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Frontiers in Cell and Developmental... 2024[This retracts the article DOI: 10.3389/fcell.2021.628573.].
[This retracts the article DOI: 10.3389/fcell.2021.628573.].
PubMed: 38946795
DOI: 10.3389/fcell.2024.1445363 -
Autoimmunity Dec 2024Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic...
BACKGROUND
Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA.
OBJECTIVE
This study aimed to investigate the role of exosomes derived from osteocytes in OA, particularly focusing on their effects on cartilage repair and molecular mechanisms.
METHODS
An injury cell model was established by treating chondrocytes with IL-1β. Cartilage repair was evaluated using cell counting kit-8, flow cytometry, scratch test, and Western Blot. Molecular mechanisms were analyzed using quantitative real-time PCR, bioinformatic analysis, and Western Blot. An OA mouse model was established to explore the role of exosomal DLX2 .
RESULTS
Osteocyte-released exosomes promoted cell viability and migration, and inhibited apoptosis and extracellular matrix (ECM) deposition. Moreover, exosomes upregulated DLX2 expression, and knockdown of DLX2 activated the Wnt pathway. Additionally, exosomes attenuated OA in mice by transmitting DLX2.
CONCLUSION
Osteocyte-derived exosomal DLX2 alleviated IL-1β-induced cartilage repair and inactivated the Wnt pathway, thereby alleviating OA progression. The findings suggested that osteocyte-derived exosomes may hold promise as a treatment for OA.
Topics: Exosomes; Animals; Osteoarthritis; Mice; Transcription Factors; Homeodomain Proteins; Osteocytes; Wnt Signaling Pathway; Chondrocytes; Disease Models, Animal; Humans; Interleukin-1beta; Cartilage, Articular; Apoptosis; Cartilage; Male; Cell Movement; Cell Survival
PubMed: 38946534
DOI: 10.1080/08916934.2024.2364686 -
Food Research International (Ottawa,... Aug 2024Lipids from cow milk fat globule membranes (MFGMs) and extracellular vesicles (EVs) are considered beneficial for neurodevelopment, cognitive maintenance and human...
Lipids from cow milk fat globule membranes (MFGMs) and extracellular vesicles (EVs) are considered beneficial for neurodevelopment, cognitive maintenance and human health in general. Nevertheless, it is largely unknown whether intake of infant formulas and medical nutrition products rich in these particles promote accretion of specific lipids and whether this affects metabolic homeostasis. To address this, we carried out a 16-week dietary intervention study where mice were supplemented with a MFGM/EV-rich concentrate, a control diet supplemented with a whey protein concentrate and devoid of milk lipids, or regular chow. Assessment of commonly used markers of metabolic health, including body weight, glucose intolerance and liver microanatomy, demonstrated no differences across the dietary regimes. In contrast, in-depth lipidomic analysis revealed accretion of milk-derived very long odd-chain sphingomyelins and ceramides in blood plasma and multiple tissues of mice fed the MFGM/EV diet. Furthermore, lipidomic flux analysis uncovered that mice fed the MFGM/EV diet have increased lipid metabolic turnover at the whole-body level. These findings help fill a long-lasting knowledge gap between the intake of MFGM/EV-containing foods and the health-promoting effects of their lipid constituents. In addition, the findings suggest that dietary sphingomyelins or ceramide-breakdown products with very long-chains can be used as structural components of cellular membranes, lipoprotein particles and signaling molecules that modulate metabolic homeostasis and health.
Topics: Animals; Sphingolipids; Extracellular Vesicles; Mice; Glycolipids; Lipid Metabolism; Lipid Droplets; Glycoproteins; Lipidomics; Mice, Inbred C57BL; Male; Sphingomyelins; Ceramides; Diet; Liver; Dietary Supplements
PubMed: 38945615
DOI: 10.1016/j.foodres.2024.114601 -
Biochimica Et Biophysica Acta.... Jun 2024The prevalence of cardiovascular diseases (CVDs) is increasing in the last decades, even is the main cause of death in first world countries being atherosclerosis one of...
Potential protective role of let-7d-5p in atherosclerosis progression reducing the inflammatory pathway regulated by NF-κB and vascular smooth muscle cells proliferation.
The prevalence of cardiovascular diseases (CVDs) is increasing in the last decades, even is the main cause of death in first world countries being atherosclerosis one of the principal triggers. Therefore, there is an urgent need to decipher the underlying mechanisms involved in atherosclerosis progression. In this respect, microRNAs dysregulation is frequently involved in the progression of multiple diseases including CVDs. Our aim was to demonstrate that let-7d-5p unbalance could contribute to the pathophysiology of atherosclerosis and serve as a potential diagnostic biomarker. We evaluated let-7d-5p levels in vascular biopsies and exosome-enriched extracellular vesicles (EVs) from patients with carotid atherosclerosis and healthy donors. Moreover, we overexpressed let-7d-5p in vitro in vascular smooth muscle cells (VSMCs) to decipher the targets and the underlying mechanisms regulated by let-7d-5p in atherosclerosis. Our results demonstrate that let-7d-5p was significantly upregulated in carotid plaques from overweight patients with carotid atherosclerosis. Moreover, in EVs isolated from plasma, we found that let-7d-5p levels were increased in carotid atherosclerosis patients compared to control subjects specially in overweight patients. Receiver Operating Characteristic (ROC) analyses confirmed its utility as a diagnostic biomarker for atherosclerosis. In VSMCs, we demonstrated that increased let-7d-5p levels impairs cell proliferation and could serve as a protective mechanism against inflammation by impairing NF-κB pathway without affecting insulin resistance. In summary, our results highlight the role of let-7d-5p as a potential therapeutic target for atherosclerosis since its overexpression induce a decrease in inflammation and VSMCs proliferation, and also, as a novel non-invasive diagnostic biomarker for atherosclerosis in overweight patients.
PubMed: 38945455
DOI: 10.1016/j.bbadis.2024.167327 -
Pharmacological Research Jun 2024Faecalibacterium prausnitzii (F. prausnitzii) has been recognized for its various intestinal and extraintestinal benefits to human. And reduction of F. prausnitzii has...
Faecalibacterium prausnitzii (F. prausnitzii) has been recognized for its various intestinal and extraintestinal benefits to human. And reduction of F. prausnitzii has been linked to an increased risk of intestinal fibrosis in patients of Crohn's disease (CD). In this study, oral administration of either live F. prausnitzii or its extracellular vesicles (FEVs) can markedly mitigate the severity of fibrosis in mice induced by repetitive administration of DSS. In vitro experiment revealed that FEVs were capable of directing the polarization of peripheral blood mononuclear cells (PBMCs) towards an M2b macrophage phenotype, which has been associated with anti-fibrotic activities. This effect of FEV was found to be stable under various conditions that promote the development of pro-fibrotic M1/M2a/M2c macrophages. Proteomics and RNA sequencing were performed to uncover the molecular modulation of macrophages by FEVs. Notably, we found that FEVs reprogramed every metabolism of macrophages by damaging the mitochondria, and inhibited oxidative phosphorylation and glycolysis. Moreover, FEV-treated macrophages showed a decreased expression of PPARγ and an altered lipid processing phenotype characterized by decreased cholesterol efflux, which may promote energy reprogramming. Taken together, these findings identify FEV as a driver of macrophage reprogramming, suggesting that triggering M2b macrophage polarization by oral admiration of FEV may serve as strategy to alleviate hyperfibrotic intestine conditions in CD.
PubMed: 38945379
DOI: 10.1016/j.phrs.2024.107277 -
Food Chemistry Jun 2024Anthocyanin (ACN) has attracted considerable attention due to its wide range of physiological effects. However, challenges such as poor stability and limited...
Anthocyanin (ACN) has attracted considerable attention due to its wide range of physiological effects. However, challenges such as poor stability and limited bioavailability have hindered its utilization in functional foods. To address these issues, this research utilized milk-derived extracellular vesicles (MEV) as carriers for encapsulating and binding ACN through various techniques, including ultrasonic, electroporation, saponin treatment, incubation, and freeze-thaw cycles. The objective of these approaches was to enhance the stability of ACN and improve its oral delivery. Notably, the ACN-loaded MEV (MEV-ACN) prepared through ultrasonic exhibited small particle sizes and good stability under processing, storage, and simulated digestion conditions. Cellular studies revealed that MEV-ACN exhibited pro-oxidant properties and induced oxidative stress, leading to cell apoptosis with greater efficacy compared to free ACN. These findings suggest that encapsulating ACN within MEV can significantly enhance its processing and oral stability, as well as strengthening its dietary defense capabilities in anti-tumor applications.
PubMed: 38944922
DOI: 10.1016/j.foodchem.2024.140152 -
Journal of Extracellular Vesicles Jul 2024Extracellular vesicles (EVs) play a crucial role in triggering tumour-aggressive behaviours. However, the energetic process by which tumour cells produce EVs remains...
Extracellular vesicles (EVs) play a crucial role in triggering tumour-aggressive behaviours. However, the energetic process by which tumour cells produce EVs remains poorly understood. Here, we demonstrate the involvement of β-hexosaminidase B (HEXB) in mediating EV release in response to oxidative stress, thereby promoting the development of hepatocellular carcinoma (HCC). Mechanistically, reactive oxygen species (ROS) stimulate the nuclear translocation of transcription factor EB (TFEB), leading to the upregulation of both HEXB and its antisense lncRNA HEXB-AS. HEXB-AS can bind HEXB to form a protein/RNA complex, which elevates the protein stability of HEXB. The stabilized HEXB interacts with lysosome-associated membrane glycoprotein 1 (LAMP1), disrupting lysosome-multivesicular body (MVB) fusion, which protects EVs from degradation. Knockdown of HEXB efficiently inhibits EV release and curbs HCC growth both in vitro and in vivo. Moreover, targeting HEXB by M-31850 significantly inhibits HCC growth, especially when combined with GW4869, an inhibitor of exosome release. Our results underscore the critical role of HEXB as a modulator that promotes EV release during HCC development.
Topics: Extracellular Vesicles; Carcinoma, Hepatocellular; Animals; Oxidative Stress; Humans; Liver Neoplasms; Mice; Up-Regulation; Cell Line, Tumor; Cell Proliferation; RNA, Long Noncoding; Reactive Oxygen Species; Gene Expression Regulation, Neoplastic; Male; Mice, Nude
PubMed: 38944674
DOI: 10.1002/jev2.12468 -
Journal of Extracellular Vesicles Jul 2024Haematopoiesis dysregulation with the presence of immature myeloid and erythroid immunosuppressive cells are key characteristics of the immune escape phase of tumour...
Haematopoiesis dysregulation with the presence of immature myeloid and erythroid immunosuppressive cells are key characteristics of the immune escape phase of tumour development. Here, the role of in vitro generated B16F10 tumour cell-derived extracellular vesicles (tEVs) as indirect cellular communicators, participating in tumour-induced dysregulation of haematopoiesis, was explored. The isolated tEVs displayed features of small EVs with a size range of 100-200 nm, expressed the common EV markers CD63, CD9, and Alix, and had a spherical shape with a lipid bilayer membrane. Proteomic profiling revealed significant levels of angiogenic factors, particularly vascular endothelial growth factor (VEGF), osteopontin, and tissue factor, associated with the tEVs. Systemic administration of these tEVs in syngeneic mice induced splenomegaly and disrupted haematopoiesis, leading to extramedullary haematopoiesis, expansion of splenic immature erythroid progenitors, reduced bone marrow cellularity, medullary expansion of granulocytic myeloid suppressor cells, and the development of anaemia. These effects closely mirrored those observed in tumour-bearing mice and were not seen after heat inactivating the tEVs. In vitro studies demonstrated that tEVs independently induced the expansion of bone marrow granulocytic myeloid suppressor cells and B cells while reducing the frequency of cells in the erythropoietic lineage. These effects of tEVs were significantly abrogated by the blockade of VEGF or heat inactivation. Our findings underscore the important role of tEVs in dysregulating haematopoiesis during the immune escape phase of cancer immunoediting, suggesting their potential as targets for addressing immune evasion and reinstating normal hematopoietic processes.
Topics: Animals; Extracellular Vesicles; Mice; Hematopoiesis; Melanoma, Experimental; Mice, Inbred C57BL; Vascular Endothelial Growth Factor A; Cell Line, Tumor
PubMed: 38944672
DOI: 10.1002/jev2.12471 -
Translational Oncology Jun 2024Tumor derived Extracellular vesicles (EVs) in circulating system may contain tumor-specific markers, and EV detection in body fluids could become an important tool for...
Tumor derived Extracellular vesicles (EVs) in circulating system may contain tumor-specific markers, and EV detection in body fluids could become an important tool for early tumor diagnosis, prognosis assessment. Meningiomas are the most common benign intracranial tumors, few studies have revealed specific protein markers for meningiomas from patients' body fluids. In this study, using proximity labeling technology and non-tumor patient plasma as a control, we detected protein levels of EVs in plasma samples from meningioma patients before and after surgery. Through bioinformatics analysis, we discovered that the levels of EV count and protein count in meningioma patients were significantly higher than those in healthy controls, and were significantly decreased postoperatively. Among EV proteins in meningioma patients, the levels of MUC1, SIGLEC11, E-Cadherin, KIT, and TASCTD2 were found not only significantly elevated than those in healthy controls, but also significantly decreased after tumor resection. Moreover, using publicly available GEO databases, we verified that the mRNA level of MUC1, SIGLEC11, and CDH1 in meningiomas were significantly higher in comparison with normal dura mater tissues. Additionally, by analyzing human meningioma specimens collected in this study, we validated the protein levels of MUC1 and SIGLEC11 were significantly increased in WHO grade 2 meningiomas and were positively correlated with tumor proliferation levels. This study indicates that meningiomas secret EV proteins into circulating system, which may serve as specific markers for diagnosis, malignancy predicting and tumor recurrent assessment.
PubMed: 38943923
DOI: 10.1016/j.tranon.2024.102046 -
Archives of Oral Biology Jun 2024This systematic review aims to evaluate existing evidence to investigate the therapeutic efficacy of M2 macrophage-derived exosomes in bone regeneration. (Review)
Review
OBJECTIVE
This systematic review aims to evaluate existing evidence to investigate the therapeutic efficacy of M2 macrophage-derived exosomes in bone regeneration.
DESIGN
A comprehensive search between 2020 and 2024 across PubMed, Web of Science, and Scopus was conducted using a defined search strategy to identify relevant studies regarding the following question: "What is the impact of M2 macrophage-derived exosomes on bone regeneration?". Controlled in vitro and in vivo studies were included in this study. The SYRCLE tool was used to evaluate the risk of bias in the included animal studies.
RESULTS
This review included 20 studies published. Seven studies were selected for only in vitro analysis, whereas 13 studies underwent both in vitro and in vivo analyses. The in vivo studies employed animal models, including 163 C57BL6 mice and 73 Sprague-Dawley rats. Exosomes derived from M2 macrophages were discovered to be efficacious in promoting bone regeneration and vascularization in animal models of bone defects. These effects were primarily confirmed through morphological and histological assessments. This remarkable outcome is attributed to the regulation of multiple signaling pathways, as evidenced by the findings of 11 studies investigating the involvement of miRNAs in this intricate process. In addition, in vitro studies observed positive effects on cell proliferation, migration, osteogenesis, and angiogenesis. Heterogeneity in study methods hinders direct comparison of results across studies.
CONCLUSION
M2 macrophage-derived exosomes demonstrate remarkable potential for promoting bone regeneration. Further research optimizing their application and elucidating the underlying mechanisms can pave the way for clinical translation.
PubMed: 38943857
DOI: 10.1016/j.archoralbio.2024.106034