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Human Placental Mesenchymal Stem Cells Relieve Primary Sclerosing Cholangitis via Upregulation of TGR5 in Mdr2^(-/-)Mice and Human Intrahepatic Cholangiocyte Organoid Models

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Research 2024年第2期2023卷 355-372页

作者： Qigu Yao Wenyi Chen Yingduo Yu feiqiong gao Jiahang Zhou Jian Wu Qiaoling Pan Jinfeng Yang Lingling Zhou Jiong Yu Hongcui Cao Lanjuan Li State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases Cllaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affliated HospitalZhejang University School of Medicine79 Qingchun Rd.Hangzhou 310003China National Clinical Research Center for Infectious Diseases HangzhouChina Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province 79 Qingchun Rd.Hangzhou 310003China Jjinan Microecological Biomedicine Shandong Laboratory Jinan 250117China

Primary sclerosing cholangitis(PSC)is a biliary disease accompanied by chronic inflammation of the liver and biliary *** stem cells(MSCs)are used to treat liver diseases because of their immune regulation and regeneration-promoting *** study was performed to explore the therapeutic potential of human placental MSCs(hP-MSCs)in PSC through the Takeda G protein-coupled receptor 5(TGR5)receptor *** tissues were collected from patients with PSC and healthy donors(n=4)for RNA sequencing and intrahepatic cholangiocyte organoid ***-MSCs were injected via the tail vein into Mdr2^(-/-),bile duct ligation(BDL),and 3,5-diethoxycarbonyl-1,4-dihydrocollidine(DDC)mouse models or co-cultured with organoids to confirm their therapeutic effect on biliary *** in bile acid metabolic profile were analyzed by liquid chromatography/tandem mass spectrometry(LC-MS/MS).Compared with healthy controls,liver tissues and intrahepatic cholangiocyte organoids from PSC patients were characterized by inflammation and cholestasis,and marked downregulation of bile acid receptor TGR5 ***-MSC treatment apparently reduced the inflammation,cholestasis,and fibrosis in Mdr2^(-/-),BDL,and DDC model *** activating the phosphatidylinositol 3 kinase/extracellular signal-regulated protein kinase pathway,hP-MSC treatment promoted the proliferation of cholangiocytes,and affected the transcription of downstream nuclear factorκB through regulation of the binding of TGR5 and Pellino3,thereby affecting the cholangiocyte inflammatory phenotype.

关键词： inflammation TGR5 Human

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Genome-wide CRISPR screening identifies critical role of phosphatase and tensin homologous (PTEN) in sensitivity of acute myeloid leukemia to chemotherapy

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第8期25卷 700-710页

作者： Liming LIN Jingjing TAO Ying MENG Yichao GAN Xin HE Shu LI Jiawei ZHANG feiqiong gao Dijia XIN Luyao WANG Yili FAN Boxiao CHEN Zhimin LU Yang XU Department of Hematology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Zhejiang Provincial Key Laboratory of Pancreatic Disease the First Affiliated Hospital and Institute of Translational MedicineCancer CenterZhejiang University School of MedicineHangzhou 310029China Institute of Genetics Zhejiang UniversityHangzhou 310058China Division of Hematopoietic Stem Cell&Leukemia Research Beckman Research Institute of City of HopeDuarteCA 91010USA Department of Hematology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most ***,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)***101 suppresses the proliferation of myeloid malignancy cells and primary AML *** induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 *** knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling *** inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell *** findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

关键词： Genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library Phosphatase and tensin homologous(PTEN) Rapamycin Acute myeloid leukemia(AML) Chemotherapy

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MSC-derived exosomes attenuate hepatic fibrosis in primary sclerosing cholangitis through inhibition of Th17 differentiation

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 119-134页

作者： Wenyi Chen Feiyan Lin Xudong Feng Qigu Yao Yingduo Yu feiqiong gao Jiahang Zhou Qiaoling Pan Jian Wu Jinfeng Yang Jiong Yu Hongcui Cao Lanjuan Li State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesNational Medical Center for Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Jinan Microecological Biomedicine Shandong Laboratory Jinan 250117China Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province Hangzhou 310003China

Primary sclerosing cholangitis(PSC)is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis,with no curative treatment available,and liver transplantation is inevitable for end-stage *** placentalmesenchymal stem cell(hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis,inhibit collagen production and possess immunomodulatory properties in autoimmune liver ***,we prepared hpMSC-derived exosomes(Exo^(MSC))and further investigated the anti-fibrotic effects and detailed mechanism on PSC based on Mdr2^(−/−)mice and multicellular organoids established from PSC *** results showed that Exo^(MSC) ameliorated liver fibrosis in Mdr2^(−/−)mice with significant collagen reduction in the preductal area where Th17 differentiation was inhibited as demonstrated by RNAseq analysis,and the percentage of CD4+IL-17A+T cells was reduced both in Exo^(MSC)-treated Mdr2^(−/−)mice(Mdr2^(−/−)-Exo)in vivo and Exo^(MSC)-treated Th17 differentiation progressed in ***,Exo^(MSC) improved the hypersecretory phenotype and intercellular interactions in the hepatic Th17 microenvironment by regulating PERK/CHOP signaling as supported by multicellular ***,our data demonstrate the antifibrosis effect of Exo^(MSC) in PSC disease by inhibiting Th17 differentiation,and ameliorating the Th17-induced microenvironment,indicating the promising potential therapeutic role of Exo^(MSC) in liver fibrosis of PSC or Th17-related diseases.

关键词： Mesenchymal stem cell Exosomes Primary sclerosing cholangitis Fibrosis Organoids Th17

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微波液相放电氧化难生物降解有机废水

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油气田环境保护 2021年第6期31卷 17-21页

作者：张桂泉吴军杨耕高飞琼成都科衡环保技术有限公司新疆师范大学化学化工学院

随着社会工业化进程的不断加快与发展,化工废水量也大幅增加,对环境的危害日益加剧。利用微波液相放电产生等离子体氧化处理难降解有机废水是一种有效的新技术。文章阐述了微波液相放电产生等离子体氧化技术的反应机理及技术优势,通过... 详细信息

随着社会工业化进程的不断加快与发展,化工废水量也大幅增加,对环境的危害日益加剧。利用微波液相放电产生等离子体氧化处理难降解有机废水是一种有效的新技术。文章阐述了微波液相放电产生等离子体氧化技术的反应机理及技术优势,通过实验验证了该技术处理难生物降解有机废水的影响因素,并针对这项技术应用中需要深化探索的关键点给出建议。实验结果表明:输入功率1 000 W,水体流速250 mL/min, pH值6.0,H_(2)O_(2)加量为0.8%的条件下,微波液相放电氧化反应能在20 min内,对有机废水(COD原值5 000 mg/L)的COD去除率达98%;在最佳条件下反应10 min后,B/C值从0.12提高到0.31以上,废水性质由难生物降解转变为可生物降解,处理成本为41.00元/m;。

关键词：微波液相放电等离子体氧化影响因素有机废水

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Piriformospora indica confers cadmium tolerance in Nicotiana tabacum

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Journal of Environmental Sciences 2015年第11期27卷 184-191页

作者： feiqiong Hui Jian Liu Qikang gao Binggan Lou Institute of Biotechnology Zhejiang University China Tobacco Guizhou Industrial Co. Ltd. Analysis Center of Agrobiology and Environmental Sciences Zhejiang University

Piriformospora indica, a root-colonizing endophytic fungus of Sebacinales, promotes plant growth and confers resistance against biotic and abiotic stresses. In order to confirm the influence of P. indica on growth, proline, malondialdehyde（MDA）, chlorophyll, and cadmium（Cd） amounts in Nicotiana tabacum under Cd stress, hydroponics, pot and field trials were conducted. The results showed that P. indica can store Cd in plant roots and reduce leaf Cd content, reduce the concentration of MDA, and increase the proline and chlorophyll content and the activities of catalase, peroxidase, and superoxide dismutase under hydroponic Cd stress. RT-PCR analysis showed that the relative expression level of genes Gsh2, Ta PCS1, oas1, GPX, and Hsp70 in colonized plants was 4.3, 1.4, 2.9, 1.7, and 6.9fold higher than in un-colonized plants respectively. Cd exposure significantly reduced un-colonized plants＇ agronomic traits compared to P. indica-colonized ones. Our results suggested that P. indica can sequester Cd in roots, so that much less cadmium was transported to leaves, and the increased concentrations of antioxidant enzymes, pigments and proline contents, as well as the higher expression of stress-related phytochelatin biosynthesis genes in P. indica-inoculated plants, may also serve to protect N. tabacum plants against oxidative damage, enhancing Cd tolerance.

关键词： Plant endophytic fungus Malondialdehyde Proline Chlorophyll Stress-related genes Tobacco plants

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印度梨形孢对烟草抗旱性的影响

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烟草科技 2017年第12期50卷 1-7页

作者：惠非琼刘剑高其康楼兵干贵州中烟工业有限责任公司贵阳市小河区开发大道96号550009 浙江大学生物技术研究所杭州市余杭塘路866号310058 浙江大学农生环分析测试中心杭州市余杭塘路866号310058

为探明印度梨形孢对烟草抗旱性的影响,采用聚乙二醇(PEG 6000)人工模拟干旱胁迫条件进行盆栽试验。在干旱胁迫下,测定了烟叶中丙二醛(MDA)和脯氨酸(Pro)的含量、叶片相对电导率以及干旱相关基因的表达量。结果表明:印度梨形孢能定殖于... 详细信息

为探明印度梨形孢对烟草抗旱性的影响,采用聚乙二醇(PEG 6000)人工模拟干旱胁迫条件进行盆栽试验。在干旱胁迫下,测定了烟叶中丙二醛(MDA)和脯氨酸(Pro)的含量、叶片相对电导率以及干旱相关基因的表达量。结果表明:印度梨形孢能定殖于烟草根部,并促进烟草地上部和地下部的生长。在干旱条件下,根部接种印度梨形孢的烟草缺水症状较轻,与未接种印度梨形孢的烟草相比,其烟叶中Pro含量显著升高,MDA含量和叶片相对电导率显著下降,干旱相关基因RD29A、ERD10A、RD26A、SDIR1、HAT、ERD1和DREB2A的表达量均明显上升。印度梨形孢提高烟草的抗旱能力,是通过降低烟草细胞生物膜的损伤程度、增强烟草的抗氧化防御能力、促进细胞渗透调节物质Pro的积累以及上调干旱胁迫相关基因的表达实现的。

关键词：植物内生真菌印度梨形孢干旱抗旱能力烟草

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印度梨形孢诱导烟草的抗病性分析

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烟草科技 2014年第11期47卷 74-79页

作者：惠非琼马杰刘剑聂长春高其康楼兵干浙江大学生物技术研究所贵州中烟工业有限责任公司贵阳市云岩区友谊路25号550001 浙江大学农生环测试中心

内生真菌印度梨形孢(Piriformospora indica)能够增强植物体抗生物和非生物胁迫能力。为了明确印度梨形孢对诱导烟草抗病性的作用,分别进行了接种病原菌长柄链格孢、胶孢炭疽菌、终极腐霉和茄丝核菌后印度梨形孢定殖的烟草对赤星病、炭... 详细信息

内生真菌印度梨形孢(Piriformospora indica)能够增强植物体抗生物和非生物胁迫能力。为了明确印度梨形孢对诱导烟草抗病性的作用,分别进行了接种病原菌长柄链格孢、胶孢炭疽菌、终极腐霉和茄丝核菌后印度梨形孢定殖的烟草对赤星病、炭疽病、猝倒病和立枯病害的抗性试验,同时分析了接种长柄链格孢后烟叶中丙二醛(MDA)和脯氨酸(Pro)含量、抗氧化酶活性以及病程相关蛋白基因表达水平。结果表明:印度梨形孢定殖的烟草,接种长柄链格孢后,烟叶病斑显著减小,烟叶中MDA含量显著降低,Pro含量显著升高,病程相关蛋白基因PR-1a,PR2,PR3和PR5的表达量明显提高;接种胶孢炭疽菌后,烟叶病斑减小;终极腐霉和茄丝核菌对烟草的危害症状显著减轻。印度梨形孢能诱导烟草产生抗病性,是通过维持生物膜系统的完整性、稳定细胞内渗透压以及膜脂过氧化在较低水平、并调控病程相关蛋白基因的表达来实现的。

关键词：内生真菌印度梨形孢丙二醛脯氨酸烟草病害病程相关蛋白基因

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儿童先天性心脏病并发感染性心内膜炎的外科治疗

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北京医学 2000年第3期22卷 163-165页

作者：黄飞琼高玲李仲智北京儿童医院心脏外科邮政编码100045

目的　探讨儿童先天性心脏病合并感染性心内膜炎的治疗经验。方法　本组患儿均使用多种抗生素 ,感染性心内膜炎 (IE)未能控制 ,体温不降。于感染活动期行手术治疗 ,摘除心内赘生物并纠正心内畸形。结果　 4例患儿施行手术治疗无手术死... 详细信息

目的　探讨儿童先天性心脏病合并感染性心内膜炎的治疗经验。方法　本组患儿均使用多种抗生素 ,感染性心内膜炎 (IE)未能控制 ,体温不降。于感染活动期行手术治疗 ,摘除心内赘生物并纠正心内畸形。结果　 4例患儿施行手术治疗无手术死亡 ,术后效果满意 ,术后无复发。结论　儿童先天性心脏病合并感染性心内膜炎经内科治疗效果欠佳时 ,应尽早手术治疗。早期诊断及时手术是控制感染降低死亡率的主要措施。

关键词：心内膜炎先天性心脏病外科手术儿童

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