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Eucommia lignans alleviate the progression of diabetic nephropathy through mediating the AR/Nrf2/HO-1/AMPK axis in vivo and in vitro

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Chinese Journal of Natural Medicines 2023年第7期21卷 516-526页

作者： HUANG Qi ZHANG Yinfan JIANG Yueping HUANG Ling LIU Qiong OUYANG Dongsheng Department of Pharmacy Xiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples Changsha Duxact Biotech Co.Ltd.Changsha 411000 China Department of Operating Room Xiangya HospitalCentral South UniversityChangsha 410008China Department of Oncology Xiangya HospitalCentral South UniversityChangsha 410008China Department of Clinical Pharmacology Xiangya HospitalCentral South UniversityChangsha 410008China Institute of Clinical Pharmacology Hunan Key Laboratory of PharmacogeneticsCentral South UniversityChangsha 410028China

Lignans derived from Eucommia ulmoides Oliver(Eucommia lignans)inhibit the progression of inflammatory diseases,while their effect on the progression of diabetic nephropathy(DN)remained *** work was designed to assess the function of Eucommia lignans in *** major constituents of Eucommia lignans were analyzed by UPLC-Q-TOF-MS/*** binding between Eucommia lignans and aldose reductase(AR)was predicted by molecular *** lignans(200,100,and 50 mg·kg^(-1))were used in model animals to evaluate their renal function *** glomerular mesangial cells(HBZY-1)were transfected with sh-AR,sh-AMPK,and oe-AR in the presence of high glucose(HG)or HG combined with Eucommia lignans to evaluate whether Eucommia lignans affected HG-induced cell injury and mitochondrial dysfunction through the AR/Nrf2/HO-1/AMPK *** lignans significantly attenuated the progression of DN in *** lignans notably reversed HG-induced upregulation of inflammatory cytokines and mitochondrial injury,while downregulating the levels of Cyto c,caspase 9,AR,and NOX4 in HBZY-1 *** contrast,HG-induced downregulation of Nrf2,HO-1 and p-AMPKαlevels were abolished by Eucommia ***,knockdown of AR exerted similar therapeutic effect of Eucommia lignans on DN progression,and AR overexpression reversed the effect of Eucommia *** lignans alleviated renal injury through the AR/Nrf2/HO-1/AMPK ***,these findings might provide evidence for the use of Eucommia lignans in treating DN.

关键词： Diabetic nephropathy(DN) Eucommia lignans Aldose reductase(AR) Nrf2/HO-1/AMPK

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Organ mimicking technologies and their applications in drug discovery

Intelligent Pharmacy

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Intelligent Pharmacy 2023年第2期1卷 73-89页

作者： Qu, Yueyang Ye, Jiaming Lin, Bingcheng Luo, Yong Zhang, Xiuli Jiangsu Key Laboratory of Neuropsychiatric Disease and College of Pharmaceutical Science Soochow University Jiangsu Province Suzhou 215127 China State Key Laboratory of Fine Chemicals Department of Pharmaceutical Sciences School of Chemical Engineering Dalian University of Technology Liaoning Province Dalian 116024 China Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples Hunan Province Changsha 410000 China Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian 116023 China Hangzhou Organ On Chip Technology Co. Ltd Zhejiang Province Hangzhou 310000 China

The significant gap between animal experimentation and clinical trials has resulted in immense expenses in time and money in drug development. The popularity of researches on alternative models to animal experimentation has grown, with the development of artificial organs at its forefront. Three state-of-the-art technologies used to simulate organs are organ-on-a-chip, organoid, and 3D bioprinting. Organ-on-a-chip technology utilizes flexible fluidic manipulation and accurate recreation of the cell microenvironment. Organoid technology allows for the development of personalized mini-organs and the testing of drugs on different human species. 3D bioprinting technology is capable of creating artificial organs with intricate 3D structures. All these technologies play a significant role in developing drugs in highly efficient mode. © 2023 The Authors

关键词： 3D bioprinting Drug discovery Microphysiological system Organ-on-a-chip Organoid

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Corrigendum to "Plasma reference interval of Trimethylamine-N-oxide in healthy adults: A multicenter study using Trimethylamine-N-oxide assay kit for analysis and validation" [Clin. Chim. Acta. 571 (2025) 120223]

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Clinica chimica acta;international journal of clinical chemistry 2025年 572卷 120264页

作者： Qing Fang Yuyan Lei Hao Wu Chao Li Junyi Jiang Shiyun Wang Yu Wu Lulu Chen Dongsheng Ouyang Xiaohui Li Ying Li Changsha Duxact Biotech Co. Ltd. Changsha China Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples Changsha China. Department of Pharmacology Xiangya School of Pharmaceutical Science Central South University Changsha China The Second Nanning People's Hospital Nanning China. Department of Health Management The Third Xiangya Hospital Central South University Changsha China. Department of Clinical Pharmacology Xiangya Hospital Central South University and Institute of Clinical Pharmacology Changsha China. The Affiliated Hospital of Xiangnan University Chenzhou Changsha China. Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples Changsha China. Electronic address: zndxchenll@***. Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples Changsha China. Electronic address: ouyangyj@***. Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples Changsha China Department of Pharmacology Xiangya School of Pharmaceutical Science Central South University Changsha China. Electronic address: xiaohuili@***. Department of Health Management The Third Xiangya Hospital Central South University Changsha China. Electronic address: lydia0312_2000@***.

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The hepatotoxicity of Polygonum multiflorum:The emerging role of the immune-mediated liver injury

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中国药理学报（英文版） 2021年第1期42卷 27-35页

作者： Tai Rao Ya-ting Liu Xiang-chang Zeng Chao-peng Li Dong-sheng Ou-Yang Department of Clinical Pharmacology Xiangya HospitalCentral South UniversityChangsha 410008China Hunan Key Laboratory of Pharmacogenetics Institute of Clinical PharmacologyCentral South UniversityChangsha 410008China Engineering Research Center of Applied Technology of Pharmacogenomics Ministry of EducationChangsha 410008China National Clinical Research Center for Geriatric Disorders Chang Department of Clinical Pharmacology Xiangya HospitalCentral South UniversityChangsha 410008China Hunan Key Laboratory of Pharmacogenetics Institute of Clinical PharmacologyCentral South UniversityChangsha 410008China Engineering Research Center of Applied Technology of Pharmacogenomics Ministry of EducationChangsha 410008China National Clinical Research Center for Geriatric Disorders Chang Department of Clinical Pharmacology Xiangya HospitalCentral South UniversityChangsha 410008China Hunan Key Laboratory of Pharmacogenetics Institute of Clinical PharmacologyCentral South UniversityChangsha 410008China Engineering Research Center of Applied Technology of Pharmacogenomics Ministry of EducationChangsha 410008China National Clinical Research Center for Geriatric Disorders Chang Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples Changsha 410205China Department of Clinical Pharmacology Xiangya HospitalCentral South UniversityChangsha 410008China Hunan Key Laboratory of Pharmacogenetics Institute of Clinical PharmacologyCentral South UniversityChangsha 410008China Engineering Research Center of Applied Technology of Pharmacogenomics Ministry of EducationChangsha 410008China National Clinical Research Center for Geriatric Disorders Chang

Herbal and dietary supplements(HDS)-induced liver injury has been a great concern all over the *** multiflorum Thunb.,a well-known Chinese herbal medicine,is recently drawn increasing attention because of its *** to the clinical and experimental studies,***-induced liver injury(PM-DILI)is considered to be immune-mediated idiosyncratic liver injury,but the role of immune response and the underlying mechanisms are not completely *** studies focused on the direct toxicity of PM-DILI by using animal models with intrinsic drug-induced liver injury(DILI).However,most epidemiological and clinical evidence demonstrate that PM-DILI is immune-mediated idiosyncratic liver *** aim of this review is to assess current epidemiological,clinical and experimental evidence about the possible role of innate and adaptive immunity in the idiosyncratic hepatotoxicity of *** potential effects of factors associated with immune tolerance,including immune checkpoint molecules and regulatory immune cells on the individual's susceptibility to PM-DILI are also *** conclude by giving our hypothesis of possible immune mechanisms of PM-DILI and providing suggestions for future studies on valuable biomarkers identification and proper immune models establishment.

关键词： Polygonum multiflorum Chinese herbal medicine idiosyncratic drug-induced liver injury inflammatory stress adaptive immunity immune tolerance

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The pharmacogenomic landscape in the Chinese: An analytics of pharmacogenetic variants in 206,640 individuals

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The Innovation 2025年第2期6卷 28-40,27页

作者： Lei-Yun Wang Bing Yu Ying Peng Kai Mou Yan Zhan Yi-Min Wang Wei Ji Chun Xu Le-Dong Xiao Yan Chen Hua Wang Zhi-Hua She Peng Dai Gan-Ye Zhao Yang Wang Lu-Lu Yu Miao Yu Ke Liu Jia-Jia Cui Rong Liu Xi Li Yuan-Fei Huang Zhao-Qian Liu Dong-Sheng Ouyang Wei Zhang Qing Li Xing-Liang Xiong Cheng-Xian Guo Jin-Gao Li Qiao-Li Lv Qing-He Xing Hai-Jian Wang Zhi-Ling Li Ji-Chu Wu Long-Jian Huang Jian He Li-Ming Tan Wen-Xu Hong Xue-Chang Wang Chao-Peng Li Qin Lu Long Zhang Xiang-Dong Kong Hong-Hao Zhou Ji-Ye Yin Department of Clinical Pharmacology Xiangya HospitalCentral South UniversityChangsha 410078China Engineering Research Center of Applied Technology of Pharmacogenomics Ministry of EducationChangsha 410078China National Clinical Research Center for Geriatric Disorders Changsha 410008China Institute of Clinical Pharmacology Hunan Key Laboratory of PharmacogeneticsCentral South UniversityChangsha 410078China The Genetics and Prenatal Diagnosis Center The Department of Obstetrics and GynecologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Genetic Laboratory Zibo Maternal and Child Health HospitalZibo 255000China The Hunan Children’s Hospital Changsha 410000China National Health Commission Key Laboratory of Birth Defects Research Prevention and TreatmentHunan Provincial Maternal and Child Health Care HospitalChangsha 410000China Department of Pharmacy Hunan Provincial Maternal and Child Health Care HospitalChangsha 410008China Genetalks Co.Ltd. Changsha 410008China Xiangya Medical Laboratory Central South UniversityChangsha 410078China Salus Med Co.Ltd. Shenzhen 518107China Department of Pharmacy Traditional Chinese and Western Medicine Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Pharmacy Wuhan No.1 HospitalWuhan 430022China Department of Pharmacy Xiangya HospitalCentral South UniversityChangsha 410078China Department of General Surgery Xiangya HospitalCentral South UniversityChangsha 410078China Department of Geriatric Surgery Xiangya HospitalCentral South UniversityChangsha 410078China Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples Changsha Duxact Biotech Co.Ltd.Changsha 410000China Center of Clinical Pharmacology The Third Xiangya HospitalCentral South UniversityChangsha 410013China Department of Radiation Oncology Jiangxi Cancer HospitalNanchang 330029China NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinom

Pharmacogenomic landscapes and related databases are important for identifying the biomarkers of drug response and ***,these data are still lacking for the Chinese *** this study,we constructed a pharmacogenomic landscape and an associated database using whole-genome sequencing data generated by non-invasive prenatal testing in 206,640 Chinese *** total,1,577,513 variants(including 331,610 novel variants)were identified among 3,538 pharmacogenes related to 2,086 *** found that the variant spectrum in the Chinese population differed among the seven major *** differences also exist among provinces in *** average numbers of drug enzyme,transporter,and receptor variants were 258,557,and 632,*** correlation analysis indicated that the pharmacogenes affecting multiple drugs had fewer *** the 16 categories of drugs,we found that nervous system,cardiovascular system,and genitourinary system/sex hormone drugs were more likely to be affected by variants of *** of the variants in the enzyme,transporter,and receptor subfamilies showed *** explore the clinical utility of these data,a genetic association study was conducted on 1,019 lung cancer *** novel variants,AKT2 chr19:40770621 C>G and SLC19A1 chr21:46934171 A>C,were identified as novel platinum response ***,a pharmacogenomic database,named the Chinese Pharmacogenomic Knowledge Base(CNPKB:http://***/),was constructed to collect all the *** summary,a pharmacogenomic landscape and database for the Chinese population were constructed in this study,which could support personalized Chinese medicine in the future.

关键词： pharmacogenomics Chinese population personalized medicine pharmacogenomic landscapes associated database whole genome sequencing identifying biomarkers pharmacogenetic variants

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Diffusion-based generative drug-like molecular editing with chemical natural language

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Journal of Pharmaceutical Analysis 2024年

作者： Jianmin Wang Peng Zhou Zixu Wang Wei Long Yangyang Chen Kyoung Tai No Dongsheng Ouyang Jiashun Mao Xiangxiang Zeng Department of Integrative Biotechnology Yonsei University Incheon 21983 Korea College of Computer Science and Electronic Engineering Hunan University Changsha Hunan 410082 China Department of Computer Science University of Tsukuba Tsukuba 3058577 Japan Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples Changsha Duxact Biotech Co. Ltd. Changsha China Department of Clinical Pharmacology Xiangya Hospital Central South University 87 Xiangya Road Changsha 410008 PR China Institute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics 110 Xiangya Road Changsha 410078 PR China School of Medical Information and Engineering Southwest Medical University Luzhou 646000 Sichuan China

Recently, diffusion models have emerged as a promising paradigm for molecular design and optimization. However, most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geometries, with limited research on molecular sequence diffusion models. The International Union of Pure and Applied Chemistry (IUPAC) names are more akin to chemical natural language than the Simplified Molecular Input Line Entry System (SMILES) for organic compounds. In this work, we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language (SMILES) and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language. We propose DiffIUPAC, a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings. Evaluation results demonstrate that our model outperforms existing methods and successfully captures the semantic rules of both chemical languages. Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints. Additionally, to illustrate the model's applicability in drug design, we conducted case studies in functional group editing, analogue design and linker design.

关键词： diffusion model IUPAC molecular generative model chemical natural language transformer

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Correction: Correlation study between bone metabolic markers, bone mineral density, and sarcopenia

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Journal of endocrinological investigation 2024年第9期47卷 2379页

作者： W Q Xie M He D J Yu H Z Li H F Jin B Z Ji G Yang L L Chen M Rahmati Y S Li Deparment of Orthopedics Xiangya Hospital Central South University Changsha 410008 Hunan China. National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University Changsha 410008 Hunan China. Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples Changsha 410000 Hunan China. Department of Physical Education and Sport Sciences Faculty of Literature and Human Sciences Lorestan University Khorramabad Iran. Department of Physical Education and Sport Sciences Faculty of Literature and Humanities Vali-E-Asr University of Rafsanjan Rafsanjan Iran. Deparment of Orthopedics Xiangya Hospital Central South University Changsha 410008 Hunan China. liyusheng@***. National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University Changsha 410008 Hunan China. liyusheng@***.

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MAFG-AS1/MAFG positive feedback loop contributes to cisplatin resistance in bladder urothelial carcinoma through antagonistic ferroptosis

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Science Bulletin 2021年第17期66卷 1773-1788,M0004页

作者： Liang Xiang Qinghai Zeng Jianye Liu Mengqing Xiao Dong He Qun Zhang Dan Xie Minhua Deng Yuxing Zhu Yan Liu Hao Bo Xiaoming Liu Ming Zhou Wei Xiong Yanhong Zhou k Jianda Zhou Xiaohui Li Ke Cao Department of Oncology Third Xiangya Hospital of Central South UniversityChangsha 410013China Department of Dermatology Third Xiangya Hospital of Central South UniversityChangsha 410013China Department of Urology Third Xiangya Hospital of Central South UniversityChangsha 410013China Department of Respiratory The Second People’s Hospital of Hunan ProvinceChangsha 410007China Department of Radiotherapy The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Department of Pathology Sun Yat-sen University Cancer CenterGuangzhou 510060China Department of Urology Sun Yat-sen University Cancer CenterGuangzhou 510060China Department of Plastic Surgery Third Xiangya Hospital of Central South UniversityChangsha 410013China Institute of Reproductive and Stem Cell Engineering Central South UniversityChangsha 410083China Department of Gastroenterology Third Xiangya Hospital of Central South UniversityChangsha 410013China Cancer Research Institute and Key Laboratory of Carcinogenesis of the Chinese Ministry of Health Central South UniversityChangsha 410078China Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples Changsha 410205China Department of Pharmaceutical Chemistry School of Pharmaceutical SciencesCentral South UniversityChangsha 410013China

Though promoting ferroptosis can reduce cisplatin resistance in tumor cells,ferroptosis and cisplatin resistance in bladder urothelial carcinoma(BUC)following long non-coding RNAs(lncRNAs)is largely ***,we found the highly expressed lncRNA MAF transcription factor G antisense RNA 1(MAFG-AS1)in BUC,and its inhibition increased the sensitivity of BUC cells to cisplatin by promoting ***,binding to iron chaperone poly(rC)-binding protein 2(PCBP2)facilitated the recruitments of MAFG-AS1 to deubiquitinase ubiquitin carboxyl-terminal hydrolase isozyme L5(UCHL5),thus stabilizing PCBP2 protein *** PCBP2 was confirmed to interact with ferroportin 1(FPN1),an iron export protein,leading to inhibition of ***,the expression of MAFG-AS1 was regulated by the transcriptional factor ***,MAFG-AS1 stimulated MAFG transcription by recruiting histone acetyltransferase p300(EP300)to promote the histone 3 at lysine 27(H3K27ac)at genomic locus of MAFG,forming a MAFG-AS1/MAFG positive feedback *** patient samples,higher expression of MAFG-AS1 and MAFG in BUC tissues was significantly correlated with T status and N status,such that MAFG-AS1,MAFG,and the combination of the two were independent prognostic indicators and chemotherapy sensitivity predictive biomarkers for BUC *** findings suggest that inhibition of MAFG-AS1 and MAFG can increase the sensitivity of BUC cells to cisplatin through promoting ferroptosis,indicating the novel chemotherapy sensitivity biomarkers and therapeutic target for BUC.

关键词： Bladder urothelial carcinoma Cisplatin Chemosensitivity Ferroptosis MAFG-AS1

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