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Biological Evaluation of Lysionotin:a Novel Inhibitor of 5-Lipoxygenase for Anti-glioma

chinese Journal of integrative medicine 2024年第9期30卷 826-834页

作者： SHAO Xin-xin CHEN Cong LIU Jie LI Qing-jun HE Shan QI Xiang-hua FU Xian-jun WANG Zhen-guo The First Clinical College of medicine Shandong University of Traditional Chinese MedicineJinan250355China Institute for Literature and Culture of chinese medicine Shandong University of Traditional Chinese MedicineJinan250355China Key Laboratory of Classical Theory of traditional chinese medicine Ministry of EducationShandong University of Traditional Chinese MedicineJinan250355China College of Pharmacy Shandong University of Traditional Chinese MedicineJinan250355China Experimental Center Shandong University of Traditional Chinese MedicineJinan250355China Neurology Department Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan250014China Marine traditional chinese medicine Research Center Qingdao Academy of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineQingdao266114Shandong ProvinceChina

Objective:To explore the potential mechanism of lysionotin in treating ***:First,target prediction based on Bernoulli Naïve Bayes profiling and pathway enrichment was used to predict the biological activity of *** binding between 5-lipoxygenase(5-LO)and lysionotin was detected by surface plasmon resonance(SPR)and molecular docking,and the inhibitory effects of lysionotin on 5-LO and proliferation of glioma were determined using enzyme inhibition assay in vitro and cell viability analysis,***,the pharmaceutical effect of lysionotin was explored by cell survival rate analysis and liquid chromatography with tandem mass spectrometry(LC-MS/MS).The protein expression,intracellular calcium ion concentration and cytoskeleton detection were revealed by Western blot,flow cytometry and fluorescence labeling,***:Target prediction and pathway enrichment revealed that lysionotin inhibited 5-LO,a key enzyme involved in the arachidonic acid metabolism pathway,to inhibit the proliferation of *** docking results demonstrated that 5-LO can be binding to lysionotin through hydrogen bonds,forming bonds with His600,Gln557,Asn554,and *** analysis further confirmed the interaction between 5-LO and ***,enzyme inhibition assay in vitro and cell survival rate analysis revealed that 50%inhibition concentration of lysionotin and the median effective concentration of lysionotin were 90 and 16.58µmol/L,respectively,and the results of LC-MS/MS showed that lysionotin inhibited the production of 5S-hydroperoxy-eicosatetraenoic acid(P<0.05),and moreover,the LC-MS/MS results indicated that lysionotin can enter glioma cells well(P<0.01)and inhibit their *** blot analysis demonstrated that lysionotin can inhibit the expression of 5-LO(P<0.05)and downstream leukotriene B4 receptor(P<0.01).In addition,the results showed that lysionotin affected intracellular calcium ion concentration by inh

关键词： 5-lipoxygenase inhibitor lysionotin 5-lipoxygenase leukotriene B4 calcium ion cytoskeleton

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Research Advance of chinese medicine in Treating Atherosclerosis:Focus on Lipoprotein-Associated Phospholipase A2

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chinese Journal of integrative medicine 2024年第3期30卷 277-288页

作者： WANG Lu-ming ZHANG Wen-lan LYU Nuan SUO Yan-rong YANG Lin YU Bin JIANG Xi-juan School of integrative medicine Tianjin University of Traditional Chinese MedicineTianjin301617China Department of traditional chinese medicine Ganzhou People’s HospitalGanzhouJiangxi Province341000China School of Medical Technology Tianjin University of Traditional Chinese MedicineTianjin301617China

As a serious cardiovascular disease,atherosclerosis(AS)causes chronic inflammation and oxidative stress in the body and poses a threat to human ***-associated phospholipase A2(Lp-PLA2)is a member of the phospholipase A2(PLA2)family,and its elevated levels have been shown to contribute to ***-PLA2 is closely related to a variety of lipoproteins,and its role in promoting inflammatory responses and oxidative stress in AS is mainly achieved by hydrolyzing oxidized phosphatidylcholine(ox PC)to produce lysophosphatidylcholine(lyso PC).Moreover,macrophage apoptosis within plaque is promoted by localized Lp-PLA2 which also promotes plaque *** paper reviews those researches of chinese medicine in treating AS via reducing Lp-PLA2 levels to guide future experimental studies and clinical applications related to AS.

关键词： lipoprotein-associated phospholipase A2 atherosclerosis inflammation oxidative stress apoptosis chinese medicine

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Electroacupuncture activates AMPKa1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer's disease by regulating hippocampal mitochondrial dynamics

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Journal of integrative medicine 2024年第5期22卷 588-599页

作者： Wei-wei Jia Hua-wei Lin Min-guang Yang Ya-ling Dai Yan-yi Ding Wen-shan Xu Si-nuo Wang Ya-jun Cao Sheng-xiang Liang Zhi-fu Wang Cong Chen Wei-lin Liu College of Rehabilitation medicine Fujian University of Traditional Chinese Medicine The Institute of Rehabilitation Industry Fujian University of Traditional Chinese Medicine National-Local Joint Engineering Research Center of Rehabilitation medicine Technology Fujian University of Traditional Chinese Medicine traditional chinese medicine Rehabilitation Research Center of State Administration of traditional chinese medicine Fujian University of Traditional Chinese Medicine

Objective: Studies have shown that electroacupuncture(EA) can alleviate cognitive impairments from Alzheimer's disease(AD) by regulating the expression of adenosine monophosphate-activated protein kinase(AMPK), but the specific mechanism involved remains to be elucidated. Therefore, this study explores the potential mechanism by which EA improves cognitive function from the perspective of mitochondrial ***: The four-month-old transgenic mice with amyloid precursor protein(APP)/presenilin 1(PS1)and AMPKa1-subunit conditional knockout(AMPKa1-cKO) were used for experiments. To evaluate the effects of EA treatment on cognitive function, the T-maze and Morris water maze were used. In addition,chemical exchange saturation transfer, thioflavin staining, transmission electron microscopy, mitochondrial membrane potential, and Western blotting were used to examine the potential mechanisms underlying the effects of EA on APP/PS1 ***: Both APP/PS1 mice and AMPKa1-cKO mice exhibited dysfunction in mitochondrial dynamics accompanied by learning and memory impairment. Inactivation of the AMPK/peroxisome proliferatoractivated receptor-γ coactivator-1a(PGC-1a) pathway increased pathological amyloid-β(Aβ) deposition and aggravated the dysfunction in mitochondrial dynamics. In addition, EA rescued learning and memory deficits in APP/PS1 mice by activating the AMPK/PGC-1a pathway, specifically by reducing pathological Aβ deposition, normalizing energy metabolism, protecting the structure and function of mitochondria,increasing the levels of mitochondrial fusion proteins, and downregulating the expression of fission proteins. However, the therapeutic effect of EA on cognition in APP/PS1 mice was hindered by ***: The regulation of hippocampal mitochondrial dynamics and reduction in Aβ deposition via the AMPK/PGC-1a pathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice.

关键词： Adenosine monophosphate-activated protein kinase Alzheimer’s disease Cognitive impairment Electroacupuncture Hippocampus Mitochondrial dynamics

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Babao Dan Inhibits Gastric Cancer Progression in vivo Through Multiple Signaling Pathways

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World Journal of traditional chinese medicine 2024年第1期10卷 14-21页

作者： Hai-Xia Shang Yi Fang Bin Guan Jian-Hua Guan Jun Peng Jin-Yan Zhao Jiu-Mao Lin Institute of Oncology of academy of integrative medicine Fujian University of Traditional Chinese MedicineFuzhouFujianChina Key Laboratory of integrative medicine of Fujian Province University Fujian University of Traditional Chinese MedicineFuzhouFujianChina Fujian Key Laboratory of integrative medicine on Geriatric Fujian University of Traditional Chinese MedicineFuzhouFujianChina Innovation and Transformation Center Fujian University of Traditional Chinese MedicineFuzhouFujianChina Xiamen traditional chinese medicine Co. Ltd.XiamenFujianChina

Objective:The aim of this study was to explore the effects of Babao dan(BBD),a traditional chinese medicine,on gastric cancer(GC)progression in *** and Methods:A subcutaneous xenograft mouse model of GC was established using MGC80-3 *** terminal deoxynucleotidyl transferase-mediated dUTP:2'-deoxyuridine 5'-triphosphate-biotin nick-end labeling method was adopted to detect cell apoptosis in *** expression levels of proteins associated with proliferation,apoptosis,and angiogenesis were measured by immunohistochemical staining or western blotting(WB).The activation and protein levels of p-c-Jun N-terminal kinase(JNK),p-p38,p-extracellular-regulated kinase 1/2,p-nuclear factor-κB(NF-κB),and p-STAT3 were examined by Bio-plex and ***:BBD significantly inhibited tumor growth in GC mouse models with no adverse effect on body weight or organ *** was also found that BBD significantly suppressed the proliferation of GC tumor cells,induced the apoptosis of tumor cells,and inhibited angiogenesis through inactivating with mitogen-activated protein kinase,NF-κB,and STAT3 ***:BBD exerts suppressive effects on GC tumor growth by regulating multiple pathways in vivo,which may provide a novel treatment option for GC therapy.

关键词： Babao dan gastric cancer multiple signaling pathways proliferation traditional chinese medicine

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Low Concentration of Wenyang Tonglin Decoction Promotes Conjugation and Transfer of Drug-Resistant Plasmids among Heterologous Strains

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chinese Journal of integrative medicine 2024年第8期30卷 721-728页

作者： WANG Bi-yan BU Hong-shi XIA Li-bo JIANG Xiang-yu TONG Yan-qing Department of traditional chinese medicine Changchun University of Traditional Chinese MedicineChangchun130000China

Objective To investigate the effect of low concentration of Wenyang Tonglin Decoction(WTD)on the binding conditions of R45 plasmid conjugative transfer under liquid phase conjugation and its *** Escherichia coli CP9(R45)and Staphylococcus aureus RN450RF were cultured in medium containing WTD,and their minimum inhibitory concentration(MIC)values were *** promoter fusion technology,*** CP9(R45)containing a promoter fusion was obtained.β-Galactosidase activity of TrfAp and TrbBp was tested,and the mRNA expression of regulatory factors(TrbA,KorA,and KorB)was detected by real-time fluorescent quantitative polymerase chain *** The MIC of *** CP9(R45)was 400 g/L and that of *** RN450RF was 200 g/*** the drug concentration in the culture medium was 200 g/L,the highest number of conjugants was(3.47±0.20)×10^(7) CFU/mL At 90 h of conjugation,the maximum number of conjugants was(1.15±0.06)×10^(8) CFU/mL When the initial bacterial concentration was 10^(8) CFU/mL,the maximum number of conjugants was(3.47±0.20)×10^(7) CFU/*** the drug concentration was 200 g/L,theβ-galactosidase activity of TrfAp and TrbBp significantly increased;the relative quantification of TrbA,KorA and KorB were significantly *** Low concentration of WTD promoted the development of bacterial resistance by affecting promoters and inhibiting the expression of regulatory factors.

关键词： urinary tract infection chinese medicine drug-resistant plasmid heterozygous strains conjugation transfer

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Molecular Mechanism of Polysaccharides Extracted from chinese medicine Targeting Gut Microbiota for Promoting Health

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chinese Journal of integrative medicine 2024年第2期30卷 171-180页

作者： ZHAO Wen-xiao WANG Tong ZHANG Ya-nan CHEN Qian WANG Yuan XING Yan-qing ZHENG Jun DUAN Chen-chen CHEN Lijun ZHAO Hai-jun WANG Shijun School of Nursing Shandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineJi'nan(250355)China Shandong Co-innovation Center of Classic traditional chinese medicine Formula Shandong University of Traditional Chinese MedicineJi'nan(250355)China College of traditional chinese medicine Shandong University of Traditional Chinese MedicineJinan(250355)China

The accumulating evidence revealed that gut microbiota plays an important role in pathological process of disease including obesity,type 2 diabetes mellitus,heart failure,and non-alcoholic fatty liver *** extracted from chinese medicine(CM)can not only alleviate pathological status but also promote health by anti-inflammatory,regulating immunity,lowering blood glucose and lipids,anti-cancer,and *** alterations of gut microbiota composition and metabolism pathways are the potential mechanisms of CM polysaccharides *** addition,they exert functions through gut-organ axis or play an indirect role by synergistic actions with other drugs or components mediated by gut *** review summarizes the molecular mechanisms of CM polysaccharides interacted with intestinal microbial inhabitants as potential prebiotics forpromoting health.

关键词： chinese medicine polysaccharides gut microbiota short-chain fatty acids lipopolysaccharides gut-organaxis synergistic actions

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

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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

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Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes

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chinese Journal of integrative medicine 2024年第3期30卷 222-229页

作者： ZHANG Shuo LI Hong-jin YANG Chun-mei LIU Liu SUN Xiao-ying WANG Jiao CHEN Si-ting LU Yi HU Man-qi YAN Ge ZHOU Ya-qiong MIAO Xiao LI Xin LI Bin Department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai200437China Institute of Dermatology Shanghai Academy of Traditional Chinese MedicineShanghai201203China Department of Integrated traditional chinese and Western medicine Shanghai Skin Disease HospitalTongji University School of MedicineShanghai200443China

Objective:To determine the role of Tripterygium wilfordii multiglycoside(TGW) in the treatment of psoriatic dermatitis from a cellular immunological ***:Mouse models of psoriatic dermatitis were established by imiquimod(IMQ).Twelve male BALB/c mice were assigned to MQ or IMQ+TGW groups according to a random number *** changes in vivo were assessed by hematoxylin and eosin *** of immune cells and cytokines in mice,as well as PAM212 cell proliferation in vitro were assessed by flow ***-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain ***:TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45^(+)cells,neutrophils and T lymphocytes(all P<0.01).Moreover,TGW significantly attenuated keratinocytes(KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin(IL)-17A,IL-23,tumor necrosis factor α,and chemokine(C-X-C motif) ligand 1(P<0.01 or P<0.05).Furthermore,it reduced the number of γδ T17 cells in skin lesion of mice and draining lymph nodes(P<0.01).Conclusions:TGW improved psoriasis-like inflammation by inhibiting KCs proliferation,as well as the associated immune cells and cytokine *** inhibited IL-17 secretion from γδ T cells,which improved the immune-inflammatory microenvironment of psoriasis.

关键词： psoriasis Tripterygium wilfordii multiglycoside γδT cells inflammation chinese medicine

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Efficacyand Safetyof Huashi Baidu Granules in Treating Patients with SARS-CoV-2Omicron Variant: A Single-Center Retrospective Cohort Study

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chinese Journal of integrative medicine 2024年第2期30卷 107-114页

作者： CHEN Cai-yu ZHANG Wen XU Xiang-ru PU Yu-ting TU Ya-dan PENG Wei YAO Xuan ZHOU Shuang FANG Bang-jiang Department of Emergency Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai(200032)China Department of Classical traditional chinese medicine Chongqing Hospital of Traditional Chinese MedicineChongqing(400021)China Acupuncture and Massage College Shanghai University of Traditional Chinese MedicineShanghai(201203)China Institute of Emergency and Critical Care medicine Shanghai University of Traditional Chinese MedicineShanghai(200032)China

Objective:To evaluate the efficacy and safety of Huashi Baidu Granules(HSBD)in treating patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron ***:A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd,*** COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group(HSBD users)and the control group(non-HSBD users).After propensity score matching in a 1:1 ratio,496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD *** in the treatment group were administrated HSBD(5 g/bag)orally for 1 bag twice a day for 7 consecutive *** in the control group received standard care and routine *** primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day *** outcomes included the hospitalized days,the time of the first nucleic acid negative conversion,and new-onset symptoms in asymptomatic *** events(AEs)that occurred during the study were *** subgroup analysis was conducted in vaccinated(378 HSBD users and 390 non-HSBD users)and unvaccinated patients(118 HSBD users and 106 non-HSBD users).Results:The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group[3 days(IQR:2-5 days)vs.5 days(IQR:4-6 days);P<0.01].The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7(91.73%vs.86.90%,P=0.014).Compared with the control group,the hospitalized days in the treatment group were significantly reduced[10 days(IQR:8-11 days)vs.11 days(IQR:10.25-12 days);P<0.01].The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups[3 days(IQR:2-4 days)vs.5 days(IQR:

关键词： Huashi Baidu Granule severe acute respiratory syndrome coronavirus 2 Omicron variant retrospective cohort trial chinese medicine

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Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia:Based on serum pharmacochemistry and network pharmacology

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Animal Models and Experimental medicine 2024年第3期7卷 259-274页

作者： Huirong Xu Meiyue Dong Ruikun Du Chengcheng Zhang Zinuo Chen Guangyu Tian Qinghua Cui Kejian Li College of traditional chinese medicine Shandong University of Traditional Chinese MedicineJinanChina Innovative Institute of chinese medicine and Pharmacy Shandong University of Traditional Chinese MedicineJinanChina Qingdao academy of chinese Medical Sciences Shandong University of Traditional Chinese MedicineQingdaoChina College of Pharmacy Shandong University of Traditional Chinese MedicineJinanChina

Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating *** present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network ***:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)*** intersection of blood component-related targets and disease-related targets was determined using Venny ***-protein interaction networks were constructed using the STRING *** Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway ***,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral ***:Fifteen compounds and 124 targets linked to viral pneumonia were detected in *** these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant *** vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 ***,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and ***:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.

关键词： network pharmacology pharmacodynamical material basis serum pharmacochemistry viral pneumonia YangshenDingzhi granules

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