35 results on '"Xinglong Han"'
Search Results
2. Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity
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Xinglong Han, Lina Qu, Miao Yu, Lingqun Ye, Liujia Shi, Guangfu Ye, Jingsi Yang, Yaning Wang, Hao Fan, Yong Wang, Yingjun Tan, Chunyan Wang, Qi Li, Wei Lei, Jianghai Chen, Zhaoxia Liu, Zhenya Shen, Yinghui Li, and Shijun Hu
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Medicine ,Biology (General) ,QH301-705.5 - Abstract
Abstract During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.
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- 2024
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3. Mitochondrial diseases and mtDNA editing
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Min Song, Lingqun Ye, Yongjin Yan, Xuechun Li, Xinglong Han, Shijun Hu, and Miao Yu
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Gene editing ,Mitochondrialdisease ,Mitochondrial DNA mutation ,Transcription activator-like effector nucleases ,Zinc finger nucleases ,Medicine (General) ,R5-920 ,Genetics ,QH426-470 - Abstract
Mitochondrial diseases are a heterogeneous group of inherited disorders characterized by mitochondrial dysfunction, and these diseases are often severe or even fatal. Mitochondrial diseases are often caused by mitochondrial DNA mutations. Currently, there is no curative treatment for patients with pathogenic mitochondrial DNA mutations. With the rapid development of traditional gene editing technologies, such as zinc finger nucleases and transcription activator-like effector nucleases methods, there has been a search for a mitochondrial gene editing technology that can edit mutated mitochondrial DNA; however, there are still some problems hindering the application of these methods. The discovery of the DddA-derived cytosine base editor has provided hope for mitochondrial gene editing. In this paper, we will review the progress in the research on several mitochondrial gene editing technologies with the hope that this review will be useful for further research on mitochondrial gene editing technologies to optimize the treatment of mitochondrial diseases in the future.
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- 2024
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4. The miR-148/152 family contributes to angiogenesis of human pluripotent stem cell- derived endothelial cells by inhibiting MEOX2
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Fengyue Ding, Hongchun Wu, Xinglong Han, Xue Jiang, Yang Xiao, Yuanyuan Tu, Miao Yu, Wei Lei, and Shijun Hu
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MT: Non-coding RNAs ,miR-148/152 family ,human pluripotent stem cells ,endothelial cells ,angiogenesis ,mesenchyme homeobox 2 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Human pluripotent stem cell-derived endothelial cells (hPSC-ECs) represent a promising source of human ECs urgently needed for the study of cardiovascular disease mechanisms, cell therapy, and drug screening. This study aims to explore the function and regulatory mechanism of the miR-148/152 family consisting of miR-148a, miR-148b, and miR-152 in hPSC-ECs, so as to provide new targets for improving EC function during the above applications. In comparison with the wild-type (WT) group, miR-148/152 family knockout (TKO) significantly reduced the endothelial differentiation efficiency of human embryonic stem cells (hESCs), and impaired the proliferation, migration, and capillary-like tube formatting abilities of their derived ECs (hESC-ECs). Overexpression of miR-152 partially restored the angiogenic capacity of TKO hESC-ECs. Furthermore, the mesenchyme homeobox 2 (MEOX2) was validated as the direct target of miR-148/152 family. MEOX2 knockdown resulted in partial restoration of the angiogenesis ability of TKO hESC-ECs. The Matrigel plug assay further revealed that the in vivo angiogenic capacity of hESC-ECs was impaired by miR-148/152 family knockout, and increased by miR-152 overexpression. Thus, the miR-148/152 family is crucial for maintaining the angiogenesis ability of hPSC-ECs, and might be used as a target to enhance the functional benefit of EC therapy and promote endogenous revascularization.
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- 2023
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5. Retinoic acid inhibits the angiogenesis of human embryonic stem cell-derived endothelial cells by activating FBP1-mediated gluconeogenesis
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Zhuangzhuang Yang, Miao Yu, Xuechun Li, Yuanyuan Tu, Chunyan Wang, Wei Lei, Min Song, Yong Wang, Ying Huang, Fengyue Ding, Kaili Hao, Xinglong Han, Xuan Ni, Lina Qu, Zhenya Shen, and Shijun Hu
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Endothelial cell ,Angiogenesis ,Retinoic acid ,Glycometabolism ,Medicine (General) ,R5-920 ,Biochemistry ,QD415-436 - Abstract
Abstract Background Endothelial cells are located in the inner lumen of blood and lymphatic vessels and exhibit the capacity to form new vessel branches from existing vessels through a process called angiogenesis. This process is energy intensive and tightly regulated. Glycolysis is the main energy source for angiogenesis. Retinoic acid (RA) is an active metabolite of vitamin A and exerts biological effects through its receptor retinoic acid receptor (RAR). In the clinic, RA is used to treat acne vulgaris and acute promyelocytic leukemia. Emerging evidence suggests that RA is involved in the formation of the vasculature; however, its effect on endothelial cell angiogenesis and metabolism is unclear. Methods Our study was designed to clarify the abovementioned effect with human embryonic stem cell-derived endothelial cells (hESC-ECs) employed as a cell model. Results We found that RA inhibits angiogenesis, as manifested by decreased proliferation, migration and sprouting activity. RNA sequencing revealed general suppression of glycometabolism in hESC-ECs in response to RA, consistent with the decreased glycolytic activity and glucose uptake. After screening glycometabolism-related genes, we found that fructose-1,6-bisphosphatase 1 (FBP1), a key rate-limiting enzyme in gluconeogenesis, was significantly upregulated after RA treatment. After silencing or pharmacological inhibition of FBP1 in hESC-ECs, the capacity for angiogenesis was enhanced, and the inhibitory effect of RA was reversed. ChIP-PCR demonstrated that FBP1 is a target gene of RAR. When hESC-ECs were treated with the RAR inhibitor BMS493, FBP1 expression was decreased and the effect of RA on angiogenesis was partially blocked. Conclusions The inhibitory role of RA in glycometabolism and angiogenesis is RAR/FBP1 dependent, and FBP1 may be a novel therapeutic target for pathological angiogenesis.
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- 2022
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6. Advances in Research on Low-dose CT Imaging Algorithm Based on Deep Learning
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Zefang HAN, Hong SHANGGUAN, Xiong ZHANG, Xinglong HAN, Zhiguo GUI, Xueying CUI, and Pengcheng ZHANG
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deep learning ,low dose ct ,artifact suppression ,noise modeling ,Geophysics. Cosmic physics ,QC801-809 ,Medicine (General) ,R5-920 - Abstract
Computed tomography (CT) is widely used in clinical diagnosis because of its fast imaging speed and high resolution. However, higher doses of radiation will cause damages to human tissues and organs, while lower doses will lead to serious deterioration of imaging quality. In order to solve the above contradiction, researchers have focused on the low-dose CT imaging technology to study how to reduce the harm caused by radiation to the human body to the greatest extent under the condition of ensuring the imaging quality to meet the needs of clinical diagnosis. In recent years, deep learning has developed rapidly in the field of artificial intelligence, and has been widely used in image processing, pattern recognition, signal processing fields. Driven by big data, LDCT imaging algorithms based on deep learning have made great progress. This paper studies the development of low-dose CT imaging algorithms in recent years in terms of three aspects: the process of CT imaging, the noise modeling of low-dose CT, and the design of imaging algorithms. In particular, the imaging algorithms in the field of deep learning are systematically elaborated and analyzed. Finally, future developments in the field of LDCT image artifact suppression are also prospected.
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- 2022
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7. Human embryonic stem cell-derived cardiomyocyte therapy in mouse permanent ischemia and ischemia-reperfusion models
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You Yu, Nianci Qin, Xing-Ai Lu, Jingjing Li, Xinglong Han, Xuan Ni, Lingqun Ye, Zhenya Shen, Weiqian Chen, Zhen-Ao Zhao, Wei Lei, and Shijun Hu
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Ischemic heart disease ,Embryonic stem cell ,Cardiomyocyte ,Cell therapy ,Medicine (General) ,R5-920 ,Biochemistry ,QD415-436 - Abstract
Abstract Background Ischemic heart diseases are still a threat to human health. Human pluripotent stem cell-based transplantation exhibits great promise in cardiovascular disease therapy, including heart ischemia. The purpose of this study was to compare the efficacy of human embryonic stem cell-derived cardiomyocyte (ESC-CM) therapy in two heart ischemia models, namely, permanent ischemia (PI) and myocardial ischemia reperfusion (IR). Methods Human embryonic stem cell-derived cardiomyocytes were differentiated from engineered human embryonic stem cells (ESC-Rep) carrying green fluorescent protein (GFP), herpes simplex virus-1 thymidine kinase (HSVtk), and firefly luciferase (Fluc). Two different heart ischemia models were generated by the ligation of the left anterior descending artery (LAD), and ESC-Rep-derived cardiomyocytes (ESC-Rep-CMs) were transplanted into the mouse hearts. Cardiac function was analyzed to evaluate the outcomes of ESC-Rep-CM transplantation. Bioluminescence signal analysis was performed to assess the cell engraftment. Finally, the inflammation response was analyzed by real-time PCR and ELISA. Results Cardiac function was significantly improved in the PI group with ESC-Rep-CM injection compared to the PBS-injected control, as indicated by increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), as well as reduced fibrotic area. However, minimal improvement by ESC-Rep-CM injection was detected in the IR mouse model. We observed similar engraftment efficiency between PI and IR groups after ESC-Rep-CM injection. However, the restricted inflammation was observed after the injection of ESC-Rep-CMs in the PI group, but not in the IR group. Transplantation of ESC-Rep-CMs can partially preserve the heart function via regulating the inflammation response in the PI model, while little improvement of cardiac function in the IR model may be due to the less dynamic inflammation response by the mild heart damage. Conclusions Our findings identified the anti-inflammatory effect of ESC-CMs as a possible therapeutic mechanism to improve cardiac function in the ischemic heart.
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- 2019
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8. Generation of an EFNB2-2A-mCherry reporter human embryonic stem cell line using CRISPR/Cas9-mediated site-specific homologous recombination
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Ying Huang, Hongchun Wu, Xinglong Han, Jie Wu, Miao Yu, Zhen-Ao Zhao, Zhenya Shen, Shijun Hu, and Wei Lei
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Biology (General) ,QH301-705.5 - Abstract
Ephrin B2 (EFNB2) is the first identified and most widely used marker for arterial endothelial cells (AECs). We generated a heterozygous EFNB2-2A-mCherry reporter H1 cell line, H1-EFNB2-2A-mCherry+/− (WAe001-A-57), by CRISPR/Cas9-mediated insertion of 2A-mCherry cassette into the EFNB2 gene locus, immediately before the translation stop codon. The H1-EFNB2-2A-mCherry reporter cells were pluripotent and could differentiate into all three germ layer lineages. Simultaneous expression of mCherry was observed when expression of EFNB2 was increased during endothelial cell differentiation. Thus, the generated reporter cells enable live identification of EFNB2-positive AECs, and screening of small molecule compound and target genes that promote AEC differentiation.
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- 2021
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9. Accelerated postero-lateral spinal fusion by collagen scaffolds modified with engineered collagen-binding human bone morphogenetic protein-2 in rats.
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Xinglong Han, Wen Zhang, Jun Gu, Huan Zhao, Li Ni, Jiajun Han, Yun Zhou, Yannan Gu, Xuesong Zhu, Jie Sun, Xianglin Hou, Huilin Yang, Jianwu Dai, and Qin Shi
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Medicine ,Science - Abstract
Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive cytokine that plays a critical role in bone regeneration and repair. However, its distribution and side effects are major barriers to its success as therapeutic treatment. The improvement of therapy using collagen delivery matrices has been reported. To investigate a delivery system on postero-lateral spinal fusion, both engineered human BMP-2 with a collagen binding domain (CBD-BMP-2) and collagen scaffolds were developed and their combination was implanted into Sprague-Dawley (SD) rats to study Lumbar 4-5 (L4-L5) posterolateral spine fusion. We divided SD rats into three groups, the sham group (G1, n = 20), the collagen scaffold-treated group (G2, n = 20) and the BMP-2-loaded collagen scaffolds group (G3, n = 20). 16 weeks after surgery, the spines of the rats were evaluated by X-radiographs, high-resolution micro-computed tomography (micro-CT), manual palpation and hematoxylin and eosin (H&E) staining. The results showed that spine L4-L5 fusions occurred in G2(40%) and G3(100%) group, while results from the sham group were inconsistent. Moreover, G3 had better results than G2, including higher fusion efficiency (X score, G2 = 2.4±0.163, G3 = 3.0±0, p
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- 2014
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10. Hybrid Beamforming for Full-Duplex Enabled Cellular System in the Unlicensed mmWave Band.
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Xinglong Han, Shengbo Liu, and Liqun Fu 0001
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- 2021
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11. Artifact and Detail Attention Generative Adversarial Networks for Low-Dose CT Denoising.
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Xiong Zhang 0006, Zefang Han, Hong Shangguan, Xinglong Han, Xueying Cui, and Anhong Wang
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- 2021
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12. Energy-Saving Clustering Routing Protocol for Wireless Sensor Networks Using Fuzzy Inference
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Jun Hou, Jianhua Qiao, and Xinglong Han
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Electrical and Electronic Engineering ,Instrumentation - Published
- 2022
13. Phosphorous-doped 1T-MoS2 decorated nitrogen-doped g-C3N4 nanosheets for enhanced photocatalytic nitrogen fixation
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Xiaoli Zhang, Yanli Zhou, Hongzhi Cui, Zhangqian Liang, Xiang Liu, Yanjun Xue, Xinglong Han, and Jian Tian
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Materials science ,Annealing (metallurgy) ,Composite number ,Intercalation (chemistry) ,Doping ,Graphitic carbon nitride ,Hydrothermal circulation ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Catalysis ,Biomaterials ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Chemical engineering ,chemistry ,Photocatalysis - Abstract
Herein, we report that the phosphorous-doped 1 T-MoS2 as co-catalyst decorated nitrogen-doped g-C3N4 nanosheets (P-1 T-MoS2@N-g-C3N4) are prepared by the hydrothermal and annealing process. The obtained P-1 T-MoS2@N-g-C3N4 composite presents an enhanced photocatalytic N2 reduction rate of 689.76 μmol L-1 g-1h−1 in deionized water without sacrificial agent under simulated sunlight irradiation, which is higher than that of pure g-C3N4 (265.62 μmol L-1 g-1h−1), 1 T-MoS2@g-C3N4 (415.57 μmol L-1 g-1h−1), 1 T-MoS2@N doped g-C3N4 (469.84 μmol L-1 g-1h−1), and P doped 1 T-MoS2@g-C3N4 (531.24 μmol L-1 g-1h−1). In addition, compared with pure g-C3N4 NSs (2.64 mmol L-1 g-1h−1), 1 T-MoS2@g-C3N4 (4.98 mmol L-1 g-1h−1), 1 T-MoS2@N doped g-C3N4 (6.21 mmol L-1 g-1h−1), and P doped 1 T-MoS2@g-C3N4 (9.78 mmol L-1 g-1h−1), P-1 T-MoS2@N-g-C3N4 (11.12 mmol L-1 g-1h−1) composite also shows a significant improvement for photocatalytic N2 fixation efficiency in the sacrificial agent (methanol). The improved photocatalytic activity of P-1 T-MoS2@N-g-C3N4 composite is ascribed to the following advantages: 1) Compared to pure g-C3N4, P-1 T-MoS2@N-g-C3N4 composite shows higher light absorption capacity, which can improve the utilization rate of the catalyst to light; 2) The P doping intercalation strategy can promote the conversion of 1 T phase MoS2, which in turn in favor of photogenerated electron transfer and reduce the recombination rate of carriers; 3) A large number of active sites on the edge of 1 T-MoS2 and the existence of N doping in g-C3N4 contribute to photocatalytic N2 fixation.
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- 2022
14. Application of Software Remote Synchronization Mode in Aerospace Products
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ManLi Li, XiaoHong Liang, and XingLong Han
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- 2022
15. Establishment of an in vitro safety assessment model for lipid-lowering drugs using same-origin human pluripotent stem cell-derived cardiomyocytes and endothelial cells
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Nan Ding, Dandan Zhao, Shijun Hu, Zhen-Ao Zhao, Zhuangzhuang Yang, Feng-Yue Ding, Hongchun Wu, Xinglong Han, Wei Lei, Lingqun Ye, Miao Yu, Xuan Ni, and Guang-Yin Xu
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Models, Molecular ,0301 basic medicine ,Cell Survival ,Atorvastatin ,Cell ,Pharmacology ,Article ,Cell Line ,Structure-Activity Relationship ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Myocytes, Cardiac ,Pharmacology (medical) ,Viability assay ,Induced pluripotent stem cell ,Alirocumab ,Tube formation ,Dose-Response Relationship, Drug ,Molecular Structure ,business.industry ,Anticholesteremic Agents ,PCSK9 ,Endothelial Cells ,Cell Differentiation ,General Medicine ,030104 developmental biology ,medicine.anatomical_structure ,Drug development ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
Cardiovascular safety assessment is vital for drug development, yet human cardiovascular cell models are lacking. In vitro mass-generated human pluripotent stem cell (hPSC)-derived cardiovascular cells are a suitable cell model for preclinical cardiovascular safety evaluations. In this study, we established a preclinical toxicology model using same-origin hPSC-differentiated cardiomyocytes (hPSC-CMs) and endothelial cells (hPSC-ECs). For validation of this cell model, alirocumab, a human antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), was selected as an emerging safe lipid-lowering drug; atorvastatin, a common statin (the most effective type of lipid-lowering drug), was used as a drug with reported side effects at high concentrations, while doxorubicin was chosen as a positive cardiotoxic drug. The cytotoxicity of these drugs was assessed using CCK8, ATP, and lactate dehydrogenase release assays at 24, 48, and 72 h. The influences of these drugs on cardiomyocyte electrophysiology were detected using the patch-clamp technique, while their effects on endothelial function were determined by tube formation and Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake assays. We showed that alirocumab did not affect the cell viability or cardiomyocyte electrophysiology in agreement with the clinical results. Atorvastatin (5–50 μM) dose-dependently decreased cardiovascular cell viability over time, and at a high concentration (50 μM, ~100 times the normal peak serum concentration in clinic), it affected the action potentials of hPSC-CMs and damaged tube formation and Dil-Ac-LDL uptake of hPSC-ECs. The results demonstrate that the established same-origin hPSC-derived cardiovascular cell model can be used to evaluate lipid-lowering drug safety in cardiovascular cells and allow highly accurate preclinical assessment of potential drugs.
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- 2021
16. CXADR‐like membrane protein protects against heart injury by preventing excessive pyroptosis after myocardial infarction
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Zhen-Ao Zhao, Yufang Zheng, Yongming Wang, Xinglong Han, Hongchun Wu, Zhenya Shen, Wei Lei, Yaning Wang, Hongyan Wang, Xing-Ai Lu, Miao Yu, Yueqiu Chen, Shiping Yan, Shijun Hu, and Jingjing Li
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0301 basic medicine ,Heart Injury ,Programmed cell death ,Coxsackie and Adenovirus Receptor-Like Membrane Protein ,Genotype ,DNA Mutational Analysis ,Interleukin-1beta ,Myocardial Infarction ,Gene Expression ,Inflammation ,Mice, Transgenic ,Pharmacology ,Models, Biological ,fibroblast ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,Pyroptosis ,Animals ,Myocardial infarction ,Mice, Knockout ,Gene knockdown ,business.industry ,CLMP ,Myocardium ,Cell Biology ,Original Articles ,Fibroblasts ,medicine.disease ,Immunohistochemistry ,Disease Models, Animal ,030104 developmental biology ,Phenotype ,inflammation ,Echocardiography ,030220 oncology & carcinogenesis ,Heart failure ,Mutation ,Molecular Medicine ,Myocardial fibrosis ,Original Article ,medicine.symptom ,Inflammation Mediators ,business ,Biomarkers - Abstract
Myocardial infarction (MI) results in cardiomyocyte death and ultimately leads to heart failure. Pyroptosis is a type of the inflammatory programmed cell death that has been found in various diseased tissues. However, the role of pyroptosis in MI heart remains unknown. Here, we showed that CXADR‐like membrane protein (CLMP) was involved in pyroptosis in the mouse MI heart. Our data showed that CLMP was strongly expressed in fibroblasts of the infarcted mouse hearts. The Clmp +/− mice showed more serious myocardial fibrosis and ventricular dysfunction post‐MI than wild‐type (Clmp +/+) mice, indicating a protective effect of the fibroblast‐expressed CLMP against MI‐induced heart damage. Transcriptome analyses by RNA sequencing indicated that Il‐1β mRNA was significantly increased in the MI heart of Clmp +/− mouse, which indicated a more serious inflammatory response. Meanwhile, cleaved caspase‐1 and Gasdermin D were significantly increased in the Clmp +/− MI heart, which demonstrated enhanced pyroptosis in the Clmp knockdown heart. Further analysis revealed that the pyroptosis mainly occurred in cardiac fibroblasts (CFs). Compared to wild‐type fibroblasts, Clmp +/− CFs showed more serious pyroptosis and inflammatory after LPS plus nigericin treatment. Collectively, our results indicate that CLMP participates in the pyroptotic and inflammatory response of CFs in MI heart. We have provided a novel pyroptotic insight into the ischaemic heart, which might hold substantial potential for the treatment of MI.
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- 2020
17. Retinoic acid inhibits the angiogenesis of human embryonic stem cell-derived endothelial cells by activating FBP1-mediated gluconeogenesis
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Zhuangzhuang Yang, Miao Yu, Xuechun Li, Yuanyuan Tu, Chunyan Wang, Wei Lei, Min Song, Yong Wang, Ying Huang, Fengyue Ding, Kaili Hao, Xinglong Han, Xuan Ni, Lina Qu, Zhenya Shen, and Shijun Hu
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Neovascularization, Pathologic ,Human Embryonic Stem Cells ,Gluconeogenesis ,Molecular Medicine ,Medicine (miscellaneous) ,Endothelial Cells ,Humans ,Tretinoin ,Cell Biology ,Fructose ,Biochemistry, Genetics and Molecular Biology (miscellaneous) - Abstract
Background Endothelial cells are located in the inner lumen of blood and lymphatic vessels and exhibit the capacity to form new vessel branches from existing vessels through a process called angiogenesis. This process is energy intensive and tightly regulated. Glycolysis is the main energy source for angiogenesis. Retinoic acid (RA) is an active metabolite of vitamin A and exerts biological effects through its receptor retinoic acid receptor (RAR). In the clinic, RA is used to treat acne vulgaris and acute promyelocytic leukemia. Emerging evidence suggests that RA is involved in the formation of the vasculature; however, its effect on endothelial cell angiogenesis and metabolism is unclear. Methods Our study was designed to clarify the abovementioned effect with human embryonic stem cell-derived endothelial cells (hESC-ECs) employed as a cell model. Results We found that RA inhibits angiogenesis, as manifested by decreased proliferation, migration and sprouting activity. RNA sequencing revealed general suppression of glycometabolism in hESC-ECs in response to RA, consistent with the decreased glycolytic activity and glucose uptake. After screening glycometabolism-related genes, we found that fructose-1,6-bisphosphatase 1 (FBP1), a key rate-limiting enzyme in gluconeogenesis, was significantly upregulated after RA treatment. After silencing or pharmacological inhibition of FBP1 in hESC-ECs, the capacity for angiogenesis was enhanced, and the inhibitory effect of RA was reversed. ChIP-PCR demonstrated that FBP1 is a target gene of RAR. When hESC-ECs were treated with the RAR inhibitor BMS493, FBP1 expression was decreased and the effect of RA on angiogenesis was partially blocked. Conclusions The inhibitory role of RA in glycometabolism and angiogenesis is RAR/FBP1 dependent, and FBP1 may be a novel therapeutic target for pathological angiogenesis.
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- 2021
18. Generation of Human Induced Pluripotent Stem Cells from Renal Epithelial Cells
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Miao, Yu, Xinglong, Han, Lingqun, Ye, Wei, Lei, and Shijun, Hu
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Induced Pluripotent Stem Cells ,Humans ,Epithelial Cells ,Embryonic Stem Cells - Abstract
In the past decades, human induced pluripotent stem cells (iPSCs) have been generated by the ectopic expression of "Yamanaka factors" in multiple somatic cells. However, the procedure to get access to donor cells is hard or invasive in most cases. Hereon, we depict a stepwise method developed in our laboratory for the generation of iPSCs from renal epithelial cells present in urine, which is noninvasive, nonintegrating, and universal. The resulting urinary iPSCs (UiPSCs) exhibit pluripotent characteristics resemble embryonic stem cells (ESCs) and thus urine may be a favorable source for generating iPSCs.
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- 2021
19. Phosphorous-doped 1T-MoS
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Xiang, Liu, Xinglong, Han, Zhangqian, Liang, Yanjun, Xue, Yanli, Zhou, Xiaoli, Zhang, Hongzhi, Cui, and Jian, Tian
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Herein, we report that the phosphorous-doped 1 T-MoS
- Published
- 2021
20. LncRNA-Safe contributes to cardiac fibrosis through Safe-Sfrp2-HuR complex in mouse myocardial infarction
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Wei Lei, Kaili Hao, Guisheng Zhong, Hongchun Wu, Zhuangzhuang Yang, Zhen Ao Zhao, Xue Xia, Wenbo Deng, Shijun Hu, Xinglong Han, Xing Ai Lu, Jie Wu, Shiping Yan, and Jingjing Li
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0301 basic medicine ,Cardiac function curve ,Cardiac fibrosis ,RNA Stability ,non-coding RNA ,Myocardial Infarction ,Medicine (miscellaneous) ,030204 cardiovascular system & hematology ,ELAV-Like Protein 1 ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,medicine ,Animals ,Humans ,Electrophoretic mobility shift assay ,Myocardial infarction ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Gene knockdown ,business.industry ,fibrosis ,Membrane Proteins ,Fibroblasts ,medicine.disease ,Non-coding RNA ,030104 developmental biology ,Heart failure ,cardiovascular system ,Cancer research ,Female ,RNA, Long Noncoding ,cardiac remodeling ,business ,Research Paper ,Protein Binding - Abstract
Rationale: As a hallmark of various heart diseases, cardiac fibrosis ultimately leads to end-stage heart failure. Anti-fibrosis is a potential therapeutic strategy for heart failure. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of heart diseases that promise to serve as therapeutic targets. However, few lncRNAs have been directly implicated in cardiac fibrosis. Methods: The lncRNA expression profiles were assessed by microarray in cardiac fibrotic and remote ventricular tissues in mice with myocardial infarction. The mechanisms and functional significance of lncRNA-AK137033 in cardiac fibrosis were further investigated with both in vitro and in vivo models. Results: We identified 389 differentially expressed lncRNAs in cardiac fibrotic and remote ventricular tissues in mice with myocardial infarction. Among them, a lncRNA (AK137033) we named Safe was enriched in the nuclei of fibroblasts, and elevated in both myocardial infarction and TGF-β-induced cardiac fibrosis. Knockdown of Safe prevented TGF-β-induced fibroblast-myofibroblast transition, aberrant cell proliferation and secretion of extracellular matrix proteins in vitro, and mended the impaired cardiac function in mice suffering myocardial infarction. In vitro studies indicated that knockdown of Safe significantly inhibited the expression of its neighboring gene Sfrp2, and vice versa. The Sfrp2 overexpression obviously disturbed the regulatory effects of Safe shRNAs in both the in vitro cultured cardiac fibroblasts and myocardial infarction-induced fibrosis. Dual-Luciferase assay demonstrated that Safe and Sfrp2 mRNA stabilized each other via their complementary binding at the 3'-end. RNA electrophoretic mobility shift assay and RNA immunoprecipitation assay indicated that RNA binding protein HuR could bind to Safe-Sfrp2 RNA duplex, whereas the knockdown of HuR dramatically reduced the stabilization of Safe and Sfrp2 mRNAs, down-regulated their expression in cardiac fibroblasts, and thus inhibited TGF-β-induced fibrosis. The Safe overexpression partially restrained the phenotype change of cardiac fibroblasts induced by Sfrp2 shRNAs, but not that induced by HuR shRNAs. Conclusions: Our study identifies Safe as a critical regulator of cardiac fibrosis, and demonstrates Safe-Sfrp2-HuR complex-mediated Sfrp2 mRNA stability is the underlying mechanism of Safe-regulated cardiac fibrosis. Fibroblast-enriched Safe could represent a novel target for anti-fibrotic therapy in heart diseases.
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- 2019
21. Generation of an EFNB2-2A-mCherry reporter human embryonic stem cell line using CRISPR/Cas9-mediated site-specific homologous recombination
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Zhen-Ao Zhao, Hongchun Wu, Miao Yu, Zhenya Shen, Ying Huang, Jie Wu, Xinglong Han, Shijun Hu, and Wei Lei
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0301 basic medicine ,Human Embryonic Stem Cells ,Ephrin-B2 ,Biology ,Endothelial cell differentiation ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,CRISPR ,Humans ,Homologous Recombination ,Gene ,lcsh:QH301-705.5 ,Endothelial Cells ,Cell Biology ,General Medicine ,Stop codon ,Cell biology ,030104 developmental biology ,lcsh:Biology (General) ,Cell culture ,CRISPR-Cas Systems ,Homologous recombination ,mCherry ,030217 neurology & neurosurgery ,Developmental Biology ,Human embryonic stem cell line - Abstract
Ephrin B2 (EFNB2) is the first identified and most widely used marker for arterial endothelial cells (AECs). We generated a heterozygous EFNB2-2A-mCherry reporter H1 cell line, H1-EFNB2-2A-mCherry+/- (WAe001-A-57), by CRISPR/Cas9-mediated insertion of 2A-mCherry cassette into the EFNB2 gene locus, immediately before the translation stop codon. The H1-EFNB2-2A-mCherry reporter cells were pluripotent and could differentiate into all three germ layer lineages. Simultaneous expression of mCherry was observed when expression of EFNB2 was increased during endothelial cell differentiation. Thus, the generated reporter cells enable live identification of EFNB2-positive AECs, and screening of small molecule compound and target genes that promote AEC differentiation.
- Published
- 2021
22. Generation of Human Induced Pluripotent Stem Cells from Renal Epithelial Cells
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Wei Lei, Xinglong Han, Shijun Hu, Miao Yu, and Lingqun Ye
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Somatic cell ,Epithelial cells present ,Urinary system ,Ectopic expression ,Human Induced Pluripotent Stem Cells ,Biology ,Induced pluripotent stem cell ,Reprogramming ,Embryonic stem cell ,Cell biology - Abstract
In the past decades, human induced pluripotent stem cells (iPSCs) have been generated by the ectopic expression of "Yamanaka factors" in multiple somatic cells. However, the procedure to get access to donor cells is hard or invasive in most cases. Hereon, we depict a stepwise method developed in our laboratory for the generation of iPSCs from renal epithelial cells present in urine, which is noninvasive, nonintegrating, and universal. The resulting urinary iPSCs (UiPSCs) exhibit pluripotent characteristics resemble embryonic stem cells (ESCs) and thus urine may be a favorable source for generating iPSCs.
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- 2021
23. Abstract 241: Retinoic Acid Promotes Metabolic Maturation of Human Embryonic Stem Cell-derived Cardiomyocytes
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Xing Fang, Xiaoxiao Wang, Wei Lei, Xinglong Han, Zhen-Ao Zhao, Miao Yu, Shijun Hu, Xuan Ni, Jingsi Yang, Lingqun Ye, Shumei Miao, Dandan Zhao, Hongchun Wu, Zhenya Shen, and Lei Li
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chemistry.chemical_compound ,Physiology ,Chemistry ,Retinoic acid ,Cardiology and Cardiovascular Medicine ,Embryonic stem cell ,Cell biology - Abstract
Cardiomyocytes differentiated from human embryonic stem cells (hESCs) represent a promising cell source for heart repair, disease modeling and drug testing. However, improving the differentiation efficiency and maturation of hESC-derived cardiomyocytes (hESC-CMs) is still a major concern. Retinoic acid (RA) signaling plays multiple roles in heart development, and studies on RA can provide clues for understanding cardiomyocyte differentiation and maturation. In this study, we studied the roles of RA during cardiomyocyte differentiation and maturation, systematically. After adding RA at different stages of cardiomyocyte differentiation, we compared the efficiency of differentiation by quantitative real-time PCR and flow cytometry. We found that RA treatment at the lateral mesoderm stage (days 2-4) significantly improved cardiomyocyte differentiation, as evidenced by the upregulation of TNNT2, NKX2.5 and MYH6 on day 10 of differentiation. In addition, flow cytometry showed that the proportion of differentiated cardiomyocytes in the RA-treated group was significantly higher than that in control group. Furthermore, RA was added at different time intervals after purification to induce cardiomyocyte maturation. Our results demonstrated that RA treatment on days 15-20 increased cardiomyocyte area, sarcomere length, multinucleation and mitochondrial copy number, and promoted RNA splicing switch. Importantly, RA-treated cardiomyocytes showed decreased glycolysis and enhanced mitochondrial oxidative phosphorylation, with the increased utilization of fatty acid and exogenous pyruvate but not glutamine. In conclusion, our data indicated that RA treatment at an early time window (days 2-4) promotes the efficiency of cardiomyocyte differentiation and that RA treatment post beating (days 15-20) promotes cardiomyocyte metabolic maturation. The biphasic effects of RA provide new insights for improving cardiomyocyte differentiation and quality.
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- 2020
24. Retinoic acid promotes metabolic maturation of human Embryonic Stem Cell-derived Cardiomyocytes
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Lei Li, Feng Lan, Jingsi Yang, Lingqun Ye, Dandan Zhao, Hongchun Wu, Zhen-Ao Zhao, Xiaoxiao Wang, Wei Lei, Lina Qu, Xinglong Han, Miao Yu, Zhenya Shen, Shumei Miao, Shijun Hu, Xing Fang, and Xuan Ni
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0301 basic medicine ,Embryonic stem cells ,Cell ,Human Embryonic Stem Cells ,Retinoic acid ,Medicine (miscellaneous) ,Tretinoin ,030204 cardiovascular system & hematology ,Biology ,Oxidative Phosphorylation ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Downregulation and upregulation ,Pyruvic Acid ,medicine ,Animals ,Humans ,Myocytes, Cardiac ,Patch clamp ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Cardiomyocyte maturation ,Mice, Inbred ICR ,Heart development ,Sequence Analysis, RNA ,Fatty Acids ,Cell Differentiation ,Embryonic stem cell ,Cell biology ,Up-Regulation ,Glutamine ,Cardiomyocyte differentiation ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,MYH6 ,Signal Transduction ,Research Paper - Abstract
Cardiomyocytes differentiated from human embryonic stem cells (hESCs) represent a promising cell source for heart repair, disease modeling and drug testing. However, improving the differentiation efficiency and maturation of hESC-derived cardiomyocytes (hESC-CMs) is still a major concern. Retinoic acid (RA) signaling plays multiple roles in heart development. However, the effects of RA on cardiomyocyte differentiation efficiency and maturation are still unknown. Methods: RA was added at different time intervals to identify the best treatment windows for cardiomyocyte differentiation and maturation. The efficiency of cardiomyocyte differentiation was detected by quantitative real-time PCR and flow cytometry. Cardiomyocytes maturation was detected by immunofluorescence staining, metabolic assays and patch clamp to verify structural, metabolic and electrophysiological maturation, respectively. RNA sequencing was used for splicing analysis. Results: We found that RA treatment at the lateral mesoderm stage (days 2-4) significantly improved cardiomyocyte differentiation, as evidenced by the upregulation of TNNT2, NKX2.5 and MYH6 on day 10 of differentiation. In addition, flow cytometry showed that the proportion of differentiated cardiomyocytes in the RA-treated group was significantly higher than that in control group. RA treatment on days 15-20 increased cardiomyocyte area, sarcomere length, multinucleation and mitochondrial copy number. RNA sequencing revealed RA promoted RNA isoform switch to the maturation-related form. Meanwhile, RA promoted electrophysiological maturation and calcium handling of hESC-CMs. Importantly, RA-treated cardiomyocytes showed decreased glycolysis and enhanced mitochondrial oxidative phosphorylation, with the increased utilization of fatty acid and exogenous pyruvate but not glutamine. Conclusion: Our data indicated that RA treatment at an early time window (days 2-4) promotes the efficiency of cardiomyocyte differentiation and that RA treatment post beating (days 15-20) promotes cardiomyocyte maturation. The biphasic effects of RA provide new insights for improving cardiomyocyte differentiation and quality.
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- 2020
25. Abstract 408: Mir148a Family Regulates Cardiac Differentiation of Human Embryonic Stem Cells by Inhibiting The Dll1 -mediated Notch Signaling Pathway
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Zhen-Ao Zhao, Shumei Miao, Wei Lei, You Yu, Xinglong Han, Xing Fang, Hongchun Wu, Yongming Wang, and Shijun Hu
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Cardiac regeneration ,Physiology ,Cardiac differentiation ,microRNA ,Notch signaling pathway ,Biology ,Cardiology and Cardiovascular Medicine ,Induced pluripotent stem cell ,Embryonic stem cell ,Stem cell biology ,In vitro ,Cell biology - Abstract
Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can differentiate into spontaneously beating cardiomyocytes in vitro, and hold great promise for cardiovascular disease modeling, therapy and drug discovery. However, these applications were hampered by low yield and purity of the in vitro differentiated cardiomyocytes. Although miRNAs represent a type of potential candidates to promote cardiac differentiation, most of cardiomyocyte-enriched miRNAs have not been functionally investigated until now. This study investigated the roles of MIR148A family in cardiac differentiation from hESCs. The MIR148A family is composed of MIR148A , MIR148B and MIR152 , three highly conserved miRNAs sharing same seed sequences. The expression levels of all MIR148A family members were progressively increased during cardiac differentiation in vitro. By using CRISPR-Cas9-mediated knockout, we demonstrated that triple knockout of MIR148A family ( MIR148A -TKO), rather than individual knockout of each members, could grossly inhibited TNNT2 + cardiomyocyte generation. Ectopic expression of MIR152 significantly restored the cardiac differentiation efficiency of MIR148A -TKO hESCs. The transcriptome analysis identified a total of 1071 upregulated genes and 766 down-regulated genes in the MIR148A -TKO hESC-derived cells compared to wild-type hESC-derived cells at day 4 of cardiac differentiation. Gene Ontology analysis revealed that most genes down-regulated in MIR148A -TKO hESC-derived cells were involved in the events of lateral/cardiac mesoderm development, while the up-regulated genes were mainly involved in the events of paraxial/somitic development. Furthermore, the NOTCH ligand Delta-like1 ( DLL1 ) was validated as the target gene of MIR148A family, and the knockdown of DLL1 could inhibit target gene expression of Notch signaling pathway, and promote cardiac differentiation of MIR148A -TKO hESCs. Our findings demonstrate a new function of MIR148A family during cardiac differentiation. Synergistic inhibition of DLL1 -mediated Notch signaling represents a major mechanism for the MIR148A family to inhibit undesired lineage formation and promote hESC differentiation into cardiomyocytes.
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- 2019
26. MIR148A family regulates cardiomyocyte differentiation of human embryonic stem cells by inhibiting the DLL1-mediated NOTCH signaling pathway
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Hongchun Wu, Shumei Miao, Feng-Yue Ding, Xing Fang, Zhen-Ao Zhao, Xinglong Han, Wei Lei, You Yu, Yongming Wang, and Shijun Hu
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0301 basic medicine ,Human Embryonic Stem Cells ,Notch signaling pathway ,030204 cardiovascular system & hematology ,Biology ,Cell Line ,Transcriptome ,Mesoderm ,03 medical and health sciences ,0302 clinical medicine ,Paraxial mesoderm ,Humans ,Myocytes, Cardiac ,Molecular Biology ,Gene knockdown ,Receptors, Notch ,Primitive streak ,Lateral plate mesoderm ,Gene Expression Profiling ,Calcium-Binding Proteins ,Membrane Proteins ,Cell Differentiation ,Embryonic stem cell ,Cell biology ,MicroRNAs ,030104 developmental biology ,HEK293 Cells ,embryonic structures ,Ectopic expression ,Cardiology and Cardiovascular Medicine ,Signal Transduction - Abstract
MicroRNAs (miRNAs), as a class of naturally occurring RNAs, play important roles in cardiac physiology and pathology. There are many miRNAs that show multifarious expression patterns during cardiomyocyte genesis. Here, we focused on the MIR148A family, which is composed of MIR148A, MIR148B and MIR152, and shares the same seed sequences. The expression levels of all MIR148A family members progressively increased during the differentiation of human embryonic stem cells (hESCs) into cardiomyocytes. The deletion of MIR148A family (MIR148A-TKO) resulted in a decreased proportion of cardiomyocytes after cardiac induction, which was restored by the ectopic expression of MIR148A family members. Transcriptome analyses indicated that the MIR148A family could partially repress paraxial mesodermal differentiation from primitive streak cells. In turn, these miRNAs promoted lateral mesoderm and cardiomyocyte differentiation. Furthermore, the NOTCH ligand Delta-like 1 (DLL1) was validated as the target gene of MIR148A family, and knockdown of DLL1 could promote the cardiomyocyte differentiation of MIR148A-TKO hESCs. Thus, our results demonstrate MIR148A family could promote cardiomyocyte differentiation by inhibiting undesired paraxial mesoderm lineage commitment, which improves our understanding on cardiomyocyte differentiation from hESCs.
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- 2019
27. Human embryonic stem cell-derived cardiomyocyte therapy in mouse permanent ischemia and ischemia-reperfusion models
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Jingjing Li, Nianci Qin, Lingqun Ye, You Yu, Xing-Ai Lu, Weiqian Chen, Shijun Hu, Xinglong Han, Zhenya Shen, Wei Lei, Zhen-Ao Zhao, and Xuan Ni
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0301 basic medicine ,Cardiac function curve ,medicine.medical_specialty ,Ischemic heart disease ,Green Fluorescent Proteins ,Human Embryonic Stem Cells ,Ischemia ,Medicine (miscellaneous) ,Cardiomyocyte ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Thymidine Kinase ,Ventricular Function, Left ,Cell therapy ,lcsh:Biochemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Humans ,lcsh:QD415-436 ,Myocytes, Cardiac ,Induced pluripotent stem cell ,Luciferases ,lcsh:R5-920 ,Ejection fraction ,business.industry ,Research ,Cell Differentiation ,Stroke Volume ,Cell Biology ,medicine.disease ,Embryonic stem cell ,Transplantation ,Disease Models, Animal ,030104 developmental biology ,030220 oncology & carcinogenesis ,Reperfusion Injury ,Cardiology ,Molecular Medicine ,Stem cell ,lcsh:Medicine (General) ,business - Abstract
Background Ischemic heart diseases are still a threat to human health. Human pluripotent stem cell-based transplantation exhibits great promise in cardiovascular disease therapy, including heart ischemia. The purpose of this study was to compare the efficacy of human embryonic stem cell-derived cardiomyocyte (ESC-CM) therapy in two heart ischemia models, namely, permanent ischemia (PI) and myocardial ischemia reperfusion (IR). Methods Human embryonic stem cell-derived cardiomyocytes were differentiated from engineered human embryonic stem cells (ESC-Rep) carrying green fluorescent protein (GFP), herpes simplex virus-1 thymidine kinase (HSVtk), and firefly luciferase (Fluc). Two different heart ischemia models were generated by the ligation of the left anterior descending artery (LAD), and ESC-Rep-derived cardiomyocytes (ESC-Rep-CMs) were transplanted into the mouse hearts. Cardiac function was analyzed to evaluate the outcomes of ESC-Rep-CM transplantation. Bioluminescence signal analysis was performed to assess the cell engraftment. Finally, the inflammation response was analyzed by real-time PCR and ELISA. Results Cardiac function was significantly improved in the PI group with ESC-Rep-CM injection compared to the PBS-injected control, as indicated by increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), as well as reduced fibrotic area. However, minimal improvement by ESC-Rep-CM injection was detected in the IR mouse model. We observed similar engraftment efficiency between PI and IR groups after ESC-Rep-CM injection. However, the restricted inflammation was observed after the injection of ESC-Rep-CMs in the PI group, but not in the IR group. Transplantation of ESC-Rep-CMs can partially preserve the heart function via regulating the inflammation response in the PI model, while little improvement of cardiac function in the IR model may be due to the less dynamic inflammation response by the mild heart damage. Conclusions Our findings identified the anti-inflammatory effect of ESC-CMs as a possible therapeutic mechanism to improve cardiac function in the ischemic heart. Electronic supplementary material The online version of this article (10.1186/s13287-019-1271-4) contains supplementary material, which is available to authorized users.
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- 2019
28. Additional file 1: of Human embryonic stem cell-derived cardiomyocyte therapy in mouse permanent ischemia and ischemia-reperfusion models
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Yu, You, Nianci Qin, Xing-Ai Lu, Jingjing Li, Xinglong Han, Ni, Xuan, Lingqun Ye, Shen, Zhenya, Weiqian Chen, Zhen-Ao Zhao, Lei, Wei, and Shijun Hu
- Subjects
embryonic structures - Abstract
Figure S1. Generation of reporter-engineered human embryonic stem cells (ESC-Rep). (A) Schematic diagram of CRISPR/Cas9-mediated homologous recombination in AAVS1 locus of PPP1R12C gene. (B) Procedure of ESC-Rep generation. Figure S2. Stage-specific gene expression during cardiomyocyte differentiation. Real-time PCR analysis for markers of pluripotency (POU5F1 and NANOG), mesoderm (T and MIXL1), cardiac mesoderm (MESP1 and EVX1), cardiac progenitors (NKX2.5 and GATA4), and cardiomyocytes (MYH6, MYH7, and TNNI3) during the cardiac differentiation. Figure S3. Characteristics of ESC-Rep-CMs. (A) Flow cytometry assay for troponin T (TNNT2)-positive cardiomyocytes after purification. (B) Patch clamp for electrophysiological characteristics of ESC-Rep-CMs. Figure S4. Postoperative cardiac evaluation in mice. (A) Electrocardiogram analysis of mice in the Sham, PI, and IR groups after surgery. (Bâ D) Heart function analysis of mice in the Sham, PI, and IR groups at day 7 post surgery. All data are presented as the mean Âą SEM; one-way ANOVA; *p < 0.05, **p < 0.01. Table S1. Primers used in this study. Table S2. Antibodies used in this study. Table S3. Cardiac parameters acquired from echocardiography at Day 28. (DOCX 12013 kb)
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- 2019
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29. Response by Zhao et al to Letter Regarding Article, 'Lack of Cardiac Improvement After Cardiosphere-Derived Cell Transplantation in Aging Mouse Hearts'
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Zhen-Ao Zhao, Zhuangzhuang Yang, Jie Wu, Wei Lei, Shijun Hu, Xing-Ai Lu, Yihuan Chen, Jingjing Li, Bin Zhou, Xinglong Han, Mengchao Yao, Lingjuan He, and Shumei Miao
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Physiology ,business.industry ,030204 cardiovascular system & hematology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Cell transplantation ,Internal medicine ,medicine ,Cardiology ,Cardiology and Cardiovascular Medicine ,business - Published
- 2018
30. Lack of Cardiac Improvement After Cardiosphere-Derived Cell Transplantation in Aging Mouse Hearts
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Zhen-Ao Zhao, Zhuangzhuang Yang, Xing-Ai Lu, Jie Wu, Shijun Hu, Wei Lei, Xinglong Han, Mengchao Yao, Jingjing Li, Yihuan Chen, Bin Zhou, and Lingjuan He
- Subjects
0301 basic medicine ,Cardiac function curve ,medicine.medical_specialty ,Ejection fraction ,Physiology ,business.industry ,Diastole ,Ischemia ,030204 cardiovascular system & hematology ,medicine.disease ,Cell therapy ,Transplantation ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Internal medicine ,Diabetes mellitus ,medicine ,Cardiology ,Stem cell ,Cardiology and Cardiovascular Medicine ,business - Abstract
Rationale: Aging is one of the most significant risk factors for cardiovascular diseases, and the incidence of myocardial ischemia increases dramatically with age. Some studies have reported that cardiosphere-derived cells (CDCs) could benefit the injured heart. Nevertheless, the convincing evidence on CDC-induced improvement of aging heart is still limited. Objective: In this study, we tested whether the CDCs isolated from neonatal mice could benefit cardiac function in aging mice. Methods and Results: We evaluated cardiac function of PBS- (n=15) and CDC-injected (n=19) aging mice. Echocardiography indicated that left ventricular (LV) ejection fraction (57.46%±3.57% versus 57.86%±2.44%) and LV fraction shortening (30.67%±2.41% versus 30.51%±1.78%) showed similar values in PBS- and CDC-injected mice. The diastolic wall thickness of LV was significantly increased after CDC injection, resulting in reduced diastolic LV volume. The pulse-wave Doppler and tissue Doppler imaging indicated that aging mice receiving PBS or CDC injection presented similar values of the peak early transmitral flow velocity, the peak late transmitral flow velocity, the ratio of the peak early transmitral flow velocity to the peak late transmitral flow velocity, and the ratio of the peak early transmitral flow velocity to the peak early diastolic mitral annular velocity, respectively. Pressure-volume loop experiment indicated that the LV end-diastolic pressure-volume relationship and end-systolic pressure-volume relationship were comparable in both PBS- and CDC-injected mice. Postmortem analysis of aging mouse hearts showed similar fibrotic degree in the 2 groups. In addition, the aging markers showed comparable expression levels in both PBS- and CDC-injected mice. The systemic aging performance measures, including exercise capacity, hair regrowth capacity, and inflammation, showed no significant improvement in CDC-injected mice. Finally, the telomere length was comparable between PBS- and CDC-injected mice. Conclusions: Together, these results indicate that CDCs do not improve heart function and systemic performances in aging mice.
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- 2018
31. Biodegradable cell-laden starch foams for the rapid fabrication of 3D tissue constructs and the application in neural tissue engineering
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Xiaoxiao Wen, Huilin Yang, Lei Yang, Changlu Xu, Yanjie Bai, Xinglong Han, and Minjie Shen
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Materials science ,Starch ,Biomedical Engineering ,02 engineering and technology ,Neural tissue engineering ,law.invention ,Cell Line ,Biomaterials ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Tissue engineering ,Magazine ,law ,Animals ,Nerve Tissue ,Cell encapsulation ,030304 developmental biology ,0303 health sciences ,Tissue Engineering ,Tissue Scaffolds ,food and beverages ,Hydrogels ,021001 nanoscience & nanotechnology ,Polymerization ,Chemical engineering ,chemistry ,Cell culture ,Self-healing hydrogels ,Printing, Three-Dimensional ,0210 nano-technology - Abstract
Cells encapsulation by biomaterials has been widely studied as a strategy of building tissue construct in tissue engineering. Conventional encapsulation of cells using hydrogels often needs the polymerization process or relatively complex molding process. In this study, we developed a facile strategy for the in situ fabrication of biodegradable cell-laden starch foams. By utilizing the unique gelatinization property of starch, cell-laden starch foams with tunable architecture were rapidly prepared in a green and biological-friendly process. The bubble size and stiffness of starch foams could be tuned by controlling the content of premixed starch in the cell culture medium. Cells were encapsulated in situ during the foaming process, and the resultant starch foams could be used as building blocks to fabricate three-dimensional tissue construct. The potential application of the cell-laden starch foams in neural tissue engineering was also validated. RSC96 Schwann cells were encapsulated in the starch foams and revealed good viability. Due to the serum-induced degradation of the starch, RSC96 Schwann cells could be released from the starch foams in a controlled manner while remaining high viability. Dorsal root ganglion (DRG) neurons co-cultured with the cell-laden starch foams extended significantly longer neurites compared with neurons cultured in minimum Eagle's medium (664.88 ± 190.39 μm vs. 311.19 ± 105.25 μm). DRG neurons retained high viability even after encapsulation in the starch foams for 3 days. This facile strategy of rapidly fabricating cell-laden starch foams can be further extended to construct centimeter-scale micro-tissue for tissue engineering applications. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:104-116, 2020.
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- 2018
32. Abstract 341: Disturbance of p53-indcued Long Noncoding RNA Meg3 - FUS Complex by AAV9 System Preserves Heart Function in Myocardial Infarction
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Hongchun Wu, Kaili Hao, You Yu, Xinglong Han, Jingjing Li, Zhen-Ao Zhao, Junwei Liu, Joseph C Wu, and Shijun Hu
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Physiology ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: The injured heart undergoes a major process of cellular apoptosis in the initial stage of MI, therefore, the most fundamental method to prevent post-MI remodeling is to suppress cardiomyocyte apoptosis. In this study, we have illustrated the key role of long noncoding RNA, Maternally expressed gene 3 ( Meg3 ), on cardiomyocyte apoptosis and the underlying mechanisms in heart. Methods: Neonatal murine cardiomyocytes and human ESC-derived cardiomyocytes were subjected to hypoxia, and cellular apoptosis was evaluated with Annexin V assay. The Meg3 regulation by p53 was measured by luciferase reporter assay. The complex of Meg3 and RNA-binding protein FUS (Fused in sarcoma) was determined by EMSA and RIP. Adeno-Associated Virus serotype 9 (AAV9) system was employed to knock down Meg3 in cardiomyocytes in vivo, and the cardiac function was evaluated by echocardiography and ex-vivo assays. Results: We first found that Meg3 was progressively upregulated in the murine injured heart after MI, and it showed the pro-apoptotic functions in primary cardiomyocytes. Meg3 could be directly upregulated by p53 during hypoxia condition, and was involved in apoptotic regulation via its direct binding with FUS. The Meg3 knockdown in cardiomyocytes by AAV9 system could preserve heart function in murine myocardial infarction. Moreover, its pro-apoptotic function was conserved in human cardiomyocytes. Conclusion: Together, these results indicate that p53-induced Meg3 - FUS complex plays an important role on cardiomyocyte apoptosis post-MI, and its specific knockdown in cardiomyocytes with AAV9 system represents a promising method to treat myocardial infarction.
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- 2017
33. Research on spacecraft assembly system integration based on PLM
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Xinglong Han and Manli Li
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Spacecraft ,business.industry ,Computer science ,Process (engineering) ,Synchronization (computer science) ,Systems engineering ,Process control ,System integration ,Process design ,business ,Data transmission ,Data modeling - Abstract
In order to solve the problem of ineffective cooperation across multiple departments and application systems in the spacecraft assembly business, the paper analyzed the transmission demand for design data and process data, proposed an integration framework of spacecraft assembly business system, and solved key issues in the integration process such as data transmission and technical state synchronization between PLM and MES.
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- 2016
34. Accelerated Postero-Lateral Spinal Fusion by Collagen Scaffolds Modified with Engineered Collagen-Binding Human Bone Morphogenetic Protein-2 in Rats
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Wen Zhang, Jun Gu, Jiajun Han, Li Ni, Huan Zhao, Yun Zhou, Xinglong Han, Yannan Gu, Huilin Yang, Qin Shi, Jianwu Dai, Xianglin Hou, Jie Sun, and Xuesong Zhu
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medicine.medical_specialty ,Bone density ,medicine.medical_treatment ,Materials Science ,H&E stain ,lcsh:Medicine ,Bone Morphogenetic Protein 2 ,Surgical and Invasive Medical Procedures ,Bone morphogenetic protein ,Bone morphogenetic protein 2 ,Biomaterials ,Rats, Sprague-Dawley ,Internal medicine ,medicine ,Medicine and Health Sciences ,Animals ,Humans ,Sports and Exercise Medicine ,lcsh:Science ,Bone regeneration ,Bone mineral ,Analysis of Variance ,Multidisciplinary ,Lumbar Vertebrae ,Tissue Scaffolds ,Ossification ,Chemistry ,lcsh:R ,Biology and Life Sciences ,Anatomy ,X-Ray Microtomography ,Protein Structure, Tertiary ,Rats ,Endocrinology ,Spinal Fusion ,Spinal fusion ,Physical Sciences ,lcsh:Q ,Collagen ,medicine.symptom ,Genetic Engineering ,Research Article ,Biotechnology ,Protein Binding - Abstract
Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive cytokine that plays a critical role in bone regeneration and repair. However, its distribution and side effects are major barriers to its success as therapeutic treatment. The improvement of therapy using collagen delivery matrices has been reported. To investigate a delivery system on posterolateral spinal fusion, both engineered human BMP-2 with a collagen binding domain (CBD-BMP-2) and collagen scaffolds were developed and their combination was implanted into Sprague-Dawley (SD) rats to study Lumbar 4-5 (L4-L5) posterolateral spine fusion. We divided SD rats into three groups, the sham group (G1, n = 20), the collagen scaffold-treated group (G2, n = 20) and the BMP-2-loaded collagen scaffolds group (G3, n = 20). 16 weeks after surgery, the spines of the rats were evaluated by X-radiographs, high-resolution micro-computed tomography (micro-CT), manual palpation and hematoxylin and eosin (H&E) staining. The results showed that spine L4-L5 fusions occurred in G2(40%) and G3(100%) group, while results from the sham group were inconsistent. Moreover, G3 had better results than G2, including higher fusion efficiency (X score, G2 = 2.4 +/- 0.163, G3 = 3.0 +/- 0, p
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- 2014
35. Collagen scaffolds modified with collagen-binding bFGF promotes the neural regeneration in a rat hemisected spinal cord injury model
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Jie Sun, Liang Chen, Qin Shi, Wei Gao, Xinglong Han, Huilin Yang, Jianwu Dai, Xuesong Zhu, Xianglin Hou, and Fang Xie
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Male ,Pathology ,medicine.medical_specialty ,Cord ,Basic fibroblast growth factor ,Nerve guidance conduit ,General Biochemistry, Genetics and Molecular Biology ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Environmental Science(all) ,medicine ,Animals ,Axon ,Spinal cord injury ,Spinal Cord Injuries ,Spinal Cord Regeneration ,General Environmental Science ,Tissue Scaffolds ,Glial fibrillary acidic protein ,biology ,Agricultural and Biological Sciences(all) ,Biochemistry, Genetics and Molecular Biology(all) ,Regeneration (biology) ,Anatomy ,medicine.disease ,Nerve Regeneration ,Rats ,Disease Models, Animal ,medicine.anatomical_structure ,chemistry ,biology.protein ,Fibroblast Growth Factor 2 ,Collagen ,General Agricultural and Biological Sciences - Abstract
Nerve conduit is one of strategies for spine cord injury (SCI) treatment. Recently, studies showed that biomaterials could guide the neurite growth and promote axon regeneration at the injury site. However, the scaffold by itself was difficult to meet the need of SCI functional recovery. The basic fibroblast growth factor (bFGF) administration significantly promotes functional recovery after organ injuries. Here, using a rat model of T9 hemisected SCI, we aimed at assessing the repair capacity of implantation of collagen scaffold (CS) modified by collagen binding bFGF (CBD-bFGF). The results showed that CS combined with CBD-bFGF treatment improved survival rates after the lateral hemisection SCI. The CS/CBD-bFGF group showed more significant improvements in motor than the simply CS-implanted and untreated control group, when evaluated by the 21-point Basso-Beattie-Bresnahan (BBB) score and footprint analysis. Both hematoxylin and eosin (H&E) and immunohistochemical staining of neurofilament (NF) and glial fibrillary acidic protein (GFAP) demonstrated that fibers were guided to grow through the implants. These findings indicated that administration of CS modified with CBD-bFGF could promote spinal cord regeneration and functional recovery.
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