Disproportionately Elevated Proinsulin Levels as an Early Indicator of -Cell Dysfunction in Nondiabetic Offspring of Chinese Diabetic Patients

Objective. To study the characteristics of -cell dysfunction and insulin resistance (IR) in the first-degree relatives (FDRs) of T2DM in Chinese population and to examine the usefulness of proinsulin (PI) for evaluating -cell dysfunction. Methods. 229 subjects of nondiabetic FDRs, 71 newly diagnosed T2DM, and 114 with normal glucose tolerance (NGT) but not FDRs (NGT-non-FDRs) were verified by a 2-hour oral glucose tolerance test. Specific insulin (SI) and PI were measured by highly sensitive ELISA. Results. Compared to NGT-non-FDRs, NGT-FDRs showed higher levels of fasting and 2-hour PI, fasting PI-to-SI ratio (FPI/SI), and HOMA-IR ( < 0.01). Meanwhile, fasting PI, FPI/SI, and HOMA-IR were increased steadily from NGT-FDRs to prediabetesFDRs and were highest in T2DM group ( < 0.001), whereas a significant decrease in HOMA-B could be observed only in T2DM group. Moreover, a progressive deterioration of -cell function in NGT-FDRs, prediabetes-FDRs, and T2DM could be identified by FPI/SI even after adjusting for HOMA-IR: relative to non-FDRs controls, mean FPI/SI levels were increased 1.5, 2.0, and 4.7-fold, respectively (all < 0.01). Conclusions. -cell dysfunction as assessed by disproportionate secretion of proinsulin and IR by HOMA (using specific insulin assay) already exist in FDRs of T2DM even with normal glucose status. Compared with HOMA-B, FPI/SI could detect -cell failure in earlier stage of diabetes development

Effect of Corilagin on the Proliferation and NF- κ

Background. This study is to explore the effect of corilagin on the proliferation and NF-κB signaling pathway in U251 glioblastoma cells and U251 glioblastoma stem-like cells. Methods. CD133 positive U251 glioblastoma cells were separated by immunomagnetic beads to isolate glioblastoma stem-like cells. U251 cells and stem-like cells were intervened by different corilagin concentrations (0, 25, 50, and 100 μg/mL) for 48 h, respectively. Cell morphology, cell counting kit-8 assay, flow cytometry, dual luciferase reporter assay, and a western blot were used to detect and analyze the cell proliferation and cell cycle and investigate the expression of IKBα protein in cytoplasm and NF-κB/p65 in nucleus. Results. Corilagin inhibited the cell proliferation of U251 cells and their stem-like cells and the inhibition role was stronger in U251 stem-like cells (P<0.05). The cell cycle was arrested at G2/M phase in the U251 cells following corilagin intervention; the proportion of cells in G2/M phase increased as the concentration of corilagin increased (P<0.05). The U251 stem-like cells were arrested at the S phase following treatment with corilagin; the proportion of cells in the S phase increased as the concentration of corilagin increased (P<0.05). The ratio of dual luciferase activities of U251 stem-like cells was lower than that of U251 cells in the same corilagin concentration. With increasing concentrations of corilagin, the IKBα expression in cytoplasm of U251 cells and U251 stem-like cells was increased, but the p65 expression in nucleus of U251 cells and U251 stem-like cells was decreased (P<0.05). Conclusion. Corilagin can inhibit the proliferation of glioblastoma cells and glioblastoma stem-like cells; the inhibition on glioblastoma stem-like cell proliferation is stronger than glioblastoma cells. This different result indicates that the effect of corilagin on U251 cells and U251 stem-like cells may have close relationships with mechanism of cell cycle and NF-κB signaling pathway; however, the real antitumor mechanism of corilagin is not yet clear and requires further study

Realization of the tradeoff between internal and external entanglement

We experimentally realize the internal and external entanglement tradeoff, which is a new kind of entanglement monogamy relation different from that usually discussed. Using a source of twin photons, we find that the external entanglement in polarization of twin photons, and the path-polarization internal entanglement of one photon, limit each other. In the extreme case, when the internal state is maximally entangled, the external entanglement must be vanishing, that illustrate entanglement monogamy. Our results of the experiment coincide with the theoretical predictions, and therefore provide a direct experimental observation of the internal and external entanglement monogamy relation.Comment: 10 pages, 7 figure

Europium-doped amorphous calcium phosphate porous nanospheres: preparation and application as luminescent drug carriers

Calcium phosphate is the most important inorganic constituent of biological tissues, and synthetic calcium phosphate has been widely used as biomaterials. In this study, a facile method has been developed for the fabrication of amorphous calcium phosphate (ACP)/polylactide-block-monomethoxy(polyethyleneglycol) hybrid nanoparticles and ACP porous nanospheres. Europium-doping is performed to enable photoluminescence (PL) function of ACP porous nanospheres. A high specific surface area of the europium-doped ACP (Eu3+:ACP) porous nanospheres is achieved (126.7 m2/g). PL properties of Eu3+:ACP porous nanospheres are investigated, and the most intense peak at 612 nm is observed at 5 mol% Eu3+ doping. In vitro cytotoxicity experiments indicate that the as-prepared Eu3+:ACP porous nanospheres are biocompatible. In vitro drug release experiments indicate that the ibuprofen-loaded Eu3+:ACP porous nanospheres show a slow and sustained drug release in simulated body fluid. We have found that the cumulative amount of released drug has a linear relationship with the natural logarithm of release time (ln(t)). The Eu3+:ACP porous nanospheres are bioactive, and can transform to hydroxyapatite during drug release. The PL properties of drug-loaded nanocarriers before and after drug release are also investigated