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Introduction
Publications
Publications (66)
To be profitably exploited in medicine, nanosized systems must be endowed with biocompatibility, targeting capability, the ability to evade the immune system, and resistance to clearance. Currently, biogenic nanoparticles, such as Extracellular Vesicles (EVs), are intensively investigated as the platform that naturally recapitulates these highly ne...
To be profitably exploited in medicine, nanosized systems must be endowed with biocompatibility, targeting capability, the ability to evade the immune system, and resistance to clearance. Currently, biogenic nanoparticles, such as Extracellular Vesicles (EVs), are intensively investigated as the platform that naturally recapitulates these highly ne...
To be profitably exploited in medicine as drug delivery carriers, nanosized systems should be endowed with essential properties, including high biocompatibility, stealth ability to escape the immune system, prolonged circulation lifetime, and targeting abilities towards the pathological tissues. Currently, the choice of biogenic nanoparticles as Ex...
Background
Synaptic dysfunction is an early mechanism in Alzheimer’s Disease (AD) which involves progressively larger areas of the brain over time. However, how it starts and propagates is unknown. We hypothesised that large extracellular vesicles (EVs) released by microglia exposed to and carrying Aβ 42 (Aβ‐EVs) may be responsible for these early...
Extracellular vesicles (EVs) large‐scale production is a crucial point for the translation of EVs from discovery to application of EV‐based products. In October 2021, the International Society for Extracellular Vesicles (ISEV), along with support by the FET‐OPEN projects, “The Extracellular Vesicle Foundry” (evFOUNDRY) and “Extracellular vesicles f...
Antithrombin (AT) is a glycoprotein produced by the liver and a principal antagonist of active clotting proteases. A deficit in AT function leads to AT qualitative deficiency, challenging to diagnose. Here we report that active AT may travel physiosorbed on the surface of plasma extracellular vesicles (EVs), contributing to form the “EV‐protein cor...
The widely overlapping physicochemical properties of lipoproteins (LPs) and extracellular vesicles (EVs) represents one of the main obstacles for the isolation and characterization of these pervasive biogenic lipid nanoparticles. We herein present the application of an atomic force microscopy (AFM)-based quantitative morphometry assay to the rapid...
Synaptic dysfunction is an early mechanism in Alzheimer’s disease that involves progressively larger areas of the brain over time. However, how it starts and propagates is unknown.
Here we show that Aβ released by microglia in association with large extracellular vesicles (Aβ-EVs) alters dendritic spine morphology in vitro, at the site of neuron in...
True-to-life nanoplastics as a closer model for environmental nanoplastics pollution.
AT is a glycoprotein produced by the liver and acts as the most important antagonist of clotting factors. A deficit in AT production or function leads to coagulation disorders. Two kinds of AT deficiencies are reported, named quantitative (or type I) and qualitative (or type II) defects. The first is characterized by low levels of AT in the bloodst...
Parkinson's disease (Pd) is an important disabling age-related disorder and is the second most common neuro-degenerative disease. currently, no established molecular biomarkers exist for the early diagnosis of Pd. circulating microRNAs (miRNAs), either vesicle-free or encapsulated in extracellular vesicles (EVs), have emerged as potential blood-bas...
Given the complexity of separating nanoplastics from environmental samples, studies have usually been conducted using synthetic polystyrene nanobeads. By mechanical fragmentation in cryogenic conditions of daily-life plastic items, we produced “true-to-life” nanoplastics (T2LNPs), that promises to give a true insight into the interaction with biolo...
[This corrects the article DOI: 10.3389/fbioe.2019.00452.].
Parkinson's disease (Pd) is an important disabling age-related disorder and is the second most common neuro-degenerative disease. currently, no established molecular biomarkers exist for the early diagnosis of Pd. circulating microRNAs (miRNAs), either vesicle-free or encapsulated in extracellular vesicles (EVs), have emerged as potential blood-bas...
Identification of extracellular vesicle (EV) subpopulations remains an open challenge. To date, the common strategy is based on searching and probing set of molecular components and physical properties intended to be univocally characteristics of the target subpopulation. Pitfalls include the risk to opt for an unsuitable marker set – which may eit...
Mesenchymal stromal/stem cells (MSCs) are increasingly employed for tissue regeneration, largely mediated through paracrine actions. Currently, extracellular vesicles (EVs) released by MSCs are major mediators of these paracrine effects. We evaluated whether rat-bone-marrow-MSC-derived EVs (rBMSCs-EVs) can ameliorate tendon injury in an in vivo rat...
This protocol paper describes how to assign a purity grade and to subsequently titrate extracellular vesicle (EV) solutions of a few microliters in volume by microplate COlorimetric NANoplasmonic (CONAN) assay. The CONAN assay consists of a solution of gold nanoparticles (AuNPs) into which the EV preparation is added. The solution turns blue if the...
Regenerative medicine is a multidisciplinary field aimed at developing methods, molecular agents, and (nano)materials to regrow, repair, or replace damaged, malfunctioning or missing tissues. Current approaches include and combine use of stem cells, tissue engineering based on functional biodegradable scaffolds, and cell-free strategies, with stem...
The term secretome, which traditionally refers only to single proteins, may be expanded to also include the great variety of nanoparticles secreted by cells (secNPs) into the extracellular space, which ranges from high-density lipoproteins of few nm to extracellular vesicles and fat globules of hundreds of nm. Widening the definition is urged by th...
After the publication of the above paper, the authors noted that the names of a couple of the authors listed on the paper were associated with the wrong affliation: Specifically, the eighth and ninth listed authors, Francesca Antonaros and Allison Piovesan, are located at DIMES at the University of Florence (fourth affiliation address), not at CSGI...
Down syndrome (DS) is caused by the presence of part or all of a third copy of chromosome 21. DS is associated with several phenotypes, including intellectual disability, congenital heart disease, childhood leukemia and immune defects. Specific microRNAs (miRNAs/miR) have been described to be associated with DS, although none of them so far have be...
Special Issue Information
Dear Colleagues,
Extracellular Vesicles (EVs) are nanosized structures known to mediate the transfer of biomaterials between cells. EV cargoes include molecules originating from a wide range of cellular districts, surprisingly including the cell nucleus. This implies that nuclear proteins and genomic DNA can be actively p...
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many...
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many...
Intersectin 1-short (ITSN1-s) is a 1220 amino acids ubiquitously-expressed scaffold protein presenting a multi-domain structure that allows to spatiotemporally regulate the functional interaction of a plethora of proteins. Beside its well-established role in endocytosis, ITSN1-s is involved in regulation of cell signaling and is implicated in tumor...
We report on the interaction of small (<150 nm) extracellular vesicles (EVs) with silicon surface. The study is conducted by leveraging Si nanomechanical microcantilever sensors actuated in static and dynamic modes, that allow tracking of EV collective adsorption energy and adsorbed mass. Upon incubation for 30 min at about 10 nM concentration, EVs...
Respiratory syncytial virus (RSV) is an important human pathogen, which infects respiratory tract epithelial cells causing bronchiolitis and pneumonia in children and the elderly. Recent studies have linked RSV matrix (M) ability to self-interaction and viral budding. However, RSV M has been crystalized both as a monomer and a dimer, and no formal...
Extracellular vesicles (EVs) are cell-derived nanoparticles, involved in cell-to-cell communication, in both normal and pathological processes. Originating by the outward budding of the plasma membrane or released by exocytosis, they are natural cargoes for lipids, carbohydrates, proteins and nucleic acids. EV-based diagnostics promises unique adva...
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many...
Sialidases are glycohydrolases that remove terminal sialic acid residues from oligosaccharides, glycolipids and glycoproteins. The plasma membrane-associated sialidase NEU3 is involved in the fine tuning of sialic acid containing glycans directly on the cell surface and plays relevant roles in important biological phenomena such as cell differentia...
Liver cancer (LC) is one of the most common cancers and represents the third highest cause of cancer-related deaths worldwide. Extracellular vesicle (EVs) cargoes, which are selectively enriched in RNA, offer great promise for the diagnosis, prognosis and treatment of LC. Our study analyzed the RNA cargoes of EVs derived from 4 liver-cancer cell li...
Background:
An increasing number of studies on stem cells suggests that the therapeutic effect they exert is primarily mediated by a paracrine regulation through extracellular vesicles (EVs) giving solid grounds for stem cell EVs to be exploited as agents for treating diseases or for restoring damaged tissues and organs. Due to their capacity to d...
Exosomes are gaining a prominent role in research due to their intriguing biology and several therapeutic opportunities. However, their accurate purification from body fluids and detailed physicochemical characterization remain open issues. We isolated exosomes from serum of patients with Multiple Myeloma by four of the most popular purification me...
Background:
Heavy/light chain assay allows the characterization and quantification of immunoglobulin light chains bound to heavy chains for each Ig'k and Ig'λ immunoglobulin class, discriminating between the involved/uninvolved isotypes in plasma cell dyscrasia. The Ig'k/Ig'λ ratio (heavy/light chain ratio) enables to monitor the trend of monoclon...
Multiple myeloma (MM) is a hematological malignancy caused by a microenviromentally aided persistence of plasma cells in the bone marrow. Monoclonal plasma cells often secrete high amounts of immunoglobulin free light chains (FLCs) that could induce tissue damage. Recently, we showed that FLCs are internalized in endothelial and myocardial cell lin...
Background:
The clinical usefulness of the serum-free light chain assays has expanded since their first description, and further applications other than plasma cell dyscrasia are emerging. Currently, we have the ability to perform the measurements with two certified methods: the Freelite™ assay (The Binding Site Ltd, Birmingham, UK) and the new N...
Plasma cell dyscrasias are immunosecretory disorders that can lead to hematological malignancies such as Multiple Myeloma (MM). MM accounts for 15% of all hematologic cancers, and those diagnosed with MM typically become severely ill and have a low life expectancy. Monoclonal immunoglobulin Free Light Chains (FLC) are present in the serum and urine...
Trypsin treatment, after internalization, efficiently eliminates all type of residual FLCs from cell membrane. (A) HVEC cells in starvation medium were incubated with serum containing FLCs from M2λ patient for 4 h at 37°C. The serum was diluted directly in starvation medium to a final FLCs concentration of 20 µg/mL. After incubation cells were wash...
Denaturing or native electrophoresis analysis of internalized FLCs. (A) HVEC cells in starvation medium were incubated with serum containing FLCs from AL amyloidosis (A1k, A2λ), two patients with monoclonal component but normal FLCs levels (IgGk and IgAλ) or healthy donor patients (c) for 4 h at 37°C. The serum was diluted in starvation media to a...
Characterization of patients’ sera. (A) Percentage of monoclonal component isotypes:. each column represent the percentage of patients producing the same monoclonal component isotype. “Others”, is a smaller group with: double IgGk, k, λ, IgAλ+ IgGk, IgGk+λ, IgMk, IgMk+IgMλ, IgMλ+IgGk. The mean value of kappa and lambda FLCs concentrations in all pa...
Characterization of the monoclonal components of all patients involved in this study. The table shows: serum immunofixation (IF-S) and urine immunofixation (IF-U) results; kappa and lambda FLCs serum concentration and ratio; immunoglobulin quantification (IgA- IgG- IgM). N.a.: not available.
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Adaptor protein (AP) complexes are key factors for the spatial and temporal regulation of intracellular trafficking events. Four complexes (AP-1, -2, -3, -4) are known, among which AP-4 is only poorly characterized. Recent work suggests a role for AP-4 in the intracellular trafficking of the β-amyloid precursor protein and molecular genetics showed...
The gene encoding brain-derived neurotrophic factor (BDNF) has been suggested as a candidate for major depression, and for depression susceptibility in different neurological and psychiatric diseases. No study has investigated the role of BDNF genetic variation and depressive symptoms in Alzheimer's disease (AD).
The aim of this study was to assess...
We developed a real-time PCR assay to simultaneously measure the mRNA level of type I interferon (IFN) receptor (IFNAR) components in peripheral blood cells of children with chronic immune stimulation due to HIV infection. All patients were undergoing antiretroviral therapy and were divided into two groups on the basis of the induction of MxA mRNA,...
Most variability in goat caseins originates from the high number of genetic polymorphisms often affecting the specific protein expression, with strong effects on milk composition traits and technological properties. At least 7 alleles have been found in the goat alpha(S2)-CN gene (CSN1S2). Five of them (CSN1S2*A, CSN1S2*B, CSN1S2*C, CSN1S2*E, and C...
The gene (lacA) coding for Escherichia coli galactoside transacetylase was cloned into the pTrcHisB plasmid, and the corresponding hexahistidine-tagged enzyme was over-expressed and purified. The kinetic constants of the tagged protein were determined, yielding values in excellent agreement with previous observations reported for the natural enzyme...
Chromosome replication in Escherichia coli is accomplished by the multimeric enzyme DNA polymerase III; the relevance, in vivo, of the epsilon subunit (encoded by dnaQ) for processivity and fidelity of DNA polymerase III has been evaluated. To this aim, dnaQ has been conditionally silenced by means of in vivo expression of different antisense RNAs....
Directed evolution of Escherichia coli β-galactosidase into variants featuring β-glucosidase activity was challenged. To this end, mutagenesis of lacZ was performed by replication in E. coli CC954, a mutator strain containing a DNA polymerase III defective in 3′→5′ exonuclease activity. β-Galactosidase variants can be isolated upon mutagenesis of l...
RNA binding proteins play key roles in the post-transcriptional regulation of gene expression. Here we present the molecular cloning and spatio-temporal expression of Xseb-4, which codes for a putative RNA binding protein containing a single RNA recognition motif (RRM). XSEB-4 shares 60-65% identity with the mammalian SEB-4 proteins. Xseb-4 is stro...
