The conformation change of Bcl-2 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in SGC7901 human gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>Arsenic trioxide has been established as a first-line agent for treating acute promyelocytic leukemia. Experimental data suggest that arsenic trioxide also can have a potential use as chemotherapeutic agent for other malignancies. The precise mechanisms of action of arsenic trioxide have though not been elucidated. As the role of Bcl-2 in arsenic trioxide-mediated cell apoptosis and conformation change of Bcl-2 in response to arsenic trioxide treatment has not been studied. The aim of the present study was to determine whether conformation change of Bcl-2 is involved in the action of arsenic trioxide.</p> <p>Methods</p> <p>Human gastric cancer SGC7901 cells were exposed to different concentrations of arsenic trioxide. Proliferation was measured by using the Kit-8 cell counting assay. Analysis of nuclear morphology was observed by DAPI staining. The apoptosis rates of cells treated with arsenic trioxide were analyzed by flow cytometry using Annexin V-FITC staining. The conformation change of Bcl-2 and Bax activation were detected by immunostaining and Western blot analysis. Total expression of Bcl-2 and Bax were examined by Western blot analysis.</p> <p>Results</p> <p>Arsenic trioxide inhibited the growth of human gastric cancer SGC7901 cells and induced apoptosis. There were two Bcl-2 phenotypes coexisting in SGC7901 cells and the Bcl-2 cytoprotective phenotype could change into a cytodestructive phenotype following conformational change of Bcl-2, triggered by arsenic trioxide exposure. Bax activation might also be involved in arsenic trioxide-induced Bcl-2 conformational change. Arsenic trioxide did not change levels of total Bcl-2 expression, but up-regulated total Bax expression for the treatment time ranging from 3 to 24 hours.</p> <p>Conclusion</p> <p>Arsenic trioxide induces apoptosis through induction of Bcl-2 conformational change, Bax activation and up-regulation of total Bax expression rather than affecting total Bcl-2 expression in human gastric cancer SGC7901 cells. The conformational change of Bcl-2 may be a novel described mechanism of arsenic trioxide-induced apoptosis in cancer cells.</p

Linezolid Inhibited Synthesis of ATP in Mitochondria: Based on GC-MS Metabolomics and HPLC Method

Linezolid has been widely used in serious infections for its effective inhibiting effect against multidrug-resistant gram-positive pathogens. However, linezolid caused severe adverse reactions, such as thrombocytopenia, anaemia, optic neuropathy, and near-fatal serotonin syndrome. In order to investigate the toxicity of linezolid, twenty-four Sprague-Dawley rats were randomly divided into: control group (n=7), low-group (n=8), and high-group (n=9). The rats of low-group and high-group were given by gavage with linezolid 60 and 120 mg/kg/day for 7 days, respectively. The serum concentration of linezolid was determined by high performance liquid chromatography (HPLC); blood metabolic change was analyzed by gas chromatography-mass spectrometer (GC-MS). Adenosine triphosphate (ATP) concentration in HepG2-C3A after being cultured with linezolid was determined by HPLC. The results showed that there were six metabolites and nine metabolites had statistical differences in low-group and high-group (P<0.05). The trimethyl phosphate was the most significant indicator in those changed metabolites. Except for d-glucose which was slightly increased in low-group, octadecanoic acid, cholest-5-ene, hexadecanoic acid, α-linolenic acid, eicosapentaenoic acid, 9,12-Octadecadienoic acid, and docosahexaenoic acid were all decreased in low-group and high-group. ATP concentration was decreased in HepG2-C3A after cultured with linezolid. In conclusion, the toxicity of linezolid is related to its serum concentration. Linezolid may inhibit the synthesis of ATP and fatty acid

Prediction of asphaltene precipitation during CO2 injection

Aimed at the possible phenomenon of asphaltene precipitation during CO2 injection, the equation of state established by Anderko was introduced to describe the phase behavior of precipitated asphaltene because of its strong polarity. The fugacity of the precipitated asphaltene component was derived and a calculation model of gas-liquid-asphaltene equilibrium was constructed. After matching of PVT experimental data from a reservoir, the model was used to calculate the volume of precipitated asphaltene during CO2 injection. The precipitation model suggests that for a constant injection pressure, the asphaltene precipitation first increases and then decreases as CO2 increases with the asphaltene precipitation reaching a maximum when the gas phase occurs in the system. When the CO2 mole percentage of the CO2-oil system is constant, the precipitated asphaltene reaches a maximum at the saturation pressure. 摘 要: 注入CO2提高原油采收率过程中可能出现沥青质固相沉淀。鉴于沉淀沥青质的强极性，采用Anderko建立的缔合混合物状态方程描述沥青质的相行为，并由此推导沉淀沥青质组分的逸度计算公式，建立注气过程中气-液-沥青质三相相平衡数值计算模型。以某油田实际原油为例，利用模型计算了CO2注入过程中沥青质沉淀量，结果与实验数据相近，表明沥青质沉淀预测模型具有一定的准确性。在此基础上，预测了注气过程中沥青质沉淀变化规律：注入压力一定的情况下，沥青质沉淀量随着注入CO2量增加呈现先增加后减小的趋势，当CO2-原油体系中出现气相时，沥青质沉淀量达到最大；当CO2-原油体系中CO2物质的量分数一定时，在泡点压力附近沥青质沉淀量达到最大。 Key words: CO2 flooding, asphaltene precipitation, fugacity calculation, phase behavior simulation, phase equilibrium calculatio

Evaluation of short-term streamflow prediction methods in Urban river basins

Efficient and accurate streamflow predictions are important for urban water management. Data-driven models, especially neural network (NN) models can predict streamflow fast, while the results are uncertain in some complex river systems. Physically based models can reveal the underlying physics, but it is relatively slow and computationally costly. This work focuses on evaluating the reliability of three NN models (artificial neural networks (ANN), long short-term memory networks (LSTM), adaptive neuro-fuzzy inference system (ANFIS)) and one physically based model (SOBEK) in terms of efficiency and accuracy for average and peak streamflow simulation. All the models are applied for a tidal river and a mountainous river in Shenzhen. The results show that, the ANN model calculates fastest since the hidden layer's structure is simple. The LSTM model is reliable in average streamflow simulation in tidal river with the lowest bias while the ANFIS model has the best accuracy for peak streamflow simulation. Furthermore, the SOBEK model shows reliability in simulating average and peak streamflow in mountainous river due to its ability to capture uneven spatial rainfall in the area. Overall, the results indicate that the LSTM model can be a helpful supplementary to physically based models in streamflow simulation of complex urban river systems, by giving fast streamflow predictions with usually acceptable accuracy. Our results can provide helpful information for hydrological engineers in the application of flooding early warning and emergency preparedness in the context of flooding risk management.</p

MOESM1 of Increased Th17 cells and IL-17A exist in patients with B cell acute lymphoblastic leukemia and promote proliferation and resistance to daunorubicin through activation of Akt signaling

Additional file 1: Table S1. The sequences of the primers used for real-time qPCR

Musashi-2 Silencing Exerts Potent Activity against Acute Myeloid Leukemia and Enhances Chemosensitivity to Daunorubicin

<div><p>RNA-binding protein Musashi-2 (Msi2) is known to play a critical role in leukemogenesis and contributes to poor clinical prognosis in acute myeloid leukemia (AML). However, the effect of Msi2 silencing on treatment for AML still remains poorly understood. In this study, we used lentivirus-mediated RNA interference targeting Msi2 to investigate the resulting changes in cellular processes and the underlying mechanisms in AML cell lines as well as primary AML cells isolated from AML patients. We found that Msi2 was highly expressed in AML cells, and its depletion inhibited Ki-67 expression and resulted in decreased in vitro and in vivo proliferation. Msi2 silencing induced cell cycle arrest in G0/G1 phase, with decreased Cyclin D1 and increased p21 expression. Msi2 silencing induced apoptosis through down-regulation of Bcl-2 expression and up-regulation of Bax expression. Suppression of Akt, Erk1/2 and p38 phosphorylation also contributed to apoptosis mediated by Msi2 silencing. Finally, Msi2 silencing in AML cells also enhanced their chemosensitivity to daunorubicin. Conclusively, our data suggest that Msi2 is a promising target for gene therapy to optimize conventional chemotherapeutics in AML treatment.</p></div