A Single Strain of Lactobacillus (CGMCC 21661) Exhibits Stable Glucose- and Lipid-Lowering Effects by Regulating Gut Microbiota.

Type 2 diabetes (T2D) is usually accompanied by obesity and nonalcoholic fatty-liver-related insulin resistance. The link between T2D and dysbiosis has been receiving increasing attention. Probiotics can improve insulin sensitivity by regulating imbalances in microbiota, but efficacy varies based on the probiotic used. This study screened the main strain in the feces of healthy adult mice and found it to be a new Lactobacillus (abbreviated as Lb., named as CGMCC No. 21661) after genetic testing. We designed the most common Bifidobacterium longum subsp. longum (CGMCC1.2186, abbreviated as B. longum. subsp.), fecal microbiota transplantation (FMT), and Lb. CGMCC No. 21661 protocols to explore the best way for modulating dysbiosis to improve T2D. After 6 weeks of gavage in T2D mice, it was found that all three protocols had a therapeutic alleviating effect. Among them, compared with the B. longum. subsp. and FMT, the Lb. CGMCC No. 21661 showed a 1- to 2-fold decrease in blood glucose (11.84 ± 1.29 mmol/L, p < 0.05), the lowest HOMA-IR (p < 0.05), a 1 fold increase in serum glucagon-like peptide-1 (5.84 ± 1.1 pmol/L, p < 0.05), and lowest blood lipids (total cholesterol, 2.21 ± 0.68 mmol/L, p < 0.01; triglycerides, 0.4 ± 0.15 mmol/L, p < 0.01; Low-density lipoprotein cholesterol, 0.53 ± 0.16 mmol/L, p < 0.01). In addition, tissue staining in the Lb. CGMCC No. 21661 showed a 2- to 3-fold reduction in T2D-induced fatty liver (p < 0.0001), a 1- to 2-fold decrease in pancreatic apoptotic cells (p < 0.05), and a significant increase in colonic mucus layer thickness (p < 0.05) compared with the B. longum. subsp. and FMT. The glucose and lipid lowering effects of this Lb. CGMCC No. 21661 indicate that it may provide new ideas for the treatment of diabetes.

5-Lipoxygenase promotes epithelial-mesenchymal transition through the ERK signaling pathway in gastric cancer.

BACKGROUND AND AIM: 5-Lipoxygenase has been reported to enhance cell proliferation, migration, and invasion. Epithelial-mesenchymal transition is considered an important process for tumor metastasis and invasion. METHODS: The 5-lipoxygenase expression levels and the prognoses in patients with gastric cancer were evaluated by immunohistochemistry and by the log-rank test on Kaplan-Meier curves. We established 5-lipoxygenase-overexpressed and 5-lipoxygenase-silenced gastric cancer cells and measured migration, invasion, and epithelial-mesenchymal transition makers to examine the role of 5-lipoxygenase in gastric cancer in vitro. In vivo, 5-lipoxygenase-overexpressed gastric cancer cells were administered into mice by subcutaneous injection, intraperitoneal injection or splenic intravenous injection to study the proliferation or metastasis of 5-lipoxygenase in mice. Using the extracellular signal-regulated kinase pathway inhibitor U0126 and activator tumor growth factor-ß, we investigated the mechanism of epithelial-mesenchymal transition induced by 5-lipoxygenase in gastric cancer cells. RESULTS: 5-Lipoxygenase was upregulated in gastric cancer tissues and was related to poor overall survival in gastric cancer patients. 5-Lipoxygenase promoted gastric cancer cell proliferation, migration, and invasion and induced the process of epithelial-mesenchymal transition in gastric cancer cells. In the nude mouse model, mice with gastric cancer tumors overexpressing 5-LOX had a faster tumor growth rate and more severe abdominal and liver metastases than the control group. Inhibition of extracellular signal-regulated kinase signaling by U0126 or activation by tumor growth factor-ß neutralized the effect of 5-LOX overexpression or silencing on epithelial-mesenchymal transition. CONCLUSION: 5-Lipoxygenase promotes epithelial-mesenchymal transition in gastric cancer by activating the extracellular signal-regulated kinase signaling pathway.