MiR-512-3p regulates malignant tumor behavior and multi-drug resistance in breast cancer cells via targeting Livin.

Breast cancer (BCa) is one of the most lethal malignancies of female reproductive organs. Increasing evidence has revealed that miRNAs participate in both tumorigenesis and multi-drug resistance. MiR-512-3p, a small non-coding RNA (miRNA), was previously found to be upregulated in breast cancer cells. In this study, we first verified that miR-512-3p expression forced a significant reorganization of the tumor architecture, affecting important cellular processes involved in cell-cell contact, cell adhesion and cell motility. Accordingly, induction of miR-512-3p expression significantly enhanced chemosensitivity and decreased metastatic potential in BCa cells. Our study demonstrated that miR-512-3p directly targets the 3'UTR of Livin, thereby decreasing its expression in MCF-7 cells. MiR-512-3p overexpression significantly inhibited breast cancer cell growth and metastasis. Both miR-512-3p overexpression and Livin knockdown significantly increased the chemosensitivity of cancer cells. Epirubicin (EPB), gemcitabine (GCB) and docetaxel (TXT) had antitumor effects in vitro against human breast cancer cell lines, and miR-512-3p overexpression increased tumor sensitivity to these drugs. In addition, miR-512-3p overexpression significantly inhibited tumor growth in vivo. Collectively, our data suggest that miR-512-3p is a significant regulator of tumorigenesis and drug resistance in breast cancer and provides evidence that miR-512-3p may represent a promising target for breast cancer therapy.

Vitamin D, the placenta and pregnancy.

Impaired vitamin D status is common to many populations around the world. However, data suggest that this is a particular problem for specific groups such as pregnant women. This has raised important questions concerning the physiological and clinical impact of low vitamin D levels during pregnancy, with implications for classical skeletal functions of vitamin D, as well as its diverse non-classical actions. The current review will discuss this with specific emphasis on the classical calciotropic effects of vitamin D as well as the less well established immunological functions of vitamin D that may influence pregnancy outcome. The review also describes the pathways that are required for metabolism and function of vitamin D, and the various clinical complications that have been linked to impaired vitamin D status during pregnancy.

Lentiviral-mediated BMP-2 gene transfer enhances healing of segmental femoral defects in rats.

The objective of the present study was to assess the ability of bone marrow cells expressing BMP-2 created via lentiviral gene transfer to heal a critical sized femoral defect in a rat model. Femoral defects in Lewis rats were implanted with 5x10(6) rat bone marrow stromal cells (RBMSC) transduced with a lentiviral vector containing either the BMP-2 gene (Group I), the enhanced green fluorescent protein (LV-GFP) gene (Group IV), or RBMSC alone (Group V). We also included femoral defects that were treated with BMP-2-producing RBMSC transduced with lentivirus, 8 weeks after infection (Group III), and a group with 1x10(6) RBMSC transduced with a lentiviral vector with the BMP-2 gene (Group II). All defects (10/10) treated in Group I healed at 8 weeks compared with none of the femora in the control groups (Groups IV and V). In Group II, only one out of 10 femora healed. In Group III, 5 out of 10 femora healed. Significantly higher amounts of in vitro BMP-2 protein production were detected in Groups I, II, and III when compared to that of the control groups (p<0.05). Histomorphometric analysis revealed significantly greater total bone volume in defects in Group I and III when compared to control specimens (p<0.003). Biomechanical testing revealed no significant differences in the healed defects in Groups I and III when compared to intact, nonoperated femora with respect to peak torque and torque to failure. Our results indicate that BMP-2-producing RBMSC created through lentiviral gene transfer have the capability of inducing long-term protein production in vitro and producing substantial new bone formation in vivo.

The distribution patterns of trace elements in the brain and erythrocytes in a rat experimental model of iodine deficiency.

Cretinism is a disease characterized by neurological defects associated with severe iodine deficiency. In a rat model of severe iodine deficiency, we investigated the distribution pattern of trace elements (iodine [I], selenium [Se], and bromine [Br] in brain tissue samples; potassium [K], calcium [Ca], manganese [Mn], iron [Fe], copper [Cu], zinc [Zn], rubidium [Rb], and lead [Pb] in erythrocytes) after supplementing the rats with I and/or Se. Neutron activation analysis, proton induced x-ray emission and x-ray fluorescence were used. The serum levels of total and free thyroxine (T4, FT4), and of total, free, and reverse triiodothyronine (T3, FT3, rT3, respectively) were assessed by radioimmunoassay. The results were statistically evaluated by one-way analysis of variance and bivariate correlation. The study indicated that the levels of T4, FT4, and rT3 increased in the serum of iodine-deficient rats supplemented with I or I + Se. In the same animals, we documented alterations of the content of Br in the brain, and of Zn, Mn, Cu, and Rb in erythrocytes, whereas the brain content of I and Se was unchanged. Thus, I and I + Se supplementation improves thyroid hormone metabolism but affects the content of selected trace elements in erythrocytes and of Br in the brain. The data stimulate further clarification of the role of trace elements in the central nervous system.

Serum selenium in liver cirrhosis: correlation with markers of fibrosis.

In 55 patients with alcoholic cirrhosis and in 47 healthy individuals we assayed the concentration of selenium in serum (S-Se) by proton induced X-ray emission, the aminoterminal peptide of type III procollagen (NPIIIP) by RIA and the plasma fibronectin (FN) by immuno-nephelometry, together with routine biochemical tests. S-Se was lower in cirrhosis than in controls (0.57, SD 0.20 vs 0.92, SD 0.16 mumol/l; p less than 0.001) and was more reduced in ascitic than in compensated patients (0.50, SD 0.19 vs 0.66, SD 0.17 mumol/l; p less than 0.001). Regression analysis showed a positive correlation of S-Se with serum albumin and FN, whereas necrotic or inflammatory activity seems unrelated to S-Se; a negative correlation was found between S-Se and NPIIIP, suggesting a protective role of selenium against fibrosis.

Selenium status and plasma glutathione peroxidase in patients with IgA nephropathy.

The abnormal proliferation of mesangial cells with IgA deposition in the glomeruli characterizes primitive mesangial glomerulonephritis (IgA nephropathy, IgAN); this disease reduces the normal renal parenchyma while renal function becomes progressively impaired. The possible role of selenium has never been considered in evaluating factors involved in the pathogenesis of IgAN. In this work we compared the Se status of 14 IgAN patients (8 with normal renal function, IgAN NRF; 6 with impaired renal function, IgAN IRF) to that of 14 normal individuals (CG NRF) before and after an oral supplementation with selenite (0.13 mol Se/kg b.w./day for 60 days). The following indices of Se status were measured: Se in plasma and urine samples by PIXE; glutathione peroxidase activity in the cytosol of platelets (PLTs-GSH-Px) and of erythrocytes (RBCs-GSH-Px). Both concentrations and activities of plasma glutathione peroxidase (pl-GPx), a selenoenzyme mainly synthesized in and secreted by the kidney, were measured in plasma samples and results compared among groups. IgAN patients showed lower pl-Se and lower activities of selenoenzymes than normal controls before Se supplementation (p < 0.001). These findings suggest that an impaired Se status coexisted with the proliferation of mesangial cells in patients. Selenite induced PLTs-GSH-Px activity in all individuals (p < 0.001), but no variation was observed in RBCs-GSH-Px activity or in the concentration of pl-GPx in the plasma. On the other hand, selenium induced pl-GPx activity in CG NRF (p < 0.001) and in IgAN NRF (p < 0.01), but poorly stimulated pl-GPx activity in IgAN IRF (p = n.s.). However, only 17% and 25% of the pl-GPx activity of normal controls was measured in the plasma of IgAN IRF and IgAN NRF patients, respectively (p < 0.001). In conclusion, selenite only partially restored a normal Se status in patients whose low pl-GPx activity probably reflects an impaired synthesis of this protein as a consequence of reduced normal functioning of the parenchyma in kidneys affected by IgA nephropathy.