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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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Tiaobu Feishen therapy inhibits inflammation induced by cigarette smoke extracts in a human monocyte/macrophage cell line

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Journal of Traditional Chinese Medicine 2021年第3期41卷 360-366页

作者： QIN Yanqin CHEN Yulong ZHAO Peng FENG Suxiang WU Yaosong LIU Xuefang DONG Haoran ZHENG Wanchun MAO Xiaoning LI Jiansheng Henan Key Laboratory of Chinese Medicine for Respiratory Disease Henan University of Chinese MedicineZhengzhou 450046China Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan&Education Ministry of China Henan University of Chinese MedicineZhengzhou 450046China

OBJECTIVE: To study the mechanistic effects of Tiaobu Feishen therapy(TBFS) on inflammation induced by cigarette smoke extract(CSE) in a human monocyte/macrophage cell ***: The human monocyte/macrophage cell line THP-1 was stimulated with 10% CSE in the presence or absence of Bufei Yishen formula(BYF),Bufei Jianpi formula(BJF) and Yiqi Zishen formula(YZF). All formulations contained serum. Pro-inflammatory cytokines were measured in the supernatants using enzyme-linked immunosorbent *** activity of stat3 DNA binding was detected using electrophoretic mobility shift assay and janus kinase/signal transducer and activator of transcription(JAK/stat) pathway activation was assessed using Western ***: The results showed that BYF, BJF and YZF treatment strongly decreased the CSE-induced secretion of interleukin(IL)-6, IL-8, tumor necrosis factor-α and matrix metalloproteinase-9 by THP-1 cells. Furthermore, BYF, BJF and YZF treatment attenuated stat3 DNA binding capacity and JAK2 and stat3 were shown to be ***: The data revealed that BYF, BJF and YZF effectively inhibited a CSE-induced inflammatory response in THP-1 cells by limiting activation of the JAK2/stat3 pathway.

关键词： cigarette smoking janus kinase 2 stat3 transcription factor THP-1 cells matrix metalloproteinases Tiaobu Feishen therapy

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Zebrafish facilitates drug screening: potential of 3-deoxy-andrographoside from Chuanxinlian(Herba Andrographitis Paniculatae) as an anti-inflammatory agent

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Journal of Traditional Chinese Medicine 2022年第5期42卷 749-757页

作者： HE Xuemei XIAO Junjie FAN Chunlin LU Zibin CAO Huihui YU Linzhong ZHENG Yuanru LIU Junshan Third Level Research Laboratory of state Administration of Traditional Chinese Medicine School of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510515China Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics Guangzhou 510515China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research College of PharmacyJinan UniversityGuangzhou 510632China School of Pharmacy Guangdong Pharmaceutical universityGuangzhou 510006China Department of Pharmacy Zhujiang HospitalSouthern Medical UniversityGuangzhou 510515China

OBJECTIVE: To systematically evaluate the in vivo antiinflammatory potential of diterpene lactones from Chuanxinlian(Herba Andrographitis Paniculatae)(AP). METHODS: We firstly adopted zebrafish, a novel and ideal animal model for high-throughput drug screening, to investigate the in vivo anti-inflammatory activities of 17 diterpene lactones isolated from ***: The results showed that most of diterpene lactones displayed significant anti-inflammatory effects in lipopolysaccharide microinjection-, copper sulfate exposure-or tail transection-induced zebrafish inflammation models. Moreover, diterpene lactone 3-deoxy-andrographoside(AP-5) was firstly found to attenuate inflammatory responses, which was closely associated with the myeloid differentiation primary response 88/nuclear factor-kappa B and signal transducer and activator of transcription 3 pathways. CONCLUSION: Our research sheds light on the inestimable roles of zebrafish in high-throughput drug screening, elucidates the potent inhibitory effects of diterpene lactones against inflammation and indicates that AP-5 may serve as a potential alternative agent for the treatment of inflammatory diseases.

关键词： diterpenes lactones inflammation zebrafish myeloid differentiation factor 88 NF-kappa B stat3 transcription factor

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Effects of peroxisome proliferator-activated receptor-β/δ on sepsis induced acute lung injury

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Chinese Medical Journal 2014年第11期127卷 2129-2137页

作者： Wang Cairui Zhou Guopeng Zeng Zeng Department of Geriatrics Peking University First Hospital Beijing100034 China

Background Acute lung injury （ALI） and acute respiratory distress syndrome （ARDS） are the first steps in the development of multiple organ failure induced by sepsis.A systemic excessive inflammatory reaction is currently the accepted mechanism of the pathogenesis of *** studies have suggested a protective role of the peroxisome proliferator activated receptor-β/δ （PPAR-β/δ） in related inflammatory *** the role of PPARβ/δ in ALI remains *** aim of this study was to investigate the role and possible mechanism of PPARβ/δ in ALI induced by *** Cecal ligation and puncture （CLP） was used as a sepsis *** were randomly divided into four groups,the control group （CON,n=6）,sham-operation group （SHAM,n=12）,cecal ligation and puncture group （CLP,n=30）,GW501516 group （CLP＋GW,n=25）,which underwent CLP and were subcutaneously injected with the PPAR-β/δ agonist GW501516 （0.05 mg/100 g body weight）.Survival was monitored to 24 hours after *** pressure,serum creatinine,blood urea nitrogen,aspartate aminotrasferase and alanine aminotrasferase were measured after *** of tumor necrosis factor α （TNF-α） and interleukin （IL）-1β in serum were detected by enzyme linked immunosorbent assay （ELISA） *** tissue samples were stained with H＆E and scored according to the degree of *** colonies were counted in the peritoneal *** macrophages were cultured and incubated with GW501516 （0.15 μmol/L） and PPARβ/δ adenovirus and then treated with Lipopolysaccharide （2 μg/ml） for 2 *** TNF-α,IL-1β and IL-6 RNA in lung and alveolar macrophages were determined by real-time *** of signal transducer and activator of transcription 3 （stat3） in lung and alveolar macrophages was detected by Western *** GW501516 significantly increased the survival of septic rats,decreased histological damage of the lungs,reduced inflammatory cytokines in serum and lung tissues of septic

关键词： peroxisome proliferator activated receptor acute lung injury sepsis alveolar macrophages stat3 transcription factor

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Effect of RNA Interference Targeting stat3 Gene Combined with Ultrasonic Irradiation and SonoVue Microbubbles on Proliferation and Apoptosis in Keratinocytes of Psoriatic Lesions

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Chinese Medical Journal 2018年第17期131卷 2097-2104页

作者： Li-Wei Ran Hao Wang Dong Lan Hong-Xia Jia Si-Si Yu Department of DermatolocIy Jinqxi Campus Beijing Chaoyang Hospital Capital Medical University Beijing 100043 China Department of Dermatology The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi 710004 China

Background： Signal transducer and activator of transcription 3 （stat3） was strongly expressed and activated in psoriatic keratinocytes （KCs） and correlated with the severity of psoriasis. The study aimed to investigate the effects of stat3 small interfering RNA （siRNA） combined with ultrasonic irradiation and SonoVue microbubbles on the proliferation and apoptosis in KCs of psoriatic lesions and the relative mechanisms. Methods： Psoriatic KCs were transfected under four experimental conditions：（1） STA T3 siRNA carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles （LUS group）; （2） STA T3 siRNA only carried by Lipofectamine 3000 （L group）; （3） the negative control ofsiRNA carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles （siRNA-NC）; （4） not treated as Blank. Cell Counting Kit-8 assay was used to evaluate the cell proliferation. Cell cycle analysis was detected with cycle test Plus DNA reagent kit associated with flow cytometer. FITC Annexin V apoptosis detection kit associated with flow cytometer was applied for apoptosis analysis. Fluo calcium indicator associated with flow cytometer was used to analyze intracellular free calcium concentration （[Ca^2＋）. The expressions of cyclin D1 and Bcl-xL were detected both at the mRNA level by real-time reverse transcription-polymerase chain reaction （RT-PCR） and at the protein level by Western blotting. The obtained data were statistically evaluated by two-way analysis of variance. Results： stat3 siRNA inhibited the growth of KCs in a time-dependent manner showing the highest proliferation inhibition in LUS group with proliferation ratio of 45.38% ± 5.85% at 72h （P 〈 0.05 vs. L group, siRNA-NC, or Blank）. stat3 siRNA induced an altered cell cycle distribution of KCs showing the highest increases in G2/M-phase population up to 18.06% ± 0.36% in LUS group （P 〈 0.05 vs. L group, siRNA-NC, or Blank）. ST,4 T3 siRNA induced late apoptosis of KCs with the

关键词： Apoptosis Cell Proliferation Keratinocytes Microbubbles Psoriasis RNA Interference Small Interfering RNA stat3 transcription factor

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Expression of interleukin-12 and its signaling molecules in peripheral blood mononuclear cells in systemic lupus erythematosus patients

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Chinese Medical Journal 2002年第6期115卷 846-850,150页

作者：李志坚李幼姬黄凌虹许韩师余学清叶任高中山医科大学附属第一医院风湿科广州510080

Objective To determine the in vitro expression of interleukin-12 (IL-12) and its effect on signal transducers and activators of transcription (stat) signaling molecules in peripheral blood mononuclear cells (PBMCs) in patients with systemic lupus erythematosus (SLE).Methods Peripheral blood mononuclear cells in 39 patients with definite systemic lupus erythematosus and 11 healthy volunteers were collected. Expression of IL-12 P40mRNA in PBMCs was determined with reverse transcription-polymerase chain reaction (RT-PCR). Quantity of IL-12 protein supernatant was measured by enzyme-linked immunosorbent assay (ELISA). The levels of phosphorylated stat3 and stat4 signaling molecules in PBMCs were detected by immunoblot. Results Levels of IL-12 protein and mRNA expression in patients with active or inactive SLE were significantly higher than those in controls. Phytohemagglutinin (PHA) may promote the expression of IL-12. IL-12 alone induced the phosphorylation of stat3 and stat4 in PBMCs from patients with SLE, especially in active SLE. However it had no obvious effect on normal PBMCs. Phosphorylated stat3 and stat4 might be observed in normal PBMCs treated with IL-12 plus *** IL-12 is produced aberrantly in patients with SLE. IL-12 might exert its biological role in SLE via the aberrantly phosphorylated stat3 and stat4 signaling molecules.

关键词： Adolescent Adult Cells, Cultured DNA-Binding Proteins Humans Interleukin-12 Leukocytes, Mononuclear Lupus Erythematosus, Systemic Middle Aged Phosphorylation RNA, Messenger Research Support, Non-U.S. Gov't stat3 transcription factor stat4 transcription factor Trans-Activators

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stat3 activation of tumor-associated macrophages is associated with cytokines of tumor microenvironment and prognostic factors in breast cancer

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The Chinese-German Journal of Clinical Oncology 2009年第7期8卷 402-405页

作者： Zhengkui Sun Shengchun Liu Zhenxiang Yao Department of Breast Surgery Jiangxi Provincial Cancer Hospital Nanchang 330029 China Department of General Surgery First Affiliated Hospital Chongqing University of Medical Sciences Chongqing 400016 China

Objective:The aim of this study was to investigate the correlation of stat3 activation of tumor-associated macrophages(TAMs) and local cytokines(IL-1β,TNF-α,TGF-β and IL-12) and prognostic factors in breast ***:TAMs in 50 primary breast cancers and macrophages in 15 normal breasts were examined by *** stat3 DNA-binding activity of TAMs in 33/50 primary breast cancers was measured by transcription factor DNA-binding *** addition,the concentrations of IL-1β,TNF-α,TGF-β and IL-12 were measured in the 33 primary breast cancers extracts by *** correlation between stat3 activity of TAMs and concentrations of IL-1β,TNF-α,TGF-β and IL-12 were *** correlation between stat3 activity of TAMs and conventional clinicopathologic parameters were also ***:The macrophages density showed a significant increase in primary breast cancers compared to normal ***3 DNA-binding activity of TAMs in breast cancer was significantly higher than that of monocytes/macrophages from peripheral blood of the ***,stat3 activity of TAMs was correlated significantly with the levels of IL-1β,TNF-α and TGF-β in breast cancer *** an inverse association was observed between stat3 activity of TAMs and *** addition,stat3 activity of TAMs was higher in high histological type than in low histological type,and stat3 activity of TAMs was higher in CerBb-2 positive than CerBb-2 ***:stat3 activation of TAMs may be associate with increasing of IL-1β,TNF-α and TGF-β and decreasing of IL-12 in breast ***3 activation of TAMs may also be correlated with histological grade and CerBb-2 status of breast cancer.

关键词： breast neoplasms macrophages stat3 transcription factor cytokines prognosis

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