Identification of distinct immune infiltration and potential biomarkers in patients with liver ischemia-reperfusion injury.

AIMS: To identify alterations of specific gene expression, immune infiltration components, and potential biomarkers in liver ischemia-reperfusion injury (IRI) following liver transplantation (LT). MATERIALS AND METHODS: GSE23649 and GSE151648 datasets were obtained from the Gene Expression Omnibus (GEO) database. To determine the differentially expressed genes (DEGs), we utilized the R package "limma". We also identify the infiltration of different immune cells through single-sample gene-set enrichment analysis (ssGSEA). Furthermore, we utilized LASSO logistic regression to select feature genes and Spearman's rank correlation analysis to determine the correlation between these genes and infiltrating immune cells. Finally, the significance of these feature genes was confirmed using a mouse model of hepatic IRI. KEY FINDINGS: A total of 17 DEGs were acquired, most of which were associated with inflammation, apoptosis, cell proliferation, immune disorders, and cellular response. 28 immune cell types were determined using ssGSEA. 5 feature genes (ADM, KLF6, SERPINE1, SLC20A1, and HBB) were screened using LASSO analysis, but the HBB gene was ultimately excluded due to the lack of statistical significance in the GSE151648 dataset. These 4 feature genes were predominantly related to immune cells. Finally, 15 significantly distinctive types of immune cells between the control and IRI groups were verified. SIGNIFICANCE: We unveiled that macrophages, dendritic cells (DCs), neutrophils, CD4 T cells, and other immune cells infiltrated the IRI that occurred after LT. Moreover, we identified ADM, KLF6, SERPINE1, and SLC20A1 as potential biological biomarkers underlying IRI post-transplant, which may improve the diagnosis and prognosis of this condition.

Increased Energy Expenditure and Energy Loss Through Feces Contribute to the Long-Term Outcome of Roux-en-Y Gastric Bypass in a Diet-Induced Obese Mouse Model.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) has been proved to be more effective than other bariatric procedures in the long term on body-weight loss and remission of diabetes. However, the mechanism remains poorly understood. Long-term changes in energy metabolism after RYGB have rarely been reported. OBJECTIVE: To investigate the long-term effects of RYGB on energy metabolism on a diet-induced obesity (DIO) mouse model. METHODS: DIO mice fed a high-fat diet were assigned to two groups: RYGB (n=8) and sham (n=7), followed by high-fat diet feeding until 12 weeks after surgery. Body weight and food intake were recorded weekly. Measurement of body composition and energy metabolism by metabolic chamber were conducted at weeks 4, 8, and 12 after surgery. Fecal energy measurement, intraperitoneal glucose-tolerance tests, and insulin-tolerance tests were conducted at postoperative week 12. RESULTS: Food intake was reduced in the RYGB group within the first 3 weeks after surgery and increased to the same as the sham group from postoperative week 4. At 12 weeks after surgery, body weight had reduced by 36%±3.2% in the RYGB group compared to a 16%±2% body-weight gain in the sham group, while fat mass had reduced significantly in the RYGB group compared to the sham group (9.2%±1.5% versus 30.1%±0.7%). Energy expenditure was significantly higher at postoperative week 8 in the RYGB group than the sham group. In comparison with the sham group, the respiratory exchange ratio was unchanged, decreased, and increased in the RYGB group at postoperative weeks 4, 8, and 12, respectively. Fecal energy measurement showed that feces from mice in the RYGB group contained higher energy levels than the sham group. Glucose metabolism had significantly improved in the RYGB group, in contrast to the sham group, demonstrated by intraperitoneal glucose tolerance tests (AUC 1,502±104 versus 2,277±198, respectively) and insulin tolerance tests (AUC 524±50 versus 838±63, respectively). CONCLUSION: Increased energy expenditure and energy loss through feces contribute to long-term body-weight control after RYGB. Enhanced glucose utilization might play a role in long-term improvement in glucose metabolism.