0000000000193026
AUTHOR
Ornella Urzì
LE VESCICOLE EXTRACELLULARI VEGETALI PER LO SVILUPPO DI NUOVI NUTRACEUTICI: STUDIO PRE-CLINICO E CLINICO DELLE PROPRIETÀ BIOLOGICHE DELLE VESCICOLE ISOLATE DA SUCCO DI LIMONE
Razionale dello studio: Le vescicole extracellulari (EVs) sono strutture lipoproteiche rilasciate dalle cellule animali e vegetali, che veicolano sostanze bioattive tra cui lipidi, proteine, acidi nucleici e altri metaboliti, rendendole più stabili e biodisponibili. EVs isolate da semi, foglie e frutti di svariate specie vegetali presentano attività anti-tumorale, anti-infiammatoria ed anti-ossidante. Metodi e Risultati: Il nostro gruppo di ricerca si occupa da anni della caratterizzazione strutturale e funzionale delle EVs da succo di limone (LEVs). Le LEVs esercitano effetti antinfiammatori sia in vitro, su linee di macrofagi murini, che ex vivo, su linfociti T, attraverso l’inibizione de…
Possible role for IL-40 and IL-40-producing cells in the lymphocytic infiltrated salivary glands of patients with primary Sjögren's syndrome
ObjectivesAim of this study was to investigate the expression of interleukin (IL)-40, a new cytokine associated with B cells homoeostasis and immune response, in primary Sjögren syndrome (pSS) and in pSS-associated lymphomas.Methods29 patients with pSS and 24 controls were enrolled. Minor salivary gland (MSG) biopsies from patients, controls and parotid gland biopsies from pSS-associated lymphoma were obtained. Quantitative gene expression analysis by TaqMan real-time PCR and immunohistochemistry for IL-40 were performed on MSG. MSG cellular sources of IL-40 were determined by flow-cytometry and immunofluorescence. Serum concentration of IL-40 was assessed by ELISA and cellular sources of I…
Extracellular Vesicle microRNAs Contribute to the Osteogenic Inhibition of Mesenchymal Stem Cells in Multiple Myeloma
Osteolytic bone disease is the major complication associated with the progression of multiple myeloma (MM). Recently, extracellular vesicles (EVs) have emerged as mediators of MM-associated bone disease by inhibiting the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Here, we investigated a correlation between the EV-mediated osteogenic inhibition and MM vesicle content, focusing on miRNAs. By the use of a MicroRNA Card, we identified a pool of miRNAs, highly expressed in EVs, from MM cell line (MM1.S EVs), expression of which was confirmed in EVs from bone marrow (BM) plasma of patients affected by smoldering myeloma (SMM) and MM. Notably,we found that miR-129-5p, whic…
Extracellular Vesicles from Plants: Current Knowledge and Open Questions.
The scientific interest in the beneficial properties of natural substances has been recognized for decades, as well as the growing attention in extracellular vesicles (EVs) released by different organisms, in particular from animal cells. However, there is increasing interest in the isolation and biological and functional characterization of these lipoproteic structures in the plant kingdom. Similar to animal vesicles, these plant-derived extracellular vesicles (PDEVs) exhibit a complex content of small RNAs, proteins, lipids, and other metabolites. This sophisticated composition enables PDEVs to be therapeutically attractive. In this review, we report and discuss current knowledge on PDEVs…
Plant-RNA in Extracellular Vesicles: The Secret of Cross-Kingdom Communication
The release of extracellular vesicles (EVs) is a common language, used by living organisms from different kingdoms as a means of communication between them. Extracellular vesicles are lipoproteic particles that contain many biomolecules, such as proteins, nucleic acids, and lipids. The primary role of EVs is to convey information to the recipient cells, affecting their function. Plant-derived extracellular vesicles (PDEVs) can be isolated from several plant species, and the study of their biological properties is becoming an essential starting point to study cross-kingdom communication, especially between plants and mammalians. Furthermore, the presence of microRNAs (miRNAs) in PDEVs repres…
The dark side of foetal bovine serum in extracellular vesicle studies
Extracellular vesicles (EVs) have been shown to be involved in cell-cell communication and to take part in both physiological and pathological processes. Thanks to their exclusive cargo, which includes proteins, lipids, and nucleic acids from the originating cells, they are gaining interest as potential biomarkers of disease. In recent years, their appealing features have been fascinating researchers from all over the world, thus increasing the number of in vitro studies focused on EV release, content, and biological activities. Cultured cell lines are the most-used source of EVs; however, the EVs released in cell cultures are influenced by the cell culture conditions, such as the use of fo…
Developing liver spheroids for elucidating the role of colorectal cancer-derived smallextracellular vesicles in the pre-metastatic niche formation
Introduction: Colorectal cancer (CRC) is the third most common tumor in the world frequently associated with liver metastasiscausing unfavorable prognosis. A recent study performed in our laboratory has demonstrated that CRC small extracellular vesi-cles (SEVs) induce an epithelial to mesenchymal transition (EMT) of hepatocytes (heps) driving them to actively participate inthe pre-metastatic niche formation, probably contributing to form a liver fibrotic microenvironment. Since 2D cell cultures par-tially reflect the structural complexity of the in vivo microenvironment to give more power to our functional model, we switchedto use hepatocyte spheroids (HeSPHs), which can give us more proper…
Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways
Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions. Non-polarized macrophages (M0) differentiated from THP-1 cells were co-cultured with SEVs derived from a colorectal cancer (CRC) cell line, SW480, and a multiple myeloma (MM) cell line, MM1.S. The expression of PD-L1, interleukin-6 (IL-6), a…
Anti-inflammatory properties of lemon-derived extracellular vesicles are achieved through the inhibition of ERK/NF-κB signalling pathways
Chronic inflammation is associated with the occurrence of several diseases. However, the side effects of anti-inflammatory drugs prompt the identification of new therapeutic strategies. Plant-derived extracellular vesicles (PDEVs) are gaining increasing interest in the scientific community for their biological properties. We isolated PDEVs from the juice of Citrus limon L. (LEVs) and characterized their flavonoid, limonoid and lipid contents through reversed-phase high-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (RP-HPLC-ESI-Q-TOF-MS). To investigate whether LEVs have a protective role on the inflammatory process, murine a…
Colorectal cancer-derived small extracellular vesicles induce TGFβ1-mediated epithelial to mesenchymal transition of hepatocytes
Abstract Background Metastatic disease is the major cause of cancer-related deaths. Increasing evidence shows that primary tumor cells can promote metastasis by preparing the local microenvironment of distant organs, inducing the formation of the so-called “pre-metastatic niche”. In recent years, several studies have highlighted that among the tumor-derived molecular components active in pre-metastatic niche formation, small extracellular vesicles (sEVs) play a crucial role. Regarding liver metastasis, the ability of tumor-derived sEVs to affect the activities of non-parenchymal cells such as Kupffer cells and hepatic stellate cells is well described, while the effects on hepatocytes, the m…
Emerging insights on the biological impact of extracellular vesicle-associated ncRNAs in multiple Myeloma
Increasing evidence indicates that extracellular vesicles (EVs) released from both tumor cells and the cells of the bone marrow microenvironment contribute to the pathobiology of multiple myeloma (MM). Recent studies on the mechanisms by which EVs exert their biological activity have indicated that the non-coding RNA (ncRNA) cargo is key in mediating their effect on MM development and progression. In this review, we will first discuss the role of EV-associated ncRNAs in different aspects of MM pathobiology, including proliferation, angiogenesis, bone disease development, and drug resistance. Finally, since ncRNAs carried by MM vesicles have also emerged as a promising tool for early diagnos…