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Wen P, Dirisala A, Guo H, Liu X, Kobayashi S, Kinoh H, Anada T, Tanaka M, Kataoka K, Li J. Engineering durable antioxidative nanoreactors as synthetic organelles for autoregulatory cellular protection against oxidative stress. J Control Release 2025; 382:113683. [PMID: 40185336 DOI: 10.1016/j.jconrel.2025.113683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Revised: 03/24/2025] [Accepted: 04/01/2025] [Indexed: 04/07/2025]
Abstract
Polymersomes, which are polymer vesicles containing an aqueous cavity enclosed in a polymer membrane, hold enormous potential for biomedical applications. In recent years, enzyme-loaded polymersomes, serving as therapeutic nanoreactors, have drawn substantial interest. A crucial requirement for effective catalytic function is to impart semipermeability to the vesicular membrane while maintaining its role as a protective barrier for encapsulated enzymes. However, achieving both long-term stability and optimal membrane permeability for sustained functionality remains a challenge in many reported examples. In this study, we introduce ROS-responsive polyion complex vesicles (PICsomes) loaded with antioxidant enzymes (catalase) as antioxidative nanoreactors. The intrinsic semipermeability and crosslinked network structure of the membrane enable long-lasting catalytic function of catalase. The nanoreactor exhibits inherent cell-protective properties against oxidative stress in fibroblasts due to the ROS-scavenging ability of polymers. Notably, triggered by ROS, the nanoreactor demonstrates autoregulatory control of redox homeostasis. This is because the cysteamine released by PICsomes not only acts as a free radical scavenger but also facilitates the transport of L-cysteine into cells, thereby enhancing glutathione (GSH) biosynthesis. The results further demonstrate significant long blood circulation of PICsomes loaded with catalase and strong protection effects against bloodstream oxidative stress, paving the way for the further development of truly effective in vivo therapeutics. These findings underscore the potential of the engineered antioxidative nanoreactor with durable functionality as synthetic organelles for cellular protection against oxidative stress.
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Affiliation(s)
- Panyue Wen
- Institute for Materials Chemistry and Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
| | - Anjaneyulu Dirisala
- Innovation Center of Nanomedicine, Kawasaki Institute of Industrial Promotion, 3-25-14, Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan
| | - Haochen Guo
- Innovation Center of Nanomedicine, Kawasaki Institute of Industrial Promotion, 3-25-14, Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan
| | - Xueying Liu
- Innovation Center of Nanomedicine, Kawasaki Institute of Industrial Promotion, 3-25-14, Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan
| | - Shingo Kobayashi
- Institute for Materials Chemistry and Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
| | - Hiroaki Kinoh
- Innovation Center of Nanomedicine, Kawasaki Institute of Industrial Promotion, 3-25-14, Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan
| | - Takahisa Anada
- Institute for Materials Chemistry and Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
| | - Masaru Tanaka
- Institute for Materials Chemistry and Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
| | - Kazunori Kataoka
- Innovation Center of Nanomedicine, Kawasaki Institute of Industrial Promotion, 3-25-14, Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
| | - Junjie Li
- Institute for Materials Chemistry and Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
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Huang J, Chen L, Li W, Chang CJ. Anti-inflammatory and antioxidative effects of Perilla frutescens-derived extracellular vesicles: Insights from Zebrafish models. Mol Immunol 2025; 182:126-138. [PMID: 40267772 DOI: 10.1016/j.molimm.2025.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 04/15/2025] [Accepted: 04/17/2025] [Indexed: 04/25/2025]
Abstract
Plant-derived extracellular vesicles have recently been extracted and recognized as promising bioactive molecules, owing to their distinctive biological properties and inherent therapeutic activities. In this study, we investigated the physicochemical characteristics, bioactive properties, and therapeutic potential of Perilla frutescens-derived exosome-like nanoparticles (PELNs). Transmission electron microscopy (TEM) revealed that PELNs exhibited a cup-shaped morphology, with a lipid bilayer and a size distribution ranging from 40 to 200 nm (mean: 68.4 ± 13.0 nm). The cargoes in PELNs were analyzed through multi-omics and small RNA sequencing. In vivo studies on zebrafish demonstrated that PELNs are non-toxic at experimental concentrations. A reduction in neutrophil migration to injured fins evidenced the anti-inflammatory properties of PELNs. Furthermore, a meta-analysis of transcriptomic data identified hundreds of differentially expressed genes (DEGs) across 12 samples of three experimental groups. These DEGs were annotated into three categories following gene ontology (GO) enrichment analysis. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these DEGs were involved in immune-related pathways, including complement and coagulation cascades, systemic lupus erythematosus, PPAR signaling pathways, and antigen processing and presentation. Twelve selected DEGs were validated by quantitative real-time PCR (qRT-PCR), with particular confirmation of the mpx and lcp1 genes via in situ hybridization. Furthermore, PELNs demonstrated antioxidative effects by mitigating reactive oxygen species (ROS) levels, as evidenced by measurements of four oxidative stress (OS) indicators (i.e., SOD, CAT, GSH, and MDA) in zebrafish larvae subjected to H2O2-induced OS. In summary, PELNs exhibit substantial anti-inflammatory and antioxidant properties, underscoring their potential as therapeutic agents for treating various inflammatory diseases.
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Affiliation(s)
- Jinghong Huang
- Engineering Research Center of Molecular Medicine of Ministry of Education, Key Laboratory of Fujian Molecular Medicine, Key Laboratory of Xiamen Marine and Gene Drugs, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen, Fujian 362021, China; School of Medicine, Huaqiao University, Quanzhou, Fujian 362021, China
| | - Linxin Chen
- Department of Traditional Chinese Medicine, Xiamen Chang Gung Hospital, Xiamen, Fujian 301028, China
| | - Wenhua Li
- Engineering Research Center of Molecular Medicine of Ministry of Education, Key Laboratory of Fujian Molecular Medicine, Key Laboratory of Xiamen Marine and Gene Drugs, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen, Fujian 362021, China; School of Medicine, Huaqiao University, Quanzhou, Fujian 362021, China.
| | - Chih-Jung Chang
- School of Medicine, Huaqiao University, Quanzhou, Fujian 362021, China; Medical Research Center, Xiamen Chang Gung Hospital, Xiamen, Fujian 301028, China; Xiamen Chang Gung Allergology Consortium, Xiamen Chang Gung Hospital, Xiamen, Fujian 301028, China.
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Safaei M, Rajabi SS, Tirgar M, Namdar N, Dalfardi M, Mohammadifar F, Goodarzi A, Farmani AR, Ramezani V, Abpeikar Z. Exosome-based approaches in cancer along with unlocking new insights into regeneration of cancer-prone tissues. Regen Ther 2025; 29:202-216. [DOI: https:/doi.org/10.1016/j.reth.2025.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2025] Open
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Atabay M, Inci F, Saylan Y. Computational studies for the development of extracellular vesicle-based biosensors. Biosens Bioelectron 2025; 277:117275. [PMID: 39999607 DOI: 10.1016/j.bios.2025.117275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 12/25/2024] [Accepted: 02/14/2025] [Indexed: 02/27/2025]
Abstract
Cancer affects millions of people, and early detection and efficient treatment are two strong levers to hurdle this disease. Recent studies on exosomes, a subset of extracellular vesicles, have deliberately shown the potential to function as a biomarker or treatment tool, thereby attracting the attention of researchers who work on developing biosensors. Due to the ability of computational methods to predict of the behavior of biomolecules, the combination of experimental and computational methods would enhance the analytical performance of the biosensor, including sensitivity, accuracy, and specificity, even detecting such vesicles from bodily fluids. In this regard, the role of computational methods such as molecular docking, molecular dynamics simulation, and density functional theory is overviewed in the development of biosensors. This review highlights the investigations and studies that have been reported using these methods to design exosome-based biosensors. This review concludes with the role of the quantum mechanics/molecular mechanics method in the investigation of chemical processes of biomolecular systems and the deficiencies in using this approach to develop exosome-based biosensors. In addition, the artificial intelligence theory is explained briefly to show its importance in the study of these biosensors.
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Affiliation(s)
- Maryam Atabay
- UNAM-National Nanotechnology Research Center, Bilkent University, Ankara, Turkey; Department of Chemistry, Hacettepe University, Ankara, Turkey
| | - Fatih Inci
- UNAM-National Nanotechnology Research Center, Bilkent University, Ankara, Turkey; Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, Turkey
| | - Yeşeren Saylan
- Department of Chemistry, Hacettepe University, Ankara, Turkey.
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Safaei M, Rajabi SS, Tirgar M, Namdar N, Dalfardi M, Mohammadifar F, Goodarzi A, Farmani AR, Ramezani V, Abpeikar Z. Exosome-based approaches in cancer along with unlocking new insights into regeneration of cancer-prone tissues. Regen Ther 2025; 29:202-216. [PMID: 40225049 PMCID: PMC11992408 DOI: 10.1016/j.reth.2025.03.005] [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: 02/09/2025] [Revised: 03/01/2025] [Accepted: 03/18/2025] [Indexed: 04/15/2025] Open
Abstract
Most eukaryotic cells secrete extracellular vesicles called exosomes, which are involved in intercellular communication. Exosomes play a role in tumor development and metastasis by transporting bioactive chemicals from cancerous cells to other cells in local and distant microenvironments. However, the potential of exosomes can be used by engineering them and considering different therapeutic approaches to overcome tumors. Exosomes are a promising drug delivery approach that can help decrease side effects from traditional treatments like radiation and chemotherapy by acting as targeted agents at the tumor site. The present review provides an overview of exosomes and various aspects of the role of exosomes in cancer development, which include these items: exosomes in cancer diagnosis, exosomes and drug delivery, exosomes and drug resistance, exosomal microRNAs and exosomes in tumor microenvironment, etc. Cancer stem cells release exosomes that nurture tumors, promoting unwanted growth and regeneration, and these types of exosomes should be inhibited. Ironically, exosomes from other cells, such as hepatocytes or mesenchymal stem cells (MSCs), are vital for healing organs like the liver and repairing gastric ulcers. Without proper treatment, this healing process can backfire, potentially leading to disease progression or even cancer. What can be found from various studies about the role of exosomes in the field of cancer is that exosomes act like a double-edged sword; on the other hand, natural exosomes in the body may play an important role in the process and progression of cancer, but by engineering exosomes, they can be directed towards target therapy and targeted delivery of drugs to tumor cells. By examining the role and application of exosomes in various mechanisms of cancer, it is possible to help treat this disease more efficiently and quickly in preclinical and clinical research.
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Affiliation(s)
- Mohsen Safaei
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Seyedeh Somayeh Rajabi
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Mahtab Tirgar
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Najmeh Namdar
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Mahsa Dalfardi
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Farnia Mohammadifar
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Arash Goodarzi
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Ahmad Reza Farmani
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Vahid Ramezani
- Department of Pharmaceutics, School of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Zahra Abpeikar
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
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Assefa F, Park EK. Spexin-induced MC3T3-E1 cell-derived exosomes enhance osteoblast differentiation. J Bone Miner Metab 2025:10.1007/s00774-025-01604-z. [PMID: 40434546 DOI: 10.1007/s00774-025-01604-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 04/22/2025] [Indexed: 05/29/2025]
Abstract
INTRODUCTION The roles of exosomes in osteoblast differentiation has been widely investigated. Low exosome production from donor cells constitutes the greatest challenges in exosome-based therapies. Spexin (SPX) is a neuropeptide that is involved in various biological activities including osteogenic differentiation and bone regeneration. Therefore, the purpose of this study was to investigate the effects of SPX on exosome production in osteogenic medium (OM)-treated MC3T3-E1 cells and SPX induced MC3T3-E1 cell-derived exosomes (OM + SPX-Exos) on osteoblast differentiation. MATERIALS AND METHODS To evaluate exosome yield, MC3T3-E1 cells were treated with SPX. Exosome marker expression and particle number were validated via reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and nanoparticle tracking analysis (NTA), respectively. MC3T3-E1 cells were then treated with various concentrations of OM + SPX-Exos and osteogenic medium treated MC3T3-E1 derived exosomes (OM-Exos). Cell proliferation, osteogenic differentiation marker expression, alkaline phosphatase (ALP) activity, and mineralization were evaluated using the CCK-8 assay, RT-qPCR, ALP staining, and alizarin red S staining, respectively. RESULTS SPX significantly increased exosome production and the expression of the exosome markers; Cd63, Rab27a and Alix in MC3T3E1 cells. Furthermore, OM + SPX-Exos significantly increased in the expression of runt-related transcription factor 2 (Runx2), alkaline phosphatase, biomineralized associated (Alpl), collagen type I alpha 1 (Col1a1), secreted phosphoprotein 1 (Spp1) and Integrin-binding sialoprotein (Ibsp) at a concentration of 5 µg/ml. ALP staining and alizarin red S staining also revealed that OM + SPX-Exos (5 µg/ml) resulted in more ALP-positive cells and markedly promoted mineralization, respectively. CONCLUSION In general, these results indicate that SPX stimulates exosome production. OM + SPX-Exos enhances MC3T3-E1 cells proliferation, osteogenic differentiation and mineralization.
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Affiliation(s)
- Freshet Assefa
- Department of Biochemistry, College of Medicine and Health Sciences, Hawassa University, P.O.Box 1560, Hawassa, Ethiopia.
| | - Eui Kyun Park
- Department of Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu, 41940, Republic of Korea
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Soltanmohammadi F, Mahmoudi Gharehbaba A, Javadzadeh Y. Synergistic strategies in tissue engineering: The role of exosomes and decellularized extracellular matrix hydrogels. Biomed Pharmacother 2025; 188:118200. [PMID: 40414001 DOI: 10.1016/j.biopha.2025.118200] [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: 03/12/2025] [Revised: 05/07/2025] [Accepted: 05/21/2025] [Indexed: 05/27/2025] Open
Abstract
Tissue engineering aims to mimic the natural microenvironment of biological structures by utilizing the distinctive characteristics of extracellular matrix (ECM) scaffolds. The combination of decellularized extracellular matrix hydrogels (dECMHs) with exosomes (EXs) represents an innovative therapeutic approach for tissue regeneration. These dECMHs, sourced from diverse tissues, provide biocompatible scaffolds that conform to irregular defect geometries, thereby addressing the limitations of conventional ECM scaffolds. EXs, which are nanovesicles secreted by virtually all cells, play crucial role in cell communication and tissue regeneration. However, their short half-life presents challenges for systemic administration. The incorporation of EXs into dECMHs enables localized and prolonged release, thereby enhancing their therapeutic merits. This review thoroughly explains the techniques for decellularization, the characteristics of dECM, as well as the preparation and applications of dECMHs in tissue engineering. It also explores the synergistic effects of EX-dECMH systems on cellular activities essential for tissue repair, including proliferation, differentiation, and neovascularization. The mechanisms of EX release from dECMHs and their applications in the regeneration of skin, intervertebral disc, cartilage, and nerve tissues are elucidated, highlighting the considerable potential of this integrated strategy to improve tissue engineering techniques. Furthermore, the synergistic effect of EX-dECMH systems in tissue healing is investigated. Finally, the limitations associated with the clinical application of EX, dECM, and dECMH as well as the future prospect are included.
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Affiliation(s)
- Fatemeh Soltanmohammadi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Adel Mahmoudi Gharehbaba
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Yousef Javadzadeh
- Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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8
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Wen X, Hao Y. The combined application of exosomes/exosome-based drug preparations and ultrasound. J Mater Chem B 2025. [PMID: 40390561 DOI: 10.1039/d4tb01530d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/21/2025]
Abstract
Exosomes are small extracellular vesicles with a diameter of 30-150 nm, secreted by a variety of cells and containing various active substances such as nucleic acids, proteins and lipids. The use of exosomes as drug carriers for targeted delivery of therapeutics has been studied for a long time. Ultrasound is recognized as a non-invasive diagnostic and therapeutic method for assisting drug loading and targeted delivery, cellular uptake and therapy. In this review, we summarize the applications of ultrasound in assisting drug loading into exosomes, targeted delivery of exosome-based drug formulations, cellular uptake, and therapy, and explore the prospects for the combined application of exosomes/exosome-based drug formulations and ultrasound.
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Affiliation(s)
- Xiuli Wen
- Department of Ultrasound, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518116, P. R. China.
| | - Yi Hao
- Department of Ultrasound, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518116, P. R. China.
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Hussain QM, Al-Hussainy AF, Sanghvi G, Roopashree R, Kashyap A, Anand DA, Panigrahi R, Shavazi N, Taher SG, Alwan M, Jawad M, Mushtaq H. Dual role of miR-155 and exosomal miR-155 in tumor angiogenesis: implications for cancer progression and therapy. Eur J Med Res 2025; 30:393. [PMID: 40383762 PMCID: PMC12087080 DOI: 10.1186/s40001-025-02618-z] [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: 02/08/2025] [Accepted: 04/18/2025] [Indexed: 05/20/2025] Open
Abstract
Tumor angiogenesis facilitates cancer progression by supporting tumor growth and metastasis. MicroRNA-155 (miR-155) plays a pivotal role in regulating angiogenesis through both direct effects on tumor and endothelial cells and indirect modulation via exosomal communication. This review highlights miR-155's pro-angiogenic influence on endothelial cell behavior and tumor microenvironment remodeling. Additionally, exosomal miR-155 enhances intercellular communication, promoting vascularization in several cancers. Emerging therapeutic strategies include miR-155 inhibition using antagomirs, exosome-mediated delivery systems, and modulation of pathways such as JAK2/STAT3 and TGF-β/SMAD2. Targeting miR-155 represents a promising approach to hinder tumor angiogenesis and improve cancer therapy outcomes.
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Affiliation(s)
| | | | - Gaurav Sanghvi
- Marwadi University Research Center, Department of Microbiology, Faculty of Science, Marwadi University, Rajkot, Gujarat, 360003, India
| | - R Roopashree
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to Be University), Bangalore, Karnataka, India
| | - Aditya Kashyap
- Centre for Research Impact and Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, Punjab, 140401, India
| | - D Alex Anand
- Department of Biomedical, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
| | - Rajashree Panigrahi
- Department of Microbiology, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to Be University), Bhubaneswar, Odisha, 751003, India
| | - Nargiz Shavazi
- Department of Obstetrics and Gynecology, Samarkand State Medical University, Samarkand, Uzbekistan
| | - Sada Ghalib Taher
- College of Dentistry, University of Thi-Qar, Thi-Qar, 64001, Iraq
- National University of Science and Technology, Thi-Qar, Iraq
| | - Mariem Alwan
- Pharmacy College, Al-Farahidi University, Baghdad, Iraq
| | - Mahmood Jawad
- Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq
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Milczek-Haduch D, Żmigrodzka M, Witkowska-Piłaszewicz O. Extracellular Vesicles in Sport Horses: Potential Biomarkers and Modulators of Exercise Adaptation and Therapeutics. Int J Mol Sci 2025; 26:4359. [PMID: 40362597 PMCID: PMC12073050 DOI: 10.3390/ijms26094359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2025] [Revised: 04/29/2025] [Accepted: 05/01/2025] [Indexed: 05/15/2025] Open
Abstract
Significant systemic metabolic benefits result from even a single exercise session by activating multiple metabolic and signaling pathways within the organism. Among these mechanisms, extracellular vesicles (EVs) play a critical role by delivering their molecular cargo to neighboring or distant cells, thereby influencing cellular metabolism and function. As research progresses, EVs represent an exciting frontier in exercise science and fitness adaptation processes. There is increasing interest in understanding the physiology of EVs as signaling particles and their use as minimally invasive diagnostic and prognostic biomarkers in the early detection of oxidative stress-related abnormalities. They also show potential to be used in monitoring exercise progress, injury prevention, or recovery, and may provide insights for personalized training programs. This review examines the current understanding of the role of physical activity in generating exercise-responsive EVs. It highlights the potential applications of EVs in exercise science and personalized fitness optimization, not only for human athletes but also for exercising animals such as horses. On the other hand, it also presents potential difficulties that researchers currently working on this topic may encounter due to technical limitations.
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Affiliation(s)
- Dominika Milczek-Haduch
- Department of Large Animals Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland
- Department of Morphological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland
| | - Magdalena Żmigrodzka
- Department of Pathology and Veterinary Diagnostic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland;
| | - Olga Witkowska-Piłaszewicz
- Department of Large Animals Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland
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11
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Tao K, Tao K, Wang J. The potential mechanisms of extracellular vesicles in transfusion-related adverse reactions: Recent advances. Transfus Clin Biol 2025; 32:205-227. [PMID: 40180029 DOI: 10.1016/j.tracli.2025.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 03/15/2025] [Accepted: 03/25/2025] [Indexed: 04/05/2025]
Abstract
Blood transfusion is an irreplaceable clinical treatment. Blood components are differentiated and stored according to specific guidelines. Storage temperatures and times vary depending on the blood component, but they all release extracellular vesicles (EVs) during storage. Although blood transfusions can be life-saving, they can also cause many adverse transfusion reactions, among which the effects of EVs are of increasing interest to researchers. EVs are submicron particles that vary in size, composition, and surface biomarkers, are encapsulated by a lipid bilayer, and are not capable of self-replication. EVs released by blood cells are important contributors to pathophysiologic states through proinflammatory, coagulant, and immunosuppressive effects, which in turn promote or inhibit the associated disease phenotype. Therefore, this review explores the potential mechanisms of hematopoietic-derived EVs in transfusion-associated adverse reactions and discusses the potential of the latest proteomics tools to be applied to the analysis of EVs in the field of transfusion medicine with a view to reducing the risk of blood transfusion.
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Affiliation(s)
- Keyi Tao
- Panzhihua University, Panzhihua 617000 Sichuan, China
| | - Keran Tao
- Institute of Medicine and Nursing, Hubei University of Medicine, Shiyan 442000 Hubei, China
| | - Jing Wang
- Southwest Medical University, Luzhou 646000 Sichuan, China; Department of Blood Transfusion, The Affiliated Hospital of Southwest Medical University, Luzhou Sichuan, 646000 China.
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12
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Garg V, Mukesh M, Kumar U, Kumar D, Amarjeet, Mahajan R, Kataria RS, Kumari P, Sodhi M. Characterization of metabolite profiles in milk derived exosomes from indicus, crossbred and taurine cows by proton nuclear magnetic resonance analysis. Food Chem 2025; 473:143015. [PMID: 39889637 DOI: 10.1016/j.foodchem.2025.143015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 01/07/2025] [Accepted: 01/20/2025] [Indexed: 02/03/2025]
Abstract
This study presents metabolome profiling of milk-derived exosomes (MDE) from cows of different genetic origins that is Sahiwal (Bos indicus), Holstein Friesian (Bos taurus) and Karan Fries (crossbred: cross of Bos indicus and Bos taurus) using 1H NMR spectroscopy. Diverse arrays of 41 metabolites were identified in all MDE groups. Comparative profiling across the three MDE groups revealed 16 metabolites to be differentially abundant (p < 0.01; log 2(FC) > 1; VIP >1) and all of these were enriched in SW-MDE. On pairwise comparison, 19 metabolites showed differential abundance (p < 0.01) between SW-HF and 10 each in SW-KF and KF-HF MDE. All the metabolites except citrate and lactose exhibited abundance in SW-MDE followed by KF and HF-MDE. Most of the metabolites (alanine, leucine, isoleucine, valine, phenylalanine, O-acetyl carnitine and 3-hydroxybutyrate) enriched in SW-MDE have positive health attributes and are involved in key metabolic pathways associated with energy production, growth, intestinal proliferation, and immune regulation. The differential quantification highlighted the source specific metabolome of MDE and also the advantageous nutritional and therapeutic potential of indicus cow milk derived exosomes.
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Affiliation(s)
- Vidhi Garg
- ICAR- National Bureau of Animal Genetic Resources, Karnal, Haryana, India; Kurukshetra University, Kurukshetra, Haryana, India
| | - Manishi Mukesh
- ICAR- National Bureau of Animal Genetic Resources, Karnal, Haryana, India
| | - Umesh Kumar
- ICAR- National Bureau of Animal Genetic Resources, Karnal, Haryana, India
| | - Dinesh Kumar
- Centre of BioMedical Research, Lucknow, Uttar Pradesh, India
| | - Amarjeet
- ICAR- National Bureau of Animal Genetic Resources, Karnal, Haryana, India
| | - Ritu Mahajan
- Kurukshetra University, Kurukshetra, Haryana, India
| | - Ranjit S Kataria
- ICAR- National Bureau of Animal Genetic Resources, Karnal, Haryana, India
| | - Parvesh Kumari
- ICAR- National Bureau of Animal Genetic Resources, Karnal, Haryana, India
| | - Monika Sodhi
- ICAR- National Bureau of Animal Genetic Resources, Karnal, Haryana, India.
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13
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Lei Y, Shu D, Xia J, Zhang T, Wei H. Extracellular nicotinamide phosphoribosyltransferase visfatin activates JAK2-STAT3 pathway in cancer-associated fibroblasts to promote colorectal cancer metastasis. Genes Genomics 2025; 47:615-624. [PMID: 39643827 PMCID: PMC12081565 DOI: 10.1007/s13258-024-01596-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Accepted: 10/29/2024] [Indexed: 12/09/2024]
Abstract
BACKGROUND Metastasis is one of the major challenges in the treatment of colorectal cancer (CRC), during which cancer-associated fibroblasts (CAFs) in the tumor microenvironment are critically involved. OBJECTIVE In this study, we aim to explore the regulatory role of extracellular nicotinamide phosphoribosyltransferase Visfatin and its impact on CRC metastasis. METHODS To examine the effect of visfatin on CAFs, human CRC tissue-derived CAFs were exposed to visfatin, and the expression of inflammatory factors, activation of JAK-STAT pathway and production of ROS in CAFs were assessed. To examine the effect of visfatin-treated CAFs on CRC metastasis, human CRC cell line SW480 or SW620 were cultured with the conditioned medium derived from visfatin-treated CAFs, and the invasion and migration ability of SW480 or SW620 cells were evaluated by transwell migration and matrigel invasion assays. RESULTS Our previous study found that visfatin, a secreted form of nicotinamide phosphoribosyltransferase that governs the rate-limiting step of NAD synthesis, promoted CRC metastasis. However, little is known about the effect of visfatin on CAFs. The conditioned medium derived from visfatin- treated CAFs promotes the migratory and invasive capability of CRC cells, and enhance lung metastasis in mouse model. Visfatin treatment stimulated the expression of a couple of inflammatory factors in CAFs, which was mediated by visfatin-induced activation of JAK- STAT pathway and accumulation of ROS. Inhibition of JAK-STAT pathway or neutralization of cellular ROS attenuated visfatin-mediated migration and invasion of CRC cells. CONCLUSIONS The present work highlights a critical role of visfatin in the crosstalk between CRC cells and CAFs, which moonlight as a non-metabolic extracellular signal molecule to hijacks JAK-STAT pathway in CAFs to promote CRC metastasis.
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Affiliation(s)
- Yun Lei
- Pathological Diagnosis Center, Zhoushan Hospital of Zhejiang Province, Zhejiang, China
| | - Dan Shu
- School of Bioscience and Technology, Chengdu Medical College, Chengdu, China
| | - Jianyu Xia
- School of Basic Medical Science, Chengdu Medical College, Chengdu, China
| | - Tao Zhang
- School of Bioscience and Technology, Chengdu Medical College, Chengdu, China.
- The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China.
| | - He Wei
- School of Bioscience and Technology, Chengdu Medical College, Chengdu, China.
- The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China.
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14
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Rajavel A, Kumar J, Essakipillai N, Anbazhagan R, Panneerselvam R, Ramakrishnan J, Venkataraman V, Natesan Sella R. Label-free Detection of Urine Extracellular Vesicles from Duchenne Muscular Dystrophy Patients Using Surface-Enhanced Raman Spectroscopy Combined with Machine Learning Models. ACS OMEGA 2025; 10:16874-16883. [PMID: 40321535 PMCID: PMC12044490 DOI: 10.1021/acsomega.5c00838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 03/01/2025] [Accepted: 03/06/2025] [Indexed: 05/08/2025]
Abstract
Duchenne muscular dystrophy (DMD) is a neuromuscular disease that affects males in the pediatric age group. Currently, there is no painless, cost-effective prognostic method available to monitor DMD progression. The main hypothesis of this study was that the biochemical composition of extracellular vesicles (EVs) isolated from the urine of DMD patients can be distinctly differentiated from that of healthy controls using surface-enhanced Raman Spectroscopy (SERS) combined with machine learning models. This differentiation is expected to provide a noninvasive, rapid, and accurate diagnostic tool for the early detection, staging, and monitoring of DMD by identifying the molecular signatures captured by SERS and leveraging the analytical power of machine learning algorithms. We collected fasting morning urine samples from 52 DMD patients and 17 healthy controls and isolated EVs using a Total Exosome Isolation kit. The SERS substrates are prepared using silver nanoparticles, which were employed to capture the molecular fingerprints of the EVs with uniformity and reproducibility, achieving relative standard deviation values of 7.3% and 8.9%. We observed alterations in phenylalanine and α-helical proteins in patients with DMD compared to controls. These spectral data were analyzed using PCA, Support Vector Machines, and k-Nearest Neighbor (KNN) algorithms to identify distinct patterns and stage DMD based on biochemical composition. Our integrated approach demonstrated 60% sensitivity and 100% specificity in distinguishing DMD patients from healthy controls, highlighting the potential of SERS and KNN for noninvasive, accurate, and rapid diagnosis of DMD. This method offers a promising avenue for early detection and personalized treatment strategies, ultimately improving patient outcomes and quality of life.
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Affiliation(s)
- Archana Rajavel
- Membrane
Protein Interaction Laboratory, Department of Genetic Engineering,
School of Bioengineering, SRM Institute
of Science and Technology, Kattankulathur, Chengalpattu 603 203, Tamil Nadu, India
| | - Jayasree Kumar
- Raman
Research Laboratory (RARE Lab), Department of Chemistry, SRM University-AP, Andhra Pradesh, Amaravati 522502, India
| | - Narayanan Essakipillai
- Department
of Computer Applications, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu 603 203, Tamil Nadu, India
| | - Ramajayam Anbazhagan
- Department
of Mathematics, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu 603 203, Tamil Nadu, India
| | - Rajapandiyan Panneerselvam
- Raman
Research Laboratory (RARE Lab), Department of Chemistry, SRM University-AP, Andhra Pradesh, Amaravati 522502, India
| | - Jayashree Ramakrishnan
- Department
of Computer Applications, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu 603 203, Tamil Nadu, India
| | - Viswanathan Venkataraman
- Department
of Paediatrics Neurology, Apollo Children’s
Hospital, Thousands Lights, Chennai 600 006, Tamil Nadu, India
| | - Raja Natesan Sella
- Membrane
Protein Interaction Laboratory, Department of Genetic Engineering,
School of Bioengineering, SRM Institute
of Science and Technology, Kattankulathur, Chengalpattu 603 203, Tamil Nadu, India
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15
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Galardi A, Di Paolo V, Lavarello C, Russo I, Romanzo A, Miele E, Vito RD, Longo D, Petretto A, Locatelli F, Di Giannatale A. Case Report: Proteomic analysis of cerebrospinal fluid in a retinoblastoma patient. Front Oncol 2025; 15:1511594. [PMID: 40342827 PMCID: PMC12058659 DOI: 10.3389/fonc.2025.1511594] [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: 10/15/2024] [Accepted: 04/01/2025] [Indexed: 05/11/2025] Open
Abstract
This study focuses on the proteomic analysis of cerebrospinal fluid (CSF) in a patient with stage III retinoblastoma (RB) with the aim to identify molecular changes associated with central nervous system (CNS) relapse. The child received systemic chemotherapy and intrathecal topotecan as CNS prophylaxis, along with enucleation of the left eye. After two chemotherapy cycles, CNS relapse occurred, evidenced by positive CSF findings and magnetic resonance imaging (MRI) showing leptomeningeal involvement at the anterior skull base. The child's condition deteriorated, and two months later, he died due to progressive CNS disease. The aim of the study was to analyze serial CSF samples collected at different stages of treatment, as well as a control sample, to identify differences in CSF protein expression profiles during CNS RB relapse. Using mass spectrometry, a total of 1,029 proteins were identified across all CSF samples, samples were analyzed in duplicate ensuring technical replication. An unsupervised heatmap revealed 46 differentially expressed proteins. Over-regulated proteins in CSF-RB samples were primarily involved in inflammation, extracellular matrix remodeling, epithelial mesenchymal transition initiation, migration, invasion, and cellular metabolism (PON1, RNPEP, MCAM, NEGR1, NID1, SERPINA1, FAT2, RELN, NEGR1, and SEZ6). These processes are key drivers of cancer progression and metastasis. Proteomic analysis could be valuable in identifying proteins modulated in CSF during disease progression in RB patients, offering potential for new prognostic biomarkers.
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Affiliation(s)
- Angela Galardi
- Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS, Ospedale Pediatrico Bambino Gesù, Rome, Italy
| | - Virginia Di Paolo
- Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS, Ospedale Pediatrico Bambino Gesù, Rome, Italy
| | - Chiara Lavarello
- Core Facilities-Clinical Proteomics and Metabolomics, IRCCS, Istituto Giannina Gaslini, Genoa, Italy
| | - Ida Russo
- Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS, Ospedale Pediatrico Bambino Gesù, Rome, Italy
| | - Antonino Romanzo
- Ophthalmology Unit, IRCCS, Ospedale Pediatrico Bambino Gesù, Rome, Italy
| | - Evelina Miele
- Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS, Ospedale Pediatrico Bambino Gesù, Rome, Italy
| | - Rita De Vito
- Department of Laboratories, Pathology Unit, IRCCS, Ospedale Pediatrico Bambino Gesù, Rome, Italy
| | - Daniela Longo
- Neuroradiology Unit, Imaging Department, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
| | - Andrea Petretto
- Core Facilities-Clinical Proteomics and Metabolomics, IRCCS, Istituto Giannina Gaslini, Genoa, Italy
| | - Franco Locatelli
- Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS, Ospedale Pediatrico Bambino Gesù, Rome, Italy
- Catholic University of the Sacred Heart, Rome, Italy
| | - Angela Di Giannatale
- Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS, Ospedale Pediatrico Bambino Gesù, Rome, Italy
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16
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Pham QN, Milanova V, Tung TT, Losic D, Thierry B, Winter MA. Affinity enrichment of placental extracellular vesicles from minimally processed maternal plasma with magnetic nanowires. Analyst 2025; 150:1908-1919. [PMID: 40172922 DOI: 10.1039/d4an01414f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2025]
Abstract
Affinity based enrichment of cell/tissue specific extracellular vesicles (EVs) with magnetic materials and analysis of their molecular cargo has the potential to improve assay sensitivity/specificity compared to whole plasma analysis. For example, syncytiotrophoblast EVs (STBEVs) shed from the placenta during pregnancy carry placental diagnostic markers relevant to pregnancy complications linked to placental insufficiency such as placental alkaline phosphatase (PLAP), Neprilysin (NEP) and Placental Protein 13 (PP13). However, the need for sample pre-enrichment of EVs from plasma adds significant complexity, time and cost. We report an affinity-based cell/tissue specific EV enrichment direct from plasma based on iron-oxide magnetic nanowires (NWs) coated with reversible-addition-fragmentation-chain-transfer (RAFT) polymers and conjugated with anti-PLAP antibodies. As anticipated the complex protein environment of minimally processed plasma significantly decreased STBEV enrichment yield. However, an optimized RAFT polymeric coating successfully mitigated the detrimental effect of the protein corona, yielding significantly improved STBEV recovery compared to Dynabeads™ in unenriched diluted plasma. Despite the presence of significant soluble PLAP protein, STBEV enrichment could be performed directly from the plasma of pregnant women (including preeclamptic samples) within 1.5 hours, enabling quantification of two placental protein markers PP13 and NEP with known diagnostic relevance to preeclampsia. Direct affinity-enrichment of STBEVs with high performance magnetic materials has the potential to underpin rapid clinical diagnostic assays for preeclampsia and related pregnancy complications.
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Affiliation(s)
- Quang Nghia Pham
- Future Industries Institute, University of South Australia, Mawson Lakes Campus, Mawson Lakes, Adelaide, South Australia 5095, Australia.
| | - Valentina Milanova
- Future Industries Institute, University of South Australia, Mawson Lakes Campus, Mawson Lakes, Adelaide, South Australia 5095, Australia.
| | - Tran Thanh Tung
- School of Chemical Engineering, The University of Adelaide, Adelaide, South Australia 5005, Australia
| | - Dusan Losic
- School of Chemical Engineering, The University of Adelaide, Adelaide, South Australia 5005, Australia
| | - Benjamin Thierry
- Future Industries Institute, University of South Australia, Mawson Lakes Campus, Mawson Lakes, Adelaide, South Australia 5095, Australia.
| | - Marnie A Winter
- Future Industries Institute, University of South Australia, Mawson Lakes Campus, Mawson Lakes, Adelaide, South Australia 5095, Australia.
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17
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Lee H, Lee J, Ko M, Lee KN, Kim Y, Seo B, Lee J, Jeong S, Heo K, Lee YK, Jung I, Do YR. Advanced Exosome Isolation through Electrophoretic Oscillation-Assisted Tangent-Flow Ultrafiltration with a PVDF-Fiber-Coated SiN x Nanofilter. ACS APPLIED BIO MATERIALS 2025; 8:2965-2976. [PMID: 40063836 DOI: 10.1021/acsabm.4c01821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/22/2025]
Abstract
This study introduces a comprehensive approach to enhancing SiNx nanofilters for exosome isolation from bovine milk using the electrophoretic oscillation-assisted tangent-flow ultrafiltration (EPOTF) process. Reinforcing the nanofilter with electro-spun poly(vinylidene fluoride) (PVDF) fibers significantly improved durability under high-pressure conditions, withstanding nearly 2.8 times greater pressures than nonreinforced nanofilters. The PVDF-fiber-coated nanofilters achieved a flow rate of over 70 mL min-1, compared to just 25 mL min-1 for nonreinforced nanofilters. A filter housing system with copper electrodes isolated from the solution flow path further enhanced the electrical stability of the entire system, widening the EPO voltage range while reducing the risk of corrosion and contamination. The PVDF-fiber-coated nanofilter with the electrode in a separated housing efficiently prevented clogging and bioparticle agglomeration, maintaining constant filtration performance across various voltages and duty cycles. Biochemical analyses confirmed the high concentration and structural integrity of exosomes isolated at high flow rates. Long-term tests verified the superior performance of PVDF-coated filters, successfully filtering 3400 mL of milk over 24 h. These results demonstrate the potential of these advances for highly efficient exosome isolation while maintaining the integrity and shape of exosomes, offering promise for the future of exosome isolation research.
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Affiliation(s)
- Hansol Lee
- Department of Chemistry, Kookmin University, Seoul 02707, Republic of Korea
| | - Jaehyuk Lee
- Department of Mechanical Engineering, Kyung Hee University, Yongin 17104, Republic of Korea
- Advanced Institutes of Convergence Technology 8F, R&D Center, Metapore Co., Ltd., Suwon 16229, Republic of Korea
| | - Minji Ko
- Department of Chemistry, Kookmin University, Seoul 02707, Republic of Korea
| | - Keyong Nam Lee
- Department of Chemistry, Kookmin University, Seoul 02707, Republic of Korea
| | - Yeonjae Kim
- R&D Center, Incospharm Corp., Daejeon 34000, Republic of Korea
| | - Bosung Seo
- Advanced Institutes of Convergence Technology 8F, R&D Center, Metapore Co., Ltd., Suwon 16229, Republic of Korea
| | - Jungwon Lee
- Advanced Institutes of Convergence Technology 8F, R&D Center, Metapore Co., Ltd., Suwon 16229, Republic of Korea
| | - Sekyoo Jeong
- R&D Center, Incospharm Corp., Daejeon 34000, Republic of Korea
| | - Kyun Heo
- Department of Biopharmaceutical Chemistry, Kookmin University, Seoul 02707, Republic of Korea
| | - Young Kwang Lee
- Department of Chemistry and Biochemistry, San Diego State University, San Diego, California 92182, United States
| | - Inhwa Jung
- Department of Mechanical Engineering, Kyung Hee University, Yongin 17104, Republic of Korea
| | - Young Rag Do
- Department of Chemistry, Kookmin University, Seoul 02707, Republic of Korea
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18
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Huang X, Zhu J, Wei T, Luo L, Li C, Zhao M. Epigenetic Modifications in Vitiligo. Clin Rev Allergy Immunol 2025; 68:39. [PMID: 40205284 DOI: 10.1007/s12016-025-09048-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] [Subscribe] [Scholar Register] [Accepted: 03/22/2025] [Indexed: 04/11/2025]
Abstract
Vitiligo is an autoimmune depigmenting skin disorder and can affect the mental health of the patients. Current research suggests that the development of vitiligo involves a combination of genetic susceptibility, immune imbalance, and oxidative stress. However, its pathogenesis has not been fully elucidated. Epigenetic modification has gained increasing attention as an emerging way to regulate gene expression at the transcriptional or post-transcriptional level. Currently known modes of epigenetic modification include the regulation of non-coding RNAs, DNA methylation, and histone modification. Studies suggest they play important roles in tumors, immune disorders, and inflammatory diseases. In recent years, the value of epigenetics in the diagnosis, treatment, and prognosis of vitiligo has been explored. They showed the potential to serve as biomarkers and play a therapeutic role. In this review, we summarize the epigenetic modification mechanisms involved in the pathogenesis of vitiligo, including physiological processes such as immune homeostasis, melanocyte survival, cell adhesion and migration, and metabolism. This will help us fully understand the progress of epigenetic research in vitiligo and lay the foundation for targeted therapeutic-related research.
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Affiliation(s)
- Xin Huang
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China
| | - Jing Zhu
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China
| | - Tianqi Wei
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China
| | - Lingling Luo
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China
| | - Chengrang Li
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China.
| | - Ming Zhao
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China.
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19
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Premathilaka C, Kodithuwakku S, Midekessa G, Godakumara K, Ul Ain Reshi Q, Andronowska A, Orro T, Fazeli A. Bovine fecal extracellular vesicles: A novel noninvasive tool for understanding gut physiology and pathophysiology in calves. J Dairy Sci 2025; 108:4116-4130. [PMID: 39892598 DOI: 10.3168/jds.2024-25920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 12/31/2024] [Indexed: 02/04/2025]
Abstract
Dairy calf gut health is linked with development and future production. Fecal extracellular vesicles (fEV) have emerged as a noninvasive tool in elucidating gut physiology and pathophysiology. Because feces is a complex matrix, the enrichment of extracellular vesicles (EV) from ruminant or preruminant feces is difficult. Nevertheless, if enriched, they have great potential as a gut health diagnostic and monitoring tool in dairy calves. Therefore, this study aimed to devise a protocol to enrich and characterize fEV from preweaning calves. We developed an fEV enrichment method by combination of differential centrifugation and double size exclusion chromatography and then characterized the fEV from the healthy calves. The study also assessed sample storage conditions, and the results indicated that storing preprocessed fecal samples at -80°C effectively preserves EV without introducing additional nanoparticles. Finally, fEV from 10-d-old healthy and Cryptosporidium spp.-positive calves were enriched, and a comparative analysis of fEV characteristics between the 2 groups was performed. Characterization results on EV specific protein biomarkers, size profile, total protein content, zeta potential, and morphology clearly established the enrichment of fEV with the developed protocol. The fEV analysis for calves positive and negative for Cryptosporidium spp. revealed a significant decrease in average nanoparticle size and zeta potential values in Cryptosporidium spp.-infected calves. Furthermore, the enriched fEV carried protein and nucleic acid cargo which could be further analyzed for other biomarkers to predict the gut physiology and pathophysiology of calves. In conclusion, our study has successfully optimized a protocol to enrich high purity grade EV from calf feces and displayed potential diagnostic application as a noninvasive tool.
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Affiliation(s)
- Chanaka Premathilaka
- Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, 51006 Tartu, Estonia
| | - Suranga Kodithuwakku
- Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, 51006 Tartu, Estonia; Department of Animal Science, Faculty of Agriculture, University of Peradeniya, 20400 Peradeniya, Sri Lanka
| | - Getnet Midekessa
- Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, 51006 Tartu, Estonia; Department of Pathophysiology, Institute of Biomedicine and Translational Medicine, Faculty of Medicine, Tartu University, 50411 Tartu, Estonia
| | - Kasun Godakumara
- Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, 51006 Tartu, Estonia
| | - Qurat Ul Ain Reshi
- Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, 51006 Tartu, Estonia; Department of Pathophysiology, Institute of Biomedicine and Translational Medicine, Faculty of Medicine, Tartu University, 50411 Tartu, Estonia
| | - Aneta Andronowska
- Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland
| | - Toomas Orro
- Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, 51006 Tartu, Estonia
| | - Alireza Fazeli
- Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, 51006 Tartu, Estonia; Department of Pathophysiology, Institute of Biomedicine and Translational Medicine, Faculty of Medicine, Tartu University, 50411 Tartu, Estonia; Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, S10 2SF Sheffield, UK.
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20
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Han Y, Zhou Z, Li R, Wang H. Tumor-Derived Exosomal circ_0020095 Promotes Colon Cancer Cell Proliferation and Metastasis by Inhibiting M1 Macrophage Polarization. J Biochem Mol Toxicol 2025; 39:e70225. [PMID: 40165503 DOI: 10.1002/jbt.70225] [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: 06/12/2024] [Revised: 01/20/2025] [Accepted: 03/03/2025] [Indexed: 04/02/2025]
Abstract
Tumor-associated macrophages (TAM) have been shown to regulate colon cancer (CC) progression. However, it is not clear whether tumor-derived exosomal circular RNA (circRNA) regulates TAM to influence CC progression. The expression levels of circ_0020095, M1 macrophage markers, M2 macrophage markers, and interleukin-1 receptor-associated kinase 1 (IRAK1) were determined by qRT-PCR. Cell proliferation, migration and invasion were examined by EdU assay, wound healing assay and transwell assay. Exosomes derived from CC cells were used to treat M0 macrophages. M1 macrophage surface marker CD86 was detected by flow cytometry, and protein expression was examined by western blot. Then, the medium of exosome-treated M0 macrophages was used to culture CC cells to determine CC cell functions. RNA pull-down assay, RIP assay and dual-luciferase reporter assay were performed to validate interaction. Circ_0020095 had elevated expression in CC tissues and cells, and its knockdown repressed CC cell proliferation and metastasis. M0 macrophages could take by CC cell-derived exosomes to regulate circ_0020095 expression. Exosomal circ_0020095 restrained M1 macrophage polarization and increased M2 macrophage polarization to enhance CC cell progression. Besides, IRAK1 silencing could promote CC cell proliferation and metastasis by inhibiting M1 macrophage polarization, and its overexpression also abolished the effect of exosomal circ_0020095. Mechanistically, circ_0020095 could competitively bind to IGF2BP1 and then reduced the binding ability of IGF2BP1 and IRAK1 3'UTR. Tumor-derived exosomal circ_0020095 promoted CC cell progression via inhibiting M1 macrophage polarization through IGF2BP1/IRAK1 axis.
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Affiliation(s)
- Yue Han
- The Second Department of Gastrointestinal Surgery, Shandong Provincial Third Hospital, Jinan City, China
| | - Zhe Zhou
- The Second Department of Gastrointestinal Surgery, Shandong Provincial Third Hospital, Jinan City, China
| | - Rudong Li
- The Second Department of Gastrointestinal Surgery, Shandong Provincial Third Hospital, Jinan City, China
| | - Hong Wang
- The Second Department of Gastrointestinal Surgery, Shandong Provincial Third Hospital, Jinan City, China
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21
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Niland S, Eble JA. Decoding the MMP14 integrin link: Key player in the secretome landscape. Matrix Biol 2025; 136:36-51. [PMID: 39828138 DOI: 10.1016/j.matbio.2025.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 01/16/2025] [Accepted: 01/16/2025] [Indexed: 01/22/2025]
Abstract
Rapid progress has been made in the exciting field of secretome research in health and disease. The tumor secretome, which is a significant proportion of the tumor proteome, is secreted into the extracellular space to promote intercellular communication and thus tumor progression. Among the many molecules of the secretome, integrins and matrix metalloproteinase 14 (MMP14) stand out as the interplay of adhesion and proteolysis drives invasion. Integrins serve as mechanosensors that mediate the contact of cells with the scaffold of the extracellular matrix and are significantly involved in the precise positioning and activity control of the membrane-bound collagenase MMP14. As a secretome proteinase, MMP14 influences and modifies the secretome itself. While integrins and MT-MMPs are membrane bound, but can be released and are therefore border crossers between the cell surface and the secretome, the extracellular matrix is not constitutively cell-bound, but its binding to integrins and other cell receptors is a stringently regulated process. To understand the mutual interactions in detail, we first summarize the structure and function of MMP14 and how it is regulated at the enzymatic and cellular level. In particular, the mutual interactions between integrins and MMP14 include the proteolytic cleavage of integrins themselves by MMP14. We then review the biochemical, cell biological and physiological effects of MMP14 on the composition and associated functions in the tumor secretome when either bound to the cell membrane, or located on extracellular microvesicles, or as a proteolytically shed non-membrane-bound ectodomain. Novel methods of proteomics, including the analysis of extravesicular vesicles, and new methods for the quantification of MMP14 will provide new research and diagnostic tools. The proteolytic modification of the tumor secretome, especially by MMP14, may bring an additional aspect to tumor secretome studies and will have an impact on the diagnosis and most likely also on the therapy of cancer patients.
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Affiliation(s)
- Stephan Niland
- Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany
| | - Johannes A Eble
- Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany.
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22
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Saadeldin IM, Pavani KC, Gnagnarelli J, Ehab S, Assiri AM, Van Soom A. Unlocking a Decade of Research on Embryo-Derived Extracellular Vesicles: Discoveries Made and Paths Ahead. Stem Cell Rev Rep 2025; 21:698-708. [PMID: 39841368 DOI: 10.1007/s12015-025-10844-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/09/2025] [Indexed: 01/23/2025]
Abstract
Over the past decade, research on embryo-derived extracellular vesicles (EVs) has unveiled their critical roles in embryonic development and intercellular communication. EVs secreted by embryos are nanoscale lipid bilayer vesicles that carry bioactive cargo, including proteins, lipids, RNAs, and DNAs, reflecting the physiological state of the source cells. These vesicles facilitate paracrine and autocrine signaling, influencing key processes such as cell differentiation, embryo viability, and endometrial receptivity. Studies reveal that EVs can traverse the zona pellucida, transferring molecular signals that enhance blastocyst formation and support embryo-maternal crosstalk. EVs have emerged as non-invasive biomarkers for embryo quality, with their cargo providing insights into genetic integrity and developmental competence. Advances in isolation and characterization techniques have identified specific microRNA (miRNAs) and transcription factors within EVs, offering potential for use in preimplantation genetic screening (PGS) and sex determination. Moreover, EV-mediated interactions with the maternal environment are critical for successful implantation, as they modulate gene expression and immune responses in endometrial and oviductal cells. Despite these advancements, challenges persist, including the standardization of EV isolation methods and the low yield of EVs DNA from spent culture media. Future research should aim to refine analytical techniques, explore EV-miRNA profiling, and investigate the mechanisms underlying EV-mediated signaling. By addressing these gaps, EVs could revolutionize embryo selection and reproductive technologies, offering new strategies to improve outcomes in assisted reproduction and animal breeding.
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Affiliation(s)
- Islam M Saadeldin
- Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia.
- College of Medicine, Alfaisal University, Riyadh, 11533, Saudi Arabia.
| | - Krishna Chaitanya Pavani
- Department of Internal Medicine, Reproduction and Population Health, Faculty of Veterinary Medicine, University of Ghent, Salisburylaan 133, Merelbeke, B-9820, Belgium
- Department for Reproductive Medicine, Ghent University Hospital, Corneel Heymanslaan 10, Gent, 9000, Belgium
| | - Juri Gnagnarelli
- Department of Internal Medicine, Reproduction and Population Health, Faculty of Veterinary Medicine, University of Ghent, Salisburylaan 133, Merelbeke, B-9820, Belgium
| | - Seif Ehab
- Zoology Graduate Program, Department of Zoology, Faculty of Science, Cairo University, Giza, 12613, Egypt
| | - Abdullah M Assiri
- Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia
- College of Medicine, Alfaisal University, Riyadh, 11533, Saudi Arabia
| | - Ann Van Soom
- Department of Internal Medicine, Reproduction and Population Health, Faculty of Veterinary Medicine, University of Ghent, Salisburylaan 133, Merelbeke, B-9820, Belgium
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23
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Li J, Wang Z, Wei Y, Li W, He M, Kang J, Xu J, Liu D. Advances in Tracing Techniques: Mapping the Trajectory of Mesenchymal Stem-Cell-Derived Extracellular Vesicles. CHEMICAL & BIOMEDICAL IMAGING 2025; 3:137-168. [PMID: 40151822 PMCID: PMC11938168 DOI: 10.1021/cbmi.4c00085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Revised: 12/30/2024] [Accepted: 01/03/2025] [Indexed: 03/29/2025]
Abstract
Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) are nanoscale lipid bilayer vesicles secreted by mesenchymal stem cells. They inherit the parent cell's attributes, facilitating tissue repair and regeneration, promoting angiogenesis, and modulating the immune response, while offering advantages like reduced immunogenicity, straightforward administration, and enhanced stability for long-term storage. These characteristics elevate MSC-EVs as highly promising in cell-free therapy with notable clinical potential. It is critical to delve into their pharmacokinetics and thoroughly elucidate their intracellular and in vivo trajectories. A detailed summary and evaluation of existing tracing strategies are needed to establish standardized protocols. Here, we have summarized and anticipated the research progress of MSC-EVs in various biomedical imaging techniques, including fluorescence imaging, bioluminescence imaging, nuclear imaging (PET, SPECT), tomographic imaging (CT, MRI), and photoacoustic imaging. The challenges and prospects of MSC-EV tracing strategies, with particular emphasis on clinical translation, have been analyzed, with promising solutions proposed.
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Affiliation(s)
- Jingqi Li
- State
Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory
of Molecular Recognition and Biosensing, Frontiers Science Centers
for Cell Responses and New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Zhaoyu Wang
- State
Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory
of Molecular Recognition and Biosensing, Frontiers Science Centers
for Cell Responses and New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Yongchun Wei
- State
Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory
of Molecular Recognition and Biosensing, Frontiers Science Centers
for Cell Responses and New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Wenshuai Li
- State
Key Laboratory for Crop Stress Resistance and High-Efficiency Production,
Shaanxi Key Laboratory of Agricultural and Environmental Microbiology,
College of Life Sciences, Northwest A&F
University, Yangling, Shaanxi 712100, China
| | - Mingzhu He
- State
Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory
of Molecular Recognition and Biosensing, Frontiers Science Centers
for Cell Responses and New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Jingjing Kang
- State
Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory
of Molecular Recognition and Biosensing, Frontiers Science Centers
for Cell Responses and New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Jia Xu
- State
Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory
of Molecular Recognition and Biosensing, Frontiers Science Centers
for Cell Responses and New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Dingbin Liu
- State
Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory
of Molecular Recognition and Biosensing, Frontiers Science Centers
for Cell Responses and New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
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24
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Yang Y, Deng C, Aldali F, Huang Y, Luo H, Liu Y, Huang D, Cao X, Zhou Q, Xu J, Li Y, Chen H. Therapeutic Approaches and Potential Mechanisms of Small Extracellular Vesicles in Treating Vascular Dementia. Cells 2025; 14:409. [PMID: 40136659 PMCID: PMC11941715 DOI: 10.3390/cells14060409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Revised: 02/26/2025] [Accepted: 03/10/2025] [Indexed: 03/27/2025] Open
Abstract
Small extracellular vesicles (sEVs), including exosomes as a subtype, with a diameter typically less than 200 nm and originating from the endosomal system, are capable of transporting a diverse array of bioactive molecules, including proteins, nucleic acids, and lipids, thereby facilitating intercellular communication and modulating cellular functions. Vascular dementia (VaD) represents a form of cognitive impairment attributed to cerebrovascular disease, characterized by a complex and multifaceted pathophysiological mechanism. Currently, the therapeutic approach to VaD predominantly emphasizes symptom management, as no specific pharmacological treatment exists to cure the condition. Recent investigations have illuminated the significant role of sEVs in the pathogenesis of vascular dementia. This review seeks to provide a comprehensive analysis of the characteristics and functions of sEVs, with a particular focus on their involvement in vascular dementia and its underlying mechanisms. The objective is to advance the understanding of the interplays between sEVs and vascular dementia, thereby offering novel insights for future research and therapeutic strategies.
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Affiliation(s)
- Yujie Yang
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Chunchu Deng
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Fatima Aldali
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Yunjie Huang
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Hongmei Luo
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Yizhou Liu
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Danxia Huang
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Xiaojian Cao
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Qiuzhi Zhou
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Jia Xu
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
- Stem Cell Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Yajie Li
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
| | - Hong Chen
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.Y.); (C.D.); (F.A.); (Y.H.); (H.L.); (Y.L.); (D.H.); (X.C.); (Q.Z.); (J.X.); (Y.L.)
- Stem Cell Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
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25
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Buttari B, Recalchi S, Riitano G, Capozzi A, Ucci FM, Manganelli V, Fratini F, Profumo E, Garofalo T, Alessandri C, Misasi R, Conti F, Longo A, Sorice M. Extracellular microvesicles from patients with Rheumatoid arthritis promote dendritic cell activation in vitro. Front Immunol 2025; 16:1532114. [PMID: 40109338 PMCID: PMC11920144 DOI: 10.3389/fimmu.2025.1532114] [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: 11/21/2024] [Accepted: 02/20/2025] [Indexed: 03/22/2025] Open
Abstract
Introduction Rheumatoid Arthritis (RA) is a systemic autoimmune disease characterized by chronic synovial inflammation affecting diarthrodial joints, with cartilage destruction and bone erosion. Environmental inflammatory stimuli can induce maturation of dendritic cells (DCs), which promote differentiation and activation of effector T lymphocytes. We previously highlighted the role of extracellular microvesicles (EMVs) in pathogenesis by carrying antigens that trigger autoantibody production. In this investigation we verified whether EMVs may activate immature monocyte-derived DCs, inducing phenotypic and functional characteristics of mature DCs. Methods EMVs were obtained from 7 RA patients naïve to biological disease-modifying anti-rheumatic drugs (DMARDs) and tested for their capability to activate DCs from healthy donors. Results We preliminary confirmed by western blot that carbamylated and citrullinated proteins are present in EMVs from RA patients. Moreover, surface marker phenotyping indicated that EMV treated-DCs exhibit increased expression of CD83 and CD86, as well as of CD83+ HLA-DR+ CD80+ CD86+ cells, indicating that the DCs are in a mature state. Furthermore, biochemical data demonstrated that EMVs from plasma of RA patients induce MAPK and NF-κB activation in DCs. EMVs from the plasma of RA patients were also able to stimulate DCs to produce IL-12, IL-1β and IL-10, inducing a proinflammatory phenotype. Conclusions These findings demonstrate that EMVs from RA patients promote DC activation in vitro, suggesting a potential mechanism by which RA microenvironment perpetuates inflammation through the modulation of DC function. These knowledges provide new insight in the role of EMVs in the pathogenesis of RA and their potential role as therapeutic targets.
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Affiliation(s)
- Brigitta Buttari
- Department of Cardiovascular and Endocrine-metabolic Diseases, and Aging, Istituto Superiore di Sanità, Rome, Italy
| | - Serena Recalchi
- Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy
| | - Gloria Riitano
- Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy
| | - Antonella Capozzi
- Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy
| | - Federica Maria Ucci
- Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, “Sapienza” University of Rome, Rome, Italy
| | - Valeria Manganelli
- Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy
| | - Federica Fratini
- Proteomics Core Facility, Istituto Superiore di Sanità (ISS), Rome, Italy
| | - Elisabetta Profumo
- Department of Cardiovascular and Endocrine-metabolic Diseases, and Aging, Istituto Superiore di Sanità, Rome, Italy
| | - Tina Garofalo
- Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy
| | - Cristiano Alessandri
- Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, “Sapienza” University of Rome, Rome, Italy
| | - Roberta Misasi
- Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy
| | - Fabrizio Conti
- Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, “Sapienza” University of Rome, Rome, Italy
| | - Agostina Longo
- Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy
| | - Maurizio Sorice
- Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy
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26
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René CA, Parks RJ. Extracellular vesicles efficiently deliver survival motor neuron protein to cells in culture. Sci Rep 2025; 15:5674. [PMID: 39955442 PMCID: PMC11830090 DOI: 10.1038/s41598-025-90083-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 02/10/2025] [Indexed: 02/17/2025] Open
Abstract
Spinal Muscular Atrophy (SMA) is a genetic neuromuscular disorder caused by homozygous mutation or deletion of the survival motor neuron 1 (SMN1) gene, leading to a low quantity of SMN protein in cells. This depletion of SMN protein preferentially leads to death of motor neurons and, consequently, muscle atrophy, in addition to defects in many other peripheral tissues. SMN protein is naturally loaded into extracellular vesicles (EVs), which are sub-micron-sized, membrane-bound particles released from all cell types. The innate ability of EVs to deliver cargo to recipient cells has caused these vesicles to gain interest as therapeutic delivery vehicles. In this study, we show that adenovirus-mediated overexpression of SMN protein in HepG2 cells leads to the release of EVs loaded with high levels of SMN protein into conditioned medium. Application of this medium to recipient cells in tissue culture led to uptake of the SMN protein, which subsequently transited to the nucleus and co-localized with Gemin2 protein, forming nuclear gem-like structures similar to the native SMN protein. Overall, this work demonstrates that SMN protein can be delivered to cells through EVs, which holds promise as a potential therapy for patients with SMA.
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Affiliation(s)
- Charlotte A René
- Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
- Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8L1, Canada
- Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON, K1Y 4E9, Canada
| | - Robin J Parks
- Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada.
- Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8L1, Canada.
- Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON, K1Y 4E9, Canada.
- Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, ON, K1H 8L6, Canada.
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27
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Sun X, Wan J, Zhang Y, Shen Y, Tang Y, Yin Y, Chamley LW, Zhao M, Chen Q. Placental extracellular vesicles induce ovarian tumour cell death in an ex vivo explant model: Possible therapeutic potential. Placenta 2025; 160:20-28. [PMID: 39752926 DOI: 10.1016/j.placenta.2024.12.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 12/18/2024] [Accepted: 12/30/2024] [Indexed: 02/11/2025]
Abstract
INTRODUCTION Placental extracellular vesicles (EVs), lipid-enclosed particles released from the placenta, can facilitate intercellular communication and are classified as micro- or nano-EVs depending on size. Placental EVs contain molecules associated with cell proliferation and death. In this study, we investigated whether treating human ovarian tumour explants with placental EVs could induce ovarian tumour cell death. METHODS Human ovarian tumours were collected. After directly treating human ovarian tumour explants with placental EVs, cellular necrosis was observed in ovarian tumour explants by HE stains. Cell death-associated miRNAs were measured. RESULTS Expression of apoptosis and senescence-associated proteins, including NF-κβ and γ H2AX, were significantly increased, while proliferation-associated proteins were significantly reduced in the explants after exposure to placental EVs. Furthermore, miRNA-519a-5p, miRNA-512-3p and miRNA-143-3p, which were reported to promote ovarian cancer cell apoptosis or inhibition of ovarian cancer cell growth, were significantly increased, and the target genes of miRNA-519a-5p and miRNA-512-3p were significantly reduced in the explants after exposure to placental EVs. Transfection of SK-OV-3 ovarian cancer cells with a mimic of miRNA-519a-5p or miRNA-143-3p reduced the viability of these cells. DISCUSSION Our study demonstrated that placental EVs could induce necrosis in ovarian tumour explants. Increased levels of apoptosis and senescence-associated proteins and miRNAs could contribute to this change in ovarian tumour cell phenotype after exposure to placental EVs.
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Affiliation(s)
- Xinyi Sun
- Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand
| | - Jiayi Wan
- Department of Pathology, Wuxi No 2 People's Hospital, Nanjing Medical University, China
| | - Yi Zhang
- Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand
| | - Ye Shen
- Department of Family Planning, Wuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Yunhui Tang
- Department of Family Planning, The Hospital of Obstetrics & Gynaecology, Fudan University, China
| | - Yongxiang Yin
- Department of Pathology, Wuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Lawrence W Chamley
- Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand
| | - Min Zhao
- Department of Gynaecological Oncology, Wuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, China.
| | - Qi Chen
- Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand.
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28
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Ma X, Peng L, Zhu X, Chu T, Yang C, Zhou B, Sun X, Gao T, Zhang M, Chen P, Chen H. Isolation, identification, and challenges of extracellular vesicles: emerging players in clinical applications. Apoptosis 2025; 30:422-445. [PMID: 39522104 DOI: 10.1007/s10495-024-02036-2] [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] [Accepted: 10/23/2024] [Indexed: 11/16/2024]
Abstract
Extracellular vesicles (EVs) serve as critical mediators of intercellular communication, encompassing exosomes, microvesicles, and apoptotic vesicles that play significant roles in diverse physiological and pathological contexts. Numerous studies have demonstrated that EVs derived from mesenchymal stem cells (MSC-EVs) play a pivotal role in facilitating tissue and organ repair, alleviating inflammation and apoptosis, enhancing the proliferation of endogenous stem cells within tissues and organs, and modulating immune function-these functions have been extensively utilized in clinical applications. The precise classification, isolation, and identification of MSC-EVs are essential for their clinical applications. This article provides a comprehensive overview of the biological properties of EVs, emphasizing both their advantages and limitations in isolation and identification methodologies. Additionally, we summarize the protein markers associated with MSC-EVs, emphasizing their significance in the treatment of various diseases. Finally, this article addresses the current challenges and dilemmas in developing clinical applications for MSC-EVs, aiming to offer valuable insights for future research.
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Affiliation(s)
- Xiaoxiao Ma
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, People's Republic of China
| | - Lanwei Peng
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, People's Republic of China
| | - Xiaohui Zhu
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, People's Republic of China
| | - Tianqi Chu
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, People's Republic of China
| | - Changcheng Yang
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, People's Republic of China
| | - Bohao Zhou
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, People's Republic of China
| | - Xiangwei Sun
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, People's Republic of China
| | - Tianya Gao
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, People's Republic of China
| | - Mengqi Zhang
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, People's Republic of China
| | - Ping Chen
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, People's Republic of China.
| | - Haiyan Chen
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, People's Republic of China.
- East China Institute of Digital Medical Engineering, Shangrao, 334000, People's Republic of China.
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29
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Pons WF, Marcus RK. Isolation of Urinary Extracellular Vesicles (EVs) via Hydrophobic Interaction Chromatography Using a Nylon-6 Capillary-Channeled Polymer (C-CP) Fiber Column. J Sep Sci 2025; 48:e70093. [PMID: 39933961 PMCID: PMC11813829 DOI: 10.1002/jssc.70093] [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: 12/03/2024] [Revised: 01/24/2025] [Accepted: 01/26/2025] [Indexed: 02/13/2025]
Abstract
Exosomes, a subset of extracellular vesicles (EVs) ranging in size from 30 to 150 nm, are of significant interest for biomedical applications such as diagnostic testing and therapeutics delivery. Biofluids, including urine, blood, and saliva, contain exosomes that carry biomarkers reflective of their host cells. However, isolation of EVs is often a challenge due to their size range, low density, and high hydrophobicity. Isolations can involve long separation times (ultracentrifugation) or result in impure eluates (size exclusion chromatography, polymer-based precipitation). As an alternative to these methods, this study evaluates the first use of nylon-6 capillary-channeled polymer (C-CP) fiber columns to separate EVs from human urine via a step-gradient hydrophobic interaction chromatography method. Different from previous efforts using polyester fiber columns for EV separations, nylon-6 shows potential for increased isolation efficiency, including somewhat higher column loading capacity and more gentle EV elution solvent strength. The efficacy of this approach to EV separation has been determined by scanning electron and transmission microscopy, nanoparticle flow cytometry (NanoFCM), and Bradford protein assays. Electron microscopy showed isolated vesicles of the expected morphology. Nanoparticle flow cytometry determined particle densities of eluates yielding up to 5 × 108 particles mL-1, a typical distribution of vesicle sizes in the eluate (60-100 nm), and immunoconfirmation using fluorescent anti-CD81 antibodies. Bradford assays confirmed that protein concentrations in the EV eluate were significantly reduced (approx. sevenfold) from raw urine. Overall, this approach provides a low-cost and time-efficient (< 20 min) column separation to yield urinary EVs of the high purities required for downstream applications, including diagnostic testing and therapeutics.
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Affiliation(s)
- William F. Pons
- Department of ChemistryBiosystems Research ComplexClemson UniversityClemsonSouth CarolinaUSA
| | - R. Kenneth Marcus
- Department of ChemistryBiosystems Research ComplexClemson UniversityClemsonSouth CarolinaUSA
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30
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Wang J, Luo Q, Gu T, An F, Zhou Y, Min Y, Zhang R, Jiang Y. Serum-Derived Exosomal TBX2-AS1 Exacerbates COPD by Altering the M1/M2 Ratio of Macrophages through Regulating the miR-423-5p/miR-23b-3p Axis. Immunol Invest 2025; 54:271-295. [PMID: 39589066 DOI: 10.1080/08820139.2024.2434692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2024]
Abstract
OBJECTIVE To investigate the mechanism of serum exosomes in chronic obstructive pulmonary disease (COPD), especially the effect of lncRNA TBX2-AS1 on macrophage polarization. METHODS Screen differentially expressed genes through bioinformatics analysis, detect the expression of related molecules in clinical samples and cell experiments, construct a mouse model and conduct functional rescue experiments, using various experimental techniques such as RT - qPCR, Western Blot, flow cytometry, ELISA, and luciferase reporter assay. RESULTS TBX2-AS1 is highly expressed in the serum and serum exosomes of COPD patients, and it can promote macrophage M1 polarization and inhibit M2 polarization; it exerts its role by negatively regulating the miR-423-5p/miR-23b - 3p axis, where miR-423-5p inhibits CELSR2 expression to prevent M1 polarization, and miR-23b-3p inhibits NEK6 expression to promote M2 polarization; in vivo experiments, down-regulation of CELSR2/NEK6 can reverse the promoting effect of COPD serum exosomes on lung injury and inflammation. CONCLUSION COPD serum exosomes deliver TBX2-AS1 to macrophages, regulate the miR-423-5p-CELSR2/miR-23b-3p-NEK6 pathway, affect macrophage polarization, and exacerbate the progression of COPD, providing new directions and potential targets for the diagnosis and treatment of COPD.
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Affiliation(s)
- JinHai Wang
- Department of Emergency, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China
| | - Qing Luo
- Department of Internal Medicine, People's Hospital of Hainan Tibetan Autonomous Prefecture, Qinghai, Hainan Tibetan Autonomous Prefecture, China
| | - TiJun Gu
- Department of Emergency, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China
| | - FenQin An
- Department of Emergency, People's Hospital of Hainan Tibetan Autonomous Prefecture, Hainan Tibetan Autonomous Prefecture, China
| | - YunZheng Zhou
- Department of Emergency, People's Hospital of Hainan Tibetan Autonomous Prefecture, Hainan Tibetan Autonomous Prefecture, China
| | - YePing Min
- Department of Emergency, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China
| | - RuiRen Zhang
- Department of Emergency, People's Hospital of Hainan Tibetan Autonomous Prefecture, Hainan Tibetan Autonomous Prefecture, China
| | - YiMing Jiang
- Department of Emergency, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China
- Department of Emergency, People's Hospital of Hainan Tibetan Autonomous Prefecture, Hainan Tibetan Autonomous Prefecture, China
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Wang L, Zhou S, Ruan Y, Wu X, Zhang X, Li Y, Ying D, Lu Y, Tian Y, Cheng G, Zhang J, Lv K, Zhou X. Hypoxia-Challenged Pancreatic Adenocarcinoma Cell-Derived Exosomal circR3HCC1L Drives Tumor Growth Via Upregulating PKM2 Through Sequestering miR-873-5p. Mol Biotechnol 2025; 67:762-777. [PMID: 38526683 DOI: 10.1007/s12033-024-01091-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] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 01/24/2024] [Indexed: 03/27/2024]
Abstract
Pancreatic adenocarcinoma (PAAD) is a fatal disease with poor survival. Increasing evidence show that hypoxia-induced exosomes are associated with cancer progression. Here, we aimed to investigate the function of hsa_circ_0007678 (circR3HCC1L) and hypoxic PAAD cell-derived exosomal circR3HCC1L in PAAD progression. Through the exoRBase 2.0 database, we screened for a circular RNA circR3HCC1L related to PAAD. Changes of circR3HCC1L in PAAD samples and cells were analyzed with real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, migration, invasion were analyzed by colony formation, cell counting, and transwell assays. Measurements of glucose uptake and lactate production were done using corresponding kits. Several protein levels were detected by western blotting. The regulation mechanism of circR3HCC1L was verified by dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Exosomes were separated by differential ultracentrifugation. Animal experiments were used to verify the function of hypoxia-derived exosomal circR3HCC1L. CircR3HCC1L was upregulated in PAAD samples and hypoxic PAAD cells. Knockdown of circR3HCC1L decreased hypoxia-driven PAAD cell proliferation, migration, invasion, and glycolysis. Hypoxic PAAD cell-derived exosomes had higher levels of circR3HCC1L, hypoxic PAAD cell-derived exosomal circR3HCC1L promoted normoxic cancer cell malignant transformation and glycolysis in vitro and xenograft tumor growth in mouse models in vivo. Mechanistically, circR3HCC1L regulated pyruvate kinase M2 (PKM2) expression via sponging miR-873-5p. Also, PKM2 overexpression or miR-873-5p silencing offset circR3HCC1L knockdown-mediated effects on hypoxia-challenged PAAD cell malignant transformation and glycolysis. Hypoxic PAAD cell-derived exosomal circR3HCC1L facilitated PAAD progression through the miR-873-5p/PKM2 axis, highlighting the contribution of hypoxic PAAD cell-derived exosomal circR3HCC1L in PAAD.
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Affiliation(s)
- Luoluo Wang
- Department of Abdominal Minimally Invasive Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, No.1111, Jiangnan Road, Yinzhou District, Ningbo, 315040, Zhejiang, China
| | - Shuping Zhou
- Ningbo College of Health Sciences, No.51, Xuefu Road, Yinzhou District, Ningbo, 315040, Zhejiang, China.
| | - Yi Ruan
- Department of Abdominal Minimally Invasive Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, No.1111, Jiangnan Road, Yinzhou District, Ningbo, 315040, Zhejiang, China
| | - Xiang Wu
- Department of Abdominal Minimally Invasive Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, No.1111, Jiangnan Road, Yinzhou District, Ningbo, 315040, Zhejiang, China
- Medical School of Ningbo University, Ningbo, 315040, Zhejiang, China
| | - Xueming Zhang
- Department of Abdominal Minimally Invasive Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, No.1111, Jiangnan Road, Yinzhou District, Ningbo, 315040, Zhejiang, China
| | - Yi Li
- College of Computer Science and Artificial Intelligence Wenzhou University, Wenzhou, 325000, Zhejiang, China
| | - Dongjian Ying
- Department of Abdominal Minimally Invasive Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, No.1111, Jiangnan Road, Yinzhou District, Ningbo, 315040, Zhejiang, China
| | - Yeting Lu
- Department of Abdominal Minimally Invasive Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, No.1111, Jiangnan Road, Yinzhou District, Ningbo, 315040, Zhejiang, China
| | - Yuan Tian
- Department of Abdominal Minimally Invasive Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, No.1111, Jiangnan Road, Yinzhou District, Ningbo, 315040, Zhejiang, China
| | - Gong Cheng
- Department of Abdominal Minimally Invasive Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, No.1111, Jiangnan Road, Yinzhou District, Ningbo, 315040, Zhejiang, China
| | - Jing Zhang
- Department of Abdominal Minimally Invasive Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, No.1111, Jiangnan Road, Yinzhou District, Ningbo, 315040, Zhejiang, China
| | - Kaiji Lv
- Department of Abdominal Minimally Invasive Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, No.1111, Jiangnan Road, Yinzhou District, Ningbo, 315040, Zhejiang, China
| | - Xinhua Zhou
- Department of Abdominal Minimally Invasive Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, No.1111, Jiangnan Road, Yinzhou District, Ningbo, 315040, Zhejiang, China.
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Niu Z, Cui M, Fu Y, Zhou L, Wang J, Lei Y, Fan X, Wang Q, Yang J. A bibliometric analysis of exosomes in aging from 2007 to 2023. Front Med (Lausanne) 2025; 11:1488536. [PMID: 39911664 PMCID: PMC11794001 DOI: 10.3389/fmed.2024.1488536] [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: 08/30/2024] [Accepted: 11/04/2024] [Indexed: 02/07/2025] Open
Abstract
Background Aging is the primary factor contributing to the development of aging-related diseases. As research on exosomes continues to advance, its relationship with aging and aging-related diseases has become a hot topic This article analyzes the research hotspots of exosomes in aging and aging-related diseases, aiming to fill the gap in bibliometric research in this field and help researchers better understand the current status and future trends of both fundamental and clinical research in this field. Methods The articles were retrieved and exported from WoSCC on December 18, 2023. The visual analysis of countries and regions, institutions, authors, references, and keywords in exosomes of aging was conducted using VOSviewer 1.6.18, CiteSpace 6.2.R7, and Bibliometrix. Results The bibliometric analysis included 1628 articles. China and the United States emerged as the top two leading countries in this field. A total of 2,321 research institutions from 78 countries and regions were primarily led by China and the United States. Both Kapogiannis D and Goetzl E were active authors in this field. Thery C, Valadi H, and Raposo G were the important promoters in this field. Thery C proposed the method of differential centrifugation and density gradient centrifugation to extract exosomes. Valadi H discovered cells could send RNA-messages to each other by loading them into exosome-vesicles. The journal with the highest number of articles was International Journal of Molecular Sciences, while PLoS One was the most frequently cited journal. The keyword analysis revealed that future research on exosomes in aging will possibly focus on "inflammation, cellular senescence, angiogenesis, insulin resistance, and Alzheimer's disease." Conclusion We identified the research trends of exosomes in the field of aging through this bibliometric analysis. The present study provides valuable new perspectives on the history and current status of exosomes in the field of aging and aging-related diseases, and also offering guidance for future research directions.
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Affiliation(s)
- Zenghui Niu
- Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
| | - Meiyu Cui
- Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yingkun Fu
- Guanganmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Lingfeng Zhou
- Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiali Wang
- Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
- Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China
| | - Yan Lei
- Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xinrong Fan
- Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qiang Wang
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jing Yang
- Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
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Shen X, Wang L, Guo Y, Wang C, Yan W, Qu J. Dynamic Monitoring of Organelle Interactions in Living Cells via Two-Color Digitally Enhanced Stimulated Emission Depletion Super-resolution Microscopy. J Phys Chem Lett 2025; 16:596-603. [PMID: 39772647 DOI: 10.1021/acs.jpclett.4c03326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
One of the most significant advances in stimulated emission depletion (STED) super-resolution microscopy is its capacity for dynamic super-resolution imaging of living cells, including the long-term tracking of interactions between various cells or organelles. Consequently, the multicolor STED plays a pivotal role in biological research. Despite the emergence of numerous fluorescent probes characterized by low toxicity, high stability, high brightness, and exceptional specificity, enabling dynamic imaging of living cells with multicolor STED, practical implementation of multicolor STED for live-cell imaging is influenced by several factors. These factors include the power and wavelength of the STED beam, the duration of imaging, the size of the imaging area, and the complexity of sample preparation. Presently, a major limitation of multicolor STED is the requirement for high STED power, which hinders the monitoring of interactions between different cells or organelles due to the associated irreversible optical damage. To address this issue, this paper emphasizes research findings based on the digitally enhanced STED (DE-STED) technique. This method overcomes the aforementioned challenge by utilizing low STED laser power to achieve prolonged two-color STED super-resolution imaging of living cells, effectively mitigating phototoxic effects and enhancing the capacity to observe intracellular dynamics. With a depletion laser power of less than 1 mW, we achieved a resolution of about 87 nm, close to that achievable with conventional high-power STED technology.
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Affiliation(s)
- Xiaochun Shen
- College of Physics and Optoelectronic Engineering, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, State Key Laboratory of Radio Frequency Heterogeneous Integration (Shenzhen University), Shenzhen University, Shenzhen 518060, P. R. China
| | - Luwei Wang
- College of Physics and Optoelectronic Engineering, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, State Key Laboratory of Radio Frequency Heterogeneous Integration (Shenzhen University), Shenzhen University, Shenzhen 518060, P. R. China
| | - Yong Guo
- College of Physics and Optoelectronic Engineering, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, State Key Laboratory of Radio Frequency Heterogeneous Integration (Shenzhen University), Shenzhen University, Shenzhen 518060, P. R. China
| | - Chenguang Wang
- State Key Laboratory of Integrated Optoelectronics, College of Electronic Science & Engineering, Jilin University, Changchun 130012, P. R. China
| | - Wei Yan
- College of Physics and Optoelectronic Engineering, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, State Key Laboratory of Radio Frequency Heterogeneous Integration (Shenzhen University), Shenzhen University, Shenzhen 518060, P. R. China
| | - Junle Qu
- College of Physics and Optoelectronic Engineering, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, State Key Laboratory of Radio Frequency Heterogeneous Integration (Shenzhen University), Shenzhen University, Shenzhen 518060, P. R. China
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Deng Q, Yao X, Fang S, Sun Y, Liu L, Li C, Li G, Guo Y, Liu J. Mast cell-mediated microRNA functioning in immune regulation and disease pathophysiology. Clin Exp Med 2025; 25:38. [PMID: 39812911 PMCID: PMC11735496 DOI: 10.1007/s10238-024-01554-2] [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: 11/08/2024] [Accepted: 12/28/2024] [Indexed: 01/16/2025]
Abstract
Upon stimulation and activation, mast cells (MCs) release soluble mediators, including histamine, proteases, and cytokines. These mediators are often stored within cytoplasmic granules in MCs and may be released in a granulated form. The secretion of cytokines and chemokines occurs within hours following activation, with the potential to result in chronic inflammation. In addition to their role in allergic inflammation, MCs are components of the tumor microenvironment (TME). MicroRNAs (miRNAs) are small RNA molecules that do not encode proteins, but regulate post-transcriptional gene expression by binding to the 3' non-coding regions of mRNAs. This plays a crucial role in the function of MC, including the key processes of MC proliferation, maturation, apoptosis, and activation. It has been demonstrated that miRNAs are also present in extracellular vesicles (EVs) secreted by MCs. EVs derived from MCs mediate intercellular communication by carrying miRNAs, affecting various diseases including allergic diseases, intestinal disorders, neuroinflammation, and tumors. These findings provide important insights into the therapeutic mechanisms and targets of miRNAs in MCs that affect diseases. This review discusses the relevance of miRNA production by MCs in regulating their own activity and the effect of miRNAs putatively produced by other cells in the control of MC activity and their participation in selected pathologies.
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Affiliation(s)
- Qiuping Deng
- Department of Clinical Laboratory, Chengdu Jinjiang Hospital for Women's and Children's Health, Chengdu, 610016, Sichuan, China
| | - Xiuju Yao
- Department of Clinical Laboratory, 363 Hospital, Chengdu, 610016, Sichuan, China
| | - Siyun Fang
- Department of Clinical Laboratory, Chengdu Jinjiang Hospital for Women's and Children's Health, Chengdu, 610016, Sichuan, China
| | - Yueshan Sun
- Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, 610031, China
| | - Lei Liu
- Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, 610031, China
| | - Chao Li
- Department of Clinical Laboratory, Chengdu Jinjiang Hospital for Women's and Children's Health, Chengdu, 610016, Sichuan, China
| | - Guangquan Li
- Department of Clinical Laboratory, 363 Hospital, Chengdu, 610016, Sichuan, China
| | - Yuanbiao Guo
- Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, 610031, China.
| | - Jinbo Liu
- The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
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Bridi A, Sangalli JR, Nociti RP, Dos Santos AC, Alves L, Bastos NM, Ferronato GDÁ, Rosa PMDS, Fiorenza MF, Pugliesi G, Meirelles FV, Chiaratti MR, da Silveira JC, Perecin F. Small extracellular vesicles derived from the crosstalk between early embryos and the endometrium potentially mediate corpus luteum function†. Biol Reprod 2025; 112:54-69. [PMID: 39388257 DOI: 10.1093/biolre/ioae143] [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: 05/09/2023] [Revised: 10/10/2023] [Accepted: 10/08/2024] [Indexed: 10/15/2024] Open
Abstract
The first interactions among the embryo, endometrium, and corpus luteum are essential for pregnancy success. Small extracellular vesicles (sEVs) are part of these interactions. We previously demonstrated that small extracellular vesicles from in vivo- or in vitro-produced bovine embryos contain different miRNA cargos. Herein we show: (1) the presence and origin (in vivo or in vitro) of the blastocyst differentially reprograms endometrial transcriptional profiles; (2) the endometrial explant (EE) cultured with in vivo or in vitro embryos release small extracellular vesicles with different miRNA contents, and (3) the luteal explant (CLE) exposed to these small extracellular vesicles have distinct mRNA and miRNA profiles. To elucidate this, the endometrial explant were cultured in the presence or absence of a single Day-7 in vivo (EE-artificial insemination; EE-AI) or in vitro (EE-in vitro fertilization; EE-IVF) embryo. After of culture we found, in the endometrial explant, 45 and 211 differentially expressed genes associated with embryo presence and origin, respectively. Small extracellular vesicles were recovered from the conditioned media (CM) in which endometrial explant and embryos were co-cultured. Four miRNAs were differentially expressed between small extracellular vesicles from CC-EE-AI and CC-EE-IVF. Luteal explants exposed in culture to these small extracellular vesicles showed 1360 transcripts and 15 miRNAs differentially expressed. The differentially expressed genes associated with embryo presence and origin, modulating cells' proliferation, and survival. These results demonstrate that in vivo- or in vitro-produced bovine embryos induce molecular alterations in the endometrium; and that the embryo and endometrium release small extracellular vesicles capable of modifying the messenger RNA (mRNA) and miRNA profile in the corpus luteum. Therefore, the small extracellular vesicles-mediated embryo-endometrium-corpus luteum interactions possibly regulate the corpus luteum viability to ensure pregnancy success.
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Affiliation(s)
- Alessandra Bridi
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Av. Duque de Caxias Norte, 225, 13635-900, Pirassununga, Brazil
| | - Juliano Rodrigues Sangalli
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Av. Duque de Caxias Norte, 225, 13635-900, Pirassununga, Brazil
| | - Ricardo Perecin Nociti
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Av. Duque de Caxias Norte, 225, 13635-900, Pirassununga, Brazil
| | - Angélica Camargo Dos Santos
- Department of Genetics and Evolution, Federal University of São Carlos, Rodovia Washington Luís, km 235, 13565-905, São Carlos, Brazil
| | - Luana Alves
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Av. Duque de Caxias Norte, 225, 13635-900, Pirassununga, Brazil
| | - Natália Marins Bastos
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Av. Duque de Caxias Norte, 225, 13635-900, Pirassununga, Brazil
| | - Giuliana de Ávila Ferronato
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Av. Duque de Caxias Norte, 225, 13635-900, Pirassununga, Brazil
| | - Paola Maria da Silva Rosa
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Av. Duque de Caxias Norte, 225, 13635-900, Pirassununga, Brazil
| | - Mariani Farias Fiorenza
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Av. Duque de Caxias Norte, 225, 13635-900, Pirassununga, Brazil
| | - Guilherme Pugliesi
- Department of Animal Reproduction, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, 05508-270, São Paulo, Brazil
| | - Flávio Vieira Meirelles
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Av. Duque de Caxias Norte, 225, 13635-900, Pirassununga, Brazil
| | - Marcos Roberto Chiaratti
- Department of Genetics and Evolution, Federal University of São Carlos, Rodovia Washington Luís, km 235, 13565-905, São Carlos, Brazil
| | - Juliano Coelho da Silveira
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Av. Duque de Caxias Norte, 225, 13635-900, Pirassununga, Brazil
| | - Felipe Perecin
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Av. Duque de Caxias Norte, 225, 13635-900, Pirassununga, Brazil
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Liu M, Teng T. Exosomes: new targets for understanding axon guidance in the developing central nervous system. Front Cell Dev Biol 2025; 12:1510862. [PMID: 39850798 PMCID: PMC11754257 DOI: 10.3389/fcell.2024.1510862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 12/19/2024] [Indexed: 01/25/2025] Open
Abstract
Axon guidance is a key event in neural circuit development that drives the correct targeting of axons to their targets through long distances and unique patterns. Exosomes, extracellular vesicles that are smaller than 100 nm, are secreted by most cell types in the brain. Regulation of cell-cell communication, neuroregeneration, and synapse formation by exosomes have been extensively studied. However, the interaction between exosomes and axon guidance molecules is poorly understood. This review summarizes the relationship between exosomes and canonical and non-canonical guidance cues and hypothesizes a possible model for exosomes mediating axon guidance between cells. The roles of exosomes in axon outgrowth, regeneration, and neurodevelopmental disorders are also reviewed, to discuss exosome-guidance interactions as potential clinical therapeutic targets.
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Affiliation(s)
- Mingyu Liu
- Key Laboratory of Tropical Translational Medicine and Ministry of Education, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, China
- School of Stomatology, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, China
| | - Teng Teng
- Key Laboratory of Tropical Translational Medicine and Ministry of Education, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, China
- School of Basic Medicine and Life Science, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, China
- Department of Histology and Embryology, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, China
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Sel FA, Oğuz FS. Cancer and Secretomes: HLA-G and Cancer Puzzle. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2025; 1479:165-179. [PMID: 39841384 DOI: 10.1007/5584_2024_843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/23/2025]
Abstract
Among the mechanisms, cancer cells develop to elude immune system, immune regulation and the use of molecules that play important roles in immune escape stand out. One of these molecules, the human leukocyte antigen G (HLA-G), plays an important role in the maintenance of immune tolerance and contributes to the progression of cancer by exerting an immunosuppressive effect. By creating an immunosuppressive field in the microscopic environment of the tumor, the aberrant expression of HLA-G facilitates the evading of cancer cells from the immune system and contributes to the progression of the disease. It is important to study how HLA-Gs interact with secretome components, especially at the level of specific components, to develop treatment strategies that prevent cancer cells evading the immune system. Cancer cells may be recognized and targeted by the immune system by reducing the inhibitory effect of HLA-G on immune cells and by neutralizing tumor-promoting components of the secretome. This review focuses on the interaction of specific cancer cell secretomes and HLA-G. Here we also investigate the role of this interaction in tumor immune escape strategies.
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Affiliation(s)
- Figen Abatay Sel
- Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
| | - Fatma Savran Oğuz
- Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Tripathi S, Sharma Y, Kumar D. Biological Cargo: Exosomes and their Role in Cancer Progression and Metastasis. Curr Top Med Chem 2025; 25:263-285. [PMID: 38984577 DOI: 10.2174/0115680266304636240626055711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 05/23/2024] [Accepted: 05/23/2024] [Indexed: 07/11/2024]
Abstract
Cancer cells are among the many types of cells that release exosomes, which are nanovesicles. Because of their many potential applications, exosomes have recently garnered much attention from cancer researchers. The bioactive substances that exosomes release as cargo have been the subject of several investigations. The substances in question may operate as biomarkers for diagnosis or affect apoptosis, the immune system, the development and spread of cancer, and other processes. Others have begun to look at exosomes in experimental therapeutic trials because they believe they may be useful in the treatment of cancer. This review started with a short description of exosome biogenesis and key features. Next, the potential of tumor-derived exosomes and oncosomes to influence the immune system throughout the development of cancer, as well as alter tumor microenvironments (TMEs) and pre-metastatic niche creation, was investigated. Finally, there was talk of exosomes' possible use in cancer treatment. Furthermore, there is emerging consensus about the potential application of exosomes to be biological reprogrammers of cancer cells, either as carriers of naturally occurring chemicals, including anticancer medications, or as carriers of anticancer vaccines for immunotherapy as well as boron neutron capture therapy (BNCT). We briefly review the key ideas and logic behind this intriguing therapy recommendation.
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Affiliation(s)
- Siddhant Tripathi
- Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be) University, Pune, Maharashtra, 411038, India
| | - Yashika Sharma
- Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be) University, Pune, Maharashtra, 411038, India
| | - Dileep Kumar
- Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be) University, Pune, Maharashtra, 411038, India
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Nashtahosseini Z, Nejatollahi M, Fazilat A, Zarif Fakoor E, Emamvirdizadeh A, Bahadori K, Hadian NS, Valilo M. The crosstalk between exosomal miRNA and ferroptosis: A narrative review. Biol Cell 2025; 117:e2400077. [PMID: 39853758 DOI: 10.1111/boc.202400077] [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: 07/10/2024] [Revised: 12/24/2024] [Accepted: 01/06/2025] [Indexed: 01/26/2025]
Abstract
Ferroptosis is a type of cell death that multiple mechanisms and pathways contribute to the positive and negative regulation of it. For example, increased levels of reactive oxygen species (ROS) induce ferroptosis. ferroptosis unlike apoptosis, it is not dependent on caspases, but is dependent on iron. Exosomes are membrane-bound vesicles with a size of about 30 to 150 nm, contain various cellular components, including DNA, RNA, microRNAs (miRNAs), lipids, and proteins, which are genetically similar to their cells of origin. Exosomes are found in all bodily fluids, including blood, saliva, and urine. Cells often release exosomes after their fusion with the cell membrane. They play an important role in immune regulation and cell-cell communication. miRNAs, which are noncoding RNAs with a length of about 18 to 24 nucleotides, are involved in regulating gene expression after transcription. Emerging data suggests that exosomal miRNAs are implicated in various pathophysiological mechanisms of cells, including metastasis, drug resistance, and cell death. In addition, functional studies have indicated that exosomal miRNAs can play a key role in the modulation of cell death by regulating ferroptosis. Therefore, in this review, given the importance of exosomal miRNAs in ferroptosis, we decided to elucidate the relationship between exosomal miRNAs and ferroptosis in various diseases.
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Affiliation(s)
| | - Masoumeh Nejatollahi
- Research center for high school students, Education System Zanjan Province, Zanjan, Iran
| | - Ahmad Fazilat
- Department of Genetics, Motamed Cancer Institute, Breast Cancer Research Center, ACECR, Tehran, Iran
| | | | - Alireza Emamvirdizadeh
- Department of Genetics, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Kamran Bahadori
- Health center of Bahar, Hamadan University of Medical Science& Health Services, Hamadan, Iran
| | | | - Mohammad Valilo
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
- Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
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Zheng B, Wang X, Guo M, Tzeng CM. Current Development of Mesenchymal Stem Cell-Derived Extracellular Vesicles. Cell Transplant 2025; 34:9636897241297623. [PMID: 39874070 PMCID: PMC11775985 DOI: 10.1177/09636897241297623] [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: 06/22/2024] [Revised: 10/11/2024] [Accepted: 10/17/2024] [Indexed: 01/30/2025] Open
Abstract
Mesenchymal stem cells (MSCs) are pluripotent stem cells with self-renewal. They play a critical role in cell therapy due to their powerful immunomodulatory and regenerative effects. Recent studies suggest that one of the key therapeutic mechanisms of MSCs seems to derive from their paracrine product, called extracellular vesicles (EVs). The EVs contain much DNA, messenger RNA (mRNA), microRNA, and protein components, which can exert intracellular communication to target cells. In clinical applications, the MSC-EVs have been widely used in tissue repair and immune disorder diseases. However, there are serval issues need to be considered such as how to accomplish the large-scale production of EVs and how to verify the exact mechanism of EVs. In this review, we summarize the current progress of MSC-EVs and discuss the challenges and future of MSC-EVs.
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Affiliation(s)
- Bingyi Zheng
- Cells Good (Xiamen) Inc. Huli, Xiamen Torch Development Zone, Fujian, China
- Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China
| | - Xueting Wang
- Cells Good (Xiamen) Inc. Huli, Xiamen Torch Development Zone, Fujian, China
- Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China
| | - Meizhai Guo
- Cells Good (Xiamen) Inc. Huli, Xiamen Torch Development Zone, Fujian, China
- Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China
| | - Chi-Meng Tzeng
- Cells Good (Xiamen) Inc. Huli, Xiamen Torch Development Zone, Fujian, China
- Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China
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41
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Xia R, Li M, Huang B. A new strategy for drug delivery systems in oral diseases using stem cell-derived extracellular vesicles: review and new perspectives. Postgrad Med J 2024:qgae187. [PMID: 39722492 DOI: 10.1093/postmj/qgae187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Revised: 10/29/2024] [Accepted: 12/04/2024] [Indexed: 12/28/2024]
Abstract
Extracellular vesicles (EVs) are membrane vesicles derived from cells and serve as an endogenous mechanism for intercellular communication. Since the discovery of their capacity to effectively transfer biological information, their potential as drug delivery vehicles has garnered significant scientific interest. Particularly, EVs derived from mesenchymal cells (MSC-EVs) have emerged as a highly promising method for drug delivery. They can transport bioactive molecules, such as nucleic acids, lipids, and proteins, and possess the ability to modulate immune responses, transmit information, and target specific cells. EVs offer several advantages over conventional drug delivery systems, including their capacity to traverse natural barriers, inherent cell targeting capabilities, and stability in circulation. Compared to their parent cells, EVs exhibit low immunogenicity, ease of storage and transport, and a reduced risk of tumorigenesis. The diagnosis and treatment of oral diseases often involve invasive measures, and MSC-EVs have demonstrated initial efficacy in oral disease treatment. This review explores the application of MSC-EVs in maxillofacial tissue regeneration, periodontitis, temporomandibular joint osteoarthritis, Sjögren's Syndrome, oral cancer, and other oral diseases. Additionally, it outlines potential future directions for the development of MSC-EVs. This review aims to provide a comprehensive understanding of MSC-EVs in oral disease treatment and to stimulate interest in their applications for targeted drug delivery.
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Affiliation(s)
- Ruyang Xia
- State Key Laboratory of Oral Diseases and National Center of Stomatology and General Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Maojiao Li
- State Key Laboratory of Oral Diseases and National Center of Stomatology and General Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Bo Huang
- State Key Laboratory of Oral Diseases and National Center of Stomatology and General Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
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Jiang J, Lin F, Wu W, Zhang Z, Zhang C, Qin D, Xu Z. Exosomal long non-coding RNAs in lung cancer: A review. Medicine (Baltimore) 2024; 103:e38492. [PMID: 39705424 PMCID: PMC11666185 DOI: 10.1097/md.0000000000038492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 05/11/2024] [Accepted: 05/16/2024] [Indexed: 12/22/2024] Open
Abstract
Lung cancer is one of the most threatening malignancies among the different kinds of tumors. The incidence and mortality rate are increasing especially in male. Advances in diagnosis and treatment have been achieve in recent years. However, the lung tumor cells also developing chemo- and radio-resistance. Novel approaches and new treatments are stilled needed to develop for early diagnosis and treatment. Recently, long non-coding RNAs (lncRNAs) original exosomes were proved different expression in lung tumor, which mediate multiple biological processes and is responsible for tumor proliferation and metastasis. In this review, we focus on the emerging roles of both lncRNAs and exosomal lncRNAs in lung cancer and their roles on angiogenesis, metastasis, diagnosis, drug resistance, and immune regulation of lung cancer. Exosome lncRNAs were proved to serve as regulatory factors for gene expression, mediating intercellular communication, and participating in the occurrence and development of various diseases. In addition, exosomes lnc RNA has advantages on the early diagnosis of lung cancer, tumor cell metastasis, drug resistance, and immune regulation. Exosome lncRNAs an provide some unique ideas on how to improve the efficiency of diagnosis and treatment of lung cancer in the future.
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Affiliation(s)
- Jingyuan Jiang
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Fengwu Lin
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Wenqi Wu
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Zhe Zhang
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Chen Zhang
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Dongliang Qin
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Zhenan Xu
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
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43
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Hu C, Wang L. Advances in the treatment of liver injury based on mesenchymal stem cell-derived exosomes. Stem Cell Res Ther 2024; 15:474. [PMID: 39696473 DOI: 10.1186/s13287-024-04087-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Accepted: 11/28/2024] [Indexed: 12/20/2024] Open
Abstract
Mesenchymal stem cells (MSCs) have shown a great potential role in treating liver injury. MSCs can promote liver regeneration by differentiating into hepatocytes, and can also secrete exosomes to participate in the repair of liver injury. Increasing evidence has shown that mesenchymal stem cell-derived exosomes (MSC-EXOs) play an important role in treating liver injury. In this review, the biogenesis and function of exosomes and the characteristics of MSC-EXOs were analyzed based on recent research results. MSC-EXOs are significant in liver injuries such as liver fibrosis, liver failure, hepatocellular carcinoma, oxidative stress, and lipid steatosis, and participate in the process of liver regeneration.
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Affiliation(s)
- Changlong Hu
- Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Military Medical University, Xi'an, 710000, China
| | - Lin Wang
- Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Military Medical University, Xi'an, 710000, China.
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Piccarducci R, Germelli L, Falleni A, Luisotti L, Masciulli B, Signore G, Migone C, Fabiano A, Bizzarri R, Piras AM, Giacomelli C, Marchetti L, Martini C. GFP Farnesylation as a Suitable Strategy for Selectively Tagging Exosomes. ACS APPLIED BIO MATERIALS 2024; 7:8305-8318. [PMID: 39632747 DOI: 10.1021/acsabm.4c01112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2024]
Abstract
Exosomes are small extracellular vesicles (EVs) constituting fully biological, cell-derived nanovesicles with great potential in cell-to-cell communication and drug delivery applications. The current gold standard for EV labeling and tracking is represented by fluorescent lipophilic dyes which, however, importantly lack selectivity, due to their unconditional affinity for lipids. Herein, an alternative EV fluorescent labeling approach is in-depth evaluated, by taking advantage of green fluorescent protein (GFP) farnesylation (GFP-f), a post-translational modification to directly anchor GFP to the EV membrane. The performance of GFP-f is analyzed, in terms of selectivity and efficiency, in several typical EV experimental setups such as delivery in recipient cells, surface engineering, and cargo loading. First, the capability of GFP and GFP-f to label exosomes was compared, showing significantly higher GFP protein levels and fluorescence intensity in GFP-f- than in GFP-labeled exosomes, highlighting the advantage of directly anchoring the GFP to the EV cell membrane. Then, the GFP-f tag was further compared to Vybrant DiD lipophilic dye labeling in exosome uptake studies, by capturing EV intracellular fluorescence in a time- and concentration-dependent manner. The internalization assay revealed a particular ability of GFP-f to monitor the uptake of tagged exosomes into recipient cells, with a significant peak of intensity reached 12 h after administration by GFP-f but not Vybrant-labeled EVs. Finally, the GFP-f labeling capability was challenged in the presence of a surface modification of exosomes and after transfection for siRNA loading. Results showed that both procedures can influence GFP-f performance compared to naïve GFP-f exosomes, although fluorescence is importantly maintained in both cases. Overall, these data provide direct insight into the advantages and limitations of GFP-f as a tagging protein for selectively and accurately tracking the exosome route from isolation to uptake in recipient cells, also in the context of EV bioengineering applications.
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Affiliation(s)
| | | | - Alessandra Falleni
- Department of Experimental and Clinical Medicine, University of Pisa, 56126 Pisa, Italy
| | | | - Benedetta Masciulli
- Department of Surgical, Medical and Molecular Pathology, and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy
| | - Giovanni Signore
- Department of Biology, University of Pisa, 56126 Pisa, Italy
- Center for Instrument Sharing, University of Pisa, 56126 Pisa, Italy
| | - Chiara Migone
- Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
| | - Angela Fabiano
- Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
- Center for Instrument Sharing, University of Pisa, 56126 Pisa, Italy
| | - Ranieri Bizzarri
- Department of Surgical, Medical and Molecular Pathology, and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy
- Center for Instrument Sharing, University of Pisa, 56126 Pisa, Italy
- NEST, Istituto Nanoscienze-CNR and Scuola Normale Superiore, 56126 Pisa, Italy
| | - Anna Maria Piras
- Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
- Center for Instrument Sharing, University of Pisa, 56126 Pisa, Italy
| | - Chiara Giacomelli
- Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
- Center for Instrument Sharing, University of Pisa, 56126 Pisa, Italy
| | - Laura Marchetti
- Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
- Center for Instrument Sharing, University of Pisa, 56126 Pisa, Italy
| | - Claudia Martini
- Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
- Center for Instrument Sharing, University of Pisa, 56126 Pisa, Italy
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Wang Y, Sun C, Liu Z, Zhang S, Gao K, Yi F, Zhou W, Liu H. Nanoengineered Endocytic Biomaterials for Stem Cell Therapy. ADVANCED FUNCTIONAL MATERIALS 2024; 34. [DOI: 10.1002/adfm.202410714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Indexed: 01/05/2025]
Abstract
AbstractStem cells, ideal for the tissue repair and regeneration, possess extraordinary capabilities of multidirectional differentiation and self‐renewal. However, the limited spontaneous differentiation potential makes it challenging to harness them for tissue repair without external intervention. Although conventional approaches using biomolecules, small organic molecules, and ions have shown specific and effective functions, they face challenges such as in vivo diffusion and degradation, poor internalization, and side effects on adjacent cells. Nanoengineered biomaterials offer a solution by solidifying and nanosizing these soluble regulating molecules and ions, facilitating their uptake by stem cells. Once inside lysosomes, these nanoparticles release their contents in a controlled “molecule or ion storm,” efficiently altering the intracellular biological and chemical microenvironment to tune the differentiation of stem cells. This newly emerged approach for regulating stem cell fate has attracted much attention in recent years. This method has shown promising results and is poised to enhance clinical stem cell therapy. This review provides an overview of the design principles for nanoengineered biomaterials, discusses the categories and characteristics of nanoparticles, summarizes the application of nanoparticles in tissue repair and regeneration, and discusses the direction of nanoparticle‐enhanced stem cell therapy and prospects for its clinical application in regenerative medicine.
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Affiliation(s)
- Yingxue Wang
- Institute for Advanced Interdisciplinary Research (iAIR) University of Jinan Jinan 250022 P. R. China
| | - Chunhui Sun
- Institute for Advanced Interdisciplinary Research (iAIR) University of Jinan Jinan 250022 P. R. China
| | - Zhaoying Liu
- Institute for Advanced Interdisciplinary Research (iAIR) University of Jinan Jinan 250022 P. R. China
| | - Shengmin Zhang
- Institute for Advanced Interdisciplinary Research (iAIR) University of Jinan Jinan 250022 P. R. China
| | - Ke Gao
- Institute for Advanced Interdisciplinary Research (iAIR) University of Jinan Jinan 250022 P. R. China
| | - Fan Yi
- School of Basic Medical Sciences Shandong University Jinan 250012 P. R. China
| | - Wenjuan Zhou
- School of Basic Medical Sciences Shandong University Jinan 250012 P. R. China
| | - Hong Liu
- Institute for Advanced Interdisciplinary Research (iAIR) University of Jinan Jinan 250022 P. R. China
- State Key Laboratory of Crystal Materials Shandong University Jinan 250100 P. R. China
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Patel SA, Park S, Zhu D, Torr EE, Dureke AG, McIntyre A, Muzyka N, Severson J, Skop AR. Extracellular vesicles, including large translating vesicles called midbody remnants, are released during the cell cycle. Mol Biol Cell 2024; 35:ar155. [PMID: 39535882 PMCID: PMC11656471 DOI: 10.1091/mbc.e23-10-0384] [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] [Received: 10/03/2023] [Revised: 11/07/2024] [Accepted: 11/07/2024] [Indexed: 11/16/2024] Open
Abstract
Extracellular vesicles (EVs) play crucial roles in cell-cell communication, but the biogenesis of large EVs has remained elusive. Here, we show that the biogenesis of large EVs (>800 nm-2 µm) occurs predominantly through the completion of successful cytokinesis, and the majority of large EVs are midbody remnants (MBRs) with translation activity, and the unique marker MKLP1. Blocking the cell cycle or cytokinesis, genetically or chemically, significantly decreases MBRs and large (800 nm-2 µm), medium (500-800 nm), and small (<300 nm) EVs, suggesting that proliferative cells can also generate all sizes of EVs. The canonical EV markers including CD9, CD63, CD81 localize to the spindle midzone, midbody, and MBRs, suggesting that these markers are not specific for detecting EVs exclusively. Importantly, all commonly used EV isolation methods isolate MBRs, confounding previous EV research. Last, isolated MBRs maintain translation activity regardless of the isolation method. We propose a model for the biogenesis of EVs throughout the cell cycle and suggest that some large EVs are primarily generated from mitotic cells. The discovery of MBRs as a unique class of large, translating EVs has implications for using them as cancer diagnostic markers and for engineering them for therapeutic cargo delivery during mitosis.
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Affiliation(s)
- Smit A. Patel
- Laboratory of Genetics, UW-Madison, Madison, WI 53706
| | - Sungjin Park
- Laboratory of Genetics, UW-Madison, Madison, WI 53706
| | - Dantong Zhu
- Laboratory of Genetics, UW-Madison, Madison, WI 53706
| | | | | | | | - Nadiya Muzyka
- Laboratory of Genetics, UW-Madison, Madison, WI 53706
| | | | - Ahna R. Skop
- Laboratory of Genetics, UW-Madison, Madison, WI 53706
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Zheng M, Chavda VP, Vaghela DA, Bezbaruah R, Gogoi NR, Patel K, Kulkarni M, Shen B, Singla RK. Plant-derived exosomes in therapeutic nanomedicine, paving the path toward precision medicine. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 135:156087. [PMID: 39388922 DOI: 10.1016/j.phymed.2024.156087] [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: 04/06/2024] [Revised: 09/15/2024] [Accepted: 09/18/2024] [Indexed: 10/12/2024]
Abstract
BACKGROUND Plant-derived exosomes (PDEs), are nanoscale vesicles secreted by multivesicular bodies, play pivotal roles in critical biological processes, including gene regulation, cell communication, and immune defense against pathogens. Recognized for their potential health-promoting properties, PDEs are emerging as innovative components in functional nutrition, poised to enhance dietary health benefits. PURPOSE To describe the efficacy of PDEs in nanoform and their application as precision therapy in many disorders. STUDY DESIGN The design of this review was carried out in PICO format using randomized clinical trials and research articles based on in vivo and in vitro studies. METHODS All the relevant clinical and research studies conducted on plant-derived nanovesicle application and efficacy were included, as retrieved from PubMed and Cochrane, after using specific search terms. This review was performed to determine PDEs' efficacy as nanomedicine and precision therapy. Sub-group analysis and primary data were included to determine the relationship with PDEs. RESULT PDEs are extracted from plant materials using sophisticated techniques like precipitation, size exclusion, immunoaffinity capture, and ultracentrifugation, encapsulating vital molecules such as lipids, proteins, and predominantly microRNAs. Although their nutritional impact may be minimal in small quantities, the broader application of PDEs in biomedicine, particularly as vehicles for drug delivery, underscores their significance. They offer a promising strategy to improve the bioavailability and efficacy of therapeutic agents carrying nano-bioactive substances that exhibit anti-inflammatory, antioxidant, cardioprotective, and anti-cancer activities. CONCLUSION PDEs enhance the therapeutic potency of plant-derived phytochemicals, supporting their use in disease prevention and therapy. This comprehensive review explores the multifaceted aspects of PDEs, including their isolation methods, biochemical composition, health implications, and potential to advance medical and nutritional interventions.
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Affiliation(s)
- Min Zheng
- Department of Pharmacy and Institutes for Systems Genetics, Center for High Altitude Medicine, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China; West China Tianfu Hospital, Sichuan University, Chengdu, Sichuan, 610218, China
| | - Vivek P Chavda
- Department of Pharmaceutics and Pharmaceutical Technology, L.M College of Pharmacy, Ahmedabad 380009, Gujrat, India.
| | - Dixa A Vaghela
- Pharmacy section, L.M College of Pharmacy Ahmedabad 380009, Gujrat, India
| | - Rajashri Bezbaruah
- Department of Pharmacology, Dibrugarh University, Dibrugarh 786004, Assam
| | - Niva Rani Gogoi
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh 786004, Assam
| | - Kaushika Patel
- Department of Pharmaceutical Technology, L. J. Institute of Pharmacy, LJ University, Ahmedabad 382210, Gujarat, India
| | - Mangesh Kulkarni
- Department of Pharmaceutical Technology, L. J. Institute of Pharmacy, LJ University, Ahmedabad 382210, Gujarat, India; Department of Pharmaceutics, Gandhinagar Institute of Pharmacy, Gandhinagar University, Moti Bhoyan, Khatraj-Kalol Road 382721, Gujarat, India
| | - Bairong Shen
- Institutes for Systems Genetics, West China Tianfu Hospital, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Rajeev K Singla
- Department of Pharmacy and Institutes for Systems Genetics, Center for High Altitude Medicine, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India.
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Wang L, Zhang J, Sun A, Yin Y, Shen Y, Zhang D, Chen Q, Zhao M. Placental extracellular vesicles promoted cervical tumour tissue undergoing death. Placenta 2024; 158:223-230. [PMID: 39504594 DOI: 10.1016/j.placenta.2024.10.069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/15/2024] [Accepted: 10/30/2024] [Indexed: 11/08/2024]
Abstract
BACKGROUND Cervical cancer is a leading cause of death in developing countries. Although the placenta is a tumor-like organ, the placental development, including invasive function, is well controlled. One mechanism is that extracellular vesicles (EVs) released from the placenta contribute to this regulation. Placental EVs carry functional proteins and regulatory RNAs. Our previous study reported that placental EVs inhibited ovarian cancer growth in vitro and in vivo. METHODS Whether the inhibitory effect induced by placental EVs also applies to cervical cancer, a non-endocrine-related cancer, in this study, we first co-cultured the cervical tumour tissues with placental explants. RESULTS Co-culturing cervical tumour tissues (n = 7) with placental explants showed necrotic signs and increased levels of senescence-associated proteins and death-associated miRNAs, including miRNA-143-3p, miRNA-519a-5p and miRNA-199a-3p in tumour tissues. Additionally, treatment of HeLa cells with placental EVs reduced the viability of HeLa cells and inhibited the ability of invasion and migration of HeLa cells. Increased levels of senescence-associated proteins and reduced levels of proliferative proteins may contribute to the inhibitory effects in HeLa cells. DISCUSSION placental EVs are involved in regulating placental development, and the delivery of cargo significantly impacts the functions of target cells. This study found that factors released from placental explants, likely placental EVs, had anti-tumour effects on the cervical tumour by inhibiting cervical cancer cell viability, invasion, and migration. Cargo in placental EVs, such as cellular death-associated miRNAs, may contribute to the inhibitory effects on cervical tumour.
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Affiliation(s)
- Lin Wang
- Department of Gynaecology, Wuxi Maternity and Child Health Care Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, China; Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Jinqiu Zhang
- Department of Pathology, Wuxi Maternity and Child Health Care Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Angang Sun
- Department of Pathology, Wuxi Maternity and Child Health Care Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Yongxiang Yin
- Department of Pathology, Wuxi Maternity and Child Health Care Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Ye Shen
- Department of Family Planning, Wuxi Maternity and Child Care Health Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Dengxin Zhang
- Department of Anesthesia, Wuxi Maternity and Child Health Care Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Qi Chen
- Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
| | - Min Zhao
- Department of Gynaecology, Wuxi Maternity and Child Health Care Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, China.
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Kumrah R, Jindal AK, Rawat A, Singh S. Proteomics approach for biomarker discovery in Kawasaki disease. Expert Rev Clin Immunol 2024; 20:1449-1460. [PMID: 39041312 DOI: 10.1080/1744666x.2024.2383236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 06/07/2024] [Accepted: 07/18/2024] [Indexed: 07/24/2024]
Abstract
INTRODUCTION Kawasaki disease (KD) is a medium vessel vasculitis mainly affecting children below the age of 5. KD is the leading cause of acquired heart disease in developed countries. Diagnosis of KD is clinical, and there are no pathognomonic laboratory tests to confirm the diagnosis. There is a paucity of studies that have utilized proteomic approach for biomarker discovery in KD. Identification of these biomarkers may be helpful for early and more effective diagnosis and may aid in the treatment of KD. AREA COVERED The present review focuses on studies that have utilized the proteomic approach in the identification of biomarkers in patients with KD. We have divided these biomarkers into three different categories: the biomarkers used for (a) assessment of risk of KD; (b) assessment of risk of coronary artery aneurysms; and (c) assessment of treatment resistance. EXPERT OPINION Efforts to improve the clinical and diagnostic evaluation of KD have focused on general markers of inflammation that are not specific for KD. Identification of a proteomic-based biomarker can reliably and specifically differentiate KD from other diseases and could help in the prompt diagnosis. Comprehensive analysis of the serum proteome of patients with KD may be helpful in identifying candidate protein biomarkers.
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Affiliation(s)
- Rajni Kumrah
- Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ankur Kumar Jindal
- Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Amit Rawat
- Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Surjit Singh
- Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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50
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Zhang Z, Zhang J, Chen H, Han C, Chen Y, Zhan X, Liu Y. The shell formation mechanism of Turbo argyrostomus based on ultrastructure and transcriptome analysis. Gene 2024; 927:148747. [PMID: 38972557 DOI: 10.1016/j.gene.2024.148747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 06/18/2024] [Accepted: 07/02/2024] [Indexed: 07/09/2024]
Abstract
The gold inner shell of Turbo argyrostomus is an important morphological classification characteristic in Gastropoda. However, the gene sets responsible for shell formation in gastropods remain poorly explored. In this study, we investigated the microstructure using scanning electron microscopy (SEM), hematoxylin-eosin (HE) and Alcian blue staining-periodic acid-Schiff (AB-PAS) staining. The SEM results illustrated that the T. argyrostomus shell exhibited a special "sandwich" microstructure. The results of histological observation demonstrated two major cell types: adipocytes and mucin cells. A total of 318 differentially expressed genes were identified between edge mantle and central mantle, among which whey acidic protein, N66, and nacre-like proteins, and Lam G and EGF domains may be related to shell microstructure. 22.39% - 25.20% of the mucin genes had biomineralization related domains, which supported for the relationship between mucins and shell formation. Moreover, this study revealed energy distribution differences between the edge mantle and central mantle. These results provide insights for further understanding of the biomineralization mechanism in Gastropoda.
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Affiliation(s)
- Zhijie Zhang
- School of Marine Biology and Fisheries, Hainan University, Haikou 570228, China; Key Laboratory of Tropical Hydrobiology and Biotechnology of Hainan Province, Hainan University Haikou 570228, China; State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, Haikou 570228, China
| | - Jiayi Zhang
- School of Marine Biology and Fisheries, Hainan University, Haikou 570228, China; Key Laboratory of Tropical Hydrobiology and Biotechnology of Hainan Province, Hainan University Haikou 570228, China; State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, Haikou 570228, China
| | - Hengda Chen
- School of Marine Biology and Fisheries, Hainan University, Haikou 570228, China; Key Laboratory of Tropical Hydrobiology and Biotechnology of Hainan Province, Hainan University Haikou 570228, China; State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, Haikou 570228, China
| | - Changqing Han
- School of Marine Biology and Fisheries, Hainan University, Haikou 570228, China; Key Laboratory of Tropical Hydrobiology and Biotechnology of Hainan Province, Hainan University Haikou 570228, China; State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, Haikou 570228, China
| | - Yi Chen
- Key Laboratory of Tropical Hydrobiology and Biotechnology of Hainan Province, Hainan University Haikou 570228, China; State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, Haikou 570228, China; School of Ecology, Hainan University, Haikou 570228, China
| | - Xin Zhan
- School of Marine Biology and Fisheries, Hainan University, Haikou 570228, China; Key Laboratory of Tropical Hydrobiology and Biotechnology of Hainan Province, Hainan University Haikou 570228, China; State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, Haikou 570228, China.
| | - Yibing Liu
- Key Laboratory of Mariculture (Ministry of Education), Fisheries College, Ocean University of China, Qingdao 266003, China.
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