Effect of the reduced graphene oxide (rGO) compaction degree and concentration on rGO-polymer composite printability and cell interactions

Graphene derivatives combined with polymers have attracted enormous attention for bone tissue engineering applications. Among others, reduced graphene oxide (rGO) is one of the preferred graphene-based fillers for the preparation of composites via melt compounding, and their further processing into 3D scaffolds, due to its established large-scale production method, thermal stability, and electrical conductivity. In this study, rGO (low bulk density 10 g L-1) was compacted by densification using a solvent (either acetone or water) prior to melt compounding, to simplify its handling and dosing into a twin-screw extrusion system. The effects of rGO bulk density (medium and high), densification solvent, and rGO concentration (3, 10 and 15% in weight) on rGO dispersion within the composite, electrical conductivity, printability and cell-material interactions were studied. High bulk density rGO (90 g L-1) occupied a low volume fraction within polymer composites, offering poor electrical properties but a reproducible printability up to 15 wt% rGO. On the other hand, the volume fraction within the composites of medium bulk density rGO (50 g L-1) was higher for a given concentration, enhancing rGO particle interactions and leading to enhanced electrical conductivity, but compromising the printability window. For a given bulk density (50 g L-1), rGO densified in water was more compacted and offered poorer dispersability within the polymer than rGO densified in acetone, and resulted in scaffolds with poor layer bonding or even lack of printability at high rGO percentages. A balance in printability and electrical properties was obtained for composites with medium bulk density achieved with rGO densified in acetone. Here, increasing rGO concentration led to more hydrophilic composites with a noticeable increase in protein adsorption. Moreover, scaffolds prepared with such composites presented antimicrobial properties even at low rGO contents (3 wt%). In addition, the viability and proliferation of human mesenchymal stromal cells (hMSCs) were maintained on scaffolds with up to 15% rGO and with enhanced osteogenic differentiation on 3% rGO scaffolds

Doxorubicin upregulates CXCR4 via miR-200c/ZEB1-dependent mechanism in human cardiac mesenchymal progenitor cells.

Doxorubicin (DOXO) treatment is limited by its cardiotoxicity, since it causes cardiac-progenitor-cell depletion. Although the cardioprotective role of the stromal cell-derived factor-1/C-X-C chemokine receptor type 4 (SDF1/CXCR4) axis is well established, its involvement during DOXO-induced cardiotoxicity has never been investigated. We showed that in a mouse model of DOXO-induced cardiomyopathy, CXCR4 <sup>+</sup> cells were increased in response to DOXO, mainly in human cardiac mesenchymal progenitor cells (CmPC), a subpopulation with regenerative potential. Our in vitro results showed a CXCR4 induction after 24 h of DOXO exposure in CmPC. SDF1 administration protected from DOXO-induced cell death and promoted CmPC migration. CXCR4 promoter analysis revealed zinc finger E-box binding homeobox 1 (ZEB1) binding sites. Upon DOXO treatment, ZEB1 binding decreased and RNA-polymerase-II increased, suggesting a DOXO-mediated transcriptional increase in CXCR4. Indeed, DOXO induced the upregulation of miR-200c, that directly targets ZEB1. SDF1 administration in DOXO-treated mice partially reverted the adverse remodeling, decreasing left ventricular (LV) end diastolic volume, LV ejection fraction and LV anterior wall thickness in diastole, recovering LV end systolic pressure and reducing±dP/dt. Moreover, in vivo administration of SDF1 partially reverted DOXO-induced miR-200c and p53 protein upregulation in mouse hearts. In addition, downmodulation of ZEB1 mRNA and protein by DOXO was significantly increased by SDF1. In keeping, p21 mRNA, that is induced by p53 and inhibited by ZEB1, is induced by DOXO treatment and is decreased by SDF1 administration. This study showed new players of the DOXO-induced cardiotoxicity, that can be exploited to ameliorate DOXO-associated cardiomyopathy

A Specific Circulating MicroRNA Cluster Is Associated to Late Differential Cardiac Response to Doxorubicin-Induced Cardiotoxicity In Vivo.

Cardiotoxicity is a detrimental side effect of the anticancer drug doxorubicin (DOX), characterized by progressive heart dysfunction. Circulating microRNAs (miRNAs) are recognized as potential biomarkers of cardiac disease; thus, we aimed to investigate their association with late cardiotoxicity in an animal model of disease. Twenty C57BL/6 female mice were administered with 24 mg/kg cumulative dose of DOX or saline during 2 weeks, followed by a recovery period of one month (T42). Echocardiography was performed at baseline and at T42, and plasma samples were collected at T42. The selection of all miRNAs of interest was conducted by literature overview and by screening, followed by RT-qPCR validation. Results. The analysis of cardiac function at T42 evidenced five DOX-treated animals indistinguishable (NoTox) from controls (CTRLs), while four presented heart impairment (Tox). Our analyses identified eight dysfunction-associated plasma miRNAs. In particular, seven miRNAs were found downregulated in comparison to CTRLs, miR-1-3p, miR-122-5p, miR-127-3p, miR-133a-3p, miR-215-5p, miR-455-3-p, and miR-499a-5p. Conversely, miR-34a-5p showed increased levels in Tox plasma samples. Noteworthy, we determined a cluster composed of miR-1-3p, miR-34a-5p, miR-133a-3p, and miR-499a-5p that distinguished with high-accuracy Tox from NoTox mice. This is the first study indicating that, similarly to what is observed in patients, DOX-administered animals present a differential cardiac response to treatment. Moreover, our results indicate the presence of specific plasma miRNAs whose expression reflect the presence of cardiac dysfunction in response to drug-induced injury

Conical nanopore membranes: solvent shaping of nanopores

We have undertaken a systematic investigation of the influence of ethanol on the shape of conical pores produced by the track-etch technique in poly(ethylene terephthalate) films. We have found that the cone angle of the conical nanopore generated is dependent on the amount of ethanol present in an alkaline etching solution. By varying the percentage of ethanol in the etch solution, precise control over the geometry of the conical nanopore and nanomaterials templated within these pores can be attained. We prove this by plating gold nanocones within the various conical nanopores prepared, dissolving the membrane to liberate the nanocones, and imaging the nanocones using scanning electron microscopy. The results of these investigations are reported here

Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)

To investigate the role of gefitinib in patients with high-grade gliomas (HGGs), a phase II trial (1839IL/0116) was conducted in patients with disease recurrence following surgery plus radiotherapy and first-line chemotherapy. Adult patients with histologically confirmed recurrent HGGs following surgery, radiotherapy and first-line chemotherapy, were considered eligible. Patients were treated with gefitinib (250 mgday−1) continuously until disease progression. The primary end point was progression-free survival at 6 months progression-free survival at 6 months (PFS-6). Tissue biomarkers (epidermal growth factor receptor (EGFR) gene status and expression, phosphorylated Akt (p-Akt) expression) were assessed. Twenty-eight patients (median age, 55 years; median ECOG performance status, 1) were enrolled; all were evaluable for drug activity and safety. Sixteen patients had glioblastoma, three patients had anaplastic oligodendrogliomas and nine patients had anaplastic astrocytoma. Five patients (17.9%, 95% CI 6.1–36.9%) showed disease stabilisation. The overall median time to progression was 8.4 (range 2–104+) weeks and PFS-6 was 14.3% (95% CI 4.0–32.7%). The median overall survival was 24.6 weeks (range 4–104+). No grade 3–4 gefitinib-related toxicity was found. Gefitinib showed limited activity in patients affected by HGGs. Epidermal growth factor receptor expression or gene status, and p-Akt expression do not seem to predict activity of this drug

Are food-deceptive orchid species really functionally specialized for pollinators?

Food-deceptive orchid species have traditionally been considered pollination specialized to bees or butterflies. However, it is unclear to which concept of specialization this assumption is related; if to that of phenotypic specialization or of functional specialization. The main aim of this work was to verify if pollinators of five widespread food-deceptive orchid species (Anacamptis morio (L.) R.M. Bateman, Pridgeon & M.W. Chase, Anacamptis pyramidalis (L.) Rich., Himantoglossum adriaticum H. Baumann, Orchis purpurea Huds. and Orchis simia Lam.) predicted from the phenotypic point of view matched with the observed ones. We addressed the question by defining target orchids phenotypic specialization on the basis of their floral traits, and we compared the expected guilds of pollinators with the observed ones. Target orchid pollinators were collected by conducting a meta-analysis of the available literature and adding unpublished field observations, carried out in temperate dry grasslands in NE Italy. Pollinator species were subsequently grouped into guilds and differences in the guild spectra among orchid species grouped according to their phenotype were tested. In contradiction to expectations derived from the phenotypic point of view, food-deceptive orchid species were found to be highly functionally generalized for pollinators, and no differences in the pollinator guild spectra could be revealed among orchid groups. Our results may lead to reconsider food-deceptive orchid pollination ecology by revaluating the traditional equation orchid-pollination specialization

3D Virtual Microphone System - Sonda Microfonica ad Elevata Direttivita'

Sono descritte la teoria del nuovo sistema di ripresa e registrazione multicanale basato su 32 capsule posizionate su una sonda sferica e alcune applicazioni pratiche. Con questo sistema si possono sintetizzare in tempo reale fino a 7 microfoni virtuali potendo scegliere dinamicamente la loro direttività (partendo da un omnidirezionale, passando ad un cardioide standard e arrivando ad un cardioide di ordine 6 ultradirettivo) e la loro posizione spaziale. Un'interfaccia grafica ne permette il posizionamento ed il movimento su un'immagine video a 360°. Il sistema è basato su un nuovo approccio matematico al calcolo della matrice di filtri FIR da convolvere in tempo reale con il segnale proveniente dalle capsule microfoniche; il tempo di latenza è ridotto grazie ad un processore di convoluzione partizionato

Carbon Nanomaterials in Electrochemical Detection

High surface-to-volume ratio, high conductivity and electrocatalytic properties are some of the most interesting characteristics of carbon nanomaterials. Such exceptional properties have found a strong application in the field of electrochemical sensing. In this chapter we present the great relevance of the introduction of carbon nanomaterials, such as carbon nanotubes and graphene, for the development of new electrochemical sensors and biosensors. The possibility to exploit carbon nanomaterials for direct electrochemical sensing is illustrated. Furthermore, the easy modification of carbon materials with biomolecules enables the development of sophisticated and ultra-sensitive electrochemical sensors and biosensors for a plethora of important analytes and biomolecules, from DNA to cancer biomarkers. The possibility of coupling nanocarbon-based electrochemical sensors as detectors in separation techniques is briefly introduced. The most typical applications are described