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Ding JY, Meng TT, Du RL, Song XB, Li YX, Gao J, Ji R, He QY. Bibliometrics of trends in global research on the roles of stem cells in myocardial fibrosis therapy. World J Stem Cells 2024; 16:1086-1105. [PMID: 39734477 PMCID: PMC11669986 DOI: 10.4252/wjsc.v16.i12.1086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 10/05/2024] [Accepted: 11/11/2024] [Indexed: 12/13/2024] Open
Abstract
BACKGROUND Myocardial fibrosis, a condition linked to several cardiovascular diseases, is associated with a poor prognosis. Stem cell therapy has emerged as a potential treatment option and the application of stem cell therapy has been studied extensively. However, a comprehensive bibliometric analysis of these studies has yet to be conducted. AIM To map thematic trends, analyze research hotspots, and project future directions of stem cell-based myocardial fibrosis therapy. METHODS We conducted a bibliometric and visual analysis of studies in the Web of Science Core Collection using VOSviewer and Microsoft Excel. The dataset included 1510 articles published between 2001 and 2024. Countries, organizations, authors, references, keywords, and co-citation networks were examined to identify evolving research trends. RESULTS Our findings revealed a steady increase in the number of publications, with a projected increase to over 200 publications annually by 2030. Initial research focused on stem cell-based therapy, particularly for myocardial infarction and heart failure. More recently, there has been a shift toward cell-free therapy, involving extracellular vesicles, exosomes, and microRNAs. Key research topics include angiogenesis, inflammation, apoptosis, autophagy, and oxidative stress. CONCLUSION This analysis highlights the evolution of stem cell therapies for myocardial fibrosis, with emerging interest in cell-free approaches. These results are expected to guide future scientific exploration and decision-making.
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Affiliation(s)
- Jing-Yi Ding
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Tian-Tian Meng
- Department of Rehabilitation, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100071, China
| | - Ruo-Lin Du
- Department of Emergency Medicine, South Branch of Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Xin-Bin Song
- Department of Intensive Care Unit, Zhumadian Hospital of Traditional Chinese Medicine, Zhumadian 463000, Henan Province, China
| | - Yi-Xiang Li
- Department of Chinese Medicine, The Third People's Hospital of Henan Province, Zhengzhou 450000 Henan Province, China
| | - Jing Gao
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Ran Ji
- Department of Intensive Care Unit, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Qing-Yong He
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
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miR-214-3p Protects and Restores the Myocardial Tissue of Rat Myocardial Infarction Model by Targeting PTEN. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:1175935. [PMID: 35899226 PMCID: PMC9313954 DOI: 10.1155/2022/1175935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 06/14/2022] [Accepted: 06/30/2022] [Indexed: 11/18/2022]
Abstract
Myocardial infarction (MI), which results in myocardial cell dysfunction and irreversible loss, is one of the most serious health threats today. This study was started with rats, by which the consequence of miRNA expression dysregulation to the occurrence and progression of cardiovascular diseases was explored. We first conducted miRNA sequencing on the myocardial tissues separately from myocardial infarction treatment and sham operation treatment to clarify those differently expressed miRNAs; then, our experiment of functional verification of those key miRNAs was initiated so as to dig out the molecular mechanism behind the miRNA's regulation in myocardial infarction. And it turned out that there were 32 upregulated miRNAs and 16 downregulated miRNAs according to our comparison from the myocardial infarction model group to the sham operation group; of all those upregulated, alteration in miR-214-3p expression was the most conspicuous. Overexpression of miR-214-3p greatly alleviated myocardial infarct area and ameliorated myocardial tissue structure, even reducing myocardial fibrosis and the devastation in the tissues. On the molecular level, miR-214-3p overexpression brought down both the apoptosis rate and cleaved caspase 3 expression. Besides that, we verified that PTEN is the target gene of miR-214-3p through a dual-luciferase assay. A cotransfection of miR-214-3p and PTEN brought about an obvious elevation in the myocardial infarct area, tissue damage, and fibrosis, even in the aspect of cellular apoptosis than a mere transfection of miR-214-3p. All the results above verified miR-214-3p′s effects in protecting myocardial tissues and reducing the infarct area, and it was reasonable to assume that those functions of miR-214-3p came into effect by targeting PTEN, which was then justified by the inversion to miR-214-3p′s protection via PTEN overexpression.
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Won E, Morodomi Y, Kanaji S, Shapiro R, Vo M, Orje JN, Thornburg CD, Yang X, Ruggeri ZM, Schimmel P, Kanaji T. Extracellular tyrosyl-tRNA synthetase cleaved by plasma proteinases and stored in platelet α-granules: Potential role in monocyte activation. Res Pract Thromb Haemost 2020; 4:1167-1177. [PMID: 33134783 PMCID: PMC7590329 DOI: 10.1002/rth2.12429] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 08/18/2020] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Tyrosyl-tRNA synthetase (YRS) belongs to the family of enzymes that catalyzes the tRNA aminoacylation reaction for protein synthesis, and it has been recently shown to exert noncanonical functions. Although database results indicate extremely low levels of YRS mRNA in platelets, YRS protein is abundantly present. The source of YRS in platelets, as well as the physiological role of platelet-stored YRS, remains largely unknown. OBJECTIVES To clarify how YRS accumulates in platelets and determine the potential role of platelet-stored YRS. METHODS Recombinant YRS proteins with epitope tags were prepared and tested in vitro for proteolytic cleavage in human plasma. Fluorescent-labeled YRS was examined for uptake by platelets, as demonstrated by western blotting and confocal microscopy analysis. Using RAW-Dual reporter cells, Toll-like receptor and type I interferon activation pathways were analyzed after treatment with YRS. RESULTS Full-length YRS was cleaved by both elastase and matrix metalloproteinases in the plasma. The cleaved, N-terminal YRS fragment corresponds to the endogenous YRS detected in platelet lysate by western blotting. Both full-length and cleaved forms of YRS were taken up by platelets in vitro and stored in the α-granules. The N-terminal YRS fragment generated by proteolytic cleavage had monocyte activation comparable to that of the constitutive-active mutant YRS (YRSY341A) previously reported. CONCLUSION Platelets take up both full-length YRS and the active form of cleaved YRS fragment from the plasma. The cleaved, N-terminal YRS fragment stored in α-granules may have potential to activate monocytes.
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Affiliation(s)
- Eric Won
- Department of Molecular MedicineMERU‐Roon Research Center on Vascular BiologyThe Scripps Research InstituteLa JollaCaliforniaUSA
- Division of Hematology/OncologyDepartment of PediatricsUC San Diego School of MedicineLa JollaCaliforniaUSA
- Hemophilia and Thrombosis Treatment CenterRady Children's HospitalSan DiegoCaliforniaUSA
| | - Yosuke Morodomi
- Department of Molecular MedicineMERU‐Roon Research Center on Vascular BiologyThe Scripps Research InstituteLa JollaCaliforniaUSA
| | - Sachiko Kanaji
- Department of Molecular MedicineMERU‐Roon Research Center on Vascular BiologyThe Scripps Research InstituteLa JollaCaliforniaUSA
- Department of Molecular MedicineThe Scripps Laboratories for tRNA Synthetase ResearchThe Scripps Research InstituteLa JollaCaliforniaUSA
| | - Ryan Shapiro
- Department of Molecular MedicineThe Scripps Laboratories for tRNA Synthetase ResearchThe Scripps Research InstituteLa JollaCaliforniaUSA
| | - My‐Nuong Vo
- Department of Molecular MedicineThe Scripps Laboratories for tRNA Synthetase ResearchThe Scripps Research InstituteLa JollaCaliforniaUSA
| | - Jennifer N. Orje
- Department of Molecular MedicineMERU‐Roon Research Center on Vascular BiologyThe Scripps Research InstituteLa JollaCaliforniaUSA
| | - Courtney D. Thornburg
- Division of Hematology/OncologyDepartment of PediatricsUC San Diego School of MedicineLa JollaCaliforniaUSA
- Hemophilia and Thrombosis Treatment CenterRady Children's HospitalSan DiegoCaliforniaUSA
| | - Xiang‐Lei Yang
- Department of Molecular MedicineThe Scripps Laboratories for tRNA Synthetase ResearchThe Scripps Research InstituteLa JollaCaliforniaUSA
| | - Zaverio M. Ruggeri
- Department of Molecular MedicineMERU‐Roon Research Center on Vascular BiologyThe Scripps Research InstituteLa JollaCaliforniaUSA
| | - Paul Schimmel
- Department of Molecular MedicineThe Scripps Laboratories for tRNA Synthetase ResearchThe Scripps Research InstituteLa JollaCaliforniaUSA
- Department of Molecular MedicineThe Scripps Research InstituteJupiterFloridaUSA
| | - Taisuke Kanaji
- Department of Molecular MedicineMERU‐Roon Research Center on Vascular BiologyThe Scripps Research InstituteLa JollaCaliforniaUSA
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Chaihu-Shugan-San and absorbed meranzin hydrate induce anti-atherosclerosis and behavioral improvements in high-fat diet ApoE-/- mice via anti-inflammatory and BDNF-TrkB pathway. Biomed Pharmacother 2019; 115:108893. [DOI: 10.1016/j.biopha.2019.108893] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 04/15/2019] [Accepted: 04/17/2019] [Indexed: 12/31/2022] Open
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Pro-BDNF Contributes to Hypoxia/Reoxygenation Injury in Myocardial Microvascular Endothelial Cells: Roles of Receptors p75 NTR and Sortilin and Activation of JNK and Caspase 3. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:3091424. [PMID: 30046375 PMCID: PMC6038493 DOI: 10.1155/2018/3091424] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 04/30/2018] [Indexed: 01/02/2023]
Abstract
The aim of this study was to identify the role of the precursor of the brain-derived neurotrophic factor (pro-BDNF) in myocardial hypoxia/reoxygenation injury (H/R) and to address the underlying mechanisms. For this purpose, myocardial microvascular endothelial cells (MMECs) exposed to a high concentration of glucose (30 mM) for 48 h were subjected to 4 h of hypoxia followed by 2 h of reoxygenation. Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining and flow-cytometric analysis were performed to detect apoptosis. Cell scratch and capillary-like-structure formation assays were employed to evaluate cell function. The levels of apoptosis-related proteins were evaluated by Western blotting and immunofluorescence assays. Our results showed that H/R resulted in MMEC injury, as indicated by significant increases in TUNEL-positive cell numbers and a reduction in MMEC migration and in capillary-like-structure formation coupled with increased pro-BDNF protein expression. In addition, overexpression of pro-BDNF in MMECs via a viral vector led to increased pro-BDNF expression, and this upregulation induced apoptosis. Mechanistic experiments revealed that H/R did not influence BDNF, JNK, and caspase 3 expression, but upregulated pro-BDNF, p75NTR, sortilin, phospho-JNK, and cleaved caspase 3 protein levels. In contrast, neutralization of endogenous pro-BDNF with an antibody significantly attenuated H/R-induced upregulation of pro-BDNF, p75NTR, sortilin, p-JNK, and cleaved caspase 3 protein levels, indicating that p75NTR-sortilin signaling and activation of JNK and caspase 3 may be involved in these effects. In conclusion, H/R-induced injury may be mediated by pro-BDNF, at least in part through the regulation of p75NTR-sortilin signaling and activation of JNK and caspase 3.
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Arif A, Jia J, Halawani D, Fox PL. Experimental approaches for investigation of aminoacyl tRNA synthetase phosphorylation. Methods 2016; 113:72-82. [PMID: 27729295 DOI: 10.1016/j.ymeth.2016.10.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Revised: 10/04/2016] [Accepted: 10/06/2016] [Indexed: 02/04/2023] Open
Abstract
Phosphorylation of many aminoacyl tRNA synthetases (AARSs) has been recognized for decades, but the contribution of post-translational modification to their primary role in tRNA charging and decryption of genetic code remains unclear. In contrast, phosphorylation is essential for performance of diverse noncanonical functions of AARSs unrelated to protein synthesis. Phosphorylation of glutamyl-prolyl tRNA synthetase (EPRS) has been investigated extensively in our laboratory for more than a decade, and has served as an archetype for studies of other AARSs. EPRS is a constituent of the IFN-γ-activated inhibitor of translation (GAIT) complex that directs transcript-selective translational control in myeloid cells. Stimulus-dependent phosphorylation of EPRS is essential for its release from the parental multi-aminoacyl tRNA synthetase complex (MSC), for binding to other GAIT complex proteins, and for regulating the binding to target mRNAs. Importantly, phosphorylation is the common driving force for the context- and stimulus-dependent release, and non-canonical activity, of other AARSs residing in the MSC, for example, lysyl tRNA synthetase (KARS). Here, we describe the concepts and experimental methodologies we have used to investigate the influence of phosphorylation on the structure and function of EPRS. We suggest that application of these approaches will help to identify new functional phosphorylation event(s) in other AARSs and elucidate their possible roles in noncanonical activities.
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Affiliation(s)
- Abul Arif
- Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Jie Jia
- Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Dalia Halawani
- Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Paul L Fox
- Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
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Liu Z, Guo F, Wang Y, Li C, Zhang X, Li H, Diao L, Gu J, Wang W, Li D, He F. BATMAN-TCM: a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine. Sci Rep 2016; 6:21146. [PMID: 26879404 PMCID: PMC4754750 DOI: 10.1038/srep21146] [Citation(s) in RCA: 517] [Impact Index Per Article: 57.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Accepted: 01/19/2016] [Indexed: 02/05/2023] Open
Abstract
Traditional Chinese Medicine (TCM), with a history of thousands of years of clinical practice, is gaining more and more attention and application worldwide. And TCM-based new drug development, especially for the treatment of complex diseases is promising. However, owing to the TCM's diverse ingredients and their complex interaction with human body, it is still quite difficult to uncover its molecular mechanism, which greatly hinders the TCM modernization and internationalization. Here we developed the first online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Its main functions include 1) TCM ingredients' target prediction; 2) functional analyses of targets including biological pathway, Gene Ontology functional term and disease enrichment analyses; 3) the visualization of ingredient-target-pathway/disease association network and KEGG biological pathway with highlighted targets; 4) comparison analysis of multiple TCMs. Finally, we applied BATMAN-TCM to Qishen Yiqi dripping Pill (QSYQ) and combined with subsequent experimental validation to reveal the functions of renin-angiotensin system responsible for QSYQ's cardioprotective effects for the first time. BATMAN-TCM will contribute to the understanding of the "multi-component, multi-target and multi-pathway" combinational therapeutic mechanism of TCM, and provide valuable clues for subsequent experimental validation, accelerating the elucidation of TCM's molecular mechanism. BATMAN-TCM is available at http://bionet.ncpsb.org/batman-tcm.
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Affiliation(s)
- Zhongyang Liu
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.,National Center for Protein Sciences Beijing, Beijing 102206, China
| | - Feifei Guo
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China
| | - Yong Wang
- Beijing University of Chinese Medicine, Beijing 100029, China
| | - Chun Li
- Beijing University of Chinese Medicine, Beijing 100029, China
| | - Xinlei Zhang
- Beijing Genestone Technology Ltd., Beijing 100085, China
| | - Honglei Li
- Beijing Genestone Technology Ltd., Beijing 100085, China
| | - Lihong Diao
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.,National Center for Protein Sciences Beijing, Beijing 102206, China
| | - Jiangyong Gu
- Beijing National Laboratory for Molecular Sciences, State Key Lab of Rare Earth Material Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
| | - Wei Wang
- Beijing University of Chinese Medicine, Beijing 100029, China
| | - Dong Li
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.,National Center for Protein Sciences Beijing, Beijing 102206, China
| | - Fuchu He
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.,National Center for Protein Sciences Beijing, Beijing 102206, China
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