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In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis

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World Journal of Gastroenterology 2017年第46期23卷 8152-8168页

作者： Guo-Zun zhang Hui-Cong Sun Li-Bo Zheng Jin-Bo Guo xiao-lan zhang Department of Gastroenterology The Second Hospital of Hebei Medical University First Department of Gastroenterology Cangzhou Central Hospital Department of Internal Medicine Ningbo Women and Children’s Hospital

AIM To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells(h UC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/*** A CCl4-induced liver fibrotic/cirrhotic rat model was used to assess the effect of h UC-MSCs. Histopathology was assessed by hematoxylin and eosin(H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time *** We demonstrated that the infused h UC-MSCs could differentiate into hepatocytes in vivo. Functionally, the transplantation of h UC-MSCs to CCl4-treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. CONCLUSION Transplanted h UC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl4-induced rat liver fibrosis model. h UC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis.

关键词： Liver fibrosis/cirrhosis Mesenchymal stem cells Collagen metabolism Hepatocyte Differentiation

Specific shRNA targeting of FAK influenced collagen metabolism in rat hepatic stellate cells

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World Journal of Gastroenterology 2010年第32期16卷 4100-4106页

作者： Zhi-Na Dun xiao-lan zhang Jun-Yan An Li-Bo Zheng Robert Barrett Shu-Rui Xie Department of Gastroenterology The Second Hospital of Hebei Medical University Hebei Key Laboratory of Gastroenterology Hebei Institute of Gastroenterology Shijiazhuang Hebei Province China Inflammatory Bowel Disease Center and Immunobiology Research Institute Cedars-Sinai Medical Center Los Angeles CA 90048 United States

AIM:To investigate the effects and mechanism of disruption of focal adhesion kinase(FAK) expression on collagen metabolism in rat hepatic stellate cells(HSC).METHODS:The plasmids expressing FAK short hairpin RNA(shRNA) were transfected into HSC-T6 cells,and the level of FAK expression was determined by both real-time quantitative polymerase chain reaction(QPCR) and Western blotting *** production of type collagen and type collagen in FAK-disrupted cells was analyzed by real-time *** level of collagen metabolism proteins,including matrix metalloproteinases-13(MMP-13) and tissue inhibitors of metalloproteinases-1(TIMP-1) was also determined by both real-time Q-PCR and Western blotting ***:The transfection of FAK shRNA plasmids into HSC resulted in disrupted FAK *** with the HK group,the levels of type collagen and type collagen mRNA transcripts in FAK shRNA plas-mid group were signif icantly decreased(0.69 ± 0.03 vs 1.96 ± 0.15,P = 0.000;0.59 ± 0.07 vs 1.62 ± 0.12,P = 0.020).The production of TIMP-1 in this cell type was also signif icantly reduced at both mRNA and protein levels(0.49 ± 0.02 vs 1.72 ± 0.10,P = 0.005;0.76 ± 0.08 vs 2.31 ± 0.24,P = 0.000).However,the expression of MMP-13 mRNA could be significantly up-regulated by the transfection of FAK shRNA plasmids into HSC(1.74 ± 0.20 vs 1.09 ± 0.09,P = 0.000).CONCLUSION:These data support the hypothesis that shRNA-mediated disruption of FAK expression could attenuate extracellular matrix(ECM) synthesis and promote ECM degradation,making FAK a potential target for novel anti-f ibrosis therapies.

关键词： Focal adhesion kinase Hepatic stellate cells Matrix metalloproteinases RNA interference Type collagen Tissue inhibitors of metallo-proteinases

Effects and mechanism of adenovirus-mediated phosphatase and tension homologue deleted on chromosome ten gene on collagen deposition in rat liver fibrosis

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World Journal of Gastroenterology 2017年第32期23卷 5904-5912页

作者： Shu-rui Xie Jun-yan An Li-bo Zheng xiao-Xia Huo Jian Guo David Shih xiao-lan zhang Department of Gastroenterology The Second Hospital of Hebei Medical University Hebei Key Laboratory of Gastroenterology Hebei Institute of Gastro- enterology Department of Gastroenterology Xingtai People's Hospital Inflammatory Bowel and Immunobiology Research Institute F. Widjaja Foundation Cedars-Sinai Medical Center

AIM To evaluate the effects of phosphatase and tension homologue deleted on chromosome ten(PTEN) gene on collagen metabolism in hepatic fibrosis and the underlying *** rat primary hepatic stellate cells(HSCs) and human LX-2 cells were transfected with adenovirus containing c DNA constructs encoding wild-type PTEN(Ad-PTEN), PTEN mutant G129 E gene(Ad-G129E), and r NA interference constructs targeting the PTEN sequence PTEN short hairpin r NA to up-regulate and downregulate the expression of PTEN. HSCs were assayed using fluorescent microscopy, real-time polymerase chain reaction, and western blotting. Moreover, a CCl_4-induced rat hepatic fibrosis model was established to investigate the in vivo effects. Hematoxylin and eosin, and Masson's trichrome were used to assess the histological changes. The expression of collagen Ⅰ and Ⅲ was assessed using immunohistochemistry and western blot *** Elevated expression of PTEN gene reduced serum levels of alanine transaminase and aspartate transaminase, decreased collagen deposition in the liver, and reduced hepatocyte necrosis. In contrast, knockdown of PTEN expression had an opposite effect, such as increased collagen deposition in the liver, and was molecularly characterized by the increased expression of matrix metalloproteinase(MMP)-13(P < 0.01) and MMP-2(P < 0.01), as well as decreased expression of the tissue inhibitor of metalloproteinase(TIMP)-1(P < 0.01) and TIMP-2(P < 0.01).CONCLUSION These data indicated that gene therapy using recombinant adenovirus encoding PTEN might be a novel way of treating hepatic fibrosis.

关键词： Collagen metabolism Hepatic stellate cells Phosphatase and tension homologue deleted on chromosome ten PTEN Gene therapy Hepatic fibrosis

Dynamic expression of extracellular signal-regulated kinase in rat liver tissue during hepatic fibrogenesis

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World Journal of Gastroenterology 2006年第39期12卷 6376-6381页

作者： xiao-lan zhang Jin-Ming Liu Chang-Chun Yang Yi-Lin Zheng Li Liu Zhan-Kui Wang Hui-Qing Jiang Department of Gastroenterology the Second Hospital of Hebei Medical University Shijiazhuang 050000 Hebei Province China

AIM： To investigate whether extracellular signal-regulated kinase 1 （ERK1） is activated and associated with hepatic stellate cell （HSC） proliferation in fibrotic rat liver tissue.METHODS： Rat hepatic fibrosis was induced by bile duct ligation （BDL）. Histopathological changes were evalo uated by hernatoxylin and eosin staining, and Masson＇ s trichrorne method. ERK1 mRNA in rat liver tissue was determined by reverse transcription-polyrnerase chain reaction, while the distribution of ERK1 was assessed by irnrnunohistochernistry. ERK1 protein was detected by Western blotting analysis. The number of activated HSCs was quantified after alpha smooth muscle actin （α-MA） staining.RESULTS： With the development of hepatic fibrosis, the positive staining cells of α-SMA increased obviously, and mainly resided in the portal ducts. Fiber sepia and perisinuses were accompanied with proliferating bile ducts. The positive staining areas of the rat livers in model groups 1-4 wk after ligation of common bile duct （12.88% ± 2.63%, 22.65% ± 2.16%, 27.45% ± 1.86%, 35.25% ± 2.34%, respectively） were significantly larger than those in the control group （5.88% ± 1.46%, P 〈 0.01）. With the development of hepatic fibrosis, the positive cells of ERK1 increased a lot, and were mainly distributed in portal ducts, fiber sepia around the bile ducts, vascular endothelial cells and perisinusoidal cells. Western blotting analysis displayed that the expression of ERK1 and ERK1 protein was up-regulated during the model course, and its level was the highest 4 wk after operation, being 3.9-fold and 7.2-fold higher in fibrotic rat liver than in controls. ERK1 mRNA was expressed in normal rat livers as well, which was up-regulated two days after BDL and reached the highest 4 wk after BDL. The expression of ERK1 was positively correlated with α-MA expression （r = 0.958, P 〈 0.05）.CONCLUSION： The expression of ERK1 protein and mRNA is greatly increased in fibrotic rat liver tissues, which may play a key r

关键词： Extracellular signal-regulated kinase Hepatic fibrosis Hepatic stellate cells Proliferation

Long noncoding RNA TNFRSF10A-AS1 promotes colorectal cancer through upregulation of HuR

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World Journal of Gastroenterology 2022年第20期28卷 2184-2200页

作者： Dan-Dan Wang Dong-Lei Sun Shao-Peng Yang Jia Song Meng-Yao Wu Wei-Wei Niu Mei Song xiao-lan zhang Department of Gastroenterology The Second Hospital of Hebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina

BACKGROUND Recent studies have emphasized the emerging importance of long noncoding RNAs(lncRNAs)in colorectal cancer(CRC).However,the functions and regulatory mechanisms of numerous lncRNAs in CRC have not been fully *** To explore the functional role and underlying molecular mechanisms of lncRNA TNFRSF10A-AS1 in *** TNFRSF10A-AS1 expression was measured by quantitative real-time polymerase chain reaction in CRC,and the relationship between TNFRSF10A-AS1 levels and the clinicopathological features of CRC patients was *** effect of TNFRSF10A-AS1 expression on CRC proliferation and metastasis was examined in vitro and in ***,we investigated how TNFRSF10A-AS1 is involved in CRC as a competitive endogenous *** TNFRSF10A-AS1 was expressed at a high level in CRC and the upregulation of TNFRSF10A-AS1 was associated with advanced T grade and tumor size in CRC patients.A functional investigation revealed that TNFRSF10A-AS1 enhanced the proliferation,migration ability and invasion ability of colon cancer cells in vitro and in vivo.A mechanistic analysis demonstrated that TNFRSF10A-AS1 acted as a miR-3121-3p molecular sponge to regulate HuR expression,ultimately promoting colorectal tumorigenesis and *** TNFRSF10A-AS1 exerts a tumor-promoting function through the miR-3121-3p/HuR axis in CRC,indicating that it may be a novel target for CRC therapy.

关键词： Colorectal cancer Long noncoding RNA TNFRSF10A-AS1 miR-3121-3p HuR

TL1A Promotes Fibrogenesis in Colonic Fibroblasts via the TGF-β1/Smad3 Signaling Pathway

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Current Medical Science 2024年第3期44卷 519-528页

作者： Jia SONG Dong-lei SUN Chen-yang LI Yu-xin LUO Qian LIU Yue YAO Hong zhang Ting-ting YANG Mei SONG Xin-li BAI xiao-lan zhang Department of Gastroenterology The Second Hospital of Hebei Medical UniversityHebei Key Laboratory of GastroenterologyHebei Institute of GastroenterologyHebei Clinical Research Center for Digestive DiseasesShijiazhuang050000China Department of Pediatrics The Second Hospital of Hebei Medical UniversityShijiazhuang050000China

Objective Intestinal fibrosis is a refractory complication of inflammatory bowel disease(IBD).Tumor necrosis factor ligand-related molecule-1A(TL1A)is important for IBD-related intestinal fibrosis in a dextran sodium sulfate(DSS)-induced experimental colitis *** study aimed to explore the effects of TL1A on human colonic *** A trinitrobenzene sulfonic acid(TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic(Tg)or wild-type(WT)mice was established to determine the effect and mechanism of TL1A on intestinal *** human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell(PBMC)*** proliferation and activation of CCD-18Co cells were detected by BrdU assays,flow cytometry,immunocytochemistry and Western *** metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction(RT-qPCR).Results The level of collagen metabolism in the TNBS+ethyl alcohol(EtOH)/Tg group was greater than that in the TNBS+EtOH/WT *** growth factor-β1(TGF-β1)and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT *** proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A,and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4%at 24 ***1A promoted cell activation and increased the levels of COL1A2,COL3A1,and TIMP-1 in CCD-18Co *** of CCD-18Co cells with TL1A increased the expression of TGF-β1 and *** TL1A promotes TGF-β1-mediated intestinal fibroblast activation,proliferation,and collagen deposition and is likely related to an increase in the TGF-β1/Smad3 signaling pathway.

关键词： tumor necrosis factor ligand-related molecule-1A fibrosis inflammatory bowel disease myofibroblasts transforming growth factor-β1

Chromoendoscopy with targeted biopsies is superior to white-light endoscopy for the long-term follow-up detection of dysplasia in ulcerative colitis patients:a multicenter randomized-controlled trial

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Gastroenterology Report 2021年第1期9卷 14-21,I0001页

作者： Jian Wan Qin zhang Shu-Hui Liang Jie Zhong Jing-Nan Li Zhi-Hua Ran Fa-Chao Zhi xiao-Di Wang xiao-lan zhang Zhong-HuiWen Jian-Qiu Sheng Hua-Xiu Shi Qiao Mei Kai-ChunWu State Key Laboratory of Cancer Biology National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi’anShaanxiP.R.China Department of Gastroenterology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiP.R.China Department of Gastroenterology Peking Union Medical College HospitalBeijingP.R.China Division of Gastroenterology and Hepatology Renji HospitalShanghai Jiao Tong University School of MedicineShanghaiP.R.China Department of Gastroenterology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China Department of Gastroenterology China-Japan Friendship HospitalBeijingP.R.China Department of Gastroenterology the Second Hospital of Hebei Medical UniversityShijiazhuangHebeiP.R.China Department of Gastroenterology West China HospitalSichuan UniversityChengduSichuanP.R.China Department of Gastroenterology PLA Army General HospitalBeijingP.R.China Department of Gastroenterology Zhongshan Hospital Affiliated to Xiamen UniversityXiamen University Institute of Digestive DiseaseXiamenFujianP.R.China Department of Gastroenterology the First Affiliated Hospital of Anhui Medical University HefeiAnhuiP.R.China

Background:Data from single-center experience or small sample-sized studies have shown that chromoendoscopy(CE)might be superior to white-light endoscopy(WLE)for dysplasia surveillance in ulcerative colitis(UC)*** performed a prospective randomized trial with a long-term follow-up to compare the detection rate of dysplasia among WLE with targeted biopsies(WLT),WLE with random biopsies(WLR),and dye-based CE with targeted biopsies(CET)in UC ***:Patients with long-standing UC were enrolled from 11 medical centers from March 2012 to December 2013 and randomized into three arms(WLT,WLR,and CET).Only high-definition endoscopy was used in all three *** patients were followed up by annual endoscopy with biopsies through December ***:With a median follow-up time of 55 months,a total of 122 patients with 447 colonoscopies were finally analysed in the per-protocol set:WLT(n=43),WLR(n=40),and CET(n=39).A total of 34 dysplastic lesions were found in 29 colonoscopies of 21 *** and CET could identify more colonoscopies that diagnosed dysplasia than WLT(8.1%and 9.7%vs 1.9%;P=0.014 and 0.004,respectively).WLR obtained more biopsied samples than WLT and CET(16.465.1 vs 4.361.4 and 4.361.4;both Plance in patients with long-standing UC,CET appeared to be more effective thanWLT and less tedious than *** was found to be particularly useful when a long-term(>3 years)follow-up was conducted for dysplasia *** trial was registered on ***(ChiCTR1900023689).

关键词： ulcerative colitis dysplasia chromoendoscopy white-light endoscopy

ELECTROANALYTICAL STUDY OF XANTHOPHYLL AND ITS APPLICATION

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Chinese Chemical Letters 1991年第1期2卷 27-28页

作者： Nai Xing WANG Jian Min CHEN xiao lan zhang Department of Chemistry,Fudan University,Shanghai 200433

The electroanalytical behaviour of xanthophyll was studied by differential pulse polarography and cyclic *** reduction wave of xanthophyll at -0.92V(***/AgCl)in 1.25% tetrabutyl ammonium chloride solution(TBAC)was found for the first *** optimum conditions for the determination of xanthophyll by DPP were established. The results from the application of cyclic voltammetry to study electrode process behaviour showed that the electrode reaction of xanthophyll at a hanging mercury electrode is quasi-reversible reaction.

关键词： ELECTROANALYTICAL STUDY OF XANTHOPHYLL AND ITS APPLICATION ITS

Bioinformatics-based analysis of the relationship between core genes and immune infiltration and tumor metastasis in esophageal cancer

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Gastroenterology & Hepatology Research 2022年第1期4卷 32-45页

作者： Fa-zhang Chen Ye Li Xue-lian zhang xiao-lan zhang Ru-yi Yang Affiliated Hospital of Qinghai University XiningQinghai.

We analysed four gene microarray datasets by GEO2R and obtained differential genes expressed in oesophageal *** further elaborate the functions of DGEs,this study performed gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of *** constructed protein interaction networks of DGEs through the String database and screened core *** used the GEPIA online database with the Kaplan-Meier plotter database to verify the expression of Hub genes in expressed normal versus tumour tissues and the effect of Hub genes on overall and disease-free survival in oesophageal *** further understand the relationship between Hub gene and tumour metastasis,we analysed the difference in Hub gene expression in patients without metastatic oesophageal cancer versus those with metastatic oesophageal cancer with the help of the HCMDB *** relationship between Hub genes and tumour immune infiltration was analysed by the TIMER *** obtained a total of 149 DEGs,of which 49 were up-regulated genes and 100 were down-regulated *** DGEs were importantly enriched in IL-17 signalling pathway,ECM-receptor interactions,p53 signalling pathway,estrogen signalling pathway,complement and coagulation cascade *** screened 10 Hub genes,MMP9,CXCL8,COL1A1,TIMP1,POSTN,MMP3,MMP1,COL3A1,SERPINE1,LUM,among 149 *** genes were all up-regulated in expression in esophageal cancer tissues,in addition,MMP9,T1MP1,CXCL8,POSTN and The expression of COL3A1,LUM,MMP1,MMP3,MMP9,POSTN,SERPINE1 and TIMP1 was positively correlated with the infiltration of immune cells in the tumor *** conclusion,our study identified 10 signature genes for oesophageal *** genes are associated with the development,metastasis,prognosis and immune infiltration of oesophageal cancer and may be markers of development,metastasis and prognosis as well as targets for immunotherapy.

关键词： bioinformatics esophageal cancer data mining GEO immune infiltration.