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Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson’s disease

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Translational Neurodegeneration 2019年第1期8卷 63-76页

作者： Zhi Dong Zhou Thevapriya Selvaratnam Ji Chao Tristan Lee Yin Xia Chao Eng-King Tan department of Research National Neuroscience Institute11 Jalan Tan Tock SengSingapore 308433Singapore department of neurology Singapore General HospitalOutram RoadSingapore 169608Singapore Signature Research Program in Neuroscience and Behavioural Disorders Duke-NUS Medical School Singapore8 College RoadSingaporeSingapore

Parkinson’s disease(PD)is the most common neurodegenerative movement disorder,which is characterized by the progressive loss of dopaminergic neurons in the Substantia Nigra pars compacta concomitant with Lewy body formation in affected brain *** detailed pathogenic mechanisms underlying the selective loss of dopaminergic neurons in PD are unclear,and no drugs or treatments have been developed to alleviate progressive dopaminergic neuron degeneration in ***,the formation ofα-synuclein-positive protein aggregates in Lewy body has been identified as a common pathological feature of PD,possibly stemming from the consequence of protein misfolding and dysfunctional *** is the mechanism for maintaining protein homeostasis via modulation of protein translation,enhancement of chaperone capacity and the prompt clearance of misfolded protein by the ubiquitin proteasome system and *** protein translation and impaired capacities of chaperone or protein degradation can disturb proteostasis processes,leading to pathological protein aggregation and neurodegeneration in *** recent years,multiple molecular targets in the modulation of protein translation vital to proteostasis and dopaminergic neuron degeneration have been *** potential pathophysiological and therapeutic significance of these molecular targets to neurodegeneration in PD is highlighted.

关键词： Molecular targets Neuron degeneration Parkinson’s disease Protein aggregation Protein translation Proteostasis

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The relationship between ischemic stroke and weather conditions in Duzce, Turkey

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World Journal of Emergency Medicine 2015年第3期6卷 207-211页

作者： Harun Gunes Hayati Kandis Ayhan Saritas Suber Dikici Ramazan Buyukkaya department of Emergency Medicine Duzce University School of Medicine department of neurology Duzce University School of Medicine department of Radiology Duzce University School of Medicine

BACKGROUND: Weather conditions are thought to increase the risk of stroke occurrence. But their mechanism has not yet been clarified. We investigated possible relationships between ischemic stroke and weather conditions including atmospheric pressure, temperature, relative humidity, and wind ***: One hundred and twenty-eight patients with ischemic stroke who had been admitted to our hospital between January 1 and December 31, 2010 were enrolled in this study. We investigated the relationship between daily cases and weather conditions the same day or 1, 2, and 3 days before ***: A negative correlation was found between maximum wind speed and daily cases 3 days before stroke. As the relationship between daily cases and changes of weather conditions in consecutive days was evaluated, a negative correlation was found between daily cases and change of atmospheric pressure in the last 24 ***: The maximum wind speed 3 days before stroke and change of atmospheric pressure in the last 24 hours were found to increase the cases of ischemic stroke. We recommend that individuals at risk of ischemic stroke should pay more attention to preventive measures, especially on days with low maximum wind speed, on subsequent 3 days, and on days with low atmospheric pressure in the last 24 hours.

关键词： Weather conditions Ischemic stroke Turkey

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Biochanin A,as the Lrg1/TGF-β/Smad2 pathway blockade,attenuates blood-brain barrier damage after cerebral ischemiareperfusion by modulating leukocyte migration patterns

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BIOCELL 2023年第8期47卷 1869-1883页

作者： LONGSHENG FU JINFANG HU FENG SHAO YAOQI WU WEI BAI MINGJIN JIANG HAO CHEN LIHUA CHEN YANNI LV department of Pharmacy The First Affiliated Hospital of Nanchang UniversityNanchang330006China Key Laboratory of Modern Preparation of TCM Ministry of EducationJiangxi University of Traditional Chinese MedicineNanchang330006China Translational Medicine Institute of Jiangxi The First Affiliated Hospital of Nanchang UniversityNanchang330006China neurology department The First Affiliated Hospital of Nanchang UniversityNanchang330006China

Background:Biochanin A is an excellent dietary isoflavone that has the concomitant function of both medicine and *** attenuation function of biochanin A on blood-brain barrier(BBB)damage induced by cerebral ischemia-reperfusion remains ***:C57BL/6 mice were subjected to 1 h middle cerebral artery occlusion(MCAO)followed by 24 h *** infarct volume of the brain was stained by TTC,while leakage of the brain was quantitatively stained by Evans blue,and the neurologic deficit score was ***-induced morphologic changes were observed via immunofluorescence staining,and rolling and adhering leukocytes in venules were observed via two-photon imaging,while the inner fluorescein isothiocyanate-albumin of venules were compared with those of surrounding interstitial area through venular albumin ***:The attenuation effect of biochanin A on tight junction injury was compared in ischemia-reperfusion mice or conventional knockdown of leucine-richα2-glycoprotein 1(Lrg1)*** A could ameliorate BBB injury in mice with cerebral ischemiareperfusion in a dose-dependent manner by strengthening the immunostaining volume of occludin,claudin-5,and zonula *** amoeba morphologic changes of microglial combined with the elevated expression of Lrg1 could be relieved under the treatment of biochanin *** A played a countervailing role on the rolling leukocytes in the vessel,while the leakage of blood vessels was *** A diminished its functions to further improved attenuation for tight junction injury on conventional Lrg1-knockout mice,as well as the inhibition effects on TGF-β1,and the phosphorylation of suppressor of mothers against decapentaplegic 2(Smad2)/Smad2 via western blot ***:Biochanin A could alleviate tight junction injury induced by cerebral ischemiareperfusion and blocked the Lrg1/TGF-β/Smad2 pathway to modulate leukocyte migration patterns.

关键词： Biochanin A Blockade Leukocyte migration Blood-brain barrier damage Ischemia-reperfusion Lrg1

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Inhibition of NLRP3 inflammasomes reduced blood brain barrier damage by DHA during early acute cerebralischemia

Inhibition of NLRP3 inflammasomes reduced blood brain barrie...

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中国解剖学会2021年年会

作者： Xinli Wang E Lv Jian Li Meng Pang Yanqiang Wang Weifang Medical University department of neurology Ⅱ The Affiliated Hospital of Weifang Medical University

The aim of this study was to explore the neuroprotective effect and mechanism of DHA on cerebral ischemia injury and blood-brain barrier (BBB) *** focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO).BBB permeability was assessed with the leaking amount of Evans Blue and the expression of occludin and ZO-1.

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The relativity of the activity change of tissue-type plasminogen activator and type 1 plasminogen activator inhibitor in patients with cerebral infarction and defect of nerve function

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中国临床康复 2003年第1期7卷 134-134页

作者：杜小平张东杨期东曹贵方郑艳珍唐健 department of neurology Xiangya HospitalCentral South Uiversity

AIM:To explore the dynamic changes of the activity of tissue type plasminogen activator (t PA) and type 1 plasminogen activator inhibitor (PAI 1)and its clinical significance by observing the activity of t PA and PAI 1 in patients in acute and recovery phases of arteriosclerotic cerebral ***:Testing the activity of plasma t PA and PAI 1 of 91 patients with arteriosclerotic cerebral infarction and 80 healthy old ages by Chromgenic substrate methods and controlling ***:The activity of t PA in acute and recovery stage of arteriosclerotic cerebral infarction patients were apparently lower than that of control and the activity of PAI 1 were higher than that of *** of cerebral infarction was negatively related to the activity of t PA and positively related to the activity of PAI 1. CONCLUSION:The plasma fibrinolytic activities of the acute and recovery stage patients with arteriosclerotic cerebral infarction declined.

关键词：脑梗死血浆组织型纤维溶酶原激活物 PAI-1 t-PA 神经功能缺损

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Chronic serotonin syndrome:A retrospective study

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World Journal of Psychiatry 2021年第4期11卷 124-132页

作者： Sanjay Prakash Chaturbhuj Rathore Kaushik Rana Diptangshu Roychowdhury Deepali Lodha department of neurology Smt.B.K.Shah Medical Institute and Research CentreSumandeep VdyapeethVadodara 391760India department of Psychiatry Smt.B.K.Shah Medical Institute and Research CentreSumandeep VdyapeethVadodara 391760India department of Medicine Smt.B.K.Shah Medical Institute and Research CentreSumandeep VdyapeethVadodara 391760India

BACKGROUND Serotonin syndrome(SS)is an underdiagnosed drug-induced clinical syndrome resulting from the excess intrasynaptic concentration of *** limited information is available about chronic *** To evaluate the epidemiological,clinical,and other aspects of the insidious onset *** We retrospectively evaluated 14 consecutive adult patients(>18 years)who had complaints for more than 6 wk at the time of consultation and met the Hunter criteria for *** The mean age was 41.1 years(range:21-61 years),with a male preponderance(64%).Although tremors were observed in all patients,this was a presenting complaint in only 43%of *** body pain,insomnia,and restlessness were common presenting features(50%each).Other common clinical features were stiffness of the limbs(43%),diaphoresis(43%),gait disturbances(36%),bowel disturbances(36%),dizziness(29%),sexual dysfunctions(21%),incoordination(14%),and fatigue(14%)The mean duration of symptoms before the diagnosis of SS was 13.5±5.8 wk(range:6-24 wk).Amitriptyline was the most common drug(n=6,43%),followed by tramadol(n=5,36%)and sodium valproate(n=5,36%).All patients received cyproheptadine,a 5-hydroxytryptamine2A antagonist,as treatment and noted an excellent response CONCLUSION This study represents the largest study on chronic *** suggest that patients receiving serotonergic drugs should be physically examined for the presence of SS upon the development of new symptoms.

关键词： Serotonin syndrome Serotonin toxicity Cyproheptadine Serotonergic agents Serotonin Clonus

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Clinical features of AMPAR2 antibody-positive autoimmune encephalitis with gastrointestinal hemorrhage: a case report

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Journal of Translational Neuroscience 2023年第3期8卷 28-32页

作者： Yi Bao Zhixuan Chen Yong Liu Jun Chen department of neurology Taihe Hospital of ShiyanAffiliated Hospital of Hubei University of MedicineShiyan 442000China

Objective:To describe the clinical features of autoimmune encephalitis complicated with gastrointestinal ***:The clinical data of one patient whose initial symptom was mental abnormality were collected and the related examinations,such as cerebrospinal fluid and magnetic resonance imaging (MRI),were ***: Cerebrospinal fluid examination found that anti-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor(AMPAR)2 antibody was strongly positive,although the patient had repeated gastrointestinal hemorrhage but,after hormone combined with immunoglobulin treatment,the symptoms gradual-ly ***:Mental disorders are not all psychosis,and autoimmune encephalitis should not be *** is very important to perform anti-AMPAR encephalitis antibody test;accurate diagnosis and timely treatment can improve the prognosis.

关键词： gastrointestinal hemorrhage autoim-mune encephalitis α-Amino-3-hydroxy-5-methylisox-azole-4-propionic acid subtype glutamate receptor(AM-PAR) cerebrospinal fluid

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Alternation of plasma c-type natriuretic peptide in cerebral infarction

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中国临床康复 2003年第1期7卷 138-138页

作者：赵文凤宋利春 department of neurology People's Hospital of Daqing City

AIM:To investigate the effects of c type natriuretic peptide (CNP) on cerebral ***:Plasma levels of CNP were concomitantly measured by radioimmunoassay in 30 patients with cerebral infarction and in 30 normal ***:Plasma levels of CNP were increased significantly in the acute stage of cerebral infarction than those in the normal controls(P< 0.01) and levels in the moderate and serious cases were lower than those in the slight cases(P< 0.01).CONCLUSION:In cerebral infarction the increase of plasma CNP was in accordance with the severity of the disease .CNP in the pathophysiology of acute cerebral ischemia had a deleterious effect on the evolution of cerebral infarction.

关键词：脑梗死血浆 C型利钠肽

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Study on Peripheral T Lymphocyte Immunity and L-Dopamine in Patients with Parkinson's Disease

Study on Peripheral T Lymphocyte Immunity and L-Dopamine in ...

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2018年浙江省神经病学学术年会

作者：胡正祥宋玮钕卢晓东周梦露邵佳辉 department of neurology The Affiliated Hospital of Hangzhou Normal University department of Obstetrics Hangzhou Obstetrics & Gynecology Hospital

The clinical efficacy of T-cell immune function and L-dopamine(L-DOPA) in patients with Parkinson’s disease(PD) has been studied. 60 patients(included in the experimental group) with PD who were hospitalized in the outpatient or inpatient ward of the neurology department of The Affiliated Hospital of Hangzhou Normal University from July 2015 to March 2017 were selected. The experimental group was then categorized into groups according to the age of the patients, the severity of the disease, the level of cognition, and the treatment of L-DOPA. The control group(30 cases) was from the healthy population of the check-up center at The Affiliated Hospital of Hangzhou Normal University. The peripheral blood T-lymphocyte subsets of 60 patients with PD were measured by direct immunofluorescence staining of flow cytometry. Thirty healthy people were compared. At the same time, the correlation analysis was carried out on patients with different diseases, different accompanying symptoms, and whether L-DOPA was used before and after treatment. The results of the study show that the levels of CD4+, CD8+, CD3+, and CD4+/CD8+ peripheral blood in PD patients were significantly lower than those in the control group(P<0.05). It was found that the levels of CD4+, CD8+, CD3+, and CD4+/CD8+ decreased with age. The CD4+, CD8+, CD3+, and CD4+/CD8+ in patients with high PD levels were more significant than those with low PD levels(P<0.05). The levels of CD4+, CD8+, CD3+, and CD4+/CD8+ in the dementia group were significantly lower than those in the non-dementia group(P<0.05). The levels of CD4+, CD8+, CD3+, and CD4+/CD8+ in PD patients treated with L-DOPA were higher than those of PD patients without L-DOPA treatment(P<0.05). In conclusion, the immune function of T-cells in patients suffering from PD is low, and the immune function of T-cells in patients with severe disease is lower. Therefore, it is of certain significance to further study the pathophysiological mechanism of PD.

关键词： Parkinson’s Disease t-lymphocyte subset L-dopamine immune function

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Influence of adjuvant levetiracetam therapy on serum nerve cytokines and apoptosis molecules in patients with refractory partial epileptic seizure

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Journal of Hainan Medical University 2017年第11期23卷 145-149页

作者： Xiang-Hong Tan Zhi-Bin Song Hui Wang Qin Wang Jian-Li He neurology department Xiaolan Hospital Affiliated to Southern Medical UniversityZhongshan CityGuangdong Province528415

Objective:To study the influence of adjuvant levetiracetam therapy on serum nerve cytokines and apoptosis molecules in patients with refractory partial epileptic ***: A total of 92 patients with refractory partial epileptic seizure treated in our hospital between July 2012 and January 2016 were divided into control group (n=46) and observation group (n=46) according to random number table. Patients in the control group were treated with routine treatment, those in observation group were treated with routine treatment plus adjuvant levetiracetam therapy, and the treatment lasted for 20 weeks. Serum contents of nerve cytokines and apoptosis molecules were compared between two groups before and after ***:Before treatment, differences in serum levels of nerve injury indexes, nerve protection indexes, monoamine neurotransmitters and apoptosis molecules were not statistically significant between two groups of patients. After treatment, serum contents of nerve injury indexes S-100β, GFAP, NSE and MBP in both groups were significantly lower than those before treatment, contents of nerve protection indexes BDNF and IGF-1 were significantly higher than those before treatment, contents of monoamine neurotransmitters DA, 5-HT and NE were significantly higher than those before treatment, contents of apoptosis molecules Bcl-2, Fas and FasL were significantly lower than those before treatment, and the changes in contents of above indexes in observation group were larger than those in control ***:The adjunctive therapy of levetiracetam can reduce the nerve injury in patients with refractory partial epileptic seizure and exert active cerebral protective effect.

关键词： Refractory epilepsy Levetiracetam Nerve cytokine Apoptosis molecule

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