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Artesunate Induces Ferroptosis in Hepatic Stellate Cells and Alleviates Liver Fibrosis via the ROCK1/ATF3 Axis

Journal of clinical and Translational Hepatology 2024年第1期12卷 36-51页

作者： Yingqian Wang Yujia Li Yangling Qiu Min Shen Ling Wang Jiangjuan Shao Feng Zhang Xuefen Xu Zili Zhang Mei Guo Shizhong Zheng Jiangsu Key Laboratory for pharmacology and Safety Evaluation of Chinese Materia Medica Nanjing University of Chinese MedicineNanjingJiangsuChina institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhouJiangsuChina Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine Nanjing University of Chinese MedicineNanjingJiangsu China

Background and Aims:Development of fibrosis in chronic liver disease requires activation of hepatic stellate cells(HSCs)and leads to a poor ***(Art)is an ester derivative of artemisinin that can induce ferroptosis in HSCs,and activated transcriptional factor 3(ATF3)is an ATF/CREB transcription factor that is induced in response to *** this study,we examined the role of the Rho-associated protein kinase 1(ROCK1)/ATF3 axis in Art-induced ferroptosis in ***:HSC activation and ferroptosis were studied in vitro by western blotting,polymerase chain reaction,immunofluorescence,and other ***3 electrophoretic mobility and ROCK1 protein stability were assayed by western *** was used to detect the interaction of ROCK1 and ATF3,as well as ATF3 phosphorylation.A ubiquitination assay was used to verify ROCK1 ***3-interfering and Rock1-overexpressing mice were constructed to validate the anti-hepatic fibrosis activity of Art in ***:Art induced ferroptosis in HSCs following glutathione-dependent antioxidant system inactivation resulting from nuclear accumulation of unphosphorylated ATF3 mediated by ROCK1-ubiquitination in *** also decreased carbon tetrachloride-induced liver fibrosis in mice,which was reversed by interfering with Atf3 or overexpressing ***:The ROCK1/ATF3 axis was involved in liver fibrosis and regulation of ferroptosis,which provides an experimental basis for further study of Art for the treatment of liver fibrosis.

关键词： Ferroptosis Liver fibrosis Antioxidant system ATF3 ROCK1

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Rapid characterization of non-volatile phenolic compounds reveals the reliable chemical markers for authentication of traditional Chinese medicine Xiang-ru among confusing Elsholtzia species

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Chinese Journal of Natural Medicines 2024年第4期22卷 375-384页

作者： ZENG Zhen ZHANG Chen HU Jiadong WANG Feiyan WU Ziding WANG Jing ZHANG Jun YANG Shuda CHEN Junfeng LI Mingming TONG Qi QIU Shi CHEN Wansheng The SATCM Key Laboratory for New Resources&Quality Evaluation of Chinese Medicine Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China Department of Pharmacy Second Affiliated Hospital of Navy Medical UniversityShanghai 200003China Kunming Plant Classification Biotechnology Co. Ltd.Kunming 650500China School of Pharmaceutical Sciences and Yunnan Key Laboratory of pharmacology for Natural Products Kunming Medical UniversityKunming 650500China State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Beijing100700China

The aerial parts of Mosla chinensis *** Mosla chinensis cv.'Jiangxiangru'(MCJ)are widely utilized in traditional Chinese medicine(TCM),known collectively as ***,due to clinical effectiveness concerns and frequent misidentification,the original plants have increasingly been substituted by various species within the genera Elsholtzia and *** challenge in distinguishing between these genera arises from their similar morphological and metabolic *** address this issue,our study introduced a rapid method for metabolic characterization,employing high-resolution mass spectrometry-based *** detailed biosynthetic and chemometric analyses,we pinpointed five phenolic compounds—salviaflaside,cynaroside,scutellarein-7-O-D-glucoside,rutin,and vicenin-2—among 203 identified compounds,as reliable chemical markers for distinguishing Xiang-ru from closely related Elsholtzia *** methodology holds promise for broad application in the analysis of plant aerial parts,especially in verifying the authenticity of aromatic traditional medicinal *** findings underscore the importance of non-volatile compounds as dependable chemical markers in the authentication process of aromatic traditional medicinal plants.

关键词： Genus Elsholtzia Genus Mosla Traditional Chinese medicine Xiang-ru Non-volatile phenolic compounds Liquid chromatography-mass spectrometry

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Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells promote alveolar bone regeneration by regulating macrophage polarization

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Science China(Life Sciences) 2024年第5期67卷 1010-1026页

作者： Ziyue Qin Yanxing Han Yifei Du Yixuan Zhang Yifeng Bian Ruyu Wang Haoran Wang Fanyi Guo Hua Yuan Yongchu Pan Jianliang Jin Qigang Zhou Yuli Wang Feng Han Yan Xu Jiandong Jiang Department of Oral and Maxillofacial Surgery The Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjing 210029China Jiangsu Province Key Laboratory of Oral Diseases Nanjing Medical UniversityNanjing 210029China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing 210029China State Key Laboratoryof BioactiveSubstances andFunction of Natural Medicine Instituteof Materia MedicaChinese Academyof MedicalSciencesandPeking Union MedicalCollegeBeijing100050China Gusu school Nanjing medical universitySuzhou 215002China Key Laboratory of Cardiovascular&Cerebrovascular Medicine Drug Target and Drug Discovery CenterSchool of PharmacyNanjing Medical UniversityNanjing 211166 China Department of Orthodontics The Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjing 210029China Department of Human Anatomy Research Centre for Bone and Stem CellsKey Laboratory for Aging&DiseaseThe State Key Laboratory of Reproductive MedicineNanjing Medical UniversityNanjing 211166China Department of clinical pharmacology School of PharmacyNanjing Medical UniversityNanjing Jiangsu211166China Department of Periodontology The Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjing 210029China Department of Virology Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Alveolar bone regeneration has been strongly linked to macrophage polarization.M1 macrophages aggravate alveolar bone loss,whereas M2 macrophages reverse this ***(BBR),a natural alkaloid isolated and refined from Chinese medicinal plants,has shown therapeutic effects in treating metabolic *** this study,we first discovered that culture supernatant(CS)collected from BBR-treated human bone marrow mesenchymal stem cells(HBMSCs)ameliorated periodontal alveolar bone *** from the BBR-treated HBMSCs contained bioactive materials that suppressed the M1 polarization and induced the M2 polarization of macrophages in vivo and in *** clarify the underlying mechanism,the bioactive materials were applied to different animal *** discovered macrophage colony-stimulating factor(M-CSF),which regulates macrophage polarization and promotes bone formation,a key macromolecule in the *** of pure M-CSF attenuated experimental periodontal alveolar bone loss in ***-stimulating factor 1 receptor(CSF1R)inhibitor or anti-human M-CSF(M-CSF neutralizing antibody,Nab)abolished the therapeutic effects of the CS of BBR-treated ***,AKT phosphorylation in macrophages was activated by the CS,and the AKT activator reversed the negative effect of the CSF1R inhibitor or *** results suggest that the CS of BBR-treated HBMSCs modulates macrophage polarization via the M-CSF/AKT *** studies also showed that CS of BBR-treated HBMSCs accelerated bone formation and M2 polarization in rat teeth extraction ***,our findings established an essential role of BBR-treated HBMSCs CS and this might be the first report to show that the products of BBR-treated HBMSCs have active effects on alveolar bone regeneration.

关键词： berberine human bone marrow mesenchymal stem cells alveolar bone regeneration macrophage colony-stimulating factor AKT phosphorylation

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Unexpected bonds:ubiquitin-like conjugation of cGAS/CDNTases supports their enzymatic activity and antiphage defense

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Signal Transduction and Targeted Therapy 2023年第9期8卷 3899-3901页

作者： Katarzyna Andryka-Cegielski Sofía Soler Eva Bartok institute of Experimental Haematology and Transfusion Medicine University HospitalUniversity of BonnBonnGermany institute of clinical Chemistry and clinical pharmacology University HospitalUniversity of BonnBonnGermany

In their recently published study in Nature,Jenson et al.1 provide compelling,unexpected evidence that bacterial cGAMP synthase(cGAS)and other cGAS/DncV-like Nucleotidyltransferases(CD-NTase)undergo ubiquitin-like conjugation(ULC)in type-II cyclic-oligonucleotide-based anti-phage signaling systems(CBASS).cGAS conjugation promotes cyclic-nucleotide(CN)formation and thus antiphage ***,the authors also reveal a new class of phage-encoded CBASS inhibitor,T4 Vs.4,a CN-sponge which limits CBASS effector function and promotes phage replication,revealing another weapon in the“arms race”between phages and their bacterial hosts.

关键词： bonds enzymatic sponge

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Arsenic Disulfide Induced Apoptosis and Concurrently Promoted Erythroid Differentiation in Cytokine-Dependent Myelodysplastic Syndrome-progressed Leukemia Cell Line F-36p with Complex Karyotype Including Monosomy 7

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Chinese Journal of Integrative Medicine 2014年第5期20卷 387-393页

作者：胡晓梅 Sachiko Tanaka Kenji Onda 袁博 Hiroo Toyoda 麻柔刘峰 Toshihiko Hirano Department of clinical pharmacology School of PharmacyTokyo University of Pharmacy and Life Sciences National Therapeutic Center of Hematology of Traditional Chinese Medicine Xiyuan HospitalChina Academy of Chinese Medical Sciences

Objective： Acute myeloid leukemia progressed from myelodysplastic syndrome （MDS/AML） is generally incurable with poor prognosis for complex karyotype including monosomy 7 （-7）. Qinghuang Powder （青黄, QHP）, which includes Qing Dai （ Indigo naturalis） and Xiong Huang （realgar） in the formula, is effective in treating MDS or MDS/AML even with the unfavorable karyotype, and its therapeutic efficacy could be enhanced by increasing the Xiong huang content in the formula, while Xiong huang contains 〉 90% arsenic disulfide （As2S2）. F-36p cell line was established from a MDS/AML patient with complex karyotype including -7, and was in cytokine-dependent. The present study was to investigate the effects of As2S2 on F-36p cells. Methods： Cell proliferation was measured by an 3-（4,5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） assay. Cell apoptosis was identified by Annexin V-staining. Cell viability was determined by a propidium iodide （PI） exclusion. Erythroid differentiation was evaluated by the expression of cell surface antigen CD235a （GpA）. Results： After treatment with As2S2 at concentrations of 0.5 to 16 p. mol/L for 72 h, As2S2 inhibited the proliferation of F-36p cells. The 50% inhibitory concentrations （IC50） of As2S2 against the proliferation of F-36p cells was 6 I~ mol/L. The apoptotic cells significantly increased in a dose-dependent mannar （P〈0.05）. The cell viabilities were significantly inhibited by As2S2 dose-dependent in a dose-dependent manner （P〈0.05）. Significant increases of CD235a-positive cells were concurrently observed （P〈0.05） also in a dose- dependent manner. Conclusions： As2S2 could inhibit proliferation and viability, induce apoptosis, and concurrently promote erythroid differentiation dose-dependently in F-36p cells. As2S2 can inhibit proliferation and viability, induce apoptosis, and concurrently promote erythroid differentiation in cytokine-dependent MDS-progressed human leukemia cell line F-36p with complex karyotype including -7

关键词： leukemia myelodysplastic syndromes arsenic disulfide karyotype F-36p apoptosis erythroid diffeerentiation

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The Theory of Homogeny of Liver and Kidney in the Treatment of Kidney and Liver Fibrosis

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Chinese Journal of Integrative Medicine 2012年第4期18卷 250-252页

作者：李平张浩军郑柳涛 Department of pharmacology Institute of Clinical Medical SciencesChina-Japan Friendship Hospital

Chronic kidney disease （CKD） and chronic liver disease are both very harmful to human health almost all over the world, which lead to the fibrosis of the two organs ultimately. Currently, there are few satisfactory therapeutic methods in treating the two diseases. Some research works from Chinese medicine and Western medicine were done in the area recently, the results showed that kidney and liver fibrosis shared similar biological signals and events such as epithelial- mesenchymal transition （EMT） and transforming growth factor β 1, the same herbal medicine exhibited significantly improving effects on both liver fibrosis and kidney fibrosis by involving similar mechanism. This coincides with the theory of homogeny of Liver （Gan） and Kidney （Shen） of Chinese medicine. It would provides new clues in exploring the treatment of liver fibrosis and kidney fibrosis.

关键词： homogeny liver kidney fibrosis saikosaponin-d

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Arsenic concentration in peripheral blood is correlated with efficacy of a Traditional Chinese Medicine regimen containing realgar for the treatment of myelodysplastic syndromes

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Journal of Traditional Chinese Medicine 2021年第4期41卷 630-635页

作者： WANG Dexiu XU Yonggang DU Yu WANG Hongzhi LI Liu HU Xiaomei YANG Xiupeng MA Rou ZHOU Qingbing Department of Hematology Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China institute of Geriatric Medicine Xiyuan HospitalChinese Academy of Chinese Medical SciencesBeijing 100091China

OBJECTIVE:To explore the relationship between the efficacy of realgar for the treatment of myelodysplastic syndromes with multilineage dysplasia(MDS-MLD)and arsenic concentration in the peripheral blood of ***:In this prospective study,a total of 50 MDS-MLD patients were treated with traditional Chinese drugs containing realgar for 3 months in xiyuan hospital from March 2018 to January *** blood examination as well as liver and kidney function were monitored before and after *** concentration of arsenic in the peripheral blood was measured using an atomic fluorescence spectrometer after *** correlation between clinical effect and arsenic concentration was analyzed by Spearman’s ***:The treatment response rate was 54%.Two patients(4%)achieved complete remission,50%(25 of 50)showed hematologic improvement,and 23 patients had stable disease(23%).No disease progression was *** concentration in the peripheral blood ranged from 14.60 to 85.96μg/*** efficacy was positively correlated with arsenic concentration(Pclinical efficacy of realgar in MDS-MLD patients.

关键词： realgar arsenic myelodysplastic syndromes multiline dysplasia

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Population Pharmacokinetics of Naringin in Total Flavonoids of Drynaria Fortunei(Kunze) *** Chinese Women with Primary Osteoporosis

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Chinese Journal of Integrative Medicine 2012年第12期18卷 925-933页

作者：王建农姜俊杰谢雁鸣魏戌李建鹏段京莉熊歆 xiyuan hospital China Academy of Chinese Medical Sciences Chinese clinical Basic institute China Academy of Chinese Medical Sciences Department of Pharmaceutics Third Hospital Affiliated Peking University

Objective： To evaluate the effect of covariates on the pharmacokinetic profiles of naringin in the total flavonoids of Drynaria fortunei （Kunze） J. Sin. in the Qianggu Capsule （强骨胶囊） by evaluating Chinese women with primary osteoporosis. Methods： A total of 98 female patients from the communities of Jingshan, Beixinqiao, Jiaodaokou, Chaoyangmen, and Donghuamen in Beijing, China, aged 40 to 80 years, were included in this study. Blood samples were collected before and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after a single oral dose of Qianggu Capsule. The concentration in blood samples from 32 patients before and 0.5, 1, 2, 3, and 4 h after drug administration were determined by liquid chromatography-tandem mass spectrometry （LC-MS/MS） method, and full set of pharmacokinetic data was analyzed with nonlinear mixed-effect modeling （NONMEM） software. The mean of population parameters clearance （C1）, central distribution volume （V）, absorption rate constant （Kal）, inter-compartmental clearance （C2）, peripheral distribution volume （V2） were set as parameters and estimated through base model, covariate model, and final model. Age, height, weight, blood urea nitrogen （BUN）, serum creatinine （Scr）, alanine transaminase （ALT）, aspartate transaminase （AST）, hyperlipidemia, Liver （Gan） Kidney （Shen） yin insufficiency （GSYI）, Kidney （Shen） yang insufficiency （SYI） were set as covariates. Results： The relationships between these parameters and covariates were analyzed. The results showed that C1 was the main parameter influenced by the selected covariates among the population parameters, and the relationships between the covariates and C1 were analyzed, among the selected covariates hyperlipidemia was identified as significant covariate of C1. Conclusion： The pharmacokinetic behaviors of naringin are altered with hyperlipidemia in Chinese women with primary osteoporosis.

关键词： naringin population pharmacokinetics Qianggu Capsule total flavonoids of Drynaria fortunei

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Mitochondrial dysfunction:mechanisms and advances in therapy

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2362-2390页

作者： Yao Zong Hao Li Peng Liao Long Chen Yao Pan Yongqiang Zheng Changqing Zhang Delin Liu Minghao Zheng Junjie Gao Centre for Orthopaedic Research Medical SchoolThe University of Western AustraliaNedlandsWA 6009Australia Department of Orthopaedics Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China institute of Microsurgery on Extremities and Department of Orthopedic SurgeryShanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell BiologyCAS Center for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Sixth People’s hospital Fujian No.16Luoshan SectionJinguang RoadLuoshan StreetJinjiang CityQuanzhouFujianChina

Mitochondria,with their intricate networks of functions and information processing,are pivotal in both health regulation and disease ***,mitochondrial dysfunctions are identified in many common pathologies,including cardiovascular diseases,neurodegeneration,metabolic syndrome,and ***,the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction complicate our understanding of their contributions to ***,these complexities do not prevent mitochondria from being among the most important therapeutic *** recent years,strategies targeting mitochondrial dysfunction have continuously emerged and transitioned to clinical *** intervention such as using healthy mitochondria to replenish or replace damaged mitochondria,has shown promise in preclinical trials of various *** components,including mtDNA,mitochondria-located microRNA,and associated proteins can be potential therapeutic agents to augment mitochondrial function in immunometabolic diseases and tissue ***,we review current knowledge of mitochondrial pathophysiology in concrete examples of common *** also summarize current strategies to treat mitochondrial dysfunction from the perspective of dietary supplements and targeted therapies,as well as the clinical translational situation of related pharmacology ***,this review discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment.

关键词： dysfunction injuries replace

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Paeoniflorin Promotes Angiogenesis in A Vascular Insufficiency Model of Zebrafish in vivo and in Human Umbilical Vein Endothelial Cells in vitro

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Chinese Journal of Integrative Medicine 2018年第7期24卷 494-501页

作者： XIN Qi-qi YANG Bin-rui ZHOU He-feng WANG Yan YI Bo-wen CONG Wei-hong LEE Simon Ming-Yuen CHEN Ke-ji clinical Medical College Beijing University of Chinese Medicine State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macao Laboratory of Cardiovascular Diseases Xiyuan Hospital China Academy of Chinese Medical Sciences Department of Pharmaceutical Preparation Xiyuan Hospital China Academy of Chinese Medical Sciences

Objective： To investigate the pro-angiogenic effects of paeoniflorin（PF） in a vascular insufficiency model of zebrafish and in human umbilical vein endothelial cells（HUVECs）. Methods： In vivo, the pro-angiogenic effects of PF were tested in a vascular insufficiency model in the Tg（fli-1：EGFP）y1 transgenic zebrafish. The 24 h post fertilization（hpf） embryos were pretreated with vascular endothelial growth factor（VEGF） receptor tyrosine kinase inhibitor Ⅱ（VRI） for 3 h to establish the vascular insufficiency model and then post-treated with PF for 24 h. The formation of intersegmental vessels（ISVs） was observed with a fluorescence microscope. The m RNA expression of fms-like tyrosine kinase-1（flt-1）, kinase insert domain receptor（kdr）, kinase insert domain receptor like（kdrl） and von Willebrand factor（v WF） were analyzed by real-time polymerase chain reaction（PCR）. In vitro, the pro-angiogenic effects of PF were observed in HUVECs in which cell proliferation, migration and tube formation were assessed. Results： PF（6.25–100 μmol/L） could rescue VRI-induced blood vessel loss in zebrafish and PF（25–100 μmol/L）, thereby restoring the m RNA expressions of flt-1, kdr, kdrl and v WF, which were down-regulated by VRI treatment. In addition, PF（0.001–0.03 μmol/L） could promote the proliferation of HUVECs while PF stimulated HUVECs migration at 1.0–10 μmol/L and tube formation at 0.3 μmol/L. Conclusion： PF could promote angiogenesis in a vascular insufficiency model of zebrafish in vivo and in HUVECs in vitro.

关键词： angiogenesis paeoniflorin zebrafish human umbilical vein endothelial cell

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