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Mashup Score: 2Microbiota-induced S100A11-RAGE axis underlies immune evasion in right-sided colon adenomas and is a therapeutic target to boost anti-PD1 efficacy - 14 hour(s) ago
Background Tumourigenesis in right-sided and left-sided colons demonstrated distinct features. Objective We aimed to characterise the differences between the left-sided and right-sided adenomas (ADs) representing the early stage of colonic tumourigenesis. Design Single-cell and spatial transcriptomic datasets were analysed to reveal alterations between right-sided and left-sided colon ADs. Cells, animal experiments and clinical specimens were used to verify the results. Results Single-cell analysis revealed that in right-sided ADs, there was a significant reduction of goblet cells, and these goblet cells were dysfunctional with attenuated mucin biosynthesis and defective antigen presentation. An impairment of the mucus barrier led to biofilm formation in crypts and subsequent bacteria invasion into right-sided ADs. The regions spatially surrounding the crypts with biofilm occupation underwent an inflammatory response by lipopolysaccharide (LPS) and an apoptosis process, as revealed by
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet
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Mashup Score: 3p53 mutation biases squamocolumnar junction progenitor cells towards dysplasia rather than metaplasia in Barrett’s oesophagus - 2 day(s) ago
Background While p53 mutations occur early in Barrett’s oesophagus (BE) progression to oesophageal adenocarcinoma (EAC), their role in gastric cardia stem cells remains unclear. Objective This study investigates the impact of p53 mutation on the fate and function of cardia progenitor cells in BE to EAC progression, particularly under the duress of chronic injury. Design We used a BE mouse model (L2-IL1β) harbouring a Trp53 mutation (R172H) to study the effects of p53 on Cck2r+ cardia progenitor cells. We employed lineage tracing, pathological analysis, organoid cultures, single-cell RNA sequencing (scRNA-seq) and computational analyses to investigate changes in progenitor cell behaviour, differentiation patterns and tumour progression. Additionally, we performed orthotopic transplantation of sorted metaplastic and mutant progenitor cells to assess their tumourigenic potential in vivo. Results The p53 mutation acts as a switch to expand progenitor cells and inhibit their differentiation
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTImage from the paper by Lian et al on "p53 mutation biases squamocolumnar junction progenitor cells towards dysplasia rather than metaplasia in Barrett’s oesophagus" via https://t.co/nRHivnCQ5W #P53 #BarrettsOesophagus https://t.co/FHp21eIlj4
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Mashup Score: 9Liquid biopsy to identify Barrett’s oesophagus, dysplasia and oesophageal adenocarcinoma: the EMERALD multicentre study - 2 day(s) ago
Background There is no clinically relevant serological marker for the early detection of oesophageal adenocarcinoma (EAC) and its precursor lesion, Barrett’s oesophagus (BE). Objective To develop and test a blood-based assay for EAC and BE. Design Oesophageal MicroRNAs of BaRRett, Adenocarcinoma and Dysplasia ( EMERALD ) was a large, international, multicentre biomarker cohort study involving 792 patient samples from 4 countries ([NCT06381583][1]) to develop and validate a circulating miRNA signature for the early detection of EAC and high-risk BE. Tissue-based miRNA sequencing and microarray datasets (n=134) were used to identify candidate miRNAs of diagnostic potential, followed by validation using 42 pairs of matched cancer and normal tissues. The usefulness of the candidate miRNAs was initially assessed using 108 sera (44 EAC, 34 EAC precursors and 30 non-disease controls). We finally trained a machine learning model (XGBoost+AdaBoost) on RT-qPCR results from circulating miRNAs fro
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTImage from the paper by Jinsei Miyoshi et al on "Liquid biopsy to identify Barrett’s oesophagus, dysplasia and oesophageal adenocarcinoma: the EMERALD multicentre study" via https://t.co/ssQMGBQObM @AlexMannucci @gaofeng21cn #BarrettsOesophagus https://t.co/WvDOQPA1N1
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Mashup Score: 26Recent advances in clinical practice: mastering the challenge—managing IBS symptoms in IBD - 3 day(s) ago
Many patients with IBD report persisting symptoms, despite resolution of the inflammatory process. Although by definition, a diagnosis of IBS cannot be made, the prevalence of ‘IBS in IBD’ surpasses the rate of IBS in the global population by fivefold. Because IBS-like symptoms are associated with a decreased quality of life and increased healthcare utilisation in IBD, diagnosis and treatment are necessary. In this review, we summarise the current knowledge on IBS-like symptoms in IBD. A pathophysiological common ground is present, which includes genetic susceptibility, environmental triggers, gut microbial dysbiosis, increased intestinal permeability, visceral hypersensitivity and involvement of brain–gut interaction. When symptoms persist after resolution of inflammation, other GI diseases should be excluded based on the chief complaint, considering any possible psychological co-morbidity early in the diagnostic work-up. Subsequent treatment should be initiated that is evidence-based
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#RecentAdvancesInClinicalPractice paper by @JudithWellens et al entitled "Recent advances in clinical practice: mastering the challenge—managing IBS symptoms in IBD" via https://t.co/nNqpLN22Pf @JoaoPGSabino @VanuytselTim @SeverineVermei1 @ibdleuven #IBS #IBD #DGBI https://t.co/DIWiQIb3km
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Mashup Score: 19Artificial intelligence applied to ‘omics data in liver disease: towards a personalised approach for diagnosis, prognosis and treatment - 3 day(s) ago
Advancements in omics technologies and artificial intelligence (AI) methodologies are fuelling our progress towards personalised diagnosis, prognosis and treatment strategies in hepatology. This review provides a comprehensive overview of the current landscape of AI methods used for analysis of omics data in liver diseases. We present an overview of the prevalence of different omics levels across various liver diseases, as well as categorise the AI methodology used across the studies. Specifically, we highlight the predominance of transcriptomic and genomic profiling and the relatively sparse exploration of other levels such as the proteome and methylome, which represent untapped potential for novel insights. Publicly available database initiatives such as The Cancer Genome Atlas and The International Cancer Genome Consortium have paved the way for advancements in the diagnosis and treatment of hepatocellular carcinoma. However, the same availability of large omics datasets remains lim
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
Excellent #RecentAdvancesInBasicScience paper by Ghosh et al entitled "Artificial intelligence applied to ‘omics data in liver disease: towards a personalised approach for diagnosis, prognosis and treatment" via https://t.co/81ddOsYDyq #AI #LiverDisease https://t.co/r4Y2vrQ3mC
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Mashup Score: 15Gut: 74 (2) - 3 day(s) ago
(19 November, 2024) Jinsei Miyoshi, Alessandro Mannucci, Marco Scarpa, Feng Gao, Shusuke Toden, Timothy Whitsett, Landon J Inge, Ross M Bremner, Tetsuji Takayama, Yulan Cheng, Teodoro Bottiglieri, Iris D Nagetaal, Martha J Shrubsole, Ali H Zaidi, Xin Wang, Helen G Coleman, Lesley A Anderson, Stephen J Meltzer, Ajay Goel (1 October, 2024) Guodong Lian, Ermanno Malagola, Chengguo Wei, Qiongyu Shi, Junfei Zhao, Masahiro Hata, Hiroki Kobayashi, Yosuke Ochiai, Biyun Zheng, Xiaofei Zhi, Feijing Wu, Ruhong Tu,
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
Colourful streamers ready for the feast in a summer day, from Girona, Spain. Read in this issue the great work by Castells-Nobau et al offering comprehensive insights into the microbiome-gut-adipose-liver axis and its impact on systemic insulin action via https://t.co/HdX7Uh2aI0… https://t.co/RdMIS89TGw https://t.co/Wy7Yfwa7vC
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Mashup Score: 32Faecal proteomics links neutrophil degranulation with mortality in patients with alcohol-associated hepatitis - 4 day(s) ago
Objective Patients with alcohol-associated hepatitis (AH) have a high mortality. Alcohol exacerbates liver damage by inducing gut dysbiosis, bacterial translocation and inflammation, which is characterised by increased numbers of circulating and hepatic neutrophils. Design In this study, we performed tandem mass tag (TMT) proteomics to analyse proteins in the faeces of controls (n=19), patients with alcohol-use disorder (AUD; n=20) and AH (n=80) from a multicentre cohort (InTeam). To identify protein groups that are disproportionately represented, we conducted over-representation analysis using Reactome pathway analysis and Gene Ontology to determine the proteins with the most significant impact. A faecal biomarker and its prognostic effect were validated by ELISA in faecal samples from patients with AH (n=70), who were recruited in a second and independent multicentre cohort (AlcHepNet). Result Faecal proteomic profiles were overall significantly different between controls, patients w
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTImage from the paper by Henriette Kreimeyer et al entitled "Faecal proteomics links neutrophil degranulation with mortality in patients with alcohol-associated hepatitis" via https://t.co/VLCVqSUUyK @DebbieShawcros1 @Bernd_Schnabl @SDDRC @UCSD_GI #Proteomics #Alcohol… https://t.co/J3gcH4NvpL https://t.co/6NyggnHeTr
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Mashup Score: 5
Inflammatory bowel diseases (IBDs) encompass chronic conditions predominantly affecting young individuals and necessitate long-term, advanced treatments to manage disease burden and mitigate progressive tissue damage.1 Within this context, the matter of treatment discontinuation in patients who have achieved sustained remission, including those undergoing combination therapy, holds significant importance for both clinicians and patients. The primary considerations for potential treatment de-escalation or cessation include safety concerns, the financial implications of prolonged therapy and patients’ willingness or preference. In Gut, Gisbert et al 2 address this important question and report the results of the EXIT trial, a randomised placebo-controlled trial on 140 patients in clinical remission under anti-tumour necrosis factor (TNF) antibody and immunomodulators who were randomly assigned to either withdraw or maintain the anti-TNF antibody. Four prospective clinical trials have inv
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
RT @Y_ECCO_IBD: Challenge of treatment de-escalation in inflammatory bowel diseases @Gut_BMJ https://t.co/1gyBPKxkU3
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Mashup Score: 4Induction of macrophage efferocytosis in pancreatic cancer via PI3Kγ inhibition and radiotherapy promotes tumour control - 5 day(s) ago
Background The immune suppression mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain unknown, but preclinical studies have implicated macrophage-mediated immune tolerance. Hence, pathways that regulate macrophage phenotype are of strategic interest, with reprogramming strategies focusing on inhibitors of phosphoinositide 3-kinase-gamma (PI3Kγ) due to restricted immune cell expression. Inhibition of PI3Kγ alone is ineffective in PDAC, despite increased infiltration of CD8+ T cells. Objective We hypothesised that the immune stimulatory effects of radiation, and its ability to boost tumour antigen availability could synergise with PI3Kγ inhibition to augment antitumour immunity. Design We used orthoptic and genetically engineered mouse models of pancreatic cancer (LSL-KrasG12D/+;Trp53R172H/+;Pdx1-Cre). Stereotactic radiotherapy was delivered using contrast CT imaging, and PI3Kγ inhibitors by oral administration. Changes in the tumour microenvironment were quantified by flow cyto
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTImage from the paper by Russell et al on "Induction of macrophage efferocytosis in pancreatic cancer via PI3Kγ inhibition and radiotherapy promotes tumour control" via https://t.co/Wp6WDnwSj4 #PancreaticCancer https://t.co/49IVJFXTGH
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Mashup Score: 2
Background and objective Gastric cancer (GC) remains a prevalent and preventable disease, yet accurate early diagnostic methods are lacking. Exosome non-coding RNAs (ncRNAs), a type of liquid biopsy, have emerged as promising diagnostic biomarkers for various tumours. This study aimed to identify a serum exosome ncRNA feature for enhancing GC diagnosis. Designs Serum exosomes from patients with GC (n=37) and healthy donors (n=20) were characterised using RNA sequencing, and potential biomarkers for GC were validated through quantitative reverse transcription PCR (qRT-PCR) in both serum exosomes and tissues. A combined diagnostic model was developed using LASSO-logistic regression based on a cohort of 518 GC patients and 460 healthy donors, and its diagnostic performance was evaluated via receiver operating characteristic curves. Results RNA sequencing identified 182 candidate biomarkers for GC, of which 31 were validated as potential biomarkers by qRT-PCR. The combined diagnostic score
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTOnline paper by Cai et al on "Construction of exosome non-coding RNA feature for non-invasive, early detection of gastric cancer patients by machine learning: a multi-cohort study" via https://t.co/Q0goi6wjTh #GastricCancer https://t.co/RXVJ7hWmGM
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#GUTImage from the paper by Zhou et al on "Microbiota-induced S100A11-RAGE axis underlies immune evasion in right-sided colon adenomas and is a therapeutic target to boost anti-PD1 efficacy" via https://t.co/0UXplOsySO #ColonicAdenomas #Microbiota https://t.co/wrzufyMQQ7