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Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

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Neural Regeneration Research 2025年第1期20卷 265-276页

作者： Yao Yuan Lingqi Yu Xudong Zhuang Dongjing Wen Jin He Jingmei Hong Jiayu Xie Shengan Ling Xiaoyue Du Wenfeng Chen Xinrui Wang institute of Life Sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate(fujian Maternity and Child Health Hospital) FuzhouFujian ProvinceChina Medical Research Center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology and institute of Neurology of The First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause *** located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： ATP1A1 Atpα bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-ATPase point mutation seizures sodium pump

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The compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one alleviates neuroinflammation and cognitive impairment in a mouse model of Alzheimer's disease

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Neural Regeneration Research 2025年第11期20卷 3330-3344页

作者： Xueyan Liu Wei Wu Xuejuan Li Chengyan Wang Ke Chai Fanru Yuan Huijuan Zheng Yuxing Yao Chenlu Li Zu-Cheng Ye Daijun Zha Department of Medicinal Chemistry School of PharmacyFujian Medical UniversityFuzhouFujian ProvinceChina fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative diseases School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina institute of Laboratory Animal Center Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurosurgery Neurosurgery Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhouFujian ProvinceChina Department of Hyperbaric Oxygen National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouFujian ProvinceChina

Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug *** this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced *** results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein ***,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by *** the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β astrocyte cognitive impairment D30 dendritic spines galectin-3 microglia neuroinflammation neuron

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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration Research 2025年第1期20卷 67-81页

作者： Yubo Wang Tingli Yuan Tianjie Lyu Ling Zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Shanghai Engineering Research Center of Stem Cells Translational Medicine ShanghaiChina National Center for Healthcare Quality Management in Neurological diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Chinese institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in cerebrovascular disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for Neurological diseases BeijingChina

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger ***,in particular,bears a high burden of stroke *** recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its *** review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and ***,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell ***,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient *** cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

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Evaluation of the relative risk of stroke in patients with hypertension using cerebrovascular hemodynamic accumulative score

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Frontiers of Medicine 2007年第3期1卷 274-278页

作者： HUANG Jiuyi WANG Guiqing GUO Jiping CAO Yifeng WANG Yan YANG Yongju YU Xuehai Shanghai institute of cerebrovascular disease Control Shanghai 201318China

The relative risk(RR)of stroke in patients with hypertension was evaluated by using synthetic index of cerebrovascular hemodynamics.A total of 7,371 patients with hypertension with ages i40 years were selected from a population-based cohort study of the risk factors for *** data on the baseline investigation of risk factors,the determination of cerebrovascular hemodynamic parameters(CVHP),and stroke follow-up were *** RR of stroke in patients with hypertension was evaluated by CVHP *** analysis indicated that hypertension,complicated by other risk factors,had significant statistical association with the onset of *** for stroke when hypertension complicated with decrease of hemodynamic scores,heart disease,cigarette smoking and alcohol consumption were 4.93(95%CI,3.26–7.45),1.90(95%CI,1.36–2.66),1.99(95%CI,1.42–2.79)and 1.73(95%CI,1.19–2.53)*** multivariate analysis,hemodynamic score,age,sex,cigarette smoking,family history of stroke and systolic blood pressure were selected by the Cox regression for inclusion in the final *** them,the RR of hemodynamic score was *** analysis of doseresponse relationships indicated that when the hemodynamic scores in patients with hypertension were lower than 75 points,the RR of stroke at 75,60,45,30 and 15 points were 2.85,4.43,4.54,5.40 and 9.88,*** risk of stroke in patients with hypertension is closely asso ciated with hemodynamic impairment and the hemodynamic score may be used for quantitative evaluation of relative risks of stroke.

关键词： hypertension stroke hemodynamic processes cohort studies

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Treadmill exercise exerts a synergistic effect with bone marrow mesenchymal stem cell-derived exosomes on neuronal apoptosis and synaptic-axonal remodeling

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Neural Regeneration Research 2023年第6期18卷 1293-1299页

作者： Xin-Hong Jiang Hang-Feng Li Man-Li Chen Yi-Xian Zhang Hong-Bin Chen Rong-Hua Chen Ying-Chun Xiao Nan Liu Department of Rehabilitation Fujian Medical University Union HospitalFuzhouFujian ProvinceChina fujian institute of cerebrovascular disease FuzhouFujian ProvinceChina Key Laboratory of Brain Aging and Neurodegenerative diseases Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology Longyan First Hospital of Fujian Medical UniversityLongyanFujian ProvinceChina Department of Neurology Fujian Medical University Union HospitalFuzhouFujian ProvinceChina

Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ***,whether there is a synergistic effect between the two remains *** this study,we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 *** models were perfused with bone marrow mesenchymal stem cell-derived exosomes(MSC-exos)via the tail vein and underwent 14 successive days of treadmill *** assessment,histopathology,and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume,evident synaptic formation and axonal regeneration,and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos *** effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment ***,further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal *** findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment,which may be related to activation of the JNK1/c-Jun signaling *** study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease.

关键词： apoptosis axonal regeneration c-Jun exosomes functional remodeling ischemic stroke JNK1 mesenchymal stem cells synaptic formation treadmill exercise

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Evaluation of the hepatoprotective and antioxidant activities of Rubus parvifolius L.

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2011年第2期12卷 135-142页

作者： Jie GAO Cui-rong SUN Jie-hong YANG Jian-mei SHI Yue-guang DU Yu-yan ZHANG Jin-hui LI Hai-tong WAN Department of Chemistry Zhejiang University Hangzhou 310027 China institute of Cardio-cerebrovascular disease Zhejiang Chinese Medical University Hangzhou 310053 China

The hepatoprotective and antioxidant activities of the n-butanol extract of Rubus parvifolius L. （RPL）, a widely used medicinal plant, were evaluated. Results demonstrated that RPL extract possessed pronounced hepatoprotective effects against carbon tetrachloride （CCI4）-induced hepatic injury in mice, which was at least partially attributed to its strong antioxidant capacity. Treatment with RPL extract markedly attenuated the increases in serum alanine ami- notransferase （ALT） and aspartate aminotransferase （AST） levels caused by CCI4 intoxication. It also significantly prevented the decrease in superoxide dismutase （SOD） activity and the increase in malondialdehyde （MDA） content of liver tissue. Meanwhile, histopathological changes of hepatic damage were also remarkably ameliorated. Phytochemical analysis based on high-performance liquid chromatography/tandem mass spectrometry （HPLC-MS/MS） revealed the presence of various phenolic compounds, including caffeic acid conjugates, ellagic acid glycosides, and flavonol glycosides, which might be responsible for the hepatoprotective and antioxidant activities of RPL.

关键词： Rubus parvifofius L. High-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) Hepatoprotective activity Antioxidant activity

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Integrative Medicine on Optimizing Clopidogrel and Aspirin Therapy

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Chinese Journal of Integrative Medicine 2019年第5期25卷 395-400页

作者： CHEN Hui Department of Internal Medicine Fujian Provincial Cardiovascular Disease Institutethe Shengli Clinical Medical College of Fujian Medical UniversityFuzhou(350001)China

This article reviews the available published data on optimizing clopidogrel and aspirin therapy using translational and integrative medicine. Translational and evidence-based medical studies show that the CYP2 C19 gene mutation(CYP2 C19*2 and CYP2 C19*3) could affect > 50% of the Chinese population, and that this mutation is closely associated with clopidogrel resistance and an increased risk of major adverse cardiovascular events, particularly stent thrombosis in patients following percutaneous coronary intervention(PCI). Adjusted-dose warfarin and aspirin reduce stroke in patients with atrial fibrillation(AF), and warfarin is substantially more efficacious than aspirin. However, a poor compliance is a big problem in warfarin use especially in China. The genetic variants of vitamin K expoxide reductase might account for the universally lower warfarin dosage used in Chinese population. The available evidence indicates that the integrating mainstream treatments(e.g., clopidogrel, CYP2 C19 genotyping) and non-mainstream medicines [e.g., Chinese medicines,Naoxintong Capsule(脑心通胶囊, NXT)] to treat CYP2 C19 gene mutation patients following PCI can be *** combined NXT and the adjusted-dose warfarin was equally effective in elderly patients with non-valvular AF in prevention of ischemic stroke.

关键词： integrative medicine clopidogrel aspirin optimizing therapy Chinese medicine

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AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

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Neural Regeneration Research 2025年第1期20卷 253-264页

作者： Zhengwei Hu Jing Yang Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan Mao Zhongxian Zhang Mibo Tang Changhe Shi Yuming Xu Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Academy of Medical Sciences of Zhengzhou University ZhengzhouHenan ProvinceChina NHC Key Laboratory of Prevention and treatment of cerebrovascular diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Henan Key Laboratory of cerebrovascular diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina institute of Neuroscience Zhengzhou UniversityZhengzhouHenan ProvinceChina Sino-British Research Centre for Molecular Oncology National Centre for International Research in Cell and Gene TherapySchool of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Department of Gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control *** this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s *** used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse *** overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated *** also alleviated the concentration of microglia and astrocytes around *** APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin *** of HSP70 and HSP40,which have functional relevance to CHIP,were also *** nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of *** research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 ***,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

关键词： adeno-associated virus Alzheimer’s disease APP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy

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Targeting synaptic pathology in Alzheimer’s disease

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Zoological Research 2024年第4期45卷 875-876页

作者： Jing Cao Yun-Wu Zhang fujian Provincial Key Laboratory of Neurodegenerative disease and Aging Research Institute of NeuroscienceSchool of MedicineXiamen UniversityXiamenFujian 361102China

Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by memory and cognitive *** two primary pathological hallmarks of AD include the accumulation ofβ-amyloid(Aβ)plaques and formation of neurofibrillary tangles(NFTs)composed predominantly of hyperphosphorylated tau protein(Zhang et al.,2023).Moreover,synaptic dysfunction is considered another crucial factor in AD pathogenesis and is closely associated with cognitive ***,synaptic damage,loss,and dysfunction manifest earlier than the pathological features of Aβplaques and NFTs(Knopman et al.,2021).Therefore,understanding the mechanisms underlying synaptic dysfunction in AD is vital for providing insights into disease mechanisms and developing novel therapeutic strategies.

关键词： Alzheimer Aβ tau

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Coronary artery aneurysm combined with myocardial bridge:A case report

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World Journal of Clinical Cases 2021年第16期9卷 3996-4000页

作者： Zhen Ye Xian-Feng Dong Yuan-Ming Yan Yu-Kun Luo Department of Cardiology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina fujian institute of Coronary Artery disease Fuzhou 350001Fujian ProvinceChina fujian Heart Medical Center Fuzhou 350001Fujian ProvinceChina

BACKGROUND Coronary artery aneurysm combined with myocardial bridge is a very rare clinical *** prognosis of this clinical situation is not yet *** SUMMARY A coronary artery aneurysm and myocardial bridge in the same segment of the coronary artery were found in a 54-year-old female patient who underwent coronary angiography and intravascular ultrasound *** conservative treatment,the patient was discharged from the hospital smoothly,and she was in good condition during 5 mo of *** Coronary artery aneurysm combined with myocardial bridge seems to have a good prognosis,but due to the rarity of this clinical situation,further research and follow-up are needed.

关键词： Coronary artery aneurysm Myocardial bridge Coronary angiography Intravascular ultrasound Chest pain Case report

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