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Autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer

Journal of Integrative medicine 2024年第3期22卷 295-302页

作者： Zhengting Deng Shufang Liang Guokai Huang Yuqian Wang Xiaoyu Tu Yani Zhang Shu Li Tao Liu Binbin Cheng Taizhou Hospital of traditional chinese medicine Nanjing University of Chinese MedicineTaizhou 225300Jiangsu ProvinceChina Oncology Department of traditional chinese medicine The First Affiliated Hospital of Naval Medical UniversityShanghai 200433China School of traditional chinese medicine Nanjing University of Chinese MedicineNanjing 210023Jiangsu ProvinceChina Department of Gastroenterology Baoshan Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 201900China

Objective: The effects of arsenic trioxide(As2O3) on hepatocellular carcinoma have been documented widely. Autophagy plays dual roles in the survival and death of cancer cells. Therefore, we investigated the exact role of autophagy in As2O3-induced apoptosis in liver cancer ***: The viability of hepatoma cells was determined using the MTT assay with or without fetal bovine serum. The rate of apoptosis in liver cancer cells treated with As2O3was evaluated using flow cytometry, Hoechst 33258 staining, and TUNEL assays. The rate of autophagy among liver cancer cells treated with As2O3was detected using immunofluorescence, Western blot assay and transmission electron ***: Upon treatment with As2O3, the viability of HepG2 and SMMC-7721 cells was decreased in a time-and dose-dependent manner. The apoptosis rates of both liver cancer cell lines increased with the concentration of As2O3, as shown by flow cytometry. Apoptosis in liver cancer cells treated with As2O3was also shown by the activation of the caspase cascade and the regulation of Bcl-2/Bax ***, As2O3treatment induced autophagy in liver cancer cells;this finding was supported by Western blot, immunofluorescence of LC3-II and beclin 1, and transmission electron microscopy. In liver cancer cells, As2O3inhibited the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) signal pathway that plays a vital role in both apoptosis and autophagy. The PI3K activator SC-79 partially reversed As2O3-induced autophagy and apoptosis. Furthermore, inhibiting autophagy with 3-methyladenine partially reversed the negative effects of As2O3on cell *** starvation increased autophagy and amplified the effect of As2O3on cell ***: As2O3induces apoptosis and autophagy in liver cancer cells. Autophagy induced by As2O3may have a proapoptotic effect that helps to reduce the viability of liver cancer cells. This study provides novel insights

关键词： Apoptosis Arsenic trioxide Autophagy Primary liver cancer

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Study on blood pressure rhythm in hypertensive patients with Yin deficiency syndrome and a random forest model for predicting hypertension with Yin deficiency syndrome

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Journal of traditional chinese medicine 2024年第3期44卷 564-571页

作者： ZHOU Ying LI Ping LUAN Jianwei SHEN Rui WU Yinglan XU Qiwen WANG Xinyue ZHU Yao XU Xiangru LIU Zitian JIANG Yuning ZHONG Yong HE Yun JIANG Weimin Department of Cardiology the Affiliated Hospital of Nanjing University of Chinese MedicineJiangsu Province Hospital of Traditional Chinese MedicineNanjing 210029China Department of Health Management Centre Jinling HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210002China Emergency Department Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Department of General Internal medicine the Affiliated Hospital of Nanjing University of Chinese MedicineJiangsu Province Hospital of Traditional Chinese MedicineNanjing 210029China

OBJECTIVE: To investigate blood pressure rhythm(BPR)in Yin deficiency syndrome of hypertension(YDSH)patients and develop a random forest model for predicting ***: Our study was consistent with technical processes and specification for developing guidelines of Evidence-based chinese medicine clinical practice(T/CACM 1032-2017). We enrolled 234 patients who had been diagnosed with primary hypertension without antihypertensive medications prior to the enrollment. All participants were divided into Yin deficiency group(YX, n = 74) and non-Yin deficiency group(NYX, n = 160).Participants were professionally grouped by three experienced chief traditional chinese medicine(TCM)physicians according to four examinations(i.e.,inspection, listening and smelling, inquiry and palpation).We collected data on 24 h ambulatory blood pressure monitoring(ABPM) and YDSH rating scale. We divided 24 h of a day into 12 two-hour periods [Chen-Shi(7:00-9:00), Si-Shi(9:00-11:00), Wu-Shi(11:00-13:00), Wei-Shi(13:00-15:00), Shen-Shi(15:00-17:00), You-Shi(17:00-19:00), Xu-Shi(19:00-21:00), Hai-Shi(21:00-23:00), ZiShi(23:00-1:00), Chou-Shi(1:00-3:00), Yin-Shi(3:00-5:00), Mao-Shi(5:00-7:00)] according to the theory of “midnight-midday ebb flow”. We used random forest to build the diagnostic model of YDSH, with whether it was Yin deficiency syndrome as the outcome. RESULTS: Compared with NYX group, YX group had more female participants with older age, lower waist circumference, body mass index(BMI), diastolic blood pressure(DBP), and smoking and drinking rate(all P < 0.05). The YDSH rating scores of YX group [28.5(21.0-36.0)] were significantly higher than NYX group [13.0(8.0-22.0)](P < 0.001), and the typical symptoms of YX group included vexing heat in the chest, palms and soles, dizziness, dry eyes, string-like and fine pulse, soreness and weakness of lumbus and knees, palpitations, reddened cheeks, and tinnitus(all P < 0.05). The ratio of non-dipper hypertension in YX group was higher t

关键词： hypertension Yin deficiency syndrome random forest blood pressure rhythm blood pressure variability

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Update on the STING Signaling Pathway in Developing Nonalcoholic Fatty Liver Disease

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Journal of Clinical and Translational Hepatology 2024年第1期12卷 91-99页

作者： Wei Liu Zhili Zhang Chen Chenhui Yang Yaofu Fan Liang Qiao Shaofeng Xie Lin Cao Department of Endocrinology and Metabolism Affiliated Hospital of Integrated Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjingJiangsuChina Jiangsu Province Academy of traditional chinese medicine NanjingJiangsuChina

Nonalcoholic fatty liver disease(NAFLD)is a prevalent chronic liver condition with limited treatment *** caused by metabolic disturbances plays a significant role in NAFLD *** of interferon gene(STING),a critical regulator of innate immunity,induces the production of interferons and other pro-inflammatory factors by recognizing cytoplasmic DNA to defend against pathogen *** STING-mediated signaling pathway appears to play a vital role in hepatic inflammation,metabolic disorders,and even ***,pharmacological interventions targeting STING have shown improvements in the pathological state of ***,dendritic cells,natural killer cells,and T cell pathways regulated by STING present potential novel druggable targets for NAFLD *** research and development in this area may offer new therapeutic options for managing NAFLD effectively.

关键词： Stimulator of interferon gene Macrophage Innate immunity Nonalcoholic fatty liver disease

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Huangqin Decoction Delays Progress of Colitis-Associated Carcinogenesis by Regulating Nrf2/HO-1 Antioxidant Signal Pathwayin Mice

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chinese Journal of Integrative medicine 2024年第2期30卷 135-142页

作者： GU Li-mei LI He-zhong GAO Lei LI Hui WEI Lan-fu PAN Cheng-yu WU Ke-xuan TIAN Yao-zhou Department of Gastrointestinal Endoscopy Affiliated Hospital of Nanjing University of Chinese MedicineNanjing(210029)China Department of Gastroenterology Affiliated Hospital of Integrated Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing(210028)China School of Integrated chinese and Western medicine Nanjing University of Chinese MedicineNanjing(210023)China

Objective:To investigate the effect of Huangqin Decoction(HQD)on nuclear factor erythroid 2 related-factor 2(Nrf2)/heme oxygenase(HO-1)signaling pathway by inducing the colitis-associated carcinogenesis(CAC)model mice with azoxymethane(AOM)/dextran sodium sulfate(DSS).Methods:The chemical components of HQD were analyzed by liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-Q-TOF-MS/MS)to determine the molecular constituents of *** 48 C57BL/6J mice were randomly divided into 6 groups by a random number table,including control,model(AOM/DSS),mesalazine(MS),low-,medium-,and high-dose HQD(HQD-L,HQD-M,and HQD-H)groups,8 mice in each *** for the control group,the mice in the other groups were intraperitoneally injected with AOM(10 mg/kg)and administrated with 2.5%DSS orally for 1 week every two weeks(totally 3 rounds of DSS)to construct a colitis-associated carcinogenesis mouse *** mice in the HQD-L,HQD-M and HQD-H groups were given HQD by gavage at doses of 2.925,5.85,and 11.7 g/kg,respectively;the mice in the MS group was given a suspension of MS at a dose of 0.043 g/kg(totally 11 weeks).The serum levels of malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by enzyme-linked immunosorbent *** mRNA and protein expression levels of Nrf2,HO-1,and inhibitory KELCH like ECH-related protein 1(Keap1)in colon tissue were detected by quantitative real-time PCR,immunohistochemistry,and Westem blot,***:LC-Q-TOF-MS/MS analysis revealed that the chemical constituents of HQD include baicalin,paeoniflorin,and glycyrrhizic *** to the control group,significantly higher MDA levels and lower SOD levels were observed in the model group(P<0.05),whereas the expressions of Nrf2 and HO-1 were significantly decreased,and the expression of Keap1 increased(P<0.01).Compared with the model group,serum MDA level was decreased and SOD level was increased in the HQD-M,HQD-H and MS groups(P<0.05).Higher expressions of

关键词： Huangqin Decoction colitis-associated carcinogenesis nuclear factor erythroid 2 related-factor 2/heme oxygenase signaling pathway oxidative stress chinese medicine

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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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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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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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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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Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

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Neural Regeneration Research 2024年第4期19卷 737-746页

作者： Hu Qi Dan Tian Fei Luan Ruocong Yang Nan Zeng State Key Laboratory of Southwestern chinese medicine Resources Chengdu University of Traditional Chinese Medicine School of Pharmacy Chengdu University of Traditional Chinese Medicine Acupuncture and Tuina School Chengdu University of Traditional Chinese Medicine

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the ***,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this *** a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous ***,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention *** treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention *** the most vital component of the limbs,skeletal muscles have become potential points of *** this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal *** current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke *** addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.

关键词： inflammation ischemic stroke mitochondria muscle atrophy muscle fiber muscle nutrition quality of life rehabilitation ubiquitin

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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 MedicineShanghai 200437China Institute of Tuina Shanghai Institute of Traditional Chinese MedicineShanghai 200437China Shuguang Hospital Shanghai University of Traditional Chinese MedicineShanghai 200021China Department of Acupuncture and Tuina Shanghai University of Traditional Chinese MedicineShanghai 201203China

OBJECTIVE:To observe the analgesic effects of Tuina on neuropathic pain(NPP)and the underlying ***:Forty-eight Sprague-Dawley(SD)rats were assigned by random into three treatment groups:sham,chronic constriction injury(CCI),and *** group contained sixteen *** model was generated by ligating the right sciatic *** 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 ***(clockwise pressing and rubbing)was performed at Chengshan(BL57)to observe the analgesic effects on CCI rats and the underlying ***:Rats with CCI experienced significant reduction in the PWT and PWL of the right hind paw relative to CCI group at day *** treatment rescued this situation significantly on days 10 and ***,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 *** expected,Tuina partially downregulated the CCI-induced overexpressed Iba-1,CD68,TNF-α,and IL-1βin the SDH of CCI ***:Tuina induces a time-dependent cumulative analgesic effect in CCI rats by inhibiting the activation of microglia and the secretion of IL-1βand TNF-αin SDH.

关键词： Tuina neuralgia microglia inflammatory cytokine spinal cord

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