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Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

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World Journal of Gastroenterology 2025年第1期31卷 126-145页

作者： Xing-Hui Yu Yan Xie Jian Yu Kun-Ning Zhang Zhou-Bo Guo Di Wang Zhao-Xian Li Wei-Qi Zhang Yu-Ying Tan Li Zhang Wen-Tao Jiang School of Medicine Nankai UniversityTianjin 300192China Tianjin Key Laboratory of Molecular Diagnosis and Treatment of Liver Cancer Tianjin First Center HospitalTianjin 300192China department of Liver transplantation Tianjin First Center HospitalTianjin 300192China first Central Clinical School Tianjin Medical UniversityTianjin 300192China

BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated *** therapeutic targets are beneficial to treat and predict the ***,the exact molecular mechanisms leading to the progression of HCC are still *** has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor *** this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between *** To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC *** In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC ***,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,*** statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank *** In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival ***1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated ***,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via *** the exploration mechanism,we found ASH1L may promote an immunosuppressive mi

关键词： Hepatocellular carcinoma MicroRNA-142-3p ASH1L Immune evasion Tumor immune microenvironment Apoptosis

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Bone-marrow mesenchymal stem cells reduce rat intestinal ischemia-reperfusion injury, ZO-1 downregulation and tight junction disruption via a TNF-α-regulated mechanism

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World Journal of Gastroenterology 2013年第23期19卷 3583-3595页

作者： Zhong-Yang Shen Jing Zhang Hong-Li Song Wei-Ping Zheng department of organ transplantation Tianjin First Central Hospital

AIM: To investigate the effect of bone-marrow mesenchymal stem cells (BM MSCs) on the intestinal mucosa barrier in ischemia/reperfusion (I/R) injury. METHODS: BM MSCs were isolated from male Sprague-Dawley rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. I/R injury was induced by occlusion of the superior mesenteric artery for 30 min. Rats were treated with saline, BM MSCs (via intramucosal injection) or tumor necrosis factor (TNF)-α blocking antibodies (via the tail vein). I/R injury was assessed using transmission electron microscopy, hematoxylin and eosin (HE) staining, immunohistochemistry, western blotting and enzyme linked immunosorbent ***: Intestinal permeability increased, tight junctions (TJs) were disrupted, and zona occludens 1 (ZO-1) was downregulated after I/R injury. BM MSCs reduced intestinal mucosal barrier destruction, ZO-1 downregulation, and TJ disruption. The morphological abnormalities after intestinal I/R injury positively correlated with serum TNF-α levels. Administration of anti-TNF-α IgG or anti-TNF-α receptor 1 antibodies attenuated the intestinal ultrastructural changes, ZO-1 downregulation, and TJ disruption. CONCLUSION: Altered serum TNF-α levels play an important role in the ability of BM MSCs to protect against intestinal I/R injury.

关键词： Bone marrow mesenchymal stem cells Zona occludens 1 Ischemia-reperfusion injury Intestinal mucosa Tumor necrosis factor-α

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Integration of perioperative features and intragraft TCF7L2 expression to predict lipid metabolic disorder in liver transplant recipients

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Science China Life Sciences 2025年第1期 297-299页

作者： Junbin Zhou Rongli Wei Guanghan Fan Zhengxing Lian Xuanyu Zhang Linsong Tang Zhetuo Qi Haiyang Xie Shusen Zheng Qiang Wei Xiao Xu department of Hepatobiliary and Pancreatic Surgery People's Hospital of LishuiAffiliated Lishui Hospital of Wenzhou Medical UniversityThe First Affiliated Hospital of Lishui University NHFPC Key Laboratory of Combined Multi-organ transplantation Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryHangzhou First People's Hospital department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of Medicine department of Urology The Second Affiliated HospitalZhejiang University School of Medicine department of Hepatobiliary and Pancreatic Surgery Department of Liver TransplantationShulan (Hangzhou) Hospital Hangzhou Medical College Zhejiang University School of Medicine

Dear Editor, Liver transplantation(LT) is the only curative therapy for patients with endstage liver disease(He et al., 2023; Ling et al., 2022). Post-transplant hypertriglyceridemia(PTHT), which has an incidence of up to 32.8% in 6 months after LT, is one of the major post-transplant complications(Toshima et al., 2020).

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Effect of CXCR3/HO-1 genes modified bone marrow mesenchymal stem cells on small bowel transplant rejection

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World Journal of Gastroenterology 2017年第22期23卷 4016-4038页

作者： Ming-Li Yin Hong-Li Song Yang Yang Wei-Ping Zheng Tao Liu Zhong-Yang Shen Tianjin first Central hospital Clinic Institute Tianjin Medical University department of organ transplantation Tianjin First Central HospitalTianjin Clinical Research Center for Organ Transplantation and Tianjin Key Laboratory of Organ Transplantation department of organ transplantation Tianjin First Central Hospital Tianjin first Central hospital and Key Laboratory of Emergency and Care Medicine of Ministry of Health

AIM To investigate whether bone marrow mesenchymal stem cells (BMMSCs) modified with the HO-1 and CXCR3 genes can augment the inhibitory effect of BMMSCs on small bowel transplant rejection. METHODS Lewis rat BMMSCs were cultured in vitro. Third-passage BMMSCs were transduced with the CXCR3 / HO-1 genes or the HO-1 gene alone. The rats were divided into six groups and rats in the experimental group were pretreated with BMMSCs 7 d prior to small bowel transplant. Six time points (instant, 1 d, 3 d, 7 d, 10 d, and 14 d) (n = 6) were chosen for each group. Hematoxylin-eosin staining was used to observe pathologic rejection, while immunohistochemistry and Western blot were used to detect protein expression. Flow cytometry was used to detect T lymphocytes and enzyme linked immunosorbent assay was used to detect cytokines. RESULTS The median survival time of BMMSCs from the CXCR3/HO-1 modified group (53 d) was significantly longer than that of the HO-1 modified BMMSCs group (39 d), the BMMSCs group (26 d), and the NS group (control group) (16 d) (P < 0.05). Compared with BMMSCs from the HO-1 modified BMMSCs, BMMSCs, and NS groups, rejection of the small bowel in the CXCR3 / HO-1 modified group was significantly reduced, while the weight of transplant recipients was also significantly decreased (P < 0.05). Furthermore, IL-2, IL-6, IL-17, IFN-gamma, and TNF-alpha levels were significantly decreased and the levels of IL-10 and TGF-beta were significantly increased (P < 0.05). CONCLUSION BMMSCs modified with the CXCR3 and HO-1 genes can abrogate the rejection of transplanted small bowel more effectively and significantly increase the survival time of rats that receive a small bowel transplant.

关键词： Bone marrow mesenchymal stem cells CXCR3 HO-1 Small bowel transplantation Rejection

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Autoimmune hepatitis-primary biliary cirrhosis concurrent with biliary stricture after liver transplantation

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World Journal of Gastroenterology 2015年第7期21卷 2236-2241页

作者： Yong-Zhen Kang Xiao-Ye Sun Yi-He Liu Zhong-Yang Shen first Central clinic of Tianjin Medical University department of organ transplantation Tianjin First Center Hospital Tianjin Key Laboratory of Organ Transplantation

Although the development of de novo autoimmune liver disease after liver transplantation(LT)has been described in both children and adults,autoimmune hepatitis(AIH)-primary biliary cirrhosis(PBC)overlap syndrome has rarely been seen in liver transplant ***,we report a 50-year-old man who underwent LT for decompensated liver disease secondary to alcoholic *** liver function tests became markedly abnormal 8 years after *** autoimmune serological tests were positive for anti-nuclear and antimitochondrial antibodies,and a marked biochemical response was observed to a regimen consisting of prednisone and ursodeoxycholic acid added to maintain immunosuppressant *** biopsy showed moderate bile duct lesions and periportal lymphocytes infiltrating along with light fibrosis,which confirmed the diagnosis of AIH-PBC overlap *** believe that this may be a case of post-LT de novo AIH-PBC overlap syndrome;a novel type of autoimmune overlap syndrome.

关键词： Autoimmune liver disease Autoimmune hepatitis Prim

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Effects of heme oxygenase-1-modified bone marrow mesenchymal stem cells on microcirculation and energy metabolism following liver transplantation

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World Journal of Gastroenterology 2017年第19期23卷 3449-3467页

作者： Liu Yang Zhong-Yang Shen Rao-Rao Wang Ming-Li Yin Wei-Ping Zheng Bin Wu Tao Liu Hong-Li Song the first Central Clinical College Tianjin Medical University department of organ transplantation Tianjin First Central Hospital Tianjin first Central hospital and Key Laboratory of Emergency and Care Medicine of Ministry of Health department of organ transplantation Tianjin First Central Hospital and Tianjin Key Laboratory of Organ Transplantation

AIM To investigate the effects of heme oxygenase-1(HO-1)-modified bone marrow mesenchymal stem cells(BMMSCs)on the microcirculation and energy metabolism of hepatic sinusoids following reduced-size liver transplantation(RLT)in a rat *** BMMSCs were isolated and cultured in vitro using an adherent method,and then transduced with HO-1-bearing recombinant adenovirus to construct HO-1/BMMSCs.A rat acute rejection model following 50%RLT was established using a two-cuff *** were divided into three groups based on the treatment received:normal saline(NS),BMMSCs and HO-1/*** function was examined at six time *** levels of endothelin-1(ET-1),endothelial nitric-oxide synthase(e NOS),inducible nitric-oxide synthase(i NOS),nitric oxide(NO),and hyaluronic acid(HA)were detected using an enzyme-linked immunosorbent *** portal vein pressure(PVP)was detected by Power Lab *** expressions of ET-1,i NOS,e NOS,and von Willebrand factor(v WF)protein in the transplanted liver were detected using immunohistochemistry and Western *** in the transplanted liver was detected by chemical colorimetry,and the ultrastructural changes were observed under a transmission electron *** HO-1/BMMSCs could alleviate the pathological changes and rejection activity index of the transplanted liver,and improve the liver function of rats following 50%RLT,with statistically significant differences compared with those of the NS group and BMMSCs group(P<0.05).In term of the microcirculation of hepatic sinusoids:The PVP on POD7 decreased significantly in the HO-1/BMMSCs and BMMSCs groups compared with that of the NS group(P<0.01);HO-1/BMMSCs could inhibit the expressions of ET-1 and i NOS,increase the expressions of e NOS and inhibit amounts of NO production,and maintain the equilibrium of ET-1/NO(P<0.05);and HO-1/BMMSCs increased the expression of v WF in hepatic sinusoidal endothelial cells(SECs),and promoted the degradation of HA,

关键词： Reduced-size liver transplantation Bone marrow mesenchymal stem cells Microcirculation Heme oxygenase-1 Energy metabolism

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Effect of donor age on graft function and longterm survival of recipients undergoing living donor liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2015年第1期14卷 50-55页

作者： Kai Wang Wen-Tao Jiang Yong-Lin Deng Cheng Pan Zhong-Yang Shen department of Transplant Surgery Tianjin First Center Hospital Key Laboratory of Organ Transplantation of Tianjin

BACKGROUND： Donor shortage is the biggest obstacle in organ transplantation. Living donor liver transplantation（LDLT） has been considered as a valuable approach to shortening waiting time. The objectives of this study were to investigate the feasibility of utilizing donors older than 50 years in LDLT and to evaluate the graft function and recipient ***： All LDLT cases（n=159） were divided into the older（donor age ≥50 years, n=10） and younger（donor age 〈50 years,n=149） donor groups. Donor graft and recipient condition pre-,intra- and post-operation were compared between the two *** particular, graft functions and recipient survivals were ***： The median donor age was 58.5（52.5-60.0） years in the older donor group and 25.0（23.0-32.0） in the younger donor group. There was no significant difference in cold ischemic time, anhepatic phase and operation time between the older and younger donor groups（P〉0.05）. However, the volume of red blood cell transfused in operation was greater in the older donor group than in the younger donor group（1900 vs 1200 m L, P=0.023）. The 1-, 3- and 5-year graft survival rates were 90%, 80% and 80% for the older donor group, and 92%, 87% and 87% for the younger donor group, respectively（P=0.459）.The 1-, 3- and 5-year survival rates were 100%, 90% and 90% for recipients with older grafts, and 93%, 87% and 87% for those with younger grafts, respectively（P=0.811）.CONCLUSION： It is safe for a LDLT recipient to receive liver from donors older than 50 years, and there is no significant adverse effect on graft function and long-term patients’ survival.

关键词： living donor liver transplantation donor age graft liver function long-term survival

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Global transplantation:Lessons from organ transplantation organizations worldwide

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World Journal of transplantation 2025年第1期15卷 44-56页

作者： Solonas Symeou Eleni Avramidou Vassilios Papalois Georgios Tsoulfas Medical School University of IoanninaIoannina 45110Greece department of transplantation Surgery Center for Research and Innovation in Solid Organ TransplantationSchool of MedicineAristotle University of ThessalonikiThessaloniki 54642Greece Imperial College Renal and Transplant Centre Imperial College Healthcare NHS TrustHammersmith HospitalLondon W120HSUnited Kingdom department of Surgery and Cancer Imperial College LondonLondon SW72AZUnited Kingdom

Although national transplant organizations share common visions and goals,the creation of a unified global organization remains *** in ethnicity,culture,religion,and education shape local practices and infrastructure,making the establishment of a single global entity *** with these social disparities aside,logistical factors such as time and distance between organ procurement and transplantation sites pose significant *** technological advancements have extended organ preservation times,they have yet to support the demands of transcontinental transplantations *** review presents a comparative analysis of the structures,operational frameworks,policies,and legislation governing various transplant organizations around the *** differences pertain to the administration of these organizations,trends in organ donation,and organ allocation policies,which reflect the financial,cultural,and religious diversity across different *** a global transplant organization may be out of reach,agreeing on best practices for the benefit of patients is essential.

关键词： organ transplantation National transplant organizations organ donation Global transplantation Transplant systems

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Application of nucleoside analogues to liver transplant recipients with hepatitis B

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World Journal of Gastroenterology 2015年第42期21卷 12091-12100页

作者： Zhuo-Lun Song Yu-Jun Cui Wei-Ping Zheng Da-Hong Teng Hong Zheng organ transplantation Center Tianjin Key Laboratory of Organ Transplantation Tianjin First Center Hospital Swiss Hepato-Pancreato-Biliary Center Department of Visceral and Transplantation Surgery University Hospital Zurich

Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus(HBV) core antibody(HBc Ab) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues(NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBc Ab-positive liver grafts.

关键词： Nucleoside analogues Liver transplantation Hepatit

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Risk factors for de novo hepatitis B infection in pediatric living donor liver transplantation

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World Journal of Gastroenterology 2014年第36期20卷 13159-13166页

作者： Wei Rao Man Xie Tao Yang Jian-Jun Zhang Wei Gao Yong-Lin Deng Hong Zheng Cheng Pan Yi-He Liu Zhong-Yang Shen department of organ transplantation Tianjin Key Laboratory of Organ Transplantation Tianjin First Central Hospital Liver Research Center Beijing Friendship Hospital Capital Medical University

AIM: To investigate the incidence of de novo hepatitis B virus (HBV) infection after pediatric living donor liver transplantation (LDLT) and to analyze the risk factors associated with this de novo HBV infection.

关键词： Pediatric liver donor liver transplantation Occult hepatitis B infection De novo hepatitis B infection

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