|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Antagonism of Protease-Activated Receptor 4 Protects Against Traumatic Brain Injury by Suppressing Neuroinflammation via Inhibition of Tab2/NF-κB Signaling显示文摘Traumatic brain injury(TBI)triggers the activation of the endogenous coagulation mechanism,and a large amount of thrombin is released to curb uncontrollable bleeding through thrombin receptors,also known as protease-activated receptors(PARs).However,thrombin is one of the most critical factors in secondary brain injury.Thus,the PARs may be effective targets against hemorrhagic brain injury.Since the PAR1 antagonist has an increased bleeding risk in clinical practice,PAR4 blockade has been suggested as a more promising treatment.Here,we explored the expression pattern of PAR4 in the brain of mice after TBI,and explored the effect and possible mechanism of BMS-986120(BMS),a novel selective and reversible PAR4 antagonist on secondary brain injury.Treatment with BMS protected against TBI in mice.mRNA-seq analysis,Western blot,and qRT-PCR verification in vitro showed that BMS significantly inhibited thrombin-induced inflammation in astrocytes,and suggested that the Tab2/ERK/NF-κB signaling pathway plays a key role in this process.Our findings provide reliable evidence that blocking PAR4 is a safe and effective intervention for TBI,and suggest that BMS has a potential clinical application in the management of TBI. | Jianing Luo Xun Wu Haixiao Liu Wenxing Cui Wei Guo Kang Guo Hao Guo Kai Tao Fei Li Yingwu Shi Dayun Feng Hao Yan Guodong Gao Yan Qu | 2021 | Neuroscience Bulletin2021，37，2： | 5 |
| 2 | Salidroside Protects Against 6-Hydroxydopamine-Induced Cytotoxicity by Attenuating ER Stress显示文摘Parkinson's disease(PD) is a neurodegenerative disease characterized by a persistent decline of dopaminergic(DA) neurons in the substantia nigra pars compacta. Despite its frequency, effective therapeutic strategies that halt the neurodegenerative processes are lacking, reinforcing the need to better understand the molecular drivers of this disease. Importantly, increasing evidence suggests that the endoplasmic reticulum(ER)stress-induced unfolded protein response is likely involved in DA neuronal death. Salidroside, a major compound isolated from Rhodiola rosea L., possesses potent antioxidative stress properties and protects against DA neuronal death. However, the underlying mechanisms are not well understood. In the present study, we demonstrate that salidroside prevents 6-hydroxydopamine(6-OHDA)-induced cytotoxicity by attenuating ER stress. Furthermore, treatment of a DA neuronal cell line(SN4741) and primary cortical neurons with salidroside significantly reduced neurotoxin-induced increases in cytoplasmic reactive oxygen species and calcium, both of which cause ER stress, and cleaved caspase-12, which is responsible for ER stress-induced cell death. Together, these results suggest that salidroside protects SN4741 cells and primary cortical neurons from 6-OHDA-induced neurotoxicity by attenuating ER stress. This provides a rationale for the investigation of salidroside as a potential therapeutic agent in animal models of PD. | Kai Tao Bao Wang Dayun Feng Wei Zhang Fangfang Lu Juan Lai Lu Huang Tiejian Nie Qian Yang | 2016 | Neuroscience Bulletin2016，32，1： | 5 |
| 3 | Transcription Factors:Potential Cell Death Markers in Parkinson's Disease显示文摘Parkinson's disease(PD) is a neurodegenerative disease with a long preclinical phase. The continuous loss of dopaminergic(DA) neurons is one of the pathogenic hallmarks of PD. Diagnosis largely depends on clinical observation, but motor dysfunctions do not emerge until70%–80% of the nigrostriatal nerve terminals have been destroyed. Therefore, a biomarker that indicates the degeneration of DA neurons is urgently needed. Transcription factors are sequence-specific DNA-binding proteins that regulate RNA synthesis from a DNA template. The precise control of gene expression plays a critical role in the development, maintenance, and survival of cells,including DA neurons. Deficiency of certain transcription factors has been associated with DA neuron loss and PD. In this review, we focus on some transcription factors and discuss their structure, function, mechanisms of neuroprotection, and their potential for use as biomarkers indicating the degeneration of DA neurons. | Ronglin Wang Shaosong Yang Tiejian Nie Gang Zhu Dayun Feng Qian Yang | 2017 | Neuroscience Bulletin2017，33，5： | 4 |
| 4 | Acrolein Induces Systemic Coagulopathy via Autophagy-dependent Secretion of von Willebrand Factor in Mice after Traumatic Brain Injury显示文摘Traumatic brain injury(TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes,but the pathogenesis remains poorly understood.In this study,we aimed to investigate the causal role of acrolein,a typical lipid peroxidation product,in TBI-induced coagulopathy,and further explore the underlying molecular mechanisms.We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy.Using a controlled cortical impact mouse model,we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor(VWF).Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion.mRNA sequencing(mRNA-seq)and transcriptome analysis indicated that acrolein over-activated autophagy,and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway.In addition,we demonstrated that acrolein was produced in the perilesional cortex,affected endothelial cell integrity,and disrupted the blood-brain barrier.In conclusion,in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage,providing an alternative therapeutic target. | Wenxing Cui Xun Wu Dayun Feng Jianing Luo Yingwu Shi Wei Guo Haixiao Liu Qiang Wang Liang Wang Shunnan Ge Yan Qu | 2021 | Neuroscience Bulletin2021，37，8： | 3 |
| 5 | Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice显示文摘Clinical advances in the treatment of intracranial hemorrhage(ICH)are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury.Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases.Our results indicated a significant increase in the level of acrolein after ICH in mouse brain.In primary neurons,acrolein induced an increase in mitochondrial fragmentation,loss of mitochondrial membrane potential,generation of reactive oxidative species,and release of mitochondrial cytochrome c.Mechanistically,acrolein facilitated the translocation of dynaminrelated protein 1(Drpl)from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission.Further studies found that treatment with hydralazine(an acrolein scavenger)significantly reversed Drpl translocation and the morphological damage of mitochondria after ICH.In parallel,the neural apoptosis,brain edema,and neurological functional deficits induced by ICH were also remarkably alleviated.In conclusion,our results identify acrolein as an important contributor to the secondary brain injury following ICH.Meanwhile,we uncovered a novel mechanism by which Drpl-mediated mitochondrial oxidative damage is involved in acroleininduced brain injury. | Xun Wu Wenxing Cui Wei Guo Haixiao Liu Jianing Luo Lei Zhao Hao Guo Longlong Zheng Hao Bai Dayun Feng Yan Qu | 2020 | Neuroscience Bulletin2020，36，10： | 3 |
| 6 | Cytoplasm and cytoplasm-nucleus interactions affect agronomic traits in Japonica rice显示文摘 | Dayun Tao Feng Hu Jiangyi Yang | 2004 | Euphytica2004，135，： | 1 |
| 7 | Death after discharge:prognostic model of 1-year mortality in traumatic brain injury patients undergoing decompressive craniectomy显示文摘Background:Despite advances in decompressive craniectomy(DC)for the treatment of traumatic brain injury(TBI),these patients are at risk of having a poor long-term prognosis.The aim of this study was to predict 1-year mortality in TBI patients undergoing DC using logistic regression and random tree models.Methods:This was a retrospective analysis of TBI patients undergoing DC from January 1,2015,to April 25,2019.Patient demographic characteristics,biochemical tests,and intraoperative factors were collected.One-year mortality prognostic models were developed using multivariate logistic regression and random tree algorithms.The overall accuracy,sensitivity,specificity,and area under the receiver operating characteristic curves(AUCs)were used to evaluate model performance.Results:Of the 230 patients,70(30.4%)died within 1 year.Older age(OR,1.066;95%CI,1.045-1.087;P<0.001),higher Glasgow Coma Score(GCS)(OR,0.737;95%CI,0.660-0.824;P<0.001),higherD-dimer(OR,1.005;95%CI,1.001-1.009;P=0.015),coagulopathy(OR,2.965;95%CI,1.808-4.864;P<0.001),hypotension(OR,3.862;95%CI,2.176-6.855;P<0.001),and completely effaced basal cisterns(OR,3.766;95%CI,2.255-6.290;P<0.001)were independent predictors of 1-year mortality.Random forest demonstrated better performance for 1-year mortality prediction,which achieved an overall accuracy of 0.810,sensitivity of 0.833,specificity of 0.800,and AUC of 0.830 on the testing data compared to the logistic regression model.Conclusions:The random forest model showed relatively good predictive performance for 1-year mortality in TBI patients undergoing DC.Further external tests are required to verify our prognostic model. | Wenxing Cui Shunnan Ge Yingwu Shi Xun Wu Jianing Luo Haixiao Lui Gang Zhu Hao Guo Dayun Feng Yan Qu | 2022 | Chinese Neurosurgical Journal2022，8，1： | 0 |
| 8 | Dynamic Change of Matrix Stiffness Switches Astrocyte Phenotype in Three Dimensions显示文摘Background Damage to the central nervous system(CNS)usually leads to the activation of astrocytes,followed by glial scar formation.For years,glial scar has been thought as a major obstacle for successful axon regeneration.However,increasing evidence suggests a beneficial role for this scar tissue as part of the endogenous local immune regulation and repair process.Surprisingly,in contrast to scars in other tissues,glial scars(mainly consist of reactive astrocytes)in both rat cortex and spinal cord were recently found to be significantly softer than healthy CNS tissues.Naive astrocytes have been found to change their phenotype to reactive astrocytes and gradually into scar-forming astrocytes,upregulating the astrocyte marker glial fibrillary acidic protein(GFAP),vimentin,and inflammatory proteins in almost all known brain disorders.Such phenotype transformation process has been widely thought unidirectional or irreversible.However,recent research revealed the environment-dependent plasticity of astrocyte phenotypes,with reactive astrocytes could revert in retrograde to naive astrocytes in proper microenvironment.In consideration of the important roles of mechanical cues in CNS and the unique softening behavior of glial scars,it is of great interesting to study the effects of dynamic changes of matrix stiffness on astrocyte phenotypic switch.Materials&methods Primary astrocyes were isolated from the cortex of SpragueDawley(SD)rats at PI.After cultured for 2 weeks,astrocytes were encapsulated into a set of three-dimensional(3D)hybrid hydrogel system composed of type I collagen and alginate.Immunofluorescence and Western blot expression analysis were applied for characterizting cell responses to different and dynamically changed matrix stiffness.A molecular dynamics model was developed for simulation.Results&discussion In this work,we established an in-vitro model to study the effects of dynamic changes of matrix stiffness on astrocyte phenotypic switchings in 3D.To simulate native cellular environment,we fabricated a set of hybrid hydrogel system composed of type I collagen and alginate.The stiffness of the hybrid hydrogels was demonstrated to be dynamically changed by adding calcium chloride or sodium citrate to crosslink or decrosslink alginate,respectively.Using 3D culture models,we showed that the decrease of matrix stiffness could promote astrocyte activation,with upregulated GFAP and IL-1β.In addition,3D cultured astrocytes spread greater with decreasing matrix stiffness.Moreover,we surprisingly found that astrocyte phenotype could be switched by dynamically changing matrix stiffness.Specifically,matrix stiffening reverted the activation of astrocytes,whereas matrix softening induced astrocyte activation.We further demonstrated that matrix stiffness-induced astrocyte activation was mediated through cytoskeletal tension and YAP protein.To some extent,YAP inhibition enhanced the responses of astrocytes to matrix stiffness.These may guide researchersto re-examine the role of matrix stiffness in reactive astrogliosis in vivo,and inspire the development of novel therapeutic approach for reducing glial scar following injury,enabling axonal regrowth and improving functional recovery by exploiting the benefits of mechanobiology studies.Conclusions Taken together,our results clarify the effects of matrix stiffness and its dynamic changes on phenotypic swtich of astrocytes in three dimensions and reveal environmental factors that regulate astrocytic phenotype transformation process,which may provide potential therapeutic approach for CNS injury. | Yan Hu Jin Tian Jinbin Qiu Dayun Feng Guoyou Huang Feng Xu | 2019 | 医用生物力学2019，34，A01： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员