Publications by authors named "Mayo Tsuboi"

Objective: This study aimed to investigate the association between proton pump inhibitor (PPI) use and the incidence of intestinal Behçet disease (BD) in patients with BD.

Methods: A retrospective cohort study was conducted at The University of Tokyo Hospital, including patients with BD diagnosed between April 2005 and November 2023. Cox models and Kaplan-Meier analyses were used to evaluate hazard ratios (HRs) and cumulative incidence of intestinal BD, respectively.

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  • Dysbiosis in the intestinal microflora is linked to inflammatory bowel disease (IBD), and this study explores the role of secreted IgA in regulating gut bacteria, particularly focusing on the effectiveness of mouse monoclonal IgA.
  • Researchers sorted IgA-bound and unbound bacteria from IBD patients to analyze the interactions between IgA and gut microbiota, using advanced sequencing techniques and testing on gnotobiotic mice.
  • The findings indicate that human IgA in IBD patients has abnormal binding patterns, while mouse IgA shows potential to bind and inhibit harmful gut bacteria, leading to a reduction in inflammation and improvement in microbiota imbalances.
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  • Gastric cancer often shows decreased levels of mucin 6 (MUC6), but its role in the disease's development is not well understood.
  • Researchers created special mice models to study how the absence of MUC6 leads to gastric issues, including inflammation and cancer, exploring various biological techniques and analyses.
  • The study found that MUC6 loss triggers specific stress responses and alters sugar molecule patterns in tumors, suggesting new ways to target treatment through therapies involving mannose-rich glycans.
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Aim: Behçet's disease (BD) can involve any gastrointestinal (GI) tract site. We analyzed the characteristics, risk factors, and treatment responses to upper GI (UGI) involvement in patients with BD.

Methods: This retrospective cohort study analyzed UGI findings in 101 patients with BD who underwent endoscopy between April 2005 and December 2022 at the University of Tokyo Hospital.

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  • A study compared the clinical usefulness of two convolutional neural network (CNN) systems for detecting abnormalities in small-bowel capsule endoscopy (SBCE) images against traditional endoscopist readings.
  • Thirty-six SBCE videos containing different types of abnormalities were analyzed through three reading processes: without CNN, with an existing CNN, and with a novel CNN.
  • Results showed that the novel CNN system led to faster reading times and lower psychological stress for endoscopists, while still effectively detecting all abnormalities, indicating its potential for improved clinical utility.
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Background And Aims: Although is the most important bacterial carcinogen in gastric cancer (GC), GC can emerge even after eradication. Studies suggest that various constituents of the gastric microbiome may influence GC development, but the role of individual pathogens is unclear.

Methods: Human gastric mucosal samples were analyzed by 16SrRNA sequencing to investigate microbiome composition and its association with clinical parameters, including GC risk.

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  • Inhibition of sterol regulatory element-binding proteins (SREBPs) in the liver was found to worsen liver damage, fibrosis, and cancer progression in NASH models, despite reducing fat buildup.
  • Research showed that blocking SREBPs disrupted fatty acid composition in liver cells, leading to stress and injury, which could be relieved by adding phosphatidylcholines.
  • Findings suggest that while SREBP inhibition may seem beneficial for reducing fat, it can actually worsen NASH and indicate that treatments targeting lipogenesis need careful consideration.
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Background & Aims: Liver lobules are typically subdivided into 3 metabolic zones: zones 1, 2, and 3. However, the contribution of zonal differences in hepatocytes to liver regeneration, as well as to carcinogenic susceptibility, remains unclear.

Methods: We developed a new method for sustained genetic labelling of zone 3 hepatocytes and performed fate tracing to monitor these cells in multiple mouse liver tumour models.

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Infection with CagA-producing Helicobacter pylori plays a causative role in the development of gastric cancer. Upon delivery into gastric epithelial cells, CagA deregulates prooncogenic phosphatase SHP2 while inhibiting polarity-regulating kinase PAR1b through complex formation. Here, we show that CagA/PAR1b interaction subverts nuclear translocation of BRCA1 by inhibiting PAR1b-mediated BRCA1 phosphorylation.

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The mechanism of -induced atrophy and metaplasia has not been fully understood. Here, we demonstrate the novel role of Apoptosis signal-regulating kinase 1 (ASK1) and downstream MAPKs as a regulator of host immune responses and epithelial maintenance against infection. ASK1 gene deficiency resulted in enhanced inflammation with numerous inflammatory cells including Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) recruited into the infected stomach.

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Background & Aims: Peribiliary glands (PBGs), clusters of epithelial cells residing in the submucosal compartment of extrahepatic bile ducts, have been suggested as biliary epithelial stem/progenitor cell niche; however, evidence to support this claim is limited because of a lack of PBG-specific markers. We therefore sought to identify PBG-specific markers to investigate the potential role of PBGs as stem/progenitor cell niches, as well as an origin of cancer.

Methods: We examined the expression pattern of the Wnt target gene Axin2 in extrahepatic bile ducts.

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In Asia, the incidences of infection and gastric cancer are high, but their association with autoimmune gastritis (AIG) is unclear. This was a retrospective cohort study of patients endoscopically diagnosed with chronic gastritis between 2005 and 2017. AIG was diagnosed according to anti-parietal cell antibody positivity.

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Background & Aims: Gastric chief cells, a mature cell type that secretes digestive enzymes, have been proposed to be the origin of metaplasia and cancer through dedifferentiation or transdifferentiation. However, studies supporting this claim have had technical limitations, including issues with the specificity of chief cell markers and the toxicity of drugs used. We therefore sought to identify genes expressed specifically in chief cells and establish a model to trace these cells.

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Aim: Early diagnosis and evaluation of the severity of sigmoid volvulus are necessary for management and early intervention. We developed a new predictive classification system for sigmoid volvulus based on X-ray findings.

Methods: We retrospectively analyzed 66 patients diagnosed with sigmoid volvulus using the electronic medical records at the Osaki Citizen's Hospital and the University of Tokyo Hospital from 2008-2015.

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  • The intestinal epithelium relies on long-lived intestinal stem cells (ISCs) for maintenance, while short-lived progenitors can dedifferentiate back into ISCs under certain conditions, a process that is not well understood in cancer.
  • Researchers used various mouse models and methods to study the behavior of intestinal cells after injury, specifically looking at gene expression patterns in both healthy tissues and tumors.
  • Key findings showed that Bhlha15 cells can convert into enterocyte progenitors after injury, and sustained Notch activation influences gene expression in these cells, suggesting a potential link between dedifferentiation and cancer development.
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Chronic inflammation and intestinal metaplasia are strongly associated with gastric carcinogenesis. Kras activation and Pten deletion are observed in intestinal-type gastric cancer, and Cdh1 mutation is associated with diffuse-type gastric cancer. Although various mouse models of gastric carcinogenesis have been reported, few mouse lines enable gene manipulation selectively in the stomach.

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Background And Aims: Disturbance of intestinal homeostasis is associated with the development of inflammatory bowel disease [IBD], and TGF-β signalling impairment in mononuclear phagocytes [MPs] causes murine colitis with goblet cell depletion. Here, we examined an organoid-MP co-culture system to study the role of MPs in intestinal epithelial differentiation and homeostasis.

Methods: Intestinal organoids were co-cultured with lamina propria leukocytes and bone marrow-derived dendritic cells [BMDCs] from CD11c-cre Tgfbr2fl/fl mice.

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During human gastric carcinogenesis, intestinal metaplasia is frequently seen in the atrophic stomach. In mice, a distinct type of metaplasia known as spasmolytic polypeptide-expressing metaplasia (SPEM) is found in several inflammatory and genetically engineered models. Given the diversity of long- and short-term models of mouse SPEM, it remains unclear whether all models have a shared or distinct molecular mechanism.

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It is often difficult to insert a long intestinal tube (LT) in patients with small bowel obstruction (SBO). We developed a novel technique for inserting an LT without endoscopy called nonendoscopic over-the-wire method via short nasogastric tube (NEWSt). We evaluated the efficacy and safety of NEWSt.

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