Background: Ulcerative colitis (UC) is a chronic inflammatory colonic disease strongly associated with intestinal epithelial cell (IEC) death. Necroptosis is characterized by a newly programmed cell death through a caspase-independent pathway. Receptor interacting protein 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) are very important in the pathway of necroptosis. However, their expression in UC remains unelucidated. This study aimed to investigate the expression of RIP3 and MLKL in patients with UC, along with its correlation with disease activity.Methods: Colonic tissue samples were taken from 22 UC patients and 19 healthy controls. RIP3 and MLKL expression levels were evaluated by immunohistochemical staining and western blotting.Results: RIP3 and MLKL were upregulated in inflamed tissues of UC (P<0.01). No variations were observed in healthy control subjects and non-inflamed colons (P>0.05). RIP3 and MLKL were positively correlated with UC disease activity (P<0.01). Conclusions:Our results suggest that necroptosis is strongly associated with intestinal inflammation in patients with UC. Further studies of necroptosis may be helpful in future treatments of UC.
Background CD137 is a target for tumor immunotherapy. However, the role of CD137 in gastric cancer (GC), especially in inducing GC cell apoptosis, has not been studied. Methods Foxp3+ and CD8+ T cells in GCs were investigated using immunohistochemistry (IHC). CD137 expression in GCs was detected using flow cytometry, IHC and immunofluorescence (IF). Peripheral blood mononuclear cells (PBMCs) and CD8+ T cells isolated from peripheral blood were stimulated with a CD137 agonist in vitro. CD8+ T cell proliferation and p65 expression was examined using flow cytometry. P65 nuclear translocation was analyzed using IF. IL-10, TGF-β, IFN-γ, perforin and granzyme B were detected using real-time quantitative PCR (real-time PCR). PBMCs and primary GC cells were cocultured and stimulated with a CD137 agonist in vitro. Apoptosis of primary GC cells was detected using flow cytometry. Results Our data demonstrated that GC tumors showed characteristics of an immunosuppressive microenvironment. CD137 was predominantly expressed in CD8+ T cells in GCs and had a positive correlation with tumor cell differentiation. The CD137 agonist promoted CD8+ T cell proliferation and increased the secretion of IFN-γ, perforin and granzyme B, which induced primary GC cell apoptosis. Mechanistically, this study found that the CD137 agonist induced NF-κB nuclear translocation in CD8+ T cells. Conclusion Our results demonstrated that a CD137 agonist induced primary GC cell apoptosis by enhancing CD8+ T cells via activation of NF-κB signaling.
Polyethylene glycol (PEG) is one of the most commonly used bowel cleansing methods. Although the safety of PEG for bowel cleansing has been proven, its impact on intestinal microbiota has not been clearly explained, especially in terms of the dynamic changes in intestinal microbiota after PEG bowel cleansing, and there are no consistent results. In this study, stool samples were collected from 12 participants at six time points before and after bowel cleansing. We obtained data on the microbiota of these samples using 16S rRNA gene sequencing and analysis. The data revealed that the structure and composition of the microbiota changed greatly approximately 7 d after intestinal cleansing. The analysis of the dynamic changes in the microbiota showed that the change was most significant at day 3, but the internal structure of the microbiota was similar to that before bowel cleansing. A comparison of the most significantly changed microbiota at different time points before and after bowel cleansing revealed four bacteria: Bacteroides, Roseburia, Eubacterium, and Bifidobacterium. We also established a humanized mouse model to simulate human bowel cleansing using PEG. The results showed that the mouse model achieved similar effects to human bowel cleansing, but its recovery speed was one stage earlier than that of humans. These findings suggest that the intestinal microbiota after bowel cleansing initially underwent a short-term change and then actively returned to its initial status. The results on key bacteria and establishment of mouse models can provide a reference for subsequent research on bowel cleansing.
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