Exposure to the natural alkaloid Berberine affects cardiovascular system morphogenesis and functionality during zebrafish development

The plant-derived natural alkaloid berberine displays therapeutic potential to treat several pathological conditions, including dyslipidemias, diabetes and cardiovascular disorders. However, data on berberine effects during embryonic development are scarce and in part controversial. In this study, using zebrafish embryos as vertebrate experimental model, we address the effects of berberine treatment on cardiovascular system development and functionality. Starting from the observation that berberine induces developmental toxicity and pericardial edema in a time- and concentration-dependent manner, we found that treated embryos display cardiac looping defects and, at later stages, present an abnormal heart characterized by a stretched morphology and atrial endocardial/myocardial detachment. Furthermore, berberine affected cardiac functionality of the embryos, promoting bradycardia and reducing the cardiac output, the atrial shortening fraction percentage and the atrial stroke volume. We also found that, during development, berberine interferes with the angiogenic process, without altering vascular permeability. These alterations are associated with increased levels of vascular endothelial growth factor aa (vegfaa) mRNA, suggesting an important role for Vegfaa as mediator of berberine-induced cardiovascular defects. Altogether, these data indicate that berberine treatment during vertebrate development leads to an impairment of cardiovascular system morphogenesis and functionality, suggesting a note of caution in its use during pregnancy and lactation

On the uniqueness of sign changing bound state solutions of a semilinear equation

We establish the uniqueness of the higher radial bound state solutions of \Delta u +f(u)=0,\quad x\in \RR^n. \leqno(P) We assume that the nonlinearity $f\in C(-\infty,\infty)$ is an odd function satisfying some convexity and growth conditions, and either has one zero at $b>0$, is non positive and not identically 0 in $(0,b)$, and is differentiable and positive $[b,\infty)$, or is positive and differentiable in $[0,\infty)$

Does Value Co-Creation Really Matter? An Investigation of Italian Millennials Intention to Buy Electric Cars

The present research aims to explore the determinants of (full) electric vehicle (EV) buying intention of Italian millennials focusing on the role that value co-creation initiatives might play in the buying decision-making process. Value co-creation initiatives in the EV domain are studied employing an enhanced version of the Theory of Reasoned Action which, in addition to the traditional variables of the model, also includes perceived importance of cars’ attributes. Structural Equation Modeling (SEM) is used to analyze the data collected though an online survey on 523 Italians aged 18–35. The outcomes provide recommendations to tailor proper initiatives to encourage millennials’ buying intention of electric vehicles supporting private companies in favoring the adoption of wide-spread pro-environmental behaviors among Italian youngsters

Actividad biológica de un furanoeremofilano aislado de Senecio filaginoides var. filaginoides

Un compuesto, 10 H-9-oxofuranoeremofilano fue aislado de Senecio filaginoides var. filaginoides, esta estructura fue establecida sobre la base del análisis  espectral y comparación con  datos bibliográficos. La actividad antimicrobiana fue demostrada contra Candida spp pero no contra las bacterias (S.aureus,  E.coli y P. aeruginosa). Además el compuesto mostró actividad antifúngica y efectos sobre el crecimiento micelial del hongo fitopatógeno Botrytis cinerea

Direct evidence for local IgE production in the human colonic mucosa

Understanding the biology of IgE in humans has become a matter of interest that remains incompletely understood due to the rarity of peripheral IgE+ cells. The increased incidence of allergic diseases and food-induced anaphylaxis overtime demands an urgent development of disease-modifying therapies that reverse the synthesis of IgE and the induction of IgE-mediated allergic reactions. Although some reports showed specific IgE in stools and IgE+ cells in the gastrointestinal tract of allergic patients,1, 2 the microanatomical location of the class-switch recombination (CSR) to ε chain is largely unknown. This isotype is produced through CSR mechanism by activated IgM-producing B cells (direct switch) or following IgG+ B memory cell-switch to ε chain (sequential switch) in a Th2 milieu with the induction of the cytidine deaminase (AID).3 It has been demonstrated that this mechanism occurs prior to germinal center (GC) formation in secondary lymphoid tissues such as lymph nodes and tonsils,4 but it is controversial whether the IgE isotype switching can occur in the human intestinal mucosa and which niches could be involved. Our study aimed to investigate the local IgE synthesis in the stroma of juvenile colonic polyps (JP) from patients with rectal bleeding and the relationship between IgE production and food sensitization, a risk factor for food allergy.Fil: Canziani, Karina Eva. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Pucci Molineris, Melisa Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Guzman, Luciana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Bernedo, Viviana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: García, Marcela. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Altamirano, Eugenia Margarita. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Muglia, Cecilia Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Docena, Guillermo H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentin

Adeno-associated virus type 5 infection via PDGFRα is associated with Interstitial lung disease in systemic sclerosis and generates composite peptides and epitopes recognized by the agonistic immunoglobulins present in patients with systemic sclerosis

Objectives: The etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet-derived growth factor receptors (PDGFRs) are overexpressed in SSc patients. Since PDGFRα is targeted of the adeno-associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFRα exposing epitopes that may induce the immune responses to the virus-PDGFRα complex. Methods: The binding of monomeric human PDGFRα to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFRα locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL). Immune responses to AAV5 and PDGFRα were evaluated by SPR using SSc monoclonal anti-PDGFRα antibodies and Immunoaffinity-purified anti-PDGFRα antibodies from sera of SSc patients. Results: AAV5 was detected in the BAL of 41 out of 66 (62.1%) SSc patients with interstitial lung disease and in 17 of 66 controls (25.75 %; p<0.001). In SSc lungs, AAV5 localized in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and PDGFRα was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti-PDGFRα antibodies identified spatially contiguous epitopes derived from PDGFRα and AAV5 that interacted with SSc agonistic antibodies to PDGFRα. These peptides were also able to bind total IgG isolated from SSc patients, not from healthy controls. Conclusions: These data link AVV5 with the immune reactivity to endogenous antigens in SSc, and provide a novel element in the pathogenesis of SSc

Statins but Not Aspirin Reduce Thrombotic Risk Assessed by Thrombin Generation in Diabetic Patients without Cardiovascular Events: The RATIONAL Trial

The systematic use of aspirin and statins in patients with diabetes and no previous cardiovascular events is controversial. We sought to assess the effects of aspirin and statins on the thrombotic risk assessed by thrombin generation (TG) among patients with type II diabetes mellitus and no previous cardiovascular events.Prospective, randomized, open, blinded to events evaluation, controlled, 2×2 factorial clinical trial including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40 mg/d, both or none. Outcome measurements included changes in TG levels after treatment (8 to 10 weeks), assessed by a calibrated automated thrombogram. At baseline all groups had similar clinical and biochemical profiles, including TG levels. There was no interaction between aspirin and atorvastatin. Atorvastatin significantly reduced TG measured as peak TG with saline (85.09±55.34 nmol vs 153.26±75.55 nmol for atorvastatin and control groups, respectively; p = 0.018). On the other hand, aspirin had no effect on TG (121.51±81.83 nmol vs 116.85±67.66 nmol, for aspirin and control groups, respectively; p = 0.716). The effects of treatments on measurements of TG using other agonists were consistent.While waiting for data from ongoing large clinical randomized trials to definitively outline the role of aspirin in primary prevention, our study shows that among diabetic patients without previous vascular events, statins but not aspirin reduce thrombotic risk assessed by TG.ClinicalTrials.gov NCT00793754

Evaluation of bond strength of silorane and methacrylate based restorative systems to dentin using different cavity models

OBJECTIVE: The aim of this in vitro study was to evaluate the microtensile bond strength (µTBS) to dentin of two different restorative systems: silorane-based (P90), and methacrylate-based (P60), using two cavity models. MATERIAL AND METHODS: Occlusal enamel of 40 human third molars was removed to expose flat dentin surface. Class I cavities with 4 mm mesial-distal width, 3 mm buccal-lingual width and 3 mm depth (C-factor=4.5) were prepared in 20 teeth, which were divided into two groups (n=10) restored with P60 and P90, bulk-filled after dentin treatment according to manufacturer's instructions. Flat buccal dentin surfaces were prepared in the 20 remaining teeth (C-factor=0.2) and restored with resin blocks measuring 4x3x3 mm using the two restorative systems (n=10). The teeth were sectioned into samples with area between 0.85 and 1.25 mm(2) that were submitted to µTBS testing, using a universal testing machine (EMIC) at speed of 0.5 mm/min. Fractured specimens were analyzed under stereomicroscope and categorized according to fracture pattern. Data were analyzed using ANOVA and Tukey Kramer tests. RESULTS: For flat surfaces, P60 obtained higher bond strength values compared with P90. However, for Class I cavities, P60 showed significant reduction in bond strength (p<0.05). No statistical difference between restorative systems was shown for Class I cavity model (p>0.05), or between Class I Cavity and Flat Surface group, considering P90 restorative system (p>0.05). Regarding fracture pattern, there was no statistical difference among groups (p=0.0713) and 56.3% of the fractures were adhesive. CONCLUSION: It was concluded that methacrylate-based composite µTBS was influenced by cavity models, and the use of silorane-based composite led to similar bond strength values compared to the methacrylate-based composite in cavities with high C-factor