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

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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

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Adenosine triphosphate mediates the pain tolerance effect of manual acupuncture at Zusanli(ST36) in mice

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Journal of traditional chinese medicine 2024年第4期44卷 660-669页

作者： LI Zhongzheng ZHAO Yadan Ma Weigang Zhang Yonglong XU Zhifang XI Qiang LI Yanqi QIN Siru ZHANG Zichen WANG Songtao ZHAO Xue LIU Yangyang GUO Yi GUO Yongming research center of Experimental Acupuncture Science Tianjin University of Traditional Chinese MedicineTianjin 301617China National Clinical research center for chinese medicine Acupuncture and Moxibustion Tianjin 301617China Department of Acupuncture and Moxibustion Qingdao Hiser Hospital Affiliated of Qingdao University(Qingdao Traditional Chinese Medicine Hospital)Qingdao 266033China School of traditional chinese medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China School of Acupuncture and Moxibustion and Tuina Tianjin University of Traditional Chinese MedicineTianjin 301617China

OBJECTIVE:To investigate the mechanisms behind the effects of acupuncture in traditional chinese medicine,we delved into the adenosine triphosphate/peripheral purinergic P2X receptor 3(ATP/P2X3)receptor signaling system as an indicator of the body's energy state,commonly referred to as"Qi".METHODS:The tail-flick test was utilized to explore the impact of acupuncture on pain tolerance threshold(PTT)in mice,while also assessing adenosine(ADO)levels and adenylate energy charge(EC)at Zusanli(ST36).The study further investigated the dose-dependent effects of acupuncture on PTT and ADO levels at Zusanli(ST36).To shed light on the underlying mechanisms of acupuncture's effects,the study examined the impact of ATP,a P2X3 receptor antagonist,and adenosine disodium on PTT following acupuncture ***:Acupuncture at Zusanli(ST36)led to significant improvements in PTT in mice,with the most effective interventions being twirling for 2 min and needle retention for 28 *** interventions also resulted in significant increases in ATP *** effects of acupuncture were further augmented by administration of different doses of ATP at Zusanli(ST36),and pretreatment with a P2X3 receptor antagonist decreased *** EC peaked at 30 min after intraperitoneal injection of ATP,and pretreatment with various doses of *** 30 min prior to acupuncture increased PTT in a dose-dependent ***,pretreatment with an *** intramuscular injection of adenosine disodium enhanced the effects of ***:This research provides compelling evidence that ATP is involved in the regulation of PTT through acupuncture,revealing new avenues for achieving enhanced clinical outcomes.

关键词： acupuncture point ST36(Zusanli) adenosine triphosphate receptors,purinergic P2X3 energy state

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

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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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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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Pathological progression of osteoarthritis:a perspective on subchondral bone

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Frontiers of medicine 2024年第2期18卷 237-257页

作者： Xuefei Li Wenhua Chen Dan Liu Pinghua Chen Shiyun Wang Fangfang Li Qian Chen Shunyi Lv Fangyu Li Chen Chen Suxia Guo Weina Yuan Pan Li Zhijun Hu Longhua Hospital Affiliated to Shanghai University of traditional chinese medicine Shanghai200032China research and Development center of chinese medicine Resources and Biotechnology Shanghai University of Traditional Chinese MedicineShanghai201203China

Osteoarthritis(OA)is a degenerative bone disease associated with *** rising global aging population has led to a surge in OA cases,thereby imposing a significant socioeconomic *** have been keenly investigating the mechanisms underlying *** studies have suggested that the disease starts with synovial inflammation and hyperplasia,advancing toward cartilage ***,subchondral-bone collapse,sclerosis,and osteophyte formation *** progression is deemed as“top to bottom.”However,recent research is challenging this perspective by indicating that initial changes occur in subchondral bone,precipitating cartilage *** this review,we elucidate the epidemiology of OA and present an in-depth overview of the subchondral bone’s physiological state,functions,and the varied pathological shifts during OA *** also introduce the role of multifunctional signal pathways(including osteoprotegerin(OPG)/receptor activator of nuclear factor-kappa B ligand(RANKL)/receptor activator of nuclear factor-kappa B(RANK),and chemokine(CXC motif)ligand 12(CXCL12)/CXC motif chemokine receptor 4(CXCR4))in the pathology of subchondral bone and their role in the“bottom-up”progression of *** vivid pattern maps and clinical images,this review highlights the crucial role of subchondral bone in driving OA progression,illuminating its interplay with the condition.

关键词： osteoarthritis subchondral bone OPG/RANKL/RANK CXCL12/CXCR4

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Neural stem cells promote neuroplasticity: a promising therapeutic strategy for the treatment of Alzheimer’s disease

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Neural Regeneration research 2024年第3期19卷 619-628页

作者： Jun Chang Yujiao Li Xiaoqian Shan Xi Chen Xuhe Yan Jianwei Liu Lan Zhao First Teaching Hospital of Tianjin University of traditional chinese medicine TianjinChina National Clinical research center for chinese medicine Acupuncture and Moxibustion TianjinChina Tianjin University of traditional chinese medicine TianjinChina

Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s ***,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be *** to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to *** events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian ***,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative *** this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.

关键词： Alzheimer’s disease amyloid-β cell therapy extracellular vesicle neural stem cell synaptic plasticity tau

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Effect on serum metabolomics of rats with premature ovarian insufficiency by Zhibian(BL54) through Shuidao(ST28) acupuncture

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Journal of traditional chinese medicine 2024年第4期44卷 722-733页

作者： YAN Jing FENG Huimin QIU Fang WANG Haijun YIN Luyun JIN Xiaofei ZHAO Jiyu WANG Hongyang YAN Xiaoqin Second Clinical College of Shanxi University of traditional chinese medicine Jinzhong 030619China research center of Experimental Acupuncture Science Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Cervical and Lumbar Vertebral Diseases Jinzhong Hospital Affiliated to Shanxi University of Traditional Chinese MedicineJinzhong 030600China

OBJECTIVE:To analyze the serum metabolic targets of the"Zhibian(BL54)through Shuidao(ST28)"acupuncture technique in cyclophosphamide(CTX)-induced premature ovarian insufficiency(POI)model rats and to elucidate the potential molecular mechanism of acupuncture in improving ***:We used an intraperitoneal injection of CTX to establish the POI rat model(POI group)and compared serum hormone levels and ovarian histopathological changes to evaluate the effect of the Zhibian(BL54)through Shuidao(ST28)technique(ZS+POI group)on ovarian ***,nontargeted metabolomics was performed using rat serum by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS).RESULTS:After acupuncture intervention,the serum hormone levels and ovarian pathological morphology of POI rats were effectively ***,UPLC-Q-TOF/MS results showed that the ZS+POI group showed a significant reversal of the levels of 6 differential *** them,the levels of four serum metabolic markers,divanillyltetrahydrofuran ferulate,trans-ferulic acid,tryptamine,and neuraminic acid,increased *** analysis of biological effects showed that all metabolites were involved in the regulation of reproductive hormone levels and antioxidant and antiapoptotic ***:The"Zhibian(BL54)through Shuidao(ST28)"acupuncture method may improve the ovarian function of POI rats by regulating serum metabolite markers to exert antioxidant and antiapoptotic effects,which provides a theoretical basis for the clinical application of acupuncture in the treatment of POI.

关键词： acupuncture premature ovarian insufficiency metabolomics ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry Zhibian(BL54)through Shuidao(ST28)

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Anti-inflammatory mechanism of the non-volatile ingredients performance liquid chromatography-heated electron spray ionization-high resolution mass spectroscope and cell metabolomics

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Journal of traditional chinese medicine 2024年第2期44卷 260-267页

作者： JING Wenguang LIN Xiaoyu LI Chu ZHAO Xiaoliang CHENG Xianlong WANG Penglong WEI Feng MA Shuangcheng Institute of Control of chinese traditional medicine and Ethnic medicine National Institutes for Food and Drug ControlBeijing 102629China School of traditional chinese medicine Beijing University of Chinese MedicineBeijing 102488China Beijing Key Laboratory of traditional chinese medicine Basic research on Prevention and Treatment of Major Diseases Experimental Research CenterChina Academy of Chinese Medical SciencesBeijing 100700China

OBJECTIVE:To explore the anti-inflammatory components and mechanism of the non-volatile ingredients of ***:High performance liquid chromatographyheated electron spray ionization-high resolution mass spectroscope(HPLC-HESI-HRMS)was used to analyze the chemical constituents of the non-volatile ingredients of *** anti-inflammatory activity of ingredients was evaluated using lipopolysaccharide(LPS)induced RAW264.7 cell inflammation model,and the antiinflammatory mechanism was investigated using multivariate statistical analysis of cell ***:The non-volatile ingredients of patchouli were characterized by HPLC-HESI-HRMS,and 36 flavonoids and 18 other components were *** ingredients of patchouli not only had a good protective effect on the LPS-induced inflammation model of RAW264.7 cells,but also regulated the expression levels of arginine,L-leucine,cholesterol,fructose and sorbitol by down-regulating arginine metabolism,aminoacyl-tRNA biosynthesis,polyol/sorbitol pathway,so as to reduce inflammation and reduce cell ***:The non-volatile ingredients of patchouli had good anti-inflammatory effect and exerted its curative effect by regulating endogenous metabolic pathway to reduce inflammatory response.

关键词： Pogostemon non-volatile ingredients anti-inflammatory cell metabolomics

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Organic Integration of traditional chinese and Western medicines—Future of Clinical Practice Guidelines of Integrated traditional chinese and Western medicines

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chinese Journal of Integrative medicine 2024年第4期30卷 359-365页

作者： XIE Ying-lan HAN Fei JIN Ying-hui DING Yan-bing GUO Jing JI Dong-xiao ZHANG Teng CHENXiao-min SHANG Hong-cai Department of traditional chinese medicine Encephalopathy Hubei Provincial Hospital of Traditional Chinese MedicineWuhan(430074)China Department of traditional chinese medicine Encephalopathy Hubei Province Traditional Chinese Medicine Research InstituteWuhan(430074)China Xuanwu Hospital of traditional chinese medicine Beijing(100000)China center for Evidence-Based and Translational medicine Zhongnan Hospital of Wuhan UniversityWuhan(430074)China College of Acupuncture and Massage College of Health and RehabilitationNanjing University of Chinese MedicineNanjing(210023)China Department of Ophthalmology Huaihe Hospital of Henan UniversityKaifengHenan Province(475000)China Ministry of Education and Beijing Key Laboratory of Internal medicine of traditional chinese medicine Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine/Ministry of Education and Beijing Key Laboratory of Internal Medicine of Traditional Chinese MedicineBeijing(100700)China

The transformation and implementation of clinical practice guidelines for integrated traditional chinese medicine(TCM)and Western medicine(WM)is crucial to the adoption of medical science and technological findings and is an important way for TCM to be made available to the ***,clinical practice guidelines(CPGs)of TCM and WM integration in recent years was analyzed to clarify the current situation and problems in the existing guidelines according to the following four perspectives:(1)perspective of TCM and WM integration in guidelines,(2)diagnosis Using integrated TCM and WM,(3)integration of TCM and WM treatment,(4)promoting TCM and WM ***,the information and quality evaluation of CPGs for integrated chinese and Western medicine in 2020–2022 were analyzed to explore the degree and methods of integration of chinese and Western medicine *** last this study aimed to lay a foundation for the further establishment of chinese characteristic,repeatable,and calculable clinical practice guidelines of TCM and WM integration.

关键词： clinical practice guidelines integrated traditional chinese and Western medicine organic integration

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Epigenetics:Mechanisms,potential roles,and therapeutic strategies in cancer progression

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Genes & Diseases 2024年第5期11卷 300-314页

作者： Dong Wang Yan Zhang Qingbo Li Yu Li Wen Li Ao Zhang Jingxuan Xu Jingyan Meng Lin Tang Shuhua Lyu Graduate School Tianjin University of Traditional Chinese MedicineTianjin 301617China College of traditional chinese medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Pathology Tianjin Union Medical CenterTianjin 300121China

Mutations or abnormal expression of oncogenes and tumor suppressor genes are known to cause *** studies have shown that epigenetic modifications are key drivers of cancer development and ***,the mechanistic role of epigenetic dysregulation in the tumor microenvironment is not fully ***,we reviewed the role of epigenetic modifications of cancer cells and non-cancer cells in the tumor microenvironment and recent research advances in cancer epigenetic *** addition,we discussed the great potential of epigenetic combination therapies in the clinical treatment of ***,there are still some challenges in the field of cancer epigenetics,such as epigenetic tumor heterogeneity,epigenetic drug heterogeneity,and crosstalk between epigenetics,proteomics,metabolomics,and other omics,which may be the focus and difficulty of cancer treatment in the *** conclusion,epigenetic modifications in the tumor microenvironment are essential for future epigenetic drug development and the comprehensive treatment of *** combination therapy may be a novel strategy for the future clinical treatment of cancer.

关键词： Cancer Epigenetics Gene expression Heterogeneity Tumor microenvironment

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