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OBJECTIVE: Neutrophils play a key role in immunity and are known to respond to exogenous threats by releasing neutrophil extracellular traps (NETs) through NETosis, a process involving the release of neutrophils nuclear DNA decorated with proteins into the extracellular space. In this study, attention has been focused on the ability of differently charged molecular systems polyhedral oligomeric silsesquioxanes (POSS) to induce NETosis. MATERIALS AND METHODS: NETs formation was induced by phorbol myristate acetate (PMA) (positive control) and POSS treatment and visualized by confocal microscopy. Moreover, NETs production was quantified by Sytox green staining. Oxidative stress, autophagy as well as endocytosis involvement in the observed phenomena was evaluated by a specific inhibitory approach. RESULTS: Results obtained in this study demonstrate a POSS time and dose-dependent ability in inducing NETs release irrespectively to their charge. POSS induced NETosis is a consequence of their internalization, as demonstrated by the strong reduction in NETs formation after endocytosis inhibition. Moreover, POSS induced NETosis involves both an increase in superoxide anion generation and autophagy pathway activation as demonstrated by the protective effect displayed by sodium azide and wortmannin. CONCLUSIONS: Data presented in this study indicate that nanomaterials and molecular systems could have a role in the onset of inflammatory phenomena. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Epiregulin is a member of the epidermal growth factor (EGF) family produced by keratinocytes: the aim of this study was to investigate the ability of biocompatible nanoparticles loaded with such growth factor to increase human keratinocytes proliferation. MATERIALS AND METHODS: Different PLGA (Poly-d,l-lactide-co-glycolide)-nanoparticles (NPs) formulations have been characterized in size and zeta potential by dynamic light scattering (DLS) analysis. The ability of the different PLGA-NPs formulations to adhere onto dental surfaces has been tested, and epiregulin-enriched PLGA-NPs has been produced. Epiregulin release from NPs has been tested by enzyme-linked immunosorbent (ELISA) assay and the proliferative effects of epiregulin-NPs on human keratinocytes have been evaluated. RESULTS: DLS analysis revealed a different size distribution depending on the PLA/PGA (poly lactic acid/poly glycolic acid) ratio used. 50:50 PLGA-NPs exhibited the smaller size and the best dental adhesive ability. Moreover, such epiregulin-loaded NPs was able to increase cell proliferation. CONCLUSIONS: Direct dental pocket drug delivery implies the NPs solution loading onto the dental surface at the cement-enamel junction level: 50:50 PLGA-NPs, with their small size and excellent adhesive ability, represent an interesting tool to deliver epiregulin directly where there is the need for epithelial proliferation. These results describe a possible strategy for periodontal pocket delivery of Epiregulin-loaded PLGA- NPs and might provide a new approach for the treatment of gingival recession, where gingival epithelium proliferation is needed. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Laser therapy is known to stimulate cell proliferation and differentiation, an effect called "biostimulation". Although many clinical applications of laser therapy take advantage from such positive effect, the underlying molecular mechanisms are not fully understood. The aim of this work was to investigate the effect of near-infrared laser stimulation on rat pre-odontoblast cells (MDPC-23 cells) and the molecular mechanism/s involved. MATERIALS AND METHODS: MDPC-23 cells were stimulated with a near-infrared (980 nm) laser source with different energy settings (1- 50 J, corresponding to 0.65-32.47 J/cm2) and cell proliferation was evaluated by manual count. ERK 1/2 pathway activation was evaluated by Western blot analysis. RESULTS: 1-10 J stimulation (corresponding to 0.65-6.5 J/cm²) significantly increase MDPC- 23 cell proliferation and such effect seems to be mediated by ERK 1/2 signalling pathway activation, showing a key role of ERK 1/2 pathway in mediating the proliferative response induced by laser stimulation. CONCLUSIONS: Near infrared laser stimulation with low energies (1-10 J) is able to increase cell proliferation through ERK 1/2 signalling pathway activation. At the same time, higher energy stimulation (25-50 J) induces an initial toxic effect, probably activating pro-apoptotic signalling molecules, downstream ERK 1/2 kinase. Such results foster the application of this therapeutic approach in different clinical settings in which a regenerative tissue response is needed. [ABSTRACT FROM AUTHOR]

In this paper an omnidirectional Distributed Vision System (DVS) is presented. The presented DVS is able to learn to navigate a mobile robot in its working environment without any prior knowledge about calibration parameters of the cameras or the control law of the robot (this is an important feature if we want to apply this system to existing camera networks). The DVS consists of different Vision Agents (VAs) implemented by omnidirectional cameras. The main contribution of the work is the explicit distribution of the acquired knowledge in the DVS. The aim is to develop a totally autonomous system able not only to learn control policies by on-line learning, but also to deal with a changing environment and to improve its performance during lifetime. Once an initial knowledge is acquired by one Vision Agent, this knowledge can be transferred to other Vision Agents in order to exploit what was already learned. In this paper, first we investigate how the Vision Agent learns the knowledge, then we evaluate its performance and test the knowledge propagation on three different VAs. Experiments are reported both using a system simulator and using a prototype of the Distributed Vision System in a real environment demonstrating the feasibility of the approach. [ABSTRACT FROM AUTHOR]

Progressive multifocal leukoencephalopathy (PML) is a serious disorder that primarily affects individuals with a suppressed immune system. Few semiological elements help clearly distinguish PML from other diseases included in the differential diagnosis. Moreover, the clinical course of disease may be chronic or rapidly progressive, with different magnetic resonance imaging (MRI) patterns. The purpose of this study was to confirm the diagnostic value of conventional MRI sequences combined with diffusion-weighted imaging (DWI) in PML to identify those patients with worst prognosis. We used both conventional MRI sequences and DWI to monitor four male patients aged between 40 and 50 years affected by PML. In two patients, the disease rapidly led to death whereas the other two patients presented a chronic course. Conventional MRI sequences enable detection of the extension of white matter lesions. DWI permits more accurate differentiation of the disease progression front, which exhibits low signal intensity in apparent diffusion coefficient (ADC) maps, from the central gliotic area of demyelinisation, characterised by high ADC values. Patients with rapidly evolving PML have a clear progression front on DWI, which seems to be very tenuous, if not absent, during the quiescent phases of the disease. The addition of DWI sequences to conventional MRI seems to be a valid method for accurately diagnosing PML and establishing the degree of disease progression. [ABSTRACT FROM AUTHOR]

Few population studies are available on epidemiological indexes of hereditary ataxias. An investigation on the prevalence rate of these movement disorders is in progress for the Veneto region, the main area of northeast Italy with a population of 4,490,586 inhabitants. The first results of this epidemiological survey concern the province of Padua, which numbers 845,203 residents (January 1, 2002). The prevalence rate of inherited ataxias has been estimated at 93.3 cases per million inhabitants. The most common types appeared to be the autosomal dominant forms, namely spinocerebellar ataxia type 1 and 2, with a prevalence of 24 per 1,000,000. In the same population, with a prevalence rate of 6 per 1,000,000, Friedreich's ataxia was defined as the prominent recessive autosomal form. There were very rare cases of ataxia telangiectasia, ataxia with vitamin E deficiency and cerebellar ataxia with congenital muscular dystrophy, a recently identified autosomal recessive disease. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a connective tissue disorder characterized by microvascular injury, extracellular matrix deposition, autoimmunity, inflammation, and fibrosis. The clinical complexity and high heterogeneity of the disease make the discovery of potential therapeutic targets difficult. However, the recent progress in the comprehension of its pathogenesis is encouraging. Growth Arrest-Specific 6 (Gas6) and Tyro3, Axl, and MerTK (TAM) receptors are involved in multiple biological processes, including modulation of the immune response, phagocytosis, apoptosis, fibrosis, inflammation, cancer development, and autoimmune disorders. In the present manuscript, we review the current evidence regarding SSc pathogenesis and the role of the Gas6/TAM system in several human diseases, suggesting its likely contribution in SSc and highlighting areas where further research is necessary to fully comprehend the role of TAM receptors in this condition. Indeed, understanding the involvement of TAM receptors in SSc, which is currently unknown, could provide valuable insights for novel potential therapeutic targets.

Introduction: The protein growth arrest-specific 6 (Gas6) and its tyrosine kinase receptors Tyro-3, Axl, and Mer (TAM) are ubiquitous proteins involved in regulating inflammation and apoptotic body clearance. Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system leading to progressive and irreversible disability if not diagnosed and treated promptly. Gas6 and TAM receptors have been associated with neuronal remyelination and stimulation of oligodendrocyte survival. However, few data are available regarding clinical correlation in MS patients. We aimed to evaluate soluble levels of these molecules in the cerebrospinal fluid (CSF) and serum at MS diagnosis and correlate them with short-term disease severity., Methods: In a prospective cohort study, we enrolled 64 patients with a diagnosis of clinical isolated syndrome (CIS), radiological isolated syndrome (RIS) and relapsing-remitting (RR) MS according to the McDonald 2017 Criteria. Before any treatment initiation, we sampled the serum and CSF, and collected clinical data: disease course, presence of gadolinium-enhancing lesions, and expanded disability status score (EDSS). At the last clinical follow-up, we assessed EDSS and calculated MS severity score (MSSS) and age-related MS severity (ARMSS). Gas6 and TAM receptors were determined using an ELISA kit (R&D Systems) and compared to neurofilament (NFLs) levels evaluated with SimplePlex™ fluorescence-based immunoassay., Results: At diagnosis, serum sAxl was higher in patients receiving none or low-efficacy disease-modifying treatments (DMTs) versus patients with high-efficacy DMTs ( p = 0.04). Higher CSF Gas6 and serum sAXL were associated with an EDSS <3 at diagnosis ( p = 0.04; p = 0.037). Serum Gas6 correlates to a lower MSSS (r 2 = -0.32, p = 0.01). Serum and CSF NFLs were confirmed as disability biomarkers in our cohort according to EDSS ( p = 0.005; p = 0.002) and MSSS (r 2  = 0.27, p = 0.03; r 2 = 0.39, p = 0.001). Results were corroborated using multivariate analysis., Conclusions: Our data suggest a protective role of Gas6 and its receptors in patients with MS and suitable severity disease biomarkers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 D’Onghia, Colangelo, Bellan, Tonello, Puricelli, Virgilio, Apostolo, Minisini, Ferreira, Sozzi, Vincenzi, Cantello, Comi, Pirisi, Vecchio and Sainaghi.)

Conductive nanocomposites play a significant role in tissue engineering by providing a platform to support cell growth, tissue regeneration, and electrical stimulation. In the present study, a set of electroconductive nanocomposite hydrogels based on gelatin (G), chitosan (CH), and conductive carbon black (CB) was synthesized with the aim of developing novel biomaterials for tissue regeneration application. The incorporation of conductive carbon black (10, 15 and 20 wt.%) significantly improved electrical conductivity and enhanced mechanical properties with the increased CB content. We employed an oversimplified unidirectional freezing technique to impart anisotropic morphology with interconnected porous architecture. An investigation into whether any anisotropic morphology affects the mechanical properties of hydrogel was conducted by performing compression and cyclic compression tests in each direction parallel and perpendicular to macroporous channels. Interestingly, the nanocomposite with 10% CB produced both anisotropic morphology and mechanical properties, whereas anisotropic pore morphology diminished at higher CB concentrations (15 and 20%), imparting a denser texture. Collectively, the nanocomposite hydrogels showed great structural stability as well as good mechanical stability and reversibility. Under repeated compressive cyclic at 50% deformation, the nanocomposite hydrogels showed preconditioning, characteristic hysteresis, nonlinear elasticity, and toughness. Overall, the collective mechanical behavior resembled the mechanics of soft tissues. The electrical impedance associated with the hydrogels was studied in terms of the magnitude and phase angle in dry and wet conditions. The electrical properties of the nanocomposite hydrogels conducted in wet conditions, which is more physiologically relevant, showed a decreasing magnitude with increased CB concentrations, with a resistive-like behavior in the range 1 kHz-1 MHz and a capacitive-like behavior for frequencies <1 kHz and >1 MHz. Overall, the impedance of the nanocomposite hydrogels decreased with increased CB concentrations. Together, these nanocomposite hydrogels are compositionally, morphologically, mechanically, and electrically similar to native ECMs of many tissues. These gelatin-chitosan-carbon black nanocomposite hydrogels show great promise for use as conducting substrates for the growth of electro-responsive cells in tissue engineering.

Background: A relevant proportion of immunocompromised patients did not reach a detectable seroconversion after a full primary vaccination cycle against SARS-CoV-2. The effect of different immunosuppressants and the potential risks for SARS-CoV-2 infection in these subjects is largely unknown., Methods: Patients from the Rivalsa prospective, observational cohort study with planned anti SARS-CoV-2 third dose mRNA vaccination between October and December 2021 were asked to participate to this follow-up study. Patients were asked about eventual confirmed positivity to SARS-CoV-2 infection within 6 months from the third dose and to undergo a blood draw to evaluate seroconversion status after the additional vaccine shot., Results: 19 out of 114 patients taking part in the survey developed a confirmed SARS-CoV-2 infection; we identified mycophenolate treatment as an independent predictor of an increased risk of infection even after the third vaccine dose (OR: 5.20, 95% CI: 1.70-20.00, p=0.0053). This result is in agreement with the in vitro evidence that MMF impairs both B and T lymphocytes driven immune responses (reduction both in memory B cells producing anti-spike antibodies and in proliferating CD4+ and CD8+ T cells)., Conclusions: Immunocompromised patients need an additional vaccine administration to reach a detectable seroconversion, thus fostering a more personalized approach to their clinical management. Moreover, patients undergoing mycophenolate treatment show a specific increased infection risk, with respect to other immunosuppressants thus supporting a closer monitoring of their health status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rizzi, Tonello, Brinno, Zecca, Matino, Cittone, Rizzi, Casciaro, D’Onghia, Colangelo, Minisini, Bellan, Castello, Chiocchetti, Pirisi, Rigamonti, Lilleri, Zavaglio, Bergami, Sola and Sainaghi.)