Ginsenoside Rg3 Protects Mouse Islet ß-Cells Injured by High Glucose.

To investigate the effect of Ginsenoside Rg3 on insulin secretion in mouse MIN6 cells and the possible mechanism. The cultured mouse pancreatic islet MIN6 cells were divided into control group (NC), Rg3 group (Rg3, 50 µg/L), high glucose group (HG, 33 mmol/L), High glucose and Rg3 group (HG + Rg3), after 48 h of continuous culture, CCK-8 was used to detect cell viability; mouse insulin enzyme-linked immunoassay kit to detect insulin release; ATP content detection kit to detect ATP; DCFH-DA to detect intracellular reactive oxygen species (ROS) levels; total glutathione (T-GSH)/oxidized glutathione (GSSG) assay kit to detect the ratio of GSH/GSSG; Using the mitochondrial membrane channel pore (MPTP) fluorescence detection kit in MIN6 cells and collect the intensity of green fluorescence; Western blot to detect the expression of antioxidant proteins Glutathione reductase (GR). The results showed that compared with the NC group, the cell viability of the HG was decreased (P < 0.05), insulin release decreased (P < 0.001), ATP content decreased significantly (P < 0.001), and ROS content increased (P < 0.01), the GSH/GSSH ratio of pancreatic islet cells decreased (P < 0.05),the green fluorescence intensity decreased (P < 0.001), indicating that the permeability of mitochondria increased and the content of antioxidant protein in the cells decreased (P < 0.05). Compared with the HG group, the cell viability of the HG + Rg3 group was significantly increased (P < 0.05), the amount of insulin released was significantly increased (P < 0.001), ATP content was significantly increased (P < 0.01), and the ROS content was significantly decreased (P < 0.01), GSH/GSSH ratio increased significantly (P < 0.05), the green fluorescence intensity was increased (P < 0.001), indicating that the permeability of mitochondria decreased and antioxidant protein GR content increased significantly (P < 0.05). Taken together, our results suggest that Rg3 has an antioxidant protective effect on mouse pancreatic islet cells damaged by high glucose and maintains pancreatic islet cell function and promotes insulin secretion.

Meta-analysis: Interleukin 6 gene -174G/C polymorphism associated with type 2 diabetes mellitus and interleukin 6 changes.

The gene coding interleukin 6 (IL-6) is a promising candidate in predisposition to type 2 diabetes mellitus (T2DM). This study aimed to meta-analytically examine the association of IL-6 gene -174G/C polymorphism with T2DM and circulating IL-6 changes across -174G/C genotypes. Odds ratio (OR) and standard mean difference (SMD) with 95% confidence interval (CI) were calculated. Twenty-five articles were meta-analysed, with 20 articles for T2DM risk and 9 articles for circulating IL-6 changes. Overall, there was no detectable significance for the association between -174G/C polymorphism and T2DM, and this association was relatively obvious under dominant model (OR: 0.82, 95% CI: 0.56-1.21). Improved heterogeneity was seen in some subgroups, with statistical significance found in studies involving subjects of mixed races (OR: 0.63, 95% CI: 0.46-0.86). Begg's and filled funnel plots, along with Egger's tests revealed week evidence of publication bias. In genotype-phenotype analyses, carriers of -174CC and -174CG genotypes separately had 0.10 and 0.03 lower concentrations (pg/mL) of circulating IL-6 than -174GG carriers. Albeit no detectable significance for the association of -174G/C with T2DM, our findings provided suggestive evidence on a dose-dependent relation between -174G/C mutant alleles and circulating IL-6 concentrations, indicating possible implication of this polymorphism in the pathogenesis of T2DM.

Susceptibility of six polymorphisms in the receptor for advanced glycation end products to type 2 diabetes: a systematic review and meta-analysis.

We did a systematic review and meta-analysis, aiming to examine the association of available polymorphisms in the receptor for advanced glycation end products (AGER) gene with the risk of type 2 diabetes. Literature search, eligibility assessment, and data extraction were independently performed by two authors. Risk was expressed as by odds ratio (OR) and 95% confidence interval (CI) under the random-effects model. A total of 26 publications, involving 29 independent studies (8,318 patients with type 2 diabetes and 5,589 healthy or orthoglycemic controls) were included in this meta-analysis. Six polymorphisms in AGER gene, rs2070600, rs1800624, rs1800625, rs184003, rs3134940, and rs55640627, were eligible for inclusion. Overall analyses indicated that the mutations of rs1800624 (-374A) and rs55640627 (2245A) were associated with a significantly increased risk of type 2 diabetes (OR = 1.17 and 1.55, 95% CI: 1.00 to 1.38 and 1.21 to 1.98, respectively). Subsidiary analyses revealed that the mutation of rs2070600 was associated with 2.13-folded increased risk of type 2 diabetes in Caucasians (95% CI: 1.28 to 3.55), and the mutation of rs1800624 was associated with 1.57-folded increased risk in South Asians (95% CI: 1.09 to 2.25), with no evidence of heterogeneity (I2: 42.5% and 44.5%). There were low probabilities of publication bias for all studied polymorphisms. Taken together, our findings indicate an ethnicity-dependent contribution of AGER gene in the pathogenesis of type 2 diabetes, that is, rs2070600 was a susceptibility locus in Caucasians, yet rs1800624 in South Asians.

Histomorphology and gene expression profiles during early ovarian folliculogenesis in duck and goose.

In contrast to the later stages of follicle development, little is known about the characteristics and mechanisms associated with early folliculogenesis in avian species. The objectives of the present study were to examine and compare the histomorphological and molecular changes of primordial, primary, and secondary follicles from duck and goose ovaries during the first 6 post-hatching week. Morphological analysis showed that the length and width of both duck and goose ovaries increased steadily during weeks 1 to 5 but increased acutely at week 6, whereas a greater increment was observed in the ovarian length of ducks than that of geese during weeks 4 to 5. Furthermore, smaller diameters of the 3 categories of follicles were observed in ducks than those in geese at the first appearance, but they reached a similar size at week 6. More importantly, secondary follicles were found in the ovaries of ducks 1 wk earlier than in those of geese. These results indicated a more rapid growth rate for ovarian follicles in ducks than in geese during early post-hatching development. At the molecular level, it was found that the mRNAs encoding follicle stimulating hormone receptor (FSHR), anti-Müllerian hormone (AMH), B-cell leukemia/lymphoma 2, and cysteine-dependent aspartate specific protease 3 (CASPASE3) were ubiquitously expressed in all ovarian follicles of ducks and geese with different expression profiles in each follicular category during the first 6 post-hatching week. Notably, transcript levels of FSHR, AMH, and CASPASE3 changed differently between ducks and geese during weeks 5 to 6, which was postulated to be one of the mechanisms inducing more rapid growth of ovarian follicles in ducks rather than in geese. In conclusion, our results revealed, for the first time, differences in early folliculogenesis, including the rate of growth of each follicular category and the timing of transition of primary to secondary follicles, between ducks and geese, and these differences could result from different expression profiles of FSHR, AMH, and CASPASE3 during early post-hatching development.

Risk factors for axillary lymph node metastases in clinical stage T1-2N0M0 breast cancer patients.

Axillary lymph node metastasis (ALNM) is commonly the earliest detectable clinical manifestation of breast cancer when distant metastasis emerges. This study aimed to explore the influencing factors of ALNM and develop models that can predict its occurrence preoperatively.Cases of sonographically visible clinical stage T1-2N0M0 breast cancers treated with breast and axillary surgery at West China Hospital were retrospectively reviewed. Univariate and multivariate logistic regression analyses were performed to evaluate associations between ALNM and variables. Decision tree analyses were performed to construct predictive models using the C5.0 packages.Of the 1671 tumors, 541 (32.9%) showed axillary lymph node positivity on final surgical histopathologic analysis. In multivariate logistic regression analysis, tumor size (P < .001), infiltration of subcutaneous adipose tissue (P < .001), infiltration of the interstitial adipose tissue (P = .031), and tumor quadrant locations (P < .001) were significantly correlated with ALNM. Furthermore, the accuracy in the decision tree model was 69.52%, and the false-negative rate (FNR) was 74.18%. By using the error-cost matrix algorithm, the FNR significantly decreased to 14.75%, particularly for nodes 5, 8, and 13 (FNR: 11.4%, 9.09%, and 14.29% in the training set and 18.1%,14.71%, and 20% in the test set, respectively).In summary, our study demonstrated that tumor lesion boundary, tumor size, and tumor quadrant locations were the most important factors affecting ALNM in cT1-2N0M0 stage breast cancer. The decision tree built using these variables reached a slightly higher FNR than sentinel lymph node dissection in predicting ALNM in some selected patients.

Akirin2 could promote the proliferation but not the differentiation of duck myoblasts via the activation of the mTOR/p70S6K signaling pathway.

The Akirin gene family normally contains two members that are essential to myoblast differentiation. Noticeably, the avian Akirin gene family comprises only one gene (Akirin2), However, it remains unknown whether avian Akirin gene family still has the function of Akirin1; moreover, it is still unclear whether and how Akirin2 plays a role in myoblast proliferation and differentiation. Interestingly, the unexpected functions of duck Akirin2 were revealed in the present study. The Real-time PCR results showed that between 12 and 48h during the process of duck myoblasts differentiation, the overexpression of Akirin2 did not significantly increase the expression of myogenic regulatory factors. Flow cytometry analysis revealed that the cell cycle transition was accelerated by Akirin2 overexpression. Moreover, the overexpression of Akirin2 did not influence the myotube formation. Strikingly, when duck myoblasts were cultured in the growth medium, the overexpression of Akirin2 significantly enhanced cell viability. Although the expression of cyclin-dependent proteins did not significantly increase after transfection, the expression of the mammalian targets of rapamycin (mTOR) and p70 S6 kinase (p70S6K) increased. Furthermore, the protein expression of phospho-p70S6K (Ser 417) also increased. However, when rapamycin and pEGFP-N1-Akirin2 plasmids were added together to the growth medium, the positive impact of Akirin2 on cell viability and the mRNA expression of mTOR and p70S6K were significantly blocked. Furthermore, the expression of phospho-mTOR (Ser 2448) and phospho-p70S6K (Ser 417) were also blocked. Taken together, these results could suggest that duck Akirin2 could promote myoblast proliferation via the activation of the mTOR/p70S6K signaling pathway.