RESUMO
Intracerebral hemorrhage (ICH) can induce intensive oxidative stress, neuroinflammation, and brain cell apoptosis. However, conventional methods for ICH treatment have many disadvantages. There is an urgent need for alternative, effective therapies with minimal side effects. Pharmacodynamics experiment, molecular docking, network pharmacology, and metabolomics were adopted to investigate the treatment and its mechanism of Jingfang Granules (JFG) in ICH. In this study, we investigated the therapeutic effects of JFG on ICH using behavioral, brain water content and Magnetic resonance imaging experiments. However, the key active component and targets of JFG remain unknown. Here we verified that JFG was beneficial to improve brain injury after ICH. A network pharmacology analysis revealed that the anti-inflammatory effect of JFG is predominantly mediated by its activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway through Luteolin, (+)-Anomalin and Phaseol and their targeting of AKT1, tumor necrosis factorα (TNF-α), and interleukin-1ß (IL-1ß). Molecular docking analyses revealed an average affinity of -8.633 kcal/mol, indicating a binding strength of less than -5 kcal/mol. Metabolomic analysis showed that JFG exerted its therapeutic effect on ICH by regulating metabolic pathways, such as the metabolism of taurine and hypotaurine, biosynthesis of valine, leucine, and isoleucine. In conclusion, we demonstrated that JFG attenuated neuroinflammation and BBB injury subsequent to ICH by activating the PI3K/Akt signaling pathway.
Assuntos
Barreira Hematoencefálica , Hemorragia Cerebral , Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/metabolismo , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Masculino , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos , Ratos , Anti-Inflamatórios/farmacologia , Farmacologia em Rede , Modelos Animais de DoençasRESUMO
Objective To evaluate the relationship between the risk of breast cancer and abortions among nulliparous women. Methods Searched the data of Cochrane Library and PubMed before June 2014 to identify potentially studies which involved the relationship between the risk of breast cancer and abortions among nulliparous women. Data was extracted by two independent authors from each study. STATA software was used for statistical analysis. Calculated the pooled RR and 95% CI as the assessment of the link between abortions and breast cancer in fixed effects models. Results 13 studies were included. The study showed the RR and 95%CI of the relationship between the risk of breast cancer and abortions was 0. 98[0. 89,1. 08],P>0. 05 in nulliparous women, and the number of abortions was not associated with the risk of breast cancer. The RR and 95%CI of the relationship between the risk of breast cancer and induced abortions or spontaneous abor-tions were 0. 96[0. 88,1. 04],1. 01[0. 88,1. 14], respectively. Conclusion There is no correlation between breast cancer and abortions a-mong the nulliparous women, and the risk of breast cancer would not increas as the number of abortions increase.
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Objective To investigate the effect of HIF-2a silencing by transfection of siRNA into MG-63 cells un-der hypoxia. Methods HIF-2αexpression level in MG-63 cells under hypoxia was determined by Western Blot. Small in-terfering RNA (siRNA) was used to construct MG-63/siHIF-2α(siHIF-2α)cells and control MG-63/scramble (NC) cells. The expression levels of HIF-2α, Vascular endothelial growth factor (VEGF), p-Erk/ErK and Mcl-1 in MG-63, NC and si-HIF-2αcells was determined by Western Blot. NC and siHIF-2αcells were cultured under hypoxia. Cell viability was as-sessed by MTT assay. Migration was identified by scratch migration assay. Tumor formation was identified by clone formation assay. Nude mouse subcutaneous xenograft model was used to investigate tumor development in vivo. Results Hypoxia im-proved HIF-2αexpression in MG-63 cells in a time-dependent manner (F=2 037.412,P<0.001). HIF-2αexpression un-der hypoxia in siHIF-2αcells was lower than that in NC cells (P<0.01). Cell viability of siHIF-2αcells under hypoxia for 12 h and 24 h were lower than that in NC cells (P<0.05 or P<0.01). The relative width of scratch in siHIF-2αgroup under hypoxia for 12 h and 24 h were larger than that in NC group (P<0.01 or P<0.01). When cell counts reach 1 000-5 000, the clone formation rates of siHIF-2αcells were lower than that in NC cells (P<0.05 or P<0.01). The expression of VEGF, p-Erk/Erk and Mcl-1 protein under hypoxia in siHIF-2αcells was lower than that in NC cells(P<0.01). Tumor sizes, weights and density of siHIF-2α group in nude mice were suppressed compared with those in NC group (P<0.01). Conclusion Blocking HIF-2αsignal pathway warrants its investigation as a potential strategy in osteosarcoma treatment.
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Objective To study the mechanism of high intensity ultrasound (HIU) on COX-2 mRNA expression and apoptosis in breast cancer cell line MDA-MB-231 cells.Methods Human breast cancer cells MDA-MB-231 in vitro were exposed in HIU (50 w/cm2).RT-PCR was performed to detect the level of COX-2 mRNA before and after exposure.The ultrastructural changes in apoptotic cells were examined by transmission electron microscopy.Results The relative level of COX-2 mRNA decreased gradually along with the increase of exposure time and apoptotic bodies in MDA-MB-231 cells considerably increased under electron microscope.When exposure time was increased to 30 seconds,a few cells died.Conclusion HIU promotes apoptosis of breast cancer MDA-MB-231 cells in a COX-2 mRNA depended way.
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Objective To study the reversal effect of tetrandrine (TET) on the multidrug resistance of Hep-2/ADM cell line and the possible mechanisms. Methods MTT method was used for the detection of the inhibitory effect of different concentrations of TET on the multidrug resistance of Hep-2/ADM cell line for selection of the non-toxicity concentration. MTT reduction assay was used to investigate the drug interaction of TET and vincristine (VCR) on HNE-1 (200) cell line. The reversal index (RI), accumulation and excretion of drug, and the apoptosis of Hep-2/ADM cell line were detected by flow cytometry. Results No toxicity to Hep-2/ADM cell line was found when TET concentration was lower than 1.5 ?g/ml. After interaction with TET (1.0 ?g/ml and 1.5 ?g/ml), RIs of VCR on Hep-2/ADM were 1.72 and 2.00 folds, respectively. TET at the concentration of 1.5 ?g/ml could increase the drug excretion and accumulation and also the apoptotic rate of VCR-induced Hep-2/ADM cell line. Conclusion TET can reverse the multidrug resistance of Hep-2/ADM cell line. The reversal effect may be related to the concentrations of TET. The possible mechanism may be that TET can increase the cell apoptosis of VCR-induced Hep-2/ADM cell line and can also increase the drug excretion and accumulation of the multidrug resistance cell line.