{"title":"Improving performance of robotic liver resections with high technical complexity by Robo-Lap approach","authors":"Francesca Ratti, R. Marino, Aldrighetti Luca","doi":"10.21037/hbsn-23-378","DOIUrl":"https://doi.org/10.21037/hbsn-23-378","url":null,"abstract":"","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"44 4","pages":""},"PeriodicalIF":8.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138626576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Natural killer (NK) cells are enriched in the liver and are the main regulators in liver transplantation regarding rejection or tolerance, viral infection, or tumor recurrence. Immunosuppression consists of a triple drug standard regimen comprising tacrolimus (TAC) and corticosteroids (CS) with either mycophenolate mofetil (MMF) or sirolimus (SIR)/everolimus (EVE). The aim of this study was to evaluate the impact of trough levels of these regimens under clinical conditions and exposure on human NK-cell activity and function in order to better understand the antiviral and anti-tumor effects of mammalian target of rapamycin inhibitor (mTORI).
Methods: Peripheral blood mononuclear cells (PBMCs) were collected from liver transplant recipients and healthy controls. Number and phenotypes of NK cells in vivo were analyzed by flow cytometry. In this study we simulated the immunosuppressive microenvironment in vitro. PBMCs were cultured at the clinically effective plasma concentration of drugs for 3 d to detect the effect of immunosuppressants on NK cells. Drug type and concentration: single drug [EVE, 5 ng/mL; SIR, 5 ng/mL; TAC, 5 ng/mL; cyclosporine A (CSA), 125 ng/mL; MMF, 15 µg/mL; CS, 0.5 µg/mL] and combined immunosuppressants (Group 1: TAC, 5 ng/mL + MMF, 15 µg/mL + CS, 0.5 µg/mL; Group 2: TAC, 5 ng/mL + SIR, 5 ng/mL + CS, 0.5 µg/mL; Group 3: TAC, 5 ng/mL + EVE, 5 ng/mL + CS, 0.5 µg/mL). In addition, NK cells were sorted from PBMCs and treated under the above conditions to detect NK cell killing function and RNA transcription characteristics.
Results: CS significantly impaired the cytolytic activity of NK cells, followed by MMF and SIR/EVE. CS and TAC/CSA significantly decreased the secretion of IFN-γ and CD107a. NK cell function in liver transplant recipients was most pronouncedly inhibited by a triple immunosuppressive regimen, with CS playing the most prominent role compared with the other drugs. The MMF-containing regimen demonstrated a significant increase in the expression of suppressive genes, especially of the Siglec7/9 family. The SIR group had stronger NK cell activity compared with that of the MMF group, although liver transplantation patients have lower NK cell activity and function.
Conclusions: Despite an overall comparable immunosuppressive efficiency in terms of prevention of acute rejection, a mTORIs-including regimen might be considered as having less impact on NK cell function.
背景：自然杀伤（NK）细胞富集于肝脏，是肝脏移植排斥或耐受、病毒感染或肿瘤复发的主要调节因子。免疫抑制包括由他克莫司（TAC）、皮质类固醇（CS）和霉酚酸酯（MMF）或西罗莫司（SIR）/依维莫司（EVE）组成的三联药物标准方案。本研究的目的是评估这些方案在临床条件下的谷值水平和暴露对人类 NK 细胞活性和功能的影响，以便更好地了解哺乳动物雷帕霉素靶抑制剂（mTORI）的抗病毒和抗肿瘤作用：方法：收集肝移植受者和健康对照组的外周血单核细胞（PBMCs）。流式细胞术分析了体内 NK 细胞的数量和表型。在这项研究中，我们在体外模拟了免疫抑制微环境。在临床有效药物血浆浓度下培养 PBMC 3 d，以检测免疫抑制剂对 NK 细胞的影响。药物类型和浓度：单一药物[EVE，5 ng/mL；SIR，5 ng/mL；TAC，5 ng/mL；环孢素A（CSA），125 ng/mL；MMF，15 µg/mL；CS，0.5 µg/mL] 和联合免疫抑制剂（第 1 组：TAC，5 ng/mL + MMF，15 µg/mL + CS，0.5 µg/mL；第 2 组：TAC，5 ng/mL + SIR，5 ng/mL + CS，0.5 µg/mL；第 3 组：TAC，5 ng/mL + EVE，5 ng/mL + CS，0.5 µg/mL）。此外，还从 PBMCs 中分拣出 NK 细胞，并在上述条件下进行处理，以检测 NK 细胞的杀伤功能和 RNA 转录特征：结果：CS明显降低了NK细胞的细胞溶解活性，其次是MMF和SIR/EVE。CS 和 TAC/CSA 能明显降低 IFN-γ 和 CD107a 的分泌。三联免疫抑制方案对肝移植受者NK细胞功能的抑制最为明显，与其他药物相比，CS的作用最为突出。含 MMF 的方案显示抑制基因的表达显著增加，尤其是 Siglec7/9 家族。与 MMF 组相比，SIR 组的 NK 细胞活性更强，尽管肝移植患者的 NK 细胞活性和功能较低：结论：尽管在预防急性排斥反应方面的免疫抑制效率总体相当，但可以认为包括mTORI的方案对NK细胞功能的影响较小。
{"title":"Influence of immunosuppressive drugs on natural killer cells in therapeutic drug exposure in liver transplantation.","authors":"Rongrong Qin, Jiwei Qin, Xuefeng Li, Zhijun Xu, Peiqi He, Xiaodong Yuan, Cheng Sun, Björn Nashan","doi":"10.21037/hbsn-22-438","DOIUrl":"10.21037/hbsn-22-438","url":null,"abstract":"<p><strong>Background: </strong>Natural killer (NK) cells are enriched in the liver and are the main regulators in liver transplantation regarding rejection or tolerance, viral infection, or tumor recurrence. Immunosuppression consists of a triple drug standard regimen comprising tacrolimus (TAC) and corticosteroids (CS) with either mycophenolate mofetil (MMF) or sirolimus (SIR)/everolimus (EVE). The aim of this study was to evaluate the impact of trough levels of these regimens under clinical conditions and exposure on human NK-cell activity and function in order to better understand the antiviral and anti-tumor effects of mammalian target of rapamycin inhibitor (mTORI).</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells (PBMCs) were collected from liver transplant recipients and healthy controls. Number and phenotypes of NK cells <i>in vivo</i> were analyzed by flow cytometry. In this study we simulated the immunosuppressive microenvironment <i>in vitro</i>. PBMCs were cultured at the clinically effective plasma concentration of drugs for 3 d to detect the effect of immunosuppressants on NK cells. Drug type and concentration: single drug [EVE, 5 ng/mL; SIR, 5 ng/mL; TAC, 5 ng/mL; cyclosporine A (CSA), 125 ng/mL; MMF, 15 µg/mL; CS, 0.5 µg/mL] and combined immunosuppressants (Group 1: TAC, 5 ng/mL + MMF, 15 µg/mL + CS, 0.5 µg/mL; Group 2: TAC, 5 ng/mL + SIR, 5 ng/mL + CS, 0.5 µg/mL; Group 3: TAC, 5 ng/mL + EVE, 5 ng/mL + CS, 0.5 µg/mL). In addition, NK cells were sorted from PBMCs and treated under the above conditions to detect NK cell killing function and RNA transcription characteristics.</p><p><strong>Results: </strong>CS significantly impaired the cytolytic activity of NK cells, followed by MMF and SIR/EVE. CS and TAC/CSA significantly decreased the secretion of IFN-γ and CD107a. NK cell function in liver transplant recipients was most pronouncedly inhibited by a triple immunosuppressive regimen, with CS playing the most prominent role compared with the other drugs. The MMF-containing regimen demonstrated a significant increase in the expression of suppressive genes, especially of the Siglec7/9 family. The SIR group had stronger NK cell activity compared with that of the MMF group, although liver transplantation patients have lower NK cell activity and function.</p><p><strong>Conclusions: </strong>Despite an overall comparable immunosuppressive efficiency in terms of prevention of acute rejection, a mTORIs-including regimen might be considered as having less impact on NK cell function.</p>","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"1 1","pages":"835-853"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10727815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42379295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rita Khoury, N. Khalife, Rebecca Ibrahim, Khalil Saleh
{"title":"Futibatinib: new targeted therapy in intrahepatic cholangiocarcinoma","authors":"Rita Khoury, N. Khalife, Rebecca Ibrahim, Khalil Saleh","doi":"10.21037/hbsn-23-476","DOIUrl":"https://doi.org/10.21037/hbsn-23-476","url":null,"abstract":"","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":" 9","pages":""},"PeriodicalIF":8.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138617988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fatty liver disease and risk of all cause and cause-specific mortality outcomes in the older population","authors":"Josh Bilson, Christopher D. Byrne","doi":"10.21037/hbsn-23-542","DOIUrl":"https://doi.org/10.21037/hbsn-23-542","url":null,"abstract":"","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":" 14","pages":""},"PeriodicalIF":8.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138618113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The significance of severe postoperative complications on liver regeneration","authors":"Yanfang Zhang, Liangliang Xu, Ming-Qin Xu","doi":"10.21037/hbsn-23-487","DOIUrl":"https://doi.org/10.21037/hbsn-23-487","url":null,"abstract":"","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"70 s287","pages":""},"PeriodicalIF":8.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138622005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Magistri, G. Guerrini, S. Di Sandro, F. di Benedetto
{"title":"Modern surgical approach to hepatocellular carcinoma","authors":"P. Magistri, G. Guerrini, S. Di Sandro, F. di Benedetto","doi":"10.21037/hbsn-23-535","DOIUrl":"https://doi.org/10.21037/hbsn-23-535","url":null,"abstract":"","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":" 21","pages":""},"PeriodicalIF":8.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138612991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Primary hospitals in China: current state, challenges, and solutions","authors":"Ziyi Wang, Ge Zhang","doi":"10.21037/hbsn-23-571","DOIUrl":"https://doi.org/10.21037/hbsn-23-571","url":null,"abstract":"","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":" 33","pages":""},"PeriodicalIF":8.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138616310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Managing portal hypertension in patients with liver cirrhosis and hepatocellular carcinoma: non-invasive diagnosis and systemic treatment considerations","authors":"Woo Kyoung Jeong","doi":"10.21037/hbsn-23-551","DOIUrl":"https://doi.org/10.21037/hbsn-23-551","url":null,"abstract":"","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":" 9","pages":""},"PeriodicalIF":8.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138617559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New insights in the metabolic function related to gut microbiota in the process of liver regeneration","authors":"Nan Jiang, Zhen Wang, Kefei Yuan","doi":"10.21037/hbsn-23-508","DOIUrl":"https://doi.org/10.21037/hbsn-23-508","url":null,"abstract":"","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"103 9","pages":""},"PeriodicalIF":8.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138608977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Single-organ cutaneous metastasis of rectal signet ring cell carcinoma","authors":"Wenqing Jia, Zichao Guo, Xi Cheng, Ren Zhao","doi":"10.21037/hbsn-23-451","DOIUrl":"https://doi.org/10.21037/hbsn-23-451","url":null,"abstract":"","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"4 11","pages":""},"PeriodicalIF":8.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138625345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号