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Therapeutic advances in neural regeneration for Huntington’s disease

Neural Regeneration Research 2024年第9期19卷 1991-1997页

作者： Francesco D’Egidio Vanessa Castelli Giorgia Lombardozzi Fabrizio Ammannito Annamaria Cimini Michele d’Angelo department of Life Health and Environmental SciencesUniversity of L’AquilaL’AquilaItaly

Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic Medium Spiny Neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington’s disease. From a clinical point of view, Huntington’s disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington’s disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington’s disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington’s disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington’s disease condition highlighting how the replacement of lost cells would be a reasonable strategy to o

关键词： cell therapy exosomes extracellular vesicles Huntingtin Huntington’s disease medium spiny neurons neurodegenerative disease neurogenesis neuronal loss stem cells

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COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

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Journal of Sport and Health Science 2024年第1期13卷 99-107页

作者： Kyle A.Smith Tiffany M.Zúñiga Forrest L.Baker Helena Batatinha Charles R.Pedlar Shane C.Burgess Michael P.Gustafson Emmanuel Katsanis Richard J.Simpson School of Nutritional sciences and wellness The University of ArizonaTucsonAZ 85721USA department of Pediatrics The University of ArizonaTucsonAZ 85724USA Faculty of Sport Allied Health and Performance ScienceSt.Mary's UniversityTwickenham TW14SXUK Institute of Sport Exercise and Health University College LondonLondon WC1E 7HUUK department of Animal and Comparative Biomedical sciences The University of ArizonaTucsonAZ 85721USA The University of Arizona Cancer Center The University of ArizonaTucsonAZ 85719USA Laboratory Medicine and Pathology Mayo Clinic ArizonaPhoenixAZ 85054USA department of Immunobiology The University of ArizonaTucsonAZ 85724USA department of Medicine The University of ArizonaTucsonAZ 85724USA department of Pathology The University of ArizonaTucsonAZ 85724USA

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb ***:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 *** major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb ***:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded ***,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent *** groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid *** increased significantly during exercise only in the hybrid immunity ***:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

关键词： Anti-viral COVID-19 Exercise immunology SARS-CoV-2 T-Cells Vaccine

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Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

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Neural Regeneration Research 2024年第7期19卷 1584-1592页

作者： Jong Mi Park Masoud Rahmati Sang Chul Lee Jae Il Shin Yong Wook Kim department and Research Institute of Rehabilitation Medicine Yonsei University College of MedicineSeoulSouth Korea department of Physical Education and Sport sciences Faculty of Literature and Human SciencesLorestan UniversityKhoramabadIran department of Pediatrics Yonsei University College of MedicineSeoulSouth Korea

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease *** cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s *** stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of *** performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal *** searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,*** study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control *** use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the *** with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational *** the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a

关键词： animal animal experimentation mesenchymal stem cells models Parkinson’s disease stem cell transplantation

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DDAH1 promotes neurogenesis and neural repair in cerebral ischemia

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2097-2118页

作者： Qiming Gao Pinfei Ni Yilin Wang Peiyun Huo Xiaojie Zhang Sihan Wang Fuyao Xiao Yixuan Li Wei Feng Juntao Yuan Teng Zhang Qiang Li Boyu Fan Yuhao Kan Zhirui Li Yimiao Qi Junfei Xing Zhenghong Yang Haixiao Cheng Xinran Gao Xiaoyan Feng Ming Xue Yang Liu Yumin Luo Zhongbing Lu Yuming Zhao department of Pharmacology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Cerebrovascular Diseases Research Institute and department of Neurology Xuanwu Hospital of Capital Medical UniversityBeijing 100053China State Key Laboratory for Structural Chemistry of Unstable and Stable Species Institute of ChemistryChinese Academy of SciencesBeijing 100190China College of Life Science University of Chinese Academy of SciencesBeijing 100049China department of Laboratory Animal School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China department of Physiology and Pathophysiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Choline acetyltransferase(ChAT)-positive neurons in neural stem cell(NSC)niches can evoke adult neurogenesis(AN)and restore impaired brain function after injury,such as acute ischemic stroke(AIS).However,the relevant mechanism by which ChAT+neurons develop in NSC niches is poorly *** RNA-seq analysis revealed that dimethylarginine dimethylaminohydrolase 1(DDAH1),a hydrolase for asymmetric NG,NG-dimethylarginine(ADMA),regulated genes responsible for the synthesis and transportation of acetylcholine(ACh)(Chat,Slc5a7 and Slc18a3)after stroke *** dual-luciferase reporter assay further suggested that DDAH1 controlled the activity of ChAT,possibly through hypoxia-inducible factor 1α(HIF-1α).KC7F2,an inhibitor of HIF-1α,abolished DDAH1-induced ChAT expression and suppressed *** expected,DDAH1 was clinically elevated in the blood of AIS patients and was positively correlated with AIS *** comparing the results among Ddah1 general knockout(KO)mice,transgenic(TG)mice and wild-type(WT)mice,we discovered that DDAH1 upregulated the proliferation and neural differentiation of NSCs in the subgranular zone(SGZ)under ischemic *** a result,DDAH1 may promote cognitive and motor function recovery against stroke impairment,while these neuroprotective effects are dramatically suppressed by NSC conditional knockout of Ddah1 in mice.

关键词： DDAH1 Neurogenesis Neural repair ChAT HIF-1α ACh Stroke ADMA

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Lower limb suspension induces threshold-specific alterations of motor units properties that are reversed by active recovery

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Journal of Sport and Health Science 2024年第2期13卷 264-276页

作者： Giacomo Valli Fabio Sarto Andrea Casolo Alessandro Del Vecchio Martino V.Franchi Marco V.Narici Giuseppe De Vito department of Biomedical sciences University of PadovaPadova 35131Italy department Artificial Intelligence in Biomedical Engineering Friedrich-Alexander UniversityErlangen-Nurnberg 91052Germany

Purpose:This study aimed to non-invasively test the hypothesis that(a) short-term lower limb unloading would induce changes in the neural control of force production(based on motor units(MUs) properties) in the vastus lateralis muscle and(b) possible changes are reversed by active recovery(AR).Methods:Ten young males underwent 10 days of unilateral lower limb suspension(ULLS) followed by 21 days of *** ULLS,participants walked exclusively on crutches with the dominant leg suspended in a slightly flexed position(15°-20°) and with the contralateral foot raised by an elevated *** AR was based on resistance exercise(leg press and leg extension) and executed at 70% of each participant’s 1repetition maximum,3 times/*** voluntary isometric contraction(MVC) of knee extensors and MUs properties of the vastus lateralis muscle were measured at baseline,after ULLS,and after *** were identified using high-density electromyography during trapezoidal isometric contractions at 10%,25%,and 50% of the current MVC,and individual MUs were tracked across the 3 data collection ***:We identified 1428 unique MUs,and 270 of them(18.9%) were accurately *** ULLS,MVC decreased by 29.77%,MUs absolute recruitment/derecruitment thresholds were reduced at all contraction intensities(with changes between the 2 variables strongly correlated),while discharge rate was reduced at 10% and 25% but not at 50% *** MVC and MUs properties fully recovered to baseline levels after *** changes were observed in the pool of total as well as tracked ***:Our novel results demonstrate,non-invasively,that 10 days of ULLS affected neural control predominantly by altering the discharge rate of lower-threshold but not of higher-threshold MUs,suggesting a preferential impact of disuse on motoneurons with a lower depolarization ***,after 21 days of AR,the impaired MUs properties were fully restored to baseline levels,highlighting the plas

关键词： Disuse High-density EMG Muscle disuse Neural impairment Neuromuscular degeneration

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Upper extremity motor function before and after the cerebrospinal fluid tap test in patients with idiopathic normal pressure hydrocephalus:A retrospective study

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Chinese Medical Journal 2024年第7期137卷 877-879页

作者： Caiyan Liu Junji Wei Liling Dong Chenhui Mao Jie Li Xinying Huang Bo Hou Feng Feng Liying Cui Jing Gao department of Neurology Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China department of Neurosurgery and Radiology Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China

To the Editor:Idiopathic normal pressure hydrocephalus(iNPH)patients present disturbances in gait,cognition,and/or control of urination with neuroimaging characterized by enlargement of the cerebral ***,gait disturbance in iNPH patients is the initial and most prominent symptom,but motor impairments can also extend to upper *** cerebrospinaluid(CSF)tap test(TT),in which the symptoms of iNPH patients are assessed before and after drainage of 30-50mL CSF by lumbar puncture,is a commonly used auxiliary test for predicting shunt *** methods for determining the CSF TT response are based on the clinical impression of changes in gait after lumber *** patients who are unable to ambulate(e.g.,the patient is wheelchair bound)may not be able to comply with the gait evaluation but still benet from shunt *** grooved pegboard test(GPT)and symbol-digit modalities test(SDMT)are psychometric measures of upper extremity motor and psychomotor ***,we sought to identify whether these tests could be used to objectively assess responsiveness to the CSF TT.

关键词： patients cerebrospinal Upper

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SCFD1 in amyotrophic lateral sclerosis: reconciling a genetic association with in vivo functional analysis

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Neural Regeneration Research 2024年第6期19卷 1201-1202页

作者： Ruben J.Cauchi Centre for Molecular Medicine and Biobanking Biomedical Sciences BuildingDepartment of Physiology and Biochemistry Faculty of Medicine and Surgery University of Malta

Amyotrophic lateral sclerosis(ALS) is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons,resulting in muscle weakness and spasticity,eventually leading to death due to respiratory *** by our group of a casecontrol cohort from an isolated island population have found that genetics plays a significant role in disease etiology(Farrugia Wismayer et al.,2023).

关键词： PROTEIN SLY1

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Progress in the generation of spinal cord organoids over the past decade and future perspectives

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Neural Regeneration Research 2024年第5期19卷 1013-1019页

作者： Gang Zhou Siyuan Pang Yongning Li Jun Gao department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina department of International Medical Service Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in *** emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past *** literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal ***,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional *** qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue *** utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord ***,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational *** of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

关键词： development organoid-on-a-chip pluripotent stem cells progress spinal cord diseases spinal cord organoids vascularization

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A dysregulated calcium homeostasis as the earliest pathological sign in stem cell-derived Parkinson's disease neurons?

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Neural Regeneration Research 2024年第7期19卷 1421-1422页

作者： Nilima Prakash Working Group Human Stem Cell Research Department Hamm 2Hamm-Lippstadt University of Applied SciencesHammGermany

Parkinson’s disease(PD) is characterized by the slow and progressive demise of dopamine(DA)-synthesizing neurons in the substantia nigra pars compacta(SNc),a nucleus located in the human ventral *** death also affects other regions in the brain at later stages of *** concomitant lack of DA in the human forebrain(striatum) leads to the typical motor symptoms of this still uncurable neurodegenerative disorder.

关键词： homeostasis dopamine death

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Alexa,let's train now!——A systematic review and classification approach to digital and home-based physical training interventions aiming to support healthy cognitive aging

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Journal of Sport and Health Science 2024年第1期13卷 30-46页

作者： Fabian Herold Paula Theobald Thomas Gronwald Navin Kaushal Liye Zou Eling D.de Bruin Louis Bherer Notger GMüller Research Group Degenerative and Chronic Diseases MovementFaculty of Health Sciences BrandenburgUniversity of PotsdamPotsdam 14476Germany Body-Brain-Mind Laboratory Shenzhen UniversityShenzhen 518060China Institute of Interdisciplinary Exercise Science and Sports Medicine MSH Medical School HamburgHamburg 20457Germany department of Health sciences School of Health&Human SciencesIndiana UniversityIndianapolisIN 46202USA department of Health sciences and Technology Institute of Human Movement Sciences and SportETH ZurichZurich 8093Switzerland department of Neurobiology Care Sciencesand SocietyKarolinska InstituteStockholm 17177Sweden department of Health OST-Eastern Swiss University of Applied SciencesSt.Gallen 9001Switzerland Montreal Heart Institute MontrealQC H1T 1C8Canada department of Medicine Universite de MontrealMontrealQC H3T 1J4Canada Centre de Recherche de l'Institut Universitaire de Geriatrie de Montreal MontrealQC H3W 1W5Canada

Background:There is mounting evidence that regular physical activity is an important prerequisite for healthy cognitive ***,the finding that almost one-third of the adult population does not reach the recommended level of regular physical activity calls for further public health *** this context,digital and home-based physical training interventions might be a promising alternative to center-based intervention ***,this systematic review aimed to summarize the current state of the literature on the effects of digital and home-based physical training interventions on adult cognitive ***:In this pre-registered systematic review(PROSPERO;ID:CRD42022320031),5 electronic databases(PubMed,Web of Science,Psyclnfo,SPORTDiscus,and Cochrane Library)were searched by 2 independent researchers(FH and PT)to identify eligible studies investigating the effects of digital and home-based physical training interventions on cognitive performance in *** systematic literature search yielded 8258 records(extra17 records from other sources),of which 27 controlled trials were considered *** reviewers(FH and PT)independently extracted data and assessed the risk of bias using a modified version of the Tool for the assEssment of Study qualiTy and reporting in EXercise(TESTEX scale).Results:Of the 27 reviewed studies,15 reported positive effects on cognitive and motor-cognitive outcomes(i.e.,performance improvements in measures of executive functions,working memory,and choice stepping reaction test),and a considerable heterogeneity concerning study-related,population-related,and intervention-related characteristics was noticed.A more detailed analysis suggests that,in particular,interventions using online classes and technology-based exercise devices(i.e.,step-based exergames)can improve cognitive performance in healthy older *** one-half of the reviewed studies were rated as having a high risk of bias with respect

关键词： Brain Cognition Digital health Exercise-cognition Physical activity

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