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Inhibition of IRE-1α Alleviates Pyroptosis and Metabolic Dysfunction-Associated Steatohepatitis by Suppressing Gasdermin D
IF 6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Liver International
Pub Date : 2025-01-07 DOI: 10.1111/liv.16234
Xin Zeng, Tian Wu, Qing Xu, Lan Li, Yujia Yuan, Min Zhu, Wen Liu, Fudong Fu, Zhenru Wu, Han Yao, Guangneng Liao, Yanrong Lu, Jingqiu Cheng, Jingping Liu, Yujun Shi, Younan Chen

Objectives

Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for cirrhosis and hepatocellular carcinoma, for which there is currently no effective treatment. This study aimed to investigate the regulatory mechanism between endoplasmic reticulum stress (ER stress) and pyroptosis in the liver under the context of MASH.

Methods and Results

Pyroptosis was examined in both in vivo and in vitro ER stress models. The expression levels of nucleotide-binding oligomerisation domain-like receptor protein 3 (NLRP3), gasdermin D (GSDMD), caspase-1, IL-1β, and IL-18 tended to increase, and “ASC specks” colocalised with the swollen ER in living cells. However, in the pyroptotic model, increased ER stress was not observed. Moreover, the overexpression of inositol-requiring enzyme 1α (IRE-1α), one of the main ER stress sensors, led to increases in the levels of NLRP3 and GSDMD. However, after IRE-1α was blocked by chemical inhibitors or siRNAs, pyroptosis was also abrogated. These data showed that ER stress regulated pyroptosis through IRE-1α. Furthermore, the immunoprecipitation results clearly indicated that GSDMD efficiently bound to IRE-1α when ER stress was stimulated. In the MASH model, IRE-1α was specifically inhibited by pharmacological or genetic methods, which improved the pathology of MASH by alleviating ER stress and pyroptosis. In patients with MASH, both ER stress markers and pyroptosis markers including IRE-1α, glucose-regulated protein 78, GSDMD/GSDMD-N, p20, and NLRP3, are highly expressed in the liver.

Conclusions

This study revealed that ER stress may regulate pyroptosis through IRE-1α-GSDMD pathway, which accelerates the progression of MASH. These findings may offer new insights for the treatment of MASH.

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引用次数: 0
Endogenous Sex Hormones and Significant Hepatic Fibrosis in US Adults 内源性性激素与美国成人肝纤维化的关系
IF 6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Liver International
Pub Date : 2025-01-04 DOI: 10.1111/liv.16233
Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Aijaz Ahmed
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引用次数: 0
Prognostic Implications of Cardiac Geometry in Cirrhosis: Findings From a Large Cohort 肝硬化患者心脏几何形状的预后意义：来自一个大队列的研究结果。
IF 6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Liver International
Pub Date : 2025-01-03 DOI: 10.1111/liv.16230
Yu Jia, Lidi Liu, Yiheng Zhou, Yi Yao, Yu Cheng, Yonglang Cheng, Can Shen, Rong Yang, Rui Zeng, Zhi Wan, Qian Zhao, Dongze Li, Bo Yuan, Xiaoyang Liao

Background and Aims

Cirrhosis is characterised by hyperdynamic circulation, which contributes to cirrhotic cardiomyopathy (CCM). However, the expert consensus on CCM did not initially include cardiac structure because of scant evidence. Therefore, this study investigated the associations of cardiac chamber geometry with mortality and CCM.

Methods

We retrospectively included 2514 cirrhotic patients from 2011 to 2023. In accordance with the guidelines for echocardiography, left ventricular (LV) hypertrophy (LVH) and LV, left atrial (LA), right ventricular (RV), and right atrial (RA) enlargement were evaluated. Cox and logistic regression analyses were performed to examine the relationships among cardiac chamber, all-cause mortality, and CCM.

Results

The prevalence rates of LV hypertrophy and LV, LA, RV, and RA enlargement were 21.9%, 21.3%, 30.4%, 5.9%, and 10.9%, respectively. Concentric LVH (HR: 1.305, 95% confidence interval (CI): 1.153–1.466), eccentric LVH (HR: 1.272, 95% CI: 1.139–1.426), LV enlargement (HR: 1.305, 95% CI: 1.153–1.466), and LA enlargement (HR: 1.254, 95% CI: 1.130–1.379) were significantly associated with mortality during the median follow-up of 2.1 years. In a subcohort of 1898 individuals, CCM, with a prevalence of 29.0%, was independently associated with concentric LVH (OR: 1.834, 95% CI: 1.214–2.707), eccentric LVH (OR: 3.063, 95% CI: 2.379–3.903), LV enlargement (OR: 2.519, 95% CI: 2.150–2.977), LA enlargement (OR: 3.559, 95% CI: 2.770–4.321), and RA enlargement (OR: 1.416, 95% CI: 1.025–1.915). LV abnormalities showed 90% specificity and 35% sensitivity for CCM diagnosis.

Conclusions

Geometric pattern changes in the LV and LA are prevalent and independently associated with all-cause mortality and CCM. These indicators have potential for hazard stratification and CCM redefinition.

背景和目的：肝硬化的特点是高动力循环，这有助于肝硬化心肌病（CCM）。然而，由于证据不足，专家对CCM的共识最初并未包括心脏结构。因此，本研究调查了心腔几何形状与死亡率和CCM的关系。方法：我们回顾性地纳入了2011年至2023年的2514例肝硬化患者。根据超声心动图指南，评估左室（LV）肥厚（LVH）和左室（LV）、左房（LA）、右室（RV）和右房（RA）扩大。采用Cox和logistic回归分析来检验心腔、全因死亡率和CCM之间的关系。结果：左室肥大和左室、左室、左室、左室扩大的患病率分别为21.9%、21.3%、30.4%、5.9%、10.9%。同心LVH （HR: 1.305, 95%可信区间（CI）： 1.153-1.466）、偏心LVH （HR: 1.272, 95% CI: 1.139-1.426）、左室增大（HR: 1.305, 95% CI: 1.153-1.466）和左室增大（HR: 1.254, 95% CI: 1.130-1.379）与中位随访2.1年期间的死亡率显著相关。在1898个个体的亚队列中，CCM患病率为29.0%，与同心LVH （OR: 1.834, 95% CI: 1.215 -2.707）、偏心性LVH （OR: 3.063, 95% CI: 2.379-3.903）、LV增大（OR: 2.519, 95% CI: 2.150-2.977）、LA增大（OR: 3.559, 95% CI: 2.770-4.321）和RA增大（OR: 1.416, 95% CI: 1.025-1.915）独立相关。左室异常诊断CCM的特异性为90%，敏感性为35%。结论：左室和左室的几何模式改变是普遍存在的，并且与全因死亡率和CCM独立相关。这些指标具有危险分层和CCM重新定义的潜力。
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引用次数: 0
A European Survey to Identify Challenges in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease 一项欧洲调查确定代谢功能障碍相关脂肪变性肝病管理中的挑战。
IF 6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Liver International
Pub Date : 2025-01-03 DOI: 10.1111/liv.16224
Laurent Castera, William Alazawi, Elisabetta Bugianesi, Cyrielle Caussy, Massimo Federici, Manuel Romero-Gómez, Jörn M. Schattenberg, Ron Basuroy, Preethy Prasad, Dmitry Estulin, Jeffrey V. Lazarus

Background and Aims

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe subtype, metabolic dysfunction-associated steatohepatitis (MASH), are highly prevalent and strongly associated with obesity and type 2 diabetes (T2D). This study sought to identify challenges to the diagnosis, treatment and management of people living with MASLD and MASH and understand the key barriers to adopting relevant clinical guidelines.

Methods

A real-world, cross-sectional study (BARRIERS-MASLD) consisting of a quantitative survey and qualitative interviews of physicians in France, Germany, Italy, Spain and the United Kingdom was conducted from March to September 2023. Descriptive statistics were used for data analysis.

Results

A total of 626 physicians completed the survey; n = 10 from each country participated in the qualitative interviews. Physicians considered the presence of MASH to be highly impactful on how they treated people living with obesity (66%) and T2D (69%). Over one-third (35%) of the respondents could not identify any MASH-specific clinical guidelines issued by medical societies or associations top-of-mind, but overall awareness rose when prompted about country-specific guidelines. Physicians said they would need evidence of success (48%) and clinical guidelines that address common MASLD comorbidities (38%) to increase their adoption.

Conclusions

This study found that lack of awareness around MASLD and MASH clinical guidelines and clearly established care pathways, particularly for addressing common comorbidities, was a key factor preventing physicians from optimising care for people living with MASH in Europe. This research highlights opportunities to improve education and training about clinical guidelines and care coordination.

背景和目的：代谢功能障碍相关脂肪性肝病（MASLD）及其更严重的亚型代谢功能障碍相关脂肪性肝炎（MASH）非常普遍，并且与肥胖和2型糖尿病（T2D）密切相关。本研究旨在确定MASLD和MASH患者的诊断、治疗和管理面临的挑战，并了解采用相关临床指南的主要障碍。方法：于2023年3月至9月对法国、德国、意大利、西班牙和英国的医生进行定量调查和定性访谈，采用现实世界的横断面研究（BARRIERS-MASLD）。采用描述性统计进行数据分析。结果：共626名医师完成调查；每个国家有10人参加了定性访谈。医生认为MASH的存在对他们如何治疗肥胖（66%）和T2D（69%）患者有很大影响。超过三分之一（35%）的受访者无法确定医学协会或协会发布的任何针对mash的临床指南，但当被提示了解针对具体国家的指南时，总体意识有所提高。医生表示，他们需要成功的证据（48%）和解决常见MASLD合并症的临床指南（38%）来增加他们的采用。结论：本研究发现，缺乏对MASLD和MASH临床指南和明确建立的护理途径的认识，特别是对常见合并症的处理，是阻碍欧洲医生优化MASH患者护理的关键因素。这项研究强调了改善临床指导和护理协调方面的教育和培训的机会。
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引用次数: 0
A Case of Difficult-To-Treat Autoimmune Hepatitis Successfully Managed by Tofacitinib 托法替尼成功治愈一例难以治愈的自身免疫性肝炎病例
IF 6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Liver International
Pub Date : 2025-01-01 DOI: 10.1111/liv.16173
Dilara Turan Gökçe, Derya Arı, Meral Akdogan Kayhan, Cumali Efe
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引用次数: 0
Global Burden, Trends, and Inequalities of Gallbladder and Biliary Tract Cancer, 1990–2021: A Decomposition and Age–Period–Cohort Analysis 1990-2021 年胆囊癌和胆道癌的全球负担、趋势和不平等：1990-2021年胆囊癌和胆道癌的全球负担、趋势和不平等：分解和年龄段队列分析》。
IF 6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Liver International
Pub Date : 2025-01-01 DOI: 10.1111/liv.16199
Sen Lei, Guizhong Huang, Xiaohui Li, Pu Xi, Zehui Yao, Xiaojun Lin

Background

Gallbladder and biliary tract cancer (GBTC) increasingly aggravates the global malignancy burden. This study aimed to evaluate the updated condition of GBTC temporal burden trends and inequalities from 1990 to 2021.

Methods

Data on GBTC were extracted from the Global Burden of Disease (GBD) 2021 study. Incidence, deaths, and disability-adjusted life years (DALYs) and their age-standardised rates (ASR) were quantified from 1990 to 2021, stratified by sex, age and sociodemographic index (SDI). The age–period–cohort (APC) model was used to elucidate the effects of age, period, and cohort. Decomposition analysis and cross-country inequality evaluation were performed to assess the contributing factors and disease imbalance, respectively. Bayesian APC analysis was used to estimate the future burden.

Results

In 2021, the global incident cases of GBTC were 216 768, with 171 961 deaths and 3 732 121 DALYs lost. From 1990 to 2021, the ASR of incidence, mortality, and DALYs decreased slightly. Males showed a slight increase in ASR of incidence, while females experienced a significant decrease. High-income regions, particularly in Asia Pacific and Latin America, exhibited a higher burden, while Western Sub-Saharan Africa had the lowest. Low and low-middle SDI regions showed a gradual rise in all metrics despite lower absolute numbers. The APC analysis indicated that the global incidence of GBTC tended to rise with age, but gender differences existed. Besides, a deteriorating cohort effect was detected amongst individuals born between 1907 and 1917. Decomposition analysis revealed that population growth was the primary driver of the increased GBTC burden globally. Significant disparities in GBTC burden by SDI were observed, with a notable decline in inequality over time. Projections indicated a slow decline in the global ASR through 2040, with a more pronounced decrease in females.

Conclusions

There are significant regional and gender differences in the global burden of GBTC. Population growth remains a major contributor to the burden. Despite the overall decline, the increasing incidence in low and lower-middle SDI regions and the persistent male burden highlight the need for targeted interventions. Future efforts should focus on addressing socio-economic inequalities and reducing risk factors, particularly in vulnerable populations.

背景：胆囊和胆道癌（GBTC）日益加重全球恶性肿瘤负担。本研究旨在评估1990 - 2021年GBTC时间负担趋势和不平等的最新状况。方法：GBTC的数据来自全球疾病负担（GBD） 2021研究。从1990年到2021年，按性别、年龄和社会人口指数（SDI）分层，对发病率、死亡率和残疾调整生命年（DALYs）及其年龄标准化率（ASR）进行量化。使用年龄-时期-队列（APC）模型来阐明年龄、时期和队列的影响。通过分解分析和跨国不平等评价，分别对致病因素和疾病不平衡进行评估。采用贝叶斯APC分析估计未来负担。结果：2021年，全球发生GBTC病例216 768例，死亡171 961例，损失3 732 121个DALYs。从1990年到2021年，发病率、死亡率和DALYs的ASR略有下降。男性的ASR发病率略有上升，而女性的ASR发病率明显下降。高收入地区，特别是亚太和拉丁美洲的负担较高，而撒哈拉以南非洲西部的负担最低。低SDI和中低SDI地区在所有指标上都逐渐上升，尽管绝对数字较低。APC分析显示，全球GBTC发病率随年龄增长呈上升趋势，但存在性别差异。此外，在1907年至1917年之间出生的个体中发现了不断恶化的群体效应。分解分析显示，人口增长是全球GBTC负担增加的主要驱动因素。观察到SDI造成的GBTC负担的显著差异，随着时间的推移，不平等显著下降。预测显示，到2040年，全球ASR将缓慢下降，其中女性的下降更为明显。结论：全球GBTC负担存在显著的地区和性别差异。人口增长仍然是造成这一负担的主要因素。尽管总体下降，但低和中低SDI地区发病率的增加以及持续存在的男性负担突出了有针对性干预措施的必要性。今后的努力应侧重于解决社会经济不平等和减少风险因素，特别是在弱势群体中。
{"title":"Global Burden, Trends, and Inequalities of Gallbladder and Biliary Tract Cancer, 1990–2021: A Decomposition and Age–Period–Cohort Analysis","authors":"Sen Lei,&nbsp;Guizhong Huang,&nbsp;Xiaohui Li,&nbsp;Pu Xi,&nbsp;Zehui Yao,&nbsp;Xiaojun Lin","doi":"10.1111/liv.16199","DOIUrl":"10.1111/liv.16199","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gallbladder and biliary tract cancer (GBTC) increasingly aggravates the global malignancy burden. This study aimed to evaluate the updated condition of GBTC temporal burden trends and inequalities from 1990 to 2021.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data on GBTC were extracted from the Global Burden of Disease (GBD) 2021 study. Incidence, deaths, and disability-adjusted life years (DALYs) and their age-standardised rates (ASR) were quantified from 1990 to 2021, stratified by sex, age and sociodemographic index (SDI). The age–period–cohort (APC) model was used to elucidate the effects of age, period, and cohort. Decomposition analysis and cross-country inequality evaluation were performed to assess the contributing factors and disease imbalance, respectively. Bayesian APC analysis was used to estimate the future burden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 2021, the global incident cases of GBTC were 216 768, with 171 961 deaths and 3 732 121 DALYs lost. From 1990 to 2021, the ASR of incidence, mortality, and DALYs decreased slightly. Males showed a slight increase in ASR of incidence, while females experienced a significant decrease. High-income regions, particularly in Asia Pacific and Latin America, exhibited a higher burden, while Western Sub-Saharan Africa had the lowest. Low and low-middle SDI regions showed a gradual rise in all metrics despite lower absolute numbers. The APC analysis indicated that the global incidence of GBTC tended to rise with age, but gender differences existed. Besides, a deteriorating cohort effect was detected amongst individuals born between 1907 and 1917. Decomposition analysis revealed that population growth was the primary driver of the increased GBTC burden globally. Significant disparities in GBTC burden by SDI were observed, with a notable decline in inequality over time. Projections indicated a slow decline in the global ASR through 2040, with a more pronounced decrease in females.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>There are significant regional and gender differences in the global burden of GBTC. Population growth remains a major contributor to the burden. Despite the overall decline, the increasing incidence in low and lower-middle SDI regions and the persistent male burden highlight the need for targeted interventions. Future efforts should focus on addressing socio-economic inequalities and reducing risk factors, particularly in vulnerable populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915458","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}
引用次数: 0
JAK Inhibitors for Autoimmune Hepatitis: One Swallow Does Not Make a Summer 治疗自身免疫性肝炎的 JAK 抑制剂：一粥一饭当思来之不易
IF 6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Liver International
Pub Date : 2025-01-01 DOI: 10.1111/liv.16223
Juan Carlos Ruiz-Cobo, Lourdes Ruiz-Ortega, Virginia Robles-Alonso, Mar Riveiro-Barciela
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引用次数: 0
Drug–Drug Interactions Between DAAs and Anticoagulants or Antiplatelets: A Position Paper of the Italian Anticoagulation Clinics DAAs与抗凝剂或抗血小板之间的药物-药物相互作用：意大利抗凝诊所的立场文件。
IF 6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Liver International
Pub Date : 2024-12-30 DOI: 10.1111/liv.16177
Elisabetta Tombolini, Alessandro Squizzato, Gian Marco Podda, Alessio Aghemo, Nicola Ferri, Simone Segato, Daniela Poli, Marco Paolo Donadini

The natural history of chronic hepatitis C virus (HCV) infection has changed after the introduction of direct-acting antiviral agents (DAAs). Screening programs have been ongoing to reach the World Health Organisation's goal of HCV elimination by 2030, and most infected people are eligible for treatment. Given the increased cardiovascular risk in people with HCV infection and the metabolic pathways of DAAs, it is not uncommon to face the issue of drug–drug interactions (DDIs) with antiplatelet or anticoagulant drugs. In the absence of clinical trials, we offer suggestions to deal with DDIs in case of treatment of patients with DAAs who are also receiving antiplatelet or anticoagulant drugs, based on the best available evidence from pharmacodynamics and pharmacokinetics studies in conjunction with clinical experience in the field of haemostasis and thrombosis.

引入直接作用抗病毒药物（DAAs）后，慢性丙型肝炎病毒（HCV）感染的自然史发生了变化。筛查项目一直在进行，以实现世界卫生组织到2030年消除丙型肝炎病毒的目标，大多数感染者都有资格接受治疗。考虑到HCV感染人群心血管风险的增加和DAAs的代谢途径，与抗血小板或抗凝药物的药物-药物相互作用（ddi）问题并不罕见。在缺乏临床试验的情况下，我们根据药效学和药代动力学研究的最佳证据，结合止血和血栓形成领域的临床经验，为同时接受抗血小板或抗凝血药物治疗的daa患者提供处理ddi的建议。
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引用次数: 0
Ganglioside GD2 Contributes to a Stem-Like Phenotype in Intrahepatic Cholangiocarcinoma 神经节苷脂GD2参与肝内胆管癌的茎样表型。
IF 6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Liver International
Pub Date : 2024-12-26 DOI: 10.1111/liv.16208
Antonella Mannini, Mirella Pastore, Alessia Giachi, Margherita Correnti, Elena Spínola Lasso, Tiziano Lottini, Benedetta Piombanti, Ignazia Tusa, Elisabetta Rovida, Cédric Coulouarn, Jesper B. Andersen, Monika Lewinska, Claudia Campani, V. Lokesh Battula, Bin Yuan, Massimo Aureli, Emma V. Carsana, Caterina Peraldo Neia, Paola Ostano, Alessia Tani, Daniele Nosi, Anna Vanni, Laura Maggi, Luca Di Tommaso, Giuseppina Comito, Stefania Madiai, Annarosa Arcangeli, Fabio Marra, Chiara Raggi

Background & Aims

GD2, a member of the ganglioside (GS) family (sialic acid-containing glycosphingolipids), is a potential biomarker of cancer stem cells (CSC) in several tumours. However, the possible role of GD2 and its biosynthetic enzyme, GD3 synthase (GD3S), in intrahepatic cholangiocarcinoma (iCCA) has not been explored.

Methods

The stem-like subset of two iCCA cell lines was enriched by sphere culture (SPH) and compared to monolayer parental cells (MON). GS profiles were evaluated by chromatography, after feeding with radioactive sphingosine. Membrane GD2 expression was evaluated by FACS, and the expression of enzymes of GS biosynthesis was analysed by RT-qPCR. The modulation of stem features by GS was investigated in vitro and in vivo using GD3S-overexpressing cells and corroborated by global transcriptomic analysis.

Results

GS composition was markedly different comparing SPH and MON. Among complex GS, iCCA-SPH showed increased GD2 levels, in agreement with the high expression levels of GD3 and GM2/GD2 synthases. iCCA cells overexpressing GD3S had higher sphere-forming ability, invasive properties and drug resistance than parental cells. NOD/SCID mice implanted with CCLP1 cells overexpressing GD3S developed larger tumours than control cells. By global transcriptomic analysis, ontology investigation identified 74 processes shared by the iCCA-SPH and GD3S-transfected cells, with enrichment for development and morphogenesis processes, MAPK signalling and locomotion. In a cohort of patients with iCCA, GD3S expression was correlated with lymph node invasion, indicating a possible relevance of GD3S in the clinical setting.

Conclusions

The profile of GS derivatives regulates the stem-like properties of iCCA cells.

背景与目的：GD2是神经节苷脂（GS）家族（含唾液酸的鞘糖脂）的成员，是几种肿瘤中癌症干细胞（CSC）的潜在生物标志物。然而，GD2及其生物合成酶GD3合成酶（GD3S）在肝内胆管癌（iCCA）中的可能作用尚未探讨。方法：采用球培养（SPH）富集两株iCCA细胞株的茎样亚群，并与单层亲本细胞（MON）进行比较。用放射性鞘氨醇饲喂后，用色谱法测定GS谱。采用流式细胞仪（FACS）检测细胞膜GD2表达，RT-qPCR检测GS生物合成酶的表达。利用过表达gd3s的细胞在体外和体内研究了GS对干细胞特征的调节，并通过全局转录组学分析得到了证实。结果：SPH和MON的GS组成有明显差异，在复合GS中，iCCA-SPH的GD2水平升高，与GD3和GM2/GD2合成酶的高表达一致。过表达GD3S的iCCA细胞比亲本细胞具有更高的成球能力、侵袭性和耐药性。植入过表达GD3S的CCLP1细胞的NOD/SCID小鼠的肿瘤比对照细胞大。通过全局转录组学分析，本体学调查确定了iCCA-SPH和gd3s转染细胞共有的74个过程，其中发育和形态发生过程、MAPK信号传导和运动富集。在一组iCCA患者中，GD3S表达与淋巴结侵袭相关，表明GD3S在临床环境中可能具有相关性。结论：GS衍生物对iCCA细胞的干细胞样特性具有调控作用。
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引用次数: 0
Regarding the ‘High end-of-treatment hepatitis B core-related antigen levels predict hepatitis flare after stopping nucleot(s)ide analogue therapy’ 关于“治疗结束时乙型肝炎核心相关抗原水平高预测停止核苷类似物治疗后肝炎爆发”。
IF 6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Liver International
Pub Date : 2024-12-26 DOI: 10.1111/liv.16105
Li Yu, Yingjun Chen
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引用次数: 0
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