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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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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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Platelets in liver disease, cancer and regeneration

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World Journal of Gastroenterology 2017年第18期23卷 3228-3239页

作者： Tomohiro Kurokawa Nobuhiro Ohkohchi Department of surgery Division of Gastroenterological and Hepatobiliary Surgery and Organ Transplantation Faculty of Medicine University of Tsukuba

Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors required for organ development, tissue regeneration and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease(CLD) and cirrhosis, can manifest from decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis, as well as the role of platelets in CLD, is poorly understood. In this paper, experimental evidence of platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. In addition, we describe our current perspective based on the results of these studies. Platelets improve liver fibrosis by inactivating hepatic stellate cells, which decreases collagen production. The regenerative effect of platelets in the liver involves a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these observations, we ascertained the direct effect of platelet transfusion on improving several indicators of liver function in patients with CLD and liver cirrhosis. However, unlike the results of our previous clinical study, the smaller incremental changes in liver function in patients with CLD who received eltrombopag for 6 mo were due to patient selection from a heterogeneous population. We highlight the current knowledge concerning the role of platelets in CLD and cancer and anticipate a novel application of platelet-based clinical therapies to treat liver disease.

关键词： Platelet Liver cirrhosis Liver regeneration Cancer Thrombopoietin Thrombopoietin agonist Eltrombopag

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Success of intravenous immunoglobulin and steroids in managing severe COVID-19 following lung transplantation:A case report

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World Journal of transplantation 2025年第1期15卷 178-184页

作者： Yen-Shou Kuo Kuan-Hsun Lin Ying-Yi Chen Yuan-Ming Tsai Ti-Hui Wu Hsu-Kai Huang Tsai-Wang Huang division of Thoracic surgery Department of SurgeryTri-Service General HospitalNational Defense Medical CenterTaipei 114202Taiwan

BACKGROUND Coronavirus disease 2019(COVID-19)pneumonia with severe septic shock and acute respiratory distress syndrome(ARDS)are critical illnesses for patients following *** immunoglobulin(IVIG)plays a role in both immune support and inflammation control,especially in immunocompromised *** case report describes the first successful experience using IVIG and pulse steroids to manage this critical condition following lung *** SUMMARY A 65-year-old male patient reported a history of chronic obstructive pulmonary disease and poor lung function and received bilateral sequential lung ***,he developed COVID-19 pneumonia,severe septic shock,and *** recovered from this critical condition after empirical antibiotics administration and veno-venous extracorporeal membrane oxygenation,in addition to IVIG and pulse *** IVIG is a valuable adjunct in managing severe sepsis in lung transplant recipients after COVID-19 *** aim,for the first time,to report the success of such a management approach for COVID-19 ARDS and sepsis in the post-lung transplant *** further investigations,this is a starting point for wider analysis of such an approach in this setting and consequently helps guide clinical practice for such a challenging patient population moving forward.

关键词： COVID-19 Septic shock Intravenous immunoglobulin Lung transplantation Post-transplant complications Case report

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Future of non-invasive graft evaluation:A systematic review of proteomics in kidney transplantation

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World Journal of transplantation 2025年第1期15卷 135-149页

作者： Eleni Avramidou Konstantina Psatha Kallisti St John Georgios Tsoulfas Michalis Aivaliotis Department of transplantation surgery Center for Research and Innovation in Solid Organ TransplantationAristotle University of ThessalonikiSchool of MedicineThessaloniki 54642Greece Laboratory of Medical Biology-Genetics School of MedicineAristotle University of ThessalonikiThessaloniki 54124Greece Functional Proteomics and Systems Biology(FunPATh) Center for Interdisciplinary Research and Innovation(CIRI-AUTH)Thessaloniki GR-57001Greece Laboratory of Biological Chemistry School of MedicineAristotle University of ThessalonikiThessaloniki 54124Greece

BACKGROUND Despite the developments in the field of kidney transplantation,the already existing diagnostic techniques for patient monitoring are considered *** biomarkers that can be derived from modern approaches of proteomic analysis of liquid biopsies(serum,urine)represent a promising innovation in the monitoring of kidney transplant *** To investigate the diagnostic utility of protein biomarkers derived from proteomics approaches in renal allograft *** A systematic review was conducted in accordance with PRISMA guidelines,based on research results from the PubMed and Scopus *** primary focus was on evaluating the role of biomarkers in the non-invasive diagnosis of transplant-related *** criteria included protein biomarkers and urine and blood samples,while exclusion criteria were language other than English and the use of low resolution and sensitivity *** selected research articles,were categorized based on the biological sample,condition and methodology and the significantly and reproducibly differentiated proteins were manually selected and *** and network analysis of the selected proteins was *** In 17 included studies,58 proteins were studied,with the cytokine CXCL10 being the most *** pathways related to immune response and fibrosis have shown to be *** of biomarkers for the assessment of renal damage as well as the prediction of short-term and long-term function of the graft were ***,all studies have shown satisfactory diagnostic accuracy of proteins alone or in combination with conventional methods,as far as renal graft assessment is *** Our review suggests that protein biomarkers,evaluated in specific biological fluids,can make a significant contribution to the timely,valid and non-invasive assessment of kidney graft.

关键词： Proteomics Kidney transplantation Graft evaluation Non-invasive diagnosis Kidney graft function

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Liver transplantation for primary sclerosing cholangitis-morbidities including disease recurrence

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Hepatobiliary surgery and Nutrition 2024年第1期13卷 143-146页

作者： Nobuhisa Akamatsu Artificial organ and transplantation surgery division Department of SurgeryUniversity of TokyoTokyoJapan

Primary sclerosing cholangitis(PSC)is one of the major diseases indicated for liver transplantation(LTx).There are some important points to be considered when discussing LTx for PSC,which makes it a unique etiology among liver transplant *** often coexists with inflammatory bowel disease(IBD),mainly ulcerative colitis(UC),and patients with PSC are prone to develop colorectal cancer and cholangiocarcinoma both before and after LTx.

关键词： Liver transplantation(LTx) primary sclerosing cholangitis(PSC) recurrent disease

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Three-dimensional imaging identified the accessory bile duct in a patient with cholangiocarcinoma

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World Journal of Gastroenterology 2014年第32期20卷 11451-11455页

作者： Ryoichi Miyamoto Yukio Oshiro Shinji Hashimoto Keisuke Kohno Kiyoshi Fukunaga Tatsuya Oda Nobuhiro Ohkohchi division of Gastroenterological and Hepatobiliary surgery and Organ Transplantation Department of Surgery University of Tsukuba Ibaraki 305-8575 Japan

The development of diagnostic imaging technology, such as multidetector computed tomography(MDCT) and magnetic resonance cholangiopancreatography(MRCP), has made it possible to obtain detailed images of the bile duct. Recent reports have indicated that a 3-dimensional(3D) reconstructed imaging system would be useful for understanding the liver anatomy before surgery. We have investigated a novel method that fuses MDCT and MRCP images. This novel system easily made it possible to detect the anatomical relationship between the vessels and bile duct in the portal hepatis. In this report, we describe a very rare case of extrahepatic cholangiocarcinoma associated with an accessory bile duct from the caudate lobe connecting with the intrapancreatic bile duct. We were unable to preoperatively detect this accessory bile duct using MDCT and MRCP. However, prior to the second operation, we were able to clearly visualise the injured accessory bile duct using our novel 3D imaging modality. In thisreport, we suggest that this imaging technique can be considered a novel and useful modality for understanding the anatomy of the portal hepatis, including the hilar bile duct.

关键词： 3-dimensional imaging Hepatobiliary and pancreatic surgery Accessory bile duct Caudate lobe bile duct Cholangiocarcinoma

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A liver donor with double hepatic artery aneurysm: a saved graft

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Hepatobiliary & Pancreatic Diseases International 2015年第4期14卷 443-445页

作者： Vincenzo Tondolo Alberto Manzoni Fausto Zamboni division of General surgery and transplantation Department of Surgery Brotzu Hospital

The shortage of organs and the increasing median age of deceased donors for orthotropic liver transplantation stimulate transplant centres to accept grafts that otherwise would have been discarded due to severe vascular abnormali- ties. We encountered a donor with two arterial aneurysms and a left accessory hepatic artery： an arterial aneurysm of the common hepatic artery and a left accessory hepatic artery arising from a second aneurysm of the left gastric artery （Mi- chels type V）. A complex reconstruction was created to trans- plant the liver. Multiple arterial anastomosis was made and the hepatic inflow of the transplanted liver restored. Although the procedure increased the risk of hepatic artery thrombosis, one more organ supposed to be discarded was saved.

关键词： liver transplantation anastomosis anatomy hepatic aneurysm arterial reconstruction

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Uncommon indications for associating liver partition and portal vein ligation for staged hepatectomy:a systematic review

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Hepatobiliary surgery and Nutrition 2021年第2期10卷 210-225页

作者： Quirino Lai Gianluca Mennini Zoe Larghi Laureiro Massimo Rossi Hepatobiliary surgery and organ transplantation Unit Department of General Surgery and Organ TransplantationSapienza University of RomeRomeItaly

Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)represents an innovative surgical technique used for the treatment of large hepatic lesions at high risk for post-resection liver failure due to a small future liver *** most significant amount of literature concerns the use of ALPPS for the treatment of hepatocellular carcinoma(HCC),cholangiocarcinoma(CCC),and colorectal liver metastases(CRLM).On the opposite,few is known about the role of ALPPS for the treatment of uncommon liver *** objective of the present study was to evaluate the current literature on this topic.A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)*** articles published up to February 2020 were included using the MEDLINE,Scopus,and Cochrane *** the 486 articles screened,45 papers met the inclusion criteria,with 136 described cases of ALPPS for rare *** 136 cases were reported in 18 different *** in two countries,namely Germany and Brazil,more than ten cases were *** for the ALPPS indications,we reported 41(30.1%)cases of neuroendocrine tumor(NET)metastases,followed by 27(19.9%)cases of gallbladder cancer(GBC),nine(6.6%)pediatric cases,six(4.4%)gastrointestinal stromal tumors,six(4.4%)adult cases of benign primary liver disease,four(2.9%)adult cases of malignant primary liver disease,and 43(31.6%)adult cases of malignant secondary liver *** to the International ALPPS Registry data,less than 10%of the ALPPS procedures have been performed for the treatment of uncommon liver *** and GBC are the unique pathologies with acceptable *** for NET appears to be a safe procedure,with satisfactory long-term *** the opposite,the results observed for the treatment of GBC are ***,these data should be considered with *** rationale for treating benign pathologies with

关键词： Neuroendocrine tumor(NET) gastrointestinal stromal tumors(GIST) gallbladder cancer(GBC) hepatoblastoma,metastases

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Hepatocellular SETDB1 Regulates Hepatic Ischemia-Reperfusion Injury through Targeting Lysine Methylation of ASK1 Signal

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Research 2024年第3期6卷 305-317页

作者： Kang Xia Tianyu Wang Zhongbao Chen Jiayu Guo Bo Yu Qi Chen Tao Qiu Jiangqiao Zhou Shusen Zheng Department of organ transplantation Renmin Hospital of Wuhan UniversityWuhanChina Department of Urology Renmin Hospital of Wuhan UniversityWuhanChina. Department of general surgery Renmin Hospital of Wuhan UniversityWuhanChina division of Hepatobiliary and Pancreatic surgery Department of SurgeryFirst Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Key Laboratory of Combined Multi-organ transplantation Ministry of Public HealthHangzhouChina Key Laboratory of organ transplantation HangzhouZhejiang ProvinceChina Key Laboratory of the Diagnosis and Treatment of organ transplantation CAMSHangzhouChina.

Background: Hepatic ischemia-reperfusion injury (HIRI) stands as an unavoidable complication arising from liver surgery, profoundly intertwined with its prognosis. The role of lysine methyltransferase SET domain bifurcated 1 (SETDB1) in HIRI remains elusive, despite its confirmation as a potential therapeutic target for diverse diseases. Here, we investigated the mechanism by which SETDB1 regulated HIRI. Methods: RNA sequencing data were used to identify the expression and potential targets of SETDB1 through bioinformatics analysis. To elucidate the impact of SETDB1 on HIRI, both an in vivo model of HIRI in mice and an in vitro model of hepatocyte hypoxia/reoxygenation were established. Biochemical and histological analyses were used to investigate the influence of SETDB1 on liver damage mediated by HIRI. Chromatin immunoprecipitation and coimmunoprecipitation were implemented to explore the in-depth mechanism of SETDB1 regulating HIRI. Results: We confirmed that hepatocellular SETDB1 was up-regulated during HIRI and had a close correlation with HIRI-related inflammation and apoptosis. Moreover, inhibition of SETDB1 could mitigate HIRI-induced liver damage, inflammation, and apoptosis. Through our comprehensive mechanistic investigation, we revealed that SETDB1 interacts with apoptosis-signal-regulating kinase 1 (ASK1) and facilitates the methylation of its lysine residues. Inhibition of SETDB1 resulted in reduced phosphorylation of ASK1, leading to a marked suppression of downstream c-Jun N-terminal kinase (JNK)/p38 signaling pathway activation. The therapeutic effect on inflammation and apoptosis achieved through SETDB1 inhibition was nullified by the restoration of JNK/p38 signaling activation through ASK1 overexpression. Conclusions: The findings from our study indicate that SETDB1 mediates lysine methylation of ASK1 and modulates the activation of the ASK1–JNK/p38 pathway, thus involved in HIRI-induced inflammation and apoptosis. These results suggest that SETD

关键词： SETDB1 inflammation ASK1

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