Featured
-
-
Article
| Open AccessPancreatic tumor eradication via selective Pin1 inhibition in cancer-associated fibroblasts and T lymphocytes engagement
Pharmacological inhibition of the prolyl isomerase PIN1, highly expressed in cancer cells and cancer associated fibroblasts (CAF), has been proposed for cancer therapy. Here the authors report the design of a DNA-barcoded micellular system functionalized with antibodies targeting CAFs and a T cell recruiting aptamer to deliver the PIN1 inhibitor AG17724, showing antitumor response in preclinical models of pancreatic cancer.
- Jiaye Liu
- , Yang Wang
- & Yong Liu
-
Article
| Open AccessInstant diagnosis of gastroscopic biopsy via deep-learned single-shot femtosecond stimulated Raman histology
Diagnosis of gastric cancer currently requires gastroscopic biopsy, which requires time and expertize to perform. Here, the authors demonstrate a femto-SRS imaging method which showed high accuracy in diagnosing gastric cancer without the need for pathologistbased diagnosis.
- Zhijie Liu
- , Wei Su
- & Minbiao Ji
-
Article
| Open AccessTRIM24 is an insulin-responsive regulator of P-bodies
Insulin promotes hepatic lipogenesis, though underlying regulation remains unclear. Here the authors show that insulin translocates TRIM24 from the nucleus into cytosolic P-bodies to stabilise hepatic Pparγ mRNA, and that inactivation of TRIM24 promotes Pparγ degradation and alleviates hepatosteatosis.
- Wen Wei
- , Qiaoli Chen
- & Shuai Chen
-
Article
| Open AccessInherited MUTYH mutations cause elevated somatic mutation rates and distinctive mutational signatures in normal human cells
Inherited mutations in MUTYH have been shown to predispose patients to colorectal cancers. Here, the authors show that MUTYH mutations lead to an increased somatic base substitution mutation rate in normal intestinal epithelial cells, which is the likely cause for the increased cancer risk.
- Philip S. Robinson
- , Laura E. Thomas
- & Michael R. Stratton
-
Article
| Open AccessAssociations between long-term drought and diarrhea among children under five in low- and middle-income countries
Increased droughts are associated with climate change. Here, the authors reveal an association between long-term drought and an elevated risk of diarrhea in children under five in low- and middle income countries, and suggest that improving water quality, sanitation, and hygiene practices might reduce the risk.
- Pin Wang
- , Ernest Asare
- & Kai Chen
-
Article
| Open AccessHigh-dimensional profiling reveals Tc17 cell enrichment in active Crohn’s disease and identifies a potentially targetable signature
The T cell compartment in patients with Crohn's disease is dysregulated. Here the authors use cytometric profiling to reveal an enrichment of distinct Tc17 cells during active Crohn's disease and may suggest CD6 as a potential target for therapeutic studies.
- A.-M. Globig
- , A. V. Hipp
- & B. Bengsch
-
Article
| Open AccessProfiling Fusobacterium infection at high taxonomic resolution reveals lineage-specific correlations in colorectal cancer
Bacteria from the genus Fusobacterium can promote colorectal cancer (CRC) development; however, the exact Fusobacterium species involved in this process remain underexplored. Here, the authors develop a rpoB amplicon sequencing approach to identify Fusobacterium species and subspecies in CRC patient samples.
- Dexi Bi
- , Yin Zhu
- & Huanlong Qin
-
Poster
| Open AccessImmune monitoring and treatment in immune-mediated inflammatory diseases
Immune monitoring assists in the diagnosis and clinical management of immune-mediated inflammatory diseases.
- Femke van Wijk
- , Marjolein de Bruin
- & Stefan Nierkens
-
Article
| Open AccessTemporal changes in gastrointestinal fungi and the risk of autoimmunity during early childhood: the TEDDY study
Here, via metagenomics and ITS2 sequencing analysis of children's stool samples from three months to four years, the authors show that the fungal composition changes and relative abundance increases at weaning, but unlike bacteria, the overall levels of fungal diversity do not change substantially over time.
- Thomas A. Auchtung
- , Christopher J. Stewart
- & Joseph F. Petrosino
-
Article
| Open AccessMutational landscape of normal epithelial cells in Lynch Syndrome patients
It is unclear whether somatic mutation rates are elevated in Lynch Syndrome (LS), which is the most common cause of hereditary colorectal cancer. Here, the authors use whole-genome sequencing and organoid cultures to show that normal tissues in LS patients are genomically stable, while ancestor cells of neoplastic tissues undergo multiple cycles of clonal evolution.
- Bernard C. H. Lee
- , Philip S. Robinson
- & Michael R. Stratton
-
Article
| Open AccessA randomized controlled trial for response of microbiome network to exercise and diet intervention in patients with nonalcoholic fatty liver disease
Exercise and diet interventions are treatments for nonalcoholic fatty liver disease (NAFLD). Here the authors report that in randomized, controlled trial in patients with NAFLD exercise and diet intervention were associated with diversified gut microbiome keystone taxa. Exploratory analysis suggests gut microbial network may be used to predict the individual liver fat response to exercise intervention, if validated in future studies.
- Runtan Cheng
- , Lu Wang
- & Sulin Cheng
-
Article
| Open AccessSomatic whole genome dynamics of precancer in Barrett’s esophagus reveals features associated with disease progression
Barrett’s esophagus is a pre-malignant condition that can progress to esophageal cancer. Here, the authors carry out whole genome sequencing of samples from patients who did or did not progress to cancer and find that mutations in many genes occur regardless of progression status, but also find features associated with progressive disease.
- Thomas G. Paulson
- , Patricia C. Galipeau
- & Xiaohong Li
-
Article
| Open AccessA systems genomics approach to uncover patient-specific pathogenic pathways and proteins in ulcerative colitis
Single Nucleotide Polymorphisms (SNPs) affect cellular regulatory networks, and SNP co-occurrences contribute to disease pathogenesis in ulcerative colitis (UC). Here the authors introduce iSNP, a precision medicine pipeline that combines genomics and network biology approaches to uncover patient specific pathways affected in complex diseases.
- Johanne Brooks-Warburton
- , Dezso Modos
- & Tamas Korcsmaros
-
Article
| Open AccessBMP feed-forward loop promotes terminal differentiation in gastric glands and is interrupted by H. pylori-driven inflammation
Helicobacter pylori causes gastric inflammation, gland hyperplasia and is linked to gastric cancer. Here the authors identify a BMP feedback loop between the stomach epithelium and surrounding stroma that controls gland homeostasis and demonstrate its interruption upon infection with H. pylori.
- Marta Kapalczynska
- , Manqiang Lin
- & Michael Sigal
-
Article
| Open AccessFibroblast activation protein activated antifibrotic peptide delivery attenuates fibrosis in mouse models of liver fibrosis
Activated hepatic stellate cells contribute towards the pathogenesis of liver fibrosis, and overexpress fibroblast activation protein. Here the authors report a targeted peptide-delivery system in which fibroblast activation protein liberates the antifibrotic peptide melittin, and demonstrate the approach attenuates fibrosis in mouse models of liver fibrosis.
- Jaiwoo Lee
- , Junho Byun
- & Yu-Kyoung Oh
-
Article
| Open AccessMulti-omic cross-sectional cohort study of pre-malignant Barrett’s esophagus reveals early structural variation and retrotransposon activity
The alterations associated with progression from Barrett’s esophagus (BE) to esophageal adenocarcinoma are not fully characterised. Here, the authors perform a multi-omics analysis of a longitudinally-sampled BE patient cohort, identifying the impact of structural variants, including mobile elements, and the timing of molecular events during progression.
- A. C. Katz-Summercorn
- , S. Jammula
- & R. C. Fitzgerald
-
Article
| Open AccessAntibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab
Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.
- Simeng Lin
- , Nicholas A. Kennedy
- & Jeannie Bishop
-
Article
| Open AccessHypoxia-induced macropinocytosis represents a metabolic route for liver cancer
Cancer cells rely on macropinocytosis to scavenge extracellular proteins for growth. Here the authors show that macropinocytosis supports the survival of hypoxic hepatocellular carcinoma cells and this is dependent on HIF-1, which in turns activates the transcription of a membrane ruffling protein, EH domain-containing protein 2.
- Misty Shuo Zhang
- , Jane Di Cui
- & Carmen Chak-Lui Wong
-
Article
| Open AccessAn efficient urine peptidomics workflow identifies chemically defined dietary gluten peptides from patients with celiac disease
Gluten peptides from wheat enter the bloodstream and are excreted in urine but are yet to be chemically characterised. Here, the authors show by mass spectrometry that quantitative and qualitative differences in urinary peptides can be detected between healthy people and patients with celiac disease.
- Brad A. Palanski
- , Nielson Weng
- & Joshua E. Elias
-
Article
| Open AccessThe spatial transcriptomic landscape of the healing mouse intestine following damage
The colon is comprised of specialized cells that interact with each other to function, however, the molecular regionalization of the colon is incompletely understood. Here, the authors use spatial transcriptomics to generate a publicly available resource defining the transcriptomic regionalization of the colon during steady state and mucosal healing.
- Sara M. Parigi
- , Ludvig Larsson
- & Eduardo J. Villablanca
-
Article
| Open AccessTransglutaminase 3 crosslinks the secreted gel-forming mucus component Mucin-2 and stabilizes the colonic mucus layer
The colonic mucus layer is an organized system providing a physical barrier against pathogens and simultaneously harbouring the commensal flora. Here the authors report that transglutaminase 3 activity contributes to homeostasis of the colonic mucus layer and the lack of this enzymatic activity leads to increased susceptibility against DSS-induced colitis in mice.
- Jack D. A. Sharpen
- , Brendan Dolan
- & Christian V. Recktenwald
-
Article
| Open AccessReduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine
Environmental enteric dysfunction (EED), a subclinical disorder of intestinal function, is associated with malnutrition, infant growth stunting and pathologies in the small intestine. Here the authors report that infant rhesus macaques that are naturally exposed to enteric pathogens commonly linked to human growth stunting present with EED and growth faltering that associates with large intestine pathologies.
- Sara M. Hendrickson
- , Archana Thomas
- & Mark K. Slifka
-
Article
| Open AccessGut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion
Metabolic conditions associated with alterations of the gut microbiome, such as obesity and diabetes, predispose to gallstone disease. Here the authors demonstrate that the gut microbiome, in particular the genus Desulfovibrionale, contribute to gallstone formation in mice.
- Hai Hu
- , Wentao Shao
- & Aihua Gu
-
Article
| Open AccessMicrobial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract
Triclosan (TCS), an antimicrobial agent commonly found in consumer products, has been reported to exacerbates colitis in animal models. Here, using in vitro and in vivo approaches, the authors show that gut bacterial enzymes can drive the metabolic activation and gut toxicity of TCS, highlighting an important role of intestinal microbial factors in the complex etiology of colitis.
- Jianan Zhang
- , Morgan E. Walker
- & Guodong Zhang
-
Article
| Open AccessIntraperitoneal microbial contamination drives post-surgical peritoneal adhesions by mesothelial EGFR-signaling
Abdominal surgery can often lead to complications including the formation of peritoneal adhesions and the molecular mechanisms underlying this process are still unknown. Here, the authors suggest that bacterial contamination drives adhesion formation through mesothelial EGFR signalling.
- Joel Zindel
- , Jonas Mittner
- & Daniel Candinas
-
Article
| Open AccessImpact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants
Oral rotavirus vaccine (ORV) efficacy varies between countries, but underlying reasons aren’t fully understood. In this prospective cohort study, authors show that maternal rotavirus-specific antibodies in serum and breastmilk and pre-vaccination microbiota diversity are negatively correlated with ORV response in India and Malawi but not in the UK.
- Edward P. K. Parker
- , Christina Bronowski
- & Miren Iturriza-Gómara
-
Article
| Open AccessThe methyltransferase METTL3 negatively regulates nonalcoholic steatohepatitis (NASH) progression
Mechanisms that underlie the progression of non-alcoholic fatty liver disease to the more severe non-alcoholic steatohepatitis are incompletely understood. Here the authors show that METTL3, a RNA methyltransferase that catalyzes mRNA m6 modifications, negatively regulates NASH progression via inhibiting the transcription of Cd36 and Ccl2.
- Xinzhi Li
- , Bingchuan Yuan
- & Zheng Chen
-
Article
| Open AccessCRIg on liver macrophages clears pathobionts and protects against alcoholic liver disease
CRIg is expressed on liver macrophages and binds Gram-positive bacteria to mediate phagocytosis, but it is not clear how its phagocytic functions contribute to liver homeostasis or disease. Here the authors report that ethanol impairs hepatic clearance of translocated pathobionts, via decreased hepatic CRIg, which facilitates progression of alcoholic liver disease.
- Yi Duan
- , Huikuan Chu
- & Bernd Schnabl
-
Article
| Open AccessNanoparticle-assembled bioadhesive coacervate coating with prolonged gastrointestinal retention for inflammatory bowel disease therapy
The development of a drug delivery system capable of prolonged retention in the gastrointestinal tract remains a clinical challenge. Here the authors present a bio-adhesive liquid coacervate coating on the intestinal tract that acts as a flowable drug carrier, mediates the sustained release of diverse drugs, and potentially enhances therapeutic efficacy against gastrointestinal diseases.
- Pengchao Zhao
- , Xianfeng Xia
- & Liming Bian
-
Article
| Open AccessGP73 is a TBC-domain Rab GTPase-activating protein contributing to the pathogenesis of non-alcoholic fatty liver disease without obesity
Dysregulation of lipid metabolism and transport contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here the authors identify GP73 as a TBC-domain Rab GTPase-activating protein that regulates very low-density lipoprotein export and promotes NAFLD development in mice.
- Yumeng Peng
- , Qiang Zeng
- & Congwen Wei
-
Article
| Open AccessDesmoplakin and periplakin genetically and functionally contribute to eosinophilic esophagitis
Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease with a complex underlying genetic etiology. Here, the authors identify a series of rare variants in DSP and PPL in multiplex families with EoE and uncover a pathogenic role for desmosomal dysfunction in EoE.
- Tetsuo Shoda
- , Kenneth M. Kaufman
- & Marc E. Rothenberg
-
Article
| Open AccessDysbiosis of human gut microbiome in young-onset colorectal cancer
The incidence of young-onset sporadic colorectal cancer (yCRC) is rapidly rising and frequently associated with an aggressive disease. Here the authors show that gut microbial diversity is increased in patients with yCRC compared to old-onset CRC and that fecal microbial markers could be used to detect individuals with yCRC.
- Yongzhi Yang
- , Lutao Du
- & Yanlei Ma
-
Article
| Open AccessPsychological stress impairs IL22-driven protective gut mucosal immunity against colonising pathobionts
Altered gut microbiome and exacerbation of symptoms at times of psychological stress are feature characteristics of Crohn’s disease. Here authors show in a mouse model that psychological stress impairs IL-22-dependent protective immunity of the ileal mucosa, which allows invasive bacteria to colonise the gut.
- Christopher R. Shaler
- , Alexandra A. Parco
- & Brian K. Coombes
-
Article
| Open AccessThree-year outcomes of the randomized phase III SEIPLUS trial of extensive intraoperative peritoneal lavage for locally advanced gastric cancer
Extensive intraoperative peritoneal lavage (EIPL) has been proposed as an approach to reduce peritoneal metastasis in patients with locally advanced gastric cancer undergoing gastrectomy. Here the authors report the results of the multicentric phase III SEIPLUS trial, showing that EIPL does not improve 3-year survival rate in patients with advanced gastric cancer.
- Jing Guo
- , Aman Xu
- & Dazhi Xu
-
Article
| Open AccessGeneration of functional ciliated cholangiocytes from human pluripotent stem cells
Current protocols to generate cholangiocytes from human pluripotent cells produce immature cells. Here the authors identify retinoic acid, BMP, cAMP and Rho kinase pathways as regulators of cholangiocyte maturation, and generate ciliated cholangiocytes expressing high levels of CFTR that form ductal structures in vivo.
- Mina Ogawa
- , Jia-Xin Jiang
- & Shinichiro Ogawa
-
Article
| Open AccessFocal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma
The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, the authors identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, as well as the potential associations of these alterations with prognosis and dietary habits.
- Xue-Ke Zhao
- , Pengwei Xing
- & Li-Dong Wang
-
Article
| Open AccessInvestigating the shared genetic architecture between multiple sclerosis and inflammatory bowel diseases
An epidemiological association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) is well-established, but a genetic link is unclear. Here, the authors investigate the shared genetic architecture between MS and IBD to shed light on the biological basis of comorbidity.
- Yuanhao Yang
- , Hannah Musco
- & Yuan Zhou
-
Article
| Open AccessA human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery
Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.
- Emilie Crouchet
- , Simonetta Bandiera
- & Thomas F. Baumert
-
Article
| Open AccessGWAS of serum ALT and AST reveals an association of SLC30A10 Thr95Ile with hypermanganesemia symptoms
Circulating liver enzymes, like alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are highly heritable and predictive of disease. Here, the authors perform a genome-wide association study on ALT and AST, revealing a rare variant in SLC30A10 associated with elevated ALT and AST.
- Lucas D. Ward
- , Ho-Chou Tu
- & Paul Nioi
-
Article
| Open AccessMitochondrial transcription factor A in RORγt+ lymphocytes regulate small intestine homeostasis and metabolism
RORγt is known to play critical roles in the regulation of a number of immune cell subsets. Here the authors implicate mitochondrial transcription factor A in the regulation of intestinal RORγt + lymphocyte homeostasis and metabolic control in a murine in vivo model.
- Zheng Fu
- , Joseph W. Dean
- & Liang Zhou
-
Article
| Open AccessArtificial intelligence guided discovery of a barrier-protective therapy in inflammatory bowel disease
Traditional drug discovery process use differential, Bayesian and other network based approaches. We developed a Boolean approach for building disease maps and prioritizing pre-clinical models to discover a first-in-class therapy to restore and protect the leaky gut barrier in inflammatory bowel disease.
- Debashis Sahoo
- , Lee Swanson
- & Pradipta Ghosh
-
Article
| Open AccessPredicting disease course in ulcerative colitis using stool proteins identified through an aptamer-based screen
Stool biomarkers hold promise for monitoring disease activity and predicting clinical course in inflammatory bowel disease (IBD) as they originate from the inflamed tissue. Here the authors report an aptamer-based proteomic screen, and discover several stool proteins that predict remission at four weeks.
- Sanam Soomro
- , Suresh Venkateswaran
- & Chandra Mohan
-
Article
| Open AccessCritical role of interferons in gastrointestinal injury repair
Despite being prevalent yet well studied, ulcerative colitis still has poorly characterized pathophysiology. Here the authors use mouse colitis models to find that type I and III interferon (IFN) both contribute to ameliorating the disease, with IFN signaling in either the epithelial or hematopoietic compartment sufficient for this protective effect.
- Constance McElrath
- , Vanessa Espinosa
- & Sergei V. Kotenko
-
Article
| Open AccessGenetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes
Plasma levels of liver enzymes provide insights into hepatic function and related diseases. Here, the authors perform a genome-wide association study on three liver enzymes, identifying genetic variants associated with their plasma concentration as well as links to metabolic and cardiovascular diseases.
- Raha Pazoki
- , Marijana Vujkovic
- & Rachel B. Ramoni
-
Article
| Open AccessEtiological, epidemiological, and clinical features of acute diarrhea in China
Diarrhoea is a major cause of morbidity and mortality in China. Here, the authors present results from a large sentinel surveillance scheme from 217 hospitals in all 31 provinces in mainland China, including ~150,000 patients with acute diarrhoea and covering years 2009-2018.
- Li-Ping Wang
- , Shi-Xia Zhou
- & Jun Wang
-
Article
| Open AccessPrimary and secondary clarithromycin resistance in Helicobacter pylori and mathematical modeling of the role of macrolides
Clarithromycin is a macrolide antibiotic widely used for eradication of Helicobacter pylori infection. Here, Kocsmár et al. study clarithromycin resistance and previous macrolide consumption in 4,744 H. pylori-infected patients, shedding light into the sources of primary resistant cases and the role played by prior consumption of macrolides for non-eradication purposes.
- Éva Kocsmár
- , György Miklós Buzás
- & Gábor Lotz
-
Article
| Open AccessSingle-cell analyses of Crohn’s disease tissues reveal intestinal intraepithelial T cells heterogeneity and altered subset distributions
Crohn’s disease results from transmural inflammation in the gut, but analyses of local immune populations are still lacking. Here, the authors show, by combining multiple single-cell approaches, that intraepithelial and lamina propria T cells are heterogenous, show unique phenotypes, and exhibit altered subsets upon inflammation.
- Natalia Jaeger
- , Ramya Gamini
- & Marco Colonna
-
Article
| Open AccessTrans-illumination intestine projection imaging of intestinal motility in mice
Current preclinical imaging of intestine in animal models cannot reveal intestinal dynamics in awake condition. Here the authors report a Transillumination Intestine Projection (TIP) imaging system for free-moving mice, and showed the intestine dynamics in conscious animal in natural physiological states.
- Depeng Wang
- , Huijuan Zhang
- & Jun Xia
-
Article
| Open AccessGWAS of peptic ulcer disease implicates Helicobacter pylori infection, other gastrointestinal disorders and depression
Genetic factors contribute to peptic ulcer disease (PUD). Here, the authors perform a genome-wide association analysis on PUD in the UK Biobank, highlighting shared architecture with other gastrointestinal disorders and possible causal links with depression.
- Yeda Wu
- , Graham K. Murray
- & Naomi R. Wray
Browse broader subjects
Browse narrower subjects
- Anal diseases
- Biliary tract disease
- Dysbiosis
- Enteric neuropathies
- Functional gastrointestinal disorders
- Gastroenteritis
- Gastrointestinal bleeding
- Gastrointestinal cancer
- Hepatitis
- Inflammatory bowel disease
- Intestinal diseases
- Liver diseases
- Motility disorders
- Nutrition disorders
- Oesophageal diseases
- Pancreatic disease
- Stomach diseases
- Ulcers