Search Results (533)

Background: A comparative study was conducted to evaluate the potential of extracellular, tumor-derived microvesicles (MVs)s in promoting kidney regeneration. Methods: MVs were collected from L929 sarcoma, LLC, and B16 melanoma cells, and mesenchymal stem cells (MSCs). The regenerative activity of MVs was evaluated in an experimental murine model of chronic kidney injury (CKI). Results: Both tumor-derived MVs (T-MVs) and MSC-derived MVs (MSC-MVs) significantly improved kidney function and histological structure. Specifically, the height of collecting tubules in the middle third of the renal medulla returned to normal levels following MV treatment. Both T-MVs and MSC-MVs reduced the proportion of pro-inflammatory CD4+CD44+ T cells in renal cell infiltrates and spleens of CKI mice. Furthermore, treatment with these MVs increased the number of natural CD4+CD25+FoxP3+ regulatory T cells in the spleen, indicating their immunomodulatory effects. Conclusions: These findings suggest that T-MVs, similar to MSC-MVs, possess a universal capacity to promote kidney tissue regeneration and exert anti-inflammatory immunomodulatory effects. Full article

Mercury (Hg) exposure is a major environmental risk factor, closely linked to oxidative stress and cardiovascular disease. Red blood cells (RBC), due to their high oxygen exposure and lack of repair mechanisms, are particularly sensitive to oxidative injury and are key indicators of systemic redox imbalance. This study evaluates the protective effects of polyphenolic extracts from Annurca apple, specifically flesh and peel, from both ripe and unripe fruit, on HgCl₂-exposed human RBCs. Key oxidative stress markers were measured, including ROS production, GSH levels, lipid peroxidation (TBARS), MetHb formation, SH group content, microvesicle (MV) generation, and morphological changes. Peel extracts, particularly those from ripe apples, consistently exhibited stronger antioxidant and cytoprotective effects than flesh extracts, effectively reversing Hg-induced oxidative damage and preserving RBC integrity. Notably, these extracts restored redox homeostasis and GSH levels, reduced ROS and TBARS accumulation, prevented MetHb formation, and mitigated MV release and morphological alterations. These protective effects appear to involve multifactorial mechanisms. These findings highlight the nutraceutical potential of Annurca apple extracts in counteracting heavy metal-induced oxidative stress and support their possible relevance for future studies aimed at health protection and waste valorization. Full article

Resistance exercise can enhance or preserve muscle mass and/or strength. Modifying factors are secreted following resistance exercise. Biomarkers like cytokines and extracellular vesicles, especially small extracellular vesicles, are released into the circulation and play an important role in cell-to-cell and inter-tissue communications. There is increasing evidence that physical activity itself promotes the release of extracellular vesicles into the bloodstream, suggesting the importance of vesicles in mediating systemic adaptations following exercise. Extracellular vesicles contain proteins, nucleic acids like miRNAs, and other molecules targeting different cell types and tissues of distant organs. Therefore, extracellular vesicles and encapsulated miRNAs are fine tuners of protein synthesis and are important in the adaptation after resistance training. However, there is a lack of strong data supporting the precise mechanisms of these processes. In this literature review, we collected publications related to miRNA and extracellular vesicle profile changes induced by resistance exercise. To the best of our knowledge, the changes in human extracellular vesicle and microRNA profiles following resistance exercise have not been reviewed yet. We aimed to assess the shortcomings and difficulties characterizing this research area, to summarize the existing results to date, and to propose possible solutions that could help standardize the implementation of future investigations. Full article

Despite notable advancements in clinical care, cardiovascular disease (CVD) remains a leading global cause of mortality. Encompassing a wide range of heart and blood vessel disorders, CVD requires targeted prevention and treatment strategies to mitigate its public health impact. In recent years, extracellular vesicles (EVs) have emerged as crucial mediators of intercellular communication, influencing key processes such as vascular remodeling, inflammation, and immune responses in CVDs. EVs, including exosomes and microvesicles, carry bioactive molecules such as miRNAs, proteins, and lipids that contribute to disease progression. They are released by various cell types, including platelets, erythrocytes, leukocytes, endothelial cells, and cardiomyocytes, each playing distinct roles in cardiovascular homeostasis and pathology. Given their presence in circulating blood and other body fluids, EVs are increasingly recognized as promising non-invasive biomarkers for CVD diagnosis and prognosis. Furthermore, EV-based therapeutic strategies, including engineered EVs for targeted drug delivery, are being explored for treating atherosclerosis, myocardial infarction, heart failure, and hypertension. However, challenges remain regarding the standardization of EV isolation and characterization techniques, which are critical for their clinical implementation. This review highlights the diverse roles of EVs in CVD pathophysiology, their potential as diagnostic and prognostic biomarkers, and emerging therapeutic applications, clearing the way for their integration into cardiovascular precision medicine. Full article

To assess the association between known (PlGF, sFlt-1, betaHCG, PAPPA) and novel (cell-free DNA, cfDNA, and total endothelial and platelet microvesicles, MVs) maternal blood biomarkers measured at the first trimester with the later development of preeclampsia (PE) and PE-related severe adverse events (SAE), we conducted a retrospective case–control study including women with an established diagnosis of preeclampsia (cases) and healthy pregnant women (controls). Biomarkers were measured from first-trimester blood samples stored in a hospital biobank. A total of 89 women, 54 women with PE and 35 controls were included. PlGF showed good performance for diagnosing overall preeclampsia (AUC: 0.71; 95% CI 0.59–0.82), early-onset preeclampsia (AUC 0.80; 95% CI 0.68–0.9) and fetal-neonatal SAEs (AUC: 0.73; 95% CI 0.63–0.84). Multivariate models including clinical variables, PlGF and other biomarkers showed good to very good discrimination for the development of PE, early-onset PE and fetal-neonatal SAEs (AUCs of 0.87, 0.89 and 0.79, respectively). Platelet-derived MVs were the best isolated biomarker for late-onset PE and, combined with systolic blood pressure, showed good discrimination (AUC: 0.81; 95% CI 0.71–0.92). For maternal SAEs, a model incorporating cfDNA and sFlt-1 provided excellent discrimination (AUC 0.92; 95% CI 0.82–1.00). Our findings suggest that multivariate models incorporating both clinical variables and first-trimester biomarkers may improve risk stratification for PE, especially for late-onset PE and for identifying women at risk of severe maternal or fetal complications. Notably, the inclusion of novel biomarkers such as cfDNA and MVs added value in clinical scenarios where the predictive performance of existing tools remains suboptimal. Full article

Extracellular vesicles (EVs) are bilayer lipid membrane particles that are released by every cell type. These secretions are further classified as exosomes, ectosomes, and microvesicles. They contain biomolecules (RNAs, proteins, metabolites, and lipids) with the ability to modulate various biological processes and have been shown to play a role in intercellular communication and cellular rejuvenation. Various studies suggest exosomes and/or microvesicles as a potential platform for drug delivery. EVs may deliver lipids and nucleotides directly to an injury site in an axon, promoting growth cone stabilization and membrane expansion as well as repair, thus positively modulating adult axon regeneration. In this review, we will provide a perspective on the metabolite composition of EVs in adult axonal regeneration relevant to the central nervous system (CNS), specifically that pertaining to the optic nerve. We will present an overview of the methods for isolation, enrichment, omics data analysis and quantification of extracellular vesicles with the goal of providing direction for future studies relevant to axon regeneration. We will also include current resources for multi-omics data integration relevant to extracellular vesicles from diverse cell types. Full article

Extracellular vesicles (EVs) have gained increasing attention in recent years as a valuable focus of scientific investigation, owing to their potential therapeutic properties and wide-ranging uses in medicine. EVs are a heterogeneous population of membrane-enclosed vesicles with lipid bilayers, released by cells from both animal and plant origins. These widespread vesicles play a crucial role in cell-to-cell communication and serve as carriers for a variety of biomolecules such as proteins, lipids, and nucleic acids. The most common method of classifying EVs is based on their biogenesis pathway, distinguishing exosomes, microvesicles, and apoptotic bodies as the major types. In recent years, there has been a growing interest in PDEs, as they offer a practical and eco-friendly alternative to exosomes sourced from mammals. Mounting data from both laboratory-based and animal model experiments indicate that PDEs have natural therapeutic properties that modulate biological activities within cells, demonstrating properties such as anti-inflammatory, antioxidant, and anticancer effects that may aid in treating diseases and enhancing human well-being. Moreover, PDEs hold promise as reliable and biologically compatible carriers for drug delivery. Although studies conducted before clinical trials have yielded encouraging results, numerous unresolved issues and gaps in understanding remain, which must be resolved to facilitate the effective advancement of PDEs toward medical use in human patients. A key concern is the absence of unified procedures for processing materials and for obtaining PDEs from different botanical sources. This article provides a comprehensive summary of existing findings on PDEs, critically examining the hurdles they face, and highlighting their substantial promise as a novel class of therapeutic tools for a range of illnesses. Full article

Lactic acid bacteria are components of the gastrointestinal tract microbiota in both humans and animals and are widely used as probiotics. Lactobacillus is the most closely related genus to probiotic activity. It is capable of releasing membrane microvesicles (MVs), whose primary functions include carrying and transmitting antigens to host tissues and modulating host defense responses. In the present study, MVs were isolated from Lactobacillus acidophilus resident in the ileum of free-living rats, and their immunostimulant effect was evaluated in two biological models. MVs were characterized using SDS-PAGE electrophoresis, electron microscopy, and nanoparticle tracking analysis. In the first model, the immunostimulatory effect of MVs was evaluated on ovine abomasal explants, which had been previously stimulated with MVs and then challenged with third-stage larvae of Haemonchus contortus. This resulted in a decrease in the percentage of larval association and favored the migration of inflammatory cells to the infection site. In the second model, the macrophage cell line RAW 264.7 was stimulated with MVs to evaluate the expression of transcripts encoding IL-1β and TNF-α. MVs isolated from L. acidophilus demonstrate immunostimulatory and probiotic effects in the two biological models assessed. This suggested that the MVs possess similar immunostimulatory effects as those reported for the parent bacteria. Full article

The increasing prevalence of liver diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD), presents considerable medical challenges, particularly given the absence of approved pharmacological treatments, which underscores the necessity to comprehend its underlying mechanisms. Extracellular vesicles (EVs), which are tiny particles released by cells, play a crucial role in facilitating communication and can transport harmful molecules that promote inflammation and tissue damage. These EVs are involved in the progression of various types of liver disorders since they aggravate inflammation and oxidative stress. Because of their critical role, it is believed that EVs are widely involved in the initiation and progression of MASLD, as well as in viral hepatitis, alcoholic liver disease, drug-induced liver injury, and hepatocellular carcinoma. This review emphasizes recent findings regarding the functions of EVs in the above liver pathologies and underscores their potential as new therapeutic targets, paving the way for innovative approaches to address those detrimental liver conditions. Full article

Phosphatidylserine (PS) is an essential phospholipid and an emerging biomarker involved in key biological processes. While annexin V (axV) is the most widely used tool for PS detection, its calcium-dependent binding and other limitations have spurred interest in alternative probes. The lactadherin C2 domain (lactC2) offers a promising alternative, addressing many of the drawbacks associated with axV. However, its broader adoption has been hindered by challenges in production and modification for convenient experimental use. Here, we demonstrate the successful in-house engineering of fully functional recombinant bovine lactC2-based fluorescent sensors and compare their key parameters to axV probes. We show that mNeonGreen–lactC2 fusion exhibits calcium-independent binding with a comparable dissociation constant for 20% PS liposomes. We also demonstrate the detrimental effects of primary amine modification on lactC2’s PS binding efficiency, suggesting the preferential use of fluorescent protein fusion or alternative approaches. Finally, we show that unlike full-length lactadherin or axV, lactC2 inhibited thrombin generation only at high concentrations (>250 nM) in coagulation assays. These findings establish recombinant lactC2 as a versatile and promising PS sensor, with potential applications in experimental settings where axV might be unsuitable Full article

Background: Diclofenac (DCF) is a widely used nonsteroidal anti-inflammatory drug (NSAID), but its conventional formulations may have limited efficacy and are associated with adverse effects. This study aimed to evaluate the anti-inflammatory and antioxidant effects of diclofenac encapsulated in chitosan-coated lipid microvesicles (DCF-m) compared to free DCF in a rat model of subacute inflammation. Method: DCF-m was prepared using L-α-phosphatidylcholine and coated with chitosan (CHIT). Subacute inflammation was induced using the cotton pellet granuloma model, and animals were divided into four groups (n = 5): a negative control group without granuloma receiving vehicle (double-distilled water), a control group with granuloma receiving vehicle, a group with granuloma treated with 15 mg/kg of free DCF, and a group with granuloma treated with 15 mg/kg of DCF-m. Results: Both DCF and DCF-m significantly reduced granuloma mass, body weight gain, and serum inflammatory markers compared to the control group with granuloma. Moreover, DCF-m treatment led to a more pronounced reduction in granulomatous inflammation and a greater enhancement of antioxidant enzyme activity than free DCF. Conclusions: These findings suggest that DCF-m exhibits superior anti-inflammatory and antioxidant properties compared to conventional diclofenac in a model of subacute inflammation. Full article

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are released into the extracellular space by almost all known cell types. They facilitate communication between cells by transferring bioactive molecules, which impact both physiological processes and the development of diseases. EVs play a crucial role in the pathogenesis of various diseases by participating in multiple pathological processes. They contribute to disease progression by triggering cytokine release, modulating immune cell activity, and inducing inflammatory and immune responses. Beyond their pathological implications, EVs also offer significant therapeutic potential. Both natural and engineered EVs show great potential in the fields of targeted therapy, drug delivery, and immune modulation in dermatological applications. The development of EV-based treatments is showing promise in advancing patient outcomes, particularly in chronic inflammatory and immune-mediated skin conditions. This review comprehensively examined the biogenesis, classification, and functional roles of EVs, including advanced methods for their isolation and characterization. Furthermore, we summarized recent studies highlighting the involvement of EVs in four major inflammatory skin diseases: psoriasis, atopic dermatitis, systemic lupus erythematosus, and wound healing. Full article

Extracellular vesicles (EVs) are cell-derived lipid-bound vesicles divided into apoptotic bodies, microvesicles (MVs), and exosomes based on their biogenesis, release pathway, size, content, and functions. EVs are intercellular mediators that significantly affect muscle diseases such as Duchenne muscular dystrophy (DMD). DMD is a fatal X-linked disorder caused by mutations in the dystrophin gene, leading to muscle degeneration. Mdx mice are the most commonly used model to study the disease, and in this study, we phenotypically characterized plasma MVs from mdx mice by flow cytometry. Furthermore, we assessed the ability of plasma MVs to modulate muscle inflammation, damage, and/or regeneration by intramuscular injection of MVs from mdx mice into mdx or DBA/2 mice as a control. In both mouse lineages, platelets and erythrocytes were the primary sources of MVs, and CD3⁺ CD4⁺ MVs were observed only in mdx mice. We also observed that plasma MVs from mdx mice induced muscle damage in mdx mice but not in DBA/2 mice, while plasma MVs from DBA/2 mice did not induce muscle damage in either mouse lineage. These results indicate that plasma MVs from mdx are potentially pathogenic. However, this condition also depends on the muscular tissue status, which must be responsive due to active inflammatory or regenerative responses. Full article

Background: Our previous study demonstrated that miR-140-3p induced osteocalcin expression in osteoblastic MC3T3-E1 cells. In this study, we investigated the direct effects of miR-140-3p on bone turnover in senescence-accelerated mice. Methods: In order to evaluate the effects of miR-140-3p, we formulated lipid nanoparticles (LNPs) containing miR-140-3p (100 μg/mL), with or without flotillin-2 (Flo2), a microvesicle marker excreted by osteoblasts. LNP was administered into the right tibia of the P6 strain of senescence-accelerated mice (SAMP6). Four-week-old SAMP6 males were divided into three groups: control, LNP, and LNP + Flo2. LNPs were administered five times, once every three days. No gait abnormalities were observed in any group. Two days after the last administration of LNPs, blood and urine samples were collected to measure bone turnover markers and blood chemistry and to perform urinalysis. Bone histomorphometry was performed on the left femur, contralateral to the administration site. The pancreas was removed for insulin staining of the Langerhans islets. Results: The LNP + Flo2 group showed greater bone volume, trabecular thickness, and osteoid thickness in bone histomorphometry. Carboxylated osteocalcin, a bone formation marker, was also higher in the LNP + Flo2 group, indicating that LNP + Flo2 activated osteoblastic function. Insulin levels in the islets of Langerhans did not differ across the groups, consistent with under-carboxylated osteocalcin levels. Conclusions: LNP + Flo2 effectively improved bone metabolism. Full article

During sexual reproduction, the freshwater ciliate Tetrahymena thermophila sheds membrane-bound vesicles into the extracellular environment (cEMVs: ciliary extracellular micro-vesicles). We provide evidence that 100 nm vesicles shed from the cilia of starved cells promote mating between cells of complementary mating types. A proteomic analysis revealed that these EMVs are decorated with mating-type proteins expressed from the MAT locus, proteins that define a cell’s sex (one of seven). Once the mating junction is established between cells, smaller 60 nm vesicles (junction vesicles) appear within the extracellular gap that separates mating partners. Junction vesicles (jEMVs) may play a role in remodeling the mating junction through which gametic pronuclei are exchanged. Evidence is presented demonstrating that cells must be able to internalize extracellular signals via some form of endocytosis in order to trigger conjugation. Finally, an evolutionarily conserved fusogen (Hap2) implicated in pore formation also appears necessary for jEMV processing. This system offers an excellent opportunity for studies on ectosome shedding, intercellular signaling and shed vesicle uptake by macro-pinocytosis, as they relate to sexual reproduction in the ciliate Tetrahymena thermophila. Full article