Current treatments for patients with Crohn9s disease (CD) are based on recent advances in elucidating the pathophysiology of the disease. A satisfactory therapeutic strategy has not been well established. A new sphingosine 1-phosphate (S1P) receptor agonist, 2-amino-2-propanediol hydrochloride (KRP-203), has been developed for immunomodulation in autoimmune diseases and organ transplantation. We aimed to evaluate the efficacy and potency of KRP-203 on the treatment of chronic colitis in an interleukin (IL)-10 gene-deficient (IL-10^–/–) mouse model. KRP-203 agonistic activity on S1P receptor was assessed in vitro. KRP-203 was administered for 1 or 4 weeks to IL-10^–/– mice with clinical signs of colitis. The histological appearance of the colon and the numbers, phenotype, and cytokine production of lymphocytes were compared with a control group. KRP-203 treatment was effective in preventing body weight loss in the IL-10^–/– colitis model. One-week administration resulted in the sequestration of circulating lymphocytes within the secondary lymphoid tissues. After 4 weeks of treatment, highly significant reductions were observed in number of CD4⁺ T cell and B220⁺ B cell subpopulations in the lamina propria of the colon and peripheral blood. KRP-203 obviously inhibited the production of interferon-γ, IL-12, and tumor necrosis factor-α by the colonic lymphocytes, but had no influence on IL-4 production. KRP-203 significantly inhibits ongoing IL-10^–/– colitis in part through decreasing the infiltration of lymphocytes at inflammatory sites and by blocking T-helper 1 cytokine production in the colonic mucosa. Therefore, the possibility arises that KRP-203 plays a potential role in control of chronic colitis.

A limited number of therapeutic strategies are currently available for patients with inflammatory bowel disease (IBD). In particular, the maintenance therapy after remission in Crohn's disease (CD) is not satisfactory and new approaches are needed. Interleukin-10 gene-deficient (IL-10^–/–) mice, a well-characterized experimental model of CD, develop severe chronic colitis due to an aberrant Th1 immune response. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), a new immunosuppressive reagent, has been used successfully in animal models for heart, liver, lung and kidney transplantation. In the present study, we examined the efficacy of everolimus in the treatment of chronic colitis in an IL-10^–/– mouse model. Everolimus was administered orally for a period of 4 weeks to IL-10^–/– mice with clinical signs of colitis. The gross and histological appearances of the colon and the numbers, phenotype and cytokine production of lymphocytes were compared with these characteristics in a control group. The 4-week administration of everolimus resulted in a significant decrease in the severity of colitis, together with a significant reduction in the number of CD4⁺ T cells in the colonic lamina propria as well as IFN-γ production in colonic lymphocytes. Everolimus treatment of established colitis in IL-10^–/– mice ameliorated the colitis, probably as a result of decreasing the number of CD4⁺ T cells in the colonic mucosa and an associated reduction in IFN-γ production.

The relationship between the gut microbiome and metabolic dysfunction-associated fatty liver disease (MAFLD) has garnered increasing attention. However, the association between the dietary index for gut microbiota (DI-GM), a measure of microbiome diversity, and MAFLD has yet to be fully explored. Data from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) were analyzed, including 7243 participants. The association between DI-GM and MAFLD was investigated using weighted logistic regression, restricted cubic spline (RCS), and subgroup analyses. A notable inverse association was identified between DI-GM and the prevalence of MAFLD, with each 1-point increase in DI-GM corresponding to a 6.1% reduction in MAFLD prevalence (OR = 0.939, 95% CI: 0.901–0.980). Individuals with a DI-GM score of 6 or higher had an adjusted OR of 0.794 (95% CI: 0.665–0.947) compared to those with a DI-GM score of 0–3. RCS analysis further revealed a linear relationship between DI-GM and MAFLD risk. Additionally, subgroup analyses suggested that race may modify the association between DI-GM and MAFLD (P for interaction < 0.05). DI-GM is inversely associated with MAFLD prevalence, and race appears to be a significant modifier of this relationship.

The efficacy of anatomical resection (AR) and non-anatomical resection (NR) in the treatment of hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remains unknown. This study compared the safety and outcomes of these surgical procedures. A systematic literature search was conducted. The main outcomes were overall survival (OS), disease-free survival (DFS). Overall hazard ratio (HR) was calculated from Kaplan-Meier plots and outcomes using random-effects models. There was no significant difference in postoperative complications between the AR and NR groups (risk ratio [RR]: 0.92, 95% confidence interval [CI]: 0.72-1.17, p = 0.496). OS was higher with AR at 1 year (RR: 0.66, 95% CI: 0.45-0.98, p = 0.037), 3 years (RR: 0.64, 95% CI: 0.50-0.82, p = 0.000), and 5 years (RR: 0.76, 95% CI: 0.65-0.89, p = 0.001). AR was associated with a higher OS rate (HR: 0.62, 95% CI: 0.47-0.82, p = 0.001). AR was associated with improved DFS at 1 year (RR: 0.65, 95% CI: 0.52 to 0.82, p = 0.000), 3 years (RR: 0.75, 95% CI: 0.66 to 0.86, p = 0.000), and 5 years (95% CI: 0.75 to 0.94, p = 0.002). Compared with NR, AR had significant advantages on overall HR of DFS (HR: 0.64, 95% CI: 0.45 to 0.91, p = 0.012). In conclusion, AR was associated with higher rates of OS and DFS in HCC patients with MVI. Thus, for well-presented liver function HCC patients which are predicted to have positive MVI, AR is recommended.