G蛋白偶联受体激酶6参与天芪平颤颗粒预防帕金森病异动症的发生

目的:研究天芪平颤颗粒对左旋多巴诱发的异动症大鼠行为学及G蛋白偶联受体激酶6(G protein-coupled receptor kinase 6,GRK6)表达的影响。方法:通过6-羟基多巴(6-hydroxydopa,6-OHDA)立体定向注射至大鼠前脑内侧束的方法成功建立帕金森病(Parkinson disease,PD)模型。25只模型大鼠随机分为5组,每组各5只。PD组:腹腔注射0.2%维生素C溶液;左旋多巴组:腹腔注射左旋多巴甲酯和苄丝肼;小、中、大剂量天芪平颤颗粒组:在给予左旋多巴甲酯和苄丝肼基础上分别加用相应剂量的天芪平颤颗粒。另设假手术组(n=5)为对照。连续给药29d后,评估不同剂量天芪平颤颗粒对PD模型大鼠行为学的影响,并用免疫组织化学法和蛋白质印迹法检测大鼠纹状体区GRK6蛋白的表达情况。结果:左旋多巴等长期使用后,PD模型大鼠出现异常不自主运动(abnormal involuntary movement,AIM),且AIM评分随治疗时间的延长逐渐增加;损伤侧纹状体区GRK6蛋白表达减少。天芪平颤颗粒能改善PD模型大鼠的AIM评分,增加GRK6蛋白的表达。免疫组织化学法结果显示,高、中剂量天芪平颤颗粒组的GRK6蛋白的表达较左旋多巴组增加(P<0.05);蛋白质印迹法结果显示,中剂量天芪平颤颗粒组的GRK6蛋白的表达较左旋多巴组增加(P<0.01)。结论:天芪平颤颗粒可能通过增加纹状体区GRK6的表达,改善PD模型大鼠的AIM评分,减少PD大鼠异动症的发生。

Relationship of GPRC6A and PKCzeta expression levels in prostate cancer lesions with cell proliferation and EMT

Objective: To study the relationship of GPRC6A and PKCzeta expression levels in prostate cancer lesions with cell proliferation and epithelial-mesenchymal transition (EMT). Methods:Patients with prostate cancer and patients with benign prostatic hyperplasia who received surgical resection in Huizhou Third People's Hospital between June 2014 and March 2017 were selected, right amount of prostate cancer tissue and tissue adjacent to carcinoma was collected from patients with prostate cancer, and the expression of GPRC6A, PKCzeta, cell proliferation genes and EMT genes in lesions were detected. Results: GPRC6A, Survivin, SRSF1, Bcl-xl, N-cadherin and Vimentin expression in prostate cancer lesions and adjacent lesions were significantly higher than those in benign prostatic hyperplasia lesions while PKCzeta, Caspase-3, Caspase-9, Apaf-1, E-cadherin and CK5/6 expression were significantly lower than those in benign prostatic hyperplasia lesions;Survivin, SRSF1 and Bcl-xl expression in prostate cancer lesions with lower PKCzeta expression were significantly higher than those in prostate cancer lesions with higher PKCzeta expression while Caspase-3, Caspase-9 and Apaf-1 expression were significantly lower than those in prostate cancer lesions with higher PKCzeta expression;E-cadherin and CK5/6 expression in prostate cancer lesions with lower GPRC6A expression were significantly higher than those in prostate cancer lesions with higher GPRC6A expression while N-cadherin and Vimentin expression were significantly lower than those in prostate cancer lesions with higher GPRC6A expression. Conclusion:Highly expressed GPRC6A and lowly expressed PKCzeta in prostate cancer lesions can promote cell EMT and proliferation respectively.

PAFR/Stat3 axis maintains the symbiotic ecosystem between tumor and stroma to facilitate tumor malignancy

Stroma surrounding the tumor cells plays crucial roles for tumor progression.However,little is known about the factors that maintain the symbiosis between stroma and tumor cells.In this study,we found that the transcriptional regulator-signal transducer and activator of transcription 3(Stat3)was frequently activated in cancer-associated fibroblasts(CAFs),which was a potent facilitator of tumor malignancy,and formed forward feedback loop with platelet-activating factor receptor(PAFR)both in CAFs and tumor cells.Importantly,PAFR/Stat3 axis connected intercellular signaling crosstalk between CAFs and cancer cells and drove mutual transcriptional programming of these two types of cells.Two central Stat3-related cytokine signaling molecules-interleukin 6(IL-6)and IL-11 played the critical role in the process of PAFR/Stat3 axis-mediated communication between tumor and CAFs.Pharmacological inhibition of PAFR and Stat3 activities effectively reduced tumor progression using CAFs/tumor co-culture xenograft model.Our study reveals that PAFR/Stat3 axis enhances the interaction between tumor and its associated stroma and suggests that targeting this axis can be an effective therapeutic strategy against tumor malignancy.