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Hydroxysafflor Yellow A Inhibits Pyroptosis and Protecting HUVECs from OGD/R via NLRP3/Caspase-1/GSDMD Pathway

Chinese Journal of Integrative Medicine 2024年第11期30卷 1027-1034页

作者： GUO Fan HAN Xiao YOU Yue XU Shu-juan ZHANG Ye-hao CHEN Yuan-yuan XIN Gao-jie LIU Zi-xin REN Jun-guo CAO Ce LI Ling-mei FU Jian-hua institute of Basic Medical Sciences of xiyuan hospital China Academy of Chinese Medical Sciences Beijing Key Laboratory of Chinese Materia pharmacology Department of Central Laboratory Kunshan Hospital of Chinese Medicine

Objective: To observe the protective effect and mechanism of hydroxyl safflower yellow A(HSYA)from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells(HUVECs). Methods:HUVECs were treated with oxygen-glucose deprivation reperfusion(OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations(1.25–160 μmol/L)of HSYA on HUVECs after OGD/R. HSYA 80 μmol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin(IL)-18, IL-1β, monocyte chemotactic protein 1(MCP-1), tumor necrosis factor α(TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3(NLRP3), gasdermin D(GSDMD) and GSDMD-N-terminal domain(GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt(CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1(Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot. Results: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18,IL-1β, MCP-1, TNF-α and IL-6(P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3,Caspase-1, GSDMD and GSDMD-N proteins(P<0.01). Conclusions: The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.

关键词： Chinese medicine NLRP3 inflammasome human umbilical vein endothelial cells hydroxysafflor yellow A myocardial reperfusion injury oxygen-glucose deprivation reperfusion pyroptosis

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Tetramethylpyrazine and paeoniflorin combination(TMP-PF)inhibits angiogenesis in atherosclerosis via miR-126/VEGF/VEGFR2 signaling pathway

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未来食品学报(英文) 2024年第3期4卷 280-287页

作者： Yahui Yuan Rong Yuan Qiqi Xin Yu Miao Ying Chen Rui Gao Weihong Cong Laboratory of Cardiovascular Diseases Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China National clinical Research Center for Chinese Medicine Cardiology Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China School of Health Economics and Management Nanjing University of Chinese MedicineNanjing 210023China Institution of clinical pharmacology Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China Key Laboratory for clinical Research and Evaluation of Traditional Chinese Medicine National Medical Products AdministrationBeijing 100091China

Angiogenesis in atherosclerosis(AS)promotes plaque ***-126 has a significant role in ***(TMP)and paeoniflorin(PF)have anti-atherosclerotic ***,the miR-126-related mechanisms of TMP and PF combination(TMP-PF)on angiogenesis in AS have not been *** explore the mechanism of TMP-PF on angiogenesis in AS targeting *** umbilical vein endothelial cells(HUVECs)were assigned into the control,model,TMP-PF,TMP-PF+miR-126 inhibitor,and simvastatin *** were transfected with miR-126 inhibitor or negative control,incubated with oxidized low-density lipoprotein(ox-LDL)to establish AS model,and then treated with TMP-PF or *** proliferation,migration,and tube formation assays are conducted,and the expression of angiogenesis-related factors were detected by enzyme-linked immunosorbent assay(ELISA)and Western *** expression level of miR-126 was confirmed by polymerase chain reaction(PCR).0x-LDL promoted HUVECs proliferation,migration,and tube formation,downregulated miR-126 expression,and increased the expression of VEGF,VEGFR2,bFGF,and ***-PF inhibited proliferation,migration,and tube formation,upregulated miR-126 expression and decreased the expression of VEGF,VEGFR2,bFGF,and FGFR1 in ox-LDL-induced ***,the effects of TMP-PF on angiogenesis and the expression of miR-126,VEGF,VEGFR2,and FGFR1 were abolished by miR-126 ***-PF suppressed angiogenesis in AS by regulating miR-126/VEGF/VEGFR2 pathway,which might elucidate the underlying mechanism of TMP-PF in alleviating AS.

关键词： Atherosclerosis Angiogenesis Tetramethylpyrazine Paeoniflorin miR-126/VEGF/VEGFR2 signaling pathway

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Proteomics analysis of coronary atherosclerotic heart disease with different Traditional Chinese Medicine syndrome types before and after percutaneous coronary intervention

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Journal of Traditional Chinese Medicine 2024年第3期44卷 554-563页

作者： WANG Zhibo LI Ying WANG Daoping MA Bo MIAO Lan REN Junguo LIU Jinghua LIU Jianxun Beijing Key Laboratory of pharmacology of Chinese Materia Region Institute of Basic Medical SciencesXiyuan HospitalChina Academy of Chinese Medical SciencesNational Clinical Research Center of Cardiovascular Disease of Traditional Chinese MedicineBeijing 100000China the National Key Facility for Crop Gene Resources and Genetic Improvement Institute of Crop ScienceChinese Academy of Agricultural ScienceBeijing 100098China Department of Cardiology Beijing Anzhen HospitalCapital Medical UniversityBeijing 100029China

OBJECTIVE: To investigate the underlying protein molecular mechanisms of "Qi stagnation and blood stasis syndrome"(QS) and "Qi deficiency and blood stasis syndrome"(QD), as two subtypes of coronary artery disease(CAD) in Traditional Chinese Medicine(TCM),following percutaneous coronary intervention(PCI).METHODS: In this study, a total of 227 CAD patients with QS and 211 CAD patients with QD were enrolled;all participants underwent PCI. Label-free quantification proteomics were employed to analyze the changes in serum in two subtypes of CAD patients before and 6 months after PCI, aiming to elucidate the intervention mechanism of PCI in treating CAD characterized by two different TCM ***: Biochemical analysis revealed significant changes in tumor necrosis factor-α, high density lipoprotein cholesterol, blood stasis clinical symptoms observation, and Gensini levels in both patient groups post-PCI;Proteomic analysis identified 79 and 95 differentially expressed proteins in the QS and QD patient groups, respectively, compared to their control *** C8 alpha chain, complement factor H,apolipoprotein H, apolipoprotein B, plasminogen,carbonic anhydrase 2, and complement factor Ⅰ were altered in both comparison groups. Furthermore,enrichment analysis demonstrated that cell adhesion and connectivity-related processes underwent changes in QS patients post-PCI, whereas lipid metabolism-related pathways, including the peroxisome proliferator-activated receptor signaling pathway and extracellular matrix receptor interaction, underwent changes in the QD *** protein-protein interaction network analysis further enriched 52 node proteins, including apolipoprotein B,lipoprotein(a), complement C5, apolipoprotein A4,complement C8 alpha chain, complement C8 beta chain,complement C8 gamma chain, apolipoprotein H,apolipoprotein A-Ⅱ, albumin, complement C4-B,apolipoprotein C3, among others. The functional network of these proteins is posited to contribute to

关键词： percutaneous coronary intervention proteomics peptide mapping coronary atherosclerotic heart disease Traditional Chinese Medicine syndrome

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GRK2 inhibits Flt-1^(+)macrophage infiltration and its proangiogenic properties in rheumatoid arthritis

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Acta Pharmaceutica Sinica B 2024年第1期14卷 241-255页

作者： Xuezhi Yang Yingjie Zhao Qi Wei Xuemin Zhu Luping Wang Wankang Zhang Xiaoyi Liu Jiajie Kuai Fengling Wang Wei Wei institute of clinical pharmacology Anhui Medical UniversityKey Laboratory of Anti-Inflammatory and Immune MedicineAnhui Collaborative Innovation Center of Anti-Inflammatory and Immune MedicineMinistry of EducationHefei 230032China Department of clinical pharmacology the Second Affiliated Hospital of Anhui Medical UniversityHefei 230601China

Rheumatoid arthritis(RA)is an autoimmune disease with a complex ***-derived macrophages(MDMs)infiltration are associated with RA *** have reported the deletion of G-protein-coupled receptor kinase 2(GRK2)reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor ***,as more GRK2-interacting proteins were discovered,the GRK2 interactome mechanisms in RA have been ***,in the collagen-induced arthritis mouse model,we performed genetic GRK2 deletion using GRK2^(f/f)Lyz2-Cre^(+/−)*** inflammation and M1 polarization were improved in GRK2^(f/f)Lyz2-Cre^(+/−)*** experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptorγ(PPARγ)as a new GRK2-interacting *** further confirmed that fms-related tyrosine kinase 1(Flt-1),which promoted macrophage migration to induce angiogenesis,was inhibited by GRK2-PPARγ***,excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγligand-binding domain and enhanced Flt-1 ***,the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology,Flt-1^(+)macrophages induced-synovial inflammation,and ***,we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular *** GRK2 activity is a viable strategy to inhibit MDMs infiltration,affording a distinct way to control joint inflammation and angiogenesis of RA.

关键词： GRK2 Monocyte-derived macrophages Rheumatoid arthritis PPARg Flt-1

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Effectiveness and Safety of Qishen Yiqi Dripping Pill in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention:3-Year Results from a Multicentre Cohort Study

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Chinese Journal of Integrative Medicine 2024年第10期30卷 877-885页

作者： BAI Rui-na GU Feng CHE Qian-zi ZHANG Xuan CAI Ya-jie XI Rui-xi ZHAO Yang GUO Ming DONG Guo-ju GAO Zhu-ye FU Chang-geng WANG Pei-li DU Jian-peng ZHANG Da-wu DUAN Wen-hui LI Li-zhi YANG Qiao-ning SHI Da-zhuo Department of Cardiovascular Xiyuan Hospital China Academy of Chinese Medical Sciences National clinical Research Center for Chinese Medicine Cardiology Department of Evidence-Based Medicine Basic Research Laboratory Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical Sciences Department of Traditional Chinese Medicine Beijing Shangdi Hospital National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Traditional Chinese Medicine

Objectives: To evaluate the effectiveness and safety of Qishen Yiqi Dripping Pill(QSYQ) in patients with acute coronary syndrome(ACS) after percutaneous coronary intervention(PCI). Methods: This multicentre prospective cohort study was conducted at 40 centers in China. Patients with ACS after PCI entered either the QSYQ or Western medicine(WM) groups naturally based on whether they had received QSYQ before enrollment. QSYQ group received QSYQ(0.52 g, 3 times a day for 12 months) in addition to WM. The primary endpoint included cardiac death, non-fatal myocardial infarction, and urgent revascularization. The secondary endpoint included rehospitalization due to ACS, heart failure, stroke, and other thrombotic events. Quality of life was assessed by the Seattle Angina Questionnaire(SAQ). Results: A total of 936 patients completed follow-up of the primary endpoint from February 2012 to December 2018. Overall, 487 patients received QSYQ and WM. During a median follow-up of 566 days(inter quartile range, IQR, 517–602), the primary endpoint occurred in 46(9.45%) and 65(14.48%) patients in QSYQ and WM groups respectively [adjusted hazard ratio(HR) 0.60, 95% confidence interval(CI) 0.41–0.90; P=0.013]. The secondary endpoint occurred in 61(12.53%) and 74(16.48%) patients in QSYQ and WM groups, respectively(adjusted HR 0.76, 95% CI 0.53–1.09; P=0.136). In sensitivity analysis, the results still demonstrated that WM combined with QSYQ reduced the risk of the primary endpoint(HR 0.67, 95% CI 0.46–0.98; P=0.039). Moreover, QSYQ improved the disease perception domain of the SAQ(P<0.05). Conclusions: In patients with ACS after PCI, QSYQ combined with WM reduced the incidence of the primary endpoint. These findings provide a promising option for managing ACS after PCI and suggest the potential treatment for reducing the risk of primary endpoint included cardiac death, non-fatal myocardial infarction, and urgent revascularization through intermittent administration of QSYQ.(Registra

关键词： Qishen Yiqi Dripping Pill acute coronary syndrome percutaneous coronary intervention primary and secondary endpoint

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Recent advances on thermosensitive hydrogels-mediated precision therapy

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Asian Journal of Pharmaceutical Sciences 2024年第3期19卷 1-21页

作者： Hao Chen Jiangmei Xu Jiangwei Sun Yongxin Jiang Wang Zheng Wei Hu Haisheng Qian Department of clinical pharmacology The Second Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China Department of Dermatology and Rheumatology Immunology Xinqiao HospitalArmy Medical UniversityChongqing 400037China School of Biomedical Engineering Anhui Provincial Institute of Translational MedicineAnhui Medical UniversityHefei 230032China

Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites,increased therapeutic efficacy,and reduced adverse *** the past few years,sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic *** can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room *** by their unique properties,thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision *** this review,the state-of-theart developments in thermosensitive hydrogels for precision therapy are investigated,which covers from the thermo-gelling mechanisms and main components to biomedical applications,including wound healing,anti-tumor activity,osteogenesis,and periodontal,sinonasal and ophthalmic *** most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.

关键词： Thermosensitive hydrogels Injectable Sprayable Stimuli-responsive Precision therapy

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GRK2 mediated degradation of SAV1 initiates hyperplasia of fibroblast-like synoviocytes in rheumatoid arthritis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1222-1240页

作者： Paipai Guo Ji Jiang Rui Chu Feng He Mingli Ge Ruhong Fang Qiuyun Guan Huijuan Cheng Chunru Jiang Tiantian Su Zhenduo Zhu Hao Liu Wei Wei Shihao Zhang Qingtong Wang institute of clinical pharmacology Anhui Medical UniversityKey Laboratory of Anti-inflammatory and Immune MedicineMinistry of EducationCollaborative Innovation Center of Anti-inflammatory and Immune MedicinesHefei 230032China School of Pharmacy Bengbu Medical CollegeBengbu 233030China The Third Affiliated hospital of Anhui Medical University(the First People’s hospital of Hefei) Hefei 230061China

Hyperplasia and migration of fibroblast-like synoviocytes(FLSs)are the key drivers in the pathogenesis of rheumatoid arthritis(RA)and joint *** Yes-associated protein(YAP),which is a powerful transcription co-activator for proliferative genes,was observed in the nucleus of inflammatory FLSs with unknown upstream *** Gene Expression Omnibus database analysis,it was found that Salvador homolog-1(SAV1),the pivotal negative regulator of the Hippo-YAP pathway,was slightly downregulated in RA ***,SAV1 protein expression is extremely ***,it was revealed that SAV1 is phosphorylated,ubiquitinated,and degraded by interacting with an important serine-threonine kinase,G protein-coupled receptor(GPCR)kinase 2(GRK2),which was predominately upregulated by GPCR activation induced by ligands such as prostaglandin E2(PGE2)in *** process further contributes to the decreased phosphorylation,nuclear translocation,and transcriptional potency of YAP,and leads to aberrant FLSs *** depletion of GRK2 or inhibition of GRK2 by paroxetine rescued SAV1 expression and restored YAP phosphorylation and finally inhibited RA FLSs proliferation and ***,paroxetine treatment effectively reduced the abnormal proliferation of FLSs in a rat model of collagen-induced arthritis which was accompanied by a significant improvement in clinical ***,these results elucidate the significance of GRK2 regulation of Hippo-YAP signaling in FLSs proliferation and migration and the potential application of GRK2 inhibition in the treatment of FLSs-driven joint destruction in RA.

关键词： Rheumatoid arthritis Fibroblast-like synoviocytes G protein-coupled receptor kinase 2 Salvador homolog-1 Yes-associated protein

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The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center Research institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

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Formulation,characterization and in vivo and in vitro evaluation of aloe-emodin-loaded solid dispersions for dissolution enhancement

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Journal of Traditional Chinese Medicine 2024年第1期44卷 54-62页

作者： LI Xiuyan LUO Yuting WANG Jinhui DU Zhimin Key Laboratory of Basic and Application Research of Beiyao Heilongjiang University of Chinese MedicineMinistry of EducationHarbin 150040China College of Pharmacy Harbin Medical UniversityHarbin 150081China institute of clinical pharmacology the Second Affliated Hospital of Harbin Medical University(University Key aboratory of Drug ResearchHeilongjiang Province)Harbin 150086China Department of clinical pharmacology College of Pharmacy Harbin Medical UniversityHarbin 150081China State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacao 999078China

OBJECTIVE:To prepare aloe-emodin solid dispersion(AE-SD)and determine the metabolic process of AE and AE-SD in ***:AE-SD was prepared via solvent evaporation or solvent melting using PEG-6000 and PVP-K30 as *** analysis,X-ray diffraction spectroscopy,differential scanning calorimetry,Fourier transform infrared spectroscopy and scanning electron microscopy were used to identify the physical state of *** prescriptions were screened via the dissolution degree determination *** Phoenix software,AE suspension and AE-SD were subjected to a pharmacokinetic comparison study analyzing the alteration of behavior in vivo after AE was prepared as a solid *** toxicity was assessed in mice,and the physiological toxicity was used as the determination criterion for ***:AE-SD showed that AE existed in the carrier in an amorphous *** with polyethylene glycol,polyvinylpyrrolidone(PVP)inhibited AE crystallization,causing the drug to transform from a dense crystalline state to an amorphous form and increasing the degree of drug ***,it was more suitable as a carrier material for *** addition of poloxamer(POL)was more beneficial to the stability of solid dispersions and could reduce the amount of *** dissolution test confirmed that the optimal ratio of AE to the composite vector AE-PVP-POL was 1:2:2,and its dissolution effect was also *** on the pharmacokinetic comparison,the drug absorption was faster and quickly reached the peak of blood drug concentration in AE-SD compared to AE,the Cmax of AE-SD was greater than that of AE,and t1/2 and mean residence time of AE-SD were less than *** results showed that the drug metabolism in AE-SD was better,and the residence time was *** toxicology study showed that both AE and AE-SD had no ***:This paper established that the solubility of the drug could be increased after preparing a solid dispersion,

关键词： aloe-emodin solid dispersion solvent evaporation drug liberation pharmacokinetics

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STING-mediated IL-6 Inhibits OATP1B1 Expression via the TCF4 Signaling Pathway in Cholestasis

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Journal of clinical and Translational Hepatology 2024年第8期12卷 701-712页

作者： Yan Guo Hongjia Zhang Nan Zhao Ying Peng Dongya Shen Yubin Chen Xiaoxun Zhang Can-E Tang Jin Chai Department of Endocrinology Xiangya HospitalCentral South UniversityChangshaHunanChina Department of Gastroenterology Institute of Digestive Diseases of PLACholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver DiseaseThe First Affiliated Hospital(Southwest Hospital)to Third Military Medical University(Army Medical University)ChongqingChina Department of clinical pharmacology Xiangya HospitalCentral South UniversityChangshaHunanChina Department of Cardiac Surgery Xiangya HospitalCentral South UniversityChangshaHunanChina National clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunanChina

Background and Aims Organic anion-transporting polypeptides(OATPs)play a crucial role in the transport of bile acids and *** our previous study,interleukin 6(IL-6)reduced OATP1B3 levels in cholestatic ***,it remains unclear whether IL-6 inhibits OATP1B1 expression in cholestatic *** study aimed to investigate whether IL-6 can inhibit OATP1B1 expression and explore the underlying *** The effect of stimulator of interferon genes(STING)signaling on inflammatory factors was investigated in a cholestatic mouse model using RT-qPCR and enzyme-linked immunosorbent *** assess the impact of inflammatory factors on OATP1B1 expression in hepatocellular carcinoma,we analyzed OATP1B1 expression by RT-qPCR and Western Blot after treating PLC/PRF/5 cells with TNF-α,IL-1β,and *** elucidate the mechanism by which IL-6 inhibits OATP1B1 expression,we examined the expression of the OATP1B1 regulator TCF4 in PLC/PRF/5 and HepG2 cells using RT-qPCR and Western *** interaction mechanism betweenβ-catenin/TCF4 and OATP1B1 was investigated by knocking downβ-catenin/TCF4 through siRNA *** The STING inhibitor decreased inflammatory factor levels in the cholestatic mouse model,with IL-6 exhibiting the most potent inhibitory effect on ***-6 downregulatedβ-catenin/TCF4,leading to decreased OATP1B1 ***-downβ-catenin/TCF4 counteracted theβ-catenin/TCF4-mediated repression of *** STING-mediated IL-6 up-regulation may inhibit OATP1B1,leading to reduced transport of bile acids and bilirubin by *** may contribute to altered pharmacokinetics in patients with diseases associated with increased IL-6 production.

关键词： Inflammation Bile acid Bilirubin Cholestasis STING IL-6 β-catenin TCF4

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