麻黄细辛附子汤对肾阳虚外感小鼠及正常小鼠的效-毒作用研究

目的研究麻黄细辛附子汤(MXF)干预肾阳虚外感小鼠的药效作用及其对正常小鼠的毒性作用差异,并考察其效-毒作用机制。方法BABL/C雄性小鼠随机分为正常组、正常毒性低、中、高剂量组;肾阳虚外感模型组;肾阳虚外感低、中、高剂量组,连续灌胃给药6 d,记录体重、肛温等药理指标并观察小鼠的一般体征,检测生化指标、炎症因子。结果药效实验中,与正常组小鼠相比,肾阳虚外感模型组小鼠生化指标肌酸激酶(CK)、肌酸激酶-同工酶(CK-MB)、羟丁酸脱氢酶(α-HBDH)、乳酸盐脱氢酶(LDH)、丙氨酸氨基转移酶(ALT)、天冬氨酸转移酶(AST)、碱性磷酸酶(ALP)、尿素(urea)含量明显升高(P<0.05),炎症因子白介素-6(IL-6)、单核细胞去化蛋白(MCP-1)、肿瘤坏死因子-α(TNF-α)、白介素-10(IL-10)、干扰素-γ(INF-γ)以及白介素12(IL-12p70)含量升高明显(P<0.05)。经给药治疗后,各给药组CK、ALT、urea等生化指标含量较模型组有所回调,各给药组IL-6、IL-10、IFN-γ等炎症因子含量较模型组有不同程度的回调;毒性研究中,各给药组生化指标CK、urea、半胱氨酸(CYS-C)的含量较正常组显著升高(P<0.05),炎症因子白介素-10(IL-10)含量明显上升、白介素-12(IL-12p70)含量明显下降(P<0.05)。结论经MXF给药治疗后,肾阳虚外感给药组小鼠的一些生化指标均有不同程度的回调,MXF可通过调节IL-6、IL-10、IFN-γ、MCP-1、肿瘤坏死因子-α(TNF-α)等炎症因子改善机体的炎症反应;而正常小鼠给予不同剂量的MXF后心脏、肝脏和肾脏功能出现失调,机体通过细胞转移、打破免疫应答的平衡,从而使正常小鼠出现炎症反应。     

Diffusion MRI changes in the anterior subventricular zone following chemoradiation in glioblastoma with posterior ventricular involvement

Journal of Neuro-Oncology - There is growing evidence that the subventricular zone (SVZ) plays a key role in glioblastoma (GBM) tumorigenesis. However, little is known regarding how the SVZ, which...     

GPER-induced signaling is essential for the survival of breast cancer stem cells

G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER⁻/PR⁺ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs.