A modified mesenchymal stem cell (MSC) transplantation is a highly effective and precise treatment for inflammatory bowel disease (IBD), with a significant curative effect. Thus, we aim to examine the efficacy of hypoxia-inducible factor (HIF)–1α-overexpressing MSC (HIF-MSC) transplantation in experimental colitis and investigate the immunity regulation mechanisms of HIF-MSC through macrophages. A chronic experimental colitis mouse model was established using 2,4,6-trinitrobenzene sulfonic acid. HIF-MSC transplantation significantly attenuated colitis in weight loss rate, disease activity index (DAI), colon length, and pathology score and effectively rebuilt the local and systemic immune balance. Macrophage depletion significantly impaired the benefits of HIF-MSCs on mice with colitis. Immunofluorescence analysis revealed that HIF-MSCs significantly decreased the number of M1-like macrophages and increased the number of M2-like macrophages in colon tissues. In vitro, co-culturing with HIF-MSCs significantly decreased the expression of pro-inflammatory factors, C-C chemokine receptor 7 (CCR-7), and inducible nitric oxide synthase (INOS) and increased the expression of anti-inflammatory factors and arginase I (Arg-1) in induced M1-like macrophages. Flow cytometry revealed that co-culturing with HIF-MSCs led to a decrease in the proportions of M1-like macrophages and an increase in that of M2-like macrophages. HIF-MSCs treatment notably upregulated the expression of downstream molecular targets of phosphatidylinositol 3-kinase-γ (PI3K-γ), including HIF-1α and p-AKT/AKT in the colon tissue. A selected PI3K-γ inhibitor, IPI549, attenuated these effects, as well as the effect on M2-like macrophage polarization and inflammatory cytokines in colitis mice. In vitro, HIF-MSCs notably upregulated the expression of C/EBPβ and AKT1/AKT2, and PI3K-γ inhibition blocked this effect. Modified MSCs stably overexpressed HIF-1α, which effectively regulated macrophage polarization through PI3K-γ. HIF-MSC transplantation may be a potentially effective precision therapy for IBD.

Objectives: To explore the safety and efficacy of injections of 1%, 2%, or 3% lauromacrogol during EUS–guided lauromacrogol ablation (EUS-LA) for the treatment of pancreatic cystic neoplasms (PCNs) and to determine the optimal concentration of lauromacrogol for use in EUS-LA therapeutic regimens. Methods: From May 2021 to January 2023, patients who met the indications for EUS-LA were randomly divided into 3 groups: A, B, and C; the patients in these groups were injected with 1%, 2%, and 3% lauromacrogol during EUS-LA, respectively. Safety was evaluated based on the incidence of postoperative complications. Efficacy was comprehensively evaluated by assessing the ablation rate and ablation effect. Results: Forty-two patients underwent EUS-LA, and 31 patients completed at least 1 postoperative re-examination. No acute pancreatitis was observed in the 1% and 2% lauromacrogol groups, and 1 case of acute pancreatitis occurred in the 3% lauromacrogol group. The total complication rate was 2.4%. The median ablation rates of the groups were 94.1%, 82.0%, and 100.0%, respectively. There were statistically significant differences in the EUS-LA ablation rate between the 1% and 3% lauromacrogol groups and between the 2% and 3% lauromacrogol groups. There was a statistically significant difference in complete disappearance between the 1% and 3% lauromacrogol groups as well as between the 2% and 3% lauromacrogol groups. Conclusion: The short-term outcomes showed that injections of 1%, 2%, and 3% lauromacrogol were safe for use in EUS-LA, and injection of 3% lauromacrogol was the most effective for EUS-LA.

The association of the triglyceride-glucose index, a validated marker of insulin resistance, with specific dietary patterns is unclear. This cross-sectional analysis of NHANES 1999-2018 included 19,016 adults. Logistic regression, restricted cubic splines, and interaction analyses were used to evaluate associations between macronutrient intake and the triglyceride-glucose index. This analysis was designed a priori to evaluate whether a low-carbohydrate, high-fat macronutrient distribution (captured by PEC, PEF, and carbohydrate-to-fat energy ratio) is associated with the TyG index. Higher quartiles of percentage energy from carbohydrates and carbohydrate-to-fat energy ratio were associated with higher odds of an elevated TyG index, whereas higher quartiles of percentage energy from fat were associated with lower odds. Restricted cubic splines showed a positive linear association for carbohydrate energy and an inverse linear association for fat energy with TyG. Interaction analyses supported that a low-carbohydrate, high-fat pattern correlated with lower fasting triglyceride levels, and mediation analysis indicated that fasting triglycerides explained ~ 49% of the association between carbohydrate-to-fat energy ratio and TyG. A low-carbohydrate, high-fat diet was significantly associated with a lower triglyceride-glucose index; this association was primarily mediated by reductions in fasting triglyceride levels.

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