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BackgroundType 2 diabetes mellitus (DM), characterized by peripheral insulin resistance, is the most common form of diabetes. Probiotics are live micro-organisms that, when administered in adequate amounts, confer delaying effect on DM development. In this study, the effects Lactobacillus reuteri GMNL-263 (Lr263), a new probiotic strain developed by our laboratory, on insulin resistance and the development of hepatic steatosis in high-fructose fed rats were explored. Furthermore, the relevant regulatory pathways involved were also investigated.MethodMale Sprague–Dawley rats were fed a high-fructose diet with or without Lr263 administration for 14 weeks. The composition of fecal microbiota, oral glucose tolerance, glycated haemoglobin, insulin, leptin, C-peptide, and incretins were measured. The markers of liver injury, serum and hepatic lipids profile, activity of hepatic antioxidant enzyme, and proinflammatory cytokines in adipose tissue were investigated. Additionally, the expression of hepatic lipogenic genes and insulin signaling related genes in adipose tissue were also studied. Liver sections were examined for hepatic steatosis using hematoxylin-eosin staining.ResultsThe levels of serum glucose, insulin, leptin, C-peptide, glycated hemoglobin, GLP-1, liver injury markers, lipid profile in serum and liver were significantly increased in high-fructose-fed rats. However, after Lr263 administration, the elevation of these parameters was significantly suppressed. Feeding of Lr263 reversed the decreased number of bifidobacterium species and lactobacillus species and increased number of clostridium species induced by high fructose treatment. The decreased activities of hepatic antioxidant enzymes in HFD rats were dramatically reversed by Lr263 treatment. Concentrations of IL-6 and TNF-α in adipose tissue which were elevated in high fructose treatment were markedly decreased after Lr263 feeding. Decreased levels of PPAR-γ and GLUT4 mRNA after high fructose treatment were significantly enhanced by Lr263 administration. Lr263 consumption normalized the increased lipogenic gene (Srebp-1c, FAS, and Elvol6) expressions stimulated by high fructose. Administration of Lr263 significantly ameliorated hepatic steatosis observed in high fructose treated rats.ConclusionOur study provided evidences clarifying the effectiveness of Lr263 on reducing insulin resistance as well as hepatic steatosis formation in high-fructose-fed rats and suggested that Lr263 may be a promising therapeutic agent in treating type 2 diabetes.

Our results indicate that HIF-1alpha is a key regulator of the angiogenic cascade. We show that HIF-1alpha is an independent prognostic factor for disease-free survival.

Our findings suggest that HIF-1alpha may play an important role in aggressive behavior and tumor angiogenesis in GIST. In addition, high expression of HIF-1alpha was significantly correlated with tumor recurrence/distant metastasis, so it may provide an ancillary prognostic factor for GIST.

Molecular characterization of endometriosis-associated ovarian cancer genes by targeted NGS. Candidate genes predictive of malignant transformation were identified. Chromatin remodeling, PI3K-AKT-mTOR, Notch signaling, and Wnt/β-catenin pathway may promote cell malignant transformation.

Our objective was to investigate and compare the effects of heat-killed (HK) and live Lactobacillus reuteri GMNL-263 (Lr263) on insulin resistance and its related complications in high-fat diet (HFD)-induced rats. Male Sprague-Dawley rats were fed with a HFD with either HK or live Lr263 for 12 weeks. The increases in the weight gain, serum glucose, insulin, and lipid profiles in the serum and liver observed in the HFD group were significantly reduced after HK or live Lr263 administration. Feeding HK or live Lr263 reversed the decreased number of probiotic bacteria and increased the number of pathogenic bacteria induced by high-fat treatment. The decreased intestinal barrier in the HFD group was markedly reversed by HK or live Lr263 treatments. The elevations of pro-inflammatory associated gene expressions in both adipose and hepatic tissues by high-fat administration were markedly decreased by HK or live Lr263 treatments. The increased macrophage infiltration noticed in adipose tissue after high-fat treatment was effectively suppressed by HK or live Lr263 consumption. The insulin resistance associated gene expressions in both adipose and hepatic tissues, which were downregulated in the HFD group, were markedly enhanced after HK or live Lr263 administration. HK or live Lr263 consumption significantly decreased hepatic lipogenic gene expressions stimulated by high-fat treatment. Administration of HK or live Lr263 significantly reduced hepatic oil red O staining and ameliorated the hepatic steatosis observed in high-fat treated rats. Our data suggested that similar to live Lr263, HK Lr263 exerted significant effects on attenuating obesity-induced metabolic abnormalities by reducing insulin resistance and hepatic steatosis formation.

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Melanins are naturally occurring pigments in both normal and pathologic tissues. Two common bleaching processes are potassium permanganate followed by oxalic acid treatment and dilute hydrogen peroxide (H2O2) process. The potassium permanganate/oxalic acid method is faster and more easily incorporated in conventional daily immunostaining protocols, whereas the dilute H2O2 method requires 24 hours. This study aimed to reduce melanin bleaching time by using a 10% H2O2 dilution. First, reaction time was reduced to 30 minutes by raising the temperature to 65°C. Second, containers with high thermal conductivity were used to improve bleaching effectiveness. Experimental comparisons of melanin treatments with H2O2 contained in an iron jar, a glass coplin jar, and a plastic steel jar obtained bleaching time of 20, 30, and 40 minutes, respectively. These modifications of the conventional bleaching method significantly improve the speed and efficiency of the procedure and are recommended when performing immunohistochemical studies.