USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesis.

Duodenogastric reflux (DGR) has been linked to the onset of gastric cancer (GC), although the precise mechanism is yet obscure. Herein, we aimed to investigate how refluxed bile acids (BAs) and macrophages are involved in gastric carcinogenesis. In both active human bile reflux gastritis and the murine DGR model, ubiquitin specific protease 50 (USP50) was dramatically raised, and macrophages were the principal leukocyte subset that upregulated USP50 expression. Enhancing USP50 expression amplified bile acid-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and subsequent high-mobility group box protein 1 (HMGB1) release, while USP50 deficiency resulted in the reversed alteration. Mechanistically, USP50 interacted with and deubiquitinated apoptosis-associated speck-like protein containing CARD (ASC) to activate NLRP3 inflammasome. The release of HMGB1 contributes to gastric tumorigenesis by PI3K/AKT and MAPK/ERK pathways. These results may provide new insights into bile reflux-related gastric carcinogenesis and options for the prevention of DGR-associated GC.

Triphenyl phosphate exposure impairs colorectal health by altering host immunity and colorectal microbiota.

Colorectal diseases such as colorectal cancer (CRC) and inflammatory bowel disease (IBD) have become one of the most common public health concerns worldwide due to the increasing incidence. Environmental factors are one of the important causes of colorectal diseases, as they can affect the intestinal barrier function, immune response and microbiota, causing intestinal inflammation and tumorigenesis. Triphenyl phosphate (TPHP), a widely used organophosphorus flame retardant that can leach and accumulate in various environmental media and biota, can enter the human intestine through drinking water and food. However, the effects of TPHP on colorectal health have not been well understood. In this study, we investigated the adverse influence of TPHP exposure on colorectal cells (in vitro assay) and C57BL/6 mice (in vivo assay), and further explored the potential mechanism underlying the association between TPHP and colorectal disease. We found that TPHP exposure inhibited cell viability, increased apoptosis and caused G1/S cycle arrest of colorectal cells. Moreover, TPHP exposure damaged colorectal tissue structure, changed immune-related gene expression in the colorectal transcriptome, and disrupted the composition of colorectal microbiota. Importantly, we found that TPHP exposure upregulated chemokine CXCL10, which was involved in colorectal diseases. Our study revealed that exposure to TPHP had significant impacts on colorectal health, which may possibly stem from alterations in host immunity and the structure of the colorectal microbial community.

Sciatic hernia led to strangulated ileum and ipsilateral ovary: A case report and review of literature.

Sciatic hernia is one of the rarely pelvic floor hernias. We report a 45-year-old woman who presented with acute crampy pain of hypogastrium which radiated down the back of the left thigh and found a mass in her left buttock area which is about fist size with local pain, so she had to force to bow position when walking. She was also associated with definite gastro-intestinal symptoms. Computed tomography (CT) of the pelvis and abdomen demonstrated the herniation of an ileal loop through the sciatic foramen on the left side. The diagnosis and management of this case are herein described and previous publications on sciatic hernias are reviewed.