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Tuina alleviates neuropathic pain through regulate the activation of microglia and the secretion of inflammatory cytokine in spinal cord

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Journal of traditional chinese medicine 2024年第4期44卷 762-769页

作者： WU Zhiwei ZHU Qingguang KONG Lingjun SONG Pengfei ZHOU Xin GUO Guangxin ZHANG Shuaipan HE Tianxiang CHENG Yanbin FANG Min Yueyang Hospital of Integrated traditional chinese and Western medicine Shanghai University of Traditional Chinese Medicine institute of Tuina Shanghai Institute of Traditional Chinese Medicine Shuguang Hospital Shanghai University of Traditional Chinese Medicine Department of Acupuncture and Tuina Shanghai University of Traditional Chinese Medicine

OBJECTIVE: To observe the analgesic effects of Tuina on neuropathic pain(NPP) and the underlying mechanisms. METHODS: Forty-eight Sprague-Dawley(SD) rats were assigned by random into three treatment groups: sham, chronic constriction injury(CCI), and Tuina. Each group contained sixteen rats. CCI model was generated by ligating the right sciatic nerve. Behavioral changes of CCI were assessed by the paw withdrawal threshold(PWT) and paw withdrawal latency(PWL). In addition, biochemical techniques such as immunofluorescence staining, enzyme-linked immunosorbent assay(ELISA) and Western blotting were used to profile levels of microglia activation and inflammatory factors in the spinal dorsal horn(SDH) of rats. Tuina(clockwise pressing and rubbing) was performed at Chengshan(BL57) to observe the analgesic effects on CCI rats and the underlying mechanisms. RESULTS: Rats with CCI experienced significant reduction in the PWT and PWL of the right hind paw relative to CCI group at day 3. Tuina treatment rescued this situation significantly on days 10 and 14. Besides, Iba-1, microglia M1 receptor CD68, tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) were higher in the right SDH for CCI group compared to the sham group on day 14. As expected, Tuina partially downregulated the CCI-induced overexpressed Iba-1, CD68, TNF-α, and IL-1β in the SDH of CCI model. CONCLUSION: Tuina induces a time-dependent cumulative analgesic effect in CCI rats by inhibiting the activation of microglia and the secretion of IL-1β and TNF-α in SDH.

关键词： Tuina inflammatory cytokine microglia neuralgia spinal cord

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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 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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The potential of herbal drugs to treat heart failure:The roles of Sirt1/AMPK

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Journal of Pharmaceutical Analysis 2024年第2期14卷 157-176页

作者： Tao Zhang Lei Xu Xiaowei Guo Honglin Tao Yue Liu Xianfeng Liu Yi Zhang Xianli Meng State Key Laboratory of Southwestern chinese medicine Resources Innovative Institute of Chinese Medicine and PharmacyChengdu University of Traditional Chinese MedicineChengdu611137China College of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu611137China School of Ethnic medicine Chengdu University of Traditional Chinese MedicineChengdu611137China Meishan Hospital of Chengdu University of traditional chinese medicine MeishanSichuan620032China

Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic *** addition to cardiac myocyte oxidative stress and apoptosis,which are considered mechanisms for the development of HF,alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately *** information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases and phosphorylated kinases,*** play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α),protein 38 mitogen-activated protein kinase(p38 MAPK),peroxisome proliferator-activated receptors(PPARs),and mammalian target of rapamycin(mTOR).We summarized the synergistic effects of Sirt1 and AMPK in the heart,and listed the traditional chinese medicine(TCM)that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway,to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases(CVDs).

关键词： Heart failure Silent information regulator 1 Adenosine monophosphate-activated protein kinase traditional chinese medicine

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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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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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An integrated strategy of UPLC-Q-TOF/MS and HPTLC/PAD-DESI-MSI for the analysis of chemical variations:A case study of Tibetan medicine Tiebangchui

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Journal of Pharmaceutical Analysis 2024年第4期14卷 615-618页

作者： Yue Liu Mengjia Li Xing Fu Yi Zhang Ce Tang State Key Laboratory of Southwestern chinese medicine Resources School of Ethnic MedicineChengdu University of Traditional Chinese MedicineChengdu611137China Meishan Hospital of Chengdu University of traditional chinese medicine MeishanSichuan620010China Innovative institute of chinese medicine and Pharmacy Chengdu University of Traditional Chinese MedicineChengdu611137China

The dried roots of Aconitum pendulum Busch are the major source of a commonly used Tibetan medicine,namely Tiebangchui(TBC)(Fig.S1).However,raw TBC contains a large amount of high toxic diester-diterpenoid alkaloids(DDAs),and the improper use would cause arrhythmia,irreversible cardiovascular damages,and even death.“Paozhi”,an appropriate processing method,is the essential prerequisite for the safe clinical application of ***-decocting and sand-frying are commonly used processing methods for toxicity attenuation and efficacy preservation for TBC.

关键词： dried irreversible roots

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Cycloastragenol induces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small cell lung cancer cell lines

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Journal of Integrative medicine 2024年第4期22卷 503-514页

作者： Li-hua Zhu Yu-pei Liang Lian Yang Feng Zhu Li-jun Jia He-gen Li Department of Oncology Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Cancer institute of traditional chinese medicine Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Department of Laboratory medicine Huadong HospitalFudan UniversityShanghai 200237China

Objective:Studies have demonstrated that cycloastragenol induces antitumor effects in prostate,colorectal and gastric cancers;however,its efficacy for inhibiting the proliferation of lung cancer cells is largely *** study explores the efficacy of cycloastragenol for inhibiting non-small cell lung cancer(NSCLC)and elucidates the underlying molecular ***:The effects of cycloastragenol on lung cancer cell proliferation were assessed using an adenosine triphosphate monitoring system based on firefly luciferase and clonogenic formation ***-induced apoptosis in lung cancer cells was evaluated using dual staining flow cytometry with an annexin V-fluorescein isothiocyanate/propidium iodide *** elucidate the role of cycloastragenol in the induction of apoptosis,apoptosis-related proteins were examined using Western *** and Western blotting were used to determine whether cycloastragenol could induce autophagy in lung cancer *** techniques,including small interfering RNA technology,were used to investigate the underlying *** effects against lung cancer and biosafety of cycloastragenol were evaluated using a mouse subcutaneous tumor ***:Cycloastragenol triggered both autophagy and ***,cycloastragenol promoted apoptosis by facilitating the accumulation of phorbol-12-myristate-13-acetate-induced protein 1(NOXA),a critical apoptosis-related ***,cycloastragenol induced a protective autophagy response through modulation of the adenosine 5'-monophosphate-activated protein kinase(AMPK)/unc-51-like autophagy-activating kinase(ULK1)/mammalian target of rapamycin(mTOR)***:Our study sheds new light on the antitumor efficacy and mechanism of action of cycloastragenol in *** insight provides a scientific basis for exploring combination therapies that use cycloastragenol and inhibiting the AMPK/ULK1/mTOR pathway as a promising approach to

关键词： Non-small cell lung cancer Cycloastragenol Autophagy Apoptosis

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Advancements in precision nanomedicine design targeting the anoikis-platelet interface of circulating tumor cells

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3457-3475页

作者： Manqing Tang Zhijie Zhang Ping Wang Feng Zhao Lin Miao Yuming Wang Yingpeng Li Yunfei Li Zhonggao Gao College of chinese Materia Medica Tianjin University of Traditional Chinese MedicineTianjin 301617China State Key Laboratory of Component-Based chinese medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China State Key Laboratory of Bioactive Substance and Function of natural medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Tumor metastasis,the apex of cancer progression,poses a formidable challenge in therapeutic *** tumor cells(CTCs),resilient entities originating from primary tumors or their metastases,significantly contribute to this process by demonstrating remarkable *** survive shear stress,resist anoikis,evade immune surveillance,and thwart *** comprehensive review aims to elucidate the intricate landscape of CTC formation,metastatic mechanisms,and the myriad factors influencing their *** signaling pathways,such as integrin-related signaling,cellular autophagy,epithelial-mesenchymal transition,and interactions with platelets,are examined in ***,we explore the realm of precision nanomedicine design,with a specific emphasis on the anoikis‒platelet *** innovative approach strategically targets CTC survival mechanisms,offering promising avenues for combatting metastatic cancer with unprecedented precision and *** review underscores the indispensable role of the rational design of platelet-based nanomedicine in the pursuit of restraining CTC-driven metastasis.

关键词： CTCs Anoikis Platelet Cancer stem cell Metastasis Platelet‒CTC interaction Platelet targeting Nanomedicines

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Danhongqing formula alleviates cholestatic liver fibrosis by downregulating long non-coding RNA H19 derived from cholangiocytes and inhibiting hepatic stellate cell activation

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Journal of Integrative medicine 2024年第2期22卷 188-198页

作者： Meng Li Yang Zhou Hui Zhu Lie-ming Xu Jian Ping institute of Liver Diseases Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China Preventive Treatment Center Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437 China Department of Gastroenterology Suzhou Traditional Chinese Medicine HospitalSuzhou 215000Jiangsu ProvinceChina Shanghai Key Laboratory of traditional chinese medicine Shanghai 201203China Key Laboratory of Liver and Kidney Diseases(Ministry of Education) Shanghai 201203China

Objective:This study explores the mechanism of action of Danhongqing formula(DHQ),a compoundbased chinese medicine formula,in the treatment of cholestatic liver ***:In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout(Mdr2-/-)mice as an animal model of cholestatic liver *** was administered orally for 8 weeks,and its impact on cholestatic liver fibrosis was evaluated by assessing liver function,liver histopathology,and the expression of liver fibrosis-related ***-time polymerase chain reaction,Western blot,immunohistochemistry and other methods were used to observe the effects of DHQ on long non-coding RNA H19(H19)and signal transducer and activator of transcription 3(STAT3)phosphorylation in the liver tissue of Mdr2-/-*** addition,cholangiocytes and hepatic stellate cells(HSCs)were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and H19 *** overexpressing H19 were constructed,and a conditioned medium containing H19 was collected to measure its effects on STAT3 protein expression and cell *** intervention effect of DHQ on these processes was also *** overexpressing H19 were constructed to measure the impact of H19 on cell activation and assess the intervention effect of ***:DHQ alleviated liver injury,ductular reaction,and fibrosis in Mdr2-/-mice,and inhibited H19expression,STAT3 expression and STAT3 *** formula also reduced hydrophobic bile acid-induced cholangiocyte injury and the upregulation of H19,inhibited the activation of HSCs induced by cholangiocyte-derived conditioned medium,and decreased the expression of activation markers in *** overexpression of H19 in a human HSC line confirmed that H19 promoted STAT3 phosphorylation and HSC activation,and DHQ was able to successfully inhibit these ***:DHQ effectively alleviated spontaneous cholestatic liver fibrosis in Md

关键词： Liver cirrhosis biliary Long non-coding RNA H19 Danhongqing formula Cholangiocyte Hepatic stellate cells STAT3 transcription factor

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