Chronic stress and elevated glucocorticoid hormone are associated with decreases in the intestinal epithelial tight junction protein claudin-1 (CLDN1). Human/rat CLDN1 promoters contain glucocorticoid response elements (GREs) and adjacent transcription repressor HES1 binding N-boxes. Notch signaling target HES1 expression was high and glucocorticoid receptor (NR3C1) low at the crypt base and the pattern reversed at the crypt apex. Chronic stress reduced overall rat colon HES1 and NR3C1 that was associated with CLDN1 downregulation. Chromatin-immunoprecipitation experiments showed that HES1 and NR3C1 bind to the CLDN1 promoter in rat colon crypts. The binding of NR3C1 but not HES1 to CLDN1 promoter significantly decreased in chronically stressed animals, which was prevented by the NR3C1 antagonist RU486. We employed the 21-day Caco-2/BBe cell model to replicate cell differentiation along the crypt axis. HES1 siRNA treatment early in differentiation increased CLDN1. In contrast, stress levels of cortisol decreased CLDN1 in late differentiation stage but not in the early stage. HES1 was high, whereas NR3C1 and CLDN1 were low in the early stage which reversed in the late stage, e.g. HES1/NR3C1 binding to CLDN1 promoter demonstrates a dynamic and reciprocal pattern. These results suggest that chronic stress impairs colon epithelium homeostasis and barrier function via different mechanisms along the crypt axis.

Backgrounds: Previous reports of foreign-body ingestion focused primarily on accidental ingestion and very few studies focused on intentional ingestion of foreign body (FB) in China. Our study aimed to compare the prevalence of different age, gender, types, locations and management of FB ingested between intentional ingestion and accidental ingestion of FB in Northern China. Methods: A retrospective case series studied all patients with suspected FB ingestion in Digestive Endoscopy Center of Beijing Friendship Hospital, between January 2011 and January 2019. The patients were divided into 2 groups. Group A included the patients who intentionally ingested FBs, and Group B included the patients who accidentally ingested FBs. Patients' database (demographics, past medical history, characteristics of FB, endoscopic findings and treatments) were reviewed. Statistical analyses were conducted using SPSS software. Results: Group A consisted of 77 prisoners, 2 suspects and 11 psychologically disabled persons. Group B consisted of 1020 patients with no prisoners, suspects or psychologically disabled persons. In Group A, there were no food-related foreign bodies, and the majority of FBs were metallic objects (54.44%). However in Group B, food-related FBs were the most common (91.37%). In Group A, 58 cases (64.44%) were located in the stomach, while in Group B, 893 cases (87.55%) were located in the esophagus (P < 0.05). 1096 patients successfully underwent endoscopic removal and 14 failed, including 9 cases in Group A and 5 cases in Group B. The duration of FBs impaction was longer in Group A than that in Group B (P < 0.05). Conclusions: In our study, the patients who intentionally ingested FB were mainly prisoners, FBs were mostly sharp metallic objects, the duration of FBs impaction was longer, and the rate of successful endoscopic treatment was lower than that of the general population. Attention should be focused on these patients.

The altered expression of miRNAs is involved in carcinogenesis of esophageal squamous cell carcinoma (ESCC), but whether miRNAs regulate COX-2 expression in ESCC is not clear. To this end, the expression levels of miR-26a and miR-144 in ESCC clinical tissues and cell lines were investigated by qRT-PCR. COX-2 and PEG2 were quantified by western blot and ELISA. Decrease in miR-26a and miR-144 expression in ESCC was found by a comparison between 30 pairs of ESCC tumor and adjacent normal tissues as well as in 11 ESCC cell lines (P < 0.001). Co-transfection of miR-26a and miR-144 in ESCC cell lines more significantly suppressed cell proliferation, migration, and invasion than did either miR-26a or miR-144 alone (all P < 0.001), as shown by assays of CCK8, migration and invasion and flow cytometry. The inhibitory effect of these two miRNAs in vivo was also verified in nude mice xenograft models. COX-2 was confirmed as a target of miR-26a and miR-144. In conclusion, miR-26a and miR-144 expression is downregulated in ESCC. Co-expression of miR-26a and miR-144 in ESCC cells resulted in inhibition of proliferation and metastasis in vitro and in vivo, suggesting that targeting COX-2 may be the mechanism of these two miRNAs.