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Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

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Neural Regeneration Research 2024年第2期19卷 440-446页

作者： Sumei Liu Baoguo Liu Qian Li Tianqi Zheng Bochao Liu Mo Li Zhiguo Chen Cell Therapy center Beijing Institute of GeriatricsXuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric Diseasesand Key Laboratory of Neurodegenerative DiseasesMinistry of EducationBeijingChina center of Neural Injury and Repair Beijing Institute for Brain DisordersBeijingChina center of Parkinson’s Disease Beijing Institute for Brain DisordersBeijingChina

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate *** a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury ***,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord *** neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury ***,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion *** of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the ***,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion ***-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

关键词： biomaterial fibrinogen functional recovery induced neural stem cell transplantation microenvironment microglia spinal cord injury thrombin

MiR-107-3p/Atp6v0e1 contributes to protective effects of two selenium-containing peptides,TSeMMM and SeMDPGQQ on lead-induced neurotoxicity

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Food Science and Human Wellness 2024年第4期13卷 2060-2067页

作者： Yong Fang Tianhang Huang Jian Wu Xieqi Luo Fengjiao Fan Peng Li Jian Ding Xinyang Sun College of Food Science and Engineering Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and SafetyNanjing 210023China Laboratory of neurodegenerative and Neuroinjury diseases Wuxi School of MedicineJiangnan UniversityWuxi 214122China

Two selenium(Se)-containing peptides from Se-enriched rice,TSeMMM and SeMDPGQQ,possess neuroprotective potency against lead(Pb2+)-induced ***,the crosstalk between mRNA and microRNAs(miRNA)involved in the neuroprotection mechanism remains to be *** this study,RNA-sequencing and miRNA-sequencing were used to independently identify differentially expressed mRNAs and small RNAs profiles in Pb^(2+)-treated primary fetal rat cortical neurons and then the correlated miRNA-mRNA target pairs were *** was found that 34 mRNAs related to oxidative phosphorylation could be reversed by pretreatment of TSeMMM and *** protective effect of TSeMMM and SeMDPGQQ was mediated by upregulation of miR-107-3p,which downregulates the ATPase H+transporting V0 subunit e1(Atp6v0e1)mRNA level.A zebrafish model was applied to verify the relevance between the targeted mRNA and miRNA by real-time quantitative *** results indicated that miR-107-3p was a potential therapeutic target to achieve neuroprotection of Se-containing peptides via stimulation of Atp6v0e1.

关键词： Lead Se-containing peptides Neuroprotection miRNA

Blood-brain barrier pathology in cerebral small vessel disease

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Neural Regeneration Research 2024年第6期19卷 1233-1240页

作者： Ruxue Jia Gemma Solé-Guardia Amanda J.Kiliaan Department of Medical imaging Anatomy Radboud University Medical Center Donders Institute for Brain Cognition & Behavior Center for Medical Neuroscience Preclinical Imaging Center PRIME Radboud Alzheimer Center

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly. Although at first it was considered innocuous, small vessel disease is nowadays regarded as one of the major vascular causes of dementia. Radiological signs of small vessel disease include small subcortical infarcts, white matter magnetic resonance imaging hyperintensities, lacunes, enlarged perivascular spaces, cerebral microbleeds, and brain atrophy; however, great heterogeneity in clinical symptoms is observed in small vessel disease patients. The pathophysiology of these lesions has been linked to multiple processes, such as hypoperfusion, defective cerebrovascular reactivity, and blood-brain barrier dysfunction. Notably, studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease. Therefore, the purpose of this review is to provide a new foundation in the study of small vessel disease pathology. First, we discuss the main structural domains and functions of the blood-brain barrier. Secondly, we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease. Finally, we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

关键词： blood-brain barrier dysfunction cerebral blood flow cerebral hypoperfusion endothelial dysfunction hypertension inflammation magnetic resonance imaging neurovascular unit oxidative stress small vessel disease tight junctions transcytosis

Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

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Neural Regeneration Research 2024年第11期19卷 2365-2376页

作者： Victoria Cunha Alves Eva Carro Joana Figueiro-Silva neurodegenerative diseases Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Network center for Biomedical Research Neurodegenerative Diseases(CIBERNED)MadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurotraumatology and Subarachnoid Hemorrhage Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research Into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain Institute of Medical Genetics University of ZurichZurichSwitzerland Department of Molecular Life Science University of ZurichZurichSwitzerland

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA *** review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease *** examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease *** entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the ***,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal ***,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory *** complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation *** the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease *** research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

关键词： Alzheimer’s disease ANK1 BIN1 DNA methylation epigenome-wide association studies HOXA3 MCF2L RHBDF2

Omics for deciphering oral microecology

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International Journal of Oral Science 2024年第2期16卷 197-207页

作者： Yongwang Lin Xiaoyue Liang Zhengyi Li Tao Gong Biao Ren Yuqing Li Xian Peng State Key Laboratory of Oral diseases&National center for Stomatology&National Clinical Research center for Oral diseases West China Hospital of StomatologySichuan UniversityChengduChina

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic *** technological innovations are propelling the characterization and manipulation of oral ***-throughput sequencing enables comprehensive taxonomic and functional profiling of oral *** long-read platforms improve genome assembly from complex ***-cell genomics provides insights into uncultured *** imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing *** techniques link phylogenetic identity with *** spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for *** facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput *** integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and ***,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic *** convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

关键词： insight holds oral

Ambroxol,the cough expectorant with neuroprotective effects

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Neural Regeneration Research 2024年第11期19卷 2345-2346页

作者： Kristin Patzwaldt Salvador Castaneda-Vega Werner Siemens imaging center Department of Preclinical Imaging and RadiopharmacyEberhard Karls University TuebingenTuebingenGermany Department of Nuclear Medicine and Clinical Molecular imaging University Clinic TuebingenTuebingenGermany

Ambroxol hydrochloride(2-amino-3,5-dibromo-N-methylbenzylamine hydrochloride)has been used as a mucolytic agent in the treatment of respiratory diseases since the late *** effects on mucus membranes such as mucus disruption,increased mucus production,and low toxicity profile were addressed in its original German patent in *** first described properties have kept Ambroxol available worldwide and over the counter in the pharmaceutical market to this day.

关键词： protective agent German

Inducing mitochondriopathy-like damages by transformable nucleopeptide nanoparticles for targeted therapy of bladder cancer

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National Science Review 2024年第4期11卷 216-227页

作者： Da-Yong Hou Ni-Yuan Zhang Lu Wang Mei-Yu Lv Xiang-Peng Li Peng Zhang Yue-Ze Wang Lei Shen Xiu-Hai Wu Bo Fu Peng-Yu Guo Zi-Qi Wang Dong-Bing Cheng Hao Wang Wanhai Xu NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics Heilongjiang Key Laboratory of Scientific Research in Urology Harbin Medical University Department of Urology Harbin Medical University Cancer Hospital CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology(NCNST) School of Chemistry Chemical Engineering & Life Science Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases Wuhan University of Technology

Mitochondriopathy inspired adenosine triphosphate(ATP) depletions have been recognized as a powerful way for controlling tumor growth. Nevertheless, selective sequestration or exhaustion of ATP under complex biological environments remains a prodigious challenge. Harnessing the advantages of in vivo self-assembled nanomaterials, we designed an Intracellular ATP Sequestration(IAS) system to specifically construct nanofibrous nanostructures on the surface of tumor nuclei with exposed ATP binding sites,leading to highly efficient suppression of bladder cancer by induction of mitochondriopathy-like ***, the reported transformable nucleopeptide(NLS-FF-T) self-assembled into nuclear-targeted nanoparticles with ATP binding sites encapsulated inside under aqueous conditions. By interaction with KPNA2, the NLS-FF-T transformed into a nanofibrous-based ATP trapper on the surface of tumor nuclei,which prevented the production of intracellular energy. As a result, multiple bladder tumor cell lines(T24,EJ and RT-112) revealed that the half-maximal inhibitory concentration(IC50) of NLS-FF-T was reduced by approximately 4-fold when compared to NLS-T. Following intravenous administration, NLS-FF-T was found to be dose-dependently accumulated at the tumor site of T24 xenograft mice. More significantly, this IAS system exhibited an extremely antitumor efficacy according to the deterioration of T24 tumors and simultaneously prolonged the overall survival of T24 orthotopic xenograft mice. Together, our findings clearly demonstrated the therapeutic advantages of intracellular ATP sequestration-induced mitochondriopathy-like damages, which provides a potential treatment strategy for malignancies.

关键词： self-assembly nucleopeptide nanomaterial bladder cancer mitochondriopathy

An end‐to‐end infant brain parcellation pipeline

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Intelligent Medicine 2024年第2期4卷 65-74页

作者： Limei Wang Yue Sun Weili Lin Gang Li Li Wang Department of Radiology and Biomedical Research imaging center UNC-Chapel HillNew Caledonia27599USA

Objective Accurate infant brain parcellation is crucial for understanding early brain development;however,it is challenging due to the inherent low tissue contrast,high noise,and severe partial volume effects in infant magnetic resonance images(MRIs).The aim of this study was to develop an end-to-end pipeline that enabled accurate parcellation of infant brain *** We proposed an end-to-end pipeline that employs a two-stage global-to-local approach for accurate parcellation of infant brain ***,in the global regions of interest(ROIs)localization stage,a combination of transformer and convolution operations was employed to capture both global spatial features and fine texture features,enabling an approximate localization of the ROIs across the whole *** the local ROIs refinement stage,leveraging the position priors from the first stage along with the raw MRIs,the boundaries of the ROIs are refined for a more accurate *** We utilized the Dice ratio to evaluate the accuracy of parcellation *** on 263 subjects from National Database for Autism Research(NDAR),Baby Connectome Project(BCP)and Cross-site datasets demonstrated the better accuracy and robustness of our method than other competing *** Our end-to-end pipeline may be capable of accurately parcellating 6-month-old infant brain MRIs.

关键词： Infant brain parcellation Isointense magnetic resonance image Convolutional neural networks Transformer

Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis

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Frontiers of Medicine 2024年第1期18卷 68-80页

作者： Yanling Liu Xi He Yanchun Yuan Bin Li Zhen Liu Wanzhen Li Kaixuan Li Shuo Tan Quan Zhu Zhengyan Tang Feng Han Ziqiang Wu Lu Shen Hong Jiang Beisha Tang Jian Qiu Zhengmao Hu Junling Wang Department of Neurology Xiangya HospitalCentral South UniversityJiangxiNational Regional Center for Neurological DiseasesNanchang330038China Provincial Laboratory for Diagnosis and Treatment of Genitourinary System Disease Department of UrologyXiangya HospitalCentral South UniversityChangsha410078China Department of Orthopedics The First Affiliated HospitalZhejiang University School of MedicineHangzhou310002China Department of Neurology Xiangya HospitalCentral South UniversityChangsha410078China National Clinical Research center for Geriatric diseases Xiangya HospitalCentral South UniversityChangsha410008China Key Laboratory of Hunan Province in neurodegenerative Disorders Central South UniversityChangsha410008China center for Medical Genetics School of Life SciencesCentral South UniversityChangsha410008China Engineering Research center of Hunan Province in Cognitive Impairment Disorders Central South UniversityChangsha410078China Hunan International Scientific and Technological Cooperation Base of neurodegenerative and Neurogenetic diseases Changsha410078China Hunan Key Laboratory of Molecular Precision Medicine Xiangya HospitalCentral South UniversityChangsha410078China

Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons,and it demonstrates high clinical heterogeneity and complex genetic architecture.A variation within TRMT2B(c.1356G>T;p.K452N)was identified to be associated with ALS in a family comprising two patients with juvenile ALS(JALS).Two missense variations and one splicing variation were identified in 10 patients with ALS in a cohort with 910 patients with ALS,and three more variants were identified in a public ALS database including 3317 patients with ALS.A decreased number of mitochondria,swollen mitochondria,lower expression of ND1,decreased mitochondrial complex I activities,lower mitochondrial aerobic respiration,and a high level of ROS were observed functionally in patient-originated lymphoblastoid cell lines and TRMT2B interfering HEK293 ***,TRMT2B variations overexpression cells also displayed decreased *** conclusion,a novel JALS-associated gene called TRMT2B was identified,thus broadening the clinical and genetic spectrum of ALS.

关键词： TRMT2B amyotrophic lateral sclerosis mitochondrial complex I tRNA methylation reactive oxygen species