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In silico analysis of lncRNA-miRNA-mRNA signatures related to Sorafenib effectiveness in liver cancer cells

World Journal of Gastroenterology 2025年第3期31卷 84-102页

作者： Patricia de la Cruz-Ojeda Ester Parras-Martínez Raquel Rey-Pérez Jordi Muntané Functional Genomics of Solid Tumors Laboratory Centre de Recherche des CordeliersParis 75006France Department of Oncology Surgery Cell Therapy and Organ TransplantationInstitute of Biomedicine of SevilleVirgen del Rocio University HospitalSeville 41013Spain Biomedical Research Center for Hepatic and Digestive Diseases CIBERehdMadrid 28029Spain Department of Medical Physiology and Biophysics University of SevilleSeville 41009Spain

BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of primary liver cancer with varied incidence and epidemiology *** is still a recommended treatment for a large proportion of patients with advanced *** patterns of treatment responsiveness have been identified in differentiated hepatoblastoma HepG2 cells and metastatic HCC SNU449 *** To define the long non-codingRNA-microRNA-mRNA(lncRNA-miRNA-mRNA)predicted signatures related to selected hallmarks of cancer(apoptosis,autophagy,cell stress,cell dedifferentiation and invasiveness)in RNAseq studies using Sorafenib-treated HepG2 and SNU449 *** available software analyses allowed us to establish the lncRNA-miRNA-mRNA regulatory axes following treatment in HepG2 and SNU449 *** HepG2 and SNU449 cells were treated with Sorafenib(10μmol/L)for 24 *** RNA,including small and long RNA,was extracted with a commercial miRNeasy *** was carried out for the identification of changes in lncRNA-miRNA-mRNA regulatory *** MALAT,THAP9-AS1 and SNGH17 appeared to coordinately regulate miR-374b-3p and miR-769-5p that led to upregulation of SMAD7,TIRARP,TFAP4 and FAXDC2 in HepG2 ***12,EPB41 L4A-AS1,LINC01578,SNHG12 and GAS5 interacted with let-7b-3p,miR-195-5p and VEGFA in SNU449 *** axes MALAT1/hsamir-374b-3p/SMAD7 and MALAT1/hsa-mir-769-5p/TFAP4 were of high relevance for Sorafenib response in HepG2 cells,whereas PVT1/hsa-miR-195-5p/VEGFA was responsible for the differential response of SNU449 cells to Sorafenib *** Critical lncRNAs acting as sponges of miRNA were identified that regulated mRNA expression,whose proteins mainly increased the antitumor effectiveness of the treatment(SMAD7,TIRARP,TFAP4,FAXDC2 and ADRB2).However,the broad regulatory axis leading to increased VEGFA expression may be related to the side effect of Sorafenib in SNU449 cells.

关键词： Cell culture Hepatocellular carcinoma Non-coding RNA RNAseq Sorafenib

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Activation of immune signals during organ transplantation

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1545-1570页

作者： Qingwen Li Peixiang Lan institute of organ transplantation Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Key Laboratory of organ transplantation Ministry of EducationNHC Key Laboratory of Organ TransplantationKey Laboratory of Organ TransplantationChinese Academy of Medical SciencesWuhanChina

The activation of host’s innate and adaptive immune systems can lead to acute and chronic graft rejection,which seriously impacts graft ***,it is particularly significant to clarify the immune signals,which are critical to the initiation and maintenance of rejection generated after *** initiation of response to graft is dependent on sensing of danger and stranger *** ischemia and reperfusion of grafts lead to cell stress or death,followed by releasing a variety of damage-associated molecular patterns(DAMPs),which are recognized by pattern recognition receptors(PRRs)of host immune cells to activate intracellular immune signals and induce sterile *** addition to DAMPs,the graft exposed to‘non-self’antigens(stranger molecules)are recognized by the host immune system,stimulating a more intense immune response and further aggravating the graft *** polymorphism of MHC genes between different individuals is the key for host or donor immune cells to identify heterologous‘non-self’components in allogeneic and xenogeneic organ *** recognition of‘nonself’antigen by immune cells mediates the activation of immune signals between donor and host,resulting in adaptive memory immunity and innate trained immunity to the graft,which poses a challenge to the long-term survival of the *** review focuses on innate and adaptive immune cells receptor recognition of damage-associated molecular patterns,alloantigens and xenoantigens,which is described as danger model and stranger *** this review,we also discuss the innate trained immunity in organ transplantation.

关键词： immunity damage graft

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Infective Artery Rupture of Renal Allografts:A Single-Center Retrospective Study in China

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Current Medical Science 2022年第4期42卷 847-855页

作者： Yu-liang GUO Xia LU Lan ZHU Dun-feng DU Bin LIU Zhong-hua Klaus CHEN Song CHEN Wei-jie ZHANG Zhi-shui CHEN Sheng CHANG institute of organ transplantation Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyKey Laboratory of Organ TransplantationMinistry of EducationNHC Key Laboratory of Organ TransplantationKey Laboratory of Organ TransplantationChinese Academy of Medical SciencesWuhan 430030China

Objective:This study investigated the composition of pathogenic microorganisms,clinical features,and therapeutic strategies of infective artery rupture of renal allografts in recipients receiving deceased donor(DD)***:We retrospectively studied the clinical data of the DD kidney transplant recipients with donor-associated infection at Tongji Hospital,Wuhan,China from January 1,2015 to December 31,2018,related recipients and corresponding *** collected the entire results of pathogenic microorganisms cultured from these related ruptured kidneys and then analyzed their distribution and ***:A total of 1440 kidney transplants from DD were performed in our *** total incidence of infective artery rupture in kidney transplants was about 0.76%(11/1440),and the annual incidence ranged from 0.25%to 1.03%.The microbial culture results revealed that 11 recipients suffered from infective artery rupture and 3 recipients who accepted the kidney from same donor had the donor-associated pathogens,including 9 fungal strains(28.1%)and 23 bacterial strains(71.9%).There were 4 recipients infected with multi-drug-resistant Staphylococcus and Klebsiella pneumoniae from the above 11 recipients,of which,10 recipients underwent graft loss,and one died of septic *** microbial cultures of the remaining 3 recipients who received appropriate anti-infective regimens turned negative eventually,and the patients were discharged successfully without significant ***:Renal recipients with infections derived from DDs were at high risk of artery rupture,graft loss,or even *** anti-infective treatment is essential to reduce the incidence of artery rupture and mortality.

关键词： kidney transplantation deceased donor renal artery rupture infection

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Role of selected criteria and preventive chemotherapy in tumor recurrence after liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2020年第4期19卷 378-383页

作者： Mei-Xi Wang Dong Chen Yuan-Yuan Zhao Bo Yang Ji-Pin Jiang Fan-Jun Zeng Lai Wei Zhi-Shui Chen institute of organ transplantation Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Key Laboratory of organ transplantation Ministry of EducationWuhan 430030China NHC Key Laboratory of organ transplantation Wuhan 430030China Key Laboratory of organ transplantation Chinese Academy of Medical SciencesWuhan 430030China

Background:Long-term survival after liver transplantation(LT)for hepatocellular carcinoma(HCC)patients remains poor because of tumor *** improve the prognosis of HCC patients after LT,we aimed to identify different transplantation criteria and risk factors related to tumor recurrence and evaluate the effect of preventive chemotherapy in a single ***:In total,data on 20 variables and the survival of 199 patients with primary HCC who underwent LT between 2005 and 2015 were included for *** patients were divided into the following three groups:Group 1,within the Milan and Hangzhou criteria(n=51);Group 2,beyond the Milan but within the Hangzhou criteria(n=36);and Group 3,beyond the Milan and Hangzhou criteria(n=112).Survival probabilities for the three groups were calculated using multivariate Cox regression *** association between preventive therapy and HCC-recurrence after LT was analyzed by multiple logistic regression ***:Child-Pugh stage C and hepatitis B virus(HBV)infection were independent risk factors for patients with tumor recurrence who did not meet the Milan *** overall survival rates of the 199 patients showed statistically significant differences among the three groups(P0.05).Multivariate logistic regression analysis showed that postoperative prophylactic chemotherapy reduced the risk of tumor recurrence in patients who did not meet the Hangzhou and Milan criteria(OR=0.478;95%CI:0.308–0.741;P=0.001).Conclusions:Child-Pugh classification and HBV infection were the independent risk factors of tumor recurrence in HCC patients with *** Hangzhou criteria were effective and analogous compared with the Milan *** chemotherapy significantly reduced the risk of recurrence and prolonged the survival time for HCC patients beyond the Milan and Hangzhou criteria after LT.

关键词： Hepatocellular carcinoma Liver transplantation Preventive chemotherapy Hangzhou criteria

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Administration of tacrolimus in 50 liver transplantation patients

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Hepatobiliary & Pancreatic Diseases International 2002年第4期1卷 492-494页

作者： Manal Abdel Ruzig the institute of organ transplantation and Tongji

Objective: To present a good tacrolimus (FK506) administration protocol in liver transplantation. Methods: Fifty liver transplantation patients were classified into FK506 high-concentration (20 pa- tients), FK506 mid-concentration (20), CsA-FK506 (5) and FK506-CsA (5) groups. Clinical manifesta- tions, FK506 side-effects and pathological changes were observed. Results: The FK506 high-concentration group show- ed complications such as infection and liver function damage. The FK506 mid-concentration group show- ed excellent therapeutic results and some complica- tions easy to deal with. Conclusion: FK506 is a highly effective immunosup- pressive agent and the mid-concentration protocol is a better one.

关键词： tacrolimus liver transplantation

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State of the art and perspectives in liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2023年第1期22卷 1-3页

作者： Xiao Xu institute of organ transplantation Zhejiang UniversityHangzhou 310003China

Since the first liver transplantation(LT)was executed by Thomas *** in 1963,the past six decades have witnessed rapid progresses in LT,especially in the immunosuppressive agents,surgical techniques,and perioperative *** has been well-recognized as the only curative intervention for end-stage liver *** this special issue on frontiers in LT,authors from several international LT centers summarized the current state and progresses in LT,including selection criteria for LT candidates,and precise management in LT recipients with HCC.

关键词： liver curative frontier

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Criteria-specific long-term survival prediction model for hepatocellular carcinoma patients after liver transplantation

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World Journal of Gastroenterology 2014年第31期20卷 10900-10907页

作者： Fei Teng Gui-Hua Wang Yi-Feng Tao Wen-Yuan Guo Zheng-Xin Wang Guo-Shan Ding Xiao-Min Shi Zhi-Ren Fu organ transplantation institute of Changzheng Hospital Second Military Medical University

AIM: To establish a model to predict long-term survival of hepatocellular carcinoma (HCC) patients after liver transplantation (MHCAT).

关键词： Criteria Hepatocellular carcinoma Liver transplantation MHCAT Survival model

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Outcomes in children with biliary atresia following liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2013年第2期12卷 143-148页

作者： Li-Ying Sun Yun-Sheng Yang Zhi-Jun Zhu Wei Gao Lin Wei Xiao-Ye Sun Wei Qu Wei Rao Zhi-Gui Zeng Chong Dong Jin-Peng Tu Jian Wang Yi-He Liu Yuan Liu Li-Xin Yu Yu Wang Jing Li Zhong-Yang Shen Nankai University School of Medicine Department of Gastroenterology and Hepatology Chinese PLA General Hospital Department of organ transplantation Tianjin First Centra Hospital

BACKGROUND: Congenital biliary atresia is a rare condition characterized by idiopathic dysgenesis of the bile ducts. If untreated, congenital biliary atresia leads to liver cirrhosis, liver failure and premature death. The present study aimed to evaluate the outcomes of orthotopic liver transplantation in children with biliary atresia. METHOD: We retrospectively analyzed 45 patients with biliary atresia who had undergone orthotopic liver transplantation from September 2006 to August 2012. RESULTS: The median age of the patients was 11.0 months (5-102). Of the 45 patients, 41 were younger than 3 years old. Their median weight was 9.0 kg (4.5-29.0), 34 of the 45 patients were less than 10 kg. Thirty-one patients had undergone Kasai portoenterostomy prior to orthotopic liver transplantation. We performed 30 living donor liver transplants and 15 split liver transplants. Six patients died during a follow-up. The median follow-up time of surviving patients was 11.4 months (1.4-73.7). The overall 1-, 2- and 3-year survival rates were 88.9%, 84.4% and 84.4%, respectively. CONCLUSION: With advances in surgical techniques and management, children with biliary atresia after liver transplantation can achieve satisfactory survival in China, although there remains a high risk of complications in the early postoperative period.

关键词： liver transplantation biliary atresia children living donor

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Carbon Monoxide Inhibits the Nuclear-cytoplasmic Translocation of HMGB1 in an In Vitro Oxidative Stress Injury Model of Mouse Renal Tubular Epithelial Cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2016年第6期36卷 791-795页

作者： Yu JIA Lu WANG Guang-yuan ZHAO Zhi-qiang WANG Song CHEN Gang CHEN institute of organ transplantation Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Key Laboratory of organ transplantation Ministry of Education Key Laboratory of Organ Transplantation Ministry of Health Wuhan 430030 China

Carbon monoxide（CO）,as a vital small molecule in signaling pathways,is found to be involved in ischemia-reperfusion injury（IRI） in renal ***-releasing molecule-2（CORM-2）,a CO-releasing molecule,is a type of metal carbonyl complexes which can quickly release CO in *** this study,an in vitro oxidative stress injury model was established to examine the effect of CORM-2 pretreatment on the nuclear-cytoplasmic translocation of high mobility group box 1 protein（HMGB1） in mouse primary renal proximal tubular epithelial cells（RPTECs）.Immunofluorescence staining showed that HMGB1 in the medium-and CORM-2-treated groups was predominantly localized in the nucleus of the cells,whereas higher amounts of HMGB1 translocated to the cytoplasm in the H2O2-and inactive CORM-2（i CORM-2）-treated *** blotting of HMGB1 showed that the total amounts of cytoplasmic HMGB1 in the H2O2-treated（0.59±0.27） and i CORM-2-treated（0.57±0.22） groups were markedly higher than those in the medium-treated（0.19±0.05） and CORM-2-treated（0.21±0.10） groups（P〈0.05）.Co-immunoprecipitation showed that the levels of acetylated HMGB1 in the H2O2-treated（642.98±57.25） and i CORM-2-treated（342.11±131.25） groups were markedly increased as compared with the medium-treated（78.72±74.17） and CORM-2-treated（71.42±53.35） groups（P〈0.05）,and no significant difference was observed between the medium-treated and CORM-2-treated groups（P〉0.05）.In conclusion,our study demonstrated that in the in vitro oxidative stress injury model of primary RPTECs,CORM-2 can significantly inhibit the nuclear-cytoplasmic translocation of HMGB1,which is probably associated with the prevention of HMGB1 acetylation.

关键词： renal tubules epithelial cell oxidative stress HMGB1 protein carbon monoxide acetylation

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Hepatocyte isolation from resected benign tissues: Results of a 5-year experience

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World Journal of Gastroenterology 2016年第36期22卷 8178-8186页

作者： Fan-Ying Meng Li Liu Jun Liu Chun-You Li Jian-Ping Wang Feng-Hui Yang Zhi-Shui Chen Ping Zhou Division of Hepato-Biliary-Pancreatic Surgery Institute of Organ Transplantation Shandong Provincial Hospital affiliated to Shandong University institute of organ transplantation Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

AIM To analyze retrospectively a 5-year experience of human hepatocyte isolation from resected liver tissues with benign *** We established a method of modified four-step retrograde perfusion to isolate primary human hepatocytes. Samples were collected from the resected livers of patients with intrahepatic duct calculi(n = 7) and liver hemangioma(n = 17). Only the samples weighing ≥ 15 g were considered suitable for hepatocyte isolation. By using the standard trypan blue exclusion technique, hepatocyte viability and yield were immediately determined after *** Twenty-four liver specimens, weighing 15-42 g, were immediately taken from the margin of the removed samples and transferred to the laboratory for hepatocyte isolation. Warm ischemia time was 5-35 min and cold ischemia time was 15-45 min. For the 7 samples of intrahepatic duct calculi, the method resulted in a hepatocyte yield of 3.49 ± 2.31 × 10~6 hepatocytes/g liver, with 76.4% ± 10.7% viability. The 17 samples of liver hemangioma had significantly higher yield of cells(5.4 ± 1.71 × 10~6 cells/g vs 3.49 ± 2.31 × 10~6 cells/g, P 0.05). We obtained a cell yield of 5.31 ± 1.87 × 10~6 hepatocytes/g liver when the samples weighed > 20 g. However, for the tissues weighing ≤ 20 g, a reduction in yield was found(3.08 ± 1.86 × 10~6 cells/g vs 5.31 ± 1.87 × 10~6 cells/g, P < 0.05).CONCLUSION Benign diseased livers are valuable sources for largenumber hepatocyte isolation. Our study represents the largest number of primary human hepatocytes isolated from resected specimens from patients with benign liver disease. We evaluated the effect of donor liver characteristics on cell isolation, and we found that samples of liver hemangioma can provide better results than intrahepatic duct calculi, in terms of cell yield. Furthermore, the size of the

关键词： Human hepatocyte Primary hepatocyte Cell isolation Benign liver disease Hepatocyte isolation

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