检索结果-南通市图书馆

chinese Journal of Natural medicines 2024年第7期22卷 582-598页

作者： JIA Kexin MA Zhi ZHANG Yinhao XIE Kaihong LI Jianan WU Jianzhi QU Jiaorong LI Fanghong LI Xiaojiaoyang school of Life Sciences Beijing University of Chinese MedicineBeijing 100029China school of chinese Materia Medica Beijing University of Chinese MedicineBeijing 100029China

Liver fibrosis is characterized by chronic inflammatory responses and progressive fibrous scar *** play a central role in the pathogenesis of hepatic fibrosis by reconstructing the immune *** Ⅱ(PIC Ⅱ),extracted from Picrorhizae Rhizoma,has demonstrated therapeutic potential for various liver ***,the mechanisms by which macrophage polarization initiates immune cascades and contributes to the development of liver fibrosis,and whether this process can be influenced by PIC Ⅱ,remain *** the current study,RNA sequencing and multiple molecular approaches were utilized to explore the underlying mechanisms of PIC Ⅱ against liver fibrosis in multidrug-resistance protein 2 knockout(Mdr2^(−/−))*** findings indicate that PIC Ⅱ activates M1-polarized macrophages to recruit natural killer cells(NK cells),potentially via the CXCL16-CXCR6 ***,PIC Ⅱ promotes the apoptosis of activated hepatic stellate cells(aHSCs)and enhances the cytotoxic effects of NK cells,while also reducing the formation of neutrophil extracellular traps(NETs).Notably,the anti-hepatic fibrosis effects associated with PIC Ⅱ were largely reversed by macrophage depletion in Mdr2^(−/−)***,our research suggests that PIC Ⅱ is a potential candidate for halting the progression of liver fibrosis.

关键词： Liver fibrosis PicrosideⅡ M1 macrophage Hepatic stellate cell Natural killer cell Neutrophil

Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

chinese Journal of Integrative medicine 2024年第7期30卷 664-672页

作者： LIU Su-su YU Tong QIAO Yan-fang GU Shu-xiao CHAI Xin-lou school of Traditional chinese medicine Beijing University of Traditional Chinese MedicineBeijing102401China

The prevalence of hyperlipidemia has increased significantly due to genetic, dietary, nutritional and pharmacological factors, and has become one of the most common pathological conditions in humans. Hyperlipidemia can lead to a range of diseases such as atherosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, and kidney failure, etc. High circulating low-density lipoprotein cholesterol (LDL-C) is one of the causes of hyperlipidemia. LDL-C in the blood binds to LDL receptor (LDLR) and regulates cholesterol homeostasis through endocytosis. In contrast, proprotein convertase subtilisin/kexin type 9 (PCSK9) mediates LDLR degradation via the intracellular and extracellular pathways, leading to hyperlipidemia. Targeting PCSK9-synthesizing transcription factors and downstream molecules are important for development of new lipid-lowering drugs. Clinical trials regarding PCSK9 inhibitors have demonstrated a reduction in atherosclerotic cardiovascular disease events. The purpose of this review was to explore the target and mechanism of intracellular and extracellular pathways in degradation of LDLR and related drugs by PCSK9 in order to open up a new pathway for the development of new lipid-lowering drugs.

关键词： hyperlipidemia proprotein convertase subtilisin/kexin type 9 low-density lipoprotein receptor intracellular pathway extracellular pathway

Differences in vascular endothelial function and serum proteome between obese people with phlegm-dampness constitution and balanced constitution

在线全文

学校读者我要写书评

暂无评论

Journal of Traditional chinese medicine 2024年第1期44卷 188-196页

作者： ZHU Linghui SUN Ziwei GUAN Yuanyuan LIU Meiyi ZHENG Yi YU Ruoxi WANG Qi LI Lingru school of chinese medicine Beijing University of Chinese MedicineBeijing 102488China National Institute of TCM Constitution and Preventive medicine Beijing University of Chinese MedicineBeijing 100029China

OBJECTIVE:To evaluate the extent of vascular endothelial dysfunction and preliminary identify serum protein biomarkers associated with obese individuals at risk for cardiovascular disease(CVD).METHODS:Fifteen obese volunteers with the phlegmdampness constitution or balanced constitution were recruited for this study *** clinical baseline data was collected,and the vascular endothelial function was evaluated using the EndoPAT?.Blood samples were collected for the serum proteome *** differences in the serum protein expression levels between the two groups were detected and the protein interaction network analysis,correlation analysis,receiver operating characteristic(ROC)curve analysis,and random forest model investigation were ***:There were no statistical differences found in the baseline *** vascular endothelial function,the reactive hyperemia index(RHI)of the phlegm-dampness constitution obese group was significantly lower than that of the balanced constitution obese group(1.46±0.30 vs 2.82±0.78,P<0.0001),indicating vascular endothelial *** are 66 differentially expressed serum proteins between the two *** A2(Apo A2),angiotensin-converting enzyme 2(ACE-2),interleukin-33(IL-33),and forkhead box P3(FoxP3)showed significant differences and area under curve values of their ROC curves were greater than 0.7 and correlated significantly with ***:Vascular endothelial dysfunction was present in the phlegm-dampness constitution obese ***,alterations in the expression levels of key serum proteins,including Apo A2,ACE-2,IL-33,and Fox P3 could serve as potential biomarkers in the obese population at risk of CVD.

关键词： obesity phlegm-dampness constitution vascular endothelial function proteome reactive hyperemia index

Suppressing FXR promotes antiviral effects of bile acids via enhancing the interferon transcription

在线全文

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2024年第8期14卷 3513-3527页

作者： Xue Liang Kunpeng Liu Xin Jia Cuiqin Cheng Meiqi Zhang Lingdong Kong Qiqi Li Zhe Liu Min Li Junliang Li Yao Wang Anlong Xu school of Life Sciences Beijing University of Chinese MedicineBeijing 100029China Guangxi Key Laboratory of Special Biomedicine School of MedicineGuangxi UniversityNanning 530004China beijing Academy of Traditional chinese medicine Beijing University of Chinese MedicineBeijing 100029China beijing Research Institute of chinese medicine Beijing University of Chinese MedicineBeijing 100029China

Bile acids(BAs)are natural metabolites in mammals and have the potential to function as drugs against viral ***,the limited understanding of chenodeoxycholic acid(CDCA)receptors and downstream signaling,along with its lower suppression efficiency in inhibiting virus infection limits its clinical *** this study,we demonstrate that farnesoid X receptor(FXR),the receptor of CDCA,negatively regulates interferon signaling,thereby contributing to the reduced effectiveness of CDCA against virus *** deficiency or pharmacological inhibition enhances interferon signaling activation to suppress virus ***,FXR impairs the DNA binding and transcriptional abilities of activated interferon regulatory factor 3(IRF3)through *** IRF3 transcriptional activity by FXReIRF3 interaction significantly undermines the expression of Interferon Beta 1(IFNB1)and the antiviral response of cells,especially upon the CDCA *** FXR-deficient cells,or when combined with Z-guggulsterone(GUGG)treatment,CDCA exhibits a more potent ability to restrict virus ***,these findings suggest that FXR serves as a limiting factor for CDCA in inhibiting virus replication,which can be attributed to the“signaling-brake”roles of FXR in interferon *** FXR inhibition represents a promising pharmaceutical strategy for the clinical application of BAs metabolites as antiviral drugs.

关键词： Bile acids FXR IRF3 Interferon transcription RNA virus Z-guggulsterone Broad-spectrum antiviral activity Synergistic inhibitory effect

The“depict”strategy for discovering new compounds in complex matrices:Lycibarbarspermidines as a case

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Pharmaceutical Analysis 2024年第3期14卷 416-426页

作者： Chen Han Zhixin Zhang Zhiyang Feng Chuanjia Zhai Xuejiao Li Yulian Shi Xiang Li Miao Li Ying Wang Gan Luo Xiaoyan Gao Department of chinese medicine Analysis School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing102488China

The comprehensive detection and identification of active ingredients in complex matrices is a crucial *** chromatography coupled with high-resolution mass spectrometry(LC-HRMS)is the most prominent analytical platform for the exploration of novel active compounds from complex ***,the LC-HRMS-based analysis workflow suffers from several bottleneck issues,such as trace content of target compounds,limited acquisition for fragment information,and uncertainty in interpreting relevant MS2 *** are vital antioxidant active ingredients in Lycii Fructus,while the reported structures are merely focused on dicaffeoylspermidines due to their low *** comprehensively detect the new structures of lycibarbarspermidine derivatives,a“depict”strategy was developed in this ***,potential new lycibarbarspermidine derivatives were designed according to the biosynthetic pathway,and a comprehensive database was established,which enlarged the coverage of lycibarbarspermidine ***,the polarity-oriented sample preparation of potential new compounds increased the concentration of the target ***,the construction of the molecular network based on the fragmentation pathway of lycibarbarspermidine derivatives broadened the comprehensiveness of ***,the weak response signals were captured by data-dependent scanning(DDA)followed by parallel reaction monitoring(PRM),and the efficiency of acquiring MS2 fragment ions of target compounds was significantly *** on the integrated strategy above,210 lycibarbarspermidine derivatives were detected and identified from Lycii Fructus,and in particular,170 potential new compounds were structurally *** integrated strategy improved the sensitivity of detection and the coverage of low-response components,and it is expected to be a promising pipeline for discovering new compounds.

关键词： Mass spectrometric detection Weak response signals Complex matrices Novel lycibarbarspermidines

Molecular characterization and structure basis of a malonyltransferase with both substrate promiscuity and catalytic regiospecificity from Cistanche tubulosa

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2024年第5期14卷 2333-2348页

作者： Xiao Liu Yuyu Liu Xiping Xu Wenqian Huang Yaru Yan Yingxia Wang Weisheng Tian Ting Mo Xiaoxue Cui Jun Li She-Po Shi Pengfei Tu Modern Research Center for Traditional chinese medicine Beijing Research Institute of Chinese MedicineBeijing University of Chinese MedicineBeijing 100029China Modern Research Center for Traditional chinese medicine School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing 100029China

Enzymatic malonylation of natural glycosides provides a promising alternative method for drug-like malonylated glycosides ***,the catalytic potential and structural basis of plant malonyltransferase are far from being fully *** work identified a new malonyltransferase CtMaT1 from Cistanche *** displayed unprecedented mono-and/or di-malonylation activity toward diverse glucosides with different aglycons.A“one-pot”system by CtMaT1 and a malonyl-CoA synthetase was established to biosynthesize nine new malonylated *** investigations revealed that CtMaT1 possesses an adequately spacious acyl-acceptor pocket capable of accommodating diverse ***,it recognizes malonyl-CoA through strong electrotactic and hydrogen ***/MM calculation revealed the H167-mediated SN2 reaction mechanism of CtMaT1,while dynamic simulations detected the formation of stable hydrogen bonds between the glucose-6-OH group and H167,resulting in its high malonylation *** energy profiles of two isomeric glycosides highlighted lower reaction energy barriers towards glucoside substrates,emphasizing CtMaT1's preference for ***,a mutant CtMaT1H36A with notably increased di-malonylation activity was *** underlying molecular mechanism was illuminated through MM/GBSA binding free energy *** study significantly advances the understanding of plant acyltransferases from both functional and protein structural perspectives,while also providing a versatile tool for enzymatic malonylation applications in pharmacology.

关键词： Plant acyltransferase Malonyltransferase Malonylated glycosides Enzymatic catalysis Enzyme promiscuity

Investigation of the active ingredients and mechanism of Shuangling extract in dextran sulfate sodium salt induced ulcerative colitis mice based on network pharmacology and experimental verification

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Traditional chinese medicine 2024年第3期44卷 478-488页

作者： CHU Mengzhen WANG Yu LIN Zhijian Lyu Jintao ZHANG Xiaomeng ZHANG Bing Department of Clinical chinese Pharmacy School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing 102488China

OBJECTIVE: To explore the pharmacodynamic effects and potential mechanisms of Shuangling extract against ulcerative colitis(UC). METHODS: The bioinformatics method was used to predict the active ingredients and action targets of Shuangling extract against UC in mice. And the biological experiments such as serum biochemical indexes and histopathological staining were used to verify the pharmacological effect and mechanism of Shuangling extract against UC in mice. RESULTS: The Shuangling extract reduced the levels of seruminterleukin-1β(IL-1β), tumor necrosis factor-α(TNF-N), interleukin-6(IL-6) and other inflammatory factors in UC mice and inhibited the inflammatory response. AKT Serine/threonine Kinase 1 and IL-6 may be the main targets of the anti-UC action of Shuangling extract, and the TNF signaling pathway, Forkhead box O signaling pathway and T-cell receptor signaling pathway may be the main signaling pathways. CONCLUSION: The Shuangling extract could inhibit the inflammatory response induced by UC and regulate intestinal immune function through multiple targets and multiple channels, which provided a new option and theoretical basis for anti-UC.

关键词： colitis ulcerative pharmacodynamic study network pharmacology molecular docking simulation Shuangling extract

Artificial Intelligence and Network Pharmacology Reveal the Medication Rules of Professor Wang Yu-Ying in the Treatment of Climacteric Syndrome

在线全文

学校读者我要写书评

暂无评论

World Journal of Traditional chinese medicine 2024年第2期10卷 180-190页

作者： Meng-Yuan Hu Tian-Xing Yi Qi-Rui Liu Xin-Yu Zhang Ai-Ping Chen Yu-Ying Wang Yi Lu school of Traditional chinese medicine Beijing University of Chinese MedicineBeijingChina

Objective: The objective of this study was to explore the medication rules and academic ideas of Professor Wang Yu-Ying in the treatment of climacteric syndrome(CLS) and to predict new prescriptions. Materials and Methods: The characteristics of frequency, clustering, four properties, and five flavors were analyzed, and new prescriptions were predicted through an artificial intelligence(AI)-based method. The potential pathways of new prescriptions were explored through network pharmacology-based analysis. Results: The top 16 medicinals used by Professor Wang Yu-Ying in the treatment of CLS included Danggui, Longgu, Muli, Fuling, Chuanxiong, Gancao, Xiangfu, and Tusizi. The AI method was applied to predict the basic prescription for treating CLS: Danggui 15 g, Duanlonggu 30 g, Duanmuli 30 g, Fuling 28 g, Chuanxiong 10 g, Gancao 6 g, Xiangfu 12 g, Tusizi 14 g, etc., Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the pathogenesis of CLS might be related to the estrogen pathway, involving typical steroid responses. Conclusions: This study summarized Professor Wang's medication experience in the treatment of CLS based on the data mining of clinical diagnoses and treatment cases. The AI method was used to predict the new prescription of CLS treatment, which was found to be reasonable by network pharmacology studies on its multi-target and multi-pathway mechanisms.

关键词： Artificial intelligence climacteric syndrome medication rules network pharmacology Professor Wang Yu-Ying

Jackknife Model Averaging for Composite Quantile Regression

在线全文

学校读者我要写书评

暂无评论

Journal of Systems Science & Complexity 2024年第4期37卷 1604-1637页

作者： YOU Kang WANG Miaomiao ZOU Guohua school of Mathematical Sciences Capital Normal UniversityBeijing 100089China school of chinese Materia Medica Beijing University of Chinese MedicineBeijing 100105China

In this paper,the authors propose a frequentist model averaging method for composite quantile regression with diverging number of *** from the traditional model averaging for quantile regression which considers only a single quantile,the proposed model averaging estimator is based on multiple *** well-known delete-one cross-validation or jackknife approach is applied to estimate the model *** resultant jackknife model averaging estimator is shown to be asymptotically optimal in terms of minimizing the out-of-sample composite final prediction *** studies are conducted to demonstrate the finite sample performance of the new model averaging *** proposed method is also applied to the analysis of the stock returns data and the wage data.

关键词： Asymptotic optimality composite quantile regression cross-validation model averaging

Epigenetic modification in liver fibrosis:Promising therapeutic direction with significant challenges ahead

在线全文

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2024年第3期14卷 1009-1029页

作者： Runping Liu Yajing Li Qi Zheng Mingning Ding Huiping Zhou Xiaojiaoyang Li school of chinese Materia Medica Beijing University of Chinese MedicineBeijing 102400China school of Life Sciences Beijing University of Chinese MedicineBeijing 102400China Department of Microbiology and Immunology Virginia Commonwealth UniversityRichmondVA 22460USA

Liver fibrosis,characterized by scar tissue formation,can ultimately result in liver ***’s a major cause of morbidity and mortality globally,often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver ***,current treatment options are limited,highlighting the urgent need for the development of new *** a reversible regulatory mechanism,epigenetic modification is implicated in many biological processes,including liver *** the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases,although the current evidence is still *** review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications,including DNA methylation,histone modification,and RNA modification,in liver fibrotic *** potential cooperation of different epigenetic modifications in promoting fibrogenesis was also ***,available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were *** summary,elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.

关键词： Liver fibrosis Epigenetics regulation DNA methylation Histone acetylation Histone methylation mRNA methylation Non-coding RNA Drug development