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Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase(G6PD)by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis

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Science China(Life Sciences) 2024年第8期67卷 1648-1665页

作者： Jie Gao Xiaoyi Shi Yaohui Sun Xudong Liu Feng Zhang Chengcheng Shi Xiao Yu Zhiping Yan Long Liu Shizhe Yu Jiacheng Zhang Xiaodan Zhang Shuijun Zhang Wenzhi Guo Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Diagnosis&Treatment League for hepatopathy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Innovative Research Group for Hepatobiliary&Pancreatic Surgery and Digestive Organ Transplantation Zhengzhou 450052China Henan Organ Transplantation Quality Control Centre Zhengzhou 450052China Henan Engineering Technology Research Center for Organ Transplantation Zhengzhou 450052China Department of Pharmacy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of General Surgery Huashan HospitalFudan University Shanghai 200040China Cancer Metastasis institute Fudan UniversityShanghai 200040China

Betaine-homocysteine methyltransferase(BHMT)regulates protein methylation and is correlated with tumorigenesis;however,the effects and regulation of BHMT in hepatocarcinogenesis remain largely ***,we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma(HCC)using tissue samples from 198 *** was to be frequently found(86.6%)expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with *** overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo,whereas complete knockout of Bhmt(Bhmt^(−/−))produced the opposite *** combined proteomics,metabolomics,and molecular biological strategies and detected that Bhmt^(−/−)promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase(G6PD)and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing *** contrast,restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated ***,coimmunoprecipitation identified monomethylated modifications of the G6PD,and BHMT regulated the methylation of *** sequence analysis,generation and application of specific antibodies,and site-directed mutagenesis indicated G6PD methylation at the arginine residue ***,we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD,thereby inhibiting G6PD activity,which in turn suppressed *** together,this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency,suggesting a potential therapeutic strategy for HCC treatment.

关键词： HCC BHMT arginine methylation G6PD PPP metabolism

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Effect of traditional Chinese medicine combined with Western therapy on primary hepatic carcinoma： a systematic review with meta-analysis

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Frontiers of Medicine 2017年第2期11卷 191-202页

作者： Li Ma Bin Wang Yuanxiong Long Hanmin Li Hubei University of Chinese Medicine Wuhan 430065 China hepatopathy institute Affiliated Hospital of Hubei University of Chinese Medicine (Chinese Medicine Hospital in Hubei Province) Wuhan 430061 China

Primary hepatic carcinoma （PHC） is a common malignant tumor in China. Cancer is comprehensively treated with various therapeutic regimes, including traditional Chinese medicine （TCM）. TCM has been widely used to improve the quality of fife, delay the time of cancer progression, and prolong the median survival time. This systematic review with meta-analysis aimed to assess the effect of TCM combined with Western therapy on primary hepatic carcinoma. A comprehensive literature search was conducted in six databases, including CNKI, VIP, Wan-Fang Database, CBM, PubMed, and Cochrane library. A total of 44 randomized controlled trials （RCTs） involving 3429 participants suffering from PHC were selected. Meta-analysis results indicated that the overall effect of TCM and Western integrative treatment on PHC was higher than that of Western intervention alone, which can postpone tumor recurrence and metastasis and prolong the overall survival time of patients with PHC. Although the obtained evidence remained weak because of the poor methodological quality of the included studies, this review provided relevant data supporting the efficacy and safety of TCM combined with Western therapies. In future research, individual RCT studies should incorporate accepted standards for trial design and reporting, proper outcome indicators according to international standards, blinding in allocation concealment, and valid follow-up periods.

关键词： traditional Chinese medicine primary hepatic carcinoma meta-analysis

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Clinical trial with traditional Chinese medicine intervention ''tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment'' for chronic hepatitis B-associated liver failure

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World Journal of Gastroenterology 2014年第48期20卷 18458-18465页

作者： Han-Min Li Zhi-Hua Ye Jun Zhang Xiang Gao Yan-Ming Chen Xin Yao Jian-Xun Gu Lei Zhan Yang Ji Jian-Liang Xu Ying-He Zeng Fan Yang Lin Xiao Guo-Guang Sheng Wei Xin Qi Long Qing-Jing Zhu Zhao-Hong Shi Lian-Guo Ruan Jia-Yao Yang Chang-Chun Li Hong-Bin Wu Sheng-Duo Chen Xin-La Luo hepatopathy institute Affiliated Hospital of Hubei University of Chinese Medicine Hubei University of Chinese Medicine Jingzhou Hospital of Traditional Chinese Medicine Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency School of Pharmaceutical Science and Technology Tianjin University

AIM:To study the clinical efficacy of traditional Chinese medicine(TCM)intervention"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")for treating liver failure due to chronic hepatitis ***:We designed the study as a randomized controlled clinical *** number of Chinese Clinical Trial Registry is Chi CTR-TRC-12002961.A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical *** were randomly assigned to the following three groups:(1)a modern medicine control group(MMC group,36patients);(2)a"tonifying qi and detoxification"("TQD")group(72 patients);and(3)a"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")group(36patients).Patients in the MMC group received general internal medicine treatment;patients in the"TQD"group were given a TCM formula"tonifying qi and detoxification"and general internal medicine treatment;patients in the"TTK"group were given a TCM formula of"TTK"and general internal medicine *** participants were treated for 8 wk and then followed at 48 wk following their final *** primaryefficacy end point was the patient fatality rate in each *** of various virological and biochemical indicators served as secondary *** one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment ***:At the 48-wk post-treatment time point,the patient fatality rates in the MMC,"TQD",and"TTK"groups were 51.61%,35.38%,and 16.67%,respectively,and the differences between groups were statistically significant(P0.05).Patients in the"TTK"group had significantly higher levels of serum to

关键词： Clinical study 'Tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment'('TTK') Liver regeneration Treatment with integrated traditional and Western medicine Chronic hepatitis B-associated liver failure

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Heme oxygenase-1 prevents liver fibrosis in rats by regulating the expression of PPAR_γ and NF-_κB

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World Journal of Gastroenterology 2012年第14期18卷 1680-1688页

作者： Hui Yang Long-Feng Zhao Zhong-Fu Zhao Yan Wang Jing-Jing Zhao Li Zhang Department of Infectious Diseases the First AffiliatedHospital of Shanxi Medical University Taiyuan 030001 ShanxiProvince China institute of hepatopathy Changzhi MedicalCollege Changzhi 046000 Shanxi Province China

AIM:To investigate the effects of heme oxygenase(HO)-1 on liver fibrosis and the expression of peroxisome proliferator-activated receptor gamma(PPARγ) and nuclear factor-kappa B(NF-κB) in ***:Sixty Wistar rats were used to construct liver fibrosis models and were randomly divided into 5 groups:group A(normal,untreated),group B(model for 4 wk,untreated),group C(model for 6 wk,untreated),group D [model for 6 wk,treated with zinc protoporphyrin Ⅸ(ZnPP-Ⅸ) from week 4 to week 6],group E(model for 6 wk,treated with hemin from week 4 to week 6).Next,liver injury was assessed by measuring serum alanine aminotransferase(ALT),aspartate aminotransferase(AST) and albumin *** degree of hepatic fibrosis was evaluated by measuring serum hyaluronate acid(HA),type Ⅳ collagen(Ⅳ-C) and by histological ***(Hyp) content in the liver homogenate was *** expres-sion levels of alpha-smooth muscle actin(α-SMA) in liver tissue were measured by real-time quantitative polymerase chain reaction(RT-PCR).The expression levels of PPARγ and NF-κB were determined by RT-PCR and Western ***:The expression of HO-1 increased with the development of *** of HO-1 by hemin significantly attenuated the severity of liver injury and the levels of liver fibrosis as compared with inhibition of HO-1 by ZnPP-Ⅸ.The concentrations of serum ALT,AST,HA and Ⅳ-C in group E decreased compared with group C and group D(P < 0.01).Amount of Hyp and α-SMA in the liver tissues in group E decreased compared with group C(0.62 ± 0.14 vs 0.84 ± 0.07,1.42 ± 0.17 vs 1.84 ± 0.17,respectively,P < 0.01) and group D(0.62 ± 0.14 vs 1.11 ± 0.16,1.42 ± 0.17 vs 2.56 ± 0.37,respectively,P < 0.01).The expression of PPARγ at levels of transcription and translation decreased with the development of fibrosis especially in group D;and it increased in group E compared with groups C and D(0.88 ± 0.15 vs 0.56 ± 0.19,0.88 ± 0.15 vs 0.41 ± 0.11,respectively,P < 0.01).The expr

关键词： Heme oxygenase-1 Peroxisome proliferator-activated receptor gamma Nuclear factor-kappa B Liver fibrosis Hemin

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Correlation between acne and Northwest dryness syndrome in Xinjiang autonomous region of China

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Journal of Traditional Chinese Medicine 2013年第6期33卷 761-765页

作者： Yan Wang Xiaozhong Wang Haiyan Yuan Jing Jing Huaike Chen Xiaohong Ren Lili Zhang Huitian Zhang Mingxin Zhou hepatopathy Department Xinjiang Uygur Autonomous Region Chinese Medicine Hospital Chinese Medical Department Xinjiang Urumqi Petrochemical Hospital Research Department National Clinical Research Base of Traditional Chinese Medicine Chinese Medical Department Armed Police Corps Headquarters Hospital Traditional Chinese Medicine institute Xinjiang Medical University

OBJECTIVE： To analyze the correlation between ac- he and Northwest dryness syndrome in the Xinji- ang region to provide an epidemiological founda- tion for the prevention and treatment of acne in the region. METHODS： The correlations among acne, clinical syndromes of Northwest dryness syndrome, and Northwest dryness syndrome were evaluated using the syndrome fitness index and canonical correla- tion analysis. RESULTS： The ache group had a Northwest drynesssyndrome rate of 24.13%, and the control group 10.34% （χ2=7.733, P〈0.01）. There was no significant difference in the fitness index for acne and for the sub-syndromes of Northwest dryness syndrome （P〉 0.05）. The first canonical correlation coefficient was 0.5656 （P〈0.01）. The acne-dependent variable group had the largest damp-heat syndrome load （0.8709）, and the independent variable had the largest lung-heart-spleen pyretic dryness load （0.6766）. CONCLUSION： Northwest dryness syndrome is a risk factor for ache in the Xinjiang region. Exoge- nous dryness and endogenous damp are frequent- ly seen as subsyndromes in Northwest dryness syn- drome in acne patients in the region. Acne was cor- related with the damp-heat and lung-heart-spleen pyretic dryness sub-syndromes of Northwest dry- ness syndrome.

关键词： Acneiform eruptions Exogenous dry-ness syndrome Northwest China Correlation

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Therapeutic potential of traditional Chinese medicine for the treatment of NAFLD:A promising drug Potentilla discolor Bunge

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Acta Pharmaceutica Sinica B 2022年第9期12卷 3529-3547页

作者： Longshan Ji Qian Li Yong He Xin Zhang Zhenhua Zhou Yating Gao Miao Fang Zhuo Yu Robim M.Rodrigues Yueqiu Gao Man Li Laboratory of Cellular Immunity Institute of Clinical ImmunologyShanghai Key Laboratory of Traditional Chinese MedicineShuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineKey Laboratory of Liver and Kidney Diseases(Shanghai University of Traditional Chinese Medicine)Ministry of EducationShanghai 201203China Shanghai institute of Materia Medica Chinese Academy of SciencesShanghai 201203China Department of hepatopathy Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of in Vitro Toxicology and Dermato-Cosmetology Faculty of Medicine and PharmacyVrije Universiteit BrusselBrussels 1000Belgium

Nonalcoholic fatty liver disease(NAFLD)is characterized by excessive accumulation of hepatic lipids and metabolic stress-induced liver *** are currently no approved effective pharmacological treatments for *** Chinese medicine(TCM)has been used for centuries to treat patients with chronic liver diseases without clear disease types and *** recently,TCM has been shown to have unique advantages in the treatment of *** performed a systematic review of the medical literature published over the last two decades and found that many TCM formulas have been reported to be beneficial for the treatment of metabolic dysfunctions,including Potentilla discolor Bunge(PDB).PDB has a variety of active compounds,including flavonoids,terpenoids,organic acids,steroids and *** compounds have been shown to exhibit a series of beneficial effects for the treatment of NAFLD,including anti-oxidative and anti-inflammatory functions,improvement of lipid metabolism and reversal of insulin *** this review,we summarize potential therapeutic effects of TCM formulas for the treatment of NAFLD,focusing on the medicinal properties of natural active compounds from PDB and their underlying *** point out that PDB can be classified as a novel candidate for the treatment and prevention of NAFLD.

关键词： Nonalcoholic fatty liver disease(NAFLD) Traditional Chinese medicine Acupuncture Potentilla discolor Bunge(PDB) Natural active compounds Anti-oxidative Anti-inflammatory Lipid metabolism Insulin resistance Endoplasmic reticulum stress Intestinal microflora

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Tenofovir alafenamide significantly increased serum lipid levels compared with entecavir therapy in chronic hepatitis B virus patients

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世界肝病学杂志:英文版(电子版) 2023年第8期15卷 964-972页

作者： Rui-Min Lai Shan Lin Miao-Miao Wang Na Li Jia-Hui Zhou Xiao-Yu Lin Tian-Bin Chen Yue-Yong Zhu Qi Zheng Department of Hepatology Hepatology Research InstituteThe First Affiliated HospitalFujian Medical UniversityFujian Clinical Research Center for Hepatopathy and Intestinal DiseasesFuzhou 350005Fujian ProvinceChina Department of Hepatology National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhou 350212Fujian ProvinceChina Department of Endocrinology The 910th Hospital of The Joint Service Support ForceQuanzhou 362000Fujian ProvinceChina Department of Laboratory Medicine The First Affiliated HospitalFujian Medical UniversityFuzhou 350005Fujian ProvinceChina

BACKGROUND Tenofovir alafenamide(TAF)has a serum lipid-raising effect in patients with HIV;however,its effect on serum lipids and nonalcoholic fatty liver disease(NAFLD)risk in patients with chronic hepatitis B(CHB)is *** To compare the effects of TAF and entecavir(ETV)on serum lipid levels in patients with *** In this retrospective cohort study,the data including the clinical features,serum lipids,and metabolic factors of patients with CHB at baseline and approximately 1 year after TAF or ETV treatment were collected and *** used propensity score-matched models to assess the effects on high-density lipoprotein,lowdensity lipoprotein,triglycerides,and total cholesterol(TCHO).RESULTS A total of 336 patients(75.60%male)were included;63.69%received TAF and 36.31%received *** with the ETV group,the TAF group had significantly higher TCHO levels after treatment(4.67±0.90 vs 4.36±1.05,P=0.006).In a propensity score-matched model for body mass index,age,sex,smoking,drinking,presence of comorbidities such as NAFLD,cirrhosis,diabetes mellitus,and hypertension,TAF-treated patients had significantly increased TCHO levels compared to that at baseline(P=0.019).There was no difference for the ETV *** mass index,sex,hypertension,baseline TCHO,and creatine kinase-MB isoenzyme levels were significantly associated with elevated TCHO levels in logistic regression ***,1-year TAF treatment did not increase the incidence of *** A greater increase in TCHO was observed in patients with CHB receiving TAF compared to those receiving ***,TAF-induced dyslipidemia did not increase the incidence of NAFLD.

关键词： Tenofovir alafenamide Entecavir Hepatitis B virus Serum lipid Metabolic factor

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Glycogenic hepatopathy

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Hepatobiliary & Pancreatic Diseases International 2018年第2期17卷 113-118页

作者： Johad Khoury Yaniv Zohar Naim Shehadeh Tarek Saadi Internal Medicine B Rambam Health Care Campus and Rappaport Faculty of Medicine Technion-Israel Institute of Technology Liver Unit Rambam Health Care Campus and Rappaport Faculty of Medicine Technion-Israel Institute of Technology Department of Pathology Rambam Health Care Campus and Rappaport Faculty of Medicine Technion-Israel Institute of Technology Meyer Children's Hospital of Haifa Rambam Health Care Campus and Rappaport Faculty of Medicine Technion-Israel Institute of Technology institute of Diabetes Endocrinology and Metabolism Rambam Health Care Campus and Rappaport Faculty of Medicine Technion-Israel Institute of Technology Department of Gastroenterology Rambam Health Care Campus and Rappaport Faculty of Medicine Technion-Israel Institute of Technology

Background: Glycogenic hepatopathy(GH) is a disorder associated with uncontrolled diabetes mellitus,most commonly type 1, expressed as right upper quadrant abdominal pain, hepatomegaly and increased liver enzymes. The diagnosis may be difficult, because laboratory and imaging tests are not pathognomonic. Although GH may be suggested based on clinical presentation and imaging studies, the gold standard for diagnosis is a liver biopsy, showing a significant accumulation of glycogen within the hepatocytes. GH may be diagnosed also after elevated liver enzymes in routine blood tests. GH usually regresses after tight glycemic control. Progression to end-stage liver disease has never been reported. This review aims to increase the awareness to this disease, to suggest a pathway for investigation that may reduce the use of unnecessary tests, especially invasive *** sources: A Pub Med database search(up to July 1, 2017) was done with the words "glycogenic hepatopathy", "hepatic glycogenosis", "liver glycogenosis" and "diabetes mellitus-associated glycogen storage hepatopathy". Articles in which diabetes mellitus-associated liver glycogen accumulation was described were included in this ***: A total of 47 articles were found, describing 126 patients with GH. Hepatocellular disturbance was more profound than cholestatic disturbance. No synthetic failure was ***: GH may be diagnosed conservatively, based on corroborating medical history, physical examination, laboratory tests, imaging studies and response to treatment, even without liver biopsy. In case of doubt about the diagnosis or lack of clinical response to treatment, a liver biopsy may be *** is no role for noninvasive tests like fibroscan or fibrotest for the diagnosis of GH or for differentiation of this situation from nonalcoholic fatty liver disease.

关键词： Glycogenic hepatopathy Diabetes mellitus Hepatic glycogenosis Mauriac syndrome

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Mitochondrial hepatopathy: Anticipated difficulties in management of fatty acid oxidation defects and urea cycle defects

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World Journal of Hepatology 2022年第1期14卷 180-194页

作者： Aathira Ravindranath Moinak Sen Sarma Division of Pediatric Gastroenterology Institute of Gastrointestinal SciencesApollo BGS HospitalsMysore 570023KarnatakaIndia Pediatric Gastroenterology Sanjay Gandhi Postgraduate Institute of Medical SciencesLucknow 226014Uttar PradeshIndia

Fatty acid oxidation defects(FAOD)and urea cycle defects(UCD)are among the most common metabolic liver *** of these disorders is dotted with challenges as the strategies differ based on the type and severity of the *** those with FAOD the cornerstone of management is avoiding hypoglycemia which in turn prevents the triggering of fatty acid *** this review,we discuss the role of carnitine supplementation,dietary interventions,newer therapies like triheptanoin,long-term treatment and approach to positive newborn *** UCD the general goal is to avoid excessive protein intake and indigenous protein ***,one size does not fit all and striking the right balance between avoiding hyperammonemia and preventing deficiencies of essential nutrients is a formidable *** issues during the acute presentation including differential diagnosis of hyperammonemia,dietary dilemmas,the role of liver transplantation,management of the asymptomatic individual and monitoring are described in detail.A multi-disciplinary team consisting of hepatologists,metabolic specialists and dieticians is required for optimum management and improvement in quality of life for these patients.

关键词： Mitochondrial hepatopathy Metabolic liver disease Liver transplantation Hyperammonemia Hypoglycemia Carnitine

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A 3D bio-printed spheroids based perfusion in vitro liver on chip for drug toxicity assays

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Chinese Chemical Letters 2022年第6期33卷 3167-3171页

作者： Tian Tian Yuhan Ho Chen Chen Hebin Sun Janan Hui Panhui Yang Yuqing Ge Ting Liu Jian Yang Hongju Mao institute of Microsystem and Information Technology(SIMIT) Chinese Academy of Sciences(CAS)Shanghai 200050China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China Shanghai Industrial Technology Research institute(SITRI) Shanghai 201800China School of Stomatology Dalian Medical UniversityDalian 116044China State Key Laboratory of component-based Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China institute of Traditional Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China

Liver is the foremost organ of human being for drug metabolism,and it played a significant role in toxicity evaluation of *** a liver model in vitro can accelerate the process of the drug screening and new drug research and *** provide a 3D printing based hepatic sinusoid-on-a-chip microdevice that reconstitutes organ-level liver functions to create a drug screening model of toxicity evaluation on *** microfluidic device,which recapitulates the hepatic sinusoid microenvironment,consists of PET polyporous membranes which mimic the perisinusoidal space,and experience fluid flow to mimic the hepatic arterial *** PET membrane was used to separate the hepatocyte and *** endotheliocyte was cultured on the downside of the membrane and the hepatocyte were 3D seeded on the membrane via the 3D *** device was used to reproduce the in vitro liver model for drug toxicity *** expression of several biomarkers of liver was compared with the monoculture and 2D cultured conditions,and the results reveal that this organ-on-a-chip microdevice mimics the drug hepatoxicity that has not been possible by 2D cell-based and animal models,providing a useful platform for screening the drugs and developing an effective therapy in hepatopathy.

关键词： Liver-on-chip Drug screening Drug toxicity 3D-printing 3D-culture

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