Objective To investigate the research hotspots， development trends， and potential challenges in the field of stroke and exosomes based on bibliometric and visual analyses， and to provide scientific evidence for basic research and clinical translation. Methods The Web of Science database was used to obtain related articles published up to 2024， and CiteSpace and other tools were used to perform visual analyses from various aspects such as publication trends， collaboration networks， co-occurrence and clustering of keywords， and literature burst analysis. Results A total of 1 153 articles were included. The analysis showed an overall increasing trend in the number of publications per year. The institution with the highest number of publications was Henry Ford Health System， the author with the highest number of publications was Professor Chopp， and the journal with the highest number of articles Int J Mol Sci. High-frequency keywords included "extracellular vesicles" "ischemic stroke" and "stroke"， forming 12 research clusters， with neural repair and barrier protection as the key research directions. Conclusion The research on stroke and exosomes has been increasing year by year， with rapid development in recent years and the formation of an interdisciplinary pattern. Future studies should focus on the molecular mechanisms mediated by exosomes and their clinical application in stroke treatment， so as to promote the development of precision medicine and provide new therapeutic approaches.
Stroke ; Exosomes ; Bibliometrics

BACKGROUND: Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP. METHODS: Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts. METTL3 small interfering RNA and an overexpression vector were transfected into vaginal fibroblasts to evaluate the effects of METTL3 silencing and overexpression on matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the ECM. Both procedures were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining, Western blotting (WB), quantitative real-time polymerase chain reaction (RT-qPCR), and immunofluorescence (IF). RESULTS: Vaginal fibroblasts from POP patients exhibited increased proliferation ability, increased expression of α-smooth muscle actin (α-SMA), decreased expression of collagen I/III, and significantly decreased expression of tissue inhibitors of matrix metalloproteinases (TIMPs) in the stiff matrix ( P <0.05). Compared with those from non-POP patients, vaginal wall tissues from POP patients demonstrated a significant increase in METTL3 content ( P <0.05). However, silencing METTL3 expression in vaginal fibroblasts with high ECM stiffness resulted in decreased proliferation ability, decreased α-SMA expression, an increased ratio of collagen I/III, and increased TIMP1 and TIMP2 expression. Conversely, METTL3 overexpression significantly promoted the process of increased proliferation ability, increased α-SMA expression, decreased ratio of collagen I/III and decreased TIMP1 and TIMP2 expression in the soft matrix ( P <0.05). CONCLUSIONS Elevated ECM stiffness can promote excessive proliferation, differentiation, and abnormal ECM modulation, and the expression of METTL3 plays an important role in alleviating or aggravating matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal ECM modulation.
Humans ; Female ; Extracellular Matrix/metabolism* ; Cell Differentiation/genetics* ; Methyltransferases/metabolism* ; Pelvic Organ Prolapse/pathology* ; Fibroblasts/metabolism* ; Myofibroblasts/metabolism* ; Vagina/metabolism* ; Cell Proliferation/physiology* ; Cells, Cultured ; Middle Aged

The production of high-quality oocytes requires precisely orchestrated intercellular communication. Extracellular vesicles (EVs) are cell-derived nanoparticles that play a vital role in the transfer of bioactive molecules, which has gained much attention in the field of diagnosis and treatment. Over the past ten years, the participation of EVs in the reproductive processes of oocytes has been broadly studied and has shown great potential for elucidating the intricacies of female reproductive health. This review provides an extensive discussion of the influence of EVs on oocytes, emphasizing their involvement in normal physiology and altered cargo under pathological conditions. In addition, the positive impact of therapeutic EVs on oocyte quality and their role in alleviating ovarian pathological conditions are summarized.
Humans ; Extracellular Vesicles/physiology* ; Oocytes/cytology* ; Female ; Animals ; Cell Communication/physiology*

Obstructive sleep apnea (OSA) is a global public health concern characterized by repeated upper airway collapse during sleep. Research indicates that OSA is a risk factor for the development of various diseases, including cardiovascular disease, metabolic disorders, respiratory diseases, neurodegenerative diseases, and cancer. Exosomes, extracellular vesicles released by most cell types, play a key role in intercellular communication by transporting their contents-such as microRNA, messenger RNA, DNA, proteins, and lipids-to target cells. Intermittent hypoxia associated with OSA alters circulating exosomes and promotes a range of cellular structural and functional disturbances involved in the pathogenesis of OSA-related diseases. This review discusses the potential roles of exosomes and exosome-derived molecules in the onset and progression of OSA-associated diseases, explores the possible underlying mechanisms, and highlights novel strategies for developing exosome-based therapies for these conditions.
Humans ; Exosomes/physiology* ; Sleep Apnea, Obstructive/metabolism* ; Animals ; MicroRNAs/metabolism*

BACKGROUND: Cluster of differentiation 8 positive (CD8 + ) T cells play a crucial role in the response against tumors, including hepatocellular carcinoma (HCC), where their dysfunction is commonly observed. While the association between elevated peroxisome proliferator-activated receptor alpha (PPARα) expression in HCC cells and exosomes and unfavorable prognosis in HCC patients is well-established, the underlying biological mechanisms by which PPARα induces CD8 + T cell exhaustion mediated by HCC exosomes remain poorly understood. METHODS: Bioinformatics analyses and dual-luciferase reporter assays were used to investigate the regulation of microRNA-27b-3p ( miR-27b-3p ) and thymocyte selection-associated high mobility group box ( Tox ) by Pparα . In vitro and in vivo experiments were conducted to validate the effects of HCC-derived exosomes, miR-27b-3p overexpression, and Pparα on T cell function. Exosome characterization was confirmed using transmission electron microscopy, Western blotting, and particle size analysis. Exosome tracing was performed using small animal in vivo imaging and confocal microscopy. The expression levels of miR-27b-3p , Pparα , and T cell exhaustion-related molecules ( Tox , Havcr2 , and Pdcd1 ) were detected using quantitative reverse transcription polymerase chain reaction analysis, Western blotting analysis, immunofluorescence staining, and flow cytometry analysis. RESULTS: Pparα expression was significantly increased in HCC and negatively correlated with prognosis. It showed a positive correlation with Tox and a negative correlation with miR-27b-3p . The overexpressed Pparα from HCC cells was delivered to CD8 + T cells via exosomes, which absorbed miR-27b-3p both in vitro and in vivo , acting as "miRNA sponges". Further experiments demonstrated that Pparα can inhibit the negative regulation of Tox mediated by miR-27b-3p through binding to its 3'untranslated regions. CONCLUSIONS HCC-derived exosomes deliver Pparα to T cells and promote CD8 + T cell exhaustion and malignant progression of HCC via the miR-27b-3p /TOX regulatory axis. The mechanisms underlying T-cell exhaustion in HCC can be utilized for the advancement of anticancer therapies.
MicroRNAs/metabolism* ; PPAR alpha/genetics* ; Carcinoma, Hepatocellular/genetics* ; Humans ; Liver Neoplasms/genetics* ; CD8-Positive T-Lymphocytes/immunology* ; Exosomes/metabolism* ; Animals ; Cell Line, Tumor ; Mice ; High Mobility Group Proteins/genetics* ; Male ; T-Cell Exhaustion

Atherosclerosis (AS) is a prevalent clinical vascular condition and serves as a pivotal pathological foundation for cardiovascular diseases. Understanding the pathogenesis of AS has significant clinical and societal implications, aiding in the development of targeted drugs. Neutrophils, the most abundant leukocytes in circulation, assume a central role during inflammatory responses and closely interact with AS, which is a chronic inflammatory vascular disease. Neutrophil extracellular traps (NETs) are substantial reticular formations discharged by neutrophils that serve as an immune defense mechanism. These structures play a crucial role in inducing dysfunction of the vascular barrier following endothelial cell injury. Components released by NETs pose a threat to the integrity of vascular endothelium, which is essential as it acts as the primary barrier to maintain vascular wall integrity. Endothelial damage constitutes the initial stage in the onset of AS. Recent investigations have explored the intricate involvement of NETs in AS progression. The underlying structures of NETs and their active ingredients, including histone, myeloperoxidase (MPO), cathepsin G, neutrophil elastase (NE), matrix metalloproteinases (MMPs), antimicrobial peptide LL-37, alpha-defensin 1-3, and high mobility group protein B1 have diverse and complex effects on AS through various mechanisms. This review aims to comprehensively examine the interplay between NETs and AS while providing insights into their mechanistic underpinnings of NETs in this condition. By shedding light on this intricate relationship, this exploration paves the way for future investigations into NETs while guiding clinical translation efforts and charting new paths for therapeutic interventions.
Extracellular Traps/physiology* ; Humans ; Atherosclerosis/immunology* ; Neutrophils/physiology* ; Leukocyte Elastase/metabolism* ; Peroxidase/physiology* ; Matrix Metalloproteinases/physiology* ; Cathepsin G/metabolism* ; Cathelicidins ; HMGB1 Protein/physiology* ; Histones ; Animals ; Endothelium, Vascular

A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) represent a diverse family of secreted metalloproteinases, comprising 19 distinct members categorized into five groups based on their substrate specificity: proteoglycanases, procollagen N-peptidases, von Willebrand factor-cleaving protease, cartilage oligomeric matrix proteases and other proteases. Among these, ADAMTS proteoglycanases predominantly target hyalectans, pivotal components in extracellular matrix (ECM) remodeling and inflammation. Dysfunction of ADAMTS proteoglycanases disrupts the structure and function of hyalectans, thereby perturbing ECM homeostasis, resulting in reproduction disorders, including abnormal follicular development, ovulation dysfunction, impaired implantation, placentation and preterm labor. Hence, investigation of the role of ADAMTS proteoglycanases offers valuable insights into the molecular mechanisms underlying the physiological or pathological processes within the female reproductive system, thereby paving the way for innovative strategies in predicting, preventing and treating reproductive system diseases. This review summarizes the recent research advances in the structure and regulation of ADAMTS proteoglycanases and their role in female reproductive system.
Humans ; Female ; ADAMTS Proteins/physiology* ; ADAM Proteins/physiology* ; Pregnancy ; Animals ; Genitalia, Female/enzymology* ; Extracellular Matrix/metabolism*

Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male

The timely and efficient repair of the plasma membrane in skeletal muscle cells following injury is critical for maintaining cellular function and tissue integrity. Extracellular vesicles (EVs) play a pivotal role in this process through multi-level mechanisms. This review systematically summarizes the generation, secretion, and multifunctional roles of EVs in the repair of skeletal muscle plasma membrane damage: (1) removing damaged membrane fragments and cellular debris via endocytosis and exocytosis to maintain plasma membrane stability; (2) fusing with the injured plasma membrane to supply essential components for membrane repair and restore membrane integrity; and (3) serving as a vital mediator of intercellular communication, transmitting repair signals, promoting intercellular interactions, and orchestrating multi-level responses to facilitate tissue regeneration and functional recovery. Additionally, this article explores the potential applications of EVs in the treatment of exercise-induced injuries and muscular diseases, aiming to provide theoretical insights and novel strategies for future research and EV-based therapeutic approaches.
Extracellular Vesicles/physiology* ; Humans ; Muscle, Skeletal/physiology* ; Cell Membrane/physiology* ; Animals ; Regeneration/physiology* ; Exocytosis/physiology* ; Endocytosis/physiology* ; Cell Communication/physiology*

Intervertebral disc degeneration (IDD) is the main cause of low back pain. Immune cells play an extremely important role in regulating the progression of IDD by interacting with nucleus pulposus (NP) cells and the extracellular matrix (ECM). Healthy NP tissue is a vascular-free and immune-privileged tissue that does not normally interact with macrophages. However, the establishment of neovascularization channels in damaged intervertebral discs has led to extensive cross-talk between NP and macrophages, with different results depending on microenvironmental stimuli. Based on this, this review reviewed the correlation between IDD and low back pain, summarized the source and function of macrophages, and discussed the possible regulatory mechanism between macrophages and discogenic pain. Finally, potential therapies targeting macrophages to delay IDD in recent years were also discussed, aiming to emphasize the important role of immunology in IDD and provide a new direction for the prevention and treatment of IDD.
Humans ; Intervertebral Disc Degeneration/complications* ; Macrophages/immunology* ; Low Back Pain/immunology* ; Nucleus Pulposus ; Animals ; Extracellular Matrix