Kidney injury and cell therapy: Preclinical study

The aim of this study is to show histological and immunofluorescence analysis of renal parenchyma of agoutis affected by gentamicin‐induced renal disease after the infusion of bone marrow mononuclear cells (BMMC) stained with Hoechst®. Nine agouti's males were divided into three groups: Test group (TG): renal disease by gentamicin induced (n = 3), cell therapy group (CTG): renal disease by gentamicin induced and BMMC infusion (n = 3), and control group (CG): nonrenal disease and BMMC infusion (n = 3). TG and CTG were submitted to the protocol of renal disease induction using weekly application of gentamicin sulfate for 4 months. CG and CTG received a 1 × 108 BMMC stained with Hoechst and were euthanized for kidney examination 21 days after BMMC injection and samples were collected for histology and immunofluorescence analysis. Histological analysis demonstrated typical interstitial lesions in kidney similarly to human disease, as tubular necrosis, glomerular destruction, atrophy tubular, fibrotic areas, and collagen deposition. We conclude that histological analysis suggest a positive application of agouti's as a model for a gentamicin inducing of kidney disease, beyond the immunofluorescence analysis suggest a significant migration of BMMC to sites of renal injury in CTG. Microsc. Res. Tech., 2012. © 2011 Wiley Periodicals, Inc.     

Effects of the heterogeneity of game complexity and user population in learning performance of business simulation games

Previous studies on business simulation games (BSGs) have concluded that improved performance may not be the primary benefit of using BSGs, due to mixed results between student performance and perceptions. Two relevant and insightful issues attract our attention, namely, the impacts of the heterogeneous student population and the different complexity levels of BSG software. To address these issues, the present study aims to understand the relationship between student profile/characteristics and performance in the classroom with BSG-facilitated learning. An in-depth case study is conducted on a general college course designed to teach three different complexities of BSGs to students enrolled in different majors. Four student profile factors are individually tested for differences in performance scores as evaluated by the teacher. Additionally, the influences of 11 student characteristics are assessed with regard their self-reported perceived learning performances. Regression analysis and ANOVA are used to investigate the impacts of heterogeneous users and game complexity on student performance. Based on the regression analyses of the data collected from 43 respondents who participated in the general course, the study concludes that knowledge and skill may influence the heterogeneous student population; moreover, student participation and tacit learning preference improve performance, and students with an auditory learning preference or high learning motivation may not perform well in classroom BSG learning. However, the low value of adjusted R square implies that more dimensions or variables are needed to increase the explaining power of the performance scores in the regression analyses. In contrast, heterogeneous BSG software with different complexity levels present different results. The current research contributes practical and incremental knowledge on the complexity of heterogeneous BSG software on performance scores and the perceived learning performance of heterogeneous student populations. With the research limitations acknowledged, a series of suggestions for teachers pertaining to appropriate applications of BSGs in classes is offered as well as recommendations to BSG providers. Nevertheless, in-depth analyses are required, preferably with larger student population samples, to further explore the insignificant relationship between student perceptions and attitude under nonlinear extended complexity.     

Modeling and gradient pattern analysis of irregular SFM structures of porous silicon

Technological applications in opto-electronic devices have increased the interest in characterizing porous silicon structure patterns. Due to its physical properties, solutions from KPZ 2D are adopted to simulate the structure of porous material interface whose spatial characteristics are equivalent to those found in porous silicon samples. The analysis of the simulated and real Scanning Force Microscopy (SFM) surfaces was done using the Gradient Pattern Analysis (GPA). We found that the KPZ 2D model presented asymmetry levels compatible with the irregular surfaces observed by means of SFM images of π-Si.     

A Novel Human Neutralizing mAb Recognizes Delta,Gamma and Omicron Variants of SARS-CoV-2 and Can Be Used in Combination with Sotrovimab

The dramatic experience with SARS-CoV-2 has alerted the scientific community to be ready to face new epidemics/pandemics caused by new variants. Among the therapies against the pandemic SARS-CoV-2 virus, monoclonal Antibodies (mAbs) targeting the Spike glycoprotein have represented good drugs to interfere in the Spike/ Angiotensin Converting Enzyme-2 (ACE-2) interaction, preventing virus cell entry and subsequent infection, especially in patients with a defective immune system. We obtained, by an innovative phage display selection strategy, specific binders recognizing different epitopes of Spike. The novel human antibodies specifically bind to Spike-Receptor Binding Domain (RBD) in a nanomolar range and interfere in the interaction of Spike with the ACE-2 receptor. We report here that one of these mAbs, named D3, shows neutralizing activity for virus infection in cell cultures by different SARS-CoV-2 variants and retains the ability to recognize the Omicron-derived recombinant RBD differently from the antibodies Casirivimab or Imdevimab. Since anti-Spike mAbs, used individually, might be unable to block the virus cell entry especially in the case of resistant variants, we investigated the possibility to combine D3 with the antibody in clinical use Sotrovimab, and we found that they recognize distinct epitopes and show additive inhibitory effects on the interaction of Omicron-RBD with ACE-2 receptor. Thus, we propose to exploit these mAbs in combinatorial treatments to enhance their potential for both diagnostic and therapeutic applications in the current and future pandemic waves of coronavirus.     

Improvement of Glycaemia and Endothelial Function by a New Low-Dose Curcuminoid in an Animal Model of Type 2 Diabetes

Curcumin has been suggested as a promising treatment for metabolic diseases, but the high doses required limit its therapeutic use. In this study, a new curcuminoid is synthesised to increase curcumin anti-inflammatory and antioxidant potential and to achieve hypoglycaemic and protective vascular effects in type 2 diabetic rats in a lower dose. In vitro, the anti-inflammatory effect was determined through the Griess reaction, and the antioxidant activity through ABTS and TBARS assays. In vivo, Goto-Kakizaki rats were treated for 2 weeks with the equimolar dose of curcumin (40 mg/kg/day) or curcuminoid (52.4 mg/kg/day). Fasting glycaemia, insulin tolerance, plasma insulin, insulin signalling, serum FFA, endothelial function and several markers of oxidative stress were evaluated. Both compounds presented a significant anti-inflammatory effect. Moreover, the curcuminoid had a marked hypoglycaemic effect, accompanied by higher GLUT4 levels in adipose tissue. Both compounds increased NO-dependent vasorelaxation, but only the curcuminoid exacerbated the response to ascorbic acid, consistent with a higher decrease in vascular oxidative and nitrosative stress. SOD1 and GLO1 levels were increased in EAT and heart, respectively. Altogether, these data suggest that the curcuminoid developed here has more pronounced effects than curcumin in low doses, improving the oxidative stress, endothelial function and glycaemic profile in type 2 diabetes.     

Circulating Monocyte Subsets and Transcatheter Aortic Valve Replacement

Transcatheter aortic valve replacement (TAVR), as an alternative to open heart surgery, has revolutionized the treatment of severe aortic valve stenosis (AVS), the most common valvular disorder in the elderly. AVS is now considered a form of atherosclerosis and, like the latter, partly of inflammatory origin. Patients with high-grade AVS have a highly disturbed blood flow associated with high levels of shear stress. The immediate reopening of the valve during TAVR leads to a sudden restoration of a normal blood flow hemodynamic. Despite its good prognosis for patients, TAVR remains associated with bleeding or thrombotic postprocedural complications, involving mechanisms that are still poorly understood. Many studies report the close link between blood coagulation and inflammation, termed thromboinflammation, including monocytes as a major actor. The TAVR procedure represents a unique opportunity to study the influence of shear stress on human monocytes, key mediators of inflammation and hemostasis processes. The purpose of this study was to conduct a review of the literature to provide a comprehensive overview of the impact of TAVR on monocyte phenotype and subset repartition and the association of these parameters with the clinical outcomes of patients with severe AVS who underwent TAVR.     

Evaluation of damage in composites by using thermoelastic stress analysis: A promising technique to assess the stiffness degradation

The stiffness degradation represents one of the most interesting damage phenomena used for describing the fatigue behaviour of composites. A critical aspect of modelling the damage is represented by the simulation of the whole behaviour of the composite and by the assessment of the actual stiffness for the models validation. In this work, the stiffness degradation of quasi‐isotropic carbon fibre reinforced polymer (CFRP) obtained by automated fibre placement has been assessed by means of thermoelastic stress analysis. The amplitude of temperature signal at the mechanical frequency (thermoelastic signal) was considered as an indicator of material degradation and compared with the data provided by an extensometer. The correlation between thermoelastic and mechanical data allowed to build a new experimental model for evaluating and predicting material stiffness degradation by just using thermoelastic data. The proposed approach seems to be very promising for stiffness degradation assessment of real and complex mechanical components subjected to actual loading conditions.     

Characterization and photo-Fenton treatment of used tires leachate

In this study the leachates derived from used tires were firstly characterized by means of the evaluation of their organic matter content. The leachate from tire powder presented a COD value of 508 mg O(2) l(-1) and a TOC of 214 mg Cl (-1). The main identified organic substances were constituents of the rubber structure: benzothiazole derivatives, phthalates, phenolic derivatives, hydrocarbons and fatty acids. The application of photo-Fenton treatment was investigated in order to obtain the maximum organic matter removal. When a solar chamber as light source was used (light intensity=500 Wm(-2)), the best operational conditions were the following: [H(2)O(2)]=3703 mg l(-1), [Fe(2+)]=92.1 mg l(-1), initial pH 2.7-3.0, reaction time=100 min. After the photo-Fenton treatment at optimum conditions, the reached COD and TOC reduction was 64% and 48%, respectively. The main initial organic substances were eliminated after the reaction and no significant by-products were identified. A complementary treatment consisted of coagulation-flocculation carried out with FeCl(3) x 6H(2)O at pH 12 produced a maximum organic matter removal of 43% as COD and 39% as TOC. A combination of photo-Fenton followed by coagulation-flocculation enhanced the organic matter removal: a reduction of 77% of COD and 64% of TOC was attained.     

Fenretinide in Cancer and Neurological Disease: A Two-Face Janus Molecule

Recently, several chemotherapeutic drugs have been repositioned in neurological diseases, based on common biological backgrounds and the inverse comorbidity between cancer and neurodegenerative diseases. Fenretinide (all-trans-N-(4-hydroxyphenyl) retinamide, 4-HPR) is a synthetic derivative of all-trans-retinoic acid initially proposed in anticancer therapy for its antitumor effects combined with limited toxicity. Subsequently, fenretinide has been proposed for other diseases, for which it was not intentionally designed for, due to its ability to influence different biological pathways, providing a broad spectrum of pharmacological effects. Here, we review the most relevant preclinical and clinical findings from fenretinide and discuss its therapeutic role towards cancer and neurological diseases, highlighting the hormetic behavior of this pleiotropic molecule.