Aspirin protects human trophoblast HTR-8/SVneo cells from H2O2-Induced oxidative stress via NADPH/ROS pathway.

INTRODUCTION: Pre-eclampsia (PE) is a pregnancy complication that can lead to maternal, fetal, and neonatal deaths in clinical practice. Accumulation of trophoblastic reactive oxygen species (ROS), which could result in oxidative stress and cell apoptosis, is considered to play an important role in PE pathology. It has been reported that aspirin has a positive effect on PE treatment in high-risk pregnant women. METHODS: In vitro, extravillous trophoblast cell line (HTR-8/SVneo) were treated with hydrogen peroxide (H2O2, 150 µM) after the presence of aspirin (90 and 120 µM) with or without GKT137831 (a Nox4 inhibitor, 20 µM). A series of experiments including CCK-8 assays, flow cytometry, biochemical testing, and Western Blotting etc. verified the protective effects and potential mechanisms of aspirin against oxidative stress-induced damage in PE. RESULTS: Our results demonstrated that H2O2 induces oxidative stress and apoptosis in HTR8/SVneo cells. However, aspirin pretreatment rescue cell viability and reduce LDH activity of HTR-8/SVneo cells. Aspirin can suppress the ROS overproduction and MDA level while increase SOD content and CAT activity. In addition, aspirin pretreatment significantly alleviated cell apoptosis and suppressed the expression of Nox4 and its subunits (p22phox and p47phox) at protein and mRNA levels. The above results were more obvious after the combination of aspirin with GKT137831. DISCUSSION: This study demonstrated that aspirin protects human trophoblasts against H2O2-induced oxidative stress and cell apoptosis via suppressing NADPH/ROS pathway. These findings provide novel insights for the application of aspirin as a protective and curative agent against PE.

The beneficial effects of the composite probiotics from camel milk on glucose and lipid metabolism, liver and renal function and gut microbiota in db/db mice.

BACKGROUND: Probiotics may have beneficial effects on patients with type 2 diabetes mellitus (T2DM). We separated 4 lactobacillus and 1 saccharomycetes from traditional fermented cheese whey (TFCW) and prepared composite probiotics from camel milk (CPCM) and investigated their effects on glucose and lipid metabolism, liver and renal function and gut microbiota in db/db mice. METHODS: CPCM was prepared in the laboratory and 40 db/db mice were randomly divided into 4 groups as metformin, low-dose and high-dose group and model group, and treated for 6 weeks. In addition, 10 C57BL/Ks mice as normal control group were used for comparison. Fasting blood glucose (FBG), body weight (BW), oral glucose tolerance test (OGTT), glycated hemoglobin (HbAlc), C-peptide (CP), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), 24 h urinary microalbumin (24 h malb), urine ketone, urine sugar, pancreas and liver tissue and intestinal flora were tested. RESULTS: Compared to diabetic group, high dose CPCM significantly decreased FBG, OGTT, HbAlc and IRI, plasma TC, TG, LDL-C, 24 h malb, urine ketone and urine sugar, increased CP, HDL-C levels, improved the liver and kidney function, protected the function of islets, also increased intestinal tract lactic acid bacteria and Bifidobacterium, decreased Escherichia in db/db mice. CONCLUSION: CPCM decreased FBG, OGTT and HbAlc, increased CP, modulated lipid metabolism and improved liver and kidney protected injury in db/db mice, which may be related to various probiotics acting through protecting the function of islets and regulating intestinal flora disturbance.

Composite probiotics alleviate type 2 diabetes by regulating intestinal microbiota and inducing GLP-1 secretion in db/db mice.

BACKGROUD/AIM: Previous studies have found that probiotic fermented camel milk has anti-diabetic effect by inducing (glucagon-like peptide-1) GLP-1 secretion. Probiotics are valuable in prevention and treatment of diabetes. As a result, our team islolated 14 probiotics from fermented camel milk. These probiotics have beneficial characteristics, but the possible anti-diabetic mechanisms remains unclear. The present study aimed to explore the possoble anti-diabetic mechanisms of 14 probiotics. METHODS: C57BL/Ks mice were normal group. The db/db mice were randomized into five groups: model group, metformin group, liraglutide group, low-dose and high-dose probiotic group. Biochemical parameters were determined by the respective assay kits. The levels of the short-chain fatty acids (SCFAs) and microbiota were respectively determined by gas chromatography and qRT-PCR. HE staining and immunofluorescence were used for histomorphological observation. Quantitative PCR and western-blot were determined the gene and protein expression of Bax, Bcl-2, Caspase-3 and PI3K/AKT. RESULTS: Probiotics significantly improved blood glucose and blood lipid parameters, as well as the morphological changes of pancreas, liver and kidney. Probiotics improved the gut barrier function through increasing the levels of SCFA-producing bacteria and SCFAs as well as the expression of claudin-1 and mucin-2, and decreasing Escherichia coli and LPS level. In additon, probiotics enhanced insulin secretion through glucose-triggered GLP-1 secretion by upregulating G protein-coupled receptor 43/41 (GPR43/41), proglucagon and proconvertase 1/3 activity. Forthermore, probiotics protected pancreas against apoptosis, which may be dependent on the upregulation of PI3K/AKT pathway. CONCLUSIONS: The anti-diabetic effect of 14 probiotics in db/db mice seem to be related to an increase of SCFA-producing bacteria, the improvement of intestinal barrier function and the upregulation of GLP-1 production, and indicate these probiotics might be a good candidate to prevent and treat diabetes.