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Genistein:a possible solution for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2903-2905页

作者： Karolina Pierzynowska Bartosz Karaszewski Grzegorz Węgrzyn Department of Molecular Biology University of GdanskGdanskPoland Gdansk Polandand Department of Adult NeurologyFaculty of MedicineMedical University of GdanskGdanskPoland

Neurodegenerative diseases are defined as disorders resulting from the slow and progressive loss of function and eventual death of neural cells that result from the primary pathology of nervous *** can lead to severe nervous system dysfunction,eventually affecting multiple organs and *** hundred neurodegenerative diseases have been described,and owing to their prevalence,severity.

关键词： organs Alzheimer death

Nucleoside modified mRNA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord

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Neural Regeneration Research 2025年第8期20卷 2311-2312页

作者： Krisztián Pajer Tamás Bellák Antal Nógrádi Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary

Spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular *** the spinal cord neurons have the capacity to regenerate their axons,the expression of growth inhibitory factors,lack or suppression of proper guidance cues,and profound inflammatory responses do not permit successful regeneration(Khyeam et al.,2021).

关键词： injured capacity modified

Modifying oxygen tension affects bone marrow stromal cell osteogenesis for regenerative medicine

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World Journal of Stem Cells 2017年第7期9卷 98-106页

作者： Yusuke Inagaki Manabu Akahane Takamasa Shimizu Kazuya Inoue Takuya Egawa Tsutomu Kira Munehiro Ogawa Kenji Kawate Yasuhito Tanaka Department of Orthopedic Surgery Nara Medical University Department of Public Health Health Management and PolicyNara Medical UniversityFaculty of Medicine Departments of Artificial Joint and Regenerative Medicine for Bone and Cartilage Nara Medical University

AIM To establish a hypoxic environment for promoting osteogenesis in rat marrow stromal cells(MSCs) using osteogenic matrix cell sheets(OMCSs).METHODS Rat MSCs were cultured in osteogenic media under one of four varying oxygen conditions: Normoxia(21% O_2) for 14 d(NN), normoxia for 7 d followed by hypoxia(5% O_2) for 7 d(NH), hypoxia for 7 d followed by normoxia for 7 d(HN), or hypoxia for 14 d(HH). Osteogenesis was evaluated by observing changes in cell morphology and calcium deposition, and by measuring osteocalcin secretion(ELISA) and calcium content. In vivo syngeneic transplantation using OMCSs and β-tricalcium phosphate discs, preconditioned under NN or HN conditions, was also evaluated by histology, calcium content measurements,and real-time quantitative *** In the NN and HN groups, differentiated, cuboidal-shaped cells were readily observed, along with calcium deposits. In the HN group, the levels of secreted osteocalcin increased rapidly from day 10 as compared with the other groups, and plateaued at day 12(P < 0.05). At day 14, the HN group showed the highest amount of calcium deposition. In vivo, the HN group showed histologically prominent new bone formation, increased calcium deposition, and higher collagen type Ⅰ?messenger RNA expression as compared with the NN *** The results of this study indicate that modifying oxygen tension is an effective method to enhance the osteogenic ability of MSCs used for OMCSs.

关键词： Hypoxia Osteogenesis Tissue engineering Marrow stromal cells Regenerative medicine

MET receptor tyrosine kinase promotes the generation of functional synapses in adult cortical circuits

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Neural Regeneration Research 2025年第5期20卷 1431-1444页

作者： Yuehua Cui Xiaokuang Ma Jing Wei Chang Chen Neha Shakir Hitesch Guirram Zhiyu Dai Trent Anderson Deveroux Ferguson Shenfeng Qiu Basic medical Sciences University of Arizona College of Medicine-PhoenixPhoenixAZUSA Department of Medicine University of Arizona College of Medicine-PhoenixPhoenixAZUSA

Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse *** have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine *** investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing *** found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection *** findings are further corroborated by increased synaptic activity and transient generation of immature silent *** MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and *** data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult *** findings may have implications for regenerative therapy in aging and neurodegeneration conditions.

关键词： aging circuit connectivity cortical circuits molecular mechanisms neural regeneration neurodegeneration synapses

Human endogenous retrovirus type-W and multiple sclerosis–related smoldering neuroinflammation

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Neural Regeneration Research 2025年第3期20卷 813-814页

作者： Joel Gruchot Laura Reiche Andrew Chan Robert Hoepner Patrick Küry Department of Neurology Medical Faculty and University Hospital DüsseldorfHeinrich Heine University DüsseldorfDüsseldorfGermany Department of Neurology InselspitalBern University Hospital and University of BernBernSwitzerland

Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.

关键词： endogenous inflammation Human

Lipomatous ependymoma with ZFTA:RELA fusion-positive:A case report

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World Journal of Clinical Cases 2025年第1期13卷 48-55页

作者： Xiao-Yu Zhao Juan-Han Yu Yi-Hua Wang Yi-Xin Liu Lu Xu Lin Fu Ning Yi China medical university The First Hospital of China Medical UniversityShenyang 110001Liaoning ProvinceChina Department of Pathology The First Hospital of China Medical UniversityShenyang 110001Liaoning ProvinceChina Anshan Cancer Hospital Anshan 114000Liaoning ProvinceChina

BACKGROUND Ependymoma with lipomatous differentiation is a rare type of *** ZFTA fusion-positive supratentorial ependymoma is a novel tumor type in the 2021 World Health Organization classification of central nervous system *** fusion-positive lipomatous ependymoma has not been reported to *** SUMMARY We reported a case of a 15-year-old Chinese male who had a sudden convulsion lasting approximately six *** resonance imaging showed a round cystic shadow of approximately 1.9 cm×1.5 cm×1.9 cm under the right parieto-occipital *** examination showed characteristic perivascular pseudorosettes and adipose differentiation in the ***-chemical staining showed that the tumor cells were negative for cytokeratin,NeuN,Syn and p53,but positive for GFAP,vimentin and S-100 ***-ficant punctate intracytoplasmic EMA immunoreactivity was *** level of Ki-67 was about 5%.Genetic analysis revealed ZFTA:RELA fusion.A cranio-tomy with total excision of the tumor was *** follow-up time was 36 months,no evidence of disease recurrence was found in magnetic resonance *** Based on these findings,the patient was diagnosed as a ependymoma with ZFTA fusion and lipomatous *** case report provides information on the microscopic morphological features of ependymoma with ZFTA fusion and lipomatous differentiation,which can help pathologists to make a definitive diagnosis of this tumor.

关键词： Ependymoma Lipomatous Molecular classification Supratentorial ZFTA:RELA fusion Case report

Depth of invasion to the bladder wall as a prognostic factor and its association with circulating cell-free DNA levels in patients with muscle-invasive bladder cancer

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Current Urology 2023年第4期17卷 229-235页

作者： Yusuke lemura Makito Miyake Shinji Fukui Tomomi Fujii Sayuri Ohnishi Shunta Hori Yosuke Morizawa Yasushi Nakai Kazumasa Torimoto Nobumichi Tanaka Kiyohide Fujimoto Department of Urology Nara Medical UniversityKashiharaNara634-8522Japan Department of Diagnostic Pathology Nara Medical UniversityKashiharaNaraJapan Department of Prostate Brachytherapy Nara Medical UniversityKashiharaNaraJapan

Background:Radical cystectomy(RC)is the standard surgical treatment for patients with muscle-invasive bladder cancer,but the prognosis is not favorable,and new prognostic factors need to be *** investigated the potential of depth of invasion(DOI)as a prognostic factor in patients with muscle-invasive bladder cancer who underwent ***,we examined the association between preoperative levels of circulating cell-free DNA and *** and methods:We retrospectively reviewed patients who underwent RC between January 2007 and December 2017;those who received neoadjuvant chemotherapy were *** of invasion was measured using hematoxylin-eosin-stained RC ***:Of the 121 patients selected,41(33.9%)were eligible for *** median follow-up period was 14 months and mean DOI was 17 mm(range,2-75 mm).Long DOI(>17 mm)was significantly associated with shorter progression-free survival(hazard ratio,14.5;95%confidence interval,3.9-53.97,p<0.0001)and cancer-specific survival(hazard ratio,18.97;95%confidence interval,4.04-88.99,p=0.0002)compared with short *** analysis revealed that DOI was an independent risk factor for cancer-specific *** levels of circulating cell-free DNA were significantly higher in patients with a longer DOI than in those with short DOI(65 vs.20 ng/mL,respectively;p=0.028).Conclusions:Depth of invasion predicted with levels of circulating cell-free DNA and thus could be a useful prognostic factor.

关键词： Bladder cancer Depth of invasion Cell-free DNA

Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration Research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad Al Kabbani Christoph Köhler Hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301L-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301L pR5 mice TAU tauopathy tubulin code

Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway

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Neural Regeneration Research 2025年第11期20卷 3245-3258页

作者： Jiayi Wang Mengke Zhao Dong Fu Meina Wang Chao Han Zhongyue Lv Liang Wang Jing Liu Stem Cell Clinical Research Center The First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina Dalian Innovation Institute of Stem Cell and Precision Medicine DalianLiaoning ProvinceChina Institute(College)of Integrative Medicine Dalian Medical UniversityDalianLiaoning ProvinceChina

Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived *** lays a foundation for the development of potentially potent new treatment modalities for ischemic ***,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical *** promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic *** found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal *** human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase *** findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling ***,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety ***,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.

关键词： behavior exosome extracellular vesicles ischemic stroke mammalian target of rapamycin(mTOR) middle cerebral artery occlusion neural stem cells neuronal apoptosis phosphoinositide 3-kinase(PI3K) protein kinase B(AKT)