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Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke

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Neural Regeneration Research 2025年第3期20卷 845-857页

作者： Lin-Yan Huang Yi-De Zhang Jie Chen Hai-Di Fan Wan Wang Bin Wang Ju-Yun Ma Peng-Peng Li Hai-Wei Pu Xin-Yian Guo Jian-Gang Shen Su-Hua Qi School of Medical Technology Xuzhou Key Laboratory of Laboratory DiagnosticsXuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Pharmacy Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Laboratory Medicine Branch Hospital of Huai’an First People’s HospitalHuai’anJiangsu ProvinceChina Department of Laboratory Medicine the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Chinese Medicine The University of Hong KongHong Kong Special Administrative RegionChina

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late ***,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain *** previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently *** simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic *** found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous ***,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid *** results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/***,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and *** suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion *** levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-*** transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear ***,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

关键词： cell differentiation cerebral ischemia/reperfusion injury chlorination hypochlorous acid microglia neural stem cell neurogenesis nuclear translocation stroke β-catenin

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Energy landscape decomposition for cell differentiation with proliferation effect

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National Science Review 2022年第8期9卷 144-152页

作者： Jifan Shi Kazuyuki Aihara Tiejun Li Luonan Chen Research Institute of Intelligent Complex Systems Fudan University International Research Center for Neurointelligence The University of Tokyo Institutes for Advanced Study The University of Tokyo Key Laboratory of Mathematics and Its Applications (LMAM) and School of Mathematical Sciences Peking University Key Laboratory of Systems Biology Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences Key Laboratory of Systems Health Science of Zhejiang Province Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Chinese Academy of Sciences School of Life Science and Technology Shanghai Tech University Guangdong Institute of Intelligence Science and Technology

Complex interactions between genes determine the development and differentiation of cells. We establish a landscape theory for cell differentiation with proliferation effect, in which the developmental process is modeled as a stochastic dynamical system with a birth-death term. We find that two different energy landscapes, denoted U and V, collectively contribute to the establishment of non-equilibrium steady differentiation. The potential U is known as the energy landscape leading to the steady distribution, whose metastable states stand for cell types, while V indicates the differentiation direction from pluripotent to differentiated cells. This interpretation of cell differentiation is different from the previous landscape theory without the proliferation effect. We propose feasible numerical methods and a mean-field approximation for constructing landscapes U and V. Successful applications to typical biological models demonstrate the energy landscape decomposition’s validity and reveal biological insights into the considered processes.

关键词： energy landscape cell differentiation stochastic systems

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Coactivator-associated arginine methyltransferase 1: A versatile player in cell differentiation and development

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Genes & Diseases 2023年第6期10卷 2383-2392页

作者： Zhongrui Ma Xinxing Lyu Ning Qin Haoyu Liu Mengrui Zhang Yongchao Lai Bo Dong Peiyuan Lu Medical Research Center The First Affiliated Hospital of Shandong First Medical UniversityJinanShandong 250014China Department of Immunology Medical Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinanShandong 250117China Department of Biochemistry and Molecular Biology School of Basic MedicineShandong First Medical University&Shandong Academy of Medical SciencesJinanShandong 250117China Department of Cardiology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250021China

Protein arginine methylation is a common post-translational modification involved in the regulation of various cellular functions. Coactivator-associated arginine methyltransferase 1 (CARM1) is a protein arginine methyltransferase that asymmetrically dimethylates histone H3 and non-histone proteins to regulate gene transcription. CARM1 has been found to play important roles in cell differentiation and development, cell cycle progression, autophagy, metabolism, pre-mRNA splicing and transportation, and DNA replication. In this review, we describe the molecular characteristics of CARM1 and summarize its roles in the regulation of cell differentiation and development in mammals.

关键词： Arginine methylation CARM1 cell differentiation Development Epigenetic regulation

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Alreration of nuclear matrix-intermediate filament system and differential expression of nuclear matrix proteins during human hepatocarcinoma cell differentiation

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World Journal of Gastroenterology 2007年第20期13卷 2791-2797页

作者： Jian Tang Jing-Wen Niu Dong-Hui Xu Zhi-Xing Li Qi-Fu Li Jin-An Chen The Key Laboratory of Chinese Ministry of Education for cell Biology and Tumor cell Engineering School of Life Sciences Xiamen University Xiamen 361005 Fujian Province China Department of Hepatic Biliary Pancreatic Vascular Surgery 1st Hospitalof Xiamen Fujian Medical University Xiamen 361003 Fujian Province China

AIM： To investigate the association between the configurational and compositional changes of nuclear matrix and the differentiation of carcinoma cells. METHODS： cells cultured with or without 5 × 10^-3 mmol/L of hexamethylene bisacetamide （HMBA） on Nickel grids were treated by selective extraction and prepared for whole mount observation under electron microscopy. The samples were examined under transmission electron microscope. Nuclear matrix proteins were selectively extracted and subjected to subcellular proteomics study. The protein expression patterns were analyzed by PDQuest software. Spots of differentially expressed nuclear matrix proteins were excised and subjected to in situ digestion with trypsin. The peptides were analyzed by matrix-assisted laser- desorption/ionization time of flight mass spectrometry （MALDI-TOF-MS）. Data were submitted for database searching using Mascot tool （***）. RESULTS： The nuclear matrix （NM） and intermediate filament （IF） in SMMC-7721 hepatocarcinoma cells were found relatively sparse and arranged irregularly. The nuclear lamina was non-uniform, and two kinds of filaments were not tightly connected. After induction for differentiation by HMBA, the NM-IF filaments were concentrated and distributed uniformly. The heterogeneous population of filaments, including highly branched utrathin filaments could also be seen in the regular meshwork. The connection between the two kinds of filaments and the relatively thin, condensed and sharply demarcated lamina composed of intermediate- sized filaments was relatively fastened. Meanwhile, 21 NM proteins changed remarkably during SMMC-7721 cell differentiation. Four proteins, i.e. mutant Pystl, hypothetical protein, nucleophosminl, and LBP were downregulated, whereas four other proteins, eIF6, p44 subunit, 13-tubulin, and SIN3B were upregulated with the last one, SR2/ASF found only in the differentiated SMMC-7721 cells. CONCLUSION： The induced differentiation of SMMC-7

关键词： Nuclear matix-intermediate filament system Nuclear matrix protein Hexamethylamine bisacetamide SMMC-7721 cells cell differentiation

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System approaches reveal the molecular networks involved in neural stem cell differentiation

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Protein & cell 2012年第3期3卷 213-224页

作者： Kai Wang Haifeng Wang Jiao Wang Yuqiong Xie Jun Chen Huang Yan Zengrong Liu Tieqiao Wen Laboratory of Molecular Neurobiology School of Life SciencesShanghai UniversityShanghai 200444China School of Communication and Information Engineering Shanghai UniversityShanghai 200444China College of Life Science Wuhan UniversityWuhan 430072China College of Chemical Engineering and Technology Wuhan University of Science and TechnologyWuhan 430081China Institute of Systems Biology Shanghai UniversityShanghai 200444China􀀍

The self-renewal and multipotent potentials in neural stem cells(NSCs)maintain the normal physiological functions of central nervous system(CNS).The ab-normal differentiation of NSCs would lead to CNS ***,the mechanisms of how NSCs differentiate into astrocytes,oligodendrocytes(OLs)and neurons are still unclear,which is mainly due to the complexity of differentiation processes and the limita-tion of the cell separation *** this study,we modeled the dynamics of neural cell interactions in a systemic approach by mining the high-throughput genomic and proteomic data,and identified 8615 genes that are involved in various biological processes and functions with significant changes during the differentiation processes.A total of 1559 genes are specifically expressed in neural cells,in which 242 genes are NSC specific,215 are astrocyte specific,551 are OL specific,and 563 are neuron *** addition,we proposed 57 transcriptional regulators specifically expressed in NSCs may play essential roles in the development *** findings provide more comprehensive analysis for better understanding the endogenous mechanisms of NSC fate determination.

关键词： neural stem cell cell differentiation mo-lecular networks

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Effects of areca nut consumption on cell differentiation of osteoblasts, myoblasts, and fibroblasts

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BIOcell 2023年第2期47卷 283-287页

作者： YUNG-FU CHANG Department of Biomedical Science and Environmental Biology Kaohsiung Medical UniversityKaohsiung807Taiwan Department of Medical Research Kaohsiung Medical University HospitalKaohsiung807Taiwan Translational Research Center of Neuromuscular Diseases Kaohsiung Medical University HospitalKaohsiung807Taiwan

Areca nut is used worldwide as a hallucinogenic addicting drug along the tropical ***,a toxic compound,is the most important alkaloid in areca *** adverse effects of oral uptake and chewing of areca nut are well *** example,the possibility of cancer caused by chewing areca nuts is widely *** areca nut has other adverse effects on other organs,including abnormal cell differentiation,oral cancer,and several other *** use of areca nut is also associated with low *** musculature is the largest organ in the body and is attached to the *** embryo development,the differentiation of bone and muscle cells is *** this article,we reviewed the effects of areca nut and arecoline on embryonic cell differentiation,particularly osteoblasts,myoblasts,and fibroblasts.

关键词： Areca nut cell differentiation Osteoblast Myoblast Fibroblast

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NEW DESIGNED HMBA AGENTS AS INDUCERS OFERYTHROLEUKEMIA cell differentiation

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Chinese Medical Sciences Journal 2002年第1期17卷 27-31页

作者：王华力张世馥周建平章静波 Department of cell Biology Institute of Basic Medical Sciences CAMS & PUMC Beijing 100005

Searching for more potent and less toxic HMBA related agents. Methods. Human erythroleukemia cell K562, murine erythroleukemia cell (MEL) and its sub line MEL DS19 were used as target cells to select a cell line which is the most sensitive to HMBA, then analyzed the activity of inducing differentiati on of two new designed HMBA derivatives: HMBPA [hexamethylenebi (3 pyridin) ami de] and Co HDTA (ethylenediaminetetra acetic acid cobalt) using cell biology, c ytochemical and molecular biology techniques. Results. We found that the MEL DS19 cells were most sensitive to HMBA (benzidine positive, B+～76%). Co HDTA can inhibit the growth of MEL DS19, but induces differentiation just in a small population (B+ 2%～4.5%). Between 0.02～5μmo l/L, HMBPA induces 3%～8% cells committed to differentiation with little inhib ition of cell proliferation. 1μmol/L HMBPA and 2mmol/L HMBA together, can obvio usly increase the percentage of differentiated cell (B+～ 72%), inhibit DNA sy nthesis and accelerate β globin transcription. Conclusion. The new HMBA derivatives may provide potential cancer differentiatio n inducers.

关键词： cell differentiation HMBA MEL cell cell cycle

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pRb-E2F signaling in life of mesenchymal stem cells:cell cycle,cell fate,and cell differentiation

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Genes & Diseases 2014年第2期1卷 174-187页

作者： Boris Popov Nikolay Petrov Institute of Cytology Russian Academy of SciencesSt.Petersburg4Tikhoretsky Av.194064Russia

Mesenchymal stem cells(MSCs)are multipotent cells that can differentiate into various mesodermal lines forming fat,muscle,bone,and other lineages of connective *** possess plasticity and under special metabolic conditions may transform into cells of unusual phenotypes originating from ecto-and *** transplantation,MSCs release the humoral factors promoting regeneration of the damaged *** last five years,the numbers of registered clinical trials of MSCs have increased about 10 *** gives evidence that MSCs present a new promising resource for cell therapy of the most dangerous *** efficacy of the MSCs therapy is limited by low possibilities to regulate their conversion into cells of damaged tissues that is implemented by the pRb-E2F *** widely accepted viewpoint addresses pRb as ubiquitous regulator of cell cycle and tumor ***,current publications suggest that basic function of the pRb-E2F signaling in development is to regulate cell fate and *** facultative and constitutive chromatin modifications,pRb-E2F signaling promotes transient and stable cells quiescence,cell fate choice to differentiate,to senesce,or to *** of pRb is associated with cancer cell *** regulates cell fate by retaining quiescence of one cell population in favor of commitment of another or by suppression of genes of different cell *** is the founder member of the“pocket protein”family possessing functional *** increase in the efficacy of the MSCs based cell therapy will depend on precise understanding of various aspects of the pRb-E2F signaling.

关键词： cell cycle cell differentiation cell fate Mesenchymal stem cells pRb-E2F signaling

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Function of Delta4 gene and its effects on 32D cell differentiation

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Chinese Medical Journal 2004年第11期117卷 1687-1692页

作者：纪春岩崔才三马道新赵建强郭农建张茂宏 Institute of Hematology Qilu Hospital Shandong University Jinan 250012 China

Background Notch activation leads to transcriptional suppression of lineage-specific genes, inhibiting differentiation in response to inductive signals. The Notch signal system contains three parts: Notch molecules, Notch ligands and effectors. Delta4 is a newly-discovered Notch ligand which has received the attention of few detailed studies. This study sought to explore the biological function of Delta4 and observe its effects on 32D cell *** Delta4-expressing vector *** was constructed using molecular biological techniques. CHO cells stably transfected with *** were confirmed to have a Delta4 protein band via Western blotting. High-expression Delta4-CHO clones were selected for the following functional studies. Notch1-CHO and Notch2-CHO were used as host cells. After transiently transfecting with transition protein 1 (TP 1), Delta4 activity was compared in both cell lines by means of luciferase analysis. CHO cells were incubated with Notch1-32D cells that had been transfected with Notch1 and were observed for granulocyte colony-stimulating factor (G-CSF)-induced differentiation. Jagged2-CHO and Delta4-CHO cells transfected with the Notch ligands Jagged2 and Delta4, respectively, were incubated with Notch1-32D cells to observed inhibition of Notch o n G-CSF-induced differentiation. Results The vector *** was constructed successfully. CHO cells were stably transfected with the vector ***. Two CHO cell lines expressing Delta4 at high levels were selected for use in the study. Delta4 was found to induce signal activity via both Notch1 and Notch2 and the induction of signaling activity was stronger in Notch2 cells than in Notch1 cells. Compared with other Notch ligands, Delta4 was slightly weaker than Jagged2, but stronger than Delta1 and Jagged1 in terms of Notch1 ligands. In terms of Notch2, Delta4 had a strong signaling activity, but was weaker than Delta1, Jagged

关键词： Notch protein Delta-4 protein huma n cell differentiation

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Nanostructured Graphene Surfaces Promote Different Stages of Bone cell differentiation

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Nano-Micro Letters 2018年第3期10卷 103-114页

作者： F.F.Borghi P.A.Bean M.D.M.Evans T.van der Laan S.Kumar K.Ostrikov Plasma Nanoscience School of Physics The University of Sydney CSIRO Manufacturing Brazilian Centre for Physics Research (CBPF) School of Chemistry Physics and Mechanical EngineeringQueensland University of Technology CSIRO-QUT Joint Sustainable Processes and Devices Laboratory Commonwealth Scientific and Industrial Research Organization

Nanostructured graphene films were used as platforms for the differentiation of Saos-2 cells into bonelike cells. The films were grown using the plasma-enhanced chemical vapor deposition method, which allowed the production of both vertically and horizontally aligned carbon nanowalls(CNWs). Modifications of the techniqueallowed control of the density of the CNWs and their orientation after the transfer process. The influence of two different topographies on cell attachment, proliferation,and differentiation was investigated. First, the transferred graphene surfaces were shown to be noncytotoxic and were able to support cell adhesion and growth for over 7 ***, early cell differentiation(identified by cellular alkaline phosphatase release) was found to be enhanced on the horizontally aligned CNW surfaces, whereas mineralization(identified by cellular calcium production), a later stage of bone cell differentiation, was stimulated by the presence of the vertical CNWs on the surfaces. These results show that the graphene coatings, grown using the presented method, are biocompatible. And their topographies have an impact on cell behavior, which can be useful in tissue engineering applications.

关键词： Carbon nanowalls Graphene films Bone cell cell differentiation Plasma nanoscience

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