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Labeling of cynomolgus monkey bone marrow-derived mesenchymal stem cells for cell tracking by multimodality imaging

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Science China(Life Sciences) 2011年第11期54卷 981-987页

作者： REN ZhenHua WANG JiaYin zou chunlin GUAN YunQian ZHANG Yu Alex Cell Therapy Center Xuanwu Hospital Capital Medical University and Key Laboratory of Neurodegeneration Ministry of Education Beijing 100053 China Department of Anatomy Anhui Medical University Hefei 230032 China

Recently,transplantation of allogeneic and autologous cells has been used for regenerative medicine.A critical issue is monitoring migration and homing of transplanted cells,as well as engraftment efficiency and functional capability in *** of superparamagnetic iron oxide(SPIO) particles by magnetic resonance imaging(MRI) has been used in animal models and clinical settings to track labeled cells.A major limitation of MRI is that the signals do not show biological characteristics of transplanted cells in *** marrow mesenchymal stem cells(MSCs) have been extensively investigated for their various therapeutic properties,and exhibit the potential to differentiate into cells of diverse *** this study,cynomolgus monkey MSCs(cMSCs) were labeled with Molday ION Rhodamine-BTM(MIRB),a new SPIO agent,to investigate and characterize the biophysical and MRI properties of labeled cMSCs in vitro and in *** results indicate that MIRB is biocompatible and useful for cMSCs labeling and cell tracking by multimodality *** method is helpful for detection of transplanted stem cells in vivo,which is required for understanding mechanisms of cell therapy.

关键词： bone marrow mesenchymal stem cells MRI Molday ION Rhodamine-BTM transplantation nonhuman primate

Inducible regulation of GDNF expression in human neural stem cells

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Science China(Life Sciences) 2013年第1期56卷 32-39页

作者： WANG ShuYan REN Ping GUAN YunQian zou chunlin FU LinLin ZHANG Yu Cell Biology Room Xuanwu HospitalCapital Medical Universityand Key Laboratory of NeurodegenerationMinistry of Education

Glial cell derived neurotrophic factor （GDNF） holds promises for treating neurodegenerative diseases such as Parkinson＇s dis- ease. Human neural stem cells （hNSCs） have proved to be a suitable cell delivery vehicle for the safe and efficient introduction of GDNF into the brain. In this study, we used hNSCs-infected with a lentivirus encoding GDNF and the hygromycin re- sistance gene as such vehicles. A modified tetracycline operator 7 （tetO7） was inserted into a region upstream of the EFI-α promoter to drive GDNF expression. After hygromycin selection, hNSCs were infected with a lentivirus encoding a KRAB-tetracycline repressor fusion protein （TTS）. TTS bound to tetO7 and suppressed the expression of GDNF in hNSCs. Upon administration of doxycycline （Dox） the TTS-tetO7 complex separated and the expression of GDNF resumed. The hNSCs infected with GDNF expressed the neural stem cell specific markers, nestin and sox2, and exhibited no significant change in proliferation rate. However, the rate of apoptosis in hNSCs expressing GDNF was lower compared with normal NSCs in response to actinomycin treatment. Furthermore, a higher percentage of Tuj-I positive cells were obtained from GDNF-producing NSCs under conditions that induced differentiation compared to control NSCs. The inducible expression of GDNF in hNSCs may provide a system for the controllable delivery of GDNF in patients with neurodegenerative diseases.

关键词： neural stem cells GDNF lentivirus vectors tetracycline operator

Characterizing the induction of diabetes in juvenile cynomolgus monkeys with different doses of streptozotocin

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Science China(Life Sciences) 2012年第3期55卷 210-218页

作者： zou chunlin WANG JiaYin WANG ShuYan HUANG Fen REN ZhenHua CHEN ZhiGuo ZHANG YU Cell Therapy Center Xuanwu HospitalCapital Medical UniversityBeijing 100053China Key Laboratory of Neurogeneration Ministry of EducationBeijing 100053China Center for Translational Medicine Guangxi Medical UniversityGuangxi 530021China Guangxi Nanning Wincon TheraCeUs Biotechnologies Co. Guangxi 530003China

Juvenile （2-3 years old） cynomolgus monkeys are frequently used as recipients in non-human primate islet transplantation studies. The aim of this study was to examine the effects of different doses of streptozotocin （STZ）, and find the optimal dose for inducing diabetes in these monkeys. Fifteen juvenile （2-3 years old） cynomolgus monkeys were separated into three groups and administered with different doses of STZ （100, 68 or 60 mg kg-l）. Basal and glucose-stimulated blood glucose, in- sulin, and C-peptide levels, as well as body weights were monitored. Hepatic and renal function tests and pancreatic immuno- histochemistry were performed before and after STZ treatment. Monkeys treated with both 100 and 68 mg kg-1 of STZ exhib- ited continuous hyperglycemia, which coincided with a nearly complete loss of islet 13-cells. Two monkeys received 60 mg kg-1 of STZ, but only one became completely diabetic. During the first week following STZ treatment, hepatic and renal func- tion slightly increased in these three groups. However. 24 hours post-STZ, serum total bile acid levels were significantly in- creased in monkeys treated with 100 mg kg-1 than those treated with 68 mg kg-I of STZ （P〈0.05）. These data suggest that 100 mg kg-1 and 68 mg kg-1 of STZ can safely induce diabetes in cynomolgus monkeys aged 2-3 years, but 68 mg kg-1 of STZ, rather than 100 mg kg-1 of STZ, may be more appropriate for inducing diabetes in these monkeys. Furthermore, body surface area, rather than body weight, was a more reliable determinant of dosage, where 700 mg m-2 of STZ should be the lower limit for inducing diabetes in juvenile monkeys.

关键词： cynomolgus monkeys diabetes streptozotocin

*** of *** enhances prostate cancer chemoresistance via Notch signaling

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Chinese Journal of Cancer 2017年第3期36卷 150-162页

作者： Wenchu Wang Lihui Wang Atsushi Mizokami Junlin Shi chunlin zou Jinlu Dai Evan T. Keller Yi Lu Jian Zhang Center for Translational Medicine Guangxi Medical University 12th FloorMedical Science Research Building No. 22 Shuangyong Road NanningGuangxi 530021 P. R. China Key Laboratory of Longevity and Ageingrelated Diseases Ministry of Education Nanning Guangxi 530021 P. R. China Department of Urology and Pathology School of Medicine University of Michigan Ann Arbor MI 48109 USA Department of Urology Graduate School of Medical Sciences Kanazawa University Kanazawa 920.1192 Japan Department of Biology and School of Medicine Southern University of Science and Technology Shenzhen Guangdong 518055 P. R. China Department of Urology University of Pittsburgh School of Medicine Pittsburgh PA 15232 USA

Background:The chemoresistance of prostate cancer(PCa)is invariably associated with the aggressiveness and metastasis of this *** emerging evidence indicates that the epithelial-to-mesenchymal transition(EMT)may play pivotal roles in the development of chemoresistance and *** a hallmark of EMT,E-cadherin is suggested to be a key marker in the development of ***,the molecular mechanisms underlying PCa chemoresistance remain *** current study aimed to explore the association between EMT and chemoresistance in PCa as well as whether changing the expression of E-cadherin would affect PCa ***:Parental PC3 and DU145 cells and their chemoresistant PC3-Tx R and DU145-Tx R cells were ***3-Tx R and DU145-Tx R cells were transfected with E-cadherin-expressing lentivirus to overexpress E-cadherin;PC3 and DU145 cells were transfected with small interfering RNA to silence *** of EMT phenotype-related markers and signaling pathways were assessed by Western blotting and quantitative real-time polymerase chain *** cell migration,invasion,and colony formation were then evaluated by wound healing,transwell,and colony formation assays,*** drug sensitivity was evaluated using MTS ***:Chemoresistant PC3-Tx R and DU145-Tx R cells exhibited an invasive and metastatic phenotype that associated with EMT,including the down-regulation of E-cadherin and up-regulation of Vimentin,Snail,and N-cadherin,comparing with that of parental PC3 and DU145 *** E-cadherin was overexpressed in PC3-Tx R and DU145-Tx R cells,the expression of Vimentin and Claudin-1 was down-regulated,and tumor cell migration and invasion were *** particular,the sensitivity to paclitaxel was reactivated in E-cadherin-overexpressing PC3-Tx R and DU145-Tx R *** E-cadherin expression was silenced in parental PC3 and DU145 cells,the expression of Vimentin and Snail was up-regulated,and,pa

关键词： Epithelial-to-mesenchymal transition E-cadherin Chemoresistance Notch signaling Prostate cancer

Prostate cancer tends to metastasize in the bone-mimicking microenvironment via activating NF-κB signaling

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The Journal of Biomedical Research 2018年第5期32卷 343-353页

作者： Haibo Tong chunlin zou Siyuan Qin Jie Meng Evan T.Keller Jian Zhang Yi Lu Key Laboratory of Longevity and Aging-related Diseases Guangxi Medical University Ministry of Education Nanning Guangxi 530021 China Southern University of Science and Technology School of Medicine Shenzhen Guangdong 518055 China Department of Pathology and Internal Medicine University of Michigan Ann Arbor MI 48109 USA

Prostate cancer preferentially metastasizes to the bone. However, the underlying molecular mechanisms are still unclear. To explore the effects of a bone-mimicking microenvironment on PC3 prostate cancer cell growth and metastasis, we used osteoblast differentiation medium（ODM; minimal essential medium alpha supplemented with L-ascorbic acid） to mimic the bone microenvironment. PC3 cells grown in ODM underwent epithelial-mesenchymal transition and showed enhanced colony formation, migration, and invasion abilities compared to the cells grown in normal medium. PC3 cells grown in ODM showed enhanced metastasis when injected in mice. A screening of signaling pathways related to invasion and metastasis revealed that the NF-κB pathway was activated, which could be reversed by Bay 11-7082, a NF-κB pathway inhibitor. These results indicate that the cells in different culture conditions manifested significantly different biological behaviors and the NF-κB pathway is a potential therapeutic target for prostate cancer bone metastasis.

关键词： prostate cancer metastasis NF-κB Bay 11-7082 EMT

Multifunctional electroactive bio-adhesive for robustly-integrated wound therapy and postoperative wound-status warning and assessment

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Nano Research 2024年第5期17卷 4359-4370页

作者： Ouyang Yue Xuechuan Wang Mengdi Hou Siwei Sun Manhui Zheng Xiaoliang zou Zhongxue Bai chunlin Liu Xinhua Liu College of Bioresources Chemical and Materials Engineering Shaanxi University of Science&TechnologyXi’an 710021China College of Pharmacy Shaanxi University of Chinese MedicineXi’an 710021China Institute of Basic and Translational Medicine Xi’an Medical UniversityXi’an 710021China School of Mechanical Engineering Chengdu UniversityChengdu 610000China

Wound abnormalities such as secondary wound laceration and inflammation are common postoperative health hazards during clinical *** continuous treatment,healing induction,and real-time visualization of wound status and complications,including wound re-tearing,inflammation,and morphology,are key focal points for comprehensive ***,an on-demand quadruple energy dissipative strategy was proposed for the nanoengineering of a physically and chemically synergistic double-layer gelatin-based bio-adhesive(DLGel)by combining a multi-network adhesive layer and a versatile electroactive energy dissipative layer based on contrivable interlocking micro-pillar arrays and crosslinked polymer *** subtly multiple energy dissipation designs enable DLGel with robust adhesive strength to omnipotently wet and dynamic tissue,providing a basis for reliable wound *** achieves comprehensive wound-healing induction through electrical stimulation and possesses reversible underwater light/thermal adhesion,excellent hemostatic performance,outstanding antimicrobial properties,and self-repair ***,a novel deep-learning strategy is creatively established to respond to mechanical deformation due to wound *** strategy translates biological information into visual graphics,providing real-time early warning and assessment of postoperative wound-abnormality/-morphology,such as laceration,inflammation,and ***,DLGel and its associated signal collection and processing protocol enable the integration of reliable wound closure,wound healing,and real-time postoperative wound-status warning and assessment within the unobservable and undetectable“black box”regions in a context of non-clinical comprehensive therapy.

关键词： electroactive bio-adhesive quadruple energy dissipation comprehensive wound therapy postoperative wound-status warning and assessment

Single-cell transcriptomics reveals cell type diversity of human prostate

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Journal of Genetics and Genomics 2022年第11期49卷 1002-1015页

作者： Yang Chen Peng Zhang Jinling Liao Jiwen Cheng Qin Zhang Tianyu Li Haiying Zhang Yonghua Jiang Fangxing Zhang Yanyu Zeng Linjian Mo Haibiao Yan Deyun Liu Qinyun Zhang chunlin zou Gong-Hong Wei Zengnan Mo Center for Genomic and Personalized Medicine Guangxi Key Laboratory for Genomic and Personalized MedicineGuangxi Collaborative Innovation Center for Genomic and Personalized MedicineGuangxi Medical UniversityNanningGuangxi 530021China Department of Urology The First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530021China Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education&Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFudan University Shanghai Cancer CenterFudan UniversityShanghai 201114China Biocenter Oulu Faculty of Biochemistry and Molecular MedicineUniversity of OuluOuluFinland Key Laboratory of Longevity and Ageing-Related Disease of Chinese Ministry of Education Center for Translational Medicine and School of Preclinical MedicineGuangxi Medical UniversityNanningGuangxi 530021China

Extensive studies have been performed to describe the phenotypic changes occurring during malignant transformation of the ***,the cell types and associated changes that contribute to the development of prostate diseases and cancer remain elusive,largely due to the heterogeneous composition of prostatic ***,we conduct a comprehensive evaluation of four human prostate tissues by singlecell RNA sequencing(sc RNA-seq)to analyze their cellular *** identify 18 clusters of cell types,each with distinct gene expression profiles and unique features;of these,one cluster of epithelial cells(Ep)is found to be associated with immune *** addition,we characterize a special cluster of fibroblasts and aberrant signaling changes associated with prostate cancer(PCa).Moreover,we provide insights into the epithelial changes that occur during the cellular senescence and *** results expand our understanding of the unique functional associations between the diverse prostatic cell types and the contributions of specific cell clusters to the malignant transformation of prostate tissues and PCa development.

关键词： scRNA-seq Human prostate Cell type diversity Immunity Cellular senescence Prostate cancer

Analyzing the Dissemination of News by Model Averaging and Subsampling

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Journal of Systems Science & Complexity 2024年第5期37卷 2104-2131页

作者： zou Jiahui School of Statistics Capital University of Economics and BusinessBeijing 100070China

The dissemination of news is a vital topic in management science,social science and data *** the development of technology,the sample sizes and dimensions of digital news data increase *** alleviate the computational burden in big data,this paper proposes a method to deal with massive and moderate-dimensional data for linear regression models via combing model averaging and subsampling *** author first samples a subsample from the full data according to some special probabilities and split covariates into several groups to construct candidate ***,the author solves each candidate model and calculates the model-averaging weights to combine these estimators based on this ***,the asymptotic optimality in subsampling form is proved and the way to calculate optimal subsampling probabilities is *** author also illustrates the proposed method via simulations,which shows it takes less running time than that of the full data and generates more accurate estimations than uniform ***,the author applies the proposed method to analyze and predict the sharing number of news,and finds the topic,vocabulary and dissemination time are the determinants.

关键词： Asymptotic optimality dissemination of news linear regression models model averaging optimal subsampling.

The underlying mechanism of variety–water–nitrogen–stubble damage interactions on yield formation in ratoon rice with low stubble height under mechanized harvesting

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Journal of Integrative Agriculture 2024年第3期23卷 806-823页

作者： Jingnan zou Ziqin Pang Zhou Li chunlin Guo Hongmei Lin Zheng Li Hongfei Chen Jinwen Huang Ting Chen Hailong Xu Bin Qin Puleng Letuma Weiwei Lin Wenxiong Lin College of Life Sciences Fujian Agriculture and Forestry University(FAFU)/Fujian Key Laboratory for Agroecological Processes and Safety MonitoringFuzhou 350002China College of Agriculture FAFU/Fujian Key Laboratory for Crop Physiology and Molecular EcologyFuzhou 350002China Institute of Oceanography College of Geography and OceanographyMinjiang UniversityFuzhou 350108China Crop Science Department The National University of LesothoRoma 00100Lesotho The Agricultural Extension Station of Pucheng County Nanping 353400China

Agronomic measures are the key to promote the sustainable development of ratoon rice by reducing the damage from mechanical crushing to the residual stubble of the main crop, thereby mitigating the impact on axillary bud sprouting and yield formation in ratoon rice. This study used widely recommended conventional rice Jiafuzhan and hybrid rice Yongyou 2640 as the test materials to conduct a four-factor block design field experiment in a greenhouse of the experimental farm of Fujian Agricultural and Forestry University, China from 2018 to *** treatments included fertilization and no fertilization, alternate wetting and drying irrigation and continuous water flooding irrigation, and plots with and without artificial crushing damage on the rice stubble. At the same time, a 13C stable isotope in-situ detection technology was used to fertilize the pot experiment. The results showed significant interactions among varieties, water management, nitrogen application and stubble *** to the long-term water flooding treatment, the treatment with sequential application of nitrogen fertilizer coupled with moderate field drought for root-vigor and tiller promotion before and after harvesting of the main crop, significantly improved the effective tillers from low position nodes. This in turn increased the effective panicles per plant and grains per panicle by reducing the influence of artificial crushing damage on rice stubble and achieving a high yield of the regenerated rice. Furthermore, the partitioning of 13C assimilates to the residual stubble and its axillary buds were significantly improved at the mature stage of the main crop, while the translocation rate to roots and rhizosphere soil was reduced at the later growth stage of ratooning season rice. This was triggered by the metabolism of hormones and polyamines at the stem base regulated by the interaction of water and fertilizer at this time. We therefore suggest that to achieve a high yield of ratoon rice

关键词： mechanized harvesting ratoon rice rice stubble yield attributes