The Protective Role of TLR4 in Intestinal Epithelial Cells through the Regulation of the Gut Microbiota in DSS-Induced Colitis in Mice.

BACKGROUND: The cause of ulcerative colitis (UC) is not yet fully understood. Previous research has pointed towards a potential role for mutations in nucleotide-binding oligomerization domain-containing protein 2 (NOD2) in promoting the onset and progression of inflammatory bowel disease (IBD) by altering the microbiota of the gut. However, the relationship between toll-like receptor 4 (TLR4) and gut microbiota in IBD is not well understood. To shed light on this, the interaction between TLR4 and gut microbiota was studied using a mouse model of IBD. METHODS: To examine the function of TLR4 signaling in intestinal injury repair, researchers developed Dextran Sulfate Sodium Salt (DSS)-induced colitis and injury models in both wild-type (WT) mice and TLR4 knockout (TLR4-KO) mice. To assess changes in the gut microbiota, 16S rRNA sequencing was conducted on fecal samples from both the TLR4-KO and WT enteritis mouse models. RESULTS: The data obtained depicted a protective function of TLR4 against DSS-induced colitis. The gut microbiota composition was found to vary considerably between the WT and TLR4-KO mice groups as indicated by ß-diversity analysis and operational taxonomic units (OTUs) cluster. Statistical analysis of microbial multivariate variables depicted an elevated abundance of Escherichia coli/Shigella, Gammaproteobacteria, Tenerlcutes, Deferribacteres, Enterobacteria, Rikenellaceae, and Proteobacteria in the gut microbiota of TLR4-KO mice, whereas there was a considerable reduction in Bacteroidetes at five different levels of the phylogenetic hierarchy including phylum, class, order, family, and genus in comparison with the WT control. CONCLUSIONS: TLR4 may protect intestinal epithelial cells from damage in response to DSS-induced injury by controlling the microbiota in the gut.

Discovery of extracellular vesicle-delivered miR-185-5p in the plasma of patients as an indicator for advanced adenoma and colorectal cancer.

BACKGROUND: We aimed to evaluate whether extracellular vesicles (EV)-derived microRNAs (miRNAs) can be used as biomarkers for advanced adenoma (AA) and colorectal cancer (CRC). METHODS: We detected the changes in the plasma EV-delivered miRNA profiles in healthy donor (HD), AA patient, and I-II stage CRC patient groups using miRNA deep sequencing assay. We performed the TaqMan miRNA assay using 173 plasma samples (two independent cohorts) from HDs, AA patients, and CRC patients to identify the candidate miRNA(s). The accuracy of candidate miRNA(s) in diagnosing AA and CRC was determined using the area under the receiver-operating characteristic curve (AUC) values. Logistic regression analysis was performed to evaluate the association of candidate miRNA(s) as an independent factor for the diagnosis of AA and CRC. The role of candidate miRNA(s) in the malignant progression of CRC was explored using functional assays. RESULTS: We screened and identified four prospective EV-delivered miRNAs, including miR-185-5p, which were significantly upregulated or downregulated in AA vs. HD and CRC vs. AA groups. In two independent cohorts, miR-185-5p was the best potential biomarker with the AUCs of 0.737 (Cohort I) and 0.720 (Cohort II) for AA vs. HD diagnosis, 0.887 (Cohort I) and 0.803 (Cohort II) for CRC vs. HD diagnosis, and 0.700 (Cohort I) and 0.631 (Cohort II) for CRC vs. AA diagnosis. Finally, we demonstrated that the upregulated expression of miR-185-5p promoted the malignant progression of CRC. CONCLUSION: EV-delivered miR-185-5p in the plasma of patients is a promising diagnostic biomarker for colorectal AA and CRC. Trial registration The study protocol was approved by the Ethics Committee of Changzheng Hospital, Naval Medical University, China (Ethics No. 2022SL005, Registration No. of China Clinical Trial Registration Center: ChiCTR220061592).

A retrospective case-series of influence of chronic hepatitis B on synchronous liver metastasis of colorectal cancer.

Main point: Our retrospective analysis of a large number of cases found in patients with primary colorectal cancer (CRC) carrying positive HBsAg inhibited the occurrence of synchronous liver metastases (SLM). However, liver cirrhosis caused by non-HBV factors promoted the occurrence of SLM. Objectives: This study aimed to investigate the effect of HBV on the occurrence of synchronous liver metastases (SLM) of colorectal cancer (CRC). Methods: Univariate and multivariate analyses were used to analyze the influence of clinical parameters on the occurrence of SLM. Results: A total of 6, 020 patients with primary CRC were included in our study, of which 449 patients carrying HBsAg(+) accounted for 7.46%. 44 cases of SLM occurred in the HBsAg(+) group, accounting for 9.80%, which was much lower than 13.6% (758/5571) in the HBsAg(-) group (X=5.214, P=0.022). Among CRC patients with HBsAg(-), the incidence of SLM was 24.9% and 14.9% in the group with high APRI and FIB-4 levels, respectively, which were significantly higher than that in the compared groups (12.3% and 12.5%, all P<0.05). Compared with the control group, female patients, late-onset patients, and HBV-infective patients had lower risks of SLM (HR=0.737, 95%CI: 0.614-0.883, P<0.001; HR=0.752, 95%CI: 0.603-0.943, P=0.013; HR=0.682, 95%CI: 0.473-0.961, P=0.034). Conclusions: The carriage of HBsAg(+) status inhibited the occurrence of SLM from CRC. HBV-causing liver cirrhosis did not further influence the occurrence of SLM, whereas non-HBV-factor cirrhosis promoted the occurrence of SLM. Nevertheless, this still required prospective data validation.

Prognostic significance for colorectal carcinoid tumors based on the 8th edition TNM staging system.

The aim of our study was to explore the value of the 8th edition TNM staging system on evaluating the prognosis of colorectal carcinoid. Colorectal carcinoid patients between 1988 and 2015 were selected in the Surveillance, Epidemiology, and End Results Program (SEER) database for analysis. About 4286 patients with colorectal carcinoid tumors were identified, of which were carcinoid tumor NOS (n = 1726), neuroendocrine carcinoma (NEC) (n = 1346) and other carcinoid tumor (OCT) (n = 591). Worsening 10-year CSS rates with increasing N status, M status, and SEER historic stage were demonstrated across all three above groups (all P < .05). In carcinoid tumor NOS, significant differences in CSS were found with increasing combined 8th AJCC stages (P < .001), except for that between stage II and stage III (10-year CSS rate: 82.6% vs 84.3%, P = .68). While combined 8th TNM stage in NEC and OTC exhibited greater separations in CSS despite on-going overlaps between groups. For carcinoid tumor NOS, stage II (HR = 3.37; 95% CI: 0.97-11.76), and stage III (HR = 2.09; 95% CI: 0.51-8.66) conferred no significant difference in CSS compared with stage I, while stage IV had an increasing HR of 5.09 (95% CI: 1.08-24.08). Although combined 8th AJCC stage had a good ability to distinguish 10-year CSS of patients with NEC or OCT, detailed 8th AJCC stage did not seem to be applicable. Detailed 8th AJCC categories of advanced stages in all the three groups conferred increased HRs with overlapping CIs. However, in the early and middle status, HRs did not increase with the increase of stages, or there was no difference in HRs between adjacent stages. Combined 8th TNM stage was not practical for judging the survival outcomes of colorectal carcinoid tumor NOS, especially in patients with stages II and III, but it provided useful prognostic information for NEC and OCT. However, for all carcinoid tumors, the prognostic values of detailed 8th AJCC stage were not enough accurate in the clinic. More optimized staging methods should be developed and validated in the future.