The development and use of nanosystems is an emerging strategy for the diagnosis and treatment of a broad number of diseases, such as Alzheimer's disease (AD).

BackgroundPerinatal asphyxia interferes with neonatal development, resulting in long-term deficits associated with systemic and neurological diseases. Despite the important role of poly (ADP-ribose) polymerase 1 (PARP-1) in the regulation of gene expression and DNA repair, overactivation of PARP-1 in asphyxia-exposed animals worsens the ATP-dependent energetic crisis. Inhibition of PARP-1 offers a therapeutic strategy for diminishing the effects of perinatal asphyxia.MethodsWe designed a nanosystem that incorporates a specific siRNA for PARP-1 knockdown. The siRNA was complexed with gold nanorods (AuNR) conjugated to the peptide CLPFFD for brain targeting.ResultsThe siRNA was efficiently delivered into PC12 cells, resulting in gene silencing. The complex was administered intraperitoneally in vivo to asphyxia-exposed rat pups, and the ability of the AuNR-CLPFFD/siRNA complex to reach the brain was demonstrated.ConclusionThe combination of a nanosystem for delivery and a specific siRNA for gene silencing resulted in effective inhibition of PARP-1 in vivo.

There is a significant amount of arsenic species in the environment and in biological systems; however, the toxicity and possibly the carcinogenicity of ingested arsenic depend on the species and the oxidation state. Therefore, analytical methodologies and techniques that are fast and robust, that involve highly efficient separation and are powerful tools of detection are necessary for the correct quantification of individual arsenic species. The field of speciation analysis of arsenic in this area has grown rapidly in recent years, especially with the application of liquid chromatography and mass spectrometry with inductively coupled plasma. This study aimed to develop and apply this technique to human urine samples in order to reduce the treatment needed for speciation, maintain maximum recovery and avoid interconversion and / or degradation between species. In order to optimize the separation of species, several experiments were performed by preparing the mobile phase at different pH values. The optimal pH value and the linearity of the method were determined and the methodology was validated using a Certified Reference Material. Student`s t-test and Fisher F-test for determination of accuracy and precision were applied. A simple, rapid and reliable method for the separation and quantification of several species of arsenic, As III (Arsenite), As V (Arsenate), MMA (Monomethyl Arsonic Acid), DMA (Dimethyl Arsinic Acid), AB (Arsenobetaine) was developed in human urine samples with minimal prior sample preparation. The time required for sample processing and isocratic chromatographic analysis is about 15 minutes. Detection limits of 0.020 µgL -1 of AsB, 0.020 µgL -1 of As III, 0.040 µgL -1 of DMA, 0.060 µgL -1 of MMA and 0.060 µgL -1 of As V were achieved under the analytical conditions mentioned above.