Protective effects of exosomes derived from lyophilized porcine liver against acetaminophen damage on HepG2 cells

Background: Recently, extracellular vesicles have come to the fore following their emerging role in cell communication, thanks to their ability to reach cells into the human body without dissipating their cargo, transferring biological active molecules, such as proteins, nucleic acids, lipids, etc. They appear as a promising tool in medicine, because of their capability to modulate cellular response in recipient cells. Moreover, a considerable number of publications suggests that exosome uptake is selective but not specific, and it can cross species and cell-type boundaries. This study aims to explore the potential role of porcine liver derived extracellular vesicles, exosomes in particular, to protect human cells from acute damage induced by acetaminophen. Methods: Extracellular vesicles were isolated from porcine lyophilized liver using polymer-based precipitation and a further enrichment was performed using affinity beads. The effects of obtained fractions, total extracellular vesicles and enriched extracellular vesicles, were assessed on human liver derived HepG2 cells. Cell growth and survival were tested, with MTT and area coverage analysis designed by us, as well as protein expression, with immunofluorescence and Western blot. Oxidative stress in live cells was also measured with fluorogenic probes. Results: After proving that porcine extracellular vesicles did not have a toxic effect on HepG2, quite the contrary total extracellular vesicle fraction improved cell growth, we investigated their protective capability with a preconditioning strategy in APAP-induced damage. EVs displayed not only the ability to strongly modulate cell survival responses, but they also were able to boost cell cycle progression. Conclusions: Extracellular vesicles derived from farm animal food derivatives are able to modulate human hepatic cell metabolism, also improving cell survival in a damaged context

Intracrine endorphinergic systems in modulation of myocardial differentiation

A wide variety of peptides not only interact with the cell surface, but govern complex signaling from inside the cell. This has been referred to as an "intracrine" action, and the orchestrating molecules as "intracrines". Here, we review the intracrine action of dynorphin B, a bioactive end-product of the prodynorphin gene, on nuclear opioid receptors and nuclear protein kinase C signaling to stimulate the transcription of a gene program of cardiogenesis. The ability of intracrine dynorphin B to prime the transcription of its own coding gene in isolated nuclei is discussed as a feed-forward loop of gene expression amplification and synchronization. We describe the role of hyaluronan mixed esters of butyric and retinoic acids as synthetic intracrines, controlling prodynorphin gene expression, cardiogenesis, and cardiac repair. We also discuss the increase in prodynorphin gene transcription and intracellular dynorphin B afforded by electromagnetic fields in stem cells, as a mechanism of cardiogenic signaling and enhancement in the yield of stem cell-derived cardiomyocytes. We underline the possibility of using the diffusive features of physical energies to modulate intracrinergic systems without the needs of viral vector-mediated gene transfer technologies, and prompt the exploration of this hypothesis in the near future

Association between exposure to fine particulate matter and osteoporosis: a population-based cohort study

Long-term environmental air pollution exposure was associated with osteoporosis' risk in a cohort of women at high risk of fracture. Cortical sites seemed to be more susceptible to the exposure's effect

Silica-magnesium-titanium Ziegler-Natta catalysts. Part 1: Structure of the pre-catalyst at a molecular level

In this paper, which is the first part of a more extended work, we elucidate the molecular level structure of a highly active SiO2-supported Ziegler-Natta precatalyst obtained by reacting a dehydroxylated silica and a solution of an organomagnesium compound with TiCl4. The synergetic combination of Ti K-edge and Ti L3-edge X-ray Absorption spectroscopy (XAS) and diffuse reflectance UV–Vis spectroscopies, complemented by Density Functional Theory (DFT) simulations, indicate that small TiCl3 clusters similar to β-TiCl3 coexist with isolated monomeric Ti(IV) species. Ti K-edge Extended X-ray Absorption Fine Structure (EXAFS) Spectroscopy allows the quantification of these two phases and demonstrates that the Ti(IV) sites are 6-fold coordinated (either by six chlorine ligands or by five chlorine and one oxygen ligands), but highly distorted, similar to what is modelled for TiCl4-capped MgCl2 nanoplatelets. Finally, IR spectroscopy suggests that the MgCl2 phase has a molecular character (Far-IR) and that the only accessible Mg2+ sites are uncoordinated cations acting as Lewis acid sites (IR of CO adsorbed at 100 K). Based on these experimental findings, we propose the co-existence in the precatalyst of small TiCl3 clusters and of mixed oxo-chloride magnesium-titanium structures deposited at the silica surface. The evolution of the precatalyst in the presence of the activator and of the monomer is discussed in the second part of this work

PDGFRα depletion attenuates glioblastoma stem cells features by modulation of STAT3, RB1 and multiple oncogenic signals.

Platelet derived growth factor receptors (PDGFRs) play an important role in tumor pathogenesis, and they are frequently overexpressed in glioblastoma (GBM). Earlier we have shown a higher protein expression of PDGFR isoforms (α and β) in peritumoral-tissue derived cancer stem cells (p-CSC) than in tumor core (c-CSC) of several GBM affected patients. In the current study, in order to assess the activity of PDGFRα/PDGF-AA signaling axis, we performed time course experiments to monitor the effects of exogenous PDGF-AA on the expression of downstream target genes in c-CSC vs p-CSC. Interestingly, in p-CSC we detected the upregulation of Y705-phosphorylated Stat3, concurrent with a decrement of Rb1 protein in its active state, within minutes of PDGF-AA addition. This finding prompted us to elucidate the role of PDGFRα in self-renewal, invasion and differentiation in p-CSC by using short hairpin RNA depletion of PDGFRα expression. Notably, in PDGFRα-depleted cells, protein analysis revealed attenuation of stemness-related and glial markers expression, alongside early activation of the neuronal marker MAP2a/b that correlated with the induction of tumor suppressor Rb1. The in vitro reduction of the invasive capacity of PDGFRα-depleted CSC as compared to parental cells correlated with the downmodulation of markers of epithelial-mesenchymal transition phenotype and angiogenesis. Surprisingly, we observed the induction of anti-apoptotic proteins and compensatory oncogenic signals such as EDN1, EDNRB, PRKCB1, PDGF-C and PDGF-D. To conclude, we hypothesize that the newly discovered PDGFRα/Stat3/Rb1 regulatory axis might represent a potential therapeutic target for GBM treatment.BRC, Q

Decision Making on Vestibular Schwannoma: Lessons from a Multidisciplinary Board

Background: Management of vestibular schwannoma (VS) is a complex process aimed at identifying a clinical indication for fractionated stereotactic radiotherapy (sRT) or radiosurgery, microsurgical resection, or wait and scan (WS). We describe the experience of our VS multidisciplinary team (MDT) at a tertiary university referral center created for diagnosis, treatment, and follow-up of VS patients. Methods: We conducted a retrospective study on 132 consecutive patients referred to the MDT and managed by observation (WS), microsurgery, or fractionated sRT. The analysis included patient age, tumor size, hearing level, facial nerve function, tumor control, complications, and quality of life questionnaires. Results: Among the patients, 21% were subjected to microsurgery, 10% to sRT, and 69% to WS. The median follow-up time was 30 months. Outcomes based on different management modalities are described. Statistically significant differences among groups were detected in terms of quality of life (physical domain). Conclusions: MDT may provide the best individualized therapy for VS patients compared with a single gold-standard strategy

Defect Engineering of Ta3N5 Photoanodes: Enhancing Charge Transport and Photoconversion Efficiencies via Ti Doping

While Ta3N5 shows excellent potential as a semiconductor photoanode for solar water splitting, its performance is hindered by poor charge carrier transport and trapping due to native defects that introduce electronic states deep within its bandgap. Here, it is demonstrated that controlled Ti doping of Ta3N5 can dramatically reduce the concentration of deep-level defects and enhance its photoelectrochemical performance, yielding a sevenfold increase in photocurrent density and a 300 mV cathodic shift in photocurrent onset potential compared to undoped material. Comprehensive characterization reveals that Ti4+ ions substitute Ta5+ lattice sites, thereby introducing compensating acceptor states, reducing the concentrations of deleterious nitrogen vacancies and reducing Ta3+ states, and thereby suppressing trapping and recombination. Owing to the similar ionic radii of Ti4+ and Ta5+, substitutional doping does not introduce lattice strain or significantly affect the underlying electronic structure of the host semiconductor. Furthermore, Ti can be incorporated without increasing the oxygen donor content, thereby enabling the electrical conductivity to be tuned by over seven orders of magnitude. Thus, Ti doping of Ta3N5 provides a powerful basis for precisely engineering its optoelectronic characteristics and to substantially improve its functional characteristics as an advanced photoelectrode for solar fuels applications

Breakdown of Scale Invariance in the Phase Ordering of Fractal Clusters

Our numerical simulations with the Cahn-Hilliard equation show that coarsening of fractal clusters (FCs) is not a scale-invariant process. On the other hand, a typical coarsening length scale and interfacial area of the FC exhibit power laws in time, while the mass fractal dimension remains invariant. The initial value of the lower cutoff is a relevant length scale. A sharp-interface model is formulated that can follow the whole dynamics of a diffusion controlled growth, coarsening, fragmentation and approach to equilibrium in a system with conserved order parameter.Comment: 4 pages, 4 figures, RevTex, submitted to PR

Heterogeneity matters: Different regions of glioblastoma are characterized by distinctive tumor-supporting pathways

The glioblastoma microenvironment plays a substantial role in glioma biology. However, few studies have investigated its spatial heterogeneity. Exploiting 5-ALA Fluorescence Guided Surgery (FGS), we were able to distinguish between the tumor core (ALA+), infiltrating area (ALAPALE) and healthy tissue (ALA-) of the glioblastoma, based on the level of accumulated fluorescence. The aim of this study was to investigate the properties of the microenvironments associated with these regions. For this purpose, we isolated glioma-associated stem cells (GASC), resident in the glioma microenvironment, from ALA+, ALA-PALE and ALA-samples and compared them in terms of growth kinetic, phenotype and for the expression of 84 genes associated with cancer inflammation and immunity. Differentially expressed genes were correlated with transcriptomic datasets from TCGA/GTEX. Our results show that GASC derived from the three distinct regions, despite a similar phenotype, were characterized by different transcriptomic profiles. Moreover, we identified a GASC-based genetic signature predictive of overall survival and disease-free survival. This signature, highly expressed in ALA+ GASC, was also well represented in ALA PALE GASC. 5-ALA FGS allowed to underline the heterogeneity of the glioma microenvironments. Deepening knowledge of these differences can contribute to develop new adjuvant therapies targeting the crosstalk between tumor and its supporting microenvironment

Single atom Cu(I) promoted mesoporous titanias for photocatalytic Methyl Orange depollution and H 2 production

Tailoring the physicochemical properties and hence reactivity of semiconductor photocatalysts in a predictable fashion, remains a challenge to their industrial application. Here we demonstrate the striking promotional effect of incorporating single Cu(I) atoms, on aqueous phase photocatalytic dye degradation and H2 production over surfactant-templated mesoporous TiO2. X-ray absorption spectroscopy reveals that ultra-low concentrations of copper (0.02-0.1 wt%) introduced into the mesoporous TiO2 surface create isolated Cu (I) species which suppress charge recombination, and confer a six-fold photocatalytic promotion of Methyl Orange degradation and four-fold enhancement of H2 evolution. The impact of mesopore structure and photophysical properties on photocatalytic activity is also quantified for the first time: calcination increases mesopore size and nanocrystalline order, and induces an anatase to rutile phase transition that is accompanied by a decrease in the optical band gap, increased charge carrier lifetime, and a concomitant significant activity enhancement