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Characterization of cancer stem-like cells in the side population cells of human gastric cancer cell line MKN-45

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2013年第3期14卷 216-223页

作者： Hai-hong ZHANG Ai-zhen CA Xue-ming WEI Li DING Feng-zhi LI Ai-ming ZHENG Da-jiang DAI Rong-rong HUANG Hou-jun CAO Hai-yang ZHOU Jian-mei WANG Xue-jing WANG Wei SHI Heng ZHU Xiao-ying YUAN Lin CHEN department of General surgery General Hospital of the Air ForcePLA department of General surgery Chinese PLA General Hospital department of cell biology Institute of Basic Medical SciencesAcademy of Military Medical Sciences

Objective:Side population(SP) cells may play a crucial role in tumorigenesis and the recurrence of *** kinds of cell lines and tissues have demonstrated the presence of SP cells,including several gastric cancer cell *** study is aimed to identify the cancer stem-like cells in the SP of gastric cancer cell line ***:We used fluorescence activated cell sorting(FACS) to sort SP cells in the human gastric carcinoma cell line MKN-45(cells labeled with Hoechst 33342) and then characterized the cancer stem-like properties of SP ***:This study found that the SP cells had higher clone formation efficiency than major population(MP) *** stemness-related gene expression profiles,including OCT-4,SOX-2,NANOG,CD44,and adenosine triphosphate(ATP)-binding cassette transporters gene ABCG2,were tested in SP and MP cells using quantitative real-time reverse transcription polymerase chain reaction(RT-PCR).Western blot was used to show the difference of protein expression between SP and MP *** results show that there was significantly higher protein expression in SP cells than in MP *** inoculated into non-obese diabetic/severe combined immunodeficiency(NOD/SCID) mice,SP cells show higher tumorigenesis tendency than MP ***:These results indicate that SP cells possess cancer stem cell properties and prove that SP cells from MKN-45 are gastric cancer stem-like cells.

关键词： ATP-binding cassette transporters Side population cells stem cells Benzimidazole (Hoechst 33342),Stomach neoplasm

New strategies for the repair of spinal cord injury

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Chinese Science Bulletin 2014年第31期59卷 4041-4049页

作者： Zhourui Wu Ziru Zhao Yan Yu Xiao Hu Wei Xu Zhili Zeng Yi Eve Sun Liming Cheng department of Spine surgery Shanghai Tongji HospitalTongji University School of Medicine Translational stem cell Center Shanghai Tongji HospitalTongji University School of Medicine

Spinal cord injury(SCI)leads to several neurologic damages to patients with sensory and motor function *** some inspiring results were reported in animal,even in non-human primate models,the clinical translation of these research achievements barely move forward for the SCI *** review mainly focused on the pathogenesis of the primary and secondary injury,the clinical therapies and the new technologies in spinal cord ***,the key scientific issues on this field were discussed in the ***,some suggestions were proposed for the scientific and clinical researches.

关键词：脊髓损伤修复临床治疗动物模型科学问题运动功能研究成果发病机制

Molecular Cloning and Characterization of Porcine Indoleamine 2,3-Dioxygenase and Its Expression in Various Tissues

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2012年第4期32卷 473-479页

作者：陈超魏明发王璐向莹付向宁朱珉 department of Anesthesiology department of pediatric surgery Institute of Organ Transplantation Key laboratory of Organ Transplantation Ministry of Education Key laboratory of Organ Transplantation Ministry of Health department of General Thoracic surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology

In order to confirm the existence of indoleamine 2,3-dioxygenase(IDO) gene in swine,and to clone the novel gene followed by the molecule structure properties and expression pattern analysis,the porcine mRNA sequences homologous to human IDO were obtained from GenBank database by bioinformatics *** using RT-PCR,the IDO gene was cloned from porcine endothelial cell line and the accuracy of the nucleic acid sequence was confirmed,and the expression pattern of the gene was *** three-dimensional structure model of porcine IDO was built referring to the tertiary structure of human IDO using biological sequence analysis software and *** results showed that the porcine IDO was identified by *** nucleotide sequences were confirmed as a novel gene after submitted to *** IDO was expressed in the lung,thymus,epididymis and anterior chamber with a basic level,however in peripheral blood mononuclear cells(PBMCs) the IDO gene was highly *** three-dimensional structure model of porcine IDO was similar to that of human *** was suggested that identification of the structure information of porcine IDO is essential to further investigate the immunologic function of the *** of IDO on NK cells-mediated xenograft rejection will be a novel therapeutic target for the development of xenotransplantation.

关键词： expressed sequence tag indoleamine 2,3-dioxygenase bioinformatics porcine endothelial cell

Mechanism of Endogenous Peptide PDYBX1 and Precursor Protein YBX1 in Hirschsprung’s Disease

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Neuroscience Bulletin 2024年第6期40卷 695-706页

作者： Qiaochu Sun Zhengke Zhi Chenglong Wang Chunxia Du Jie Tang Hongxing Li Weibing Tang department of pediatric surgery Children’s Hospital of Nanjing Medical UniversityNanjing210008China

Endogenous peptides,bioactive agents with a small molecular weight and outstanding absorbability,regulate various cellular processes and ***,their role in the occurrence of Hirschsprung’s disease(HSCR)remains ***,we found that the expression of an endogenous peptide derived from YBX1(termed PDYBX1 in this study)was upregulated in the aganglionic colonic tissue of HSCR patients,whereas its precursor protein YBX1 was *** shown by Transwell and cytoskeleton staining assays,silencing YBX1 inhibited the migration of enteric neural cells,and this effect was partially reversed after treatment with ***,immunoprecipitation and immunofluorescence revealed that ERK2 bound to YBX1 and *** of YBX1 blocked the ERK1/2 pathway,but upregulation of PDYBX1 counteracted this effect by binding to ERK2,thereby promoting cell migration and *** together,the endogenous peptide PDYBX1 may partially alleviate the inhibition of the ERK1/2 pathway caused by the downregulation of its precursor protein YBX1 to antagonize the impairment of enteric neural ***1 may be exploited to design a novel potential therapeutic agent for HSCR.

关键词： Hirschsprung’s disease YBX1 Endogenous peptide PDYBX1 Enteric neural cell

Induction of corneal epithelial progenitors from bone-marrow mesenchymal stem cells of rhesus monkeys in vitro

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Chinese Science Bulletin 2007年第16期52卷 2216-2225页

作者： YUAN Jing YU JianXiong HUANG Bing LIU BingQian LIU JingBo JIANG RuZhang GE Jian State Key laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat-sen University Guangzhou 510060 China Center for stem cell biology and Tissue Engineering Sun Yat-sen University Guangzhou 510080 China department of General surgery The Third Affiliated Hospital of SUR Yat-sen University Guangzhou 510630 China

Bioengineered corneas are substitutes for human donor tissue that are designed to treat severe dis-ease affecting ocular surfaces. However,a shortage of candidate seed cells for bioengineering corneas is still a problem. Bone-marrow mesenchymal stem cells (MSCs) are capable of multilineage differen-tiation. Therefore,we determined whether MSCs differentiate into corneal epithelial cells (ECs). We applied three exoteric-microenvironmental systems to induce MSCs to become ECs. Induced MSC were identified by means of morphologic examination,immunocytochemical analysis,and flow cytometry. MSCs grown in one microenvironment had characteristics similar to those of corneal epithelial pro-genitors. Induced MSCs expressed markers for EC,including integrin β1,Cx43,Pax6,and P63. MSCs were successfully induced to become corneal epithelial progenitors. Therefore,the use of MSCs may hold substantial promise for reconstructing the ocular surface after corneal injury.

关键词：猕猴角膜内皮细胞骨髓间叶干细胞生长因子脂多糖

Human iP SC-derived mesenchymal stem cells relieve high blood pressure in spontaneously hypertensive rats via splenic nerve activated choline acetyltransferase-positive cells

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Science China Life Sciences 2024年

作者： Zhen Zhang Weijun Huang Xiaoran Zhang Zhecun Wang Manting Xie Bingbing Xie Yiling Wang Xiaoyong Chen Andy Peng Xiang Qiuling Xiang Center for stem cell biology and Tissue Engineering Key Laboratory for Stem Cells and Tissue Engineering Ministry of Education Sun Yat-sen University department of Physiology Zhongshan School of Medicine Sun Yat-sen University department of Vascular surgery the First Affiliated Hospital Sun Yat-sen University

Despite substantial advancements in modern medicine, the management of hypertension remains a major challenge. stem cell-based therapies have recently demonstrated remarkable efficacy in treating cardiovascular diseases, including hypertension. However, the antihypertensive mechanism of mesenchymal stem cells（MSCs） has not been extensively explored. This study aimed to investigate the role of injected MSCs in regulating blood pressure homeostasis. Our previous study demonstrated that human induced pluripotent stem cellderived mesenchymal stem cells（hiPSC-MSCs） are functional and homogeneous sources for MSC-based therapy. After the injection of hiPSCMSCs, a significant reduction in blood pressure and end target organ inflammation were observed in spontaneously hypertensive rats（SHRs）. cell tracking assays demonstrated that the injected hiPSC-MSCs accumulated in the spleens of the SHRs. The injected hiPSC-MSCs accumulated adjacent to the splenic nerve, potentially contributing to the antihypertensive effects. Furthermore, the hiPSC-MSCs released abundant glutamate, which acts as a neuromodulator to activate the splenic sympathetic nerve. After inhibition of glutamate synthesis by siRNA, the ability of hiPSC-MSCs to activate sympathetic nerves was significantly diminished. In addition, the antihypertensive effects of hiPSC-MSCs were eliminated after splenic nerve denervation（SND）, underscoring the critical role of the splenic nerve. Moreover, activation of the splenic nerve resulted in increased release of norepinephrine（NE）, which increased the number of choline acetyltransferase-positive（ChAT+） cells in the spleen and peripheral blood. Consequently, the acetylcholine（ACh） produced by elevated ChAT+cells could act as a vasodilator, lowering blood pressure and mitigating inflammation in end target organs. In summary, our findings indicate that hiPSC-MSCs effectively lower blood pressure in hypertension by influencing the splenic nerves and regulating ChAT+cells. The co

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Activation of β-catenin signaling in aggrecan-expressing cells in temporomandibular joint causes osteoarthritis-like defects

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International Journal of Oral Science 2018年第2期10卷 102-109页

作者： Tianqian Hui Yachuan Zhou Tingyu Wang Jun Li Shanxing Zhang Lifan Liao Jianhong Gu Ling Ye Lan Zhao Di Chen department of pediatric Dentistry Peking University School and Hospital of Stomatology State Key laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology Sichuan University department of Orthopaedic surgery Rush University Medical Center department of Pharmacy Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine department of Medical cell biology and Genetics Shenzhen Key Laboratory and the Center for Anti-Ageing and Regenerative Medicine Shenzhen University Medical School

β-Catenin plays a critical role in cartilage formation and development. To further understand the role of β-catenin in osteoarthritis（OA） development in temporomandibular joint（TMJ）, we have generated β-catenin conditional activation mice（β-cat（ex3）^Agc1CreER）by breeding Agc1-CreER mice with β-catenin^flox（ex3/＋）mice. Results of histologic analysis showed the progressive TMJ defects in 3-and 6-month-old β-cat（ex3）^Agc1CreERmice（tamoxifen induction was performed at 2 weeks of age）, including decreased chondrocyte numbers in the superficial layer associated with less Alcian blue staining, increased numbers of hypertrophic chondrocytes in deep layers, and rough articular surface. Compared to the TMJ phenotype of β-cat（ex3）^（Col2CreER）mice, β-cat（ex3）^（Agc1CreER）mice showed much severe morphological defects in the superficial layer of TMJ. This may reflect that Agc1-CreER mice could efficiently target cells in the superficial layer of TMJ. Results of immunostaining showed significantly increased expression of MMP13, Col-X, Adamts4,and Adamts5 in TMJ of β-cat（ex3）^（Agc1CreER）mice. Results of proliferating cell nuclear antigen（PCNA）, Ki67, and terminal deoxinucleotidyl transferase-mediated d UTP-fluorescein nick end labeling（TUNEL） staining further demonstrated that cell proliferation was decreased and cell apoptosis was increased in condylar cartilage of β-cat（ex3）^Agc1CreERmice. Our findings indicate that abnormal upregulation of β-catenin in TMJ leads to defects assembling to OA-like phenotype, further demonstrating that β-catenin plays a critical role in TMJ pathogenesis.

关键词： TMJ OA Activation

Trehalose attenuates abdominal aortic aneurysm formation by inducing autophagy in smooth muscle cells

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Journal of Geriatric Cardiology 2023年第3期20卷 214-222页

作者： Bo JIANG Xuan LI Mo WANG Guang-Xin LI Peng-Wei REN Yu-Qi WANG Shi-Jie XIN Ling-Feng QIN department of Vascular surgery the First Hospital of China Medical UniversityKey Laboratory of PathogenesisPrevention and Therapeutics of Aortic AneurysmShenyangChina department of surgery Yale School of MedicineNew HavenCTUSA department of Breast and Thyroid surgery Peking University Shenzhen HospitalShenzhenChina Yale stem cell Center Yale School of MedicineNew HavenCTUSA department of Biomedical Engineering Yale UniversityNew HavenCTUSA

BACKGROUND Trehalose is a naturally occurring disaccharide,which has been identified as an autophagy inducer and ex-hibits protective effect in cardiovascular diseases such as myocardial infraction and ***,the functional role of trehalose in abdominal aortic aneurysm(AAA)remains *** To study the effect of trehalose in AAA,trehalose(1 g/kg per day)were given for 14 continuous days in a mouse model of elastase-induced abdominal aortic *** day 14,ultrasound was performed to measure aortic diameter before the abdominal aortas were harvested and processed for further ***-Van Gieson staining and TUNEL staining were performed on paraffin sections to evaluate vascular histology and apoptosis,immunofluorescence staining and Western-blot were performed to evaluate expression of autophagy *** Echocardiography and in situ pictures demonstrated that trehalose attenuated infrarenal aorta ***-Van Gieson staining showed elastin degradation was improved in trehalose-treated *** with vehicle-treated mice,trehalose treatment restored smooth muscle cell contractile phenotype with increasedα-SMA,Calponin and Myh11 ***,trehalose also attenuated cell apoptosis and leukocytes ***,trehalose induced autophagy with decrease SQSTM1/p62 accumulation,increased lamp2 expression and LC3B *** Trehalose attenuated AAA progression with decreased inflammation and restored SMC contractile phenotype by inducing *** results demonstrated the therapeutic potential of trehalose in AAA.

关键词： abdominal aneurysm protective

Osteogenesis of Adipose-Derived stem cells

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Bone Research 2013年第2期1卷 133-145页

作者： Brian E. Grottkau Yunfeng Lin department of Orthopaedic surgery MassGeneral Hospital for Children and the Pediatric Orthopaedic Laboratory for Tissue Engineering and Regenerative MedicineHarvard Medical SchoolBostonMassachusettsUSA

Current treatment options for skeletal repair, including immobilization, rigid fixation, alloplastic materials and bone grafts, have significant limitations. Bone tissue engineering offers a promising method for the repair of bone deficieny caused by fractures, bone loss and tumors. The use of adipose derived stem cells （ASCs） has received attention because of the self-renewal ability, high proliferative capacity and potential of osteogenic differentiation in vitro and in vivo studies of bone regeneration. Although cell therapies using ASCs are widely promising in various clinical fields, no large human clinical trials exist for bone tissue engineering. The aim of this review is to introduce how they are harvested, examine the characterization of ASCs, to review the mechanisms of osteogenic differentiation, to analyze the effect of mechanical and chemical stimuli on ASC osteodifferentiation, to summarize the current knowledge about usage of ASC in vivo studies and clinical trials, and finally to conclude with a general summary of the field and comments on its future direction.

关键词： adipose derived stem cells osteogenesis bone tissue engineering osteogenic differentiation