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The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

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Neural Regeneration Research 2025年第4期20卷 1153-1163页

作者： Susana Mellado María JoséMorillo-Bargues Carla Perpiñá-Clérigues Francisco García-García Victoria Moreno-Manzano Consuelo Guerri María Pascual department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain bioinformatics and Biostatistics Unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue Regeneration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain *** stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent *** the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge *** demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent *** analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling *** together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

关键词： adolescence binge-like ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)

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Single-cell technologies: current and near future

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Science China Life Sciences 2025年第1期68卷 1-4页

作者： Chenfei Wang Qi Liu Xiaohui Fan Tieliu Shi Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration Ministry of EducationOrthopedics DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science Center for Stem Cells School of Life Sciences and TechnologyTongji University Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research Institute of Intelligent Computing Zhejiang Lab Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang University National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University Center for bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Key Laboratory of Advanced Theory and Application in Statistics and Data Science (MOE) School of StatisticsEast China Normal University

Single-cell technologies enable the indepth exploration of multiple biological hierarchies at the scale of individual cells,which have deepened our knowledge of cellular diversity, tissue organization, and overall organism function(Sun et al.,2024). In 2009, single-cell RNA sequencing(sc RNA-seq) was first developed as a powerful tool to dissect gene expression and uncover transcriptional *** the rapid advancement of technology, single-cell approaches have expanded to encompass other omics, such as genomics, epigenomics, proteomics,and metabolomics.

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Small extrachromosomal circular DNA in amyotrophic lateral sclerosis matter

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Neural Regeneration Research 2025年第5期20卷 1411-1413页

作者： Marcos J.Arauzo-Bravo Daniela Gerovska Matthias Schwab Alexandra Kretz Computational Biology and Systems Biomedicine Biodonostia Health Research InstituteSan SebastianSpain Basque Foundation for Science IKERBASQUEBilbaoSpainMax Planck Institute for Molecular BiomedicineComputational Biology and Bioinformatics GroupMünsterNorth Rhine-WestphaliaGermany department of Cell Biology and Histology Faculty of Medicine and NursingUniversity of Basque Country(UPV/EHU)LeioaSpain department of Neurology Jena University HospitalJenaThuringiaGermany

Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 Motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fALS),most cases are considered sporadic(sALS).However,population-based studies suggest that even cases without a common index mutation impart heritability(Ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.

关键词： amyotrophic sclerosis

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Single-cell omics: experimental workflow, data analyses and applications

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Science China Life Sciences 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science Center for Stem Cells School of Life Sciences and TechnologyTongji University Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research Institute of Intelligent Computing Zhejiang Lab Shanghai Research Institute for Intelligent Autonomous Systems Center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University Center for bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Beijing Institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of StatisticsEast China Normal University

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

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Levels and activities of von Willebrand factor and metalloproteinase with thrombospondin type-1 motif, number 13 in inflammatory bowel diseases

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World Journal of Gastroenterology 2017年第26期23卷 4796-4805页

作者： Dorota Cibor Danuta Owczarek Saulius Butenas Kinga Salapa Tomasz Mach Anetta Undas department of Gastroenterology Hepatology and Infectious DiseasesJagiellonian University Medical College department of Biochemistry College of MedicineUniversity of Vermont department of bioinformatics and telemedicine Jagiellonian University Medical College Institute of Cardiology Jagiellonian University Medical College

To evaluate the levels of von Willebrand factor (VWF) and metalloproteinase with thrombospondin type-1 motif, number 13 (ADAMTS13) in inflammatory bowel disease (IBD) and correlate them with the disease activity. METHODSConsecutive patients with IBD aged 18 years or older were enrolled in the study. Forty-seven patients with ulcerative colitis (UC), 38 with Crohn’s disease (CD), and 50 healthy controls were included. The white blood cell count, haematocrit, platelet count, fibrinogen, partial activated thromboplastin time, C-reactive protein, albumin, VWF antigen level (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), VWF collagen-binding activity (VWF:CB), and ADAMTS13 antigen level (ADAMTS13:Ag) and activity (ADAMTS13act) were measured. The following ratios were assessed: VWF:RCo/VWF:Ag, VWF:CB/VWF:Ag, VWF:Ag/ADAMTS13act, and ADAMTS13act/ADAMTS13:Ag. RESULTSCompared to controls, the odds ratio (OR) of an elevated VWF: Ag > 150% was 8.7 (95%CI: 2.7-28.1) in the UC group and 16.2 (95%CI: 4.8-54.0) in the CD group. VWF:CB was lower in UC patients, and active CD was associated with a higher VWF: RCo (+38%). The ORs of VWF:CB/VWF:Ag < 0.7 (a marker of acquired von Willebrand syndrome) in the UC and CD groups were 11.9 (95%CI: 4.4-32.4) and 13.3 (95%CI: 4.6-38.1), respectively. Active UC was associated with lower ADAMTS13:Ag (-23%) and ADAMTS13act (-20%) compared to UC in remission. Patients with active CD had a 15% lower ADAMTS13act than controls. The activity of UC, but not that of CD, was inversely correlated with ADAMTS13:Ag (r = -0.76) and ADAMTS13act (r = -0.81). CONCLUSIONComplex VWF-ADAMTS13-mediated mechanisms disturb haemostasis in IBD. A reduced WVF:CB is a risk factor for bleeding, while a lower ADAMTS13 level combined with an elevated VWF:Ag could predispose one to thrombosis.

关键词： ADAMTS13 Inflammatory bowel disease Thrombosis Acquired von Willebrand syndrome von Willebrand factor

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Feature Rescaling of Support Vector Machines

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Tsinghua Science and Technology 2011年第4期16卷 414-421页

作者：武征鹏张学工 MOE Key Laboratory of bioinformatics and bioinformatics Division Department of Automation Tsinghua University

Support vector machines （SVMs） have widespread use in various classification problems. Although SVMs are often used as an off-the-shelf tool, there are still some important issues which require improvement such as feature rescaling. Standardization is the most commonly used feature rescaling method. However, standardization does not always improve classification accuracy. This paper describes two feature rescaling methods： multiple kernel learning-based rescaling （MKL-SVM） and kernel-target alignment-based rescaling （KTA-SVM）. MKL-SVM makes use of the framework of multiple kernel learning （MKL） and KTA-SVM is built upon the concept of kernel alignment, which measures the similarity between kernels. The proposed meth- ods were compared with three other methods： an SVM method without rescaling, an SVM method with standardization, and SCADSVM. Test results demonstrate that different rescaling methods apply to different situations and that the proposed methods outperform the others in general.

关键词： support vector machines (SVMs) feature rescaling multiple kernel learning (MKL) kernel-targetalignment (KTA)

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Contribution of β-phenethylamine, a component of chocolate and wine, to dopaminergic neurodegeneration: implications for the pathogenesis of Parkinson's disease

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Neuroscience Bulletin 2013年第5期29卷 655-660页

作者： Anupom Borah Rajib Paul Muhammed Khairujjaman Mazumder Nivedita Bhattacharjee department of Life Science and bioinformatics Assam University

While the cause of dopaminergic neuronal cell death in Parkinson＇s disease（PD）is not yet understood,many endogenous molecules have been implicated in its pathogenesis.β-phenethylamine（β-PEA）,a component of various food items including chocolate and wine,is an endogenous molecule produced from phenylalanine in the *** has been reported recently that long-term administration ofβ-PEA in rodents causes neurochemical and behavioral alterations similar to that produced by parkinsonian *** toxicity ofβ-PEA has been linked to the production of hydroxyl radical（.OH）and the generation of oxidative stress in dopaminergic areas of the brain,and this may be mediated by inhibition of mitochondrial *** significant observation is that administration ofβ-PEA to rodents reduces striatal dopamine content and induces movement disorders similar to those of parkinsonian ***,no reports are available on the extent of dopaminergic neuronal cell death after administration ofβ-*** on the literature,we set out to establishβ-PEA as an endogenous molecule that potentially contributes to the progressive development of *** sequence of molecular events that could be responsible for dopaminergic neuronal cell death in PD by consumption ofβ-PEA-containing foods is proposed ***,long-term over-consumption of food items containingβ-PEA could be a neurological risk factor having significant pathological consequences.

关键词： oxidative stress hydroxyl radical mitochondrial complex-I α-synuclein Lewy body ubiquitinproteasome system

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A Novel Structural Measure Separating Non-Coding RNAs from Genomic Backgrounds

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Tsinghua Science and Technology 2015年第5期20卷 474-483页

作者： Yingfeng Wang Russell L.Malmberg Liming Cai the School of Information Technology Middle Georgia State University department of Plant Biology and Institute of bioinformatics University of Georgia department of Computer Science and Institute of bioinformatics University of Georgia

RNA secondary structure has become the most exploitable feature for ab initio detection of non-coding RNA（nc RNA） genes from genome sequences. Previous work has used Minimum Free Energy（MFE） based methods developed to identify nc RNAs by measuring sequence fold stability and certainty. However, these methods yielded variable performances across different nc RNA species. Designing novel reliable structural measures will help to develop effective nc RNA gene finding tools. This paper introduces a new RNA structural measure based on a novel RNA secondary structure ensemble constrained by characteristics of native RNA tertiary structures. The new method makes it possible to achieve a performance leap from the previous structure-based methods. Test results on standard nc RNA datasets（benchmarks） demonstrate that this method can effectively separate most nc RNAs families from genome backgrounds.

关键词： RNA secondary structure RNA tertiary structure Inside algorithm

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Highly Regional Genes:graph-based gene selection for single-cell RNA-seq data

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Journal of Genetics and Genomics 2022年第9期49卷 891-899页

作者： Yanhong Wu Qifan Hu Shicheng Wang Changyi Liu Yiran Shan Wenbo Guo Rui Jiang Xiaowo Wang Jin Gu MOE Key Laboratory of bioinformatics BNRIST Bioinformatics DivisionDepartment of AutomationTsinghua UniversityBeijing 100084China

Gene selection is an indispensable step for analyzing noisy and high-dimensional single-cell RNA-seq(scRNA-seq)*** with the commonly used variance-based methods,by mimicking the human maker selection in the 2D visualization of cells,a new feature selection method called HRG(Highly Regional Genes)is proposed to find the informative genes,which show regional expression patterns in the cell-cell similarity *** mathematically find the optimal expression patterns that can maximize the proposed scoring *** comparison with several unsupervised methods,HRG shows high accuracy and robustness,and can increase the performance of downstream cell clustering and gene correlation ***,it is applicable for selecting informative genes of sequencing-based spatial transcriptomic data.

关键词： Single-cell RNA-sequencing Feature selection Spatially resolved transcriptomic data Regional patterns Graphical models

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Translational bioinformatics: Past, Present, and Future

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Genomics, Proteomics & bioinformatics 2016年第1期14卷 31-41页

作者： Jessica D.Tenenbaum department of Biostatistics and bioinformatics Duke University School of Medicine

Though a relatively young discipline, translational bioinformatics （TBI） has become a key component of biomedical research in the era of precision medicine. Development of high-throughput technologies and electronic health records has caused a paradigm shift in both healthcare and biomedical research. Novel tools and methods are required to convert increasingly voluminous datasets into information and actionable knowledge. This review provides a definition and contex- tualization of the term TBI, describes the discipline＇s brief history and past accomplishments, as well as current loci, and concludes with predictions of future directions in the field.

关键词： Translational bioinformatics Biomarkers Genomics Precision medicine Personalized medicine

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