: Doxorubicin (DOX) is one of the widely used anti-cancer drugs, whereas it can induce irreversible cardiac injury in a dose-dependent manner which limits its utility in clinic. Our study aimed to ...investigate the relationship between miR-25 and DOX-induced cardiac injury and its underlying mechanism.
: Mice and H9c2 cells were exposed to DOX. The overexpressed or knockdown of miR-25 in H9c2 cells was achieved by miR-25 mimic or inhibitor and the efficiency of transfection was identified by qRT-PCR or Western blotting. Cell viability, apoptotic cell rate, and levels of apoptosis-related proteins were determined by CCK-8, flow cytometry, and Western blotting, respectively. Furthermore, Western blotting and immunofluorescence staining (IF) were performed to assess the expression levels of reactive oxygen species and degree of DNA damage.
: As a result, DOX significantly upregulated miR-25 expression in mice and H9c2 cells and reduced cell viability and increased cell apoptosis
and
. miR-25 overexpression expedited cell injury induced by DOX in H9c2 cells demonstrated by the increased cell apoptosis and reactive oxygen species (ROS) production, whereas miR-25 inhibition attenuated the cell injury. Furthermore, miR-25 negatively controlled the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Intervention the expression of PTEN using si-PTEN reversed the beneficial effects of miR-25 inhibition on DOX-injured H9c2 cells.
: In conclusion, this study demonstrated that miR-25 is involved in DOX-induced cell damage through the regulation of PTEN expression.
Amphiphilic block copolymer micelles in aqueous solution have been used extensively in delivery of hydrophobic drugs with the hydrophobic core serving as the reservoir. However, encapsulation of ...hydrophilic drugs by polymeric micelles with hydrophobic core is relatively difficult because of the poor interaction between them. Herein, we report a novel kind of pH/GSH dual-responsive complex micelles with a hydrophilic drug loaded,
via
direct subcomponent self-assembly of block copolymer poly(ethyleneglycol)-
block
-poly(
l
-lysine) (PEG-
b
-PLys), 2-formylbenzeneboronic acid (2-FPBA) and hydrophilic 1,2-diol-containing drugs (
e.g.
capecitabine (CAPE)) under physiological pH 7.4 based on the synergistic formation of an iminoboronate structure. The PEG-
b
-PLys/2-FPBA micelles without CAPE are well-characterized in terms of micellization mechanism, size, morphology, pH- and GSH-responsiveness. Encapsulation of CAPE by forming PEG-
b
-PLys/2-FPBA/CAPE complex micelles
via
synergistic formation of the iminoboronate structure is discussed and pH- and GSH-responsive drug-release studies are carried out. The complex micelles are stable under physiological neutral conditions but could be destroyed in response to the stimuli of physiological acidic condition (pH 5.0) and/or glutathione (GSH) at pH 7.4. pH- and GSH-responsive drug-releases are successfully achieved. The drug-loaded complex micelles could be endocytosed by HepG2 cells and efficiently deliver hydrophilic drugs into them. This type of complex micelles could be used as a promising platform for the delivery of hydrophilic 1,2-diol-containing drugs.
Iminoboronate-based dual-responsive micelles were fabricated
via
simple subcomponent self-assembly for delivery of hydrophilic 1,2-diol-containing drugs.
Yan M, Zhang KP, Shi YH, Feng LF, Lv L, Li BX. Drug Des Devel Ther. 2015 Oct 22;9:5737-5747.On page 5742, Figure 3C, an incorrect Western blot image is shown.Read the original article.
TU375.4%TU352.11; According to the Code for Seismic Design of Buildings (GBS0011-2001),ten typical reinforced concrete (RC) frame structures,used as school classroom buildings,are designed with ...different seismic fortification intensities (SFIs) (SFI=6 to 8.5) and different seismic design categories (SDCs) (SDC=B and C).The collapse resistance of the frames with SDC=B and C in terms of collapse fragility curves are quantitatively evaluated and compared via incremental dynamic analysis (IDA).The results show that the collapse resistance of structures should be evaluated based on both the absolute seismic resistance and the corresponding design seismic intensity.For the frames with SFI from 6 to 7.5,because they have relatively low absolute seismic resistance,their collapse resistance is insufficient even when their corresponding SDCs are upgraded from B to C.Thus,further measures are needed to enhance these structures,and some suggestions are proposed.
The nonlinear finite element method (FEM) was used in the paper by using LS-DYNA software to numerically study the failure mechanism of light steel columns under fire and explosion. The constitutive ...model under the combined effects of fire and explosion was established, and the numerical simulation analysis of the columns under combined effects of fire and explosion was performed. The results showed that the failure modes of the mentioned columns were all bending shear failures. The deformation diagrams of the column under the blast and different temperatures, respectively, were proposed and this will provide a foundation for establishing the failure modes and the simplified calculation method. According to the relationship between rotation angles at the ends of the column and temperatures, the damage index of D was proposed in this paper for the evaluation of the damage level of the simulated light steel column.
The aim of the present study was to examine the effects of the human chorionic gonadotropin (hCG) dose on the pulsatility indices (PI) of the intraovarian artery on the day of follicle aspiration and ...the oocyte quality, intrafollicular oxidative stress and luteinization. PI was also measured on the day of hCG administration. A total of 15 patients were undergoing the
fertilization and embryo transfer (IVF-ET) program. To estimate whether there was any difference between the intraovarian artery blood flow and oocyte development of the same patients treated with 5,000 or 10,000 IU hCG, the intraovarian artery blood flow was measured by transvaginal color ultrasonography pulsed wave Doppler, and the follicular fluids and the granulosa cells were collected at follicle aspiration. There were statistically significant differences between the same patients undergoing the two different hCG-dose treatments in which the first protocol included 10,000 IU and the second protocol included 5,000 IU hCG treatment. These differences were apparent in the PI of intraovarian artery blood flow on the day of follicle aspiration (P=0.0023), in the incidence of apoptosis in cumulus (ApoC) and mural (ApoM) granulosa cells (ApoC, P=0.0077; ApoM, P=0.0128), in the total oocytes retrieved (P=0.0342) and in the follicle fluid progesterone concentration (P=0.0044). There were no significant differences between the two protocols in the PI of intraovarian artery blood flow on the day of hCG administration (P=0.4326), serum steroid on the day of follicle aspiration serum P, P>0.9999; serum estradiol (E
), P=0.8589, follicle fluid E
concentration (P=0.8939), mature oocyte rate (P=0.3743) and total mature oocytes retrieved (P=0.2026). In conclusion, the dose of hCG administration can significantly affect the intraovarian artery blood flow and the development of follicles and oocytes in an IVF-ET program.
The dynamic response and failure mode of light-weight steel columns under blast loads were studied in this paper by using nonlinear finite element analysis (FEA) software ANSYS/ LS-DYNA, aiming to ...develop the degree and modes of the excessive plastic deformation during failures of the columns under diverse parameters. The damaged columns with initial blast-induced deformation may evidently influence vertical stability of light-weight steel frame structures. During the numerical simulation, the element of three dimensional solid SOLID164 was used, and the strain rate effect on material strength was included in the material model with Plastic-Kinematic (MAT-03). The main parameters included in the analysis were boundary conditions, scaled distances of explosions, and the vertical compressive load ratios applied on tops of the columns. The results showed that the column with both two fixed ends was the most beneficial to resist blast shock wave, the horizontal displacement at the middle span of the columns were obviously decreasing as increasing of the scaled distances of the explosion, and the axial compression ratio only significantly influenced the column with a sliding end. The failure modes of the developed columns may be summarized as bending failure, direct shear failure, and bending shear combination failure.
In order to improve the energy efficiency and achieve the purpose of energy saving ad pollutant emission reductions, a model of solar combined cooling heating and power (CCHP) system integrated with ...energy storage is presented. The indices of prime energy consumption, environment and economy are established and formed as a comprehensive evaluation index using the judgment matrix method. A two-stage optimal planning and design method is applied to optimize the capacity design and operation strategy of CCHP system. The simulation results demonstrate that the comprehensive performances of the solar CCHP system in prime energy consumption and pollutant emission are better than that of the separation production.
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