A new Cu(II)-containing coordination polymer: protective effect and mechanism exploration on elderly osteoporotic hip fractures via regulating the wnt signaling pathway.

Elderly osteoporosis hip fracture has drawn the attention of the researcher. The coordination polymer was now widely used in clinic because their multiple structures and biological activities. In this present research, the new coordination polymer was designed and synthesized and their application values on elderly osteoporosis hip were evaluated. The reaction between Cu(II) salt and 4,4'-(1H-1,2,4-triazol-1-yl)methylene-bis(benzoic acid) (H2tzmb), an aromatase inhibitor letrozole derivative with the aid of the organic linker 4,4-bipyridine (4,4'-bpy) affords a new coordination polymer based on Cu(II) ions as nodes of {[Cu2(tzmb)2(4,4'-bpy) (µ2-H2O)2(DMA) (H2O)2]·10DMA}n (1). The complex 1 gained is totally investigated with the powder X-ray diffraction study, thermogravimetric analyses, the diffraction of single-crystal X-ray, elemental analysis as well as the Fourier transform infrared spectrometer spectra. The osteogenic differentiation of mesenchymal stem cell was measured with the western blotting assay through determining the Runx2 expression. The wnt signaling pathway relative expression in mesenchymal stem cell was detected through the determination of real-time RT-PCR. The cytotoxicity of the compound on the mesenchymal stem cell was determined with CCK-8 assay. The result of single-crystal X-ray diffraction reflects that the complex 1 has crystallized in space group R-3c of trigonal system and exhibits a three-dimensional skeleton architecture on the bases of the SBUs {Cu(tzmb)(µ2-H2O)}n. The western blotting assay results revealed that this compound could significantly promote the osteogenic differentiation of mesenchymal stem cell. Besides, the activation of wnt signaling pathway in mesenchymal stem cell was also increased by the compound exposure. Finally, it can be summed up that this compound has excellent application values on the elderly osteoporotic hip fractures treatment by increasing the activation of wnt signaling pathway in mesenchymal stem cell. The results of the CCK-8 assay indicated that the compound has no cytotoxicity on the mesenchymal stem cell. The molecular docking simulation results have identified that only the carboxyl group on the Cu complex exhibits the activity for the hydrogen bond formation, however, the pyridine ring does not have such activity, instead, the pyridine ring only acts as the ligand that binds to the Cu ion. This Cu(II) coordination polymer has excellent application values on the elderly osteoporotic hip fractures treatment by increasing the activation of wnt signaling pathway in mesenchymal stem cell.

The heterogeneity of islet autoantibodies and the progression of islet failure in type 1 diabetic patients.

Type 1 diabetes mellitus is heterogeneous in many facets. The patients suffered from type 1 diabetes present several levels of islet function as well as variable number and type of islet-specific autoantibodies. This study was to investigate prevalence and heterogeneity of the islet autoantibodies and clinical phenotypes of type 1 diabetes mellitus; and also discussed the process of islet failure and its risk factors in Chinese type 1 diabetic patients. A total of 1,291 type 1 diabetic patients were enrolled in this study. Demographic information was collected. Laboratory tests including mixed-meal tolerance test, human leukocyte antigen alleles, hemoglobinA1c, lipids, thyroid function and islet autoantibodies were conducted. The frequency of islet-specific autoantibody in newly diagnosed T1DM patients (duration shorter than half year) was 73% in East China. According to binary logistic regressions, autoantibody positivity, longer duration and lower Body Mass Index were the risk factors of islet failure. As the disease developed, autoantibodies against glutamic acid decarboxylase declined as well as the other two autoantibodies against zinc transporter 8 and islet antigen 2. The decrease of autoantibodies was positively correlated with aggressive beta cell destruction. Autoantibodies can facilitate the identification of classic T1DM from other subtypes and predict the progression of islet failure. As there were obvious heterogeneity in autoantibodies and clinical manifestation in different phenotypes of the disease, we should take more factors into consideration when identifying type 1 diabetes mellitus.