Acta materia medica最新文献_第2页

Arenobufagin suppresses the progression of early-stage hepatocellular carcinoma by inhibiting EpCAM-mediated tumor stemness arennobufagin通过抑制epcam介导的肿瘤干性抑制早期肝细胞癌的进展

Acta materia medica Pub Date : 2025-01-01 DOI: 10.15212/amm-2024-0064

Lijuan Deng, Lifang Zou, Chunhong Zhou, Fan Yang, Fen Ouyang, Zhu Y, Huihui Cao, Min Hu, Xiaoshen Zhang, Junshan Liu

{"title":"Arenobufagin suppresses the progression of early-stage hepatocellular carcinoma by inhibiting EpCAM-mediated tumor stemness","authors":"Lijuan Deng, Lifang Zou, Chunhong Zhou, Fan Yang, Fen Ouyang, Zhu Y, Huihui Cao, Min Hu, Xiaoshen Zhang, Junshan Liu","doi":"10.15212/amm-2024-0064","DOIUrl":"https://doi.org/10.15212/amm-2024-0064","url":null,"abstract":"Epithelial cell adhesion molecule (EpCAM) is a biomarker for epithelial cell-derived tumors. However, the specific role of EpCAM itself in early-stage hepatocellular carcinoma progression remains unclear, and small molecules targeting EpCAM have not yet been reported. Here, the protein expression profile of EpCAM in tumor-adjacent regions was found to be higher than that in tumor regions, and to be positively associated with the progression of early-stage liver cancer, as well as high frequency of recurrence, cirrhosis, lymph node metastasis, microvascular invasion and cancer stemness, in 68 patients with hepatocellular carcinoma (HCC). In vitro , EpCAM enhanced cancer cell stemness, as reflected by increased abilities of proliferation, self-renewal, migration and invasion, which was counteracted by arenobufagin. Furthermore, arenobufagin inhibited the viability of Hep3B and Huh7 cells with IC 50 values of 36.4 nM and 123.4 nM after 72 h of treatment, respectively. Molecular docking data further indicated that arenobufagin binds EpCAM. Moreover, arenobufagin inhibited early progression of HCC through EpCAM in a zebrafish xenograft tumor model mimicking early-stage hepatocellular carcinoma without blood vessels in vivo . This study supports a tumor-promoting role of EpCAM in early-stage hepatocellular carcinoma by facilitating cancer stemness and suggests that arenobufagin might be promising candidate for EpCAM inhibition.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147333428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative drug-drug interactions of berberine and astragaloside IV in normal and type 2 diabetes mellitus rats based on UPLC-QqQ-MS/MS 基于UPLC-QqQ-MS/MS的小檗碱与黄芪甲苷在正常与2型糖尿病大鼠体内的药物相互作用比较

Acta materia medica Pub Date : 2025-01-01 DOI: 10.15212/amm-2024-0078

Yan Lei, Jiaqi Xie, Zhongshui Xie, Xiaojun Zhao, Jianmei Huang, Can Wang

{"title":"Comparative drug-drug interactions of berberine and astragaloside IV in normal and type 2 diabetes mellitus rats based on UPLC-QqQ-MS/MS","authors":"Yan Lei, Jiaqi Xie, Zhongshui Xie, Xiaojun Zhao, Jianmei Huang, Can Wang","doi":"10.15212/amm-2024-0078","DOIUrl":"https://doi.org/10.15212/amm-2024-0078","url":null,"abstract":"The UPLC-QqQ-MS/MS method was established, validated, and used for the simultaneous detection of berberine (BBR), astragaloside IV (AST), and the main metabolites to demonstrate the comparative pharmacokinetics of BBR and AST in normal and T2DM rats. BBR and AST had reduced the internal exposure of each other and their main metabolites in normal rats. However, AST had few significant effects on the pharmacokinetic parameters of BBR and the main metabolites in T2DM rats. Similarly, BBR had no significant effect on the pharmacokinetic parameters of AST but significantly increased the exposure to cycloastragenol (CAG) in vivo . Molecular docking of BBR and AST with the P-glycoprotein (P-gp) was performed, which indicated that both BBR and AST are potential substrates for P-gp. The differences in gut microbiota between normal and T2DM rats were compared by 16S rRNA sequencing. Git microbiota that could produce β-glucosidase and β-xylosidase were highly abundant in T2DM rats. The current study indicated that BBR and AST had reduced oral bioavailability. The gut microbiota was enriched in the intestines of T2DM rats and promoted the hydrolysis of AST to produce CAG, while the drug-drug interaction between AST and BBR was blocked.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.scienceopen.com/document_file/b323a2e5-71b9-45a5-b6ec-69bdba5facee/ScienceOpen/amm20240078.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147879961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

New generation estrogen receptor-targeted agents in breast cancer: present situation and future prospectives. 乳腺癌中的新一代雌激素受体靶向药物：现状与前景。

Acta materia medica Pub Date : 2024-02-21 Epub Date: 2024-03-15 DOI: 10.15212/amm-2024-0006

Jian Min, Xin Liu, Rouming Peng, Chun-Chi Chen, Wei Wang, Rey-Ting Guo

引用次数: 0

Application of PROTACs in Target Identification and Target Validation. PROTACs 在目标识别和目标验证中的应用。

Acta materia medica Pub Date : 2024-02-21 Epub Date: 2024-03-21 DOI: 10.15212/amm-2024-0010

Yang Liu, Jing Liang, Rui Zhu, Yueying Yang, Yali Wang, Wenyi Wei, Hua Li, Lixia Chen

引用次数: 0

The andrographolide derivative, AND7, and TRAIL combination attenuates acute lymphoblastic leukemia through P53-regulated ROS accumulation 穿心莲内酯衍生物、AND7和TRAIL联合通过p53调控的ROS积累来减轻急性淋巴细胞白血病

Acta materia medica Pub Date : 2024-01-01 DOI: 10.15212/amm-2024-0008

Letian Xu, Yuting Zhou, Rui Ma, Xinqin Guo, Hao Chen, Lei Fan, Xiaoming Wang

{"title":"The andrographolide derivative, AND7, and TRAIL combination attenuates acute lymphoblastic leukemia through P53-regulated ROS accumulation","authors":"Letian Xu, Yuting Zhou, Rui Ma, Xinqin Guo, Hao Chen, Lei Fan, Xiaoming Wang","doi":"10.15212/amm-2024-0008","DOIUrl":"https://doi.org/10.15212/amm-2024-0008","url":null,"abstract":"Acute lymphoblastic leukemia (ALL) is a malignant disease of the hematologic system. The current treatment is based on chemotherapeutic drugs, which are becoming less effective due to drug resistance. TNF-related apoptosis-inducing ligand (TRAIL) is an apoptotic protein used to treat cancer that does not affect healthy cells. In recent years, however, ALL cells (e.g., U937) have become more resistant to TRAIL. A novel andrographolide derivative (AND7) with high efficiency and low toxicity was synthesized and combined with TRAIL after the optimal combination ratio was screened using U937 cells. We used peripheral blood mononuclear cells (PBMCs) from patients before the initial treatment of ALL as a model and PBMCs from healthy subjects as a control to determine the mechanism underlying ALL treatment. AND7/TRAIL combination treatment was shown to prevent the original TRAIL-resistant cells from activating the caspase-8/caspase-3 pathway through DR4/DR5 and promote apoptosis via expression of ROS and the apoptotic gene, P53, to achieve an anti-cancer effect. Notably, this study demonstrated that the AND7/TRAIL combination enhanced the anti-cancer effect of AND7 and improved TRAIL resistance. Therefore, the AND7/TRAIL combination is promising for treating ALL and lays the foundation for clinical research.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.scienceopen.com/document_file/972c322f-5a91-4c2a-b660-c5a6a554a7b5/ScienceOpen/amm20240008.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147909052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Multi-omics strategy reveals that Cordyceps sinensis ameliorates sepsis-associated acute kidney injury via reprogramming of mitochondrial energy metabolism and macrophage polarization 多组学研究表明，冬虫夏草通过线粒体能量代谢重编程和巨噬细胞极化改善脓毒症相关急性肾损伤

Acta materia medica Pub Date : 2024-01-01 DOI: 10.15212/amm-2024-0018

Lin Chen, Tong Yang, Jiangpeng Wu, Guangqing Cheng, Minghong Zhao, Yanyan Zhou, Yin Kwan Wong, Junzhe Zhang, Qiuyan Guo, Huan Tang, Jigang Wang

{"title":"Multi-omics strategy reveals that Cordyceps sinensis ameliorates sepsis-associated acute kidney injury via reprogramming of mitochondrial energy metabolism and macrophage polarization","authors":"Lin Chen, Tong Yang, Jiangpeng Wu, Guangqing Cheng, Minghong Zhao, Yanyan Zhou, Yin Kwan Wong, Junzhe Zhang, Qiuyan Guo, Huan Tang, Jigang Wang","doi":"10.15212/amm-2024-0018","DOIUrl":"https://doi.org/10.15212/amm-2024-0018","url":null,"abstract":"Cordyceps sinensis (CS) has been widely used as a dietary supplement or traditional medicine for the prevention, treatment, and prognostication of various diseases, because of its pleiotropic pharmacological properties. However, the potential pharmacological action of CS in sepsis-associated acute kidney injury (S-AKI) remains poorly understood. Herein, we investigated the potential pharmacological action of CS against S-AKI and the underlying mechanisms. CS treatment effectively ameliorated renal dysfunction and injury in mice with lipopolysaccharide (LPS)-induced S-AKI, as indicated by the suppression of inflammatory cytokine expression and secretion. Multi-omic analyses suggested that the promotion of mitochondrial energy metabolism might be a potential mechanism through which CS protects mice against S-AKI induced by LPS. Subsequent validation assays confirmed that CS treatment substantially restored the activity of mitochondrial complexes, mitochondrial membrane potential, and ATP production. Moreover, CS concomitantly promoted transition of M1 macrophages to M2 macrophages with increased oxidative phosphorylation, thus indicating that macrophage polarization may also be a potential target for S-AKI treatment. Our findings demonstrated that CS significantly ameliorated renal injury and inflammation in S-AKI by regulating mitochondrial energy metabolism and macrophage polarization, thus providing new insights into the clinical use of CS for the prevention and treatment of S-AKI.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.scienceopen.com/document_file/7e1f22ce-6e96-440a-9f4c-3aa7a5de0239/ScienceOpen/amm20240018.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147910771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Identification of GPR35-associated metabolic characteristics through LC-MS/MS-based metabolomics and lipidomics 通过LC-MS/MS-based代谢组学和脂质组学鉴定gpr35相关代谢特征

Acta materia medica Pub Date : 2024-01-01 DOI: 10.15212/amm-2023-0046

Qiqing Zhang, Xian Zhao, Siyuan Qin, Qinwen Xiao, Yuan Tian, Zunjian Zhang, Pei Zhang, Fengguo Xu

{"title":"Identification of GPR35-associated metabolic characteristics through LC-MS/MS-based metabolomics and lipidomics","authors":"Qiqing Zhang, Xian Zhao, Siyuan Qin, Qinwen Xiao, Yuan Tian, Zunjian Zhang, Pei Zhang, Fengguo Xu","doi":"10.15212/amm-2023-0046","DOIUrl":"https://doi.org/10.15212/amm-2023-0046","url":null,"abstract":"G protein-coupled receptor 35 (GPR35) has gained increasing attention as a promising target in treating inflammatory and gastrointestinal tract conditions, cardiovascular diseases, and cancer. Metabolites including kynurenic acid, lysophosphatidic acids, chemokine 17, and 5-hydroxyindole acetic acid have been suggested to be endogenous ligands of GPR35. However, little is known regarding the downstream metabolic characteristics upon GPR35 regulation. Herein, four GPR35 interventions in cell models, comprising GPR35 knock-down, over-expression, activation, or inhibition, were established through lentiviral transduction, or the use of a potent agonist (pamoic acid) or antagonist (ML194). Targeted metabolomics and pseudotargeted lipidomics were performed on these cell models to capture GPR35-associated metabolites and lipids. Levels of 75 metabolites and 204 lipids were significantly altered in response to one or more GPR35 interventions. Levels of metabolites involved in fatty acid β-oxidation and phosphatidylethanolamine metabolism were notably altered. This study reports the first exploration of the metabolic characteristics of GPR35, and may aid in understanding of the potential mechanisms and functions of GPR35 in various physiological and pathological conditions.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.scienceopen.com/document_file/d7ace878-ba6b-4b5d-a665-2a6198dfbe68/ScienceOpen/amm20230046.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147892474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Macrophage differentiation in enhancing hematopoietic function of ribonucleic acid for injection II via multi-omics analysis 巨噬细胞分化增强注射用核糖核酸造血功能的多组学分析

Acta materia medica Pub Date : 2024-01-01 DOI: 10.15212/amm-2024-0001

Yuan Li, Meng Teng, Siyu Li, Hongxin Yang, Yuebo Zhang, Meihua Cui, Lanzhou Li, Di Wang

引用次数: 3

Exploring the efficacious subfractions and underlying mechanisms of Herba Siegesbeckiae against myocardial ischemia/reperfusion injury via the UCHL5/NLRP3 pathway 通过UCHL5/NLRP3途径探讨茜草抗心肌缺血再灌注损伤的有效亚组分及其机制

Acta materia medica Pub Date : 2024-01-01 DOI: 10.15212/amm-2024-0030

Xue-Fen Wu, Huan Xia, Wanting Li, Jie Chen, Linnan Zhou, Qian Zhang, Hongcai Shang, Gui‐Yang Xia, Xiao‐Hong Wei, Sheng Lin

{"title":"Exploring the efficacious subfractions and underlying mechanisms of Herba Siegesbeckiae against myocardial ischemia/reperfusion injury via the UCHL5/NLRP3 pathway","authors":"Xue-Fen Wu, Huan Xia, Wanting Li, Jie Chen, Linnan Zhou, Qian Zhang, Hongcai Shang, Gui‐Yang Xia, Xiao‐Hong Wei, Sheng Lin","doi":"10.15212/amm-2024-0030","DOIUrl":"https://doi.org/10.15212/amm-2024-0030","url":null,"abstract":"Herba Siegesbeckiae (HS) has been traditionally used for managing cardio- and cerebro-vascular diseases. Our previous study demonstrated that HS ameliorates myocardial ischemia/reperfusion (I/R) injury. Also, the differentially expressed proteins between HS and I/R groups were shown to be displayed as UCHL5 and were mainly enriched in the NLRP3 inflammasome pathway. However, further elucidation is required concerning the effective subfractions, constituents, and HS influence on the UCHL5/NLRP3 pathway. A co-immunoprecipitation assay and UCHL5 overexpression in cardiomyocyte explores were used to determine the interaction between UCHL5 and NLRP3 during myocardial I/R. The water extracts of HS were subjected to column chromatography using a macroporous adsorption resin. Four HS subfractions (HS-A [H 2 O elution], HS-B [20% ethanol elution], HS-C [50% ethanol elution], and HS-D [95% ethanol elution]) were obtained in this study. HS-C exhibited the most significant protective effect against myocardial I/R and improved I/R injury in vivo . HS-C markedly restrained the expression of UCHL5 and NLRP3 and resisted the role of UCHL5/NLRP3 in the pathogenesis of I/R. Eleven main constituents of HS-C were identified, among which kirenol best displayed anti-I/R injury activity and binding energy. Kirenol accounted for 62.4% of HS-C. Thus, HS-C effectively protected against myocardial I/R injury, which was attributed to mitigation of the UCHL5/NLRP3 pathway and kirenol was identified as the core active constituent.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.scienceopen.com/document_file/9bb0b69a-ec75-4f46-abdd-5f71bff3f6b0/ScienceOpen/amm20240030.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147921164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Pristimerin inhibits thioredoxin reductase in the treatment of non-small cell lung cancer pritimin抑制硫氧还蛋白还原酶治疗非小细胞肺癌

Acta materia medica Pub Date : 2024-01-01 DOI: 10.15212/amm-2024-0015

Yajun Chu, Qianhe Xu, Xiedong Zhou, Qiuying Nie, Xiaojun Yao, Jianguo Fang, Junmin Zhang

{"title":"Pristimerin inhibits thioredoxin reductase in the treatment of non-small cell lung cancer","authors":"Yajun Chu, Qianhe Xu, Xiedong Zhou, Qiuying Nie, Xiaojun Yao, Jianguo Fang, Junmin Zhang","doi":"10.15212/amm-2024-0015","DOIUrl":"https://doi.org/10.15212/amm-2024-0015","url":null,"abstract":"Elevated cellular oxidative stress is a common marker of cancer cell dysregulation caused by malignant transformation. Thioredoxin reductase (TrxR, encoded by TXNRD ) is a crucial enzyme that regulates cellular oxidative stress and the survival of many types of cancer cells. Therefore, targeting TrxR may lead to selective cell death in cancer cells. Pristimerin, a plant triterpenoid, increases the accumulation of reactive oxygen species (ROS) in cells, but its specific regulatory mechanism is unclear. Herein, we found that pristimerin selectively targets TrxR and subsequently induces apoptosis in human non-small cell lung cancer cells, and inhibits tumor growth in vivo with low toxicity to normal cells. Pristimerin was found to inhibit cancer cell growth primarily by inhibiting cellular TrxR, thereby compromising TrxR’s antioxidant function in cells and resulting in the accumulation of oxidized Trx. Furthermore, excessive ROS accumulation stimulated by pristimerin triggered tumor-specific amplification of oxidative stress in cancer cells and ultimately led to targeted destruction of cancer cells. Our data may support the development of potential therapeutic molecules as selective anticancer agents targeting highly enriched TrxR in cancer cells.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147878532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7