Does inclusion of bioactive n-3 PUFAs in parenteral nutrition benefit postoperative patients undergoing liver surgery? A systematic review and meta-analysis of randomised control trials.

OBJECTIVES: This meta-analysis aims to evaluate the effect of n-3 polyunsaturated fatty acids (PUFAs) as a part of parenteral nutrition in patients undergoing liver surgery. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, the Cochrane Central Register of Controlled Trials, Springer link, Web of Science, China National Knowledge Infrastructure and VIP Database. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) and evaluated the outcomes of liver function, inflammatory reaction, the influence of certain markers of the immune system, and specific clinical indexes for patients undergoing liver surgery and receiving parenteral nutrition with n-3 PUFAs. DATA EXTRACTION AND SYNTHESIS: The Cochrane Collaboration's tool was used to assess the risk of bias for each study. Findings were summarised in Grades of Recommendation, Assessment, Development and Evaluation evidence profiles and synthesised qualitatively. RESULTS: Eight RCTs, including 748 patients (trial: 374; control: 374), were included in the meta-analysis. Compared with patients in the control group, the patients in the n-3 PUFA group who underwent liver surgery had significantly lower aspartate aminotransferase (mean difference, MD -42.72 (95% CI -71.91 to -13.52); p=0.004), alanine aminotransferase (MD -38.90 (95% CI -65.44 to -12.37); p=0.004), white cell count (MD -0.93 (95% CI -1.60 to -0.26); p=0.007) and IL-6 (MD -11.37 (95% CI -14.62 to -8.13); p<0.00001) levels and a higher albumin level (MD 0.42 (95% CI 0.26 to 0.57); p<0.00001). They also had fewer infection complications (OR 0.44 (95% CI 0.28 to 0.68); p=0.0003) and a shorter duration of hospital stay (MD -2.17 (95% CI -3.04 to -1.3); p<0.00001) than the controls. However, there were no significant differences in terms of total bilirubin, TNF-α, IL-2, IgA, IgG, IgM and CD3, biliary leakage and mortality between the two groups. CONCLUSIONS: We found that n-3 PUFAs can benefit patients undergoing liver surgery by improving liver function and certain clinical indexes and decreasing related inflammation factors. However, there are limited RCTs on the application of n-3 PUFAs for patients undergoing liver surgery. Further evidence of the benefit of n-3 PUFAs in these patients warrants further exploration.

The gut microbial metabolite phenylacetylglycine protects against cardiac injury caused by ischemia/reperfusion through activating ß2AR.

BACKGROUND: Myocardial ischemia/reperfusion (I/R) injury is closely related to cardiomyocyte apoptosis. Stimulating ß2 adrenergic receptor (ß2AR) can effectively combat cardiomyocyte apoptosis. Previous studies demonstrate that the gut microbial metabolite phenylacetylglycine (PAGly) can stimulate ß2AR. However, the effect of PAGly on myocardial I/R injury remains unknown. METHODS: The hypoxia/reoxygenation (H/R) model was established using the neonatal mouse cardiomyocytes (NMCMs). Different doses of PAGly were used to treat NMCMs, and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining. Additionally, the level of cyclic adenosine monophosphate (cAMP) was examined by using a cAMP detection kit. Mouse model of myocardial I/R injury was established in C57BL/6 mice, and different doses of phenylacetic acid were administrated intraperitoneally. Apoptosis of myocardial cells was detected by TUNEL and α-actin staining. The area at risk and the infarct areas were identified by 2,3,5-triphenyltetrazolium chloride (TTC) and Evans blue staining. Western blotting was used to measure the protein expression levels of phosphorylated phosphatidylinositol 3-kinase (p-PI3K), total Akt (t-Akt), phosphorylated Akt (p-AKT), Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), cleaved caspase-3. RESULTS: PAGly significantly suppressed H/R injury-induced apoptosis in NMCMs and inhibited apoptosis in myocardial I/R injured mice in vivo. We verified that PAGly activated the anti-apoptotic Gαi/PI3K/AKT signaling cascade in NMCMs via stimulating ß2AR signaling. Continuous administration of PAGly at an appropriate dose could inhibit apoptosis and reduce the infarct size resulting from I/R injury in mice. However, high-dose PAGly treatment was associated with a higher mortality rate. Moreover, we demonstrated that Aspirin reduced the infarct size and the high mortality caused by high doses of PAGly in I/R injured mice. CONCLUSIONS: These findings suggest that treatment with the gut microbial metabolite PAGly could suppress cardiomyocyte apoptosis caused by myocardial I/R injury and reduce the infarct size, which provides a novel therapeutic strategy for patients with myocardial infarction.