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Safety and efficiency of Wharton’s Jelly-derived mesenchymal stem cell administration in patients with traumatic brain injury:First results of a phase I study

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World Journal of Stem Cells 2024年第6期16卷 641-655页

作者： Serdar Kabatas ErdinçCivelek Osman Boyalı Gülseli Berivan Sezen Omer Ozdemir Yeliz Bahar-Ozdemir Necati Kaplan Eyüp Can Savrunlu Erdal Karaöz department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34360Türkiye Center for Stem Cell&Gene Therapy Research and Practice University of Health Sciences TurkeyIstanbul 34255Türkiye department of Neurosurgery University of Health SciencesGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye department of Physical Medicine and Rehabilitation Health Sciences University Sultan Abdulhamid Han Training and Research HospitalIstanbul 34668Türkiye department of Neurosurgery Istanbul Rumeli UniversityÇorlu Reyap HospitalTekirdağ59860Türkiye department of Neurosurgery Nevşehir State HospitalNevşehir 50300Türkiye Center for Regenerative Medicine and Stem Cell Research&Manufacturing(LivMedCell) Liv HospitalIstanbul 34340Türkiye department of Histology and Embryology Istinye UniversityFaculty of MedicineIstanbul 34010Türkiye Center for Stem Cell and Tissue Engineering Research and Practice Istinye UniversityIstanbul 34340Türkiye

BACKGROUND Traumatic brain injury(TBI)is characterized by a disruption in the normal function of the brain due to an injury following a trauma,which can potentially cause severe physical,cognitive,and emotional *** cell transplantation has evolved as a novel treatment modality in the management of TBI,as it has the potential to arrest the degeneration and promote regeneration of new cells in the ***’s Jelly-derived mesenchymal stem cells(WJ-MSCs)have recently shown beneficial effects in the functional recovery of neurological *** To evaluate the safety and efficiency of MSC therapy in *** We present 6 patients,4 male and 2 female aged between 21 and 27 years who suffered a *** 6 patients underwent 6 doses of intrathecal,intramuscular(i.m.)and intravenous transplantation of WJ-MSCs at a target dose of 1×106/kg for each application *** was assessed using the Modified Ashworth scale(MAS),motor function according to the Medical Research Council Muscle Strength Scale,quality of life was assessed by the Functional Independence Measure(FIM)scale and Karnofsky Performance Status *** Our patients showed only early,transient complications,such as subfebrile fever,mild headache,and muscle pain due to ***,which resolved within 24 *** the one year follow-up,no other safety issues or adverse events were *** 6 patients showed improvements in their cognitive abilities,muscle spasticity,muscle strength,performance scores and fine motor skills when compared before and after the *** values,which we used to assess spasticity,were observed to statistically significantly decrease for both left and right sides(P<0.001).The FIM scale includes both motor scores(P<0.05)and cognitive scores(P<0.001)and showed a significant increase in pretest posttest *** difference observed in the participants’Karnofsky Performance Scale values pre and post the intervention was statistically si

关键词： Traumatic brain injury Wharton Jelly Stem cell therapy Transplantation Mesenchymal stem cell

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Does mesenchymal stem cell’s secretome affect spinal sensory circuits?Implication for pain therapies

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Neural Regeneration Research 2025年第1期20卷 181-183页

作者： Francesco Ferrini Esri H.Juárez Adalberto Merighi department of Veterinary sciences University of TurinGrugliascoTOItaly department of Psychiatry and Neuroscience UniversitéLavalQuébec CityQCCanada

Mesenchymal stem cells(MSCs)are multipotent adult stem cells of mesodermal origin that can be isolated from various tissues,including bone marrow,tooth pulp,adipose tissue,and umbilical *** have gained significant attention in regenerative medicine due to their ability to modulate the immune system and favor tissue *** enrich the medium in which they are cultivated with a broad range of bioactive molecules,including growth factors,cytokines,chemokines,enzymes,nucleic acids,and extracellular vesicles that collectively compose the MSC *** increasing number of pre-clinical studies suggest that delivering in vivo an MSC-conditioned medium(i.e.,the medium collected from MSC cultures after at least 3 days of exposure)exerts neuroprotective and anti-inflammatory effects in a variety of neurological conditions.

关键词： protective clinical collective

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Serum metabolism alteration behind different etiology, diagnosis, and prognosis of disorders of consciousness

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中华神经外科杂志(英文) 2024年第3期10卷 1-12页

作者： Ge Qianqian Lu Hezhen Geng Xiaoli Chen Xueling Liu Xiaoyan Sun Haidan Guo Zhengguang Sun Jiameng Qi Feng Niu Xia Wang Aiwei He Jianghong Sun Wei Xu Long department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing China China-Japan Union Hospital of Jilin University Changchun China Core Instrument Facility Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Beijing China China National Clinical Research Center for neurological Diseases (NCRC-ND) Beijing China

Background Patients with disorders of consciousness (DoC) exhibit varied revival outcomes based on different etiologies and diagnoses, the mechanisms of which remain largely unknown. The fluctuating clinical presentations in DoC pose challenges in accurately assessing consciousness levels and prognoses, often leading to misdiagnoses. There is an urgent need for a deeper understanding of the physiological changes in DoC and the development of objective diagnostic and prognostic biomarkers to improve treatment *** To explore biomarkers and understand the biological processes, we conducted a comprehensive untargeted metabolomic analysis on serum samples from 48 patients with DoC. Patients were categorized based on etiology (TBI vs. non-TBI), CRS-R scores, and prognosis. Advanced analytical techniques, including PCA and OPLS-DA models, were employed to identify differential *** Our analysis revealed a distinct separation in metabolomic profiles among the different groups. The primary differential metabolites distinguishing patients with varying etiologies were predominantly phospholipids, with a notable decrease in glycerophospholipids observed in the TBI group. Patients with higher CRS-R scores exhibited a pattern of impaired carbohydrate metabolism coupled with enhanced lipid metabolism. Notably, serum concentrations of both LysoPE and PE were reduced in patients with improved outcomes, suggesting their potential as prognostic *** Our study underscores the critical role of phospholipid metabolism in the brain’s metabolic alterations in patients with DoC. It identifies key biomarkers for diagnosis and prognosis, offering insights that could lead to novel therapeutic targets. These findings highlight the value of metabolomic profiling in understanding and potentially treating DoC.

关键词： Disorders of consciousness Serum biomarkers Untargeted metabolomic analysis

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BACE1 inhibitors:A promising therapeutic approach for the management of Alzheimer’s disease

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Asian Pacific Journal of Tropical Biomedicine 2024年第9期14卷 369-381页

作者： Richa Arya Smita Jain Sarvesh Paliwal Kirtika Madan Swapnil Sharma Achal Mishra Prashant Tiwari Sunil Kumar Kadiri Banasthali University Banasthali-304022(Raj.)India department of Pharmacy Guru Ghasidas VishwavidyalayaBilaspurChhattisgarh-495009India department of Pharmacology College of Pharmaceutical SciencesDayananda Sagar UniversityBengaluru-560111India

Alzheimer’s disease is a neurological disorder marked by the accumulation of amyloid beta(Aβ)aggregates,resulting from mutations in the amyloid precursor *** enzymeβ-secretase,also known asβ-site amyloid precursor protein cleaving enzyme 1(BACE1),plays a crucial role in generating Aβ*** no targeted therapy available for Alzheimer’s disease,inhibiting BACE1 aspartic protease has emerged as a primary treatment *** 1999,compounds demonstrating potential binding to the BACE1 receptor have advanced to human *** optimization of synthetically derived compounds,coupled with computational approaches,has offered valuable insights for developing highly selective leads with drug-like *** review highlights pivotal studies on the design and development of BACE1 inhibitors as anti-Alzheimer’s disease *** summarizes computational methods employed in facilitating drug discovery for potential BACE1 inhibitors and provides an update on their clinical status,indicating future directions for novel BACE1 *** promising clinical results of Elenbecestat(E-2609)catalyze the development of effective,selective BACE1 inhibitors in the future.

关键词： BACE1 inhibitors Amyloid precursor protein β-secretase Structure-based drug design 3D-QSAR β-amyloid precursor protein

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Neuroprotective potential of traditional Ayurvedic Kadha:age-related neurological disorders:a comprehensive literature review

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Traditional Medicine Research 2024年第9期9卷 51-77页

作者： Sarvin Sadreddini Mohammad Javad Emami Kazemabad Sogand Sheikholeslami Kosar Chitzan-Zadeh Mohammad Taha Kouchaki Midia Rashidi Amir Abbas Ghayerin Shahin Sabaghi Ghazal Tavakoli Sepehr Nanbakhsh Tina Mansourian Arefeh Tabashiri Fariba Arbab Mojeni Mohammed Namiq Amin Zahra Taheri Seyed Esmaeil Sedighi Taraneh Tarkashvand Parham Amirazodi Mobina Fathi Shirin Yaghoobpoor Niloofar Deravi School of Medicine Tabriz University of Medical SciencesTabriz ***Iran School of Medicine Qom University of Medical SciencesQom ***Iran School of Medicine Hamadan University of Medical SciencesHamadan ***Iran School of Medicine Ahvaz Jundishapur University of Medical SciencesAhvaz ***Iran Faculty of Medicine Tabriz University of Medical SciencesTabriz ***Iran School of Medicine Iran University of Medical SciencesTehran ***Iran School of Medicine Shahid Beheshti University of Medical SciencesTehran ***Iran School of Medicine Mazandaran University of Medical SciencesSari ***Iran School of Medicine Kermanshah University of Medical SciencesKermanshah ***Iran Faculty of Pharmacy Pharmaceutical Sciences BranchIslamic Azad UniversityTehran ***Iran department of Biology Faculty of SciencePayamNoor UniversityTehran ***Iran Faculty of Medicine Islamic Azad University of Medical ScienceTehran 193951495Iran International Campus Shahid Sadoughi University of Medical SciencesYazd ***Iran

Despite modern medicine’s advancements,age-related neurological diseases like Alzheimer’s disease and Parkinson’s disease remain challenging due to high costs,side effects,and limited ***,a traditional Indian medicine system,offers Kadha tea as a potential herbal *** review explores Kadha’s components(basil(Ocimum basilicum L.),black pepper(Piper nigrum L.),Cinnamon(Cinnamomum verum ***),ginger(Zingiber officinale Roscoe),and raisin(Vitis vinifera L.))and their interaction with various neurological *** suggest Kadha exhibits anti-inflammatory,antioxidant,and antiviral properties,potentially impacting Alzheimer’s disease,Parkinson’s disease,neurotoxicity,neuroinflammation,and brain *** focusing on specific disease mechanisms and Kadha’s intergrade effects,this review aims to elucidate its potential role in managing age-related neurological disorders.

关键词： Ayurveda Kadha neuroprotective neurological disorders traditional medicine

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多肽靶向嵌合体通过促进tau蛋白特异性去磷酸化治疗阿尔茨海默病和其他tau蛋白病

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Science Bulletin 2024年第8期69卷 1137-1152页

作者：苏静芬肖越魏林郁雷慧杨孙飞王围霞尹君熊瑞李师宏张配周颖王小川郑杰王建枝 department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China/Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China School of Artificial Intelligence and Automation Huazhong University of Science and TechnologyWuhan 430030China Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province Department of Physiology and PathophysiologySchool of Basic Medical SciencesXinxiang Medical UniversityXinxiang 453003China department of Pathophysiology School of Basic Medical SciencesWuhan UniversityWuhan 430030China department of Anesthesiology The First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000China The Core Facility and Technical Support Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430030China Research Center for Medicine and Structural Biology Wuhan UniversityWuhan 430030China Neuroscience Research Institute and department of Neurobiology School of Basic Medical SciencesPeking UniversityKey Laboratory for NeuroscienceMinistry of Education/National Health CommissionBeijing 100083China Co-innovation Center of Neuroregeneration Nantong UniversityNantong 226000China

Abnormal hyperphosphorylation and accumulation of tau protein play a pivotal role in neurodegeneration in Alzheimer’s disease(AD)and many other *** elimination of hyperphosphorylated tau is promising for the therapy of these *** have conceptualized a strategy,named dephosphorylation-targeting chimeras(DEPTACs),for specifically hijacking phosphatases to tau to debilitate its ***,we conducted the step-by-step optimization of each constituent motif to generate DEPTACs with reasonable effectiveness in facilitating the dephosphorylation and subsequent clearance of pathological ***,for one of the selected chimeras,D16,we demonstrated its significant efficiency in rescuing the neurodegeneration caused by neurotoxic K18-tau seeds in ***,intravenous administration of D16 also alleviated tau pathologies in the brain and improved memory deficits in AD *** results suggested DEPTACs as targeted modulators of tau phosphorylation,which hold therapeutic potential for AD and other tauopathies.

关键词： tau Dephosphorylation-targeting chimeras Therapeutic potential Tauopathy

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Longitudinal associations of cardiovascular health and vascular events with incident dementia

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Stroke & Vascular Neurology 2024年第4期9卷 418-428,I0066-I0130页

作者： Ya-Nan Ou Kevin Kuo Liu Yang Ya-Ru Zhang Shu-Yi Huang Shi-Dong Chen Yue-Ting Deng Yu Guo Rui-Qi Zhang Bang-Sheng Wu Lan Tan Qiang Dong Jian-Feng Feng Wei Cheng Jin-Tai Yu department of Neurology Qingdao Municipal HospitalQingdao UniversityQingdaoShandongPeople's Republic of China department of Neurology and National Center for neurological Disorders Huashan HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceShanghai Medical CollegeFudan UniversityShanghaiPeople's Republic of China Institute of Science and Technology for Brain-inspired Intelligence Fudan UniversityShanghaiPeople's Republic of China Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence Fudan UniversityMinistry of EducationShanghaiPeople's Republic of China

Introduction Evidence supporting cardiovascular diseases could increase the risk of dementia remains fragmented.A comprehensive study to illuminate the distinctive associations across different dementia types is still *** study is sought to:(1)determine the clinical validity of Framingham General Cardiovascular Risk Score(FGCRS)for dementia assessment and(2)examine the associations between cardiovascular diseases and the risk of *** A total of 432079 dementia-free individuals at baseline from UK Biobank were *** Cox proportional hazard models were used to investigate the prospective associations for FGCRS and a series of cardiovascular diseases with all-cause dementia(ACD)and its major components,Alzheimer’s disease(AD)and vascular dementia(VaD).Results During a median follow-up of 110.1 months,4711 individuals were diagnosed with *** was associated with increased risks across the dementia *** stratification analysis,high-risk groups have demonstrated the greatest dementia burdens,particularly to *** 74 traits,9 adverse associations,such as chronic ischaemic heart disease(ACD:HR=1.354;AD:HR=1.269;VaD:HR=1.768),atrioventricular block(ACD:HR=1.562;AD:HR=1.556;VaD:HR=2.069),heart failure(ACD:HR=1.639;AD:HR=1.543;VaD:HR=2.141)and hypotension(ACD:HR=2.912;AD:HR=2.361;VaD:HR=3.315)were *** distinctions were also found,with atrial fibrillation,cerebral infarction,and haemorrhage only associated with greater risks of ACD and *** By identifying distinctive associations between cardiovascular diseases and dementia,this study has established a comprehensive‘mapping’that may untangle the long-standing *** has demonstrated its predictivity beyond cardiovascular diseases burdens,suggesting potential opportunities for implantation.

关键词： cardiovascular diseases supporting

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DPABINet:脑网络和图论分析工具箱

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Science Bulletin 2024年第11期69卷 1628-1631页

作者：严超赣王鑫迪鲁彬邓昭宇高青林 CAS Key Laboratory of Behavioral Science Institute of PsychologyBeijing 100101China department of Psychology University of Chinese Academy of SciencesBeijing 100101China International Big-Data Center for Depression Research Institute of PsychologyChinese Academy of SciencesBeijing 100101China Magnetic Resonance Imaging Research Center Institute of PsychologyChinese Academy of SciencesBeijing 100101China McGill Centre for Integrative Neuroscience Montreal Neurological InstituteMcGill UniversityMontréal H3A 2B4Canada

The human brain, a marvel of intricate connections, functions as a complex network comprising structurally and functionally integrated regions. This network orchestrates a multitude of complex patterns through high-le... 详细信息

关键词：图论分析脑网络工具箱

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Toxicity of a seafood toxin， domoic acid， in the retina via modulation of the NRF2 and NF-κB pathways

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Food Science and Human Wellness 2024年

作者： Gabriel Mbuta Tchivelekete Yanqun Cao Mohammad Almarhoun Xinzhi Zhou Agostinho Francisco Cachapa Sebasti?o Tumitangua James Reilly Patricia E.Martin Xinhua Shu department of Biological and Biomedical sciences， Glasgow Caledonian University department of Marine Biology， Faculty of Natural Science， University of Namibe Puai Medical School， Shaoyang University department of Vision Science， Glasgow Caledonian University

Domoic acid (DA)， a biotoxin， is produced by several species of marine dinoflagellate and diatom during harmful algal bloom events. DA is a neurotoxin， in humans and non-human primates， oral exposure to DA results in gastrointestinal effects， while DA at higher doses leads to neurological symptoms， seizures and memory deficiency. Exposure of humans to DA occurs mainly through consumption of contaminated seafoods containing an accumulation of the toxin. Previously， it was unclear if DA can have toxic effects on the retina. We assessed the toxicity of DA in human retinal cells (ARPE-19) and in zebrafish embryos. DA significantly lowered ARPE-19 cell viability dose-dependently， and decreased anti-oxidative capacity， increased inflammation， and promoted cell death， possibly through modulating the NRF2 and NF-κB signalling pathways. Zebrafish embryos exposed to DA for four days from one day post fertilization (dpf) had an increase in mortality and a decrease in both hatching and heartbeat rate and exhibited morphological abnormalities. DA treatment also significantly downregulated expression of antioxidant genes and upregulated expression of inflammation mediators， as well as causing photoreceptor death in zebrafish embryos. The results demonstrate that consuming seafood containing DA will have potential toxic effects in human retinas.

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Effects of exosomes from mesenchymal stem cells on functional recovery of a patient with total radial nerve injury: A pilot study

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World Journal of Stem Cells 2024年第1期16卷 19-32页

作者： ErdinçCivelek Serdar Kabatas Eyüp Can Savrunlu Furkan Diren Necati Kaplan Demet Ofluoğlu Erdal Karaöz department of Neurosurgery University of Health SciencesGaziosmanpaşa Training and Research HospitalGaziosmanpaşa 34255IstanbulTurkey department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalGaziosmanpaşa 34255IstanbulTurkey Center for Stem Cell&Gene Therapy Research and Practice University of Health Sciences TurkeyGaziosmanpaşa 34255IstanbulTurkey department of Neurosurgery Nevşehir State HospitalNevşehir 50300Turkey department of Neurosurgery Istanbul Rumeli UniversityÇorlu Reyap HospitalÇorlu 59860TekirdağTurkey department of Physical Medicine and Rehabilitation Ofluoğlu KlinikGöztepe 34728IstanbulTurkey Liv Hospital Center for Regenerative Medicine and Stem Cell Research&Manufacturing(LivMedCell)Beşiktaş34340IstanbulTurkey department of Histology and Embryology Istinye UniversityFaculty of MedicineZeytinburnu 34010IstanbulTurkey Istinye University Center for Stem Cell and Tissue Engineering Research and PracticeBeşiktaş34340IstanbulTurkey

BACKGROUND Peripheral nerve injury can result in significant clinical complications that have uncertain ***,there is a lack of effective pharmacological interventions for nerve damage,despite the existence of several small compounds,Despite the objective of achieving full functional restoration by surgical intervention,the persistent challenge of inadequate functional recovery remains a significant concern in the context of peripheral nerve *** To examine the impact of exosomes on the process of functional recovery following a complete radial nerve *** A male individual,aged 24,who is right-hand dominant and an immigrant,arrived with an injury caused by a knife *** cut is located on the left arm,specifically below the *** neurological examination and electrodiagnostic testing reveal evidence of left radial nerve *** sural autograft was utilized for repair,followed by the application of 1 mL of mesenchymal stem cell-derived exosome,comprising 5 billion *** exosome was split into four equal volumes of 0.25 mL each and delivered microsurgically to both the proximal and distal stumps using the subepineural *** patient was subjected to a period of 180 d during which they had neurological examination and electrodiagnostic *** The duration of the patient’s follow-up period was 180 *** increasing Tinel’s sign and sensory-motor recovery were detected even at the 10th wk following nerve *** the conclusion of the 6-mo post-treatment period,an evaluation was conducted to measure the extent of improvement in motor and sensory functions of the *** assessment was based on the British Medical Research Council scale and the Mackinnon-Dellon *** results indicated that the level of improvement in motor function was classified as M5,denoting an excellent ***,the level of improvement in sensory function was classified as S3+,indicating a good *** is

关键词： Mesenchymal stem cell Exosomes Radial nerve Sural nerve

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