Cyclic Nigerosyl-Nigerose as Oxygen Nanocarrier to Protect Cellular Models from Hypoxia/Reoxygenation Injury: Implications from an In Vitro Model

Heart failure (HF) prevalence is increasing among the aging population, and the mortality rate remains unacceptably high despite improvements in therapy. Myocardial ischemia (MI) and, consequently, ischemia/reperfusion injury (IRI), are frequently the basis of HF development. Therefore, cardioprotective strategies to limit IRI are mandatory. Nanocarriers have been proposed as alternative therapy for cardiovascular disease. Controlled reoxygenation may be a promising strategy. Novel nanocarriers, such as cyclic nigerosyl-nigerose (CNN), can be innovative tools for oxygen delivery in a controlled manner. In this study we analyzed new CNN-based formulations as oxygen nanocarriers (O₂-CNN), and compared them with nitrogen CNN (N₂-CNN). These different CNN-based formulations were tested using two cellular models, namely, cardiomyoblasts (H9c2), and endothelial (HMEC) cell lines, at different concentrations. The effects on the growth curve during normoxia (21% O₂, 5% CO₂ and 74% N₂) and their protective effects during hypoxia (1% O₂, 5% CO₂ and 94% N₂) and reoxygenation (21% O₂, 5% CO₂ and 74% N₂) were studied. Neither O₂-CNN nor N₂-CNN has any effect on the growth curve during normoxia. However, O₂-CNN applied before hypoxia induces a 15–30% reduction in cell mortality after hypoxia/re-oxygenation when compared to N₂-CNN. O₂-CNN showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for the future medical application of soluble nanocarrier systems for MI treatment.     

University-owned and university-invented patents: a network analysis on two Italian universities

The paper presents results from social network analysis applied to data on patenting of academics inventors employed in two Italian universities (Trieste University and Udine university, both located in Friuli Venezia Giulia region). The aim is to compare the co-invention networks generated by the academic inventors, tenured by one of the two universities, in their patenting activity with several organisations—firms, public research organisations—and in their activity for patents owned by one of the two universities. Results show that, despite the structural similarity, non-marginal differences emerge in the interaction of the two forms of patenting across the two universities. Empirical evidence suggests new research questions related in particular to the role played by the differing university patenting strategies in shaping local networks.     

Combined effect of lignosulfonate and carbonate on pure portland clinker compounds hydration. III. Hydration of tricalcium silicate alone and in the presence of tricalcium aluminate

The effect of carbonate and/or lignosulfonate on the hydration of C₃S alone and in the presence of C₃A has been examined by DTG and TG curves and by zeta potential measurements. The combined addition of sodium carbonate and lignosulfonate strongly retards C₃A hydration. However by mixing 20 % C₃A with C₃S the retarding effect is significantly lower. On the other hand the early C₃A hydration is completely blocked by sodium carbonate and lignosulfonate simultaneously added. It seems that the fluidifying effect of the combined addition of those admixtures could be ascribed to both the dispersing action and the completely blocking effect on the early C₃A hydration.     

Percutaneous Coronary Intervention (PCI) Reprograms Circulating Extracellular Vesicles from ACS Patients Impairing Their Cardio-Protective Properties

Extracellular vesicles (EVs) are promising therapeutic tools in the treatment of cardiovascular disorders. We have recently shown that EVs from patients with Acute Coronary Syndrome (ACS) undergoing sham pre-conditioning, before percutaneous coronary intervention (PCI) were cardio-protective, while EVs from patients experiencing remote ischemic pre-conditioning (RIPC) failed to induce protection against ischemia/reperfusion Injury (IRI). No data on EVs from ACS patients recovered after PCI are currently available. Therefore, we herein investigated the cardio-protective properties of EVs, collected after PCI from the same patients. EVs recovered from 30 patients randomly assigned (1:1) to RIPC (EV-RIPC) or sham procedures (EV-naive) ({"type":"clinical-trial","attrs":{"text":"NCT02195726","term_id":"NCT02195726"}}NCT02195726) were characterized by TEM, FACS and Western blot analysis and evaluated for their mRNA content. The impact of EVs on hypoxia/reoxygenation damage and IRI, as well as the cardio-protective signaling pathways, were investigated in vitro (HMEC-1 + H9c2 co-culture) and ex vivo (isolated rat heart). Both EV-naive and EV-RIPC failed to drive cardio-protection both in vitro and ex vivo. Consistently, EV treatment failed to activate the canonical cardio-protective pathways. Specifically, PCI reduced the EV-naive Dusp6 mRNA content, found to be crucial for their cardio-protective action, and upregulated some stress- and cell-cycle-related genes in EV-RIPC. We provide the first evidence that in ACS patients, PCI reprograms the EV cargo, impairing EV-naive cardio-protective properties without improving EV-RIPC functional capability.     

Scleroderma-like Impairment in the Network of Telocytes/CD34+ Stromal Cells in the Experimental Mouse Model of Bleomycin-Induced Dermal Fibrosis

Considerable evidence accumulated over the past decade supports that telocytes (TCs)/CD34⁺ stromal cells represent an exclusive type of interstitial cells identifiable by transmission electron microscopy (TEM) or immunohistochemistry in various organs of the human body, including the skin. By means of their characteristic cellular extensions (telopodes), dermal TCs are arranged in networks intermingled with a multitude of neighboring cells and, hence, they are thought to contribute to skin homeostasis through both intercellular contacts and releasing extracellular vesicles. In this context, fibrotic skin lesions from patients with systemic sclerosis (SSc, scleroderma) appear to be characterized by a disruption of the dermal network of TCs, which has been ascribed to either cell degenerative processes or possible transformation into profibrotic myofibroblasts. In the present study, we utilized the well-established mouse model of bleomycin-induced scleroderma to gain further insights into the TC alterations found in cutaneous fibrosis. CD34 immunofluorescence revealed a severe impairment in the dermal network of TCs/CD34⁺ stromal cells in bleomycin-treated mice. CD31/CD34 double immunofluorescence confirmed that CD31⁻/CD34⁺ TC counts were greatly reduced in the skin of bleomycin-treated mice compared with control mice. Ultrastructural signs of TC injury were detected in the skin of bleomycin-treated mice by TEM. The analyses of skin samples from mice treated with bleomycin for different times by either TEM or double immunostaining and immunoblotting for the CD34/α-SMA antigens collectively suggested that, although a few TCs may transition to α-SMA⁺ myofibroblasts in the early disease stage, most of these cells rather undergo degeneration, and then are lost. Taken together, our data demonstrate that TC changes in the skin of bleomycin-treated mice mimic very closely those observed in human SSc skin, which makes this experimental model a suitable tool to (i) unravel the pathological mechanisms underlying TC damage and (ii) clarify the possible contribution of the TC loss to the development/progression of dermal fibrosis. In perspective, these findings may have important implications in the field of skin regenerative medicine.     

Influence of lignosulphonate,glucose and gluconate on the C3A hydration

The influence of desugarized sodium lignosulphonate, glucose and sodium gluconate on the C₃A hydration has been examined using DTG analysis. At relatively low concentration levels of admixtures in the aqueous phase (1 to 3 g/l), such as those practically used for concrete mixes, lignosulphonate and glucose retard only slightly the C₃A hydration. Sodium gluconate is significantly more efficient in retarding C₃A hydration than lignosulphonate and glucose.     

Water reducers for the high alumina cement-silica fume system

High early strength mortars or concretes can be produced with high alumina cement. However, at later ages, particularly at temperatures higher than 20°C, there is a strength loss caused by a transformation of hexagonal hydrates into the cubic form. Silica fume is capable of hindering or blocking this transformation. However, a water reducing admixture is required to counterbalance the higher amount of mixing water caused by the very high specific surface area of silica fume. Since traditional water reducers (based on sulphonated naphtalene or melamine polymers) are not effective with high alumina cement, two alternative candidates have been tested: sodium tripoliphosphate and carboxylic acrylic ester. The sodium tripoliphosphate admixture is capable of reducing the mixing water; however, the simultaneous presence of silica fume and sodium tripoliphosphate causes a surprising and not yet fully-explained strength loss (only at 20°C with liquid water), although the transformation of hexagonal hydrates into the cubic form is truly hindered. In the presence of the carboxylic acrylic ester admixture, the amount of mixing water is reduced without any side effect on the strength loss of the high alumina cement-silica fume system. Therefore, the combination of silica fume with carboxylic acrylic ester appears to be a successful solution to produce mortars or concrete mixes based on high alumina cement content without any strength loss at later ages.

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Résumé Des mortiers et des bétons développant des résistances mécaniques élevées à court terme peuvent être produits avec les ciments alumineux. Toutefois, au cours du temps, en particulier pour des températures supérieures à 20°C, une diminution de la résistance mécanique survient suite à la transformation des hydrates hexagonaux en structure cubique. La fumée de silice est capable de ralentir ou de bloquer cette transformation. Toutefois, il faut ajouter un réducteur d'eau afin d'équilibrer la plus haute teneur en eau de gachage requise par la surface spécifique importante de la fumée de silice. Puisque les réducteurs d'eau traditionnels (basés sur le naphtalène sulphonate ou sur la mélamine) n'ont pas d'action sur les ciments alumineux, deux produits alternatifs ont été testés: le tripolyphosphate de sodium et l'ester carboxylique acrylique. Le tripolyphosphate de sodium est capable de réduire l'eau de gachage, mais la présence simultanée de fumée de silice et de tripolyphosphate de sodium conduit à une surprenante et non encore expliquée diminution de la résistance (seulement à 20°C avec l'eau liquide), bien que la transformation des hydrates hexagonaux en hydrate cubique soit vraiment limitée. En présence d'ester carboxylique acrylique, la quantité d'eau de gachage est réduite sans avoir de diminution de la résistance mécanique du système ciment alumineux-fumée de silice. C'est pourquoi la combinaison fumée de silice-ester carboxylique acrylique semble être une bonne solution pour produire des mortiers ou des bétons ne subissant pas de perte de résistance à long terme.

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Editorial note Prof, Saveria Monosi and Prof. Marío Collepardi are working at the Department of Materials and Earth Science, University of Ancona, Italy, which is a RILEM Associate Member. Prof. Collepardi is a member of the Board of Advisors for Materials and Structures.