M1-derived extracellular vesicles polarize recipient macrophages into M2-like macrophages and alter skeletal muscle homeostasis in a hyper-glucose environment.

BACKGROUND: Macrophages release not only cytokines but also extracellular vesicles (EVs). which are small membrane-derived nanovesicles with virus-like properties transferring cellular material between cells. Until now, the consequences of macrophage plasticity on the release and the composition of EVs have been poorly explored. In this study, we determined the impact of high-glucose (HG) concentrations on macrophage metabolism, and characterized their derived-EV subpopulations. Finally, we determined whether HG-treated macrophage-derived EVs participate in immune responses and in metabolic alterations of skeletal muscle cells. METHODS: THP1-macrophages were treated with 15mM (MG15) or 30mM (MG30) glucose. Then, M1/M2 canonical markers, pro- and anti-inflammatory cytokines, activities of proteins involved in glycolysis or oxidative phosphorylation were evaluated. Macrophage-derived EVs were characterized by TEM, NTA, MRSP, and 1H-Nuclear magnetic resonance spectroscopy for lipid composition. Macrophages or C2C12 muscle cells were used as recipients of MG15 and MG30-derived EVs. The lipid profiles of recipient cells were determined, as well as proteins and mRNA levels of relevant genes for macrophage polarization or muscle metabolism. RESULTS: Untreated macrophages released small and large EVs (sEVs, lEVs) with different lipid distributions. Proportionally to the glucose concentration, glycolysis was induced in macrophages, associated to mitochondrial dysfunction, triacylglycerol and cholesterol accumulation. In addition, MG15 and MG30 macrophages had increased level of CD86 and increase release of pro-inflammatory cytokines. HG also affected macrophage sphingolipid and phospholipid compositions. The differences in the lipid profiles between sEVs and lEVs were abolished and reflected the lipid alterations in MG15 and MG30 macrophages. Interestingly, MG15 and MG30 macrophages EVs induced the expression of CD163, Il-10 and increased the contents of triacylglycerol and cholesterol in recipient macrophages. MG15 lEVs and sEVs induced insulin-induced AKT hyper-phosphorylation and accumulation of triacylglycerol in myotubes, a state observed in pre-diabetes. Conversely, MG30 lEVs and sEVs induced insulin-resistance in myotubes. CONCLUSIONS: As inflammation involves first M1 macrophages, then the activation of M2 macrophages to resolve inflammation, this study demonstrates that the dialog between macrophages through the EV route is an intrinsic part of the inflammatory response. In a hyperglycemic context, EV macrophages could participate in the development of muscle insulin-resistance and chronic inflammation.

Occurrence and Biological Activities of Seco-Iridoids from Jasminum L.

In this paper, the first complete review on the seco-iridoids from the genus Jasminum L. was presented. In particular, their occurrence in the genus was detailed together with their biological activities. The literature survey has clearly pointed out that only a few Jasminum species have been studied for their seco-iridoid content evidencing oleoside derivatives as main compounds. In addition, the biological studies performed on them are very scarce focusing mainly on antioxidant and anti-inflammatory assays with modest effectiveness. All these results greatly underline the need for further in-depth analyses on these compounds under both the aspects.

Active microbial ecosystem in Iron-Age tombs of the Etruscan civilization.

Earth's microbial biosphere extends down through the crust and much of the subsurface, including those microbial ecosystems located within cave systems. Here, we elucidate the microbial ecosystems within anthropogenic 'caves'; the Iron-Age, subterranean tombs of central Italy. The interior walls of the rock (calcium-rich macco) were painted ~2500 years ago and are covered with CaCO3 needles (known as moonmilk). The aims of the current study were to: identify biological/geochemical/biophysical determinants of and characterize bacterial communities involved in CaCO3 precipitation; challenge the maxim that biogenic activity necessarily degrades surfaces; locate the bacterial cells that are the source of the CaCO3 precipitate; and gain insight into the kinetics of moonmilk formation. We reveal that this environment hosts communities that consist primarily of bacteria that are mesophilic for temperature and xerotolerance (including Actinobacteria, Bacteroidetes and Proteobacteria); is populated by photosynthetic Cyanobacteria exhibiting heterotrophic nutrition (Calothrix and Chroococcidiopsis); and has CaCO3 precipitating on the rock surfaces (confirmation that this process is biogenic) that acts to preserve rather than damage the painted surface. We also identified that some community members are psychrotolerant (Polaromonas), acidotolerant or acidophilic (members of the Acidobacteria), or resistant to ionizing radiation (Brevundimonas and Truepera); elucidate the ways in which microbiology impacts mineralogy and vice versa; and reveal that biogenic formation of moonmilk can occur rapidly, that is, over a period of 10 to 56 years. We discuss the paradox that these ecosystems, that are for the most part in the dark and lack primary production, are apparently highly active, biodiverse and biomass-rich.

Bile acid derivative-based catanionic mixtures: versatile tools for superficial charge modulation of supramolecular lamellae and nanotubes.

Self-assembled structures formed by mixtures of cationic and anionic surfactants are interesting tools for applications requiring interactions with charged particles and molecules. Nevertheless, they present instability close to the equimolar composition and poor morphological versatility, which is generally restricted to vesicles and micelles. Against this general trend, we report on bile salt derivative based catanionic mixtures assembling in tubules and lamellae depending on the mixture composition. Electrophoretic mobility measurements prove that the composition also dictates their superficial charge, which can be tuned from negative to positive by increasing the positively charged surfactant fraction in the mixtures. The study of the catanionic aggregates was conducted by means of microscopy and spectroscopy techniques and compared to the self-assembly behaviors of the individual building blocks. This study broadens the so far small array of bile salt derivative catanionic systems, confirming their distinctive behavior in the spectrum of catanionic mixtures.

Behaviour of Bdellovibrio bacteriovorus in the presence of Gram-positive Staphylococcus aureus.

The present study aimed to characterize the behavior of Bdellovibrio bacteriovorus in the presence of Staphylococcus aureus. B. bacteriovorus was co-cultured with S. aureus or Pseudomonas aeruginosa or Streptococcus mutans, in planktonic and sessile conditions. Co-cultures were studied by Field-Emission Scanning Electron Microscopy (FESEM), Scanning Transmission Electron Microscopy (STEM), turbidimetry, quantitative PCR (qPCR), and sequencing of gene Bd0108 of B. bacteriovorus. Results indicated that B. bacteriovorus comparably inhibited planktonic growth of P. aeruginosa and S. aureus, but not of S. mutans. FESEM and STEM showed that B. bacteriovorus interacts with S. aureus affecting its cell wall and membrane. Sequencing of gene Bd0108 did not reveal any of the mutations that can arise from the host-interaction (hit) locus. Although some Gram-negative species are reported to be B. bacteriovorus prey, it seems that in case of nutrient deficiency this predatory bacterium can also take advantage of some Gram-positive species. B. bacteriovorus behaviour in the presence of S. aureus is relevant for its possible therapeutic use in several pathologies, like cystic fibrosis in which S. aureus and P. aeruginosa frequently coexist as infectious agents.

Intracellular Transport of Silver and Gold Nanoparticles and Biological Responses: An Update.

Medicine, food, and cosmetics represent the new promising applications for silver (Ag) and gold (Au) nanoparticles (NPs). AgNPs are most commonly used in food and cosmetics; conversely, the main applications of gold NPs (AuNPs) are in the medical field. Thus, in view of the risk of accidentally or non-intended uptake of NPs deriving from the use of cosmetics, drugs, and food, the study of NPs⁻cell interactions represents a key question that puzzles researchers in both the nanomedicine and nanotoxicology fields. The response of cells starts when the NPs bind to the cell surface or when they are internalized. The amount and modality of their uptake depend on many and diverse parameters, such as NPs and cell types. Here, we discuss the state of the art of the knowledge and the uncertainties regarding the biological consequences of AgNPs and AuNPs, focusing on NPs cell uptake, location, and translocation. Finally, a section will be dedicated to the most currently available methods for qualitative and quantitative analysis of intracellular transport of metal NPs.

Bandgap Energy of Wurtzite InAs Nanowires.

InAs nanowires (NWs) have been grown on semi-insulating InAs (111)B substrates by metal-organic chemical vapor deposition catalyzed by 50, 100, and 150 nm-sized Au particles. The pure wurtzite (WZ) phase of these NWs has been attested by high-resolution transmission electron microscopy and selected area diffraction pattern measurements. Low temperature photoluminescence measurements have provided unambiguous and robust evidence of a well resolved, isolated peak at 0.477 eV, namely 59 meV higher than the band gap of ZB InAs. The WZ nature of this energy band has been demonstrated by high values of the polarization degree, measured in ensembles of NWs both as-grown and mechanically transferred onto Si and GaAs substrates, in agreement with the polarization selection rules for WZ crystals. The value of 0.477 eV found here for the bandgap energy of WZ InAs agrees well with theoretical calculations.

Behind Resveratrol Stabilization by Carboxymethylated (1,3/1,6)-ß-d-Glucan: Does the Polyphenol Play a Role in Polymer Structural Organization?

Resveratrol stability in solution can be improved by combining the polyphenol with carboxymethylated (1,3/1,6)-ß-d-glucan (CM-glucan), a carbohydrate polymer widely used in the food and pharmaceutical industries. The present work was undertaken to elucidate the mechanism behind this stabilizing effect. The supramolecular structural, physico-chemical and morphological features of the CM-glucan/resveratrol complex have been studied under different physical and chemical stimuli by means of spectroscopic techniques, microscopy and physical methods such as UV-Visible spectroscopy (UV-Vis), spectrofluorimetry, Circular Dichroism (CD), Infrared spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM). Our experimental data indicate that CM-glucan conformational organized architecture in aqueous solution is enhanced in the presence of resveratrol, suggesting that the polyphenol is able to confer a high degree of order to the polymer by a probable cooperative structural organization that results in a long term stabilization for the polyphenol.

Predation risk of the sea urchin Paracentrotus lividus juveniles in an overfished area reveal system stability mechanisms and restocking challenges.

Where sea urchin harvest has been so intense that populations have drastically regressed, concerns have arisen about the effectiveness of harvesting management. According to the theory of phase transition in shallow rocky reefs between vegetated and barren habitats, sea urchin recruitment, a key population structuring process, seems hampered by some stabilizing feedback despite an end to local human harvest of sea urchins. To shed a light on predation effects on sea urchin recruits, a 27-day field experiment was conducted using mega-predator exclusion cages (40x40x40 cm, 1 cm in mesh size) in barren and turf substrates. To facilitate this, 672 recruits (1.1 ± 0.02 cm in size) reared under control conditions were positioned in groups of 42 in each experimental unit (n = 4). Exclusion of mega-predators had a significant effect regardless the substrate, since a higher number of recruits was found under cages both in turf and barren. However, the results showed that in uncaged treatments the size of recruits that survived was larger in turf than in barren, as in the former substrate predation had reduced the abundance of the smallest recruits, highlighting that mega-predator presence affects differently the size of the recruits that had survived depending on the substrate. Overall, these results provide valuable information to address restocking actions of sea urchin populations in overharvested areas, where algal turfs are widespread, and assist studies on habitat stability mechanisms.

Toward the nanoscale chemical and physical probing of milk-derived extracellular vesicles using Raman and tip-enhanced Raman spectroscopy.

Tip-enhanced Raman spectroscopy (TERS) is an advanced technique to perform local chemical analysis of the surface of a sample through the improvement of the sensitivity and the spatial resolution of Raman spectroscopy by plasmonic enhancement of the electromagnetic signal in correspondence with the nanometer-sized tip of an atomic force microscope (AFM). In this work, TERS is demonstrated to represent an innovative and powerful approach for studying extracellular vesicles, in particular bovine milk-derived extracellular vesicles (mEVs), which are nanostructures with considerable potential in drug delivery and therapeutic applications. Raman spectroscopy has been used to analyze mEVs at the micrometric and sub-micrometric scales to obtain a detailed Raman spectrum in order to identify the 'signature' of mEVs in terms of their characteristic molecular vibrations and, therefore, their chemical compositions. With the ability to improve lateral resolution, TERS has been used to study individual mEVs, demonstrating the possibility of investigating a single mEV selected on the surface of the sample and, moreover, analyzing specific locations on the selected mEV with nanometer lateral resolution. TERS potentially allows one to reveal local differences in the composition of mEVs providing new insights into their structure. Also, thanks to the intrinsic properties of TERS to acquire the signal from only the first few nanometers of the surface, chemical investigation of the lipid membrane in correspondence with the various locations of the selected mEV could be performed by analyzing the peaks of the Raman shift in the relevant range of the spectrum (2800-3000 cm-1). Despite being limited to mEVs, this work demonstrates the potential of TERS in the analysis of extracellular vesicles.

Ferritin nanocage-enabled detection of pathological tau in living human retinal cells.

Tauopathies, including Alzheimer's disease and Frontotemporal Dementia, are debilitating neurodegenerative disorders marked by cognitive decline. Despite extensive research, achieving effective treatments and significant symptom management remains challenging. Accurate diagnosis is crucial for developing effective therapeutic strategies, with hyperphosphorylated protein units and tau oligomers serving as reliable biomarkers for these conditions. This study introduces a novel approach using nanotechnology to enhance the diagnostic process for tauopathies. We developed humanized ferritin nanocages, a novel nanoscale delivery system, designed to encapsulate and transport a tau-specific fluorophore, BT1, into human retinal cells for detecting neurofibrillary tangles in retinal tissue, a key marker of tauopathies. The delivery of BT1 into living cells was successfully achieved through these nanocages, demonstrating efficient encapsulation and delivery into retinal cells derived from human induced pluripotent stem cells. Our experiments confirmed the colocalization of BT1 with pathological forms of tau in living retinal cells, highlighting the method's potential in identifying tauopathies. Using ferritin nanocages for BT1 delivery represents a significant contribution to nanobiotechnology, particularly in neurodegenerative disease diagnostics. This method offers a promising tool for the early detection of tau tangles in retinal tissue, with significant implications for improving the diagnosis and management of tauopathies. This study exemplifies the integration of nanotechnology with biomedical science, expanding the frontiers of nanomedicine and diagnostic techniques.

Glucose level determination with a multi-enzymatic cascade reaction in a functionalized glass chip.

In this work we show the functionalization of the interior of microfluidic glass chips with poly(2-hydroxyethyl methacrylate) polymer brushes as anchors for co-immobilization of the enzymes glucose-oxidase and horseradish peroxidase. The formation of the brush layer and subsequent immobilization of these enzymes have been characterized on flat surfaces by atomic force microscopy and Fourier transform infrared spectroscopy, and studied inside glass chips by field emission scanning microscopy. Enzyme-functionalized glass chips have been applied for performing a multi-enzymatic cascade reaction for the fast (20 s) determination of glucose in human blood samples and the result is in excellent agreement with values obtained from the conventional hospital laboratory. The limit of detection of this bi-enzymatic method is 60 µM. With the advantages of high selectivity and reproducibility, this functionalization method can be used for improving the efficiency of glucose sensors.

Advances in Focused Ion Beam Tomography for Three-Dimensional Characterization in Materials Science.

Over the years, FIB-SEM tomography has become an extremely important technique for the three-dimensional reconstruction of microscopic structures with nanometric resolution. This paper describes in detail the steps required to perform this analysis, from the experimental setup to the data analysis and final reconstruction. To demonstrate the versatility of the technique, a comprehensive list of applications is also summarized, ranging from batteries to shale rocks and even some types of soft materials. Moreover, the continuous technological development, such as the introduction of the latest models of plasma and cryo-FIB, can open the way towards the analysis with this technique of a large class of soft materials, while the introduction of new machine learning and deep learning systems will not only improve the resolution and the quality of the final data, but also expand the degree of automation and efficiency in the dataset handling. These future developments, combined with a technique that is already reliable and widely used in various fields of research, are certain to become a routine tool in electron microscopy and material characterization.

3D fractures analysis and conservation assessment of wrought iron javelin through advanced non-invasive techniques.

3D imaging is a powerful tool of high resolution and non-destructive imaging technology for the study of ancient weapons and military technology, which reveals the original microstructures and corrosion patterns that threaten these artefacts. Here we report quantitative analysis of the 3D distribution and the orientation of fractures, and uncorroded metal particles within a wrought iron javelin unearthed at the Phoenician-Punic site of Motya, Italy. The study aimed to gain a better understanding of the relationship between corrosion and local stresses within the artifact and to evaluate its manufacturing technology, as well as the effects of post-treatment with Paraloid B72 on concretion and mineralized layers. The cracks were quantified in terms of content, size, and orientation. The condition of artefact storage was evaluated by a multi-analytical approach, including X-ray microscopy, field emission electron microscopy and micro-Raman spectroscopy. The results indicated that a specific technique was used to create a sturdy, lightweight javelin with a central shaft for piercing or thrusting. The fractures appear elongated in the direction of the longitudinal axis of the blade, showing the forging direction of the original metallic block. The study concluded that the artifact had not yet been stabilized due to the presence of lepidocrocite.

Upscaling of Electrospinning Technology and the Application of Functionalized PVDF-HFP@TiO2 Electrospun Nanofibers for the Rapid Photocatalytic Deactivation of Bacteria on Advanced Face Masks.

In recent years, Electrospinning (ES) has been revealed to be a straightforward and innovative approach to manufacture functionalized nanofiber-based membranes with high filtering performance against fine Particulate Matter (PM) and proper bioactive properties. These qualities are useful for tackling current issues from bacterial contamination on Personal Protective Equipment (PPE) surfaces to the reusability of both disposable single-use face masks and respirator filters. Despite the fact that the conventional ES process can be upscaled to promote a high-rate nanofiber production, the number of research works on the design of hybrid materials embedded in electrospun membranes for face mask application is still low and has mainly been carried out at the laboratory scale. In this work, a multi-needle ES was employed in a continuous processing for the manufacturing of both pristine Poly (Vinylidene Fluoride-co-Hexafluoropropylene) (PVDF-HFP) nanofibers and functionalized membrane ones embedded with TiO2 Nanoparticles (NPs) (PVDF-HFP@TiO2). The nanofibers were collected on Polyethylene Terephthalate (PET) nonwoven spunbond fabric and characterized by using Scanning Electron Microscopy and Energy Dispersive X-ray (SEM-EDX), Raman spectroscopy, and Atomic Force Microscopy (AFM) analysis. The photocatalytic study performed on the electrospun membranes proved that the PVDF-HFP@TiO2 nanofibers provide a significant antibacterial activity for both Staphylococcus aureus (~94%) and Pseudomonas aeruginosa (~85%), after only 5 min of exposure to a UV-A light source. In addition, the PVDF-HFP@TiO2 nanofibers exhibit high filtration efficiency against submicron particles (~99%) and a low pressure drop (~3 mbar), in accordance with the standard required for Filtering Face Piece masks (FFPs). Therefore, these results aim to provide a real perspective on producing electrospun polymer-based nanotextiles with self-sterilizing properties for the implementation of advanced face masks on a large scale.

Towards the Development of a Device for Assessing the Pliability of Burn Scars.

Burn injuries requires post-accident medical treatment. However, the treatment of burns does not end with first aid because scarred skin must be managed for many years, and in some circumstances, for life. The methods used to evaluate the state of a burn scar based, for instance, on Patient and Observer Scar Assessment Scale or similar ones, often lacks in univocally assessing the scarred skin's state of health. As a result, the primary aim of this research is to design and build a prototype that can support the doctor during scar assessment, and eventually therapy, by providing objective information on the state of the lesion, particularly the value of skin pliability. The developed tool is based on the depressomassage treatment probe named LPG, currently used to treat burn scars in a number of hospitals. It consists of a non-invasive massage technique using a mechanical device to suction and mobilize scar tissue and is used as a post-operative treatment to speed up the healing process to make the mark of the scar less visible. The prototype is specifically designed to be manufactured using Additive Manufacturing and was validated comparing its performances against the ones of a certified instrument (i.e., the Romer Absolute ARM with RS1 probe). Validation was carried out by designing and developing a tool to put the RS1 probe in the same measurement conditions of the new prototype probe. Tests performed to assess the performance of the devised prototype show that the probe developed in this work is able to provide measurements with a sufficient degree of accuracy (maximum error ±0.1 mm) to be adopted for a reliable estimation of the pliability value in a hospital environment.

Enabling water-free PEDOT as hole selective layer in lead-free tin perovskite solar cells.

Metal halide perovskites are set to revolutionise photovoltaic energy harvesting owing to an unmatched combination of high efficiency and low fabrication costs. However, to improve the sustainability of this technology, replacing lead with less toxic tin is highly desired. Tin halide perovskites are approaching 15% in power conversion efficiency (PCE), mainly employing PEDOT:PSS as a hole-selective layer. Unfortunately, PEDOT:PSS is processed from an aqueous solution, which is hardly compatible with the strict anoxic requirements for processing tin halide perovskites due to tin's instability to oxidation. Here, we present a water-free PEDOT formulation for developing tin-based lead-free perovskite solar cells. We show that the main difference between the PCE of devices made from aqueous and water-free PEDOT is due to the marked hydrophobicity of the latter, which complicates the perovskite deposition. By modifying the surface of water-free PEDOT with a thin Al2O3 interlayer, we could achieve good perovskite morphology that enabled perovskite solar cells with a PCE of 7.5%.

Synchronous colorectal neoplasias: our experience about laparoscopic-TEM combined treatment.

Synchronous colorectal neoplasias are defined as 2 or more primary tumors identified in the same patient and at the same time. The most voluminous synchronous cancer is called "first primitive" or "index" cancer. The aim of this work is to describe our experience of minimally invasive approach in patients with synchronous colorectal neoplasias.Since January 2001 till December 2009, 557 patients underwent colectomy for colorectal cancer at the Department of General and Emergency Surgery of the University of Perugia; 128 were right colon cancers, 195 were left colon cancers while 234 patients were affected by rectal cancers. We performed 224 laparoscopic colectomies (112 right, 67 left colectomies and 45 anterior resections of rectum), 91 Transanal Endoscopic Microsurgical Excisions (TEM) and 53 Trans Anal Excisions (TAE). In the same observation period 6 patients, 4 males and 2 females, were diagnosed with synchronous colorectal neoplasias. Minimal invasive treatment of colorectal cancer offers the opportunity to treat two different neoplastic lesions at the same time, with a shorter post-operative hospitalization and minor complications. According to our experience, laparoscopy and TEM may ease the treatment of synchronous diseases with a lower morbidity rate.

Efficacy of surgery and imatinib mesylate in the treatment of advanced gastrointestinal stromal tumor: a systematic review.

AIMS AND BACKGROUND: In patients with localized gastrointestinal stromal tumors, surgery remains the elective treatment. Nowadays, imatinib therapy has been standardized in advanced gastrointestinal stromal tumors, showing continuous improvements in progression-free and overall survival. A combination of imatinib therapy and surgery may also be effective in a subset of patients with metastatic or unresectable gastrointestinal stromal tumors. In this review, the authors analyzed the role of imatinib mesylate associated to surgery in unresectable and/or metastatic gastrointestinal stromal tumors. METHODS AND STUDY DESIGN: We searched for all published and unpublished randomized controlled clinical trials and controlled clinical trials. We conducted the review according to the recommendations of The Cochrane Collaboration. We used Review Manager 5 software for the statistical analysis. RESULTS: There are currently no randomized controlled clinical trials or controlled clinical trials on this issue. We performed a subgroup analysis in the patients preoperatively treated with imatinib mesylate. This subgroup revealed a minor incidence of recurrent or metastatic gastrointestinal stromal tumors and a greater incidence of locally unresectable gastrointestinal stromal tumors in the responsive disease group (P = 0.001). In this patient group, more complete resections were observed (P = 0.00001). Furthermore, in the same patient group we observed a more significant 12 and 24-month disease-free survival after imatinib treatment and complete resection (respectively P= 0.06 and P= 0.003) and also a better 24-month overall survival (P = 0.004). CONCLUSIONS: There is actually only one ongoing European randomized study evaluating surgery of residual disease in patients with metastatic gastrointestinal stromal tumors responding to imatinib mesylate. Imatinib mesylate represents the standard treatment as preoperative supplement for locally unresectable and/or metastatic gastrointestinal stromal tumors, and a trial to compare the approach versus surgery alone is not necessary. For patients responding to imatinib or patients with prolonged stable disease, resection of residual disease should be considered. A phase III randomized study evaluating surgery of residual disease in patients with metastatic gastrointestinal stromal tumor responding to imatinib mesylate, EORTC 62063, has been opened. Moreover, surgery should be considered for patients at higher risk of complications during pharmacological debulking. In advanced gastrointestinal stromal tumors, the advantages of the integrated treatment are significant in the complete or partial response disease group in terms of more complete resections and better disease-free and overall survival.

Blueberry-Derived Exosome-Like Nanoparticles Counter the Response to TNF-α-Induced Change on Gene Expression in EA.hy926 Cells.

Exosome-like nanoparticles (ELNs) are attracting interest as important vehicles of intercellular communication, both in prokaryotes and eukaryotes. Recently, dietary nanoparticles similar to mammalian exosomes have attracted attention for these features. In particular they appear to be relevant in the modulation of several cellular processes as well as candidate carriers of bioactive molecules (proteins, lipids, and nucleic acids, including miRNAs) with therapeutic value. Herein, we investigated the cellular uptake of blueberry-derived ELNs (B-ELNs) by a human stabilized endothelial cell line (EA.hy926) and the ability of B-ELNs to modulate the expression of inflammatory genes as the response of tumor necrosis factor-α (TNF-α). Our results indicate that 1) EA.hy926 cells internalize B-ELNs in a dose-dependent manner; 2) pretreatment with B-ELNs counters TNF-α-induced reactive oxygen species (ROS) generation and loss of cell viability and modulates the differential expression of 29 genes (fold change > 1.5) induced by TNF-α compared to control; 3) pathway analysis reveals their involvement in a total of 340 canonical pathways, 121 KEGG pathways, and 121 GO Biological processes; and 4) the intersection between differentially expressed (DE) genes and miRNAs contained in B-ELNs unveils a set of candidate target genes, such as prostaglandin I2 synthase (PTGIS), mitogen-activated protein kinase 14 (MAPK14), and phosphodiesterase 7A (PDE7A), for ELNs-contained cargo. In conclusion, our study indicates that B-ELNs can be considered candidate therapeutic carriers of bioactive compounds potentially able to protect vascular system against various stressors.