Shumei Song, Qiongrong Chen, Yuan Li, Guang Lei, Ailing Scott, Longfei Huo, Cordelia Y Li, Jeannelyn Santiano Estrella, Arlene Correa, Melissa Pool Pizzi, Lang Ma, Jiankang Jin, Bin Liu, Ying Wang, Lianchun Xiao, Wayne L Hofstetter, Jeffrey H Lee, Brian Weston, Manoop Bhutani, Namita Shanbhag, Randy L Johnson, Boyi Gan, Shaozhong Wei, Jaffer A Ajani
OBJECTIVE: Gastro-oesophageal cancers (GEC) are resistant to therapy and lead to poor prognosis. The cancer stem cells (CSCs) and antiapoptotic pathways often confer therapy resistance. We sought to elucidate the antitumour action of a BCL-2 inhibitor, AT101 in GEC in vitro, in vivo and in a clinical trial. METHODS: Extensive preclinical studies in vitro and in vivo were carried out to establish the mechanism action of AT101 on targeting CSCs and antiapoptotic proteins...
January 24, 2021: Gut
Tao Chen, Aiping Xu, Jingjing Lian, Yuan Chu, Haibin Zhang, Meidong Xu
No abstract text is available yet for this article.
January 22, 2021: Gut
Jonel Trebicka, Wenyi Gu, Victor de Ledinghen, Christophe Aubé, Aleksander Krag, Michael Praktiknjo, Laurent Castera, Jerome Dumortier, David Josef Maria Bauer, Mireen Friedrich-Rust, Stanislas Pol, Ivica Grgurevic, Rongqin Zheng, Sven Francque, Halima Gottfriedovà, Sanda Mustapic, Ioan Sporea, Annalisa Berzigotti, Frank Erhard Uschner, Benedikt Simbrunner, Maxime Ronot, Christophe Cassinotto, Maria Kjaergaard, Filipe Andrade, Martin Schulz, Georg Semmler, Ida Tjesic Drinkovic, Johannes Chang, Maximilian Joseph Brol, Pierre Emmanuel Rautou, Thomas Vanwolleghem, Christian P Strassburg, Jerome Boursier, Philip Georg Ferstl, Ditlev Nytoft Rasmussen, Thomas Reiberger, Valerie Vilgrain, Aymeric Guibal, Olivier Guillaud, Stefan Zeuzem, Camille Vassord, Xue Lu, Luisa Vonghia, Renata Senkerikova, Alina Popescu, Cristina Margini, Wenping Wang, Maja Thiele, Chrisitan Jansen
OBJECTIVE: Liver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients. DESIGN: This international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded...
January 21, 2021: Gut
Rüdiger Schmitz, Rene Werner, Alessandro Repici, Raf Bisschops, Alexander Meining, Michael Zornow, Helmut Messmann, Cesare Hassan, Prateek Sharma, Thomas Rösch
No abstract text is available yet for this article.
January 21, 2021: Gut
Corey A Siegel, Gil Y Melmed, Dermot Pb McGovern, Victoria Rai, Florian Krammer, David T Rubin, Maria T Abreu, Marla C Dubinsky
No abstract text is available yet for this article.
January 20, 2021: Gut
Min-Seok Rha, Ji Won Han, June-Young Koh, Ha Seok Lee, Jong Hoon Kim, Kyungjoo Cho, Soon Il Kim, Myoung Soo Kim, Jae Geun Lee, Su-Hyung Park, Dong Jin Joo, Jun Yong Park, Eui-Cheol Shin
OBJECTIVE: The liver acts as a frontline barrier against diverse gut-derived pathogens, and the sinusoid is the primary site of liver immune surveillance. However, little is known about liver sinusoidal immune cells in the context of chronic liver disease (CLD). Here, we investigated the antibacterial capacity of liver sinusoidal γδ T cells in patients with various CLDs. DESIGN: We analysed the frequency, phenotype and functions of human liver sinusoidal γδ T cells from healthy donors and recipients with CLD, including HBV-related CLD (liver cirrhosis (LC) and/or hepatocellular carcinoma (HCC)), alcoholic LC and LC or HCC of other aetiologies, by flow cytometry and RNA-sequencing using liver perfusates obtained during living donor liver transplantation...
January 20, 2021: Gut
Benjamin Goeppert, Damian Stichel, Reka Toth, Sarah Fritzsche, Moritz Anton Loeffler, Anna Melissa Schlitter, Olaf Neumann, Yassen Assenov, Monika Nadja Vogel, Arianeb Mehrabi, Katrin Hoffmann, Bruno Köhler, Christoph Springfeld, Dieter Weichenhan, Christoph Plass, Irene Esposito, Peter Schirmacher, Andreas von Deimling, Stephanie Roessler
OBJECTIVE: A detailed understanding of the molecular alterations in different forms of cholangiocarcinogenesis is crucial for a better understanding of cholangiocarcinoma (CCA) and may pave the way to early diagnosis and better treatment options. DESIGN: We analysed a clinicopathologically well-characterised patient cohort (n=54) with high-grade intraductal papillary (IPNB) or tubulopapillary (ITPN) neoplastic precursor lesions of the biliary tract and correlated the results with an independent non-IPNB/ITPN associated CCA cohort (n=294)...
January 19, 2021: Gut
Ren Mao, Genevieve Doyon, Ilyssa O Gordon, Jiannan Li, Sinan Lin, Jie Wang, Thi Hong Nga Le, Michael Elias, Satya Kurada, Brian Southern, Mitchell Olman, Minhu Chen, Shuai Zhao, Dina Dejanovic, Jyotsna Chandra, Pranab K Mukherjee, Gail West, David R Van Wagoner, Claudio Fiocchi, Florian Rieder
OBJECTIVE: Creeping fat, the wrapping of mesenteric fat around the bowel wall, is a typical feature of Crohn's disease, and is associated with stricture formation and bowel obstruction. How creeping fat forms is unknown, and we interrogated potential mechanisms using novel intestinal tissue and cell interaction systems. DESIGN: Tissues from normal, UC, non-strictured and strictured Crohn's disease intestinal specimens were obtained. The muscularis propria matrisome was determined via proteomics...
January 19, 2021: Gut
Claudio Luchini, Robert C Grant, Aldo Scarpa, Steven Gallinger
No abstract text is available yet for this article.
January 19, 2021: Gut
Anat Yaskolka Meir, Ehud Rinott, Gal Tsaban, Hila Zelicha, Alon Kaplan, Philip Rosen, Ilan Shelef, Ilan Youngster, Aryeh Shalev, Matthias Blüher, Uta Ceglarek, Michael Stumvoll, Kieran Tuohy, Camilla Diotallevi, Urska Vrhovsek, Frank Hu, Meir Stampfer, Iris Shai
OBJECTIVE: To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss. DESIGN: For the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), MED and green-MED weight-loss diet groups, all accompanied by physical activity...
January 18, 2021: Gut
Jeroen M Schuitenmaker, Froukje B van Hoeij, Marlies P Schijven, Jan Tack, José M Conchillo, Eric J Hazebroek, André J P M Smout, Albert J Bredenoord
OBJECTIVE: There is no evidence-based treatment for persistent dysphagia after laparoscopic fundoplication. The aim of this study was to evaluate the effect of pneumatic dilation on persistent dysphagia after laparoscopic fundoplication. DESIGN: We performed a multicentre, single-blind, randomised sham-controlled trial of patients with persistent dysphagia (>3 months) after laparoscopic fundoplication. Patients with an Eckardt symptom score ≥4 were randomly assigned to pneumatic dilation (PD) using a 35 mm balloon or sham dilation...
January 15, 2021: Gut
Mabrouka Salem, Joanna Lecka, Julie Pelletier, Danielle Gomes Marconato, Aline Dumas, Luc Vallières, Gaetan Brochu, Bernard Robaye, Christian Jobin, Jean Sévigny
OBJECTIVE: Nucleotides are danger signals that activate inflammatory responses via binding P2 receptors. The nucleoside triphosphate diphosphohydrolase-8 (NTPDase8) is an ectonucleotidase that hydrolyses P2 receptor ligands. We investigated the role of NTPDase8 in intestinal inflammation. DESIGN: We generated NTPDase8-deficient ( Entpd8 -/- ) mice to define the role of NTPDase8 in the dextran sodium sulfate (DSS) colitis model. To assess inflammation, colons were collected and analysed by histopathology, reverse transcriptase-quantitative real-time PCR (RT-qPCR) and immunohistochemistry...
January 15, 2021: Gut
Zhen Ding, Weijun Wang, Kun Zhang, Fanhua Ming, Tianyi Yangdai, Tao Xu, Huiying Shi, Yuhui Bao, Hailing Yao, Hangyu Peng, Chaoqun Han, Weiwei Jiang, Jun Liu, Xiaohua Hou, Rong Lin
OBJECTIVE: Intestinal flora and metabolites are associated with multiple systemic diseases. Current approaches for acquiring information regarding microbiota/metabolites have limitations. We aimed to develop a precise magnetically controlled sampling capsule endoscope (MSCE) for the convenient, non-invasive and accurate acquisition of digestive bioinformation for disease diagnosis and evaluation. DESIGN: The MSCE and surgery were both used for sampling both jejunal and ileal GI content in the control and antibiotic-induced diarrhoea groups...
January 15, 2021: Gut
Luoyan Ai, Yimeng Ren, Mingming Zhu, Shiyuan Lu, Yun Qian, Zhaofei Chen, Antao Xu
OBJECTIVE: As a canonical membrane tethering factor, the function of synbindin has been expanding and indicated in immune response. Here, we investigated the role of synbindin in the regulation of toll-like receptor 4 (TLR4) signalling and macrophage response to microbiota during colitis. DESIGN: Three distinct mouse models allowing global, myeloid-specific or intestinal epithelial cell-specific synbindin heterozygous deletion were constructed and applied to reveal the function of synbindin during dextran sodium sulfate (DSS) colitis...
January 13, 2021: Gut
Hanno Ehlken, Rüdiger Schmitz, Sabine Riethdorf, Lutz Riethdorf, Jenny Krause, Karl-Frederick Karstens, Jörg Schrader, Fabrice Viol, Anastasios Giannou, William Sterlacci, Michael Vieth, Till Clauditz, Christian Kähler, Oliver Mann, Jakob R Izbicki, Samuel Huber, Klaus Pantel, Thomas Rösch
BACKGROUND AND AIMS: Endoscopic resection has been established as curative therapy for superficial cancer arising from Barrett's oesophagus (BE); recurrences are very rare. Based on a case series with unusual and massive early recurrences, we analyse the issue of tumour cell reimplantation. METHODS: This hypothesis was developed on the basis of two out of seven patients treated by circumferential (n=6) or nearly circumferential (n=1) en bloc and R0 endoscopic resection of T1 neoplastic BE...
January 13, 2021: Gut
Laura Rosa Mangiapane, Annalisa Nicotra, Alice Turdo, Miriam Gaggianesi, Paola Bianca, Simone Di Franco, Davide Stefano Sardina, Veronica Veschi, Michele Signore, Sven Beyes, Luca Fagnocchi, Micol Eleonora Fiori, Maria Rita Bongiorno, Melania Lo Iacono, Irene Pillitteri, Gloria Ganduscio, Gaspare Gulotta, Jan Paul Medema, Alessio Zippo, Matilde Todaro, Ruggero De Maria, Giorgio Stassi
OBJECTIVE: Cancer stem cells are responsible for tumour spreading and relapse. Human epidermal growth factor receptor 2 (HER2) expression is a negative prognostic factor in colorectal cancer (CRC) and a potential target in tumours carrying the gene amplification. Our aim was to define the expression of HER2 in colorectal cancer stem cells (CR-CSCs) and its possible role as therapeutic target in CRC resistant to anti- epidermal growth factor receptor (EGFR) therapy. DESIGN: A collection of primary sphere cell cultures obtained from 60 CRC specimens was used to generate CR-CSC mouse avatars to preclinically validate therapeutic options...
January 12, 2021: Gut
Gabriel Mezzano, Adria Juanola, Andres Cardenas, Esteban Mezey, James P Hamilton, Elisa Pose, Isabel Graupera, Pere Ginès, Elsa Solà, Ruben Hernaez
BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is characterised by acute decompensation of cirrhosis associated with organ failures. We systematically evaluated the geographical variations of ACLF across the world in terms of prevalence, mortality, aetiology of chronic liver disease (CLD), triggers and organ failures. METHODS: We searched EMBASE and PubMed from 3/1/2013 to 7/3/2020 using the ACLF-EASL-CLIF (European Association for the Study of the Liver-Chronic Liver Failure) criteria...
January 12, 2021: Gut
Yun Kit Yeoh, Tao Zuo, Grace Chung-Yan Lui, Fen Zhang, Qin Liu, Amy Yl Li, Arthur Ck Chung, Chun Pan Cheung, Eugene Yk Tso, Kitty Sc Fung, Veronica Chan, Lowell Ling, Gavin Joynt, David Shu-Cheong Hui, Kai Ming Chow, Susanna So Shan Ng, Timothy Chun-Man Li, Rita Wy Ng, Terry Cf Yip, Grace Lai-Hung Wong, Francis Kl Chan, Chun Kwok Wong, Paul Ks Chan, Siew C Ng
OBJECTIVE: Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus. METHODS: In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection...
January 11, 2021: Gut
Shuichi Aoki, Koetsu Inoue, Sebastian Klein, Stefan Halvorsen, Jiang Chen, Aya Matsui, Mohammad R Nikmaneshi, Shuji Kitahara, Tai Hato, Xianfeng Chen, Kazumichi Kawakubo, Hadi T Nia, Ivy Chen, Daniel H Schanne, Emilie Mamessier, Kohei Shigeta, Hiroto Kikuchi, Rakesh R Ramjiawan, Tyge Ce Schmidt, Masaaki Iwasaki, Thomas Yau, Theodore S Hong, Alexander Quaas, Patrick S Plum, Simona Dima, Irinel Popescu, Nabeel Bardeesy, Lance L Munn, Mitesh J Borad, Slim Sassi, Rakesh K Jain, Andrew X Zhu, Dan G Duda
OBJECTIVE: Intrahepatic cholangiocarcinoma (ICC)-a rare liver malignancy with limited therapeutic options-is characterised by aggressive progression, desmoplasia and vascular abnormalities. The aim of this study was to determine the role of placental growth factor (PlGF) in ICC progression. DESIGN: We evaluated the expression of PlGF in specimens from ICC patients and assessed the therapeutic effect of genetic or pharmacologic inhibition of PlGF in orthotopically grafted ICC mouse models...
January 11, 2021: Gut
Jiang Li, Xi Liang, Jing Jiang, Lingling Yang, Jiaojiao Xin, Dongyan Shi, Yingyan Lu, Jun Li, Keke Ren, Hozeifa Mohamed Hassan, Jianing Zhang, Pengcheng Chen, Heng Yao, Jiaqi Li, Tianzhou Wu, Linfeng Jin, Ping Ye, Tan Li, Huafen Zhang, Suwan Sun, Beibei Guo, Xingping Zhou, Qun Cai, Jiaxian Chen, Xiaowei Xu, Jianrong Huang, Shaorui Hao, Jinqiu He, Shaojie Xin, Di Wang, Jonel Trebicka, Xin Chen, Jun Li
OBJECTIVE: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathophysiology remains unclear. This study aims to characterise the molecular basis of HBV-ACLF using transcriptomics. METHODS: Four hundred subjects with HBV-ACLF, acute-on-chronic hepatic dysfunction (ACHD), liver cirrhosis (LC) or chronic hepatitis B (CHB) and normal controls (NC) from a prospective multicentre cohort were studied, and 65 subjects (ACLF, 20; ACHD, 10; LC, 10; CHB, 10; NC, 15) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs)...
January 11, 2021: Gut
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