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991.
Fang Shen Xiang Xu Zhengquan Yu Haiying Li Haitao Shen Xiang Li Meifen Shen Gang Chen 《Journal of cerebral blood flow and metabolism》2021,41(3):530
RNA-binding protein fox-1 homolog 1 (Rbfox-1), an RNA-binding protein in neurons, is thought to be associated with many neurological diseases. To date, the mechanism on which Rbfox-1 worsens secondary cell death in ICH remains poorly understood. In this study, we aimed to explore the role of Rbfox-1 in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) and to identify its underlying mechanisms. We found that the expression of Rbfox-1 in neurons was significantly increased after ICH, which was accompanied by increases in the binding of Rbfox-1 to Ca2+/calmodulin-dependent protein kinase II (CaMKIIα) mRNA and the protein level of CaMKIIα. In addition, when exposed to exogenous upregulation or downregulation of Rbfox-1, the protein level of CaMKIIα showed a concomitant trend in brain tissue, which further suggested that CaMKIIα is a downstream-target protein of Rbfox-1. The upregulation of both proteins caused intracellular-Ca2+ overload and neuronal degeneration, which exacerbated brain damage. Furthermore, we found that Rbfox-1 promoted the expression of CaMKIIα via blocking the binding of micro-RNA-124 to CaMKIIα mRNA. Thus, Rbfox-1 is expected to be a promising therapeutic target for SBI after ICH. 相似文献
992.
Nolan A. Huck Janelle Siliezar-Doyle Elena S. Haight Ryosuke Ishida Thomas E. Forman Shaogen Wu Huaishuang Shen Yoshinori Takemura J. David Clark Vivianne L. Tawfik 《The Journal of neuroscience》2021,41(19):4349
Complex regional pain syndrome (CRPS) is a chronic pain disorder with a clear acute-to-chronic transition. Preclinical studies demonstrate that toll-like receptor 4 (TLR4), expressed by myeloid-lineage cells, astrocytes, and neurons, mediates a sex-dependent transition to chronic pain; however, evidence is lacking on which exact TLR4-expressing cells are responsible. We used complementary pharmacologic and transgenic approaches in mice to more specifically manipulate myeloid-lineage TLR4 and outline its contribution to the transition from acute-to-chronic CRPS based on three key variables: location (peripheral vs central), timing (prevention vs treatment), and sex (male vs female). We demonstrate that systemic TLR4 antagonism is more effective at improving chronic allodynia trajectory when administered at the time of injury (early) in the tibial fracture model of CRPS in both sexes. In order to clarify the contribution of myeloid-lineage cells peripherally (macrophages) or centrally (microglia), we rigorously characterize a novel spatiotemporal transgenic mouse line, Cx3CR1-CreERT2-eYFP;TLR4fl/fl (TLR4 cKO) to specifically knock out TLR4 only in microglia and no other myeloid-lineage cells. Using this transgenic mouse, we find that early TLR4 cKO results in profound improvement in chronic, but not acute, allodynia in males, with a significant but less robust effect in females. In contrast, late TLR4 cKO results in partial improvement in allodynia in both sexes, suggesting that downstream cellular or molecular TLR4-independent events may have already been triggered. Overall, we find that the contribution of TLR4 is time- and microglia-dependent in both sexes; however, females also rely on peripheral myeloid-lineage (or other TLR4 expressing) cells to trigger chronic pain.SIGNIFICANCE STATEMENT The contribution of myeloid cell TLR4 to sex-specific pain progression remains controversial. We used complementary pharmacologic and transgenic approaches to specifically manipulate TLR4 based on three key variables: location (peripheral vs central), timing (prevention vs treatment), and sex (male vs female). We discovered that microglial TLR4 contributes to early pain progression in males, and to a lesser extent in females. We further found that maintenance of chronic pain likely occurs through myeloid TLR4-independent mechanisms in both sexes. Together, we define a more nuanced contribution of this receptor to the acute-to-chronic pain transition in a mouse model of complex regional pain syndrome. 相似文献
993.
Several lines of evidence have indicated that rapamycin acts as an inhibitor of mammalian target of rapamycin (mTOR) and this produces therapeutic benefits as a treatment for Alzheimer’s disease (AD) by activating an autophagic pathway. Similarly, postoperative cognitive dysfunction (POCD) is a decline in cognitive function for weeks or months after surgery. POCD and AD are both characterized by cognitive dysfunction, and more importantly, are both related to aging. We therefore hypothesized that rapamycin may have a therapeutic effect to relieve POCD. Inhibition of mTOR induces autophagic effect, thereby leading to a slower aging process, so this would be a novel target for the prevention and treatment of POCD. 相似文献
994.
Dedong Yu Bing Fang Fang Wang Xudong Wang Wenbin Zhang Jiewen Dai Steve G.F. Shen 《Medical hypotheses》2013
In orthognathic surgery, many serious medical disputes and postsurgical dissatisfactions are not caused by the doctors’ reasons, but due to the patients’ psychological problems. These adverse events obsess not only surgeons, but also patients to a great extent. An effective method is expected to screen patients for orthognathic surgery. So far, most selecting approaches in orthognathic surgery are based on explicit cognition, which inevitably include the following faults: patients’ intentional concealment, uncertain errors, and imprecise subjective judgment from the doctors. However, these errors can be avoided by the tests based on implicit cognition, i.e., Implicit Association Test (IAT). Avoiding the faults of explicit cognition, IAT is an objective, quantitative, and easily applicable mental measurement method. We hypothesized that all the patients for orthognathic purpose should have an IAT screening before treatment. By IAT method, the right patients for orthognathic surgery can be picked out. As a result, postoperative dissatisfaction, medical dispute, and even violent conflict can be avoided to a great extent. To the best of our knowledge, there is no relevant report on the use of IAT as a tool to select the right orthognathic patients to avoid postsurgical dissatisfaction, medical disputes and violent conflict events. 相似文献
995.
Yi-Min Sun MD PhD Hui-Ling Yu MD Xin-Yue Zhou MD Wei-Xi Xiong MD Su-Shan Luo MD PhD Chen Chen MD PhD Feng-Tao Liu MD PhD Jue Zhao MD Yi-Lin Tang MD PhD Xiao-Niu Liang PhD Yu-Jie Yang PhD Bo Shen MD PhD Yan Shen MD PhD Wen-Bo Yu MD PhD Zheng-Tong Ding MD PhD Yu An PhD Jian-Jun Wu MD PhD Jian Wang MD PhD 《Movement disorders》2021,36(2):442-448
996.
Whitley W. Aamodt MD MPH Teresa Waligorska MSc Junchao Shen BS Thomas F. Tropea DO MPH MSTR Andrew Siderowf MD MSCE Daniel Weintraub MD Murray Grossman MD David Irwin MD MSTR David A. Wolk MD Sharon X. Xie PhD John Q. Trojanowski MD PhD Leslie M. Shaw PhD Alice S. Chen-Plotkin MD 《Movement disorders》2021,36(12):2945-2950
997.
目的评价机械取栓治疗不同类型基底动脉(BA)闭塞的疗效。方法回顾性分析2013年9月至2019年9月海军军医大学附属长海医院脑血管病中心连续收治的95例行机械取栓治疗的BA闭塞患者的临床资料。根据BA闭塞是否为串联病变,分为非串联病变组(67例)和串联病变组(28例)。比较两组血管成功再通(改良脑梗死溶栓分级2b~3级)的比例、90 d预后良好(改良Rankin量表评分为0~3分)的比例、术中挽救措施及不良事件发生率等的差异。结果与非串联病变组相比,串联病变组的年龄偏低(P=0.002),而男性(P=0.009)、有吸烟史(P=0.014)、缺血性卒中TOAST分型为大动脉粥样硬化型(P=0.001)以及存在一侧椎动脉发育不良(P=0.036)的比例更高。两组患者在术前及术后24 h的美国国立卫生院卒中量表评分、股动脉穿刺至BA再灌注时间、血管成功再通比例及90 d预后良好比例方面的差异均无统计学意义(均P>0.05)。串联病变组的发病至就诊时间(P=0.049)、发病至BA再灌注时间(P=0.046)均较非串联病变组延长,且术中挽救措施(包括单纯球囊扩张、急诊支架置入、静脉应用替罗非班)的使用比例均更高(均P<0.05)。两组在手术相关的不良事件及病死率方面的差异均无统计学意义(均P>0.05)。结论对于不同类型的BA闭塞患者,应用机械取栓治疗的临床结局及不良事件的发生率无明显差异,但该结论仍需进一步扩大样本量或进行随机对照试验加以证实。 相似文献
998.
999.
Fan Yang Xi Sun Jia Shen Li-ping Yu Jin-yi Liang Huan-qin Zheng Zhong-dao Wu 《Parasitology research》2013,112(3):1261-1272
rSj16, a recombined protein from Schistosoma japonicum, has been identified as an anti-inflammatory molecule. In this study, we demonstrated that rSj16 strongly suppressed the growth of murine myeloid leukemia WEHI-3B JCS cells in a dose- and time-dependent manner. rSj16 induced apoptosis by increasing the proportion of sub-G1 apoptotic cells as well as causing cell cycle arrest at the G0/G1 phase. The expressions of cyclin D1, D2, D3, and E, and Cdk 2, 4, and 6 genes in WEHI-3B JCS cells were significantly down-regulated at 24 h as measured by real-time PCR. Furthermore, apoptosis induced by rSj16 was confirmed by 4,6-diamidino-2-phenylindole nuclear staining assay and annexin V/propidium iodide double staining. A reduction of the mitochondrial membrane potential indicated an active involvement of mitochondria in the apoptosis process. rSj16 treatment induced an increase in the activity of caspase 3, 6, and 9, and expression of pro-apoptotic Bax. Meanwhile, the decreased expression of anti-apoptotic Bcl-2 was observed after rSj16 treatment. Taken together, our results implied that rSj16 can inhibit proliferation by inducing G0/G1 cell cycle arrest and apoptosis of murine myeloid leukemia cells via activation of the caspase-mediated mechanism by regulating the expression of Bcl-2 family. 相似文献
1000.
Wu Nan Huang Zhe Shen Yiqiu Park Jungkyu Phang Jason Makino Taro Gene Kim S. Cho Kyunghyun Heacock Laura Moy Linda Geras Krzysztof J. 《Journal of digital imaging》2021,34(6):1414-1423
Journal of Digital Imaging - Breast cancer is the most common cancer in women, and hundreds of thousands of unnecessary biopsies are done around the world at a tremendous cost. It is crucial to... 相似文献