Despite significant progress in the medical field, there is still a pressing need for minimal-invasive tools to assist with decision-making, especially in cases of polytrauma. Our team explored the potential of serum-derived large extracellular vesicles, so called microparticles/microvesicles/ectosomes, to serve as a supportive tool in decision-making in polytrauma situations. We focused on whether monocyte derived large EVs may differentiate between polytrauma patients with internal organ injury (ISS > 15) and those without. Thus, we compared our EV data to soluble biomarkers such as tumour necrosis factor alpha (TNF alpha) and Interleukin-8 (IL-8). From the blood of 25 healthy and 26 patients with polytrauma large EVs were isolated, purified, and characterized. TNF alpha and IL-8 levels were quantified. We found that levels of these monocyte derived large EVs were significantly higher in polytrauma patients with internal organ damage and correlated with the ISS. Interestingly, we also observed a decline in AnnV+CD14+ large EVs during normal recovery after trauma. Thus, inflammatory serological markers as TNF alpha and as IL-8 demonstrated an inability to discriminate between polytrauma patients with or without internal organ damage, such as spleen, kidney, or liver lacerations/ruptures. However, TNF and IL-8 levels were elevated in polytrauma cases overall when contrasted with healthy non-traumatic controls. These findings suggest that delving deeper into the potential of AnnV+ large EVs derived from monocytes could highly beneficial in the managment of polytrauma, potentially surpassing the efficacy of commonly used serum markers.

A promising method for non-invasive cancer diagnosis and prognosis is through salivary biomarkers. By utilizing the distinct characteristics of saliva and the progress made in biomarker studies, these markers provide more accurate diagnoses for a wider range of malignancies. An attempt was made to thoroughly investigate the field of salivary biomarkers for tumor prognosis and diagnosis, with an emphasis on their use in various cancer forms. Predetermined search criteria were utilized for a systematic search across numerous databases for peer-reviewed papers from 2009 to 2021. Studies concentrating on the detection, validation, and clinical use of salivary biomarkers for different types of cancers were included in the inclusion criteria. Initially, 238 articles were found, of which 15 relevant articles satisfied the inclusion requirements. Information on study aims, methodology, findings, and conclusions were gathered for data extraction. We identified recurrent themes, patterns, and contradictions by a thematic analysis. We also assessed state-of-the-art salivary biomarkers for tumor diagnosis and prognosis. One major finding is the identification of biomolecules in saliva linked to several cancer forms, including pancreatic, oral, breast, lung, and stomach cancers. There is an increasing amount of evidence demonstrating the value of saliva-based diagnostics in oncology. This is due to new detection methods and developments in salivary proteomics and genomics. Identification of exosomes and microvesicles as salivary biomarker profiles offered molecular understandings of the etiology and evolution of cancer, thereby opening new avenues for diagnosis and treatment. Salivary biomarkers are a non-invasive approach for the early detection and prediction of cancer, thanks to the unique properties of saliva and advancements in biomarker research. This potential revolution could enhance patient outcomes and reduce cancer-related deaths.

Crohn\'s disease (CD) is a type of inflammatory bowel disease (IBD) affecting the gastrointestinal tract that can also cause extra-intestinal complications. Following exposure to the mRNA vaccine BNT162b2 (Pfizer-BioNTech) encoding the SARS-CoV-2 Spike (S) protein, some patients experienced a lack of response to the biological drug Adalimumab and a recrudescence of the disease. In CD patients in progression, resistant to considered biological therapy, an abnormal increase in intestinal permeability was observed, more often with a modulated expression of different proteins such as Aquaporin 8 (AQP8) and in tight junctions (e.g., ZO-1, Claudin1, Claudin2, Occludin), especially during disease flares. The aim of this study is to investigate how the SARS-CoV-2 vaccine could interfere with IBD therapy and contribute to disease exacerbation. We investigated the role of the SARS-CoV-2 Spike protein, transported by extracellular vesicles (EVs), and the impact of various EVs components, namely, exosomes (EXOs) and microvesicles (MVs), in modulating the expression of molecules involved in the exacerbation of CD, which remains unknown.

Mesenchymal stem cells (MSCs) are involved in tissue repair and anti-inflammatory activities and have shown promising therapeutic efficiency in different animal models of neurodegenerative disorders. Microvesicles (MVs), implicated in cellular communication, are secreted from MSCs and play a key role in determining the fate of cell differentiation. Our study examines the effect of human umbilical cord MSC-derived MVs (hUC-MSC MVs) on the proliferation and differentiation potential of adult neural stem cells (NSCs). Results showed that 0.2 μg MSC derived MVs significantly increased the viability of NSCs and their proliferation, as demonstrated by an increase in the number of neurospheres and their derived cells, compared to controls. In addition, all hUC-MSC MVs concentrations (0.1, 0.2 and 0.4 µg) induced the differentiation of NSCs toward precursors (Olig2 + ) and mature oligodendrocytes (MBP+). This increase in mature oligodendrocytes was inversely proportional to the dose of MVs. Moreover, hUC-MSC MVs induced the differentiation of NSCs into neurons (β-tubulin + ), in a dose-dependent manner, but had no effect on astrocytes (GFAP+). Furthermore, treatment of NSCs with hUC-MSC MVs (0.1 and 0.2 μg) significantly increased the expression levels of the proliferation marker Ki67 gene, compared to controls. Finally, hUC-MSC MVs (0.1 μg) significantly increased the expression level of Sox10 transcripts; but not Pax6 gene, demonstrating an increased NSC ability to differentiate into oligodendrocytes. In conclusion, our study showed that hUC-MSC MVs increased NSC proliferation in vitro and induced NSC differentiation into oligodendrocytes and neurons, but not astrocytes.

OBJECTIVE: Several pathological conditions trigger the formation of microvesicles (MVs), including infectious diseases such as COVID-19. The shedding of MVs increases the levels of inflammatory factors (e.g., interleukin-6; IL-6) and ultimately leads to an inflammatory cascade response, while also increasing the procoagulant response. The current study aimed to evaluate the level of circulating MVs and their procoagulant activity as well as the serum level of IL-6 in patients with COVID-19 and healthy controls. In this case-control study, 65 patients with COVID-19 and 30 healthy individuals were sampled after obtaining written informed consent. MVs counting was measured using conjugated CD61, CD45, CD235a, and Annexin-V antibodies. Additionally, the procoagulant activity of MVs and the IL-6 level were estimated using enzyme-linked immunosorbent assay (ELISA).
RESULTS: The majority of MVs were platelet-derived MVs (PMVs). Patients with COVID-19 had significantly higher levels of MVs, procoagulant MVs, and IL-6 compared to healthy controls (p < 0.001). MVs were significantly correlated with procoagulant MVs, D-Dimer levels, fibrinogen, and IL-6, but not with platelet, lymphocyte, and neutrophil counts.
CONCLUSIONS: Elevated levels of procoagulant MVs and their association with inflammatory and coagulation markers in patients with COVID-19 are suggested as a novel circulatory biomarker to evaluate and predict the procoagulant activity and severity of COVID-19.

The pathogenesis of type 2 diabetes (T2D) involves dysfunction in multiple organs, including the liver, muscle, adipose tissue, and pancreas, leading to insulin resistance and β cell failure. Recent studies highlight the significant role of extracellular vesicles (EVs) in mediating inter-organ communication in T2D. This review investigates the role of EVs, focusing on their presence and biological significance in human plasma and tissues affected by T2D. We explore specific EV cargo, such as miRNAs and proteins, which affect insulin signaling and glucose metabolism, emphasizing their potential as biomarkers. By highlighting the diagnostic and therapeutic potential of EVs, we aim to provide new insights into their role in early detection, disease monitoring, and innovative treatment strategies for T2D.

Recently, the therapeutic potential of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) has been extensively studied in both human and veterinary medicine. EVs are nano-sized particles containing biological components commonly found in other biological materials. For that reason, EV isolation and characterization are critical to draw precise conclusions during their investigation. Research on EVs within veterinary medicine is still considered in its early phases, yet numerous papers were published in recent years. The conventional adult tissues for deriving MSCs include adipose tissue and bone marrow. Nonetheless, alternative sources such as synovial fluid, endometrium, gingiva, and milk have also been intermittently used. Fetal adnexa are amniotic membrane/fluid, umbilical cord and Wharton\'s jelly. Cells derived from fetal adnexa exhibit an intermediate state between embryonic and adult cells, demonstrating higher proliferative and differentiative potential and longer telomeres compared to cells from adult tissues. Summarized here are the principal and recent preclinical and clinical studies performed in domestic animals such as horse, cattle, dog and cat. To minimize the use of antibiotics and address the serious issue of antibiotic resistance as a public health concern, they will undoubtedly also be utilized in the future to treat infections in domestic animals. A number of concerns, including large-scale production with standardization of EV separation and characterization techniques, must be resolved for clinical application.

MicroRNAs (miRs) regulate physiological and pathological processes, including ischemia-induced angiogenesis and neovascularization. They can be transferred between cells by extracellular vesicles (EVs). However, the specific miRs that are packaged in EVs released from skeletal muscles, and how this process is modulated by ischemia, remain to be determined. We used a mouse model of hindlimb ischemia and next generation sequencing (NGS) to perform a complete profiling of miR expression and determine the effect of ischemia in skeletal muscles, and in EVs of different sizes (microvesicles (MVs) and exosomes) released from these muscles. Ischemia significantly modulated miR expression in whole muscles and EVs, increasing the levels of several miRs that can have pro-angiogenic effects (angiomiRs). We found that specific angiomiRs are selectively enriched in MVs and/or exosomes in response to ischemia. In silico approaches indicate that these miRs modulate pathways that play key roles in angiogenesis and neovascularization, including HIF1/VEGF signaling, regulation of actin cytoskeleton and focal adhesion, NOTCH, PI3K/AKT, RAS/MAPK, JAK/STAT, TGFb/SMAD signaling and the NO/cGMP/PKG pathway. Thus, we show for the first time that angiomiRs are selectively enriched in MVs and exosomes released from ischemic muscles. These angiomiRs could be targeted in order to improve the angiogenic function of EVs for potential novel therapeutic applications in patients with severe ischemic vascular diseases.

Extracellular vesicles (EVs) are nanosized heat-stable vesicles released by virtually all cells in the body, including tumor cells and tumor-infiltrating dendritic cells (DCs). By carrying molecules from originating cells, EVs work as cell-to-cell communicators in both homeostasis and cancer but may also represent valuable therapeutic and diagnostic tools. This review focuses on the role of tumor-derived EVs (TEVs) in the modulation of DC functions and on the therapeutic potential of both tumor- and DC-derived EVs in the context of immunotherapy and DC-based vaccine design. TEVs were originally characterized for their capability to transfer tumor antigens to DCs but are currently regarded as mainly immunosuppressive because of the expression of DC-inhibiting molecules such as PD-L1, HLA-G, PGE2 and others. However, TEVs may still represent a privileged system to deliver antigenic material to DCs upon appropriate engineering to reduce their immunosuppressive cargo or increase immunogenicity. DC-derived EVs are more promising than tumor-derived EVs since they expose antigen-loaded MHC, costimulatory molecules and NK cell-activating ligands in the absence of an immunosuppressive cargo. Moreover, DC-derived EVs possess several advantages as compared to cell-based drugs such as a higher antigen/MHC concentration and ease of manipulation and a lower sensitivity to immunosuppressive microenvironments. Preclinical models showed that DC-derived EVs efficiently activate tumor-specific NK and T cell responses either directly or indirectly by transferring antigens to tumor-infiltrating DCs. By contrast, however, phase I and II trials showed a limited clinical efficacy of EV-based anticancer vaccines. We discuss that the future of EV-based therapy depends on our capability to overcome major challenges such as a still incomplete understanding of their biology and pharmacokinetic and the lack of standardized methods for high-throughput isolation and purification. Despite this, EVs remain in the limelight as candidates for cancer immunotherapy which may outmatch cell-based strategies in the fullness of their time.

Chronic exposure to heavy metals as aluminum chloride (AlCl3) could result in severe health hazards such as chronic renal injury. The present study aimed to evaluate the therapeutic potential of adipose tissue-derived stem cells (ASCs) in comparison to their microvesicles (MV) in AlCl3-induced chronic renal injury. Forty-eight adult male Wistar rats were divided into four groups: Control group, AlCl3-treated group, AlCl3/ASC-treated group, and AlCl3/MV-treated group. Biochemical studies included estimation of serum urea and creatinine levels, oxidative biomarkers assay, antioxidant biomarkers, serum cytokines (IL-1β, IL-8, IL-10, and IL-33), real time-PCR analysis of renal tissue MALT1, TNF-α, IL-6, and serum miR-150-5p expression levels. Histopathological studies included light and electron microscopes examination of renal tissue, Mallory trichrome stain for fibrosis, Periodic acid Schiff (PAS) stain for histochemical detection of carbohydrates, and immunohistochemical detection of Caspase-3 as apoptosis marker, IL-1B as a proinflammatory cytokine and CD40 as a marker of MVs. AlCl3 significantly deteriorated kidney function, enhanced renal MDA and TOS, and serum cytokines concentrations while decreased the antioxidant parameters (SOD, GSH, and TAC). Moreover, serum IL-10, TNF-α, miR-150-5p, and renal MALT1 expression values were significantly higher than other groups. Kidney sections showed marked histopathological damage in both renal cortex and medulla in addition to enhanced apoptosis and increased inflammatory cytokines immunoexpression than other groups. Both ASCs and MVs administration ameliorated the previous parameters levels with more improvement was detected in MVs-treated group. In conclusion: ASCs-derived MVs have a promising ameliorating effect on chronic kidney disease.