Serum exosomal miR-4772-3p is a predictor of tumor recurrence in stage II and III colon cancer Serum exosomal miR-4772-3p is a predictor of tumor recurrence in stage II and III colon cancer

Background: Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine characterized by a compromised intestinal epithelial barrier. Mucin glycans are crucial in preserving barrier function during bacterial infections, although the underlying mechanisms remain largely unexplored. Methods: A cohort comprising 15 patients diagnosed with UC and 15 healthy individuals was recruited. Stool samples were collected to perform 16S rRNA gene sequencing, while biopsy samples were subjected to nanocapillary liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) to assess O-glycosylation. Gene expression was evaluated through qPCR analysis and Western blotting. Furthermore, animal experiments were conducted to investigate the effects of Escherichia coli and/or O-glycan inhibitor benzyl-α-GalNAc on the development of colitis in mice. Results: Our findings revealed that the mucus barrier was disrupted during the early stages of UC, while the MUC2 protein content remained unaltered. Additionally, a noteworthy reduction in the o-glycosylation of MUC2 was observed, along with significant changes in the intestinal microbiota during the early stages of UC. These changes included a decrease in intestinal species richness and an increase in the abundance of Escherichia coli (E. coli). Moreover, subsequent to the administration of galactose or o-glycan inhibitor to intestinal epithelial cells, it was observed that the cell culture supernatant had the ability to modify the proliferation and adhesive capacity of E. coli. Furthermore, when pathogenic E. coli or commensal E. coli were cocultured with intestinal epithelium, both strains elicited activation of the NF-KB signaling pathway in epithelial cells and facilitated the expression of serine protease in comparison to the untreated control. Consistently, the inhibition of o-glycans has been observed to enhance the pathogenicity of E. coli in vivo. Furthermore, a correlation has been established between the level of o-glycans and the development of ulcerative colitis. Specifically, a reduction in the O-glycan content of MUC2 cells has been found to increase the virulence of E. coli, thereby compromising the integrity of the intestinal epithelial barrier. Conclusions: Together, there exist complex interactions between the intestinal epithelium, o-glycans, and the intestinal microbiota, which may inform the development of novel therapeutic strategies for the treatment of ulcerative colitis.

INTRODUCTION: Although the 9-minute mean withdrawal time (m-WT) is often reported to be associated with the optimal adenoma detection rate (ADR), no randomized trials of screening colonoscopy have confirmed the impact of a 9-minute m-WT on adenoma miss rate (AMR) and ADR. METHODS: A multicenter tandem trial was conducted in 11 centers. Seven hundred thirty-three asymptomatic participants were randomized to receive segmental tandem screening colonoscopy with a 9-minute withdrawal, followed by a 6-minute withdrawal (9-minute-first group, 9MF, n = 366) or vice versa (6-minute-first group, 6MF, n = 367). The primary outcome was the lesion-level AMR. RESULTS: The intention-to-treat analysis revealed that 9MF significantly reduced the lesion-level (14.5% vs 36.6%, P < 0.001) and participant-level AMR (10.9% vs 25.9%, P < 0.001), advanced adenoma miss rate (AAMR, 5.3% vs 46.9%, P = 0.002), multiple adenomas miss rate (20.7% vs 56.5%, P = 0.01), and high-risk adenomas miss rate (14.6% vs 39.5%, P = 0.01) of 6MF without compromising detection efficiency ( P = 0.79). In addition, a lower false-negative rate for adenomas ( P = 0.002) and high-risk adenomas ( P < 0.05), and a lower rate of shortening surveillance schedule ( P < 0.001) were also found in 9MF, accompanying with an improved ADR in the 9-minute vs 6-minute m-WT (42.3% vs 33.5%, P = 0.02). The independent inverse association between m-WT and AMR remained significant even after adjusting ADR, and meanwhile, 9-minute m-WT was identified as an independent protector for AMR and AAMR. DISCUSSION: In addition to increasing ADR, 9-minute m-WT also significantly reduces the AMR and AAMR of screening colonoscopy without compromising detection efficiency.