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Mesenchymal stromal cell-dependent immunoregulation in chemically-induced acute liver failure

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World Journal of Stem Cells 2021年第3期13卷 208-220页

作者： Jia-Hang Zhou Xuan Lu cui-Lin Yan Xin-Yu Sheng hong-cui cao State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

Drug-induced liver injury(DILI),which refers to liver damage caused by a drug or its metabolites,has emerged as an important cause of acute liver failure(ALF)in recent ***-induced ALF in animal models mimics the pathology of DILI in humans;thus,these models are used to study the mechanism of potentially effective treatment *** stromal cells(MSCs)possess immunomodulatory properties,and they alleviate acute liver injury and decrease the mortality of animals with chemically-induced ***,we summarize some of the existing research on the interaction between MSCs and immune cells,and discuss the possible mechanisms underlying the immunomodulatory activity of MSCs in chemically-induced *** conclude that MSCs can impact the phenotype and function of macrophages,as well as the differentiation and maturation of dendritic cells,and inhibit the proliferation and activation of T lymphocytes or B *** also have immunomodulatory effects on the production of cytokines,such as prostaglandin E2 and tumor necrosis factor-alpha-stimulated gene 6,in animal ***,MSCs have significant benefits in the treatment of chemically-induced ALF by interacting with immune cells and they may be applied to DILI in humans in the near future.

关键词： Mesenchymal stromal cell Immune response Drug-induced liver injury Acute liver failure Dendritic cell

Development and validation of a prognostic model for patients with hepatorenal syndrome:A retrospective cohort study

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World Journal of Gastroenterology 2021年第20期27卷 2615-2629页

作者： Xin-Yu Sheng Fei-Yan Lin Jian Wu hong-cui cao State Key Laboratory for Diagnosis and Treatment of Infectious Diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina National Clinical Research Center for Infectious Diseases Hangzhou 310003Zhejiang ProvinceChina

BACKGROUND Hepatorenal syndrome(HRS)is a severe complication of cirrhosis with high mortality,which necessitates accurate clinical ***,studies on prognostic factors and scoring systems to predict overall survival of HRS are not ***,a multicenter cohort study with a long span of time could be more *** To develop a novel and effective prognostic model for patients with HRS and clarify new prognostic *** We retrospectively enrolled 1667 patients from four hospitals,and 371 eligible patients were finally analyzed to develop and validate a novel prognostic model for patients with *** were compared between survivors and non-survivors,and potential prognostic factors were selected according to the impact on 28-d *** in predicting 28-d mortality was compared between the novel and other scoring systems,including Model for End-Stage Liver Disease(MELD),Chronic Liver Failure-Sequential Organ Failure Assessment(CLIF-SOFA),and Chinese Group on the Study of Severe Hepatitis BAcute-on-Chronic Liver Failure(COSSH-ACLF).RESULTS Five prognostic factors,comprised of gender,international normalized ratio,mean corpuscular hemoglobin concentration,neutrophil percentage,and stage,were integrated into a new score,GIMNS;stage is a binary variable defined by the number of failed *** was positively correlated with MELD,CLIFSOFA,and ***,it had better accuracy[area under the receiver operating characteristic curve(AUROC):0.830]than MELD(AUROC:0.759),CLIF-SOFA(AUROC:0.767),and COSSH-ACLF(AUROC:0.759)in the derivation cohort(P<0.05).It performed better than MELD and CLIF-SOFA in the validation cohort(P<0.050)and had a higher AUROC than COSSH-ACLF(P=0.122).CONCLUSION We have developed a new scoring system,GIMNS,to predict 28-d mortality of HRS *** corpuscular hemoglobin concentration and stage were first proposed and found to be related to the mortality of ***,the GIM

关键词： Hepatorenal syndrome Prognostic factor Mean corpuscular hemoglobin concentration Mortality Scoring system Cohort study

Effect of probiotic treatment on cirrhotic patients with minimal hepatic encephalopathy: A meta-analysis

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Hepatobiliary & Pancreatic Diseases International 2018年第1期17卷 9-16页

作者： Qing cao Cheng-Bo Yu Shi-Gui Yang hong-cui cao Ping Chen Min Deng Lan-Juan Li State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated Hospital Zhejiang University School of Medicine

Background: Minimal hepatic encephalopathy(MHE) is an early and reversible form of hepatic encephalopathy. The documentations on the treatment with probiotics are inconsistent. The present meta-analysis was to verify the role of probiotics in the treatment of cirrhotic patients with *** sources: Seven electronic databases were searched for relevant randomized controlled trials(RCTs)published until July 2015. The effects of probiotics on serum ammonia, endotoxin, and MHE were ***: A total of 14 RCTs(combined n = 1132) were included in the meta-analysis. When probiotics were compared to placebo or no treatment, probiotics were more likely to reduce values in the number connection test(NCT; week 4: MD =-30.25, 95% CI:-49.85 to-10.66), improve MHE(week 4: OR = 0.18,95% CI: 0.07 to 0.47; week 12: OR = 0.15, 95% CI: 0.07 to 0.32), and prevent overt HE progression(week4: OR = 0.22, 95% CI: 0.07 to 0.67) in patients with liver cirrhosis. When probiotics was compared to lactulose, probiotics tended to reduce serum ammonia levels(week 4: MD =-0.33 μmol/L, 95% CI:-5.39 to 4.74; week 8: MD = 6.22 μmol/L, 95% CI:-24.04 to 36.48), decrease NCT(week 8: MD = 3.93, 95% CI:-0.72 to 8.58), improve MHE(week 4: OR = 0.93, 95% CI: 0.45 to 1.91; week 12: OR = 0.73, 95% CI: 0.35 to 1.51) and prevent the development of overt HE(week 4: OR = 0.96, 95% CI: 0.17 to 5.44; week 12:OR = 2.7, 95% CI: 0.50 to 14.64) in patients with liver cirrhosis. However, lactulose appears to be more effective in reducing NCT values as compared to probiotics(week 4: MD = 6.7, 95% CI: 0.58 to 12.82).Conclusion: Probiotics can decrease serum ammonia and endotoxin levels, improve MHE, and prevent overt HE development in patients with liver cirrhosis.

关键词： Randomized controlled trials Probiotics Lactulose Minimal hepatic encephalopathy

Mesenchymal stem cells from the human umbilical cord ameliorate fulminant hepatic failure and increase survival in mice

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Hepatobiliary & Pancreatic Diseases International 2015年第2期14卷 186-193页

作者： Jin-Feng Yang hong-cui cao Qiao-Ling Pan Jiong Yu Jun Li Lan-Juan Li The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases First Affiliated Hospital Zhejiang University School of Medicine Collaborative Innovation Center for Diagnosis andTreatment of Infectious Diseases

BACKGROUND：Cell therapy has been promising for various *** investigated whether transplantation of human umbilical cord mesenchymal stem cells（h UCMSCs）has any therapeutic effects on D-galactosamine/lipopolysaccharide（Gal N/LPS）-induced fulminant hepatic failure in ***：h UCMSCs isolated from human umbilical cord were cultured and transplanted via the tail vein into severe combined immune deficiency mice with Gal N/LPS-induced fulminant hepatic *** transplantation,the localization and differentiation of h UCMSCs in the injured livers were investigated by immunohistochemical and genetic analy- ses. The recovery of the injured livers was evaluated histologi- cally. The survival rate of experimental animals was analyzed by the Kaplan-Meier method and log-rank test. RESULTS： hUCMSCs expressed high levels of CD29, CD73, CD13, CD105 and CD90, but did not express CD31, CD79b, CD133, CD34, and CD45. Cultured hUCMSCs displayed adip- ogenic and osteogenic differentiation potential. Hematoxylin and eosin staining revealed that transplantation of hUCMSCs reduced hepatic necrosis and promoted liver regeneration. Transplantation of hUCMSCs prolonged the survival rate of mice with fulminant hepatic failure. Polymerase chain reaction for human alu sequences showed the presence of human cells in mouse livers. Positive staining for human albumin, human alpha-fetoprotein and human cytokeratin 18 suggested the for- mation of hUCMSCs-derived hepatocyte-like cells in ***： hUCMSC was a potential candidate for stem cell based therapies. After transplantation, hUCMSCs partially repaired hepatic damage induced by GalN/LPS in mice. hUC- MSCs engrafted into the injured liver and differentiated into hepatocyte-like cells.

关键词： human umbilical cord mesenchymal stem cells fulminant hepatic failure cell transplantation hepatic differentiation

Dynamic changes of key metabolites during liver fibrosis in rats

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World Journal of Gastroenterology 2019年第8期25卷 941-954页

作者： Jiong Yu Jian-Qin He De-Ying Chen Qiao-Ling Pan Jin-Feng Yang hong-cui cao Lan-Juan Li State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases the First Affiliated Hospital College of Medicine Zhejiang University Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases

BACKGROUND Fibrosis is the single most important predictor of significant morbidity and mortality in patients with chronic liver *** non-invasive tests for monitoring fibrosis are lacking,and new biomarkers of liver fibrosis and function are *** To depict the process of liver fibrosis and look for novel biomarkers for diagnosis and monitoring fibrosis *** CCl4 was used to establish the rat liver fibrosis *** fibrosis process was measured by liver chemical tests,liver histopathology,and Masson’s trichrome *** expression levels of two fibrotic markers includingα-smooth muscle actin and transforming growth factorβ1 were assessed using immunohistochemistry and real-time polymerase chain *** changes in metabolic profiles and biomarker concentrations in rat serum during liver fibrosis progression were investigated using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass *** discriminatory capability of potential biomarkers was evaluated by receiver operating characteristic(ROC)curve *** To investigate the dynamic changes of metabolites during the process of liver fibrosis,sera from control and fibrosis model rats based on pathological results were analyzed at five different time *** investigated the association of liver fibrosis with 21 metabolites including hydroxyethyl glycine,L-threonine,indoleacrylic acid,β-muricholic acid(β-MCA),cervonoyl ethanolamide(CEA),phosphatidylcholines,and *** metabolites,CEA andβ-MCA,differed significantly in the fibrosis model rats compared to controls(P<0.05)and showed prognostic value for *** curve analyses performed to calculate the area under the curve(AUC)revealed that CEA andβ-MCA differed significantly in the fibrosis group compared to controls with AUC values exceeding 0.8,and can clearly differentiate early stage from late stage fibrosis or *** This st

关键词： Ultra-performance liquid chromatography-mass spectrometry Metabonomics Liver fibrosis Biomarker Cervonoyl ethanolamide β-muricholic acid

Evaluation of a novel choanoid fluidized bed bioreactor for future bioartificial livers

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World Journal of Gastroenterology 2014年第22期20卷 6869-6877页

作者： Cheng-Bo Yu Xiao-Ping Pan Liang Yu Xiao-Peng Yu Wei-Bo Du hong-cui cao Jun Li Ping Chen Lan-Juan Li States Key Laboratory for Diagnosis and Treatment of Infectious Diseases First Affiliated HospitalSchool of MedicineZhejiang University Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases

AIM: To construct and evaluate the functionality of a choanoid-fluidized bed bioreactor (CFBB) based on microencapsulated immortalized human hepatocytes.

关键词： Choanoid Fluidized bed Bioreactor Immortalized human hepatocytes Bioartificial liver

Effects of plasma exchange combined with continuous renal replacement therapy on acute fatty liver of pregnancy

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Hepatobiliary & Pancreatic Diseases International 2014年第2期13卷 179-183页

作者： Cheng-Bo Yu Jia-Jia Chen Wei-Bo Du Ping Chen Jian-Rong Huang Yue-Mei Chen hong-cui cao Lan-Juan Li State Key Laboratory for Diagnosis and Treatment of Infectious Diseases the First Affiliated HospitalZhejiang University School of Medicine Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases

BACKGROUND: Acute fatty liver of pregnancy (AFLP) in the third trimester or early postpartum period can lead to fatal liver damage. Its traditional therapy is not very effective in facilitating hepatic recovery. The safety and effect of plasma exchange (PE)in combination with continuous renal replacement therapy(CRRT) (PE+CRRT) for AFLP still needs ***: Five AFLP patients with hepatic encephalopathy and renal failure were subjected to PE+CRRT in our department from 2007 to 2012. Their symptoms, physical signs and results were observed, and all relevant laboratory tests were compared before and after PE+***: All the 5 patients were well tolerated to the therapy. Four of them responded to the treatment and showed improvement in clinical symptoms/signs and laboratory results and they were cured and discharged home after the treatment One patient succeeded in bridging to transplantation for slowing down hepatic failure and its complications process after2 treatment sessions. Intensive care unit stay and hospital stay were 9.4 (range 5-18) and 25.0 days (range 11-42), ***: PE+CRRT is safe and effective and should be used immediately at the onset of hepatic encephalopathy and/or renal failure in patients with AFLP.

关键词： plasma exchange continuous renal replacement therapy acute fatty liver pregnancy liver failure

Efficient generation of functional hepatocytelike cells from mouse liver progenitor cells via indirect co-culture with immortalized human hepatic stellate cells

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Hepatobiliary & Pancreatic Diseases International 2016年第2期15卷 173-179页

作者： Xiao-Ping Pan Yi-Ni Wang Xiao-Peng Yu Chun-Xia Zhu Jian-Zhou Li Wei-Bo Du Yi-Min Zhang hong-cui cao Yan-hong Zhang Dan-Hua Zhu George C Yeoh Lan-Juan Li Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Infectious Diseases First Affiliated Hospital Zhejiang University School of Medicine College of Basic Medical Sciences Zhejiang Chinese Medical University Biochemistry & Molecular Biology Crawley University of Western Australia

BACKGROUND： Differentiation of liver progenitor cells（LPCs） to functional hepatocytes holds great potential to develop new strategies for hepatocyte transplantation and the screening of drug-induced cytotoxicity. However, reports on the efficient and convenient hepatic differentiation of LPCs to hepatocytes are few. The present study aims to investigate the possibility of generating functional hepatocytes from LPCs in an indirect co-culture ***： Mouse LPCs were co-cultured in Transwell plates with an immortalized human hepatic stellate cell line（HSCLi） we previously established. The morphology, expression of hepatic markers, and functions of mouse LPC-derived cells were monitored and compared with those of conventionally cultured LPCs. RESULTS： Co-culturing with HSC-Li cells induced differentiation of mouse LPCs into functional hepatocyte-like cells. The differentiated cells were morphologically transformed into hepatocyte-like cells 3 days after co-culture initiation. In addition, the differentiated cells expressed liver-specific genes and possessed hepatic functions, including glycogen storage, lowdensity lipoprotein uptake, albumin secretion, urea synthesis, and cytochrome P450 1A2 enzymatic ***： Our method, which employs indirect co-culture with HSC-Li cells, can efficiently induce the differentiation of LPCs into functional hepatocytes. This finding suggests that this co-culture system can be a useful method for the efficient generation of functional hepatocytes from LPCs.

关键词： liver progenitor cells indirect co-culture cell differentiation hepatocytes immortalized human hepatic stellate cells

Long non-coding RNA SNHG16 promotes human placenta-derived mesenchymal stem cell proliferation capacity through the PI3K/AKT pathway under hypoxia

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World Journal of Stem Cells 2022年第9期14卷 714-728页

作者： Xu-Dong Feng Jia-Hang Zhou Jun-Yao Chen Bing Feng Rui-Tian Hu Jian Wu Qiao-Ling Pan Jin-Feng Yang Jiong Yu hong-cui cao State Key Laboratory for The Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina Department of Chemistry Duke UniversityDurhamNC 27708United States Jinan Microecological Biomedicine Shandong Laboratory Jinan 250117Shandong ProvinceChina Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

BACKGROUND The effect of hypoxia on mesenchymal stem cells(MSCs)is an emerging topic in MSC *** long non-coding RNAs(lncRNAs)and messenger RNAs(mRNAs)are reported to play a critical role in regulating the biological characteristics of MSCs,their specific expression and co-expression profiles in human placenta-derived MSCs(hP-MSCs)under hypoxia and the underlying mechanisms of lncRNAs in hP-MSC biology are *** To reveal the specific expression profiles of lncRNAs in hP-MSCs under hypoxia and initially explored the possible mechanism of lncRNAs on hP-MSC *** Here,we used a multigas incubator(92.5%N_(2),5%CO_(2),and 2.5%O_(2))to mimic the potential of *** sequencing technology was applied to identify the exact expression profiles of lncRNAs and mRNAs under *** We identified 289 differentially expressed lncRNAs and 240 differentially expressed mRNAs between the hypoxia and normoxia *** them,the lncRNA SNHG16 was upregulated under hypoxia,which was also validated by reverse transcription-polymerase chain ***16 was confirmed to affect hP-MSC proliferation rates using a SNHG16 knockdown ***16 overexpression could significantly enhance the proliferation capacity of hP-MSCs,activate the PI3K/AKT pathway,and upregulate the expression of cell cycle-related *** Our results revealed the specific expression characteristics of lncRNAs and mRNAs in hypoxiacultured hP-MSCs and that lncRNA SNHG16 can promote hP-MSC proliferation through the PI3K/AKT pathway.

关键词： Human placenta-derived mesenchymal stem cell Hypoxia Long non-coding RNAs Proliferation Mesenchymal stem cell