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To explore the causal association between the serum lipid profile and inflammatory bowel disease using bidirectional Mendelian randomisation analysis 利用双向孟德尔随机分析法探讨血清脂质状况与炎症性肠病之间的因果关系
eGastroenterology Pub Date : 2024-06-01 DOI: 10.1136/egastro-2023-100034
Xiaoli Pang, Huizhong Yang, Mingyu Li, Mayte Suárez-Fariñas, Suyan Tian
{"title":"To explore the causal association between the serum lipid profile and inflammatory bowel disease using bidirectional Mendelian randomisation analysis","authors":"Xiaoli Pang, Huizhong Yang, Mingyu Li, Mayte Suárez-Fariñas, Suyan Tian","doi":"10.1136/egastro-2023-100034","DOIUrl":"https://doi.org/10.1136/egastro-2023-100034","url":null,"abstract":"Despite studies confirming that patients with inflammatory bowel disease (IBD) present with dyslipidaemia, the associations between IBD and the serum lipid profile have not been determined. The present study aimed to investigate the causal relationship between the serum lipid profile and IBD risk and elucidate the nature of the interactions between them.Two-sample Mendelian randomisation (MR) analysis was performed to investigate the causal links between total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (Apo A), apolipoprotein B (Apo B) and lipoprotein (a) (Lp(a)) and IBD. The study was carried out using the R TwoSampleMR and Mendelian randomisation packages.All MR methods, including the weighted median, weighted mode, inverse-variance weighted model, MR-PRESSO, contamination mixture and MR Egger, supported a null causal relationship between TG, TC, HDL-C, LDL-C, Apo A, Apo B and Lp(a) and between IBD, Crohn’s disease and ulcerative colitis. Null causal effects of lipid indices on IBD were validated through independent genome-wide association studies (GWAS), indicating that the findings are robust.Our findings suggest that none of the seven lipid indices may be a potential risk factor for the onset of IBD. However, additional research is needed since our MR analyses cannot assess the potential non-linear causal relationship between serum lipids and IBD.","PeriodicalId":504469,"journal":{"name":"eGastroenterology","volume":"38 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141280348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Environmental PM2.5-triggered stress responses in digestive diseases 环境 PM2.5 触发的消化系统疾病应激反应
eGastroenterology Pub Date : 2024-05-01 DOI: 10.1136/egastro-2024-100063
Kezhong Zhang
{"title":"Environmental PM2.5-triggered stress responses in digestive diseases","authors":"Kezhong Zhang","doi":"10.1136/egastro-2024-100063","DOIUrl":"https://doi.org/10.1136/egastro-2024-100063","url":null,"abstract":"Airborne particulate matter in fine and ultrafine ranges (aerodynamic diameter less than 2.5 µm, PM2.5) is a primary air pollutant that poses a serious threat to public health. Accumulating evidence has pointed to a close association between inhalation exposure to PM2.5and increased morbidity and mortality associated with modern human complex diseases. The adverse health effect of inhalation exposure to PM2.5pollutants is systemic, involving multiple organs, different cell types and various molecular mediators. Organelle damages and oxidative stress appear to play a major role in the cytotoxic effects of PM2.5by mediating stress response pathways related to inflammation, metabolic alteration and cell death programmes. The organs or tissues in the digestive tract, such as the liver, pancreas and small intestines, are susceptible to PM2.5exposure. This review underscores PM2.5-induced inflammatory stress responses and their involvement in digestive diseases caused by PM2.5exposure.","PeriodicalId":504469,"journal":{"name":"eGastroenterology","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141026662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recent insights about autophagy in pancreatitis 关于胰腺炎中自噬作用的最新见解
eGastroenterology Pub Date : 2024-05-01 DOI: 10.1136/egastro-2023-100057
Wen-Xing Ding, Xiaowen Ma, Sydney Kim, Shaogui Wang, Hong-Min Ni
{"title":"Recent insights about autophagy in pancreatitis","authors":"Wen-Xing Ding, Xiaowen Ma, Sydney Kim, Shaogui Wang, Hong-Min Ni","doi":"10.1136/egastro-2023-100057","DOIUrl":"https://doi.org/10.1136/egastro-2023-100057","url":null,"abstract":"Acute pancreatitis is a common inflammatory gastrointestinal disease without any successful treatment. Pancreatic exocrine acinar cells have high rates of protein synthesis to produce and secrete large amounts of digestive enzymes. When the regulation of organelle and protein homeostasis is disrupted, it can lead to endoplasmic reticulum (ER) stress, damage to the mitochondria and improper intracellular trypsinogen activation, ultimately resulting in acinar cell damage and the onset of pancreatitis. To balance the homeostasis of organelles and adapt to protect themselves from organelle stress, cells use protective mechanisms such as autophagy. In the mouse pancreas, defective basal autophagy disrupts ER homoeostasis, leading to ER stress and trypsinogen activation, resulting in spontaneous pancreatitis. In this review, we discuss the regulation of autophagy and its physiological role in maintaining acinar cell homeostasis and function. We also summarise the current understanding of the mechanisms and the role of defective autophagy at multiple stages in experimental pancreatitis induced by cerulein or alcohol.","PeriodicalId":504469,"journal":{"name":"eGastroenterology","volume":"6 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141054588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis: a comprehensive review 原发性硬化性胆管炎患者胆管癌的治疗：综述
eGastroenterology Pub Date : 2024-03-01 DOI: 10.1136/egastro-2023-100045
Christina Villard, Carl Jorns, A. Bergquist
{"title":"Treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis: a comprehensive review","authors":"Christina Villard, Carl Jorns, A. Bergquist","doi":"10.1136/egastro-2023-100045","DOIUrl":"https://doi.org/10.1136/egastro-2023-100045","url":null,"abstract":"Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease, characterised by persistent biliary inflammation resulting in fibrosis and multifocal strictures of the biliary tree. The course of disease is highly variable, ranging from asymptomatic disease to the development of end-stage biliary cirrhosis and an increased risk of biliary tract cancer (BTC), particularly cholangiocarcinoma (CCA).PSC is the most important risk factor for CCA in younger people, with a reported lifetime prevalence ranging from 6% to 13%. Perihilar CCA (pCCA), involving the hepatic duct bifurcation, is the most common CCA amounting to approximately 50% of all cases, whereas intrahepatic CCA (iCCA), located within the hepatic parenchyma, represents less than 10%.CCA is an aggressive tumour, and only a minority of patients are amenable to surgical resection with curative intent. Radical liver resection and liver transplantation are potentially curative therapeutic options in patients with PSC in the absence of metastatic or locally advanced disease. Liver transplantation with neoadjuvant chemoradiation could be considered in selected patients with unresectable pCCA and without pretreatment in patients with PSC with bile duct high-grade dysplasia. Recent reports demonstrating favourable outcomes in transplanted patients with small iCCA and patients with locally advanced disease following neoadjuvant therapy have challenged the previously described poor outcome in transplanted patients with iCCA.Treatment for CCA is challenged by the inherent difficulties in enabling an early diagnosis and thereby preventing an otherwise dismal prognosis. This comprehensive review aims to describe therapeutic considerations and challenges in patients with PSC-CCA.","PeriodicalId":504469,"journal":{"name":"eGastroenterology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140406563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ABCC2p.R393W variant contributes to Dubin-Johnson syndrome by targeting MRP2 to proteasome degradation ABCC2p.R393W变体通过靶向蛋白酶体降解MRP2而导致杜宾-约翰逊综合征
eGastroenterology Pub Date : 2024-03-01 DOI: 10.1136/egastro-2023-100039
Rong-Yue Sun, Yi-Ming Chen, Mian-Mian Zhu, Ji-an Sun, Hong-Wei Wang, Chen-Yu Wu, Ting Zhu, Yu-Jing Gong, Chao-Sheng Lu, L. Ronzoni, Luca Valenti, M. Zheng, Dan Wang
{"title":"ABCC2p.R393W variant contributes to Dubin-Johnson syndrome by targeting MRP2 to proteasome degradation","authors":"Rong-Yue Sun, Yi-Ming Chen, Mian-Mian Zhu, Ji-an Sun, Hong-Wei Wang, Chen-Yu Wu, Ting Zhu, Yu-Jing Gong, Chao-Sheng Lu, L. Ronzoni, Luca Valenti, M. Zheng, Dan Wang","doi":"10.1136/egastro-2023-100039","DOIUrl":"https://doi.org/10.1136/egastro-2023-100039","url":null,"abstract":"Dubin-Johnson syndrome (DJS), a rare autosomal recessive liver condition, is caused by biallelic loss-of-function mutations of theABCC2gene. This study aimed to investigate genetic variations in the drug efflux transporterABCC2(MRP2) gene in patients with DJS and to characterise the expression and mechanism of theABCC2gene variant.Trio whole exome sequencing was performed in the family to identify the genetic causes. Bioinformatics analysis was performed to assess pathogenicity. Inin vitroexperiments, site-directed mutagenesis was used to introduceABCC2variants in constructs then expressed in HEK293T, HuH-7 and HepG2 cell lines. The expression of total and cell membrane MRP2 was quantified in cells expressing the wild-type or variant forms. Chloroquine and MG132 were used to evaluate the effects of p.R393W on lysosomal and/or proteasomal degradation.The twin probands carry DJS-associated variants c.1177C>T (rs777902199) in theABCC2gene inherited from the father and the c.3632T>C mutation in the other allele inherited from the mother. TheABCC2variant, c.1177C>T, results in a p.R393W substitution in MRP2 that is highly conserved among vertebrates, drastically decreasing the expression of mutant protein by promoting proteasomal degradation. Another variant c.3632T>C results in a p.L1211P substitution in MRP2, decreasing the expression of membrane MRP2 but not changing the expression of total protein.These results strongly suggest that the p.R393W variant affects the stability of the MRP2 protein and decreases its expression by ubiquitin-mediated proteasomal degradation, and the p.L1211P decreases the expression of membrane MRP2, indicating that these two variants, respectively, cause a loss-of-function of the MRP2 protein and membrane MRP2 ultimately leading to DJS development.","PeriodicalId":504469,"journal":{"name":"eGastroenterology","volume":"7 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140408128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Extracellular vesicles targeting non-parenchymal cells: the therapeutical effect on liver fibrosis 针对非肾小球细胞的细胞外囊泡：对肝纤维化的治疗效果
eGastroenterology Pub Date : 2024-03-01 DOI: 10.1136/egastro-2023-100040
Yingying Liu, Lin Wang
{"title":"Extracellular vesicles targeting non-parenchymal cells: the therapeutical effect on liver fibrosis","authors":"Yingying Liu, Lin Wang","doi":"10.1136/egastro-2023-100040","DOIUrl":"https://doi.org/10.1136/egastro-2023-100040","url":null,"abstract":"Liver fibrosis is the formation of a fibrous scar due to chronic liver disease including viral hepatitis, alcohol and non-alcoholic fatty liver disease. Without treatment, it will develop into cirrhosis and hepatocellular carcinoma. Up to now, there is no effective way to cure liver fibrosis. Extracellular vesicles (EVs) are biological nanoparticles with potential to be therapeutical agents or delivery tools. A lot of studies have demonstrated the therapeutical effect of EVs on liver fibrosis. In this review, we mainly pay attention to roles of liver non-parenchymal cells in pathology of fibrosis, the basic information about EVs and therapeutical effect on liver fibrosis of EVs when they act on non-parenchymal cells.","PeriodicalId":504469,"journal":{"name":"eGastroenterology","volume":"59 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140272173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spleen stiffness measurement as a non-invasive assessment in patients with portal hypertension 将脾脏硬度测量作为门脉高压症患者的无创评估方法
eGastroenterology Pub Date : 2024-02-01 DOI: 10.1136/egastro-2023-100031
Xiaoming Xu, Jiacheng Liu, Yixuan Zhu, F. Rui, Chao Wu, Jie Li
{"title":"Spleen stiffness measurement as a non-invasive assessment in patients with portal hypertension","authors":"Xiaoming Xu, Jiacheng Liu, Yixuan Zhu, F. Rui, Chao Wu, Jie Li","doi":"10.1136/egastro-2023-100031","DOIUrl":"https://doi.org/10.1136/egastro-2023-100031","url":null,"abstract":"For patients with advanced chronic liver disease who are in a compensated state, the development of portal hypertension (PHT) can lead to a heightened risk of hepatic decompensation and mortality. This underscores the importance of timely and appropriate treatment to manage the condition and prevent further complications. The current gold standard procedure for determining PHT is the hepatic venous pressure gradient, but its invasiveness limits its usage in clinical practice and larger trials of novel agents. The current clinical demand for accurate, validated and non-invasive methods to assess the severity of PHT remains unmet. One potential non-invasive option is tissue elastography, which examines the elastic behaviour of tissue after a force has been applied. This method involves quantifying alterations in the biomechanical properties of the liver or spleen in patients with cirrhosis. Available methods are various, including transient elastography, shear wave elastography, acoustic radiation force impulse and magnetic resonance elastography. Importantly, the measurement of spleen stiffness appears to outperform liver stiffness as a direct and dynamic indicator of portal pressure, offering the potential to monitor PHT and evaluate improvements in PHT as a marker for clinical outcomes.","PeriodicalId":504469,"journal":{"name":"eGastroenterology","volume":"1216 43","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140466945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Perspectives of mitochondria-lysosome-related organelle in hepatocyte dedifferentiation and implications in chronic liver disease 线粒体-溶酶体相关细胞器在肝细胞去分化中的作用及其对慢性肝病的影响
eGastroenterology Pub Date : 2024-02-01 DOI: 10.1136/egastro-2023-100046
Xiaowen Ma, Hong-Min Ni, Wen-Xing Ding
{"title":"Perspectives of mitochondria-lysosome-related organelle in hepatocyte dedifferentiation and implications in chronic liver disease","authors":"Xiaowen Ma, Hong-Min Ni, Wen-Xing Ding","doi":"10.1136/egastro-2023-100046","DOIUrl":"https://doi.org/10.1136/egastro-2023-100046","url":null,"abstract":"","PeriodicalId":504469,"journal":{"name":"eGastroenterology","volume":"66 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139824687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Perspectives of mitochondria-lysosome-related organelle in hepatocyte dedifferentiation and implications in chronic liver disease 线粒体-溶酶体相关细胞器在肝细胞去分化中的作用及其对慢性肝病的影响
eGastroenterology Pub Date : 2024-02-01 DOI: 10.1136/egastro-2023-100046
Xiaowen Ma, Hong-Min Ni, Wen-Xing Ding
{"title":"Perspectives of mitochondria-lysosome-related organelle in hepatocyte dedifferentiation and implications in chronic liver disease","authors":"Xiaowen Ma, Hong-Min Ni, Wen-Xing Ding","doi":"10.1136/egastro-2023-100046","DOIUrl":"https://doi.org/10.1136/egastro-2023-100046","url":null,"abstract":"","PeriodicalId":504469,"journal":{"name":"eGastroenterology","volume":"94 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139884458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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