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NKX2-3 and IRGM variants are associated with diseasesu sceptibility to IBD in Eastern European patients

World Journal of Gastroenterology 2010年第41期16卷 5233-5240页

作者： Nora Meggyesi Lajos S Kiss Magdalena Koszarska Martin Bortlik Dana Duricova Laszlo Lakatos Tamas Molnar Martin Lenicek Libor Vítek Istvan Altorjay Maria Papp zsolt Tulassay Pal Miheller Janos Papp Attila Tordai Hajnalka Andrikovics Milan Lukas Peter Laszlo Lakatos Department of Molecular Diagnostics Hun-garian National Blood Transfusion Service H-1113 BudapestHungary 1st Depart-ment of Medicine Semmelweis University H-1083 BudapestHungary IBD Clinicaland Research Centre ISCARE IVF and 1st Medical FacultyCharles University 170 04 Prague Czech Republic 1st Department of Medicine Csolnoky F.County Hospital H8200 Veszprem Hungary 1st Department of Medicine University ofSzeged H6720 Szeged Hungary Department of Biochemistry andLaboratory Diagnostics 1st Medical Faculty Charles Univer-sity 170 04 Prague Czech Republic 2nd Department of Medicine University of Debrecen H4032 Debrecen Hungary 2nd Department of Medicine Semmelweis University H1085 Budapest Hungary

AIM: To investigate variants of immunity-related GT-Pase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD).METHODS: We analyzed 1707 Hungarian and Czech subjects with Crohn’s disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCy-cler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: NKX2-3 rs10883365 variant allele was as-sociated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associat-ed with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathio-prine, efficacy of infliximab, or need for surgery. CONCLUSION: NKX2-3 and IRGM are susceptibility locifor IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations.

关键词： Crohn’s disease Ulcerative colitis NKX2-3 Immunity-related GTPase family M ECM1 Genotype Phenotype Pharmacogenetics

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DNA extraction from paraffin embedded colorectal carcinoma samples: A comparison study of manual vs automated methods,using four commercially kits

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World Journal of Clinical Oncology 2019年第9期10卷 307-317页

作者： zsolt Kovacs Ioan Jung Erzsebet Csernak Zoltan Szentirmay Laura Banias Genoveva Rigmanyi Simona Gurzu Department of Pathology University of MedicinePharmacySciences and TechnologyTargu-Mures 530149Romania Research Center(CCAMF) University of MedicinePharmacySciences and TechnologyTargu-Mures 540139Romania

BACKGROUND Nucleic acid isolation from formalin-fixed, paraffin-embedded tissue(FFPET)samples is a daily routine in molecular pathology laboratories, but extraction from FFPET is not always easily achieved. Choosing the right extraction technique is key for further *** To compare the performance of four commercially available kits used for DNA extraction in routine *** DNA isolation was performed on 46 randomly selected formalin-fixed, paraffinembedded(FFPE) colorectal adenocarcinoma(CRC) surgical specimens. Four commercially available extraction kits were used: two for manual DNA extraction(the Pure Link Genomic DNA Mini Kit from Invitrogen and the High Pure FFPE DNA Isolation Kit from Roche) and two for automated DNA extraction(the i Prep Genomic DNA Kit from Invitrogen and the Magna Pure LC DNA Isolation Kit from Roche). The DNA concentration and quality(odds ratio) among the four systems were compared. The results were correlated with the clinicopathological aspects of CRC cases: age, gender, localization, macro-and microscopic features,lymph node metastases, and the lymph node *** The highest DNA concentration was obtained using the manual kits: 157.24 ±62.99 ng/μL for the Pure Link Genomic DNA Mini Kit and 86.64 ng/μL± 43.84 for the High Pure FFPE DNA Isolation Kit(P < 0.0001). Lower concentrations were obtained with automated systems: 20.39 ± 21.19 ng/μL for the Magna Pure LC DNA Isolation Kit and 8.722 ± 6.408 ng/μL for the i Prep Genomic DNA Kit,with differences between the systems used(P < 0.0001). The comparison between age, gender, tumor localization, pT or pN stage and the lymph node ratio indicated no statistically significant difference in DNA concentration using any of the nucleic acid isolation kits. DNA concentration was influenced by the macroscopic features and grade of differentiation. A higher DNA concentration was obtained for well-differentiated polypoid colorectal adenocarcinomas(CRCs), compared with undif

关键词： DNA isolation Colorectal cancer Paraffin-embedded PureLink Genomic DNA Mini Kit High Pure FFPE DNA Isolation Kit iPrep Genomic DNA Kit MagnaPure LC DNA Isolation Kit

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荧光假单胞菌ZX对葡萄采后灰霉病的防治

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食品工业科技 2021年第22期42卷 125-132页

作者：魏雪江孟遥钟涛张曼王智荣 zsolt Zalan FERENC Hegyi KRISZTINA Takacs 杜木英西南大学食品科学学院重庆400715 中匈食品科学联合研究中心重庆400715 匈牙利国家农业创新研究中心匈牙利布达佩斯1022 农业部农产品贮藏保鲜质量安全风险评估实验室(重庆) 重庆400715

研究荧光假单胞菌(Pseudomonas fluorescens)ZX对葡萄采后灰霉病的防治效果。以“巨峰”葡萄为试材,测定*** ZX的控病效果和生长动态,在离体条件下通过孢子萌发观察、挥发性物质抑菌测试、扫描电镜探究其对灰葡萄孢霉(Botrytis cinerea... 详细信息

研究荧光假单胞菌(Pseudomonas fluorescens)ZX对葡萄采后灰霉病的防治效果。以“巨峰”葡萄为试材,测定*** ZX的控病效果和生长动态,在离体条件下通过孢子萌发观察、挥发性物质抑菌测试、扫描电镜探究其对灰葡萄孢霉(Botrytis cinerea)的防治。结果表明,使用*** ZX处理,葡萄果实的发病率仅为24.8%,明显低于对照组(发病率64.67%),病斑直径最小,可以明显抑制***孢子萌发、芽管伸长。*** ZX产生的挥发性物质具有较强的抑菌效果,并且能对***有重寄生作用,破坏菌丝的正常形态。另外,无论是浸泡还是接种处理,*** ZX都能在葡萄果实上快速地定殖生长。由此表明,*** ZX通过抑制***生长来控制葡萄采后灰霉病,为果实采后防腐保鲜提供一种新的选择。

关键词：荧光假单胞菌生物防治葡萄采后病害

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Association of hepatocyte-derived growth factor receptor/caudal type homeobox 2 co-expression with mucosal regeneration in active ulcerative colitis

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世界胃肠病学杂志：英文版 2015年第28期21卷 8569-8579页

作者： Ferenc Sipos Miklós Constantinovits Gábor Valcz zsolt Tulassay Gy?rgyi M?zes 2nd Department of Internal Medicine Semmelweis University Molecular Medicine Research Group Hungarian Academy of Sciences

AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were *** preparing tissue microarrays and blood smears HGFR,caudal type homeobox 2(CDX2),prominin-1(CD133) and Musashi-1conventional and double fluorescent immunolabelings were *** samples were digitalized using high-resolution Mirax Desk instrument,and analyzed with the Mirax TMA Module *** semiquantitative counting of immunopositive lamina propria(LP) cells 5 fields of view were counted at magnification x 200 in each sample core,then mean ± SD were *** case of peripheral blood smears,30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells(mean ± SD) was *** 337 nm UVA Laser MicroDissection system at least 5000 subepithelial cells from the lamina propria were *** expression analysis of HGFR,CDX2,CD133,leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5),Musashi-1 and cytokeratin20(CK20) were performed in both laser-microdisscted samples and blood samples by using real time reverse transcription polymerase chain reaction(RT-PCR).RESULTS:By performing conventional and double fluorescent immunolabelings confirmed by RT-PCR,higher number of HGFR(blood:6.7 ± 1.22 vs 38.5 ±3.18;LP:2.25 ± 0.85 vs 9.22 ± 0.65;P < 0.05),CDX2(blood:0 vs 0.94 ± 0.64;LP:0.75 ± 0.55 vs 2.11± 0.75;P < 0.05),CD133(blood:1.1 ± 0.72 vs 8.3± 1.08;LP:11.1 ± 0.85 vs 26.28 ± 1.71;P < 0.05)and Musashi-1(blood and LP:0 vs scattered) positive cells were detected in blood and lamina propria of UC samples as compared to ***/CDX2(blood:0 vs 1± 0.59;LP:0.8 ± 0.69 vs 2.06 ± 0.72,P < 0.05)and Musashi-1/CDX2(blood and LP:0 vs sc

关键词： Hepatocyte-derived growth factor receptor Caudal type homeobox 2 CD133 Musashi-1 Leucinerichrepeat-containing G-protein coupled receptor 5 Ulcerative colitis Regeneration

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复合菌发酵苦荞麸皮馒头的工艺优化

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食品工业科技 2017年第5期38卷 238-245页

作者：何瑞廖钰婷王雪婷李玉珠 zsolt Zalan 杜木英西南大学食品科学学院重庆400715 重庆啤酒股份有限公司重庆400080 匈牙利国家农业研究与创新中心

选取从酸面团筛选的酵母YCY5-2,ZKY7-1及乳酸菌YCL7-3,ZKL10-4进行组合发酵苦荞麸皮馒头,以馒头黄酮含量和感官评定分数作为指标,筛选出发酵苦荞麸皮馒头的最适菌种组合。实验采用响应面法对菌株比例,菌株接种量,发酵时间和醒发时间进... 详细信息

选取从酸面团筛选的酵母YCY5-2,ZKY7-1及乳酸菌YCL7-3,ZKL10-4进行组合发酵苦荞麸皮馒头,以馒头黄酮含量和感官评定分数作为指标,筛选出发酵苦荞麸皮馒头的最适菌种组合。实验采用响应面法对菌株比例,菌株接种量,发酵时间和醒发时间进行了优化。结果表明:最佳组合菌种为YCY5-2和ZKL10-4,苦荞麸皮添加量为20%,最佳工艺条件为YCY5-2∶ZKL10-4=2∶1,菌种添加量为3%,发酵时间为5 h、醒发时间40 min。此条件下苦荞麸皮馒头黄酮含量为(211.33±1.34)mg Rutin/100 g,感官评分为(82.2±2.30)。与安琪酵母发酵的苦荞麸皮馒头的黄酮含量((189.70±3.66 mg)Rutin/100 g),感官评价(77.1±1.4)及质构相比可知,复合菌馒头的功能和品质均比安琪酵母的好。结论:复合菌发酵的苦荞麸皮馒头具有开发利用的价值。

关键词：乳酸菌酵母菌苦荞麸皮馒头黄酮含量优化

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荧光假单胞菌ZX对采后锦橙绿霉病的防治及其抑菌机制

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微生物学报 2019年第5期59卷 950-964页

作者：王智荣梅小飞杜木英江孟遥张洪新汪开拓 zsolt Zalán Ferenc Hegyi 阚建全西南大学食品科学学院重庆400715 中匈食品科学联合研究中心重庆400715 农业部农产品贮藏保鲜质量安全风险评估实验室(重庆) 重庆400715 重庆三峡学院生命科学与工程学院重庆404100 匈牙利国家农业研究和创新中心食品科学研究所

【目的】采后柑橘极易受指状青霉(Penicillium digitatum)侵染而发生严重的绿霉病腐烂,生物防治因具有安全、有效、环保等特点近年来备受关注。论文旨在研究荧光假单胞菌(Pseudomonas fluorescens)ZX对采后柑橘绿霉病的防治效果,揭示***... 详细信息

【目的】采后柑橘极易受指状青霉(Penicillium digitatum)侵染而发生严重的绿霉病腐烂,生物防治因具有安全、有效、环保等特点近年来备受关注。论文旨在研究荧光假单胞菌(Pseudomonas fluorescens)ZX对采后柑橘绿霉病的防治效果,揭示***对***可能存在的作用机制。【方法】以"北碚447"锦橙果实为试材,先分别接种20μL拮抗菌培养液、滤液(培养液离心后,上清经0.22μm滤膜过滤)、菌悬液(培养液离心后,菌体用无菌水反复洗涤并用无菌水重悬)和热杀死液(培养液高温高压灭菌),2 h后接种20μL P. digitatum孢子悬浮液(1×10~4spores/m L),所有果实于20oC、90%相对湿度环境下恒温恒湿培养8 d后,测定果实的发病率和病斑直径;制备柑橘皮培养基,进行平板抑菌试验,探索P. fluorescens ZX对P. digitatum孢子发芽情况的影响;采用两板对扣法和生物熏蒸法研究***挥发性次级代谢产物的抑菌作用;利用插入式细胞培养皿等分析***和***之间竞争的营养物质;同时,测定***的生长曲线,利用结晶紫染色法评估P. fluorescens ZX的生物膜形成能力。【结果】P. fluorescens ZX不同处理液之间对采后锦橙绿霉病的作用效果差异显著,菌悬液抑菌效果最好,经菌悬液处理的果实,发病率和病斑直径分别仅为40.83%和1.78 cm;不论是在柑橘皮固体培养基上对峙培养还是在液体培养基中混合培养,菌悬液和原液的作用效果较好,固体平板上,相对抑制率达到了35%–45%,液体培养基中,P. digitatum孢子12 h后的发芽率不超过27%;P. fluorescens ZX产生的挥发性物质具有抑菌作用,经P. fluorescensZX熏蒸处理的锦橙果实,发病率和病斑直径都显著降低;营养竞争试验结果表明,P. fluorescens ZX能更快速有效地消耗柑橘皮培养基中的营养,并和P. digitatum竞争葡萄糖、果糖、蔗糖、天冬氨酸、苏氨酸、丝氨酸、亮氨酸、精氨酸和脯氨酸等营养物质;同时,P. fluorescens ZX生命力强,培养4 h后即进入对数生长期,约24 h后形成成熟的生物膜。【结论】P. fluorescens ZX可能通过抑制P. digitatum孢子发芽、营养与空间竞争、形成生物膜、产生抑菌物质等方式抑制***的生长繁殖,有效防治采后锦橙绿霉病。

关键词：荧光假单胞菌绿霉病生物防治锦橙采后病害拮抗机制

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传统酸面团中优良菌种的筛选、鉴定及在苦荞麸皮馒头中的应用

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食品科技 2017年第2期42卷 156-164页

作者：王雪婷廖钰婷何瑞李玉珠 zsolt Zalán 杜木英西南大学食品科学学院重庆400715 匈牙利国家农业研究和创新中心食品科学研究所匈牙利布达佩斯999024 西南大学重庆市特色食品工程技术研究中心重庆400715

为筛选传统酸面团中的有益微生物应用于馒头生产,选取河南周口、山西运城2个不同地区的传统酸面团,从中分离鉴定出优良菌株,并将优良菌种组合用于发酵苦荞麸皮馒头。结果显示:对酵母菌初筛,测定面团发酵力、产气能力、CO2失重量、生长... 详细信息

为筛选传统酸面团中的有益微生物应用于馒头生产,选取河南周口、山西运城2个不同地区的传统酸面团,从中分离鉴定出优良菌株,并将优良菌种组合用于发酵苦荞麸皮馒头。结果显示:对酵母菌初筛,测定面团发酵力、产气能力、CO2失重量、生长曲线、p H值确定筛选出2株优良酵母菌YCY5-2和ZKY7-1;对乳酸菌初筛,测定产酸能力、产味能力及繁殖能力筛选出2株优良乳酸菌YCL7-3和ZKL10-4,经分子学鉴定分别为酿酒酵母(Saccharomyces cerevisiae)、毕赤酵母(Pichia kudriavzevii strain)、植物乳杆菌(Lactobacillus plantarum)和面包乳杆菌(Lactobacillus crustorum);经组合菌种(YCY5-2:ZKL10-4为2:1)发酵的苦荞麸皮馒头与安琪酵母苦荞麸皮馒头相比,质地性状和压缩张弛性方面组合菌组最佳,且感官评分组合菌组(82.2±2.3)高于安琪酵母组(77.1±1.4)。结果表明筛选出的优良菌种组合发酵的苦荞麸皮馒头品质更佳,为馒头的工业化生产提供了菌种支撑。

关键词：酸面团筛选酵母菌乳酸菌鉴定苦荞麸皮馒头

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Serrated pathway:Alternative route to colorectal cancer

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World Journal of Gastroenterology 2013年第5期19卷 607-615页

作者： rpád V Patai Béla Molnár zsolt Tulassay Ferenc Sipos 2~(nd )Department of Internal Medicine Semmelweis University1088 BudapestHungary Molecular Medicine Research Group Hungarian Academy of Sciences1051 BudapestHungary

Serrated polyps have been an area of intense focus for gastroenterologists over the past several years. Contrary to what was thought before,a growing body of literature indicates that these polyps can be precursors of colorectal cancer(CRC).Most of these lesions, particularly those in the proximal colon,have so far been under-recognized and missed during colonoscopy,qualifying these lesions to be the main cause of interval *** is estimated that 10%-20%of CRCs evolve through this alternative,serrated pathway, with a distinct genetic and epigenetic *** DNA methylation plays a central role in the development of this CRC *** characteristic molecular background is reflected in a unique pathological and clinical manifestation different from cancers arising via the traditional *** this review we would like to highlight morphological,molecular and clinical features of this emerging pathway that are essential for gastroenterologists and may influence their everyday practice.

关键词： Serrated pathway DNA methylation Hyperplastic polyps Serrated adenomas Colorectal cancer Endoscopic surveillance

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荧光假单胞菌对采后锦橙青霉病的防治和贮藏品质的影响

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食品与发酵工业 2018年第11期44卷 176-184页

作者：王智荣江孟遥杜木英汪开拓 zsolt Zalán Ferenc Hegyi 阚建全西南大学食品科学学院重庆400715 中匈食品科学联合研究中心重庆400715 农业部农产品贮藏保鲜质量安全风险评估实验室(重庆) 重庆400715 重庆三峡学院生命科学与工程学院重庆404100 匈牙利国家农业研究和创新中心食品科学研究所匈牙利布达佩斯H-1022

以"北碚447"锦橙果实为实验材料,研究了荧光假单胞菌(Pseudomonas fluorescens)对采后锦橙青霉病的防治效果和贮藏品质及感官品质的影响。利用P. fluorescens不同浓度菌悬液和各种处理液分别进行离体和活体实验。离体实验结果表明,1×10... 详细信息

以"北碚447"锦橙果实为实验材料,研究了荧光假单胞菌(Pseudomonas fluorescens)对采后锦橙青霉病的防治效果和贮藏品质及感官品质的影响。利用P. fluorescens不同浓度菌悬液和各种处理液分别进行离体和活体实验。离体实验结果表明,1×10~8CFU/mL菌悬液在混合固体培养基上和意大利青霉孢子共同培养时,能完全抑制其生长繁殖,对峙培养时,相对抑菌率高达(52. 59±1. 59)%;在马铃薯葡萄糖液体培养基中意大利青霉孢子12 h后的萌发率和芽管长度分别为(0. 67±0. 47)%和(2. 25±0. 25)μm。活体实验结果表明,P. fluorescens菌悬液抑菌效果最好,且其浓度越高,防治效果越好,浓度为1×10~9CFU/mL时,果实的发病率和病斑直径仅为(49. 17±1. 18)%和(2. 72±0. 09) cm; 4℃下培养16 d,20℃下培养8 d,P. fluorescens在果实伤口处的活菌数分别增长了28倍和34倍;和对照相比,P. fluorescens能显著提高果实几丁质酶和β-1,3-葡聚糖酶的活性,有效增强果实的抗病性;经P. fluorescens菌悬液保鲜的果实,病情指数显著降低,且感官品质和对照差别较小,表明该P. fluorescens试验菌株在锦橙采后病害上具有极高的生物防治潜力。

关键词：荧光假单胞菌生物防治锦橙采后病害贮藏品质感官品质

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A 3D Human Liver Model of Nonalcoholic Steatohepatitis

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Journal of Clinical and Translational Hepatology 2020年第4期8卷 359-370页

作者： Marion Duriez Agnes Jacquet Lucile Hoet Sandrine Roche Marie-Dominique Bock Corinne Rocher Gilles Haussy Xavier Vigé zsolt Bocskei Tamara Slavnic Valérie Martin Jean-Claude Guillemot Michel Didier Aimo Kannt Cécile Orsini Vincent Mikol Anne-Céline Le Fèvre Translational Sciences Sanofi1 Avenue Pierre BrossoletteChilly-MazarinFrance IT&M STATS Groupe IT&MNeuilly-sur-SeineFrance Non Clinical Biostatistics SanofiVitry sur SeineFrance Diabetes and Cardiovascular Research SanofiIndustriepark HöchstFrankfurtGermany Institute of Experimental Pharmacology Medical Faculty MannheimUniversity of HeidelbergMannheimGermany

Background and Aims: To better understand nonalcoholic steatohepatitis (NASH) disease progression and to evaluate drug targets and compound activity, we undertook the devel-opment of an in vitro 3D model to mimic liver architecture and the NASH environment. Methods:We have developed an in vitro preclinical 3D NASH model by coculturing primary hu-man hepatocytes, human stellate cells, liver endothelial cells and Kupffer cells embedded in a hydrogel of rat collagen on a 96-well plate. A NASH-like environment was induced by ad-dition of medium containing free fatty acids and tumor ne-crosis factor-α. This model was then characterized by biochemical, imaging and transcriptomics analyses. Results:We succeeded in defining suitable culture conditions to main-tain the 3D coculture for up to 10 days in vitro, with the lowest level of steatosis and reproducible low level of inflammation and fibrosis. NASH disease was induced with a custom me-dium mimicking NASH features. The cell model exhibited the key NASH disease phenotypes of hepatocyte injury, steatosis, inflammation, and fibrosis. Hepatocyte injury was highlighted by a decrease of CYP3A4 expression and activity, without loss of viability up to day 10. Moreover, the model was able to stimulate a stable inflammatory and early fibrotic environ-ment, with expression and secretion of several cytokines. A global gene expression analysis confirmed the NASH induc-tion. Conclusions:This is a new in vitro model of NASH dis-ease consisting of four human primary cell-types that exhibits most features of the disease. The 10-day cell viability and cost effectiveness of the model make it suitable for medium throughput drug screening and provide attractive avenues to better understand disease physiology and to identify and characterize new drug targets.

关键词： 3D liver model Human primary cells Key features of NASH

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