Inorganofunctionalization of Ti(IV) and Zr(IV) on the MCM-41 Surface and its Interaction with a Mixed Valence Complex to use as Isoniazid Sensing

Journal of Inorganic and Organometallic Polymers and Materials - In this work, it describes the preparation of Titanium and Zirconium functionalized MCM-41 and subsequent chemical modification with...     

Expression and Localization of Thrombospondins,Plastin 3, and STIM1 in Different Cartilage Compartments of the Osteoarthritic Varus Knee

Osteoarthritis (OA) is a multifactorial disease which is characterized by a change in the homeostasis of the extracellular matrix (ECM). The ECM is essential for the function of the articular cartilage and plays an important role in cartilage mechanotransduction. To provide a better understanding of the interaction between the ECM and the actin cytoskeleton, we investigated the localization and expression of the Ca²⁺-dependent proteins cartilage oligomeric matrix protein (COMP), thrombospondin-1 (TSP-1), plastin 3 (PLS3) and stromal interaction molecule 1 (STIM1). We investigated 16 patients who suffered from varus knee OA and performed a topographical analysis of the cartilage from the medial and lateral compartment of the proximal tibial plateau. In a varus knee, OA is more pronounced in the medial compared to the lateral compartment as a result of an overloading due to the malalignment. We detected a location-dependent staining of PLS3 and STIM1 in the articular cartilage tissue. The staining intensity for both proteins correlated with the degree of cartilage degeneration. The staining intensity of TSP-1 was clearly reduced in the cartilage of the more affected medial compartment, an observation that was confirmed in cartilage extracts by immunoblotting. The total amount of COMP was unchanged; however, slight changes were detected in the localization of the protein. Our results provide novel information on alterations in OA cartilage suggesting that Ca²⁺-dependent mechanotransduction between the ECM and the actin cytoskeleton might play an essential role in the pathomechanism of OA.     

Three-dimensional printing of zirconia scaffolds for load bearing applications: Study of the optimal fabrication conditions

Yttria-stabilized zirconia (YSZ) scaffolds with a planned macroporosity fraction of about 70% were fabricated by Robocasting from inks with high solid loadings. The effects of solids loading and the concentrations of processing additives on the flow behavior of the starting suspensions and the viscoelastic properties of the resulting inks were investigated aiming at optimizing the printing process. The shear thinning flow behavior of the starting suspensions containing 45‒48 vol% solids and dispersant concentrations varying within 0.2‒0.8 wt% could be well described by the four-parameter Cross model. The flow behavior of the suspensions could be correlated with the interaction forces, and the ad-layer thickness formed around the YSZ particles. Further adding suitable amounts of a binder and a coagulating agent enabled optimizing the viscoelastic properties of inks for 3D printing. Good shape retention was observed for inks with elastic modulus, G′ ≥ 10 MPa. The green scaffolds were dried, sintered at 1350°C, and then used for the assessment of porosity and mechanical properties under compression tests. The porous structures exhibit average compressive strength (σ) of ~70 MPa. Weibull statistics applied to σ data revealed good reliability of the process, which can be used to fabricate YSZ scaffolds for orthopedic applications.     

Combinations of Histone Deacetylase Inhibitors with Distinct Latency Reversing Agents Variably Affect HIV Reactivation and Susceptibility to NK Cell-Mediated Killing of T Cells That Exit Viral Latency

The ‘shock-and-kill’ strategy to purge the latent HIV reservoir relies on latency-reversing agents (LRAs) to reactivate the provirus and subsequent immune-mediated killing of HIV-expressing cells. Yet, clinical trials employing histone deacetylase inhibitors (HDACis; Vorinostat, Romidepsin, Panobinostat) as LRAs failed to reduce the HIV reservoir size, stressing the need for more effective latency reversal strategies, such as 2-LRA combinations, and enhancement of the immune responses. Interestingly, several LRAs are employed to treat cancer because they up-modulate ligands for the NKG2D NK-cell activating receptor on tumor cells. Therefore, using in vitro T cell models of HIV latency and NK cells, we investigated the capacity of HDACis, either alone or combined with a distinct LRA, to potentiate the NKG2D/NKG2D ligands axis. While Bortezomib proteasome inhibitor was toxic for both T and NK cells, the GS-9620 TLR-7 agonist antagonized HIV reactivation and NKG2D ligand expression by HDACis. Conversely, co-administration of the Prostratin PKC agonist attenuated HDACi toxicity and, when combined with Romidepsin, stimulated HIV reactivation and further up-modulated NKG2D ligands on HIV⁺ T cells and NKG2D on NK cells, ultimately boosting NKG2D-mediated viral suppression by NK cells. These findings disclose limitations of LRA candidates and provide evidence that NK cell suppression of reactivated HIV may be modulated by specific 2-LRA combinations.     

Multifunctional Silver Nanoparticles-Decorated Silica Functionalized with Retinoic Acid with Anti-Proliferative and Antimicrobial Properties

The paper describes a rapid and simple method for preparing a multifunctional biomaterial based on retinoic acid covalently bound on silica@Ag particles. Monodispersed SiO₂ particles were prepared by Stöber method and further used for loading the Ag nanoparticles on their surface. This composite was further functionalized with retinoic acid. Characterization of the hybrid materials was made by UV–Visible spectroscopy, Transmission electron microscopy, Scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and Thermal analysis. The biological evaluation of the obtained materials revealed their potential use for multiple biomedical applications, from anti-proliferative agents to novel antimicrobial and antibiofilm strategies.     

Therapeutic Strategies To Counteract Antibiotic Resistance in MRSA Biofilm-Associated Infections

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as one of the leading causes of persistent human infections. This pathogen is widespread and is able to colonize asymptomatically about a third of the population, causing moderate to severe infections. It is currently considered the most common cause of nosocomial infections and one of the main causes of death in hospitalized patients. Due to its high morbidity and mortality rate and its ability to resist most antibiotics on the market, it has been termed a “superbug”. Its ability to form biofilms on biotic and abiotic surfaces seems to be the primarily means of MRSA antibiotic resistance and pervasiveness. Importantly, more than 80 % of bacterial infections are biofilm-mediated. Biofilm formation on indwelling catheters, prosthetic devices and implants is recognized as the cause of serious chronic infections in hospital environments. In this review we discuss the most relevant literature of the last five years concerning the development of synthetic small molecules able to inhibit biofilm formation or to eradicate or disperse pre-formed biofilms in the fight against MRSA diseases. The aim is to provide guidelines for the development of new anti-virulence strategies based on the knowledge so far acquired, and, to identify the main flaws of this research field, which have hindered the generation of new market-approved anti-MRSA drugs that are able to act against biofilm-associated infections     

The Effect of Harvesting Time on Olive Fruits and Oils Quality Parameters of Tortiglione and Dritta Olive Cultivars

Despite the fact that Italy holds the most important olives heritage in the world, with about 800 cultivars, most of them are still underestimated, in particular those from Abruzzo, a region located in the center of the peninsula. The aim of this work is to study the changes in quality parameters of olive fruits and related oils of two autochthonous Abruzzo olive cultivars, Tortiglione and Dritta during ripening (from September to November 2017). Both cultivar and ripening time affect the chemical parameters of olive fruits. Results highlight an increasing trend of the oil content with final values, based on fresh matter, of 38.7 ± 0.3% and 38.1 ± 0.9% for Tortiglione and Dritta, respectively. Olive oils chemical composition is also affected by ripening time and cultivar, with Tortiglione oils resulting generally richer than Dritta oils; on the first sampling time (30th of October) values for total phenolic content, antioxidant activity, and chlorophylls are 803.8 ± 68.2 mg gallic acid equivalent kg⁻¹, 2.7 ± 0.5 mmol trolox equivalent kg⁻¹, and 30.8 ± 1.6 mg pheophytin a kg⁻¹, respectively. Tocopherols seem to be more affected by ripening time than by cultivar, in particular for Dritta. Practical Application : The results on Abruzzo minor olive cultivars indicate that olive fruits and olive oil composition are strongly influenced by both cultivar and ripening time, giving rational indications about the optimal cultivar specific harvesting time and opening interesting opportunities for olive oil producers in a perspective of sustainable production to obtain high quality fruits and oils. The research provides detailed information about Tortiglione and Dritta olive cultivar, useful in the global context of revaluation of Italian minor olive varieties.     

Mesoglea Extracellular Matrix Reorganization during Regenerative Process in Anemonia viridis (Forskål, 1775)

Given the anatomical simplicity and the extraordinary ability to regenerate missing parts of the body, Cnidaria represent an excellent model for the study of the mechanisms regulating regenerative processes. They possess the mesoglea, an amorphous and practically acellular extracellular matrix (ECM) located between the epidermis and the gastrodermis of the body and tentacles and consists of the same molecules present in the ECM of vertebrates, such as collagen, laminin, fibronectin and proteoglycans. This feature makes cnidarians anthozoans valid models for understanding the ECM role during regenerative processes. Indeed, it is now clear that its role in animal tissues is not just tissue support, but instead plays a key role during wound healing and tissue regeneration. This study aims to explore regenerative events after tentacle amputation in the Mediterranean anemone Anemonia viridis, focusing in detail on the reorganization of the ECM mesoglea. In this context, both enzymatic, biometric and histological experiments reveal how this gelatinous connective layer plays a fundamental role in the correct restoration of the original structures by modifying its consistency and stiffness. Indeed, through the deposition of collagen I, it might act as a scaffold and as a guide for the reconstruction of missing tissues and parts, such as amputated tentacles.     

Overexpression of miR-124 in Motor Neurons Plays a Key Role in ALS Pathological Processes

miRNA(miR)-124 is an important regulator of neurogenesis, but its upregulation in SOD1G93A motor neurons (mSOD1 MNs) was shown to associate with neurodegeneration and microglia activation. We used pre-miR-124 in wild-type (WT) MNs and anti-miR-124 in mSOD1 MNs to characterize the miR-124 pathological role. miR-124 overexpression in WT MNs produced a miRNA profile like that of mSOD1 MNs (high miR-125b; low miR-146a and miR-21), and similarly led to early apoptosis. Alterations in mSOD1 MNs were abrogated with anti-miR-124 and changes in their miRNAs mostly recapitulated by their secretome. Normalization of miR-124 levels in mSOD1 MNs prevented the dysregulation of neurite network, mitochondria dynamics, axonal transport, and synaptic signaling. Same alterations were observed in WT MNs after pre-miR-124 transfection. Secretome from mSOD1 MNs triggered spinal microglia activation, which was unno-ticed with that from anti-miR-124-modulated cells. Secretome from such modulated MNs, when added to SC organotypic cultures from mSOD1 mice in the early symptomatic stage, also coun-teracted the pathology associated to GFAP decrease, PSD-95 and CX3CL1-CX3CR1 signaling im-pairment, neuro-immune homeostatic imbalance, and enhanced miR-124 expression levels. Data suggest that miR-124 is implicated in MN degeneration and paracrine-mediated pathogenicity. We propose miR-124 as a new therapeutic target and a promising ALS biomarker in patient sub-populations.