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Protein & Cell 2023年第2期14卷 153-157页

作者： Rujin Huang Jinyang Liu Xi Chen Ying Zhi Shuangyuan Ding Jia Ming Yulin Li Yangming Wang Jie Na Center for Stem Cell Biology and regenerative medicine School of MedicineTsinghua UniversityBeijing 100084China School of Life Sciences Tsinghua UniversityBeijing 100084China Capital Medical University Beijing 100084China beijing key laboratory of Cardiometabolic Molecular medicine Peking-Tsinghua Center for Life SciencesInstitute of Molecular MedicinePeking UniversityBeijing 100871China

Dear Editor,Maintenance of cardiomyocyte(CM)homeostasis is essential for normal heart ***-term imbalance in heart homeostasis could elicit irreversible adaptive change in cell structure and function and tissue architecture,exemplified as cardiac hyper-trophy and fibrosis,and eventually develop into heart failure(Shiojima et al.,2005).Therefore,identifying new genes and path-ways regulating CM homeostasis may help better understand the cause of cardiac hypertrophy.

关键词： homeostasis cardiac hypertrophy

Coordination-driven self-assembly of metallo-nanodrugs for local inflammation alleviation

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Nano Research 2023年第12期16卷 13259-13266页

作者： Lijuan Tang Zhenghan Di Jingfang Zhang Feiying Yin Lele Li Li Zheng Guangxi key laboratory of regenerative medicine Guangxi Engineering Center in Biomedical Material for Tissue and Organ RegenerationCollaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development nd Application Co-Constructed by the Province and MinistryThe First Affiliated Hospital of Guangxi Medical UniversityNanning 530021China Pharmaceutical College Guangxi Medical UniversityNanning 530021China CAS key laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and TechnologyBeijing 100190China

Developing dedicated nanomedicines to improve delivery efficacy of anti-inflammatory drugs is still a formidable *** this study,we present an extremely simple yet efficient approach to obtain hybrid nanodrugs through metal-drug coordination-driven self-assembly for carrier-free drug *** resulting metallo-nanodrugs exhibit well-defined morphology and high drug encapsulation capability,allowing for the combination of magnetic resonance imaging and anti-inflammatory *** the case of osteoarthritis(OA),the metallo-nanodrugs remarkably alleviate synovial inflammation,preventing cartilage destruction and extracellular matrix *** addition,it led to significantly improved therapeutic efficacy compared with intra-articular administration of the same dose of free drugs in OA mouse *** work provides a very simple approach for the development of anti-inflammatory nanoformulations by exploiting coordination-driven self-assembly.

关键词： drug delivery coordination-driven assembly nanomedicine anti-inflammation therapy

Microgel-based carriers enhance skeletal stem cell reprogramming towards immunomodulatory phenotype in osteoarthritic therapy

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Bioactive Materials 2024年第4期34卷 204-220页

作者： Pei-Lin Li Da-Fu Chen Xiao-Tong Li Rui-Cong Hao Zhi-Dong Zhao Zhi-Ling Li Bo-Feng Yin Jie Tang Yu-Wen Luo Chu-Tse Wu Jing-Jun Nie Heng Zhu Department of Stem Cells and regenerative medicine Beijing Institute of Radiation MedicineRoad Taiping 27Beijing100850PR China beijing key laboratory for Radiobiology Beijing Institute of Radiation MedicineBeijing100850PR China laboratory of Bone Tissue Engineering Beijing Laboratory of Biomedical MaterialsNational Center for OrthopaedicsBeijing Research Institute of Traumatology and OrthopaedicsBeijing Jishuitan HospitalCapital Medical UniversityRoad Xinjiekou 31Beijing100035PR China People’s Liberation Army General Hospital Road Fuxing 28Beijing100853PR China

Skeletal stem cells(SSC)have gained attentions as candidates for the treatment of osteoarthritis due to their osteochondrogenic ***,the immunomodulatory properties of SSC,especially under delivery operations,have been largely *** the study,we found that Pdpn+and Grem1+SSC subpopulations owned immunoregulatory potential,and the single-cell RNA sequencing(scRNA-seq)data suggested that the mechanical activation of microgel carriers on SSC induced the generation of Pdpn+Grem1+Ptgs2+SSC subpopulation,which was potent at suppressing macrophage *** microgel carriers promoted the YAP nuclear translocation,and the activated YAP protein was necessary for the increased expression of Ptgs2 and PGE2 in microgels-delivered SSC,which further suppressed the expression of TNF-ɑ,IL-1βand promoted the expression of IL-10 in *** delivered with microgels yielded better preventive effects on articular lesions and macrophage activation in osteoarthritic rats than SSC without *** blocking the YAP and Ptgs2 in microgels-delivered SSC partially abolished the enhanced protection on articular tissues and suppression on osteoarthritic ***,microgel carriers significantly prolonged SSC retention time in vivo without increasing SSC implanting into osteoarthritic ***,our study demonstrated that microgel carriers enhanced SSC reprogramming towards immunomodulatory phenotype to regulate macrophage phenotype transformation for effectively osteoarthritic therapy by promoting YAP protein translocation into *** study not only complement and perfect the immunological mechanisms of SSC-based therapy at the single-cell level,but also provide new insight for microgel carriers in stem cell-based therapy.

关键词： Microgel carriers Skeletal stem cells Immunomodulation reprogram Single-cell RNA sequence Osteoarthritis

Embryonic lineage tracing with Procr-CreER marks balanced hematopoietic stem cell fate during entire mouse lifespan

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Journal of Genetics and Genomics 2019年第10期46卷 489-498页

作者： Xiaona Zheng Guangyu Zhang Yandong Gong Xiaowei Ning Zhijie Bai Jian He Fan Zhou Yanli Ni Yu Lan Bing Liu State key laboratory of Proteomics Academy of Military Medical SciencesAcademy of Military SciencesBeijing100071China beijing Advanced Innovation Center for Genomics Department of Obstetrics and GynecologyThird HospitalSchool of Life Sciences.Peking UniversityBeijingChina Biomedical Pioneering Innovation Center and Center for Reproductive medicine Third HospitalPeking UniversityBeijingChina State key laboratory of Experimental Hematology Fifth Medical Center of Chinese PLA General HospitalBeijingW0071China Guangzhou regenerative medicine and Health-Guangdong laboratory(GRMH-CDL):key laboratory for regenerative medicine of Ministry of Education Institute of HematologyDepartment of PathophysiologySchool of MedicineJinan UniversityGuangzhou510632China State key laboratory of Experimental Hematology Institute of Hematology and Blood Diseases HospitalChinese Academy of Medical SciencesTianjin300020China

The functional heterogeneity of hematopoietic stem cells(HSCs) has been comprehensively investigated by single-cell transplantation ***,the heterogeneity regarding their physiological contribution remains an open question,especially for those with life-long hematopoietic fate of rigorous selfrenewing and balanced differentiation *** this study,we revealed that Procr expression was detected principally in phenotypical vascular endothelium co-expressing DII4 and CD44 in the midgestation mouse embryos,and could enrich all the HSCs of the embryonic day 11.5(E11.5) aortagonad-mesonephros(AGM) *** then used a temporally restricted genetic tracing strategy to irreversibly label the Procr-exp res sing cells at ***,most labeled mature HSCs in multiple sites(such as AGM) around E11.5 were functionally categorized as lymphomyeloid-balanced HSCs assessed by direct ***,the labeled cells contributed to an average of 7.8% of immunophenotypically defined HSCs in E14.5 fetal liver(FL) and 6.9% of leukocytes in peripheral blood(PB) during one-year ***,in aged mice of 24 months,the embryonically tagged cells displayed constant contribution to leukocytes with no bias to myeloid or lymphoid ***,we demonstrated,for the first time,the existence of a subtype of physiologically long-lived balanced HSCs as hypothesized,whose precise embryonic origin and molecular identity await further characterization.

关键词： Genetic lineage tracing Hematopoietic stem cells Procr Heterogeneity Aorta-gonad-mesonephros region

The genetic program Of oocytes can be modified in vivo in the zebrafish ovary

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Journal of Molecular Cell Biology 2018年第6期10卷 479-493页

作者： Xiaotong Wu Weimin Shen Bingjie Zhang Anming Meng laboratory of Molecular Developmental Biology State Key Laboratory of Membrane BiologyTsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China Center for Stem Cell Biology and regenerative medicine MOE Key Laboratory of BioinformaticsTsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China

Oocytes,the irreplaceable gametes for generating a new organism,are matured in the ovary of living female *** is unknown whether any genetic manipulations can be applied to immature oocytes inside the living *** a proof-of-concept, we here demonstrate genetic amendments of zebrafish immature oocytes within the *** microinjection in situ (OMIS) stimulates tissue repair responses,but some of the microinjected immature oocytes are matured,ovulated and *** OMIS-mediated Cas9 approach,ntla and gata5 loci of oocytes arrested at prophase I of meiosis are successfully edited before *** OMIS,high efficiency of biaUeUc mutations in single or multiple loci using Cas9/gRNAs allows immediate manifestation of mutant phenotypes in Fo embryos and multiple transgenes can co-express the reporters in Fo embryos with patterns similar to germline transgenic ***,maternal knockdown of dnmt1 by antisense morphoino via OMIS results in a dramatic decrease of global DNA methylation level at the dome stage and causes embryonic lethalityprior to segmentation ***,OMIS opens a door to efficiently modify the genome and provides a possibility to re repair genetically abnormal oocytes in situ.

关键词： oocytes microinjection gene editing transgenesis morpholino zebrafish

Dual-bionic regenerative microenvironment for peripheral nerve repair

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Bioactive Materials 2023年第8期26卷 370-386页

作者： Yanjun Guan Zhiqi Ren Boyao Yang Wenjing Xu Wenjun Wu Xiangling Li Tieyuan Zhang Dongdong Li Shengfeng Chen Jun Bai Xiangyu Song Zhibo Jia Xing Xiong Songlin He Chaochao Li Fanqi Meng Tong Wu Jian Zhang Xiuzhi Liu Haoye Meng Jiang Peng Yu Wang Institute of orthopedics The Fourth Medical Center of Chinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma&War Injuries PLANo.51 Fucheng RoadBeijing100048PR China Co-innovation Center of Neuroregeneration Nantong University NantongJiangsu Province226007PR China Graduate School of Chinese PLA General Hospital No.28 Fuxing RoadBeijing100853PR China Hebei North University Zhangjiakou075051PR China School of medicine Nankai UniversityTianjin300071PR China

Autologous nerve grafting serves is considered the gold standard treatment for peripheral nerve defects;however,limited availability and donor area destruction restrict its widespread clinical *** the performance of allogeneic decellularized nerve implants has been explored,challenges such as insufficient human donors have been a major drawback to its clinical ***-engineered neural regeneration materials have been developed over the years,and researchers have explored strategies to mimic the peripheral neural microenvironment during the design of nerve catheter grafts,namely the extracellular matrix(ECM),which includes mechanical,physical,and biochemical signals that support nerve *** this study,polycaprolactone/silk fibroin(PCL/SF)-aligned electrospun material was modified with ECM derived from human umbilical cord mesenchymal stem cells(hUMSCs),and a dual-bionic nerve regeneration material was successfully *** results indicated that the developed biomimetic material had excellent biological properties,providing sufficient anchorage for Schwann cells and subsequent axon regeneration and angiogenesis ***,the dual-bionic material exerted a similar effect to that of autologous nerve transplantation in bridging peripheral nerve defects in *** conclusion,this study provides a new concept for designing neural regeneration materials,and the prepared dual-bionic repair materials have excellent auxiliary regenerative ability and further preclinical testing is warranted to evaluate its clinical application potential.

关键词： Electrospun Umbilical cord mesenchymal stem cells Extracellular matrix Peripheral nerve regeneration Tissue engineering

Simvastatin-hydroxyapatite coatings prevent biofilm formation and improve bone formation in implant-associated infections

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Bioactive Materials 2023年第3期21卷 44-56页

作者： Tiantong Sun Jie Huang Wang Zhang Xuanqi Zheng Hong Wang Jing Liu Huijie Leng Wanqiong Yuan Chunli Song Department of orthopedics Peking University Third HospitalBeijingChina beijing key laboratory of Spinal Diseases BeijingChina Engineering Research Center of Bone and Joint Precision medicine Ministry of EducationBeijingChina Institute of Medical Sciences The Second Hospital of Shandong UniversityJinanChina

Implant-associated infections(IAIs)caused by biofilm formation are the most devastating complications of orthopedic *** have been commonly and safely used drugs for hypercholesterolemia for many ***,we report that simvastatin-hydroxyapatite-coated titanium alloy prevents biofilm-associated *** antibacterial properties of simvastatin against Staphylococcus aureus and Staphylococcus epidermidis biofilms in vitro was confirmed by crystal violet staining and live-dead bacterial *** developed a simvastatin-and hydroxyapatite(Sim-HA)-coated titanium alloy via electrochemical ***-HA coatings inhibited Staphylococcus aureus biofilm formation and improved the biocompatibility of the titanium ***-HA coatings effectively prevented Staphylococcus aureus IAI in rat femurs,as confirmed by radiological assessment and histological *** antibacterial effects of the Sim-HA coatings were attributed to their inhibitory effects on biofilm formation,as verified by scanning electron microscopic observations and bacterial spread plate *** addition,the Sim-HA coatings enhanced osteogenesis and osteointegration,as verified by micro-CT,histological evaluation,and biomechanical pull-out *** summary,Sim-HA coatings are promising implant materials for protection against biofilm-associated infections.

关键词： Implant-associated infections Simvastatin Antibacterial Biofilm Osteogenesis

Efficacy and Safety of Bushen Huoxue Formula in Patients with Discogenic Low-Back Pain:A Double-Blind,Randomized,Placebo-Controlled Trial

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Chinese Journal of Integrative medicine 2022年第11期28卷 963-970页

作者： ZHAN Jia-wen LI Kai-ming ZHU Li-guo WANG Shang-quan FENG Min-shan WEI Xu YU Jie TANG Bin YIN Xun-lu HAN Tao ZHANG Ping LI Ling-hui CHEN Ming SHAO Chen-chen General orthopedics Department Wangjing HospitalChina Academy of Chinese Medical SciencesBeijing(100102)China key laboratory of beijing of Traditional Chinese medicine Bone Setting Beijing(100102)China orthopedics Department Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing(100091)China The Second Department of Spine Wangjing HospitalChina Academy of Chinese Medical SciencesBeijing(100102)China

Objective:To assess the efficacy and safety of Bushen Huoxue Formula(BSHXF)for the treatment of discogenic low-back pain(DLBP).Methods:This was a parallel,double-blind,randomized,clinical trial performed between May 2019 and June *** patients were assigned by computerized random number table to the treatment group(lumbar traction and BSHXF,35 cases)or the control group(lumbar traction and placebo,35 cases).The patients received intervention for 3 *** was conducted before treatment and at week 1,2,3 during *** outcome was the self-reported score of Oswestry Disability Index(ODI).Secondary outcomes included Visual Analog Scale(VAS),clinical efficacy rate by minimal clinically important difference(MCID)as well as lumbar tenderness,muscle tone and lumbar spine *** reactions were ***-up was performed at 1 and 3 months after the end of ***:In the treatment group,ODI score was significantly decreased compared with baseline(P<0.05)and the control group at 2-and 3-week ***,VAS score decreased compared with the baseline(P<0.05)and was lower than that in the control group at 2-and 3-week treatment(P<0.05).The clinical efficacy rate of the treatment group was higher than that of the control group after treatment[32.35%(11/34)vs.3.13%(1/32),P<0.05].Moreover,the tenderness,and muscle tone,as well as the back extension and left flexion in lumbar spine mobility in the treatment group at 3-week treatment were significantly improved compared with the control group(P<0.05).Follow-up showed that at 1-month after treatment,the treatment group had better outcomes than the control group with regard to a total score of ODI and VAS scores,as well as clinical efficacy rate(all P<0.05).Moreover,VAS score was still significantly lower than the control group at 3-month follow-up(P<0.05).No adverse reactions were reported during the ***:BSXHF combined with lumbar traction can significantly imp

关键词： Bushen Huoxue Formula discogenic low-back pain intervertebral disc degeneration randomized controlled trial

Chemical screen identifies a geroprotective role of quercetin in premature aging

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Protein & Cell 2019年第6期10卷 417-435页

作者： Lingling Geng Zunpeng Liu Weiqi Zhang Wei Li Zeming Wu Wei Wang Ruotong Ren Yao Su Peichang Wang Liang Sun Zhenyu Ju Piu Chan Moshi Song Jing Qu Guang-Hui Liu Advaneed Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric Disorders Xuanwu Hospital of Capital Medical University Beijing 100053 China National laboratory of Biomacromolecules CAS Center for Excellenee in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China State key laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China State key laboratory of Membrane Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China Institute of Stem cell and Regeneration Chinese Academy of Sciences Beijing 100101 China key laboratory of regenerative medicine of Ministry of Education Institute of Aging and Regenerative Medicine Jinan University Guangzhou 510632 China The MOH key laboratory of Geriatrics Beijing Hospital National Center of Gerontology Beijing 100730 China

Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders.

关键词： Quercetin Stem cell Aging Werner syndrome Hutchinson-Gilford progeria syndrome

Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamics in human cells

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Protein & Cell 2022年第4期13卷 258-280页

作者： Lei Chang Mengfan Li Shipeng Shao Chen Li Shanshan Ai Boxin Xue Yingping Hou Yiwen Zhang Ruifeng Li Xiaoying Fan Aibin He Cheng Li Yujie Sun State key laboratory of Membrane Biology School of Life Sciencesand Biomedical Pioneering Innovation Center(BIOPIC)Peking UniversityBeijing 100871China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China Center for Bioinformatics School of Life SciencesPeking UniversityBeijing 100871China Institute of Molecular medicine Beijing Key Laboratory of Cardiometabolic Molecular MedicinePeking UniversityBeijing 100871China Center for Statistical Science Peking UniversityBeijing 100871China Bioland laboratory(Guangzhou regenerative medicine and Health Guangdong laboratory) Guangzhou 510530China

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome ***,the molecular machinery underlying these hierarchically organized three-dimensional(3D)chromatin architecture and dynamics remains poorly *** by combining imaging and sequencing,we studied the role of lamin B1 in chromatin architecture and *** found that lamin B1 depletion leads to detachment of lamina-associated domains(LADs)from the nuclear periphery accompanied with global chromatin redistribution and ***,the interchromosomal as well as inter-compartment interactions are increased,but the structure of topologically associating domains(TADs)is not *** live-cell genomic loci tracking,we further proved that depletion of lamin B1 leads to increased chromatin dynamics,owing to chromatin decompaction and redistribution toward *** together,our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance,chromatin compaction,genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics,supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.

关键词： lamin B1 3D genome Hi-C chromatin dynamics chromosome territories A/B compartments livecell imaging super-resolution imaging