下调基因PTTG1对人胶质瘤细胞SHG44增殖、凋亡、迁移和侵袭能力的影响

背景与目的:研究表明垂体瘤转化基因1(pituitary tumor-transforming gene 1,PTTG1)在多种癌症中高表达。该研究旨在探讨其对胶质瘤细胞SHG44增殖、凋亡、迁移和侵袭能力的影响。方法:用PTTG1 siRNA干扰胶质瘤细胞SHG44的基因表达,通过实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RTFQ-PCR)和蛋白质印迹法(Western blot)分别在mRNA和蛋白质水平上评估PTTG1沉默效率,进一步检测其对SHG44细胞增殖、凋亡、迁移和侵袭能力的影响。结果:沉默PTTG1基因表达可以显著抑制SHG44细胞增殖(P<0.05)、迁移(P<0.01)和侵袭(P<0.001)能力,增加细胞凋亡(P<0.05)。结论:下调PTTG1的表达可以降低神经胶质瘤的恶化程度,有望成为临床胶质瘤治疗的新靶点。福建省自然科学基金(2016D019);;\n福建省卫计委医学创新项目(2016-CXB-12

SNX14 deficiency-induced defective axonal mitochondrial transport in Purkinje cells underlies cerebellar ataxia and can be reversed by valproate

共济失调是一类以运动协调性紊乱为主要特征的神经系统症状，临床表现包括步态不稳、丧失平衡、吞咽困难、眼球运动异常、肌张力受损等。厦门大学医学院神经科学研究所王鑫教授团队首次从轴突线粒体运输这一全新视角揭示了一类遗传性共济失调的发病机制，并发现抗癫痫药--丙戊酸大幅度减缓模型小鼠的疾病进程，具有较强的转化应用价值，有望为共济失调提供新的治疗手段。 该研究工作由王鑫教授指导完成，厦门大学医学院助理教授张洪峰和博士生洪育娟共同完成主要实验工作。Loss-of-function mutations in SNX14 cause autosomal recessive spinocerebellar ataxia 20, which is a form of early-onset cerebellar ataxia that lacks molecular mechanisms and mouse models. We generated Snx14-deficient mouse models and observed severe motor deficits and cell-autonomous Purkinje cell degeneration. SNX14 deficiency disrupted microtubule organization and mitochondrial transport in axons by destabilizing the microtubule-severing enzyme spastin, which is implicated in dominant hereditary spastic paraplegia with cerebellar ataxia, and compromised axonal integrity and mitochondrial function. Axonal transport disruption and mitochondrial dysfunction further led to degeneration of high-energy-demanding Purkinje cells, which resulted in the pathogenesis of cerebellar ataxia. The antiepileptic drug valproate ameliorated motor deficits and cerebellar degeneration in Snx14-deficient mice via the restoration of mitochondrial transport and function in Purkinje cells. Our study revealed an unprecedented role for SNX14-dependent axonal transport in cerebellar ataxia, demonstrated the convergence of SNX14 and spastin in mitochondrial dysfunction, and suggests valproate as a potential therapeutic agent.We thank Tim Huang for helpful discussion, Wei Mo for sharing mouse lines, Li Zhong for sharing reagents, Aidong Han, Luming Yao, Caiming Wu, Mingxia Zhu, Qingfeng Liu, Lin Zhu, Shuo Zhang, Haiping Zheng, and Changchuan Xie for technical assistance, and Cui Li for providing bioinformatics software. We also thank Novogene Co., Ltd. and PTM Biolab Co., Ltd. for technical assistance in the transcriptomic and proteomic analyses, respectively. 厦门大学医学院许华曦、赵颖俊、张云武、杜丹教授在研究过程中给予大力帮助和支持。本研究工作得到国家重点研发计划项目、国家自然科学基金、福建省自然科学基金、厦门大学校长基金的资助和支持

Trisomy 21-induced Dysregulation of Microglial Homeostasis in Alzheimer’s Brains is Mediated by USP25

阿尔茨海默病（Alzheimer’s disease, AD）是一种最为常见的与记忆、认知能力退化相关的渐进性神经退行性疾病。唐氏综合征（Down’s syndrome, DS）是早发型阿尔茨海默病的一个重要风险因素，作为最常见的智力障碍遗传疾病，厦门大学医学院神经科学研究所王鑫教授团队揭示了治疗阿尔茨海默病和唐氏综合征新的治疗靶点，并且在小鼠模型上利用USP25小分子抑制剂成功地改善了阿尔茨海默病小鼠的认知功能，缓解了神经退行性病变的病理进程。该研究工作由王鑫教授指导完成，厦门大学医学院助理教授郑秋阳和博士生李桂林完成主要实验工作，王世华、朱琳、高月、邓青芳、张洪峰、张丽珊、吴美玲、狄安洁参与了部分研究工作。厦门大学医学院许华曦、赵颖俊和孙灏教授在研究过程中给予大力帮助和支持，清华大学董晨教授提供了Usp25基因敲除小鼠，厦门大学附属妇女儿童医院周裕林教授和郑良楷博士帮助收集了脑组织样品。Down syndrome (DS), caused by trisomy of chromosome 21, is the most significant risk factor for early-onset Alzheimer’s disease (AD); however, underlying mechanisms linking DS and AD remain unclear. Here, we show that triplication of homologous chromosome 21 genes aggravates neuroinflammation in combined murine DS-AD models. Overexpression of USP25, a deubiquitinating enzyme encoded by chromosome 21, results in microglial activation and induces synaptic and cognitive deficits, whereas genetic ablation of Usp25 reduces neuroinflammation and rescues synaptic and cognitive function in 5×FAD mice. Mechanistically, USP25 deficiency attenuates microglia-mediated proinflammatory cytokine overproduction and synapse elimination. Inhibition of USP25 reestablishes homeostatic microglial signatures and restores synaptic and cognitive function in 5×FAD mice. In summary, we demonstrate an unprecedented role for trisomy 21 and pathogenic effects associated with microgliosis as a result of the increased USP25 dosage, implicating USP25 as a therapeutic target for neuroinflammation in DS and AD.This work was supported by the National Natural Science Foundation of China (31871077, 81822014, and 81571176 to X.W.; 81701130 to Q.Z.), the National Key R&D Program of China (2016YFC1305900 to X.W.), the Natural Science Foundation of Fujian Province of China (2017J06021 to X.W.), the Fundamental Research Funds for the Chinese Central Universities (20720150061 to X.W.), and the BrightFocus Foundation (A2018214F to Yingjun Zhao). 该研究工作得到国家重点研发计划项目、国家自然科学基金、福建省自然科学基金、厦门大学校长基金的资助和支持

Medical care oriented visual surveillance of patient falls in the hospital

目的：提出一种面向医院患者的视觉监控跌倒检测算法，解决患者由于意外跌倒不能被及时发现的问题，为医护人员快速处理患者跌倒等异常行为提供必要的技术保障。方法：首先，基于深度神经网络模型检测监控图像中人体关节点（如肩部、肘部、腕部、胯部、膝关节等）在图像中的位置，再根据亲和度向量场模型提取人体骨架，最后计算患者躯干、腿部与地面的夹角作为判别性特征，判断监控区域内是否有患者出现意外跌倒。结果：实验结果表明，本文所提算法在实际的医院监护环境中的处理速度高达25帧/s，检测准确率高达96%。结论：该方法能够实时、准确地提取医院环境下患者的行为特征，并针对意外跌倒情况发出警报，为医护人员监测患者跌倒等异常行为提供更准确、方便的计算机辅助医疗护理方法。</p

Medical care oriented visual surveillance of patient falls in the hospital

目的：提出一种面向医院患者的视觉监控跌倒检测算法，解决患者由于意外跌倒不能被及时发现的问题，为医护人员快速处理患者跌倒等异常行为提供必要的技术保障。方法：首先，基于深度神经网络模型检测监控图像中人体关节点（如肩部、肘部、腕部、胯部、膝关节等）在图像中的位置，再根据亲和度向量场模型提取人体骨架，最后计算患者躯干、腿部与地面的夹角作为判别性特征，判断监控区域内是否有患者出现意外跌倒。结果：实验结果表明，本文所提算法在实际的医院监护环境中的处理速度高达25帧/s，检测准确率高达96%。结论：该方法能够实时、准确地提取医院环境下患者的行为特征，并针对意外跌倒情况发出警报，为医护人员监测患者跌倒等异常行为提供更准确、方便的计算机辅助医疗护理方法。</p