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Zhand S, Goss DM, Cheng YY, Warkiani ME. Recent Advances in Microfluidics for Nucleic Acid Analysis of Small Extracellular Vesicles in Cancer. Adv Healthc Mater 2025; 14:e2401295. [PMID: 39707658 DOI: 10.1002/adhm.202401295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 11/28/2024] [Indexed: 12/23/2024]
Abstract
Small extracellular vesicles (sEVs) are membranous vesicles released from cellular structures through plasma membrane budding. These vesicles contain cellular components such as proteins, lipids, mRNAs, microRNAs, long-noncoding RNA, circular RNA, and double-stranded DNA, originating from the cells they are shed from. Ranging in size from ≈25 to 300 nm and play critical roles in facilitating cell-to-cell communication by transporting signaling molecules. The discovery of sEVs in bodily fluids and their involvement in intercellular communication has revolutionized the fields of diagnosis, prognosis, and treatment, particularly in diseases like cancer. Conventional methods for isolating and analyzing sEVs, particularly their nucleic acid content face challenges including high costs, low purity, time-consuming processes, limited standardization, and inconsistent yield. The development of microfluidic devices, enables improved precision in sorting, isolating, and molecular-level separation using small sample volumes, and offers significant potential for the enhanced detection and monitoring of sEVs associated with cancer. These advanced techniques hold great promise for creating next-generation diagnostic and prognostic tools given their possibility of being cost-effective, simple to operate, etc. This comprehensive review explores the current state of research on microfluidic devices for the detection of sEV-derived nucleic acids as biomarkers and their translation into practical point-of-care and clinical applications.
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Affiliation(s)
- Sareh Zhand
- School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW, 2007, Australia
- Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, Sydney, NSW, 2007, Australia
| | - Dale Mark Goss
- School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW, 2007, Australia
| | - Yuen Yee Cheng
- Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, Sydney, NSW, 2007, Australia
| | - Majid Ebrahimi Warkiani
- School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW, 2007, Australia
- Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, Sydney, NSW, 2007, Australia
- Institute of Molecular Theranostics, Sechenov First Moscow State University, Moscow, 119991, Russia
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Zhao S, Kong H, Qi D, Qiao Y, Li Y, Cao Z, Wang H, He X, Liu H, Yang H, Gao S, Liu T, Xie J. Epidermal stem cell derived exosomes-induced dedifferentiation of myofibroblasts inhibits scarring via the miR-203a-3p/PIK3CA axis. J Nanobiotechnology 2025; 23:56. [PMID: 39881312 PMCID: PMC11776291 DOI: 10.1186/s12951-025-03157-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Accepted: 01/22/2025] [Indexed: 01/31/2025] Open
Abstract
Hypertrophic scar (HS) is a common fibroproliferative disorders with no fully effective treatments. The conversion of fibroblasts to myofibroblasts is known to play a critical role in HS formation, making it essential to identify molecules that promote myofibroblast dedifferentiation and to elucidate their underlying mechanisms. In this study, we used comparative transcriptomics and single-cell sequencing to identify key molecules and pathways that mediate fibrosis and myofibroblast transdifferentiation. Epidermal stem cell-derived extracellular vesicles (EpiSC-EVs) were isolated via ultracentrifugation and filtration, followed by miRNA sequencing to identify miRNAs targeting key molecules. After in vitro and in vivo treatment with EpiSC-EVs, we assessed antifibrotic effects through scratch assays, collagen contraction assays, Western blotting, and immunofluorescence. Transcriptomic sequencing and rescue experiments were used to investigate the molecular mechanism by which miR-203a-3p in EpiSC-EVs induces myofibroblast dedifferentiation. Our results indicate that PIK3CA is overexpressed in HS tissues and positively correlates with fibrosis. EpiSC-EVs were absorbed by scar-derived fibroblasts, promoting dedifferentiation from myofibroblasts to quiescent fibroblasts. Mechanistically, miR-203a-3p in EpiSC-EVs plays an essential role in inhibiting PIK3CA expression and PI3K/AKT/mTOR pathway hyperactivation, thereby reducing scar formation. In vivo studies confirmed that EpiSC-EVs attenuate excessive scarring through the miR-203a-3p/PIK3CA axis, suggesting EpiSC-EVs as a promising therapeutic approach for HS.
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Affiliation(s)
- Shixin Zhao
- Department of Traumatic Orthopedics, Henan Provincial People's Hospital & The People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, China
- Henan Orthopedics Research Institute, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, China
- Department of Burns, Wound Repair and Reconstruction, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China
| | - Haoran Kong
- Department of Traumatic Orthopedics, Henan Provincial People's Hospital & The People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, China
- Henan Orthopedics Research Institute, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, China
| | - Dahu Qi
- Department of Traumatic Orthopedics, Henan Provincial People's Hospital & The People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, China
- Henan Orthopedics Research Institute, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, China
| | - Yushuang Qiao
- Department of Traumatic Orthopedics, Henan Provincial People's Hospital & The People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, China
- Henan Orthopedics Research Institute, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, China
| | - Yu Li
- Department of Traumatic Orthopedics, Henan Provincial People's Hospital & The People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, China
- Henan Orthopedics Research Institute, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, China
| | - Zhiming Cao
- Department of Traumatic Orthopedics, Henan Provincial People's Hospital & The People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, China
- Henan Orthopedics Research Institute, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, China
| | - Hanwen Wang
- Department of Burns, Wound Repair and Reconstruction, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China
| | - Xuefeng He
- Department of Burns, Wound Repair and Reconstruction, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China
| | - Hengdeng Liu
- Department of Burns, Wound Repair and Reconstruction, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China
| | - Hao Yang
- Department of Burns, Wound Repair and Reconstruction, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China
| | - Suyue Gao
- Department of Burns, Wound Repair and Reconstruction, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China
| | - Tao Liu
- Department of Traumatic Orthopedics, Henan Provincial People's Hospital & The People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, China.
- Henan Orthopedics Research Institute, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, China.
| | - Julin Xie
- Department of Burns, Wound Repair and Reconstruction, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
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Mohseni A, Salehi F, Rostami S, Hadiloo K, Hashemi M, Baridjavadi Z, Ahangari F, Karami N, Samani F, Tahmasebi S, Farahani N, Taheriazam A. Harnessing the power of exosomes for diagnosis, prognosis, and treatment of hematological malignancies. Stem Cell Res Ther 2025; 16:6. [PMID: 39773361 PMCID: PMC11708188 DOI: 10.1186/s13287-024-04125-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Accepted: 12/21/2024] [Indexed: 01/11/2025] Open
Abstract
Exosomes are small extracellular vesicles of endocytic origin released by various cell types. They consist of lipid bilayers containing macromolecules such as lipids, proteins, microRNAs, growth factors, cytokines, and carbohydrates. Exosomes play a critical role in the diagnosis and treatment of various diseases. For instance, exosome contents have been utilized as biomarkers in body fluids (urine, saliva, serum) to identify cancers, autoimmune diseases, and inflammatory conditions such as sepsis. Due to their small size and ability to reach tumor microenvironments, exosomes are also used as carriers for chemotherapeutic drugs in drug delivery systems. Furthermore, evidence indicates that malignant cells release exosomes into the tumor microenvironment, influencing immune cells in a paracrine manner. Additionally, immune cell-derived exosomes, such as those from Natural Killer (NK) cells or cytotoxic T lymphocytes (CTLs), show potential as therapeutic agents in treating malignancies like leukemia. This review discusses the diagnostic role of exosomes in various hematological malignancies and explores the therapeutic potential of immune cell-derived exosomes in these diseases.
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Affiliation(s)
- Amirata Mohseni
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Fatemeh Salehi
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Samaneh Rostami
- School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Kaveh Hadiloo
- School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Zahra Baridjavadi
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fatemeh Ahangari
- Department of Immunology, Pasteur Institue of Iran, Tehran, Iran
| | - Najibeh Karami
- Hematology-Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Samani
- Blood Transfusion Research Center, High Institute for Research and Education in transfusion medicine, Iranian Blood Transfusion Organization (IBTO), Tehran, Iran
| | - Safa Tahmasebi
- Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Najma Farahani
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Afshin Taheriazam
- Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
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Kepsha MA, Timofeeva AV, Chernyshev VS, Silachev DN, Mezhevitinova EA, Sukhikh GT. MicroRNA-Based Liquid Biopsy for Cervical Cancer Diagnostics and Treatment Monitoring. Int J Mol Sci 2024; 25:13271. [PMID: 39769036 PMCID: PMC11678179 DOI: 10.3390/ijms252413271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/03/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025] Open
Abstract
Despite prevention strategies, cervical cancer remains a significant public health issue. Human papillomavirus plays a critical role in its development, and early detection is vital to improve patient outcomes. The incidence of cervical cancer is projected to rise, necessitating better diagnostic tools. Traditional screening methods like the cytological examination and human papillomavirus testing have limitations in sensitivity and reproducibility. Liquid-based cytology offers some improvements, but the need for more reliable and sensitive techniques persists, particularly for detecting precancerous lesions. Liquid biopsy is a non-invasive method that analyzes cancer-derived products in biofluids like blood, offering potential for real-time monitoring of tumor progression, metastasis, and treatment response. It can be based on detection of circulating tumor cells (CTCs), circulating free DNA (cfDNA), and microRNAs (miRNAs). This review particularly underlines the potential of microRNAs, which are transported by extracellular vesicles. Overall, this article underscores the importance of continued research into non-invasive diagnostic methods like liquid biopsy to enhance cervical cancer screening and treatment monitoring.
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Affiliation(s)
| | | | - Vasiliy S. Chernyshev
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov, Ministry of Healthcare of the Russian Federation, Moscow 117997, Russia (D.N.S.)
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Liu X, Chen R, Cui G, Feng R, Liu K. Exosomes derived from platelet-rich plasma present a novel potential in repairing knee articular cartilage defect combined with cyclic peptide-modified β-TCP scaffold. J Orthop Surg Res 2024; 19:718. [PMID: 39497084 PMCID: PMC11533314 DOI: 10.1186/s13018-024-05202-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Accepted: 10/23/2024] [Indexed: 11/06/2024] Open
Abstract
BACKGROUND The aim of this study was to investigate the therapeutic effects and mechanisms of PRP-exos combined with cyclic peptide-modified β-TCP scaffold in the treatment of rabbit knee cartilage defect. METHODS PRP-exos were extracted and characterized by TEM, NTA and WB. The therapeutic effects were evaluated by ICRS score, HE staining, Immunohistochemistry, qRT-PCR and ELISA. The repair mechanism of PRP-exos was estimated and predicted by miRNA sequencing analysis and protein-protein interaction network analysis. RESULTS The results showed that PRP-exos had a reasonable size distribution and exhibited typical exosome morphology. The combination of PRP-exos and cyclic peptide-modified β-TCP scaffold improved ICRS score and the expression level of COL-2, RUNX2, and SOX9. Moreover, this combination therapy reduced the level of MMP-3, TNF-α, IL-1β, and IL-6, while increasing the level of TIMP-1. In PRP-exos miRNA sequencing analysis, the total number of known miRNAs aligned across all samples was 252, and a total of 91 differentially expressed miRNAs were detected. The results of KEGG enrichment analysis and the protein-protein interaction network analysis indicated that the PI3K/AKT signaling pathway could impact the function of chondrocytes by regulating key transcription factors to repair cartilage defect. CONCLUSION PRP-exos combined with cyclic peptide-modified β-TCP scaffold effectively promoted cartilage repair and improved chondrocyte function in rabbit knee cartilage defect. Based on the analysis and prediction of PRP-exos miRNAs sequencing, PI3K/AKT signaling pathway may contribute to the therapeutic effect. These findings provide experimental evidence for the application of PRP-exos in the treatment of cartilage defect.
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Affiliation(s)
- Xuchang Liu
- Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, 250021, Shandong, China
- Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Jinan, 250103, Shandong, China
- Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan, 250103, Shandong, China
| | - Rudong Chen
- Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, 250021, Shandong, China
| | - Guanzheng Cui
- Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, 250021, Shandong, China
| | - Rongjie Feng
- Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, 250021, Shandong, China.
| | - Kechun Liu
- Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Jinan, 250103, Shandong, China.
- Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan, 250103, Shandong, China.
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Salehpour A, Karimi Z, Ghasemi Zadeh M, Afshar M, Kameli A, Mooseli F, Zare M, Afshar A. Therapeutic potential of mesenchymal stem cell-derived exosomes and miRNAs in neuronal regeneration and rejuvenation in neurological disorders: a mini review. Front Cell Neurosci 2024; 18:1427525. [PMID: 39429946 PMCID: PMC11486650 DOI: 10.3389/fncel.2024.1427525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 09/24/2024] [Indexed: 10/22/2024] Open
Abstract
Mesenchymal stem cells (MSCs) have gained considerable attention in the field of regenerative medicine due to their ability to secrete small extracellular vesicles (EVs) known as exosomes. This review delves into the various biological activities of MSCs and the cell interactions enabled by these exosomes, with a focus on their potential for neuronal regeneration and the treatment of neurological disorders. We scrutinize findings from multiple studies that underscore the neuroprotective and neuro-regenerative effects of exosomes derived from MSCs, illuminating their mechanisms of action and therapeutic applications. This review thoroughly investigates all related pathways, miRNAs, and factors to suggest potential strategies for enhancing therapy for neurological disorders using exosomes and miRNAs, and for boosting neuronal regeneration.
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Affiliation(s)
- Aria Salehpour
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Zahra Karimi
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Mokhtar Ghasemi Zadeh
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
- Student Research Committee, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Mohammadreza Afshar
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
- Student Research Committee, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Ali Kameli
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Fatemeh Mooseli
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
- Student Research Committee, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Masoud Zare
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Alireza Afshar
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
- Student Research Committee, Bushehr University of Medical Sciences, Bushehr, Iran
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Guo J, Zhong L, Momeni MR. MicroRNA-155 and its exosomal form: Small pieces in the gastrointestinal cancers puzzle. Cell Biol Toxicol 2024; 40:77. [PMID: 39283408 PMCID: PMC11405467 DOI: 10.1007/s10565-024-09920-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 09/04/2024] [Indexed: 09/22/2024]
Abstract
Gastrointestinal (GI) cancers are common cancers that are responsible for a large portion of global cancer fatalities. Due to this, there is a pressing need for innovative strategies to identify and treat GI cancers. MicroRNAs (miRNAs) are short ncRNAs that can be considered either cancer-causing or tumor-inhibiting molecules. MicroRNA-155, also known as miR-155, is a vital regulator in various cancer types. This miRNA has a carcinogenic role in a variety of gastrointestinal cancers, including pancreatic, colon, and gastric cancers. Since the abnormal production of miR-155 has been detected in various malignancies and has a correlation with increased mortality, it is a promising target for future therapeutic approaches. Moreover, exosomal miR-155 associated with tumors have significant functions in communicating between cells and establishing the microenvironment for cancer in GI cancers. Various types of genetic material, such as specifically miR-155 as well as proteins found in cancer-related exosomes, have the ability to be transmitted to other cells and have a function in the advancement of tumor. Therefore, it is critical to conduct a review that outlines the diverse functions of miR-155 in gastrointestinal malignancies. As a result, we present a current overview of the role of miR-155 in gastrointestinal cancers. Our research highlighted the role of miR-155 in GI cancers and covered critical issues in GI cancer such as pharmacologic inhibitors of miRNA-155, miRNA-155-assosiated circular RNAs, immune-related cells contain miRNA-155. Importantly, we discussed miRNA-155 in GI cancer resistance to chemotherapy, diagnosis and clinical trials. Furthermore, the function of miR-155 enclosed in exosomes that are released by cancer cells or tumor-associated macrophages is also covered.
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Affiliation(s)
- Jinbao Guo
- Department of Thoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
| | - Li Zhong
- Department of Gynecology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
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Zhao Y, Xia Q, Zhu L, Xia J, Xiang S, Mao Q, Dong H, Weng Z, Liao W, Xin Z. Mapping knowledge structure and themes trends of non-surgical treatment in intervertebral disc degeneration. Heliyon 2024; 10:e36509. [PMID: 39286189 PMCID: PMC11402762 DOI: 10.1016/j.heliyon.2024.e36509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 03/23/2024] [Accepted: 08/16/2024] [Indexed: 09/19/2024] Open
Abstract
Background Intervertebral disc degeneration (IDD) is a chronic disabling disease caused by degeneration of nucleus pulposus cells, decreased activity and the number of nucleus pulposus cells, decreased extracellular matrix, and infiltration of inflammatory factors, resulting in low back and leg pain. Recent studies have shown that non-surgical treatment is of great significance in reversing the progression of degenerative disc disease, and there are more relevant literature reports. However, there is no bibliometric analysis in this area. This study aimed to describe the knowledge structure and thematic trends of non-surgical treatment methods for IDD through bibliometrics. Methods Articles and reviews on non-surgical treatment of disc degeneration from 1998 to 2022 were collected on the Web of Science. VOSviewer 1.6.18, CiteSpace 6.1.R3, R package "bibliometrix" and two online analysis platforms were used for bibliometric and visual literature analysis. Results 961 articles were screened for inclusion, including 821 articles and 140 reviews. The analysis of our study shows that publications in the non-surgical treatment of disc degeneration are increasing annually, with publications coming mainly from North America and Asia, with China and the United States dominating. Huazhong Univ Sci & Technol and Wang K are the most prolific institutions and authors, respectively, and Le Maitre CL is the most co-cited author. However, there is less collaboration between institutions in different countries. Spine is both the most published and the most cited journal. According to the co-citation and co-occurrence analysis results, "mesenchymal stem cells," "exosomes," "medication," and "tissue engineering" are the current research hotspots in this field. Conclusions This study employs bibliometric analysis to explore the knowledge structure and trends of non-surgical treatments for IDD from 2013 to 2022. Key research hotspots include mesenchymal stem cells, exosomes, medication, and tissue engineering. The number of publications, especially from China and the USA, has increased significantly, though international collaboration needs improvement. Influential contributors include Wang K and the journal Spine. These findings provide a comprehensive overview and highlight important future directions for the field.
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Affiliation(s)
- Yan Zhao
- Department of Orthopedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Qiuqiu Xia
- Department of Orthopedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Lu Zhu
- Department of Orthopedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Jiyue Xia
- Department of Orthopedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Shaojie Xiang
- Department of Orthopedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Qiming Mao
- Department of Orthopedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Huaize Dong
- Department of Orthopedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Zijing Weng
- Department of Orthopedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Wenbo Liao
- Department of Orthopedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Zhijun Xin
- Department of Orthopedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China
- Institut Curie, PSL Research University, CNRS UMR3244, Dynamics of Genetic Information, Sorbonne Université, 75005, Paris, France
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Li Q, Liu Y, Li B, Zheng C, Yu B, Niu K, Qiao Y. Bioinformatics analysis of oxidative stress genes in the pathogenesis of ulcerative colitis based on a competing endogenous RNA regulatory network. PeerJ 2024; 12:e17213. [PMID: 39161963 PMCID: PMC11332386 DOI: 10.7717/peerj.17213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 03/19/2024] [Indexed: 08/21/2024] Open
Abstract
Background Ulcerative colitis (UC) is a common chronic disease associated with inflammation and oxidative stress. This study aimed to construct a long noncoding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) network based on bioinformatics analysis and to explore oxidative stress-related genes underlying the pathogenesis of UC. Methods The GSE75214, GSE48959, and GSE114603 datasets were downloaded from the Gene Expression Omnibus database. Following differentially expressed (DE) analysis, the regulatory relationships among these DERNAs were identified through miRDB, miRTarBase, and TargetScan; then, the lncRNA-miRNA-mRNA network was established. The Molecular Signatures Database (MSigDB) was used to search oxidative stress-related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for functional annotation and enrichment analyses. Based on the drug gene interaction database DGIdb, drugs that interact with oxidative stress-associated genes were explored. A dextran sulfate sodium (DSS)-induced UC mouse model was used for experimental validation. Results A total of 30 DE-lncRNAs, 3 DE-miRNAs, and 19 DE-mRNAs were used to construct a lncRNA-miRNA-mRNA network. By comparing these 19 DE-mRNAs with oxidative stress-related genes in MSigDB, three oxidative stress-related genes (CAV1, SLC7A11, and SLC7A5) were found in the 19 DEM sets, which were all negatively associated with miR-194. GO and KEGG analyses showed that CAV1, SLC7A11, and SLC7A5 were associated with immune inflammation and steroid hormone synthesis. In animal experiments, the results showed that dexamethasone, a well-known glucocorticoid drug, could significantly decrease the expression of CAV1, SLC7A11, and SLC7A5 as well as improve UC histology, restore antioxidant activities, inhibit inflammation, and decrease myeloperoxidase activity. Conclusion SLC7A5 was identified as a representative gene associated with glucocorticoid therapy resistance and thus may be a new therapeutic target for the treatment of UC in the clinic.
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MESH Headings
- Animals
- Humans
- Mice
- Colitis, Ulcerative/genetics
- Colitis, Ulcerative/metabolism
- Colitis, Ulcerative/chemically induced
- Computational Biology
- Databases, Genetic
- Dextran Sulfate/toxicity
- Disease Models, Animal
- Gene Expression Profiling
- Gene Regulatory Networks/drug effects
- MicroRNAs/genetics
- MicroRNAs/metabolism
- Oxidative Stress/genetics
- Oxidative Stress/drug effects
- RNA, Competitive Endogenous/genetics
- RNA, Competitive Endogenous/metabolism
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/metabolism
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
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Affiliation(s)
- Qifang Li
- Department of Traditional Chinese Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Yuan Liu
- College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, Shandong, China
| | - Bingbing Li
- College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, Shandong, China
| | - Canlei Zheng
- College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, Shandong, China
| | - Bin Yu
- College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, Shandong, China
| | - Kai Niu
- College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, Shandong, China
| | - Yi Qiao
- School of Public Health, Jining Medical University, Jining, Shandong, China
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10
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Jiang F, Hong J, Jiang J, Li L, Zheng X, Zhao K, Wu X. The Effect of Human Umbilical Cord Mesenchymal Stem Cell on Premature Ovarian Cell Senilism Through miR-10a. Int J Womens Health 2024; 16:1023-1032. [PMID: 38835833 PMCID: PMC11149645 DOI: 10.2147/ijwh.s453125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 05/11/2024] [Indexed: 06/06/2024] Open
Abstract
Objective To investigate the potential protective impact of miR-10a-modified HUMSCs-derived exosomes on both premature ovarian failure and the functionality of ovarian granulosa cells in a POF model. Methods KGN cells were co-cultured with cisplatin-diaminedichloroplatinum (II) (10 μM) for 24 h to establish an in vitro POF model. The cells were distributed into three distinct groups: the control group, the POF group, and the POF + HUCMSC group. The plasmid sh-NC, sh-miR-10 a and miR-10 a mimic were transfected into KGN cells. After co-cultured with HUCMSC-EVs for 48 h, they were divided into HUCMSC group, sh-miR-10 a-HUMSCs-exosomes group and miR-10 a-HUMSCs-exosomes group. Flow cytometry was adopted to assess the impact of HUMSCs surface immune antigens and miR-10a-HUCMSCs-exosomes on KGN cell apoptosis. Additionally, the evaluation of cell proliferation was carried out through CCK-8 and EDU assays. Western blot analysis was utilized to detect the Caspase-3, Bax, and Bcl-2 proteins levels. Furthermore, the levels of TNF-α, IL-6, IL-10, MDA, SOD, and CAT were quantified using ELISA. Results Compared with the Control group, the POF group inhibited the growth of ovarian granulosa cells (P<0.01), reduced the number of EDU cells (P<0.01), and increased the protein expression of Caspase-3 (P<0.05) and Bax (P<0.01). HUMSCs treatment significantly down-regulated the expression of IL-6, TNF-α and MDA, while up-regulating the expression of IL-10, SOD and CAT (P<0.01); the overexpression of miR-10a promoted cell growth, besides, the introduction of miR-10a-HUMSCs-derived exosomes led to an elevation in the proliferation rate of OGCs affected by POF and concurrently suppressed the apoptosis rate. Conclusion HUMSCs-derived exosomes modified by miR-10a have protective effects on premature ovarian failure and ovarian granulosa cell function in POF model.
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Affiliation(s)
- Fan Jiang
- Reproductive Medicine Center, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, People's Republic of China
| | - Jingzhen Hong
- Reproductive Medicine Center, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, People's Republic of China
| | - Juanjuan Jiang
- Reproductive Medicine Center, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, People's Republic of China
| | - Ling Li
- Reproductive Medicine Center, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, People's Republic of China
| | - Xianrui Zheng
- Reproductive Medicine Center, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, People's Republic of China
| | - Kun Zhao
- Fujian Heze Biotechnology Company Limited, Fuzhou, 350000, People's Republic of China
| | - Xuebin Wu
- Reproductive Medicine Center, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, People's Republic of China
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11
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Chen S, Pan J, Gong Z, Wu M, Zhang X, Chen H, Yang D, Qi S, Peng Y, Shen J. Hypochlorous acid derived from microglial myeloperoxidase could mediate high-mobility group box 1 release from neurons to amplify brain damage in cerebral ischemia-reperfusion injury. J Neuroinflammation 2024; 21:70. [PMID: 38515139 PMCID: PMC10958922 DOI: 10.1186/s12974-023-02991-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 12/11/2023] [Indexed: 03/23/2024] Open
Abstract
Myeloperoxidase (MPO) plays critical role in the pathology of cerebral ischemia-reperfusion (I/R) injury via producing hypochlorous acid (HOCl) and inducing oxidative modification of proteins. High-mobility group box 1 (HMGB1) oxidation, particularly disulfide HMGB1 formation, facilitates the secretion and release of HMGB1 and activates neuroinflammation, aggravating cerebral I/R injury. However, the cellular sources of MPO/HOCl in ischemic brain injury are unclear yet. Whether HOCl could promote HMGB1 secretion and release remains unknown. In the present study, we investigated the roles of microglia-derived MPO/HOCl in mediating HMGB1 translocation and secretion, and aggravating the brain damage and blood-brain barrier (BBB) disruption in cerebral I/R injury. In vitro, under the co-culture conditions with microglia BV cells but not the single culture conditions, oxygen-glucose deprivation/reoxygenation (OGD/R) significantly increased MPO/HOCl expression in PC12 cells. After the cells were exposed to OGD/R, MPO-containing exosomes derived from BV2 cells were released and transferred to PC12 cells, increasing MPO/HOCl in the PC12 cells. The HOCl promoted disulfide HMGB1 translocation and secretion and aggravated OGD/R-induced apoptosis. In vivo, SD rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus different periods of reperfusion. Increased MPO/HOCl production was observed at the reperfusion stage, accomplished with enlarged infarct volume, aggravated BBB disruption and neurological dysfunctions. Treatment of MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) and HOCl scavenger taurine reversed those changes. HOCl was colocalized with cytoplasm transferred HMGB1, which was blocked by taurine in rat I/R-injured brain. We finally performed a clinical investigation and found that plasma HOCl concentration was positively correlated with infarct volume and neurological deficit scores in ischemic stroke patients. Taken together, we conclude that ischemia/hypoxia could activate microglia to release MPO-containing exosomes that transfer MPO to adjacent cells for HOCl production; Subsequently, the production of HOCl could mediate the translocation and secretion of disulfide HMGB1 that aggravates cerebral I/R injury. Furthermore, plasma HOCl level could be a novel biomarker for indexing brain damage in ischemic stroke patients.
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Affiliation(s)
- Shuang Chen
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Jingrui Pan
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Zhe Gong
- Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Meiling Wu
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Xiaoni Zhang
- Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Hansen Chen
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Dan Yang
- Department of Chemistry, University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Suhua Qi
- Medical and Technology School, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, China.
| | - Ying Peng
- Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
| | - Jiangang Shen
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, China.
- Medical and Technology School, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, China.
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12
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Shi H, Hao X, Sun Y, Zhao Y, Wang Y, Cao X, Gong Z, Ji S, Lu J, Yan Y, Yu X, Luo X, Wang J, Wang H. Exercise-inducible circulating extracellular vesicle irisin promotes browning and the thermogenic program in white adipose tissue. Acta Physiol (Oxf) 2024; 240:e14103. [PMID: 38288566 DOI: 10.1111/apha.14103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 01/06/2024] [Accepted: 01/11/2024] [Indexed: 02/24/2024]
Abstract
AIM Exercise can reduce body weight and promote white fat browning, but the underlying mechanisms remain largely unknown. This study investigated the role of fibronectin type III domain-containing protein 5 (FNDC5)/Irisin, a hormone released from exercising muscle, in the browning of white fat in circulating extracellular vesicles (EVs). METHODS Mice were subjected to a 4 weeks of running table exercise, and fat browning was analyzed via histology, protein blotting and qPCR. Circulating EVs were extracted by ultrahigh-speed centrifugation, and ELISA was used to measure the irisin concentration in the circulating EVs. Circulating EVs that differentially expressed irisin were applied to adipocytes, and the effect of EV-irisin on adipocyte energy metabolism was analyzed by immunofluorescence, protein blotting, and cellular oxygen consumption rate analysis. RESULTS During sustained exercise, the mice lost weight and developed fat browning. FNDC5 was induced, cleaved, and secreted into irisin, and irisin levels subsequently increased in the plasma during exercise. Interestingly, irisin was highly expressed in circulating EVs that effectively promoted adipose browning. Mechanistically, the circulating EV-irisin complex is transported intracellularly by the adipocyte membrane receptor integrin αV, which in turn activates the AMPK signaling pathway, which is dependent on mitochondrial uncoupling protein 1 to cause mitochondrial plasmonic leakage and promote heat production. After inhibition of the AMPK signaling pathway, the effects of the EV-irisin on promoting fat browning were minimal. CONCLUSION Exercise leads to the accumulation of circulating EV-irisin, which enhances adipose energy metabolism and thermogenesis and promotes white fat browning in mice, leading to weight loss.
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Affiliation(s)
- Hongwei Shi
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, P.R. China
| | - Xiaojing Hao
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, P.R. China
| | - Yaqin Sun
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, P.R. China
| | - Yating Zhao
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, P.R. China
| | - Yue Wang
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, P.R. China
| | - Xiaorui Cao
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, P.R. China
| | - Zeen Gong
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, P.R. China
| | - Shusen Ji
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, P.R. China
| | - Jiayin Lu
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, P.R. China
| | - Yi Yan
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, P.R. China
| | - Xiuju Yu
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, P.R. China
| | - Xiaomao Luo
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, P.R. China
| | - Juan Wang
- Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China
| | - Haidong Wang
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, P.R. China
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13
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Shahcheraghi SH, Asl ER, Lotfi M, Ayatollahi J, Khaleghinejad SH, Aljabali AAA, Bakshi HA, El-Tanani M, Charbe NB, Serrano-Aroca Á, Mishra V, Mishra Y, Goyal R, Hromić-Jahjefendić A, Uversky VN, Lotfi M, Tambuwala MM. Non-coding RNAs as Key Regulators of the Notch Signaling Pathway in Glioblastoma: Diagnostic, Prognostic, and Therapeutic Targets. CNS & NEUROLOGICAL DISORDERS DRUG TARGETS 2024; 23:1203-1216. [PMID: 38279763 DOI: 10.2174/0118715273277458231213063147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 10/20/2023] [Accepted: 10/31/2023] [Indexed: 01/28/2024]
Abstract
Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.
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Affiliation(s)
- Seyed Hossein Shahcheraghi
- Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Infectious Diseases Research Center, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Elmira Roshani Asl
- Social Determinants of Health Research Center, Saveh University of Medical Sciences, Saveh, Iran
| | - Malihe Lotfi
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Jamshid Ayatollahi
- Infectious Diseases Research Center, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Hematology and Oncology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | | | - Alaa A A Aljabali
- Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University, Irbid, Jordan
| | - Hamid A Bakshi
- The Hormel Institute, University of Minnesota, Austin, MN 55912, USA
| | - Mohamed El-Tanani
- Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates
| | - Nitin B Charbe
- Center for Pharmacometrics & Systems Pharmacology, Department of Pharmaceutics (Lake Nona), University of Florida, Orlando, FL, USA
| | - Ángel Serrano-Aroca
- Biomaterials & Bioengineering Lab, Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia, San Vicente Mártir, Valencia, 46001, Spain
| | - Vijay Mishra
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Yachana Mishra
- Department of Zoology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, 144411, India
| | - Rohit Goyal
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology & Management Sciences, Solan, India
| | - Altijana Hromić-Jahjefendić
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnicka cesta 15, 71000 Sarajevo, Bosnia and Herzegovina
| | - Vladimir N Uversky
- Department of Molecular Medicine and USF Health Byrd Alzheimer's Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
| | - Marzieh Lotfi
- Abortion Research Center, Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Murtaza M Tambuwala
- Lincoln Medical School, University of Lincoln, Brayford Pool Campus, Lincoln LN6 7TS, UK
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14
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Soltani-Fard E, Asadi M, Taghvimi S, Vafadar A, Vosough P, Tajbakhsh A, Savardashtaki A. Exosomal microRNAs and long noncoding RNAs: as novel biomarkers for endometriosis. Cell Tissue Res 2023; 394:55-74. [PMID: 37480408 DOI: 10.1007/s00441-023-03802-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 06/23/2023] [Indexed: 07/24/2023]
Abstract
Endometriosis is a gynecological inflammatory disorder characterized by the development of endometrial-like cells outside the uterine cavity. This disease is associated with a wide range of clinical presentations, such as debilitating pelvic pain and infertility issues. Endometriosis diagnosis is not easily discovered by ultrasound or clinical examination. Indeed, difficulties in noninvasive endometriosis diagnosis delay the confirmation and management of the disorder, increase symptoms, and place a significant medical and financial burden on patients. So, identifying specific and sensitive biomarkers for this disease should therefore be a top goal. Exosomes are extracellular vesicles secreted by most cell types. They transport between cells' bioactive molecules such as noncoding RNAs and proteins. MicroRNAs and long noncoding RNAs which are key molecules transferred by exosomes have recently been identified to have a significant role in endometriosis by modulating different proteins and their related genes. As a result, the current review focuses on exosomal micro-and-long noncoding RNAs that are involved in endometriosis disease. Furthermore, major molecular mechanisms linking corresponding RNA molecules to endometriosis development will be briefly discussed to better clarify the potential functions of exosomal noncoding RNAs in the therapy and diagnosis of endometriosis.
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Affiliation(s)
- Elahe Soltani-Fard
- Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Marzieh Asadi
- Department of Medical Biotechnology, School of Advanced Medical Sciences and, Technologies, Shiraz University of, Medical Sciences, Shiraz, 71362 81407, Iran
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sina Taghvimi
- Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Asma Vafadar
- Department of Medical Biotechnology, School of Advanced Medical Sciences and, Technologies, Shiraz University of, Medical Sciences, Shiraz, 71362 81407, Iran
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Parisa Vosough
- Department of Medical Biotechnology, School of Advanced Medical Sciences and, Technologies, Shiraz University of, Medical Sciences, Shiraz, 71362 81407, Iran
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Tajbakhsh
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Savardashtaki
- Department of Medical Biotechnology, School of Advanced Medical Sciences and, Technologies, Shiraz University of, Medical Sciences, Shiraz, 71362 81407, Iran.
- Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
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15
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Liu Y, Lyu X, Tan S, Zhang X. Research Progress of Exosomal Non-Coding RNAs in Cardiac Remodeling. Int J Med Sci 2023; 20:1469-1478. [PMID: 37790853 PMCID: PMC10542190 DOI: 10.7150/ijms.83808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 08/18/2023] [Indexed: 10/05/2023] Open
Abstract
Exosomes are vesicles with a size range of 50 to 200 nm and released by different cells, which are essential for the exchange of information between cells. They have attracted a lot of interest from medical researchers. Exosomal non-coding RNAs play an important part in pathological cardiac remodelings, such as cardiomyocyte hypertrophy, cardiomyocyte apoptosis, and cardiac fibrosis. This review summarizes the origins and functions of exosomes, the role of exosomal non-coding RNAs in the process of pathological cardiac remodeling, as well as their theoretical basis for clinical application.
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Affiliation(s)
- Yang Liu
- Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
| | - Xing Lyu
- Department of Clinical laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
| | - Shengyu Tan
- Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Hunan Clinical Medical Research Center for Geriatric Syndrome, Changsha, Hunan 410011, China
| | - Xiangyu Zhang
- Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Hunan Clinical Medical Research Center for Geriatric Syndrome, Changsha, Hunan 410011, China
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16
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Wang Z, Tan W, Li B, Zou J, Li Y, Xiao Y, He Y, Yoshida S, Zhou Y. Exosomal non-coding RNAs in angiogenesis: Functions, mechanisms and potential clinical applications. Heliyon 2023; 9:e18626. [PMID: 37560684 PMCID: PMC10407155 DOI: 10.1016/j.heliyon.2023.e18626] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 07/14/2023] [Accepted: 07/21/2023] [Indexed: 08/11/2023] Open
Abstract
Exosomes are extracellular vesicles that can be produced by most cells. Exosomes act as important intermediaries in intercellular communication, and participate in a variety of biological activities between cells. Non-coding RNAs (ncRNAs) usually refer to RNAs that do not encode proteins. Although ncRNAs have no protein-coding capacity, they are able to regulate gene expression at multiple levels. Angiogenesis is the formation of new blood vessels from pre-existing vessels, which is an important physiological process. However, abnormal angiogenesis could induce many diseases such as atherosclerosis, diabetic retinopathy and cancer. Many studies have shown that ncRNAs can stably exist in exosomes and play a wide range of physiological and pathological roles including regulation of angiogenesis. In brief, some specific ncRNAs can be enriched in exosomes secreted by cells and absorbed by recipient cells through the exosome pathway, thus activating relevant signaling pathways in target cells and playing a role in regulating angiogenesis. In this review, we describe the physiological and pathological functions of exosomal ncRNAs in angiogenesis, summarize their role in angiogenesis-related diseases, and illustrate potential clinical applications like novel drug therapy strategies and diagnostic markers in exosome research as inspiration for future investigations.
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Affiliation(s)
- Zicong Wang
- Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- Hunan Clinical Research Center of Ophthalmic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
| | - Wei Tan
- Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- Hunan Clinical Research Center of Ophthalmic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
| | - Bingyan Li
- Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- Hunan Clinical Research Center of Ophthalmic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
| | - Jingling Zou
- Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- Hunan Clinical Research Center of Ophthalmic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
| | - Yun Li
- Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- Hunan Clinical Research Center of Ophthalmic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
| | - Yangyan Xiao
- Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- Hunan Clinical Research Center of Ophthalmic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
| | - Yan He
- Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- Hunan Clinical Research Center of Ophthalmic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
| | - Shigeo Yoshida
- Department of Ophthalmology, Kurume University School of Medicine, Fukuoka, 830-0011, Japan
| | - Yedi Zhou
- Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- Hunan Clinical Research Center of Ophthalmic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
- National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China
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Li J, Peng S, Zou X, Geng X, Wang T, Zhu W, Xia T. Value of negatively correlated miR-205-5p/ HMGB3 and miR-96-5p/ FOXO1 on the diagnosis of breast cancer and benign breast diseases. CANCER PATHOGENESIS AND THERAPY 2023; 1:159-167. [PMID: 38327836 PMCID: PMC10846318 DOI: 10.1016/j.cpt.2023.04.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 04/01/2023] [Accepted: 04/20/2023] [Indexed: 02/09/2024]
Abstract
Background MicroRNA (miRNA) and mRNA levels in matching specimens were used to identify miRNA-mRNA interactions. We aimed to integrate transcriptome, immunophenotype, methylation, mutation, and survival data analyses to examine the profiles of miRNAs and target mRNAs and their associations with breast cancer (BC) diagnosis. Methods Based on the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA), differentially expressed miRNAs and targeted mRNAs were screened from experimentally verified miRNA-target interaction databases using Pearson's correlation analysis. We used real-time quantitative reverse transcription polymerase chain reaction to verify BC and benign disease samples, and logistic regression analysis was used to establish a diagnostic model based on miRNAs and target mRNAs. Receiver operating characteristic curve analysis was performed to test the ability to recognize the miRNA-mRNA pairs. Next, we investigated the complex interactions between miRNA-mRNA regulatory pairs and phenotypic hallmarks. Results We identified 27 and 359 dysregulated miRNAs and mRNAs, respectively, based on the GEO and TCGA databases. Using Pearson's correlation analysis, 10 negative miRNA-mRNA regulatory pairs were identified after screening both databases, and the related miRNA and target mRNA levels were assessed in 40 BC tissues and 40 benign breast disease tissues. Two key regulatory pairs (miR-205-5p/High mobility group box 3 (HMGB3) and miR-96-5p/Forkhead Box O1 (FOXO1)) were selected to establish the diagnostic model. They also had utility in survival and clinical analyses. Conclusions A diagnostic model including two miRNAs and their respective target mRNAs was established to distinguish between BC and benign breast diseases. These markers play essential roles in BC pathogenesis.
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Affiliation(s)
- Jiaying Li
- Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
- Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China
| | - Shuang Peng
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Xuan Zou
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032 China
| | - Xiangnan Geng
- Department of Clinical Engineering, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Tongshan Wang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Wei Zhu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Tiansong Xia
- Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
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18
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Oh S, Lee CM, Kwon SH. Extracellular Vesicle MicroRNA in the Kidney. Compr Physiol 2023; 13:4833-4850. [PMID: 37358511 PMCID: PMC11514415 DOI: 10.1002/cphy.c220023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/27/2023]
Abstract
Most cells in our body release membrane-bound, nano-sized particles into the extracellular milieu through cellular metabolic processes. Various types of macromolecules, reflecting the physiological and pathological status of the producing cells, are packaged into such so-called extracellular vesicles (EVs), which can travel over a distance to target cells, thereby transmitting donor cell information. The short, noncoding ribonucleic acid (RNA) called microRNA (miRNA) takes a crucial part in EV-resident macromolecules. Notably, EVs transferring miRNAs can induce alterations in the gene expression profiles of the recipient cells, through genetically instructed, base-pairing interaction between the miRNAs and their target cell messenger RNAs (mRNAs), resulting in either nucleolytic decay or translational halt of the engaged mRNAs. As in other body fluids, EVs released in urine, termed urinary EVs (uEVs), carry specific sets of miRNA molecules, which indicate either normal or diseased states of the kidney, the principal source of uEVs. Studies have therefore been directed to elucidate the contents and biological roles of miRNAs in uEVs and moreover to utilize the gene regulatory properties of miRNA cargos in ameliorating kidney diseases through their delivery via engineered EVs. We here review the fundamental principles of the biology of EVs and miRNA as well as our current understanding of the biological roles and applications of EV-loaded miRNAs in the kidney. We further discuss the limitations of contemporary research approaches, suggesting future directions to overcome the difficulties to advance both the basic biological understanding of miRNAs in EVs and their clinical applications in treating kidney diseases. © 2023 American Physiological Society. Compr Physiol 13:4833-4850, 2023.
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Affiliation(s)
- Sekyung Oh
- Department of Medical Science, Catholic Kwandong University College of Medicine, Incheon 22711, South Korea
| | - Chang Min Lee
- Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, U.S.A
| | - Sang-Ho Kwon
- Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, U.S.A
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19
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Ding N, Yin Z, Chen C. Targeting non-coding RNAs in sEVs: The biological functions and potential therapeutic strategy of diabetic cardiomyopathy. Biomed Pharmacother 2023; 163:114836. [PMID: 37156118 DOI: 10.1016/j.biopha.2023.114836] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 04/15/2023] [Accepted: 05/02/2023] [Indexed: 05/10/2023] Open
Abstract
Diabetic cardiomyopathy (DCM) is defined as abnormalities in myocardial structure and function in the setting of diabetes and in the absence of cardiovascular diseases, such as coronary artery disease, hypertension, and valvular heart disease. DCM is one of the leading causes of mortality in patients with diabetes. However, the underlying pathogenesis of DCM has not been fully elucidated. Recent studies have revealed that non-coding RNAs (ncRNAs) in small extracellular vesicles (sEVs) are closely associated with DCM and may act as potential diagnostic and therapeutic targets. Here, we introduced the role of sEV-ncRNAs in DCM, summarized the current therapeutic advancements and limitations of sEV-related ncRNAs against DCM, and discussed their potential improvement.
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Affiliation(s)
- Nan Ding
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China
| | - Zhongwei Yin
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China
| | - Chen Chen
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China.
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20
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Bararia A, Chakraborty P, Roy P, Chattopadhay BK, Das A, Chatterjee A, Sikdar N. Emerging role of non-invasive and liquid biopsy biomarkers in pancreatic cancer. World J Gastroenterol 2023; 29:2241-2260. [PMID: 37124888 PMCID: PMC10134423 DOI: 10.3748/wjg.v29.i15.2241] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 02/02/2023] [Accepted: 03/15/2023] [Indexed: 04/14/2023] Open
Abstract
A global increase in the incidence of pancreatic cancer (PanCa) presents a major concern and health burden. The traditional tissue-based diagnostic techniques provided a major way forward for molecular diagnostics; however, they face limitations based on diagnosis-associated difficulties and concerns surrounding tissue availability in the clinical setting. Late disease development with asymptomatic behavior is a drawback in the case of existing diagnostic procedures. The capability of cell free markers in discriminating PanCa from autoimmune pancreatitis and chronic pancreatitis along with other precancerous lesions can be a boon to clinicians. Early-stage diagnosis of PanCa can be achieved only if these biomarkers specifically discriminate the non-carcinogenic disease stage from malignancy with respect to tumor stages. In this review, we comprehensively described the non-invasive disease detection approaches and why these approaches are gaining popularity for their early-stage diagnostic capability and associated clinical feasibility.
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Affiliation(s)
- Akash Bararia
- Human Genetics Unit, Indian Statistical Institute, Kolkata 700108, India
| | - Prosenjeet Chakraborty
- Department of Molecular Biosciences, SVYASA School of Yoga and Naturopathy, Bangalore 560105, India
| | - Paromita Roy
- Department of Pathology, Tata Medical Center, Kolkata 700160, India
| | | | - Amlan Das
- Department of Biochemistry, Royal Global University, Assam 781035, India
| | - Aniruddha Chatterjee
- Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9061, New Zealand
- School of Health Sciences and Technology, University of Petroleum and Energy Studies, Dehradun 248007, India
| | - Nilabja Sikdar
- Human Genetics Unit, Indian Statistical Institute, Kolkata 700108, India
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21
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Someya M, Hasegawa T, Tsuchiya T, Kitagawa M, Fukushima Y, Gocho T, Mafune S, Ikeuchi Y, Kozuka Y, Idogawa M, Hirohashi Y, Torigoe T, Iwasaki M, Matsuura M, Saito T, Sakata KI. Predictive value of an exosomal microRNA-based signature for tumor immunity in cervical cancer patients treated with chemoradiotherapy. Med Mol Morphol 2023; 56:38-45. [PMID: 36367588 DOI: 10.1007/s00795-022-00338-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 10/25/2022] [Indexed: 11/13/2022]
Abstract
Resistance of cervical cancer to radiotherapy with concurrent chemotherapy (CCRT) results in a poor prognosis. To identify new biomarkers for predicting the treatment response and prognosis, we explored exosomal microRNA (miRNA) expression signatures associated with the outcome of cervical cancer patients treated with CCRT. Exosomes were isolated from the plasma of 45 patients prior to CCRT during 2014-2020, and miRNA analysis was performed by next-generation sequencing. At a median follow-up of 38 months, 26 patients were recurrence free, 15 patients had died of the disease, and 4 patients received salvage chemotherapy due to distant metastasis. Of the 2522 miRNAs detected, 9 (miR-148a-5p, 1915-3p, 3960, 183-5p, 196b-5p, 200c-3p, 182-5p, 374a-5p, and 431-5p) showed differential expression between the recurrence-free and recurrence groups. Patients were divided into high- and low-risk groups according to the cutoff of the miRNAs-based risk score calculated from respective expression levels. The high-risk group had significantly worse disease-specific survival than the low-risk group (p < 0.001). In addition, miR-374a-5p and miR-431-5p expression showed a weak inverse correlation with tumor-infiltrating CD8+ and FOXP3+ T cells, suggesting a potential inhibitory effect on CCRT by suppressing tumor immunity. This miRNA signature could improve non-invasive monitoring and personalized treatment for cervical cancer.
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Affiliation(s)
- Masanori Someya
- Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan.
| | - Tomokazu Hasegawa
- Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan
| | - Takaaki Tsuchiya
- Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan
| | - Mio Kitagawa
- Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan
| | - Yuki Fukushima
- Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan
| | - Toshio Gocho
- Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan
| | - Shoh Mafune
- Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan
| | - Yutaro Ikeuchi
- Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan
| | - Yoh Kozuka
- Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan
| | - Masashi Idogawa
- Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Yoshihiko Hirohashi
- Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Toshihiko Torigoe
- Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Masahiro Iwasaki
- Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Motoki Matsuura
- Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Tsuyoshi Saito
- Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Koh-Ichi Sakata
- Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8543, Japan
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Recent progress in aptamer-based microfluidics for the detection of circulating tumor cells and extracellular vesicles. J Pharm Anal 2023; 13:340-354. [PMID: 37181295 PMCID: PMC10173182 DOI: 10.1016/j.jpha.2023.03.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 02/14/2023] [Accepted: 03/01/2023] [Indexed: 03/09/2023] Open
Abstract
Liquid biopsy is a technology that exhibits potential to detect cancer early, monitor therapies, and predict cancer prognosis due to its unique characteristics, including noninvasive sampling and real-time analysis. Circulating tumor cells (CTCs) and extracellular vesicles (EVs) are two important components of circulating targets, carrying substantial disease-related molecular information and playing a key role in liquid biopsy. Aptamers are single-stranded oligonucleotides with superior affinity and specificity, and they can bind to targets by folding into unique tertiary structures. Aptamer-based microfluidic platforms offer new ways to enhance the purity and capture efficiency of CTCs and EVs by combining the advantages of microfluidic chips as isolation platforms and aptamers as recognition tools. In this review, we first briefly introduce some new strategies for aptamer discovery based on traditional and aptamer-based microfluidic approaches. Then, we subsequently summarize the progress of aptamer-based microfluidics for CTC and EV detection. Finally, we offer an outlook on the future directional challenges of aptamer-based microfluidics for circulating targets in clinical applications.
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23
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Kuang L, Zhang C, Li B, Deng H, Chen R, Li G. Human Keratinocyte-Derived Exosomal MALAT1 Promotes Diabetic Wound Healing by Upregulating MFGE8 via microRNA-1914-3p. Int J Nanomedicine 2023; 18:949-970. [PMID: 36852184 PMCID: PMC9961177 DOI: 10.2147/ijn.s399785] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 02/14/2023] [Indexed: 02/25/2023] Open
Abstract
Purpose Diabetic wound is a highly prevalent and refractory disease. Extensive studies have confirmed that keratinocytes and macrophages play an important role in the process of wound healing. Additionally, exosomes are regarded as a vital intercellular communication tool. This study aimed to investigate the role of human keratinocyte-derived exosomal MALAT1 in the treatment of diabetic wound by influencing the biological function of macrophages. Methods We mainly assessed the function of MALAT1 on the biological changes of macrophages, and the expression of MALAT1 in the keratinocyte-exosomes analyzed by quantitative real-time polymerase chain reaction (RT-qPCR). The downstream interaction between RNAs or proteins was assessed by mechanistic experiments. Besides, we evaluated the effects of human keratinocyte-derived exosomal MALAT1 on diabetic wound healing in vivo to verify in vitro results. Results We demonstrated that human keratinocyte-derived exosomal MALAT1 enhanced the biological functions of high glucose-injured macrophages, including phagocytosis, converting to a pro-healing phenotype and reducing apoptosis. Mechanistically, MALAT1 accelerated the expression of MFGE8 by competitively binding to miR-1914-3p, thereby affecting the function of macrophages and the signal axis of TGFB1/SMAD3, and finally promoting the healing of diabetic wounds. Human keratinocyte-derived exosomal MALAT1 might promote collagen deposition, ECM remodeling, and expression of MFGE8, VEGF, and CD31 but reduce the expression of TGFB and SMAD3 in an in vivo model of diabetic mice wounds, which accelerated diabetic wound healing and restored its function. Conclusion The current study revealed that human keratinocyte-derived exosomal MALAT1 would suppress miR-1914-3p to activate MFGE8 and eventually promote wound healing by enhancing macrophage phagocytosis, converting to a pro-healing phenotype and reducing apoptosis. It proposed that keratinocyte-derived exosomes might have the capacity to serve as a new method for the clinical treatment of diabetic wound.
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Affiliation(s)
- Liwen Kuang
- Department of Wound Repair Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430062, People’s Republic of China
| | - Chenchen Zhang
- Department of Wound Repair Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430062, People’s Republic of China
| | - Binghui Li
- Department of Wound Repair Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430062, People’s Republic of China
| | - Haibo Deng
- Department of Wound Repair Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430062, People’s Republic of China
| | - Ran Chen
- Department of Wound Repair Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430062, People’s Republic of China
| | - Gongchi Li
- Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China,Correspondence: Gongchi Li, Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Road, Wuhan, Hubei, 430022, People’s Republic of China, Tel +8613618615209, Email
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24
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An Update on Peripheral Blood Extracellular Vesicles as Biomarkers for Parkinson's Disease Diagnosis. Neuroscience 2023; 511:131-146. [PMID: 36435476 DOI: 10.1016/j.neuroscience.2022.11.017] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 10/27/2022] [Accepted: 11/17/2022] [Indexed: 11/24/2022]
Abstract
Parkinson's disease (PD) is the world's second primary neurodegenerative disease, and the diagnosis and treatment of PD have become mainstream research. Over the past decades, several studies have identified potential biomarkers for diagnosing PD. Among them, extracellular vesicles (EVs) can carry specific biomarkers reflecting the physiological and pathological state of the body. Due to the blood-brain barrier (BBB) limitation, peripheral blood is limited in diagnosing neurodegenerative diseases. With the increasing research on EVs, their ability to pass through BBB indicated that peripheral blood could depict disease status like cerebrospinal fluid (CSF). Peripheral blood is a clinically available sample and has recently been widely used by researchers in various studies. In this review, we summarized previous studies on PD diagnosis biomarkers in peripheral blood EVs and evaluated their diagnostic value. Some EV surface markers were also described, which can extract EVs from specific cell origins. In addition, the combination of several biomarkers demonstrated good diagnostic performance in PD diagnosis compared with a single biomarker, suggesting the focus of future research.
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25
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Jiapaer Z, Li C, Yang X, Sun L, Chatterjee E, Zhang L, Lei J, Li G. Extracellular Non-Coding RNAs in Cardiovascular Diseases. Pharmaceutics 2023; 15:pharmaceutics15010155. [PMID: 36678784 PMCID: PMC9865796 DOI: 10.3390/pharmaceutics15010155] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 12/22/2022] [Accepted: 12/27/2022] [Indexed: 01/04/2023] Open
Abstract
Cardiovascular diseases (CVDs) remain the world's leading cause of death despite the best available healthcare and therapy. Emerging as a key mediator of intercellular and inter-organ communication in CVD pathogenesis, extracellular vesicles (EVs) are a heterogeneous group of membrane-enclosed nano-sized vesicles released by virtually all cells, of which their RNA cargo, especially non-coding RNAs (ncRNA), has been increasingly recognized as a promising diagnostic and therapeutic target. Recent evidence shows that ncRNAs, such as small ncRNAs, circular RNAs, and long ncRNAs, can be selectively sorted into EVs or other non-vesicular carriers and modulate various biological processes in recipient cells. In this review, we summarize recent advances in the literature regarding the origin, extracellular carrier, and functional mechanisms of extracellular ncRNAs with a focus on small ncRNAs, circular RNAs, and long ncRNAs. The pathophysiological roles of extracellular ncRNAs in various CVDs, including atherosclerosis, ischemic heart diseases, hypertension, cardiac hypertrophy, and heart failure, are extensively discussed. We also provide an update on recent developments and challenges in using extracellular ncRNAs as biomarkers or therapeutical targets in these CVDs.
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Affiliation(s)
- Zeyidan Jiapaer
- College of Life Science & Technology, Xinjiang University, Urumqi 830046, China
- Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, Urumqi 830046, China
| | - Chengyu Li
- College of Life Science & Technology, Xinjiang University, Urumqi 830046, China
- Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, Urumqi 830046, China
| | - Xinyu Yang
- Fangshan Hospital Beijing University of Chinese Medicine, Beijing 102400, China
| | - Lingfei Sun
- Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Emeli Chatterjee
- Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Lingying Zhang
- College of Life Science & Technology, Xinjiang University, Urumqi 830046, China
- Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, Urumqi 830046, China
| | - Ji Lei
- Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
- Correspondence: (J.L.); (G.L.)
| | - Guoping Li
- Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
- Correspondence: (J.L.); (G.L.)
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26
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Abstract
Exosomes are extracellular vesicles, which have the ability to convey various types of cargo between cells. Lately, a great amount of interest has been paid to exosomal microRNAs (miRNAs), since much evidence has suggested that the sorting of miRNAs into exosomes is not an accidental process. It has been shown that exosomal miRNAs (exo-miRNAs) are implicated in a variety of cellular processes including (but not limited to) cell migration, apoptosis, proliferation, and autophagy. Exosomes can play a role in cardiovascular diseases and can be used as diagnostic biomarkers for several diseases, especially cancer. Tremendous advances in technology have led to the development of various platforms for miRNA profiling. Each platform has its own limitations and strengths that need to be understood in order to use them properly. In the current review, we summarize some exo-miRNAs that are relevant to exo-miRNA profiling studies and describe new methods used for the measurement of miRNA profiles in different human bodily fluids.
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27
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Ding M, Pei Y, Zhang C, Qi Y, Xia J, Hao C, Yao W. Exosomal miR-125a-5p regulates T lymphocyte subsets to promote silica-induced pulmonary fibrosis by targeting TRAF6. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2023; 249:114401. [PMID: 36508789 DOI: 10.1016/j.ecoenv.2022.114401] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/01/2022] [Accepted: 12/05/2022] [Indexed: 06/17/2023]
Abstract
Silicosis caused by long-term inhalation of crystalline silica during occupational activities seriously threatens the health of occupational populations. Imbalances in T helper 1(Th1), Th2, Th17, and regulatory T cells (Tregs) promote the development of pulmonary silicosis. Exosomes and their contents, especially microRNAs (miRNAs), represent a new type of intercellular signal transmission mediator related to various diseases including pulmonary fibrosis. However, whether exosomal miRNAs can affect the progression of silicosis by regulating T cell differentiation remains to be determined. To test this hypothesis, we established a miR-125a-5p antagomir mouse model and examined changes in miR-125a-5p levels and T cell subtypes. We found that miR-125a-5p levels were increased in lung tissues and serum exosomes in the silica group at 7 days and 28 days. Downregulation of miR-125a-5p attenuated α-smooth muscle actin (α-SMA), collagen I, fibronectin, p-p65, and p-inhibitor of nuclear factor kappa B (NF-κB) kinase (IKK) protein expression, while tumor necrosis factor receptor-associated factor 6 (TRAF6) and p-inhibitor of κBα (IKBα) expression were increased. MiR-125a-5p anta-miR treatment contributes to the maintenance of Th1/Th2 balance during the progression of pulmonary fibrosis. Our findings indicated that knockdown miR-125a-5p could regulate T lymphocyte subsets and significantly reduce pulmonary fibrosis by targeting TRAF6.
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Affiliation(s)
- Mingcui Ding
- Department of Occupational Health and Occupational Disease, School of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China
| | - Yangqing Pei
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, Henan, China
| | - Chengpeng Zhang
- Department of Occupational Health and Occupational Disease, School of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China
| | - Yuanmeng Qi
- Department of Occupational Health and Occupational Disease, School of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China
| | - Jiarui Xia
- Department of Occupational Health and Occupational Disease, School of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China
| | - Changfu Hao
- Department of child and Adolecence health, School of public health, Zhengzhou University, Zhengzhou 450001, Henan, China.
| | - Wu Yao
- Department of Occupational Health and Occupational Disease, School of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China.
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Kong H, Liu P, Li H, Zeng X, Xu P, Yao X, Liu S, Cheng CK, Xu J. Mesenchymal Stem Cell-Derived Extracellular Vesicles: The Novel Therapeutic Option for Regenerative Dentistry. Stem Cell Rev Rep 2023; 19:46-58. [PMID: 35132538 DOI: 10.1007/s12015-022-10342-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/23/2022] [Indexed: 01/29/2023]
Abstract
Dental mesenchymal stem cells (MSCs) are characterized by unlimited self-renewal ability and high multidirectional differentiation potential. Since dental MSCs can be easily isolated and exhibit a high capability to differentiate into odontogenic cells, they are considered as attractive therapeutic agents in regenerative dentistry. Recently, MSC-derived extracellular vesicles (MSC-EVs) have attracted widespread attention as carriers for cell-free therapy due to their potential functions. Many studies have shown that MSC-EVs can mediate microenvironment at tissue damage site, and coordinate the regeneration process. Additionally, MSC-EVs can mediate intercellular communication, thus affecting the phenotypes and functions of recipient cells. In this review, we mainly summarized the types of MSCs that could be potentially applied in regenerative dentistry, the possible molecular cargos of MSC-EVs, and the major effects of MSC-EVs on the therapeutic induction of osteogenic differentiation.
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Affiliation(s)
- Haiying Kong
- Department of Dentistry, Longgang E.N.T. Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T, Shenzhen, Guangdong, China
| | - Peiqi Liu
- Department of Dentistry, Longgang E.N.T. Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T, Shenzhen, Guangdong, China.,Second School of Clinical Medicine, Guangdong Medical University, Dongguan, Guangdong, China
| | - Hongwen Li
- Department of Dentistry, Longgang E.N.T. Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T, Shenzhen, Guangdong, China.,Shenzhen Longgang Institute of Stomatology, Shenzhen, Guangdong, China
| | - Xiantao Zeng
- Department of Dentistry, Longgang E.N.T. Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T, Shenzhen, Guangdong, China
| | - Peiwu Xu
- Department of Dentistry, Longgang E.N.T. Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T, Shenzhen, Guangdong, China
| | - Xinhui Yao
- Department of Dentistry, Longgang E.N.T. Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T, Shenzhen, Guangdong, China
| | - Senqing Liu
- Department of Dentistry, Longgang E.N.T. Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T, Shenzhen, Guangdong, China
| | - Chak Kwong Cheng
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
| | - Jian Xu
- Department of Dentistry, Longgang E.N.T. Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T, Shenzhen, Guangdong, China. .,Shenzhen Longgang Institute of Stomatology, Shenzhen, Guangdong, China.
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Truong AD, Kang S, Dang HV, Hong Y, Vu TH, Heo J, Chu NT, Nguyen HT, Tran HTT, Hong YH. Small RNA sequencing and profiling of serum-derived exosomes from African swine fever virus-infected pigs. J Anim Sci 2022; 101:6881709. [PMID: 36478238 PMCID: PMC9940739 DOI: 10.1093/jas/skac400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022] Open
Abstract
African swine fever (ASF) virus (ASFV) is responsible for one of the most severe swine diseases worldwide, with a morbidity rate of up to 100%; no vaccines or antiviral medicines are available against the virus. Exosomal miRNAs from individual cells can regulate the immune response to infectious diseases. In this study, pigs were infected with an ASFV Pig/HN/07 strain that was classified as acute form, and exosomal miRNA expression in the serum of infected pigs was analyzed using small RNA sequencing (small RNA-seq). Twenty-seven differentially expressed (DE) miRNAs were identified in the ASFV-infected pigs compared to that in the uninfected controls. Of these, 10 were upregulated and 17 were downregulated in the infected pigs. All DE miRNAs were analyzed using gene ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the DE miRNAs were found to be highly involved in T-cell receptor signaling, cGMP-PKG signaling, Toll-like receptor, MAPK signaling, and mTOR signaling pathways. Furthermore, the Cytoscape network analysis identified the network of interactions between DE miRNAs and target genes. Finally, the transcription levels of four miRNA genes (ssc-miR-24-3p, ssc-miR-130b-3p, ssc-let-7a, and ssc-let-7c) were examined using quantitative real-time PCR (qRT-PCR) and were found to be consistent with the small RNA-seq data. These DE miRNAs were associated with cellular genes involved in the pathways related to immune response, virus-host interactions, and several viral genes. Overall, our findings provide an important reference and improve our understanding of ASF pathogenesis and the immune or protective responses during an acute infection in the host.
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Affiliation(s)
| | | | | | - Yeojin Hong
- Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea
| | - Thi Hao Vu
- Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea
| | - Jubi Heo
- Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea
| | - Nhu Thi Chu
- Department of Biochemistry and Immunology, National Institute of Veterinary Research, 86 Truong Chinh, Dong Da, Hanoi 100000, Vietnam
| | - Huyen Thi Nguyen
- Department of Biochemistry and Immunology, National Institute of Veterinary Research, 86 Truong Chinh, Dong Da, Hanoi 100000, Vietnam
| | - Ha Thi Thanh Tran
- Department of Biochemistry and Immunology, National Institute of Veterinary Research, 86 Truong Chinh, Dong Da, Hanoi 100000, Vietnam
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An Z, Tian J, Liu Y, Zhao X, Yang X, Yong J, Liu L, Zhang L, Jiang W, Song X, Zhang H. Exosomes as a Cell-free Therapy for Myocardial Injury Following Acute Myocardial Infarction or Ischemic Reperfusion. Aging Dis 2022; 13:1770-1786. [PMID: 36465167 PMCID: PMC9662265 DOI: 10.14336/ad.2022.0416] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 04/16/2022] [Indexed: 08/13/2023] Open
Abstract
Exosomes, which contain miRNA, have been receiving growing attention in cardiovascular therapy because of their role in mediating cell-cell communication, autophagy, apoptosis, inflammation, and angiogenesis. Several studies have suggested that miRNA derived from exosomes can be used to detect myocardial infarctions (MI) in patients. Basic research also suggests that exosomes could serve as a potential therapeutic target for treating acute myocardial infarction. Ischemia/reperfusion (IR) injury is associated with adverse cardiac events after acute MI. We aim to review the potential benefits and mechanisms of exosomes in treating MI and IR injury.
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Affiliation(s)
- Ziyu An
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
| | - Jinfan Tian
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
| | - Yue Liu
- Cardiovascular disease center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
| | - Xin Zhao
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
| | - Xueyao Yang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
| | - Jingwen Yong
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
| | - Libo Liu
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
| | - Lijun Zhang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
| | - Wenjian Jiang
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
| | - Xiantao Song
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
| | - Hongjia Zhang
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
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Wei FS, Rao MW, Huang YL, Chen SB, Wu YQ, Yang L. miR-182-5p Delivered by Plasma Exosomes Promotes Sevoflurane-Induced Neuroinflammation and Cognitive Dysfunction in Aged Rats with Postoperative Cognitive Dysfunction by Targeting Brain-Derived Neurotrophic Factor and Activating NF-κB Pathway. Neurotox Res 2022; 40:1902-1912. [PMID: 36308704 DOI: 10.1007/s12640-022-00597-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 10/12/2022] [Accepted: 10/18/2022] [Indexed: 12/31/2022]
Abstract
The objective of this study was to discuss the possible mechanism and effect of miR-182-5p delivered by plasma exosomes on sevoflurane-induced neuroinflammation and cognitive disorder in aged rats with postoperative cognitive dysfunction (POCD). Firstly, aged POCD rat models were constructed by sevoflurane anesthesia and superior mesenteric artery occlusion. Subsequently, exosomes and miR-182-5p were inhibited by injection of GW4869 and miR-182-5p-sponge, respectively. Then, exosomes were extracted from the plasma of rats in each group, followed by the determination of the morphology and diameters of exosomes as well as the expression of exosome markers CD63 and CD81 by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. Besides, the Morris water maze (MWM) and fear conditioning test were used to evaluate the learning and memory ability of rats; Western blot to detect the expression levels of neurotrophic factors (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) as well as NF-κB pathway-related proteins (p65 and p-p65) in rat hippocampal tissues or PC-12 cells; qRT-PCR to assess the expression levels of miR-182-5p and BDNF in rat plasma, plasma exosomes, hippocampal tissues, and PC-12 cells; ELISA to evaluate the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in rat hippocampal tissues; and dual-luciferase reporter assay to verify the targeting relationship between miR-182-5p and BDNF. After examination, the results were obtained as follows. miR-182-5p expression was up-regulated in POCD rats and could be delivered by plasma exosomes. Inhibition of plasma exosomes or miR-182-5p could significantly ameliorate learning and memory disorders; decrease the levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β; increase the expression of BDNF and NGF; and inhibit the activity of NF-κB signaling pathway in POCD rat hippocampus. In addition, miR-182-5p could also target and inhibit BDNF. All in all, miR-182-5p delivered by plasma exosomes promotes sevoflurane-induced neuroinflammation and cognitive dysfunction in aged POCD rats by targeting BDNF and activating the NF-κB pathway.
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Affiliation(s)
- Fu-Sheng Wei
- Department of Anesthesiology and Operation, The First Affiliated Hospital of Nanchang University, Nanchang, 330052, Jiangxi, China
| | - Mu-Wen Rao
- Department of Anesthesiology and Operation, The First Affiliated Hospital of Nanchang University, Nanchang, 330052, Jiangxi, China
| | - Yuan-Lu Huang
- Department of Anesthesiology and Operation, The First Affiliated Hospital of Nanchang University, Nanchang, 330052, Jiangxi, China
| | - Shi-Biao Chen
- Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, 330052, Jiangxi, China
| | - Yu-Qian Wu
- Science and Technology Division, The First Affiliated Hospital of Nanchang University, Nanchang, 330052, Jiangxi, China
| | - Lei Yang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, 330052, Jiangxi, China.
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Xu H, Ye BC. Integrated microfluidic platforms for tumor-derived exosome analysis. Trends Analyt Chem 2022. [DOI: 10.1016/j.trac.2022.116860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Dalmizrak A, Dalmizrak O. Mesenchymal stem cell-derived exosomes as new tools for delivery of miRNAs in the treatment of cancer. Front Bioeng Biotechnol 2022; 10:956563. [PMID: 36225602 PMCID: PMC9548561 DOI: 10.3389/fbioe.2022.956563] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 09/01/2022] [Indexed: 11/13/2022] Open
Abstract
Although ongoing medical research is working to find a cure for a variety of cancers, it continues to be one of the major causes of death worldwide. Chemotherapy and immunotherapy, as well as surgical intervention and radiation therapy, are critical components of cancer treatment. Most anti-cancer drugs are given systemically and distribute not just to tumor tissues but also to normal tissues, where they may cause side effects. Furthermore, because anti-cancer drugs have a low delivery efficiency, some tumors do not respond to them. As a result, tumor-targeted drug delivery is critical for improving the safety and efficacy of anti-cancer treatment. Exosomes are microscopic extracellular vesicles that cells produce to communicate with one another. MicroRNA (miRNA), long non-coding RNA (lncRNA), small interfering RNA (siRNA), DNA, protein, and lipids are among the therapeutic cargos found in exosomes. Recently, several studies have focused on miRNAs as a potential therapeutic element for the treatment of cancer. Mesenchymal stem cells (MSC) have been known to have angiogenic, anti-apoptotic, anti-inflammatory and immunomodulatory effects. Exosomes derived from MSCs are gaining popularity as a non-cellular alternative to MSC-based therapy, as this method avoids unwanted lineage differentiation. Therefore more research have focused on transferring miRNAs to mesenchymal stem cells (MSC) and targeting miRNA-loaded exosomes to cancer cells. Here, we initially gave an overview of the characteristics and potentials of MSC as well as the use of MSC-derived exosomes in cancer therapy. Finally, we emphasized the utilization of MSC-derived exosomes for miRNA delivery in the treatment of cancer.
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Affiliation(s)
- Aysegul Dalmizrak
- Department of Medical Biology, Faculty of Medicine, Balıkesir University, Balıkesir, Turkey
| | - Ozlem Dalmizrak
- Department of Medical Biochemistry, Faculty of Medicine, Near East University, Nicosia, Mersin, Turkey
- *Correspondence: Ozlem Dalmizrak,
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Tsukada F, Takashima S, Wakihara Y, Kamatari YO, Shimizu K, Okada A, Inoshima Y. Characterization of miRNAs in Milk Small Extracellular Vesicles from Enzootic Bovine Leukosis Cattle. Int J Mol Sci 2022; 23:ijms231810782. [PMID: 36142686 PMCID: PMC9503721 DOI: 10.3390/ijms231810782] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/09/2022] [Accepted: 09/12/2022] [Indexed: 11/17/2022] Open
Abstract
Enzootic bovine leukosis (EBL) is a B-cell lymphosarcoma caused by the bovine leukemia virus (BLV). Most BLV-infected cattle show no clinical signs and only some develop EBL. The pathogenesis of EBL remains unclear and there are no methods for predicting EBL before its onset. Previously, it was reported that miRNA profiles in milk small extracellular vesicles (sEVs) were affected in cattle in the late stage of BLV infection. It raised a possibility that miRNA profile in milk sEVs from EBL cattle could be also affected. To characterize the difference in milk of EBL cattle and healthy cattle, we examined the miRNA profiles in milk sEVs from four EBL and BLV-uninfected cattle each using microarray analysis. Among the detected miRNAs, three miRNAs—bta-miR-1246, hsa-miR-1290, and hsa-miR-424-5p—which were detectable using quantitative real-time PCR (qPCR) and are associated with cancers in humans—were selected as biomarker candidates for EBL. To evaluate the utility of these miRNAs as biomarkers for EBL, their levels were measured using milk that was freshly collected from 13 EBL and seven BLV-uninfected cattle. bta-miR-1246 and hsa-miR-424-5p, but not hsa-miR-1290, were detected using qPCR and their levels in milk sEVs from EBL cattle were significantly higher than those in BLV-uninfected cattle. bta-miR-1246 and hsa-miR-424-5p in sEVs may promote metastasis by targeting tumor suppressor genes, resulting in increased amounts in milk sEVs in EBL cattle. These results suggest that bta-miR-1246 and hsa-miR-424-5p levels in milk sEVs could serve as biomarkers for EBL.
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Affiliation(s)
- Fumi Tsukada
- Laboratory of Food and Environmental Hygiene, Cooperative Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1193, Japan
| | - Shigeo Takashima
- Division of Genomics Research, Life Science Research Center, Gifu University, Gifu 501-1193, Japan
- Institute of Glyco-Core Research (iGCORE), Gifu University, Gifu 501-1193, Japan
- The United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1193, Japan
| | - Yoshiko Wakihara
- Division of Genomics Research, Life Science Research Center, Gifu University, Gifu 501-1193, Japan
| | - Yuji O. Kamatari
- Institute of Glyco-Core Research (iGCORE), Gifu University, Gifu 501-1193, Japan
- The United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1193, Japan
- Division of Instrumental Analysis, Life Science Research Center, Gifu University, Gifu 501-1193, Japan
| | - Kaori Shimizu
- Laboratory of Food and Environmental Hygiene, Cooperative Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1193, Japan
| | - Ayaka Okada
- Laboratory of Food and Environmental Hygiene, Cooperative Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1193, Japan
- Education and Research Center for Food Animal Health, Gifu University (GeFAH), Gifu 501-1193, Japan
| | - Yasuo Inoshima
- Laboratory of Food and Environmental Hygiene, Cooperative Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1193, Japan
- Education and Research Center for Food Animal Health, Gifu University (GeFAH), Gifu 501-1193, Japan
- The United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan
- Joint Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan
- Correspondence:
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Circulating and non-circulating proteins and nucleic acids as biomarkers and therapeutic molecules in ovarian cancer. Genes Dis 2022. [DOI: 10.1016/j.gendis.2022.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Ashrafizadeh M, Rabiee N, Kumar AP, Sethi G, Zarrabi A, Wang Y. Long noncoding RNAs (lncRNAs) in pancreatic cancer progression. Drug Discov Today 2022; 27:2181-2198. [PMID: 35589014 DOI: 10.1016/j.drudis.2022.05.012] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Revised: 02/18/2022] [Accepted: 05/12/2022] [Indexed: 02/07/2023]
Abstract
Long noncoding RNAs (lncRNAs) are RNA molecules involved in gene regulation at transcriptional, post-transcriptional, and epigenetic levels. LncRNAs participate in regulating apoptosis and autophagy in pancreatic cancer (PCa) and can promote and/or decrease the proliferation rate of tumor cells. The metastasis of PCa cells is tightly regulated by lncRNAs and they can affect the mechanism of epithelial-mesenchymal transition (EMT) to modulate metastasis. The drug resistance of PCa cells, especially to gemcitabine, can be affected by lncRNAs. In addition, lncRNAs enriched in exosomes can be transferred among tumor cells to regulate their proliferation and metastasis. Antitumor compounds, such as curcumin and ginsenosides, can regulate lncRNA expression in PCa therapy. As we discuss here, the expression level of lncRNAs can be considered as both a diagnostic and prognostic tool in patients with PCa.
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Affiliation(s)
- Milad Ashrafizadeh
- Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Üniversite Caddesi No. 27, Orhanlı, Tuzla, 34956 Istanbul, Turkey.
| | - Navid Rabiee
- Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, South Korea; School of Engineering, Macquarie University, Sydney, NSW 2109, Australia
| | - Alan Prem Kumar
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117599, Singapore; NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117599, Singapore; NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Ali Zarrabi
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Sariyer 34396, Istanbul, Turkey.
| | - Yuzhuo Wang
- Department of Urological Sciences, Vancouver, BC V6H3Z6, Canada; Vancouver Prostate Centre, University of British Columbia, Vancouver, BC V6H3Z6, Canada.
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Oxidative stress-induced endothelial cells-derived exosomes accelerate skin flap survival through Lnc NEAT1-mediated promotion of endothelial progenitor cell function. Stem Cell Res Ther 2022; 13:325. [PMID: 35850692 PMCID: PMC9290268 DOI: 10.1186/s13287-022-03013-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 06/08/2022] [Indexed: 12/14/2022] Open
Abstract
Background Flap transplantation is commonly used in reconstructive surgery. A prerequisite for skin flap survival is sufficient blood supply. However, such approaches remain unclear. This study aimed to explore the underlying mechanisms of exosomes derived from human umbilical vascular endothelial cells (HUVECs) exposed to oxidative stress on endothelial progenitor cells (EPCs) and their subsequent influence on the survival of skin flaps. Methods HUVECs were treated with various concentrations of H2O2 to establish an oxidative stress model. To investigate the effects of H2O2-HUVEC-Exos and HUVEC-Exos, Cell Counting Kit-8, tube formation, invasion assays, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed in EPCs. Microarray analysis was used to reveal the differentially expressed long non-coding RNAs (lncRNAs) in the H2O2-HUVEC-Exos and HUVEC-Exos. In addition, gene silencing and western blotting were employed to determine the mechanism behind lncRNA nuclear enrichment enriched transcript 1 (Lnc NEAT1) in EPCs. Further, a rat skin flap model was used to determine the role of the exosomes in skin flap survival in vivo. Results HUVECs were stimulated with 100 μmol/L H2O2 for 12 h to establish an oxidative stress model. H2O2-HUVEC-Exos promoted the proliferation, tube formation, and invasion of EPCs and remarkably increased skin flap survival compared to the HUVEC-Exos and control groups. Sequencing of exosome RNAs revealed that the Lnc NEAT1 level was dramatically increased in the H2O2-HUVEC-Exos, leading to activation of the Wnt/β-catenin signaling pathway. Comparatively, knockdown of Lnc NEAT1 in HUVEC-Exos and H2O2-HUVEC-Exos significantly inhibits the angiogenic capacity of EPCs, reduced the survival area of skin flap and downregulated the expression levels of Wnt/β-catenin signaling pathway proteins, whereas Wnt agonist partly reversed the negative effect of NEAT1 downregulation on EPCs through the Wnt/β-catenin signaling pathway. Conclusions Exosomes derived from HUVECs stimulated by oxidative stress significantly promoted the pro-angiogenic ability of EPCs through the Wnt/β-catenin signaling pathway mediated by Lnc NEAT1 and hence enhanced random flap survival in vivo. Therefore, the application of H2O2-HUVEC-Exos may serve as an alternative therapy for improving random skin flap survival. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-03013-9.
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Yenuganti VR, Afroz S, Khan RA, Bharadwaj C, Nabariya DK, Nayak N, Subbiah M, Chintala K, Banerjee S, Reddanna P, Khan N. Milk exosomes elicit a potent anti-viral activity against dengue virus. J Nanobiotechnology 2022; 20:317. [PMID: 35794557 PMCID: PMC9258094 DOI: 10.1186/s12951-022-01496-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 06/08/2022] [Indexed: 11/10/2022] Open
Abstract
Background Exosomes are nano-sized vesicles secreted by various cells into the intra and extracellular space and hence is an integral part of biological fluids including milk. In the last few decades, many research groups have proved the potential of milk exosomes as a sustainable, economical and non-immunogenic drug delivery and therapeutic agent against different pathological conditions. However, its anti-viral properties still remain to be unearthed. Methods Here, we have been able to isolate, purify and characterize the milk derived exosomes from Cow (CME) and Goat (GME) and further studied its antiviral properties against Dengue virus (DENV), Newcastle Disease Virus strain Komarov (NDV-K) and Human Immunodeficiency Virus (HIV-1) using an in-vitro infection system. Results TEM, NTA and DLS analysis validated the appropriate size of the isolated cow and goat milk exosomes (30–150 nm). Real-time PCR and immunoblotting results confirmed the presence of several milk exosomal miRNAs and protein markers. Our findings suggest that GME significantly decreased the infectivity of DENV. In addition, we confirmed that GME significantly reduces DENV replication and reduced the secretion of mature virions. Furthermore, heat inactivation of GME did not show any inhibition on DENV infection, replication, and secretion of mature virions. RNase treatment of GME abrogates the anti-viral properties indicating direct role of exosomes in DENV inhibition. In addition GME inhibited the infectivity of NDV-K, but not HIV-1, suggesting that the GME mediated antiviral activity might be virus specific. Conclusion This study demonstrates the anti-viral properties of milk exosomes and opens new avenues for the development of exosome-based therapies to treat viral diseases. Graphical Abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s12951-022-01496-5.
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Huang D, Zhang M, Tan Z. Bone Marrow Stem Cell-Exo-Derived TSG-6 Attenuates 1-Methyl-4-Phenylpyridinium+-Induced Neurotoxicity via the STAT3/miR-7/NEDD4/LRRK2 Axis. J Neuropathol Exp Neurol 2022; 81:621-634. [PMID: 35773961 DOI: 10.1093/jnen/nlac049] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Bone marrow mesenchymal stem cell-derived exosome (BMSCs-Exo)-derived TNF-stimulated gene-6 (TSG-6) has anti-inflammatory and antioxidative stress-related properties that may be beneficial in the treatment of Parkinson disease (PD) patients. To elucidate the mechanisms involved, we analyzed the effects of BMSCs-Exo-derived TSG-6 on in vitro models of PD induced with 1-methyl-4-phenylpyridinium (MPP+). TSG-6 was abundant in BMSCs-Exo and it attenuated MPP+-induced neurotoxicity. Moreover, BMSCs-Exo reversed the MPP+-induced toxicity accelerated by neural precursor cells expressed developmentally downregulated 4 (NEDD4) knockdown or miR-7 mimics. Further analysis indicated that NEDD4 combined with leucine-rich repeat kinase 2 (LRRK2) to accelerate ubiquitin degradation of LRRK2. Signal transducer and activator of transcription 3 (STAT3) bound to the miR-7 promoter and miR-7 targeted NEDD4. These data indicate that BMSCs-Exo-derived TSG-6 attenuated neurotoxicity via the STAT3-miR-7-NEDD4 axis. Our results define the specific mechanisms for BMSCs-Exo-derived TSG-6 regulation of MPP+-induced neurotoxicity that are relevant to understanding PD pathogenesis and developing therapies for PD patients.
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Affiliation(s)
- Dezhi Huang
- From the Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, P.R. China
| | - Mingming Zhang
- From the Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, P.R. China
| | - Zhigang Tan
- From the Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, P.R. China
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Chen XM, Yao DN, Wang MJ, Wu XD, Deng JW, Deng H, Huang RY, Lu CJ. Deep Sequencing of Plasma Exosomal microRNA Level in Psoriasis Vulgaris Patients. Front Med (Lausanne) 2022; 9:895564. [PMID: 35665333 PMCID: PMC9160332 DOI: 10.3389/fmed.2022.895564] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 04/27/2022] [Indexed: 12/29/2022] Open
Abstract
Psoriasis is a chronic skin disease affecting 1% to 3% of the world population. Psoriasis vulgaris (PV) is the most common form of psoriasis. PV patients suffer from inflamed, pruritic and painful lesions for years (even a lifetime). However, conventional drugs for PV are costly. Considering the need for long-term treatment of PV, it is urgent to discover novel biomarkers and therapeutic targets. Plasma exosomal miRNAs have been identified as the reliable biomarkers and therapy targets of human diseases. Here, we described the levels of serum exosomal miRNAs in PV patients and analyzed the functional features of differently expressed miRNAs and their potential target genes for the first time. We identified 1182 miRNAs including 336 novel miRNAs and 246 differently expressed miRNAs in serum exosomes of healthy people and PV patients. Furthermore, the functional analysis found differently expressed miRNA-regulated target genes enriched for specific GO terms including primary metabolic process, cellular metabolic process, metabolic process, organic substance metabolic process, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway containing cellular processes, human diseases, metabolic pathways, metabolism and organismal systems. In addition, we found that some predicted target genes of differentially expressed miRNAs, such as CREB1, RUNX2, EGFR, are both involved in inflammatory response and metabolism. In summary, our study identifies many candidate miRNAs involved in PV, which could provide potential biomarkers for diagnosis of PV and targets for clinical therapies against PV.
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Affiliation(s)
- Xiu-Min Chen
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
- Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou, China
- Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Dan-Ni Yao
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
| | - Mao-Jie Wang
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
- Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiao-Dong Wu
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
| | - Jing-Wen Deng
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
| | - Hao Deng
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
| | - Run-Yue Huang
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
- Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Chuan-Jian Lu
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
- Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, China
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Yang ZL, Rao J, Lin FB, Liang ZY, Xu XJ, Lin YK, Chen XY, Wang CH, Chen CM. The Role of Exosomes and Exosomal Noncoding RNAs From Different Cell Sources in Spinal Cord Injury. Front Cell Neurosci 2022; 16:882306. [PMID: 35518647 PMCID: PMC9062236 DOI: 10.3389/fncel.2022.882306] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 03/21/2022] [Indexed: 11/13/2022] Open
Abstract
Spinal cord injury (SCI) not only affects the quality of life of patients but also poses a heavy burden on their families. Therefore, it is essential to prevent the occurrence of SCI; for unpreventable SCI, it is critical to develop effective treatments. In recent years, various major breakthroughs have been made in cell therapy to protect and regenerate the damaged spinal cord via various mechanisms such as immune regulation, paracrine signaling, extracellular matrix (ECM) modification, and lost cell replacement. Nevertheless, many recent studies have shown that the cell therapy has many disadvantages, such as tumorigenicity, low survival rate, and immune rejection. Because of these disadvantages, the clinical application of cell therapy is limited. In recent years, the role of exosomes in various diseases and their therapeutic potential have attracted much attention. The same is true for exosomal noncoding RNAs (ncRNAs), which do not encode proteins but affect transcriptional and translational processes by targeting specific mRNAs. This review focuses on the mechanism of action of exosomes obtained from different cell sources in the treatment of SCI and the regulatory role and therapeutic potential of exosomal ncRNAs. This review also discusses the future opportunities and challenges, proposing that exosomes and exosomal ncRNAs might be promising tools for the treatment of SCI.
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Affiliation(s)
| | | | | | | | | | | | | | - Chun-Hua Wang
- Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Chun-Mei Chen
- Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, China
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Shen K, Duan A, Cheng J, Yuan T, Zhou J, Song H, Chen Z, Wan B, Liu J, Zhang X, Zhang Y, Xie R, Liu F, Fan W, Zuo Q. Exosomes derived from hypoxia preconditioned mesenchymal stem cells laden in a silk hydrogel promote cartilage regeneration via the miR-205-5p/PTEN/AKT pathway. Acta Biomater 2022; 143:173-188. [PMID: 35202856 DOI: 10.1016/j.actbio.2022.02.026] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 02/15/2022] [Accepted: 02/17/2022] [Indexed: 12/15/2022]
Abstract
Tissue engineering has promising prospects for cartilage regeneration. However, there remains an urgent need to harvest high quality seed cells. Bone marrow mesenchymal cells (BMSCs), and in particular their exosomes, might promote the function of articular chondrocytes (ACs) via paracrine mechanisms. Furthermore, preconditioned BMSCs could provide an enhanced therapeutic effect. BMSCs naturally exist in a relatively hypoxic environment (1%-5% O2); however, they are usually cultured under higher oxygen concentrations (21% O2). Herein, we hypothesized that hypoxia preconditioned exosomes (H-Exos) could improve the quality of ACs and be more conducive to cartilage repair. In our study, we compared the effects of exosomes derived from BMSCs preconditioned with hypoxia and normoxia (N-Exos) on ACs, demonstrating that H-Exos significantly promoted the proliferation, migration, anabolism and anti-inflammation effects of ACs. Furthermore, we confirmed that hypoxia preconditioning upregulated the expression of miR-205-5p in H-Exos, suggesting that ACs were promoted via the miR-205-5p/PTEN/AKT pathway. Finally, an injectable silk fibroin (SF) hydrogel containing ACs and H-Exos (SF/ACs/H-Exos) was utilized to repair cartilage defects and effectively promote cartilage regeneration in vivo. The application of SF/ACs/H-Exos hydrogel in cartilage regeneration therefore has promising prospects. STATEMENT OF SIGNIFICANCE: Cartilage tissue engineering (CTE) has presented a promising prospect. However, the quality of seed cells is an important factor affecting the repair efficiency. Our study demonstrates for the first time that the exosomes derived from hypoxia preconditioned BMSCs (H-Exos) effectively promote the proliferation, migration and anabolism of chondrocytes and inhibit inflammation through miR-205-5p/PTEN/AKT pathway. Furthermore, we fabricated an injectable silk fibrion (SF) hydrogel to preserve and sustained release H-Exos. A complex composed of SF hydrogel, H-Exos and chondrocytes can effectively promote the regeneration of cartilage defects. Therefore, this study demonstrates that hypoxia pretreatment could optimize the therapeutic effects of BMSCs-derived exosomes, and the combination of exosomes and SF hydrogel could be a promising therapeutic method for cartilage regeneration.
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Chen Z, Yuan R, Hu S, Yuan W, Sun Z. Roles of the Exosomes Derived From Myeloid-Derived Suppressor Cells in Tumor Immunity and Cancer Progression. Front Immunol 2022; 13:817942. [PMID: 35154134 PMCID: PMC8829028 DOI: 10.3389/fimmu.2022.817942] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 01/12/2022] [Indexed: 12/23/2022] Open
Abstract
Tumor immunity is involved in malignant tumor progression. Myeloid-derived suppressor cells (MDSCs) play an irreplaceable role in tumor immunity. MDSCs are composed of immature myeloid cells and exhibit obvious immunomodulatory functions. Exosomes released by MDSCs (MDSCs-Exos) have similar effects to parental MDSCs in regulating tumor immunity. In this review, we provided a comprehensive description of the characteristics, functions and mechanisms of exosomes. We analyzed the immunosuppressive, angiogenesis and metastatic effects of MDSCs-Exos in different tumors through multiple perspectives. Immunotherapy targeting MDSCs-Exos has demonstrated great potential in cancers and non-cancerous diseases.
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Affiliation(s)
- Zhuang Chen
- Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Rui Yuan
- Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shengyun Hu
- Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Weitang Yuan
- Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhenqiang Sun
- Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Jia M, Wang Z. MicroRNAs as Biomarkers for Ionizing Radiation Injury. Front Cell Dev Biol 2022; 10:861451. [PMID: 35309926 PMCID: PMC8927810 DOI: 10.3389/fcell.2022.861451] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 02/15/2022] [Indexed: 01/04/2023] Open
Abstract
Accidental radiation exposures such as industrial accidents and nuclear catastrophes pose a threat to human health, and the potential or substantial injury caused by ionizing radiation (IR) from medical treatment that cannot be ignored. Although the mechanisms of IR-induced damage to various organs have been gradually investigated, medical treatment of irradiated individuals is still based on clinical symptoms. Hence, minimally invasive biomarkers that can predict radiation damage are urgently needed for appropriate medical management after radiation exposure. In the field of radiation biomarker, finding molecular biomarkers to assess different levels of radiation damage is an important direction. In recent years, microRNAs have been widely reported as several diseases’ biomarkers, such as cancer and cardiovascular diseases, and microRNAs are also of interest to the ionizing radiation field as radiation response molecules, thus researchers are turning attention to the potential of microRNAs as biomarkers in tumor radiation response and the radiation toxicity prediction of normal tissues. In this review, we summarize the distribution of microRNAs, the progress on research of microRNAs as markers of IR, and make a hypothesis about the origin and destination of microRNAs in vivo after IR.
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Chen YH, Zhong LF, Hong X, Zhu QL, Wang SJ, Han JB, Huang WJ, Ye BZ. Integrated Analysis of circRNA-miRNA-mRNA ceRNA Network in Cardiac Hypertrophy. Front Genet 2022; 13:781676. [PMID: 35211156 PMCID: PMC8860901 DOI: 10.3389/fgene.2022.781676] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 01/14/2022] [Indexed: 01/01/2023] Open
Abstract
Cardiac hypertrophy is an adaptive cardiac response that accommodates the variable hemodynamic demands of the human body during extended periods of preload or afterload increase. In recent years, an increasing number of studies have pointed to a potential connection between myocardial hypertrophy and abnormal expression of non-coding RNAs. Circular RNA (circRNA), as one of the non-coding RNAs, plays an essential role in cardiac hypertrophy. However, few studies have systematically analyzed circRNA-related competing endogenous RNA (ceRNA) regulatory networks associated with cardiac hypertrophy. Therefore, we used public databases from online prediction websites to predict and screen differentially expressed mRNAs and miRNAs and ultimately obtained circRNAs related to cardiac hypertrophy. Based on this result, we went on to establish a circRNAs-related ceRNA regulatory network. This study is the first to establish a circRNA-mediated ceRNA regulatory network associated with myocardial hypertrophy. To verify the results of our analysis, we used PCR to verify the differentially expressed mRNAs and miRNAs in animal myocardial hypertrophy model samples. Our findings suggest that three mRNAs (Col12a1, Thbs1, and Tgfbr3), four miRNAs (miR-20a-5p, miR-27b-3p, miR-342-3p, and miR-378a-3p), and four related circRNAs (circ_0002702, circ_0110609, circ_0013751, and circ_0047959) may play a key role in cardiac hypertrophy.
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Affiliation(s)
- Yang-Hao Chen
- The Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of WenZhou Medical University, WenZhou, China
| | - Ling-Feng Zhong
- The Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of WenZhou Medical University, WenZhou, China
| | - Xia Hong
- Coronary Care Unit, The First Affiliated Hospital of Wenzhou Medical University, WenZhou, China
| | - Qian-Li Zhu
- The Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of WenZhou Medical University, WenZhou, China
| | - Song-Jie Wang
- The Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of WenZhou Medical University, WenZhou, China
| | - Ji-Bo Han
- Department of Cardiology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Wei-Jian Huang
- The Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of WenZhou Medical University, WenZhou, China
| | - Bo-Zhi Ye
- The Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of WenZhou Medical University, WenZhou, China
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Ahmed F, Tamma M, Pathigadapa U, Reddanna P, Yenuganti VR. Drug Loading and Functional Efficacy of Cow, Buffalo, and Goat Milk-Derived Exosomes: A Comparative Study. Mol Pharm 2022; 19:763-774. [PMID: 35195427 DOI: 10.1021/acs.molpharmaceut.1c00182] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Quite recently, milk exosomes have been recognized as efficient drug delivery systems owing to their biocompatibility and easy availability for scale-up technologies. However, there are no reports of comparative studies with regards to drug delivery by milk exosomes derived from different species. In this study, we isolated and characterized milk exosomes of cow, buffalo, and goat by various techniques and tried to understand their drug loading capacity and functional efficiency in HepG2, HCT116, and A549 cells by using doxorubicin. Doxorubicin was loaded to milk exosomes by three methods, that is, incubation, saponin treatment, and sonication. The isolated exosomes were found to be spherical with a size of <200 nm and displayed specific markers, namely, CD81, HSP70, HSC70, and miRNAs. Drug loading studies revealed that goat milk exosomes had the highest loading capacity across all three methods. Doxorubicin-encapsulated goat milk exosomes resulted in the inhibition of cell viability, with low IC50 values in HepG2, HCT-116, and A549 cells. Doxorubicin-encapsulated goat exosomes displayed better IC50 values than cow and buffalo milk-derived counterparts. In line with this, the ability of doxorubicin-encapsulated goat milk exosomes to induce apoptosis in HepG2 and HCT-116 cells was higher than that of cow and buffalo milk exosomes and free doxorubicin. Furthermore, unbound goat milk exosomes significantly reduced cell viability as compared to cow and buffalo milk exosomes. The transepithelial transport assay shows that doxorubicin-loaded milk exosomes transport doxorubicin efficiently as compared to free doxorubicin in vitro. Doxorubicin released from milk exosomes shows a biphasic release pattern, burst release followed by sustained release. These observations are important in light of the emerging importance of milk-derived exosomes as drug carriers to treat cancers.
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Affiliation(s)
- Farhan Ahmed
- Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, Telangana, India
| | - Mounipriya Tamma
- Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, Telangana, India
| | - Umamaheswari Pathigadapa
- Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, Telangana, India
| | - Pallu Reddanna
- Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, Telangana, India
| | - Vengala Rao Yenuganti
- Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, Telangana, India
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Yin Z, Chen C. Biological Functions and Clinical Prospects of Extracellular Non-Coding RNAs in Diabetic Cardiomyopathy: an Updated Review. J Cardiovasc Transl Res 2022; 15:469-476. [PMID: 35175553 DOI: 10.1007/s12265-022-10217-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 02/09/2022] [Indexed: 12/17/2022]
Abstract
Diabetic cardiomyopathy (DCM) is one of the major causes of heart failure in diabetic patients. However, the pathogenesis of diabetic cardiomyopathy has not been fully elucidated. Diagnosis and therapeutic strategy of DCM is still challenging. Various non-coding RNAs (ncRNA) are implicated in the onset and progression of DCM. Interestingly, ncRNAs not only are regulators intracellularly, but also can exist and function in extracellular space. Recent evidences have demonstrated that extracellular ncRNAs play emerging roles in both intracardiac and inter-organ communication during the pathogenesis of DCM; thus, extracellular ncRNAs are attractive diagnostic biomarkers and potential therapeutic targets for DCM. This article will review the current knowledge of the roles of extracellular ncRNAs in DCM, especially focusing on their physio-pathological properties and perspectives of potential clinical translation for biomarkers and therapies. Recent evidences have demonstrated that extracellular ncRNA play emerging roles in both intracardiac and inter-organ communication involved in the pathogenesis of diabetic cardiomyopathy (DCM), thus shown as attractive diagnostic biomarkers and potential therapeutics for DCM. In the current review, we first summarize the progress regarding the paracrine role of extracellular ncRNA in DCM. miRNAs and circRNAs have been shown to mediate the communication among cardiomyocytes, endothelial cells, and vascular smooth muscle cells in the diabetic heart. Subsequently, we systematically describe that extracellular ncRNAs contribute to the crosstalk between the heart and other organs in the context of diabetes. Researches have indicated that miRNAs acted as hepatokines and adipokines to mediates the injure effect of distal organs on hearts. As for clinical application, extracellular ncRNAs are promising biomarker and have therapeutic potential. (Created with BioRender.com).
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Affiliation(s)
- Zhongwei Yin
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, 430030, China
| | - Chen Chen
- Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Ave., Wuhan, 430030, China.
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Deciphering specific miRNAs in brain tumors: a 5-miRNA signature in glioblastoma. Mol Genet Genomics 2022; 297:507-521. [PMID: 35175428 DOI: 10.1007/s00438-022-01866-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 01/26/2022] [Indexed: 12/20/2022]
Abstract
MicroRNAs are endogenous non-coding RNAs with a marked impact on the development and progression of brain tumors. However, they commonly share different expression patterns in other types of tumors, thereby exhibiting lack of tissue specificity. Here, an integrative holistic analysis of microarray data is established for deciphering dysregulated miRNAs in glioblastoma, distinguishing them from eight other CNS tumors. The identification of dysregulated miRNAs was performed in a pool of 176 patients, 118 of which diagnosed with glioblastoma. Dysregulated miRNAs commonly expressed in glioblastoma were then discriminated from those co-expressed in other CNS tumors and further characterized. Overall, 21 miRNAs were found to be commonly dysregulated in glioblastoma. Notwithstanding, 16 miRNAs also exhibited a differential expression in at least one other CNS tumor. The remaining 5, specifically, hsa-miR-21-3p, hsa-miR-338-5p, hsa-miR-485-5p, hsa-miR-491-5p and hsa-miR-1290, were solely associated to glioblastoma. This signature is in-depth characterized, with the spotlight on tumor progression, invasion and patient survival. These five endogenous molecules, differentially expressed in glioblastoma, are thus suggested as potential therapeutic targets, modulating several genes involved in major signalling pathways, including MAPK/ERK, calcium, PI3K/AKT, mTOR and Wnt. In summary, these findings lay a foundation for further research on the expression and function of specific patterns of miRNAs expression in glioblastoma, providing reference for potential novel targets.
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Preethi KA, Selvakumar SC, Ross K, Jayaraman S, Tusubira D, Sekar D. Liquid biopsy: Exosomal microRNAs as novel diagnostic and prognostic biomarkers in cancer. Mol Cancer 2022; 21:54. [PMID: 35172817 PMCID: PMC8848669 DOI: 10.1186/s12943-022-01525-9] [Citation(s) in RCA: 106] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 01/26/2022] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Detecting cancer at an early stage before clinical manifestation could be an effective strategy to decrease cancer mortality. Thus, identifying liquid biopsy biomarkers with high efficacy could be a promising approach for non-invasive diagnosis of cancer. MAIN TEXT Liquid biopsies are increasingly used as a supplement to biopsy, as it enables disease progression to be detected months before clinical and radiographic confirmation. Many bodily fluids contain exosomal microRNAs (miRNAs) which could provide a new class of biomarkers for early and minimally invasive cancer diagnosis due to the stability of miRNAs in exosomes. In this review, we mainly focused on the exosomal miRNAs (liquid biopsy) as biomarkers in the diagnosis and prognosis of various cancers. CONCLUSION Exosomal miRNAs can be used as diagnostic and prognosis biomarkers that provide unique insights and a more dynamic perspective of the progression and therapeutic responses in various malignancies. Therefore, the development of novel and more sensitive technologies that exploit exosomal miRNAs should be a priority for cancer management.
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Affiliation(s)
- K Auxzilia Preethi
- Centre for Cellular and Molecular Research, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, 600077, India
| | - Sushmaa Chandralekha Selvakumar
- Centre for Cellular and Molecular Research, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, 600077, India
| | - Kehinde Ross
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK
| | - Selvaraj Jayaraman
- Department of Biochemistry, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, 600077, India
| | - Deusdedit Tusubira
- Biochemistry Department, Mbarara University of Science and Technology, Mbarara, Uganda.
| | - Durairaj Sekar
- Centre for Cellular and Molecular Research, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, 600077, India.
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Abstract
A favorable outcome of the COVID-19 crisis might be achieved with massive vaccination. The proposed vaccines contain several different vaccine active principles (VAP), such as inactivated virus, antigen, mRNA, and DNA, which are associated with either standard adjuvants or nanomaterials (NM) such as liposomes in Moderna's and BioNTech/Pfizer's vaccines. COVID-19 vaccine adjuvants may be chosen among liposomes or other types of NM composed for example of graphene oxide, carbon nanotubes, micelles, exosomes, membrane vesicles, polymers, or metallic NM, taking inspiration from cancer nano-vaccines, whose adjuvants may share some of their properties with those of viral vaccines. The mechanisms of action of nano-adjuvants are based on the facilitation by NM of targeting certain regions of immune interest such as the mucus, lymph nodes, and zones of infection or blood irrigation, the possible modulation of the type of attachment of the VAP to NM, in particular VAP positioning on the NM external surface to favor VAP presentation to antigen presenting cells (APC) or VAP encapsulation within NM to prevent VAP degradation, and the possibility to adjust the nature of the immune response by tuning the physico-chemical properties of NM such as their size, surface charge, or composition. The use of NM as adjuvants or the presence of nano-dimensions in COVID-19 vaccines does not only have the potential to improve the vaccine benefit/risk ratio, but also to reduce the dose of vaccine necessary to reach full efficacy. It could therefore ease the overall spread of COVID-19 vaccines within a sufficiently large portion of the world population to exit the current crisis.
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Affiliation(s)
- Edouard Alphandéry
- Sorbonne Université, Muséum National d'Histoire Naturelle, UMR CNRS 7590, IRD, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, 75005 Paris, France. .,Nanobacterie SARL, 36 Boulevard Flandrin, 75116, Paris, France.,Institute of Anatomy, UZH University of Zurich, Instiute of Anatomy, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland
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