Reengineering of cancer cell surface charges can modulate cell migration

The ability to modulate the cell surface structure provides a powerful tool to understand fundamental processes and also to elicit desired cellular responses. Here we report the development of a new class of ‘clickable labels’ to reengineer the cell surface charges of live cells. The method relies on the use of metabolic oligosaccharide engineering (MOE) combined with chemo selective labeling of cell surface azido-containing sialic acids with dibenzocyclooctyne (DBCO) ionic-probes. Using this strategy, we demonstrate that reducing the negative charge induced by the overexpression of cell surface sialic acids in cancer cells leads to a reduction in cell migration without affecting drug supceptibility

Carbon Dots as an Emergent Class of Antimicrobial Agents

Antimicrobial resistance is a recognized global challenge. Tools for bacterial detection can combat antimicrobial resistance by facilitating evidence-based antibiotic prescribing, thus avoiding their overprescription, which contributes to the spread of resistance. Unfortunately, traditional culture-based identification methods take at least a day, while emerging alternatives are limited by high cost and a requirement for skilled operators. Moreover, photodynamic inactivation of bacteria promoted by photosensitisers could be considered as one of the most promising strategies in the fight against multidrug resistance pathogens. In this context, carbon dots (CDs) have been identified as a promising class of photosensitiser nanomaterials for the specific detection and inactivation of different bacterial species. CDs possess exceptional and tuneable chemical and photoelectric properties that make them excellent candidates for antibacterial theranostic applications, such as great chemical stability, high water solubility, low toxicity and excellent biocompatibility. In this review, we will summarize the most recent advances on the use of CDs as antimicrobial agents, including the most commonly used methodologies for CD and CD/composites syntheses and their antibacterial properties in both in vitro and in vivo models developed in the last 3 years.Peer reviewe

SERPINB3 delays glomerulonephritis and attenuates the lupus-like disease in lupus murine models by inducing a more tolerogenic immune phenotype

Objective: To explore the effects of SERPINB3 administration in murine lupus models with a focus on lupus-like nephritis. Methods: 40 NZB/W F1 mice were subdivided into 4 groups and intraperitoneally injected with recombinant SERPINB3 (7.5 \u3bcg/0.1 mL or 15 \u3bcg/0.1 mL) or PBS (0.1 mL) before (group 1 and 2) or after (group 3 and 4) the development of proteinuria ( 65100 mg/dl). Two additional mice groups were provided by including 20 MRL/lpr mice which were prophylactically injected with SERPINB3 (10 mice, group 5) or PBS (10 mice, group 6). Time of occurrence and levels of anti-dsDNA and anti-C1q antibodies, proteinuria and serum creatinine, overall- and proteinuria-free survival were assessed in mice followed up to natural death. Histological analysis was performed in kidneys of both lupus models. The Th17:Treg cell ratio was assessed by flow-cytometry in splenocytes of treated and untreated MRL/lpr mice. Statistical analysis was performed using non parametric tests and Kaplan-Meier curves, when indicated. Results: Autoantibody levels and proteinuria were significantly decreased and time of occurrence significantly delayed in SERPINB3-treated mice vs. controls. In agreement with these findings, proteinuria-free and overall survival were significantly improved in SERPINB3-treated groups vs. controls. Histological analysis demonstrated a lower prevalence of severe tubular lesions in kidneys of group 5 vs. group 6. SERPINB3-treated mice showed an overall trend toward a reduced prevalence of severe lesions in both strains. Th17:Treg ratio was significantly decreased in splenocytes of MRL/lpr mice treated with SERPINB3, compared to untreated control mice. Conclusions: SERPINB3 significantly improves disease course and delays the onset of severe glomerulonephritis in lupus-prone mice, possibly inducing a more tolerogenic immune phenotype

Glioma stem-like cells and metabolism:Potential for novel therapeutic strategies

Glioma stem-like cells (GSCs) were first described as a population which may in part be resistant to traditional chemotherapeutic therapies and responsible for tumour regrowth. Knowledge of the underlying metabolic complexity governing GSC growth and function may point to potential differences between GSCs and the tumour bulk which could be harnessed clinically. There is an increasing interest in the direct/indirect targeting or reprogramming of GSC metabolism as a potential novel therapeutic approach in the adjuvant or recurrent setting to help overcome resistance which may be mediated by GSCs. In this review we will discuss stem-like models, interaction between metabolism and GSCs, and potential current and future strategies for overcoming GSC resistance

Polarization of TH2 response is decreased during pregnancy in systemic lupus erythematosus

This study evaluated some cytokines involved in the Th1-Th2 shift during pregnancy in patients with systemic lupus erythematosus (SLE) and healthy women. Twenty-seven consecutive successful pregnancies in 26 SLE patients and 28 pregnancies in 28 matched healthy subjects, as controls, were enrolled and prospectively studied. Sera obtained at first and third trimesters of pregnancy were tested for IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, INF-γ, and TNF-α with a highly sensitive, multiplexed sandwich ELISA (SearchLight Human Inflammatory Cytokine Array). Statistics were performed by SPSS package. IL-8 serum levels were higher in the first (P<0.0001) and third (P=0.003) trimesters of pregnancy in SLE patients compared with controls, INF-γ serum levels in the third trimester (P=0.009), and IL-10 serum levels in the first and third trimesters (P=0.055 and P<0.0001, respectively). IL-2 (r=0.524 P=0.010), IL-12 (r=0.549 P=0.007), IFN-γ (r=0.492 P=0.017), and IL-6 (r=0.515 P=0.020) serum levels correlated with disease activity in SLE patients in the first trimester of pregnancy. Cytokine profile was similar in patients with and without lupus nephritis both in the first and in the third trimesters of pregnancy. IL-8 serum levels were lower in patients with a previous diagnosis of antiphospholipid antibody syndrome compared with those without, both in the first and in the third trimesters of pregnancy. In SLE patients, a lower than expected decrease in Th1 cytokine serum levels was observed in the third trimester of gestation which could contribute to a lower Th2 cytokine polarization during pregnancy

Application of Synchrotron Radiation-Based Micro-Analysis on Cadmium Yellows in Pablo Picasso's Femme

The cultural heritage community is increasingly exploring synchrotron radiation (SR) based techniques for the study of art and archaeological objects. When considering heterogeneous and complex micro-samples, such as those from paintings, the combination of different SR X-ray techniques is often exploited to overcome the intrinsic limitations and sensitivity of the single technique. Less frequently, SR X-ray analyses are combined with SR micro-photoluminescence or micro-Fourier Transform Infrared spectroscopy, which provide complementary information on the molecular composition, offering a unique integrated analysis approach. Although the spatial correlation between the maps obtained with different techniques is not straightforward due to the different volumes probed by each method, the combination of the information provides a greater understanding and insight into the paint chemistry. In this work, we discuss the advantages and disadvantages of the combination of X-ray techniques and SR-based photoluminescence through the study of two paint micro-samples taken from Pablo Picasso's Femme (1907). The painting contains two cadmium yellow paints (based on CdS): one relatively intact and one visibly degraded. SR micro-analyses demonstrated that the two Cd-yellow paints differ in terms of structure, chemical composition, and photoluminescence properties. In particular, on the basis of the combination of different SR measurements, we hypothesize that the degraded yellow is based on nanocrystalline CdS with high presence of Cd(OH)Cl. These two characteristics have enhanced the reactivity of the paint and strongly influenced its stability