未复发组比较,复发组患者年龄较大,HbA1c水平较高,AST、ALT、总胆红素和γ-谷氨酰转肽酶水平较低,TG>1.82 mmol/L、LDL>3.1 mmol/L、TC>5.2 mmol/L比例较高,HDL≥0.9 mmol/L比例较低(P5.2 mmol/L是复发性胆总管结石的独立危险因素,HDL≥0.9 mmol/L是复发性胆总管结石的独立保护因素(P<0.01)。结论对于行ERCP胆总管取石术及胆囊切除术的患者,血脂水平是复发性胆总管结石的影响因素。

关键词：复发性胆总管结石血脂胆总管取石术胆囊切除术

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Identification of potential anti-pneumonia pharmacological components of Glycyrrhizae Radix et Rhizoma after the treatment with Gan An He Ji oral liquid

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Journal of Pharmaceutical Analysis 2022年第6期12卷 839-851页

作者： Xiaojuan Jiang Yihua Lin Yunlong Wu Caixia Yuan Xuli Lang jiayun chen Chunyan Zhu Xinyi Yang Yu Huang Hao Wang Caisheng Wu Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cell Stress Biology School of Pharmaceutical SciencesXiamen UniversityXiamenFujian361102China Department of Respiratory and Critical Care Medicine The Third Clinical Medical CollegeFujian Medical UniversityFuzhou350122China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Xiamen UniversityXiamenFujian361003China Laboratory of Pharmacology/Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China School of Pharmacy Ningxia Medical UniversityYinchuan750004China School of Pharmacy Minzu University of ChinaBeijing100081China Key Laboratory of Ethnomedicine(Minzu University of China) Ministry of EducationBeijing100081China Institute of National Security Minzu University of ChinaBeijing100081China

Glycyrrhizae Radix et Rhizoma,a traditional Chinese medicine also known as Gan Cao(GC),is frequently included in clinical prescriptions for the treatment of ***,the pharmacological components of GC for pneumonia treatment are rarely *** An He Ji oral liquid(GAHJ)has a simple composition and contains GC liquid extracts and paregoric,and has been used clinically for many ***,GAHJ was selected as a compound preparation for the study of GC in the treatment of *** conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three *** the intelligent mass spectrometry data-processing technologies to analyze the metabolism of GC in vivo,we obtained 168 related components of GC in humans,consisting of 24 prototype components and 144 metabolites,with 135 compounds screened in plasma and 82 in *** analysis of the metabolic transformation relationship and relative exposure,six components(liquiritin,liquiritigenin,glycyrrhizin,glycyrrhetinic acid,daidzin,and formononetin)were selected as potential effective *** experimental results based on two animal pneumonia models and the inflammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase(iNOS).Interestingly,glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in *** following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and ***,the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.

关键词： Glycyrrhizae Radix et Rhizoma Pneumonia Active components Inducible nitric oxide synthase Glycyrrhetinic acid

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Chemical proteomic profiling with photoaffinity labeling strategy identifies antimalarial targets of artemisinin

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Chinese Chemical Letters 2023年第12期34卷 486-491页

作者： Peng Gao jiayun chen Peng Sun Jianyou Wang Huan Tang Fei Xia Liwei Gu Huimin Zhang chen Wang Yin Kwan Wong Yinhua Zhu chengchao Xu Jigang Wang Artemisinin Research Center and Institute of Chinese Materia MedicaChina Academy of Chinese Medical Sciences Pharmaceutical College Henan University Shandong Academy of Chinese Medicine Department of Nephrology Shenzhen Key Laboratory of Kidney DiseasesShenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and Technology

Present research on the antimalarial mechanisms of artemisinin(ART) is mainly focused on covalent drug binding targets alkylated by free radicals, while non-covalent binding targets have rarely been ***, we developed a novel photoaffinity probe of ART to globally capture and identify the antimalarial target proteins of ART through chemical proteomics. The results demonstrated that ART can bind to parasite proteins by both covalent and non-covalent modification, and these may jointly contribute to the antimalarial effects. Our work enriches the research on the antimalarial targets of ART, and provides a new perspective for further exploring the antimalarial mechanism of ART.

关键词： Artemisinin Antimalarial Chemical proteomic Target identification Photoaffinity probe

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Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis

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药物分析学报:英文版 2023年第7期13卷 817-829页

作者： jiayun chen Xueling He Yunmeng Bai Jing Liu Yin Kwan Wong Lulin Xie Qian Zhang Piao Luo Peng Gao Liwei Gu Qiuyan Guo Guangqing cheng chen Wang Jigang Wang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing100700China Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong518020China Department of Gastroenterology Shenzhen HospitalSouthern Medical UniversityShenzhenGuangdong518020China

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ *** on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain *** study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental *** scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during *** could restore neutrophils’chemotaxis and immune function in the septic *** inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during *** also promoted the differentiation and activity of splenic B cells in mice with *** results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the ***,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

关键词： Artesunate Sepsis Single-cell RNA sequencing Immunomodulatory activity

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Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice

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药物分析学报:英文版 2023年第8期13卷 908-925页

作者： Qiuyan Guo Jiangpeng Wu Qixin Wang Yuwen Huang Lin chen Jie Gong Maobo Du Guangqing cheng Tianming Lu Minghong Zhao Yuan Zhao Chong Qiu Fei Xia Junzhe Zhang jiayun chen Feng Qiu Jigang Wang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing100700China School of Chinese Materia Medica and State Key Laboratory of Component-Based Chinese MedicineTianjin University of Traditional Chinese MedicineTianjin301617China Department of Nephrology Shenzhen Key Laboratory of Kidney DiseasesShenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong518020China College of Food Science and Engineering Institute of OceanBohai UniversityJinzhouLiaoning121013China State Key Laboratory of Infectious Disease Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesNational Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing100700China The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine ShenzhenGuangdong518033China

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii *** been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune ***,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing *** present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)*** TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total *** the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate *** analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling ***,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.

关键词： Tripterygium glycosides tablet Acute liver injury scRNA-seq

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Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2300-2314页

作者： Piao Luo Dandan Liu Qian Zhang Fan Yang Yin-Kwan Wong Fei Xia Junzhe Zhang jiayun chen Ya Tian Chuanbin Yang Lingyun Dai Han-Ming Shen Jigang Wang Artemisinin Research Center Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Central People’s Hospital of Zhanjiang Zhanjiang 524037China Department of Urology the Second Clinical Medical CollegeJinan University(Shenzhen People’s Hospital)Shenzhen 518020China Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan UniversityGuangzhou 510632China Faculty of Health Sciences University of MacaoTaipaMacao 999078China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron-and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species(ROS) and inducing ferroptosis in activated hepatic stellate cells(HSCs). By using activity-based protein profiling(ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay(CETSA), we show that celastrol directly binds to peroxiredoxins(PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6,through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1(HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2,PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.

关键词： Celastrol Ferroptosis Peroxiredoxin HO-1 Hepatic fibrosis ABPP Anti-oxidant Reactive oxygen species

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