Whey Protein Peptide Pro-Glu-Trp Ameliorates Hyperuricemia by Enhancing Intestinal Uric Acid Excretion, Modulating the Gut Microbiota, and Protecting the Intestinal Barrier in Rats.

Hyperuricemia (HUA) is a metabolic disorder characterized by an increase in the concentrations of uric acid (UA) in the bloodstream, intricately linked to the onset and progression of numerous chronic diseases. The tripeptide Pro-Glu-Trp (PEW) was identified as a xanthine oxidase (XOD) inhibitory peptide derived from whey protein, which was previously shown to mitigate HUA by suppressing UA synthesis and enhancing renal UA excretion. However, the effects of PEW on the intestinal UA excretion pathway remain unclear. This study investigated the impact of PEW on alleviating HUA in rats from the perspective of intestinal UA transport, gut microbiota, and intestinal barrier. The results indicated that PEW inhibited the XOD activity in the serum, jejunum, and ileum, ameliorated intestinal morphology changes and oxidative stress, and upregulated the expression of ABCG2 and GLUT9 in the small intestine. PEW reversed gut microbiota dysbiosis by decreasing the abundance of harmful bacteria (e.g., Bacteroides, Alloprevotella, and Desulfovibrio) and increasing the abundance of beneficial microbes (e.g., Muribaculaceae, Lactobacillus, and Ruminococcus) and elevated the concentration of short-chain fatty acids. PEW upregulated the expression of occludin and ZO-1 and decreased serum IL-1ß, IL-6, and TNF-α levels. Our findings suggested that PEW supplementation ameliorated HUA by enhancing intestinal UA excretion, modulating the gut microbiota, and restoring the intestinal barrier function.

α-Lactalbumin Peptide Asp-Gln-Trp Ameliorates Hepatic Steatosis and Oxidative Stress in Free Fatty Acids-Treated HepG2 Cells and High-Fat Diet-Induced NAFLD Mice by Activating the PPARα Pathway.

SCOPE: Dietary intervention has emerged as a promising strategy for the management of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to investigate the ameliorative effects of the α-lactalbumin peptide Asp-Gln-Trp (DQW) against NAFLD and the underlying mechanism. METHODS AND RESULTS: The models of lipid metabolism disorders are established both in HepG2 cells and in C57BL/6J mice. The results demonstrate that DQW activates peroxisome proliferator-activated receptor α (PPARα) and subsequently ameliorates lipid deposition and oxidative stress in vitro. Interestingly, GW6471 markedly attenuates the modulatory effects of DQW on the PPARα pathway in HepG2 cells. Moreover, results of in vivo experiments indicate that DQW alleviates body weight gain, dyslipidemia, hepatic steatosis, and oxidative stress in high-fat-diet (HFD)-induced NAFLD mice. At the molecular level, DQW activates PPARα, subsequently enhances fatty acid ß-oxidation, and reduces lipogenesis, thereby ameliorating hepatic steatosis. Meanwhile, DQW may ameliorate liver injury and oxidative stress via activating the PPARα/nuclear-factor erythroid 2 (Nrf2)/heme-oxygenase 1 (HO-1) pathway. CONCLUSION: Those results indicate that α-lactalbumin peptide DQW may be an effective dietary supplement for alleviating NAFLD by alleviating lipid deposition and oxidative stress.

Efficacy Evaluation of High-Dose Atorvastatin Pretreatment in Patients with Acute Coronary Syndrome: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND It is unclear whether high-dose atorvastatin pretreatment benefits acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). To clarify this issue, we performed a meta-analysis of the published literature. MATERIAL AND METHODS Randomized controlled trials (RCTs) assessing high-dose atorvastatin pretreatment in ACS patients undergoing PCI were enrolled. Short-term major adverse cardiac events (MACEs), changes in serum high-sensitivity C-reactive protein (hs-CRP), peak creatine kinase-myocardial band (CK-MB) level, and thrombolysis in myocardial infarction (TIMI) grade 3 flow after PCI were studied as clinical outcomes. RESULTS Seventeen RCTs including 10 072 patients were retrieved. High-dose atorvastatin showed greater benefits in reducing the incidence of short-term MACEs (OR 0.72; 95% CI: 0.56 to 0.94; P=0.01) and hs-CRP level (SMD -1.59; 95% CI: -2.38 to -0.80; P<0.0001) among ACS patients after PCI. No significant difference was found between the 2 groups in terms of peak CK-MB (SMD -0.34; 95% CI: -0.79 to 0.10; P=0.13) or final TIMI flow grade 3 (OR 1.31; 95% CI: 0.73 to 2.36; P=0.36) after PCI. High-dose atorvastatin therapy also was not associated with alanine aminotransferase (ALT) elevation (OR 1.95; 95% CI: 0.95 to 4.03; P=0.07). CONCLUSIONS The results of this meta-analysis suggest that high-dose atorvastatin pretreatment reduces the incidence of short-term MACEs and hs-CRP level without increasing drug-induced hepatotoxicity in ACS patients after PCI.