Inhibition effects of paeonol on mice bearing EMT6 breast cancer through inducing rumor cell apoptosis

Paeonol, a phenolic component from the root bark of Paeonia moutan, has been identified to possess antitumor effects on mice bearing EMT6 breast cancer in our previous studies. However, the underlying mechanisms remain unknown. In the present study the molecular mechanisms of paeonol were further investigated in EMT6 mice model. The results showed that treatment of mice with 175 and 350 mg/kg/day of paeonol significantly inhibited the growth of the EMT6 tumor in mice, and induced tumor cell apoptosis which were demonstrated by light microscopy after hematoxylin and eosin staining and apoptosis analysis by flow cytometry. In addition, compared with the control group, paeonol increased the number of tumor cells in G0/G1 phase but decreased the number of cells in S and G2/M phase. Paeonol treatment (350 mg/kg body weight) also resulted in a decrease of Bcl-2 and an increase in Bax and caspase-3 expressions, which were demonstrated by immunohistochemical and western blot analysis. These results indicate that the antitumor effects of paeonol might be associated with arresting tumor cells in the G0/G1 phase, inducing cell apoptosis and regulation of the expression of Bcl-2, Bax and activation of caspase-3

The dependence of the IR-radio correlation on the metallicity

We have compiled a sample of 26 metal-poor galaxies with 12 + log(O/H) < 8.1 with both infrared continuum and 1.4 GHz radio continuum data. By comparing to galaxies at higher metallicity, we have investigated the dependence on the metallicity of the IR-radio relationship at 24 um, 70 um, 100 um and 160 um bands as well as the integrated FIR luminosity. It is found that metal-poor galaxies have on average lower qIR than metal-rich ones with larger offsets at longer IR wavelengths, from -0.06 dex in q24um to -0.6 dex in q160um. The qIR of all galaxies as a whole at 160 um show positive trends with the metallicity and IR-to-FUV ratio, and negative trends with the IR color, while those at lower IR wavelengths show weaker correlations. We proposed a mechanism that invokes combined effects of low obscured-SFR/total-SFR fraction and warm dust temperature at low metallicity to interpret the above behavior of qIR, with the former reducing the IR radiation and the latter further reducing the IR emission at longer IR wavelength. Other mechanisms that are related to the radio emission including the enhanced magnetic field strength and increased thermal radio contribution are unable to reconcile the IR-wavelength-dependent differences of qIR between metal-poor and metal- rich galaxies. In contrast to qIR, the mean total-SFR/radio ratio of metal-poor galaxies is the same as the metal-rich one, indicating the 1.4 GHz radio emission is still an effective tracer of SFRs at low metallicity.Comment: 25 pages, 11 figures, 4 tables. ApJ in pres

Antitumor effect of salidroside on mice bearing HepA hepatocellular carcinoma

Salidroside, a phenylpropanoid glycoside extracted from Rhodiola rosea L., has antiproliferative effects on tumour cells in mice. However it’s antitumor mechanism remains largely unknown. In this study, 4 groups of mice bearing hepatocarcinoma cells were given treatment with vehicle alone, cyclophosphamide (25 mg/kg, i.p.) and salidroside, either 100 or 200 mg/kg (p.o.) for 14 days. The morphology of tumour specimens was analysed by transmission electron microscopy. Apoptotic cells in sections of mouse tumour tissue were analysed using an in situ apoptosis kit. The expression of Bcl-2, Bax and caspase 3 mRNA were examined with RT-PCR. The results showed that the tumour weights in groups 100 or 200 mg/kg/day of salidroside were reduced significantly (45.34 and 52.48% respectively), compared to vehicle groups. Salidroside increased apoptotic cells index, e.g. in 200 mg/kg group, it was four times higher compared to the control group. Even more, treatment with salidroside decreased Bcl-2 mRNA expression and increased Bax and caspase 3 mRNA expressions. These indicated that the antitumor mechanism of salidroside may induce tumour cell apoptosis in mice by triggering the mitochondrial-dependent pathway and activation of caspase 3

Antitumor and apoptosis induction effects of paeonol on mice bearing EMT6 breast carcinoma

Paeonol is a major phenolic micromolecular component of Moutan cortex Radicis, a traditional Chinese Medicine. It has shown antitumor effects in previous studies; however, the underlying mechanisms remain unknown. This study investigated the mechanism by giving treatments of placebo, cyclophosphamide, paeonol of 150 and 300 mg/kg to 4 groups of mice bearing EMT6 breast cancer. Apoptosis in tumor cells were confirmed by morphology analysis, including hematoxylin, eosin staining and TUNEL staining. The results showed that the weight of EMT6 breast tumor was significantly reduced in the groups treated with both 150 and 300 mg/kg of paeonol. Immunohistochemical and Western blot results showed that the expression of Bcl-2 was down-regulated while the expression of Bax, caspase 8 and caspase 3 was up-regulated respectively. These results suggest that paeonol exhibits antitumor effects and the mechanism of the inhibition is via induction of apoptosis, regulation of Bcl-2 and Bax expression, and activation of caspase 8 and caspase 3

A novel 4-(1,3,4-thiadiazole-2-ylthio)pyrimidine derivative inhibits cell proliferation by suppressing the MEK/ERK signaling pathway in colorectal cancer

Colorectal cancer (CRC) is one of the most common types of malignant cancers worldwide. Although molecularly targeted therapies have significantly improved treatment outcomes, most of these target inhibitors are resistant. Novel inhibitors as potential anti-cancer drug candidates are still needed to be discovered. Therefore, in the present study, we synthesized a novel 4-(1,3,4-thiadiazole-2-ylthio)pyrimidine derivative (compound 4) using fragment- and structure-based techniques and then investigated the anti-cancer effect and underlying mechanism of anti-CRC. The results revealed that compound 4 significantly inhibited HCT116 cell proliferation with IC50 values of 8.04 ± 0.94 µmol L–1 after 48 h and 5.52 ± 0.42 µmol L–1 after 72 h, respectively. Compound 4 also inhibited colony formation, migration, and invasion of HCT116 cells in a dose-dependent manner, as well as inducing cell apoptosis and arresting the cell cycle in the G2/M phase. In addition, compound 4 was able to inhibit the activation of the MEK/ERK signaling in HCT116 cells. And compound 4 yielded the same effects as the MEK inhibitor U0126 on cell apoptosis and MEK/ERK-related proteins. These findings suggested that compound 4 inhibited cell proliferation and growth, and induced cell apoptosis, indicating its use as e a novel and potent anti-cancer agent against CRC via the MEK/ERK signaling pathway

Effects of contusion load on cervical spinal cord:A finite element study

Injury of cervical spine is a common injury of locomotor system usually accompanied by spinal cord injury, however the injury mechanism of contusion load to the spinal cord is not clear. This study aims to investigate its injury mechanism associated with the contusion load, with different extents of spinal cord compression. A finite element model of cervical spinal cord was established and two scenarios of contusion injury loading conditions, i.e. back-to-front and front-to-back loads, were adopted. Four different compression displacements were applied to the middle section of the cervical spinal cord. The distributions of von Mises stress in middle transverse cross section were obtained from the finite element analysis. For the back-to-front loading scenario, the stress concentration was found in the area at and near the central canal and the damage may lead to the central canal syndrome from biomechanical point of view. With the front-to-back load, the maximum von Mises stress located in central canal area of gray matter when subject to 10% compression, whilst it appeared at the anterior horn when the compression increased. For the white matter, the maximum von Mises stress appeared in the area of the anterior funiculus. This leads to complicated symptoms given rise by damage to multiple locations in the cervical spinal cord. The illustrative results demonstrated the need of considering different loading scenarios in understanding the damage mechanisms of the cervical spinal cord, particularly when the loading conditions were given rise by different pathophysiological causes

Design Optimization of a Disc Brake Based on a Multi-Objective Optimization Algorithm and Analytic Hierarchy Process Method

Multiple optimization objectives and the Pareto set often arise from engineering structural optimization. Normalization methods (such as the weighting method) have the disadvantage that the weighted value is not set by the decision maker but the designer and is greatly influenced by the opinion of the designer. On this basis, in this paper a non-dominated sorting genetic algorithm - analytic hierarchy process (NSGA-AHP) method is proposed for decision making and analysis of the Pareto solution set of the multiple-objective optimization in a structural optimal model. In addition, illustrated by the example of a disc brake, a multiple-objective optimization model for a disc brake has been here developed. Besides, the NSGA-AHP method is adopted for the analysis optimization. The research results show that the NSGA-AHP method can be utilized to select the Pareto solution set in an effective way and that this method is effective in solving a multiple-objective problem in the structural optimization design