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Communications biology 2023年第1期6卷 548页

作者： Ju-Yi Hsieh Kun-Chi Chen Chun-Hsiung Wang Guang-Yaw Liu Jie-An Ye Yu-Tung Chou Yi-Chun Lin Cheng-Jhe Lyu Rui-Ying Chang Yi-Liang Liu Yen-Hsien Li Mau-Rong Lee Meng-Chiao Ho Hui-Chih Hung Department of Life Sciences National Chung Hsing University Taichung 402 Taiwan ROC. Ph.D. Program in Tissue Engineering and Regenerative Medicine National Chung Hsing University Taichung 402 Taiwan ROC. Institute of Biological Chemistry Academia Sinica Taipei 115 Taiwan ROC. Institute of Medicine College of Medicine Chung Shan Medical University Taichung 402 Taiwan ROC. Instrument Center Office of Research and Development National Chung Hsing University Taichung 40227 Taiwan ROC. Department of Chemistry National Chung Hsing University Taichung 402 Taiwan ROC. Institute of Biological Chemistry Academia Sinica Taipei 115 Taiwan ROC. joeho@gate.sinica.edu.tw. Institute of Biochemical Sciences National Taiwan University Taipei 106 Taiwan ROC. joeho@gate.sinica.edu.tw. Department of Life Sciences National Chung Hsing University Taichung 402 Taiwan ROC. hchung@dragon.nchu.edu.tw. Ph.D. Program in Tissue Engineering and Regenerative Medicine National Chung Hsing University Taichung 402 Taiwan ROC. hchung@dragon.nchu.edu.tw. Institute of Genomics and Bioinformatics National Chung Hsing University Taichung 402 Taiwan ROC. hchung@dragon.nchu.edu.tw. Advanced Plant and Food Crop Biotechnology Center National Chung Hsing University Taichung 402 Taiwan ROC. hchung@dragon.nchu.edu.tw.

Human mitochondrial NAD(P)-dependent malic enzyme (ME2) is well-known for its role in cell metabolism, which may be involved in cancer or epilepsy. We present potent ME2 inhibitors based on cyro-EM structures that target ME2 enzyme activity. Two structures of ME2-inhibitor complexes demonstrate that 5,5'-Methylenedisalicylic acid (MDSA) and embonic acid (EA) bind allosterically to ME2's fumarate-binding site. Mutagenesis studies demonstrate that Asn35 and the Gln64-Tyr562 network are required for both inhibitors' binding. ME2 overexpression increases pyruvate and NADH production while decreasing the cell's NAD/NADH ratio; however, ME2 knockdown has the opposite effect. MDSA and EA inhibit pyruvate synthesis and thus increase the NAD/NADH ratio, implying that these two inhibitors interfere with metabolic changes by inhibiting cellular ME2 activity. ME2 silence or inhibiting ME2 activity with MDSA or EA decreases cellular respiration and ATP synthesis. Our findings suggest that ME2 is crucial for mitochondrial pyruvate and energy metabolism, as well as cellular respiration, and that ME2 inhibitors could be useful in the treatment of cancer or other diseases that involve these processes.

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Investigation of the extremely weak interaction between the Japanese encephalitis virus and CLEC5A using a multivalent-interaction-enhancement sensing electrode

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Biosensors and Bioelectronics: X 2019年 2卷

作者： Tung, Yen-Ting Liang, Jian-Jong Feng, Hsiao-Ting Jhang, Ruei-Ning Hsieh, Shie-Liang Lin, Yi-Ling Wang, Gou-Jen Department of Mechanical Engineering National Chung-Hsing University Taichung Taiwan Institute of Biomedical Sciences Academia Sinica Taipei Taiwan Genomics Research Center Academia Sinica Taipei Taiwan Institute of Clinical Medicine National Yang-Ming University Taipei Taiwan Graduate Institute of Biomedical Engineering National Chung-Hsing University Taichung402 Taiwan Program in Tissue Engineering and Regenerative Medicine National Chung-Hsing University Taichung Taiwan

A lectin receptor, CLEC5A, plays an important role in the pathogenic mechanism of dengue virus (DV). The binding affinity between the DV envelope E-protein and CLEC5A is extremely weak and not easily detected using traditional methods, such as ELISA, making the characterization of the binding epitope even more difficult. Therefore, an efficient sensing method for weak binding detection is needed. We propose a novel sensing scheme with an electrode structure of a uniformly distributed nano-hemisphere array that enables multivalent interactions between the viral E-protein and its receptor for effective detection of weak binding. Japanese encephalitis virus (JEV), which belongs to the same flavivirus genus as DV, was used as a model to investigate the binding epitope between viral E-protein and CLEC5A. To study the influence of glycosylation on the binding, point mutations of JEV E-protein were introduced on amino acids D67 and N154 to gain or lose glycosylation on each site. The glycosylation on D67 of the JEV E-protein is critical for virus-CLEC5A interactions. However, the glycosylation on N154 hinders the interaction between D67 and CLEC5A, reducing the binding affinity between the virus and CLEC5A. The proposed approach provides an effective biosensor method for determining the binding epitope between a virus and CLEC5A. © 2019 The Author(s)

关键词： Viruses

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The Effects of Tensioning of the Anterior Cruciate Ligament Graft on Healing after Soft tissue Reconstruction

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The Journal of Knee Surgery 2019年第5期34卷 561-569页

作者： Richard Ma Michael Schaer Tina Chen Joseph Nguyen Clifford Voigt Xiang-Hua Deng Scott A. Rodeo Missouri Orthopaedic Institute Thompson Laboratory for Regenerative Orthopaedics University of Missouri Columbia Missouri Department of Orthopaedic Surgery and Traumatology Shoulder Elbow and Orthopaedic Sports Medicine Inselspital Bern University Hospital University of Bern Switzerland Sports Medicine and Shoulder Service Hospital for Special Surgery New York Department of Orthopaedic Surgery Lennox Hill Hospital New York Tissue Engineering Repair and Regeneration Program Hospital for Special Surgery New York

The purpose of this study is to determine the effect of the magnitude of static mechanical tension on the anterior cruciate ligament (ACL) graft at the time of surgery on healing within the graft tunnels. Ninety male rats underwent unilateral ACL resection followed by reconstruction with a soft tissue tendon autograft. The ACL graft mechanical environment was modulated by different ACL graft pretension levels at the time of surgery (no pretension: 0N; moderate tension: 5N; over tension: 10N). External fixators were used to eliminate graft and joint motion during cage activity. Graft–tunnel healing was assessed at 3- and 6-week postoperatively, and articular joint surfaces were assessed at 9 weeks. Our results demonstrate that the ACL graft–tunnel healing was sensitive to different static graft pretension levels as demonstrated by different load-to-failure and stiffness properties among the different pretension levels. Pretensioning the graft to 5N (7–8% of the rat ACL ultimate load to failure) resulted in the best graft–tunnel healing as shown by higher graft–tunnel failure load and stiffness. Higher bone volume fraction was also seen in the 5N group relative to other pretension levels. Histological analysis of the graft–tunnel interface revealed differences in cellularity of the ACL graft between the 5N group and the other two groups. Furthermore, the highest graft pretension level (10N) resulted in loss of proteoglycan content among articular joint surfaces. In conclusion, we found that ACL graft–tunnel healing is sensitive to the magnitude of graft pretension at the time of surgery in a preclinical model of ACL reconstruction with joint immobilization. The combination of high-graft tension and immobilization is also deleterious for the articular surface. Further study is necessary to understand the interaction between the magnitude of graft tensioning and joint motion.

关键词： anterior cruciate ligament healing graft healing graft pretension bone tunnel healing anterior cruciate ligament

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Publisher Correction: A postnatal network of co-hepato/pancreatic stem/progenitors in the biliary trees of pigs and humans

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NPJ regenerative medicine 2023年第1期8卷 47页

作者： Wencheng Zhang Xicheng Wang Giacomo Lanzoni Eliane Wauthier Sean Simpson Jennifer Ashley Ezzell Amanda Allen Carolyn Suitt Jonah Krolik Alexander Jhirad Juan Dominguez-Bendala Vincenzo Cardinale Domenico Alvaro Diletta Overi Eugenio Gaudio Praveen Sethupathy Guido Carpino Christopher Adin Jorge A Piedrahita Kyle Mathews Zhiying He Lola McAdams Reid Department of Cell Biology and Physiology University of North Carolina (UNC) School of Medicine Chapel Hill NC 27599 USA. Institute for Regenerative Medicine Shanghai East Hospital School of Life Sciences and Technology Tongji University School of Medicine 200123 Shanghai China. Shanghai Engineering Research Center of Stem Cells Translational Medicine 200335 Shanghai China. Shanghai Institute of Stem Cell Research and Clinical Translation 200120 Shanghai China. Diabetes Research Institute Leonard Miller School of Medicine 1450 N.W. 10th Avenue Miami FL 33136 USA. Department of Molecular Biomedical Sciences North Carolina State University (NCSU) College of Veterinary Medicine Raleigh NC 27606 USA. Comparative Medicine Institute NCSU Raleigh NC 27606 USA. Center for Gastrointestinal Biology and Disease (CGIBD) UNC School of Medicine Chapel Hill NC 27599 USA. Department of Medico-Surgical Sciences and Biotechnologies Sapienza University Rome Latina 04100 Italy. Department of Translational and Precision Medicine Sapienza University Rome 00185 Italy. Department of Anatomical Histological Forensic Medicine and Orthopedics Sciences Sapienza University Rome 00161 Italy. Department of Biomedical Sciences Cornell University College of Veterinary Medicine Ithaca NY 14853 USA. pr46@cornell.edu. Department of Anatomical Histological Forensic Medicine and Orthopedics Sciences Sapienza University Rome 00161 Italy. guido.carpino@uniroma1.it. Department of Clinical Sciences Soft Tissue and Oncologic Surgery Service College of Veterinary Medicine NCSU Raleigh NC 27606 USA. adinc@ufl.edu. Department of Small Animal Clinical Sciences University of Florida College of Veterinary Medicine Gainesville FL 32608 USA. adinc@ufl.edu. Department of Molecular Biomedical Sciences North Carolina State University (NCSU) College of Veterinary Medicine Raleigh NC 27606 USA. japiedra@ncsu.edu. Comparative Medicine Institute NCSU Raleigh NC 27606 USA. japiedra@ncsu

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Molecular landscape of sex- and modality-specific exercise adaptation in human skeletal muscle through large-scale multi-omics integration

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Cell reports 2025年第6期44卷 115750页

作者： Macsue Jacques Shanie Landen Adam P Sharples Andrew Garnham Ralf Schittenhelm Joel Steele Aino Heikkinen Elina Sillanpää Miina Ollikainen James Broatch Navabeh Zarekookandeh Ola Hanson Ola Ekström Olof Asplund Séverine Lamon Sarah E Alexander Cassandra Smith Carlie Bauer Mary N Woessner Itamar Levinger Andrew E Teschendorff Linn Gillberg Ida Blom Jørn Wulff Helge Nicholas R Harvey Larisa M Haupt Lyn R Griffiths Atul S Deshmukh Kirsi H Pietiläinen Päivi Piirilä Robert A E Seaborne Marie Klevjer Anja Bye Ulrik Wisløff Bernadette Jones-Freeman Nir Eynon Australian Regenerative Medicine Institute Monash University Clayton VIC Australia Institute for Health and Sport (iHeS) Victoria University Footscray VIC Australia. Centre for Endocrinology and Metabolism Hudson Institute of Medical Research Melbourne VIC Australia. Institute of Physical Performance Norwegian School of Sport Sciences Oslo Norway. Monash Proteomics & Metabolomics Platform Monash Biomedicine Discovery Institute Monash University Melbourne VIC Australia. Institute for Molecular Medicine Finland (FIMM) Helsinki University Helsinki Finland. Faculty of Sport and Health Sciences University of Jyväskylä Jyväskylä Finland Wellbeing Services County of Central Finland Jyväskylä Finland. Institute for Molecular Medicine Finland (FIMM) Helsinki University Helsinki Finland Minerva Foundation Institute for Medical Research Helsinki Finland. Department of Clinical Sciences Translational Muscle Research Unit Lund University Diabetes Center Lund University Lund Sweden. Institute for Physical Activity and Nutrition (IPAN) School of Exercise and Nutrition Sciences Deakin University 221 Burwood Highway Burwood VIC 3125 Australia. Cardiometabolic Health and Exercise Physiology Laboratory Baker Heart and Diabetes Institute 75 Commercial Road Melbourne VIC 3004 Australia. Nutrition & Health Innovation Research Institute Edith Cowan University Joondalup WA Australia Medical School The University of Western Australia Perth WA Australia. Institute for Health and Sport (iHeS) Victoria University Footscray VIC Australia Australian Institute for Musculoskeletal Science (AIMSS) Victoria University Melbourne VIC Australia. CAS Key Lab of Computational Biology Shanghai Institute of Nutrition and Health Shanghai China. Department of Biomedical Sciences University of Copenhagen Copenhagen Denmark. Faculty of Health Sciences and Medicine Bond University Gold Coast QLD Australia Genomics Research Centre Centre for Genomics and Personalised Health School of

We investigated the molecular mechanisms of exercise adaptations in human muscle by integrating genome, methylome, transcriptome, and proteome data from over 1,000 participants (2,340 muscle samples). We identified distinctive signatures associated with maximal oxygen consumption (VO), and multi-omics integration uncovered five key genes as robust exercise markers across layers, with transcription factors functioning as activators, synergizing with DNA methylation to regulate gene expression. Minimal sex differences were observed, while modality-specific analysis highlighted distinct pathways for aerobic and resistance exercise, contrasting with muscle disuse patterns. Finally, we created a webtool, OMAx, featuring our individual omics and integration analysis. These findings provide a comprehensive multi-omics framework for understanding exercise-induced molecular adaptations, offering insights into muscle health, cardiorespiratory fitness, and their roles in aging and disease prevention.

关键词： CP: Metabolism DNA methylation Multi Omics VO(2 max) epigenetics exercise gene expression proteomic skeletal muscle transcriptomic

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Large-scale production of extracellular vesicles: Report on the “massivEVs” ISEV workshop

Journal of Extracellular Biology

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Journal of Extracellular Biology 2022年第10期1卷 e63页

作者： Paolini, Lucia Monguió-Tortajada, Marta Costa, Marta Antenucci, Fabio Barilani, Mario Clos-Sansalvador, Marta Andrade, André Cronemberger Driedonks, Tom A. P. Giancaterino, Sara Kronstadt, Stephanie M. Mizenko, Rachel R. Nawaz, Muhammad Osteikoetxea, Xabier Pereira, Carla Shrivastava, Surya Boysen, Anders Toftegaard van de Wakker, Simonides Immanuel van Herwijnen, Martijn J. C. Wang, Xiaoqin Watson, Dionysios C. Gimona, Mario Kaparakis-Liaskos, Maria Konstantinov, Konstantin Lim, Sai Kiang Meisner-Kober, Nicole Stork, Michiel Nejsum, Peter Radeghieri, Annalisa Rohde, Eva Touzet, Nicolas Wauben, Marca H. M. Witwer, Kenneth W. Bongiovanni, Antonella Bergese, Paolo Department of Molecular and Translational Medicine University of Brescia Brescia Italy Center for Colloid and Surface Science (CSGI) Department of Chemistry University of Florence Sesto Fiorentino (FI) Italy Department of Medical and Surgical Specialties Radiological Sciences and Public Health University of Brescia Brescia Italy CREC Research Program Health Science Research Institute Germans Trias i Pujol (IGTP) Badalona Spain Heart Institute (iCor) Cardiology Department Germans Trias i Pujol University Hospital Badalona Spain iBET Instituto de Biologia Experimental e Tecnológica Oeiras Portugal Instituto de Tecnologia Química e Biológica António Xavier Universidade Nova de Lisboa Oeiras Portugal Department of Veterinary and Animal Sciences University of Copenhagen Copenhagen Denmark Laboratory of Regenerative Medicine ‒ Cell Factory Department of Transfusion Medicine and Hematology Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Italy REMAR-IGTP Group Germans Trias i Pujol Research Institute (IGTP) & Nephrology Department University Hospital Germans Trias i Pujol (HUGTiP) Catalonia Badalona (Barcelona) Spain Department of Cell Biology Physiology and Immunology Universitat Autònoma de Barcelona (UAB) Bellaterra Spain Experimental and Clinical Cell Therapy Institute (ExCT) Spinal Cord Injury and Tissue Regeneration Center Paracelsus Medical University Salzburg Austria CDL Research University Medical Center Utrecht Utrecht University Utrecht Netherlands Department of Molecular and Comparative Pathology Johns Hopkins School of Medicine Baltimore MD United States Department of Civil Chemical Environmental and Materials Engineering Alma Mater Studiorum University of Bologna Bologna Italy Fischell Department of Bioengineering University of Maryland College Park MD United States Department of Biomedical Engineering University of California Davis CA United States Department of Rheumatology and Inflammation Research Institute of Medicine

Extracellular vesicles (EVs) large-scale production is a crucial point for the translation of EVs from discovery to application of EV-based products. In October 2021, the International Society for Extracellular Vesicles (ISEV), along with support by the FET-OPEN projects, “The Extracellular Vesicle Foundry” (evFOUNDRY) and “Extracellular vesicles from a natural source for tailor-made nanomaterials” (VES4US), organized a workshop entitled “massivEVs” to discuss the potential challenges for translation of EV-based products. This report gives an overview of the topics discussed during “massivEVs”, the most important points raised, and the points of consensus reached after discussion among academia and industry representatives. Overall, the review of the existing EV manufacturing, upscaling challenges and directions for their resolution highlighted in the workshop painted an optimistic future for the expanding EV field. © 2022 The Authors. Journal of Extracellular Biology published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.

关键词： EV-based products extracellular vesicles ISEV workshop large-scale production manufacturing processing regulatory issues

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Guidelines and definitions for research on epithelial-mesenchymal transition (vol 21, pg 341, 2020)

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NATURE REVIEWS MOLECULAR CELL BIOLOGY 2021年第12期22卷 834-834页

作者： Yang, Jing Antin, Parker Berx, Geert Blanpain, Cedric Brabletz, Thomas Bronner, Marianne Campbell, Kyra Cano, Amparo Casanova, Jordi Christofori, Gerhard Dedhar, Shoukat Derynck, Rik Ford, Heide L. Fuxe, Jonas Garcia de Herreros, Antonio Goodall, Gregory J. Hadjantonakis, Anna-Katerina Huang, Ruby Y. J. Kalcheim, Chaya Kalluri, Raghu Kang, Yibin Khew-Goodall, Yeesim Levine, Herbert Liu, Jinsong Longmore, Gregory D. Mani, Sendurai A. Massague, Joan Mayor, Roberto McClay, David Mostov, Keith E. Newgreen, Donald F. Nieto, M. Angela Puisieux, Alain Runyan, Raymond Savagner, Pierre Stanger, Ben Stemmler, Marc P. Takahashi, Yoshiko Takeichi, Masatoshi Theveneau, Eric Thiery, Jean Paul Thompson, Erik W. Weinberg, Robert A. Williams, Elizabeth D. Xing, Jianhua Zhou, Binhua P. Sheng, Guojun Departments of Pharmacology and Pediatrics Moores Cancer Center University of California San Diego La Jolla CA USA Department of Cellular and Molecular Medicine University of Arizona Tucson AZ USA Molecular and Cellular Oncology Lab Department of Biomedical Molecular Biology Ghent University Cancer Research Institute Ghent (CRIG) VIB Center for Inflammation Research Ghent Belgium Laboratory of Stem Cells and Cancer Université Libre de Bruxelles Bruxelles Belgium Department of Experimental Medicine 1 Nikolaus-Fiebiger-Center for Molecular Medicine Friedrich-Alexander-University Erlangen-Nürnberg Erlangen Germany Division of Biology and Biological Engineering California Institute of Technology Pasadena CA USA Department of Biomedical Science and Bateson Centre University of Sheffield Sheffield UK Departamento de Bioquímica Universidad Autónoma de Madrid (UAM) Instituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM) IdiPAZ & Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) Madrid Spain Institute for Research in Biomedicine (IRB Barcelona) Barcelona Institute of Science and Technology/Institut de Biologia Molecular de Barcelona (IBMB-CSIC) Barcelona Spain Department of Biomedicine University of Basel Basel Switzerland Department of Biochemistry and Molecular Biology University of British Columbia and British Columbia Cancer Research Centre Vancouver BC Canada Departments of Cell and Tissue Biology and Anatomy University of California at San Francisco San Francisco CA USA Department of Pharmacology University of Colorado Anschutz Medical Campus Aurora CO USA Department of Laboratory Medicine (LABMED) Division of Pathology Karolinska University Hospital and Department of Microbiology Tumor and Cell Biology (MTC) Karolinska Institutet Stockholm Sweden Programa de Recerca en Càncer Institut Hospital del Mar d’Investigacions Mèdiques (IMIM) and Departament de Ciències Experimentals i de la Salut Universitat Pompeu Fabra Barcelona Spain C

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Guanylate-binding protein 1(GBP1) contributes to the immunity of human mesenchymal stromal cells against Toxoplasma gondii

Guanylate-binding protein 1(GBP1) contributes to the immunit...

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中国动物学会寄生虫学专业委员会第十六次全国学术会议暨第七次国际寄生虫学学术研讨会

作者： Aiping Qin De-Hua Lai Qifa Liu Weijun Huang Geoff Hide Zhao-Rong Lun Francisco J.Ayala Andy Peng Xiang Department of Hematology Nanfang HospitalSouthern Medical University Center for Stem Cell Biology and Tissue Engineering The Key Laboratory for Stem Cells and Tissue EngineeringMinistry of EducationZhongshan School of MedicineSun Yat-Sen University Center for Parasitic Organisms State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-Sen University Program of Stem Cells and Regenerative Medicine Affiliated Guangzhou Women and Children’s HospitalZhongshan School of MedicineSun Yat-Sen University Ecosystems and Environment Research Centre School of Environment and Life SciencesUniversity of Salford Biomedical Research Centre School of Environment and Life SciencesUniversity of Salford Department of Ecology and Evolutionary Biology University of California Department of Biochemistry Zhongshan School of MedicineSun Yat-Sen University

Mesenchymal stromal cells(MSCs) have recently been shown to play important roles in mammalian host defenses against intracellular pathogens,but the molecular mechanism still needs to be *** confirmed that human MSCs(hMSCs) prestimulated with IFN-γ showed a significant and dose-dependent ability to inhibit the growth of two types of Toxoplasma gondii [type I RH strain with green fluorescent proteins(RH/GFP) or type II PLK strain with red fluorescent proteins(PLK/RED)].However,in contrast to previous reports,the *** activity of hMSCs was not mediated by indoleamine 2,3-dioxygenase(IDO).Genome-wide RNA sequencing(RNA-seq) analysis revealed that IFN-γ increased the expression of the p65 family of human guanylate-binding proteins(h GBPs) in hMSCs,especially *** analyze the functional role of h GBPs,stable knockdowns of h GBP1,-2,and-5 in hMSCs were established using a lentiviral transfection ***1 knockdown in hMSCs resulted in a significant loss of the *** host defense property,compared with hMSCs infected with nontargeted control sequences.h BP2 and-5 knockdowns had no ***,the h GBP1 accumulation on the parasitophorous vacuole(PV) membranes of IFN-γ–stimulated hMSCs might protect against *** *** together,our results suggest that h GBP1 plays a pivotal role in *** protection of hMSCs and may shed new light on clarifying the mechanism of host defense properties of hMSCs.

关键词： human stem cells parasitic protozoan innate immunity in vitro cultivation

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TALEN-based generation of a cynomolgus monkey disease model for human microcephaly

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细胞研究（英文版） 2016年第9期26卷 1048-1061页

作者： Qiong Ke Weiqiang Li Xingqiang Lai Hong Chen Lihua Huang Zhuang Kang Kai Li Program of Stem Cells and Regenerative Medicine Affiliated Guangzhou Women and Children's HospitalZhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510623China Center for Stem Cell Biology and Tissue Engineering Key Laboratory for Stem Cells and Tissue EngineeringMinistry of EducationSun Yat-Sen UniversityGuangzhou 510080China Department of Biology Zhongshan Medical SchoolSun Yat-Sen UniversityGuangzhou 510080China Guangdong Key Laboratory of Reproductive Medicine Guangzhou 510080China Program of Stem Cells and Regenerative Medicine Affiliated Guangzhou Women and Children's HospitalZhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510623China Center for Stem Cell Biology and Tissue Engineering Key Laboratory for Stem Cells and Tissue EngineeringMinistry of EducationSun Yat-Sen UniversityGuangzhou 510080China Guangdong Key Laboratory of Reproductive Medicine Guangzhou 510080China Department of Biochemistry Zhongshan Medical SchoolSun Yat-Sen UniversityGuangzhou 510080China Center for Stem Cell Biology and Tissue Engineering Key Laboratory for Stem Cells and Tissue EngineeringMinistry of EducationSun Yat-Sen UniversityGuangzhou 510080China Program of Stem Cells and Regenerative Medicine Affiliated Guangzhou Women and Children's HospitalZhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510623China Department of Radiology the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510632China Department of Ultrasound the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510632China

Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size.

关键词： MCPH1 microcephaly TALEN gene mutant cynomolgus monkey

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The micro/nanohybrid structures enhancing B35 cell guidance on chitosan

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Journal of Nanotechnology in engineering and medicine 2015年第3期6卷 031005页

作者： Lin, Ying-Ting Li, Ching-Wen Wang, Gou-Jen Graduate Institute of Biomedical Engineering National Chung-Hsing University 250 Kuo Kuang Road Taichung40227 Taiwan Ph.D. Program in Tissue Engineering and Regenerative Medicine National Chung-Hsing University 250 Kuo Kuang Road Taichung40227 Taiwan Department of Mechanical Engineering Graduate Institute of Biomedical Engineering National Chung-Hsing University 250 Kuo Kuang Road Taichung40227 Taiwan

A novel chitosan scaffold with micro- and nano-hybrid structures was proposed in this study. The hemispheric array of the barrier layer of an anodic aluminum oxide (AAO) film was used as the substrate. Microelectromechanical systems and nickel electroforming techniques were integrated for fabricating chitosan scaffolds with different micro/ nanohybrid structures. Nerve cells were then cultured on the conduits. It was demonstrated that the scaffold with pure microstructures can guide the nerve cells to grow along the ridges of the microstructure and some cells to grow across the groove in between two ridges of the microstructure. It was also shown that the scaffold with microscale ridges and nanopatterns on the groove between two ridges can more effectively guide the cells to grow along the ridges, thus enhancing the proliferation of nerve cells. © 2016 by ASME.

关键词： Chitosan

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