In vivo assessment of CdSe-ZnS quantum dots: coating dependent bioaccumulation and genotoxicity.

Semiconductor nanocrystals, or Quantum Dots (QDs), have gained considerable attention due to their unique size-dependent optical and electronic properties that make them attractive for a wide range of applications, including biology and nanomedicine. Their widespread use, however, poses urgent questions about their potential toxicity, especially because of their heavy metal composition that could cause harmful effects to human health and environment. In this work, we evaluated in vivo the long-term toxicity of CdSe-ZnS QDs with different surface coatings, probing oral administration in the model system Drosophila melanogaster. In particular, we found that all the differently coated QDs significantly affect the lifespan of treated Drosophila populations and induce a marked increase in reactive oxygen species (ROS) levels. Furthermore, we observed that these QDs induce severe genotoxic effects and increased rate of apoptosis in Drosophila haemocytes. These toxic effects were found to be mainly related to the in vivo degradation of QDs with consequent release of Cd(2+) ions, while the coating of QDs can modulate their bioaccumulation in the organism, partly decreasing their overall toxicity

Effect of Nedocromil Sodium on Aspecific Bronchial Hyper-Reactivity in Asthmatic Children

The purpose of this study was to evaluate whether nedocromil sodium benefits urban asthmatic children showing seasonal bronchial hyper-reactivity to ultrasonic nebulization of distilled water (UNDW). A prospective, randomized, placebo-controlled, parallel-group, double-blind study was carried out at the outpatient pulmonology service at a tertiary-care teaching hospital. Twelve children living in Milan, who were 7–17 years of age, who were SPT and RAST-negative to perennial allergens, who were suffering from episodic asthma, and showing seasonal bronchial hyper-reactivity to UNDW during winter, participated in this study. All the children received either placebo or nedocromil sodium, 4 mg every 6 h for 6 weeks. Spirometry and UNDW challenge were done at the following times: day−7; day 0; day 1; day 7; day 14; day 28; day 42. No differences were found in the basal spirometric parameters, which were normal in both nedocromil and placebo groups. Bronchial reactivity to UNDW was found to be significantly decreased in the group treated with nedocromtl starting from day 7. It is therefore concluded that nedocromil sodium can reverse bronchial hyper-reactivity caused by seasonal factors such as cold, viral infections and atmospheric pollutants in children suffering from asthma

Investigating the properties of TBA variants with twin thrombin binding domains

In this paper, we report studies concerning thrombin binding aptamer (TBA) dimeric derivatives in which the 3'-ends of two TBA sequences have been joined by means of linkers containing adenosine or thymidine residues and/or a glycerol moiety. CD and electrophoretic investigations indicate that all modified aptamers are able to form G-quadruplex domains resembling that of the parent TBA structure. However, isothermal titration calorimetry measurements of the aptamer/thrombin interaction point to different affinities to the target protein, depending on the type of linker. Consistently, the best ligands for thrombin show anticoagulant activities higher than TBA. Interestingly, two dimeric aptamers with the most promising properties also show far higher resistances in biological environment than TBA

Structural properties and anticoagulant/cytotoxic activities of heterochiral enantiomeric thrombin binding aptamer (TBA) derivatives

The thrombin binding aptamer (TBA) possesses promising antiproliferative properties. However, its development as an anticancer agent is drastically impaired by its concomitant anticoagulant activity. Therefore, suitable chemical modifications in the TBA sequence would be required in order to preserve its antiproliferative over anticoagulant activity. In this paper, we report structural investigations, based on circular dichroism (CD) and nuclear magnetic resonance spectroscopy (NMR), and biological evaluation of four pairs of enantiomeric heterochiral TBA analogues. The four TBA derivatives of the D-series are composed by D-residues except for one L-thymidine in the small TT loops, while their four enantiomers are composed by L-residues except for one D-thymidine in the same TT loop region. Apart from the left-handedness for the L-series TBA derivatives, CD and NMR measurements have shown that all TBA analogues are able to adopt the antiparallel, monomolecular, 'chair-like' G-quadruplex structure characteristic of the natural D-TBA. However, although all eight TBA derivatives are endowed with remarkable cytotoxic activities against colon and lung cancer cell lines, only TBA derivatives of the L-series show no anticoagulant activity and are considerably resistant in biological environments

Aptamers against the β-conglutin allergen: Insights into the behavior of the shortest multimeric (intra)molecular dna gquadruplex

In previous work, a 93-mer aptamer was selected against the anaphylactic allergen, β-conglutin and truncated to an 11-mer, improving the affinity by two orders of magnitude, whilst maintaining the specificity. This 11-mer was observed to fold in a G-quadruplex, and preliminary results indicated the existence of a combination of monomeric and higher-order structures. Building on this previous work, in the current study, we aimed to elucidate a deeper understanding of the structural forms of this 11-mer and the effect of the structure on its binding ability. A battery of techniques including polyacrylamide gel electrophoresis, high-performance liquid chromatography in combination with electrospray ionization time-of-flight mass spectrometry, matrix-assisted laser desorption/ionization time-of-flight, thermal binding analysis, circular dichroism and nuclear magnetic resonance were used to probe the structure of both the 11-mer and the 11-mer flanked with TT- at either the 5′ or 3′ end or at both ends. The TT-tail at the 5′ end hinders stacking effects and effectively enforces the 11-mer to maintain a monomeric form. The 11-mer and the TT- derivatives of the 11-mer were also evaluated for their ability to bind its cognate target using microscale thermophoresis and surface plasmon resonance, and biolayer interferometry confirmed the nanomolar affinity of the 11-mer. All the techniques utilized confirmed that the 11-mer was found to exist in a combination of monomeric and higher-order structures, and that independent of the structural form present, nanomolar affinity was observed

Physical assessment of toxicology at nanoscale: nano dose-metrics and toxicity factor

In this work, we propose a systematic and reproducible evaluation of nanoparticles (NPs) toxicology in living systems, based on a physical assessment and quantification of the toxic effects of NPs by the experimental determination of the key parameter affecting the toxicity outcome (i.e., the number of NPs) and of the NPs "toxicity factor". Such a strategy was applied to a well determined scenario, i.e., the ingestion of citrate-capped gold NPs (AuNPs) of different sizes by the model system Drosophila melanogaster. Using these AuNPs as a reference toxicity standard, we were able to define different regions in the multiparametric space of toxicity, enabling the classification of the toxic levels of other nanomaterials, such as quantum dots and pegylated AuNPs. This approach may pave the way to a systematic classification of nanomaterials, leading to important developments in risk assessment and regulatory approval, as well as in a wide range of nanomedicine applications

Fried foods, olive oil and colorectal cancer

Background: The epidemiologic evidence for an etiologic role of fried foods and heterocyclic amines in colorectal carcinogenesis is inconsistent. Patients and methods: We have investigated the relation between fried foods and colorectal cancer risk using data from a large, multicentric case-control study conducted in Italy and Switzerland between 1992 and 2000, with 1394 cases of colon cancer, 886 cases of rectal cancer and 4765 controls. Results: After allowing for major relevant covariates, the multivariate odds ratios (ORs) for an increment of one portion per week of fried foods were 0.97 [95% confidence interval (CI) = 0.93-1.01] for colon cancer and 1.04 (95% CI = 1.00-1.09) for rectal cancer. When we analyzed the type of fats mainly used for frying, we found that olive oil, but not other types of oils, appeared to protect from colon cancer risk (OR = 0.89, 95% CI = 0.82-0.98). Conclusions: Our results do not indicate a relevant role of fried foods on colorectal cancer risk. We found a possible favorable effect of (fried) olive oil on colon cancer risk but not on rectal cancer ris