Laminin as a Biomarker of Blood–Brain Barrier Disruption under Neuroinflammation: A Systematic Review

Laminin, a non-collagenous glycoprotein present in the brain extracellular matrix, helps to maintain blood–brain barrier (BBB) integrity and regulation. Neuroinflammation can compromise laminin structure and function, increasing BBB permeability. The aim of this paper is to determine if neuroinflammation-induced laminin functional changes may serve as a potential biomarker of alterations in the BBB. The 38 publications included evaluated neuroinflammation, BBB disruption, and laminin, and were assessed for quality and risk of bias (protocol registered in PROSPERO; CRD42020212547). We found that laminin may be a good indicator of BBB overall structural integrity, although changes in expression are dependent on the pathologic or experimental model used. In ischemic stroke, permanent vascular damage correlates with increased laminin expression (β and γ subunits), while transient damage correlates with reduced laminin expression (α subunits). Laminin was reduced in traumatic brain injury and cerebral hemorrhage studies but increased in multiple sclerosis and status epilepticus studies. Despite these observations, there is limited knowledge about the role played by different subunits or isoforms (such as 411 or 511) of laminin in maintaining structural architecture of the BBB under neuroinflammation. Further studies may clarify this aspect and the possibility of using laminin as a biomarker in different pathologies, which have alterations in BBB function in common.     

Laser surface texturing of ceramics and ceramic composite materials – A review

The surface texturing of ceramics is generally performed through acid-based etching and machining; however, laser texturing may be considered as a more precise, reproducible and eco-friendly process. Furthermore, laser ablation may be used to produce complex patterns on ceramic surfaces, thus offering new surface engineering opportunities. The studies so far conducted on this topic have mainly been application-driven, and since a wide variety of lasers have been used for surface texturing, it is difficult to have a comprehensive understanding of this technique applied to ceramics and ceramic composite materials. Laser texturing requires a great deal of knowledge of the material and the laser source parameters to optimise the process in order to obtain the expected results. It is therefore important to expand the research on the laser texturing of ceramics and CMCs in order to build a relevant amount of literature that can be used to identify the most appropriate parameters for each application. This review provides an overview of most of the technological aspects considered relevant for the laser surface texturing of ceramics and CMCs, and includes the fundamentals of laser-material interactions and a summary of the used equipment and parameters. Furthermore, most of the techniques related to the modifications of surface material induced by a laser are critically reviewed, and the new horizons that are opening up, in the context of the modification of surfaces to improve the performances of materials for several applications, are discussed.     

The Ability of the Nitric Oxide Synthases Inhibitor T1023 to Selectively Protect the Non-Malignant Tissues

Previously, we showed that a nitric oxide synthase (NOS) inhibitor, compound T1023, induces transient hypoxia and prevents acute radiation syndrome (ARS) in mice. Significant efficacy (according to various tests, dose modifying factor (DMF)—1.6–1.9 against H-ARS/G-ARS) and safety in radioprotective doses (1/5–1/4 LD10) became the reason for testing its ability to prevent complications of tumor radiation therapy (RT). Research methods included studying T1023 effects on skin acute radiation reactions (RSR) in rats and mice without tumors and in tumor-bearing animals. The effects were evaluated using clinical, morphological and histological techniques as well as RTOG classification. T1023 administration prior to irradiation significantly limited the severity of acute RSR. This was due to a decrease in radiation alteration of the skin and underlying tissues, and the preservation of the functional activity of cell populations that are critical in the pathogenesis of radiation burn. The DMF values for T1023 for skin protection were 1.4–1.7. Moreover, its radioprotective effect was fully selective to normal tissues in RT models of solid tumors—T1023 reduced the severity of acute RSR and did not modify the antitumor effects of γ-radiation. The results indicate that T1023 can selectively protect the non-malignant tissues against γ-radiation due to hypoxic mechanism of action and potentiate opportunities of NOS inhibitors in RT complications prevention.     

Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer

Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.     

Kuwanon‐L as a New Allosteric HIV‐1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation

HIV‐1 integrase (IN) active site inhibitors are the latest class of drugs approved for HIV treatment. The selection of IN strand‐transfer drug‐resistant HIV strains in patients supports the development of new agents that are active as allosteric IN inhibitors. Here, a docking‐based virtual screening has been applied to a small library of natural ligands to identify new allosteric IN inhibitors that target the sucrose binding pocket. From theoretical studies, kuwanon‐L emerged as the most promising binder and was thus selected for biological studies. Biochemical studies showed that kuwanon‐L is able to inhibit the HIV‐1 IN catalytic activity in the absence and in the presence of LEDGF/p75 protein, the IN dimerization, and the IN/LEDGF binding. Kuwanon‐L also inhibited HIV‐1 replication in cell cultures. Overall, docking and biochemical results suggest that kuwanon‐L binds to an allosteric binding pocket and can be considered an attractive lead for the development of new allosteric IN antiviral agents.     

Metallopolymers based on a polyazomethine ligand containing rigid oxadiazole and flexible tetramethyldisiloxane units

Soluble, easily processable polymer–metal complexes with improved optical and dielectric properties for optoelectronic functional materials were obtained. For this, a new polyazomethine (PAZ2) was prepared by the reaction of a siloxane dialdehyde and bis(formyl‐p‐phenoxymethyl) tetramethyldisiloxane with 2,5‐bis(p‐aminophenyl)‐1,3,4‐oxadiazole, and it was used as a ligand for Cu(II), Co(II), and Zn(II) ions on the basis of the presence of the electron‐donor nitrogen atoms from the azomethine group and oxadiazole ring. The structure of the PAZ2 was determined by spectral [Fourier transform infrared (FTIR) and ¹H‐NMR spectroscopy] techniques. The metal complexation was proven by FTIR spectroscopy, and the silicon‐to‐metal ratios in the complexes were established by energy‐dispersive X‐ray fluorescence. The new materials were characterized by gel permeation chromatography, thermogravimetric analysis, and differential scanning calorimetry. The optical properties of PAZ2 and the derived metal complexes were studied by ultraviolet–visible and fluorescence spectroscopies. PAZ2 shows fluorescence emission, and it was significantly enhanced by metal complexation. The emission was enhanced by protonation; this behavior is useful, especially for sensors. The electrical properties were investigated by dielectric spectroscopy at various frequencies and temperatures, and this emphasized the existence of dipolar relaxations. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41631.     

Short communication: Comparison of growth kinetics at different temperatures of Streptococcus macedonicus and Streptococcus thermophilus strains of dairy origin

Within the genus Streptococcus, S. thermophilus and S. macedonicus are the 2 known species related to foods. Streptococci are widely used as starter cultures to rapidly lower milk pH. As S. macedonicus has been introduced quite recently, much less information is available on its technological potential. Because temperature is an important factor in fermented food production, we compared the growth kinetics over 24 h of 8 S. thermophilus and 7 S. macedonicus strains isolated from various dairy environments in Italy, at 4 temperatures, 30°C, 34°C, 37°C and 42°C. We used the Gompertz model to estimate the 3 main growth parameters; namely, lag phase duration (λ), maximum growth rate (µ_max), and maximum cell number at the stationary phase (N_max). Our results showed significant differences in average growth kinetics between the 2 species. Among the strains tested, 37°C appeared to be the optimal temperature for the growth of both species, particularly for S. macedonicus strains, which showed mean shorter lag phases and higher cell numbers compared with S. thermophilus. Overall, the growth curves of S. macedonicus strains were more similar to each other whereas S. thermophilus strains grew very differently. These results help to better define and compare technological characteristics of the 2 species, in view of the potential use of S. macedonicus in place of S. thermophilus in selected technological applications.     

Monitoring of perfluorinated compounds in edible fish from the Mediterranean Sea

Perfluorooctanoic acid (PFOA) and perfluorooctane sulphonate (PFOS) are environmental contaminants belonging to a chemical group known as perfluorinated compounds (PCFs). The United States Environmental Protection Agency (US EPA) considers both compounds to be carcinogenic. The goal of the present study was to evaluate the contamination levels of PFOS and PFOA in edible fish of the Mediterranean Sea. Twenty six fish muscles, 17 fish livers, five series of cephalopods (each composed of ten specimens) and thirteen series of bivalves (each composed of about 50 specimens) were used for the investigation. A fast sample treatment, followed by an LC–ESI–MS/MS method is described for the identification, and quantification of PFOA and PFOS in fish. The method was in-house-validated through the determination of precision, accuracy, specificity, calibration curve, decision limit (CCα), and detection capability (CCβ). The results showed PFOA and PFOS levels in fishes and molluscs lower than those reported for analogue matrices in different geographic areas. Therefore, our biomonitoring results did not show that the Mediterranean Sea had any particularly alarming pollution by PFCs, although it is located in a semi-closed basin with scarce water change. Nonetheless, a worrying element is that a few fish showed extremely high contamination by PFOA and PFOS. This finding needs further clarification in order to assess whether such unusual contamination is linked to “dot-like” pollutant release, which could explain the anomaly.