61 research outputs found

    Sodium Ascorbate induces apoptosis in neuroblastoma cell lines by interfering with iron uptake

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    <p>Abstract</p> <p>Background</p> <p>Neuroblastoma (NB) is an extra-cranial solid tumour of childhood. In spite of the good clinical response to first-line therapy, complete eradication of NB cells is rarely achieved. Thus, new therapeutic strategies are needed to eradicate surviving NB cells and prevent relapse. Sodium ascorbate has been recently reported to induce apoptosis of B16 melanoma cells through down-regulation of the transferrin receptor, CD71. Since NB and melanoma share the same embryologic neuroectodermal origin, we used different human NB cell lines to assess whether the same findings occurred.</p> <p>Results</p> <p>We could observe dose- and time-dependent induction of apoptosis in all NB cell lines. Sodium ascorbate decreased the expression of CD71 and caused cell death within 24 h. An increase in the global and specific caspase activity took place, as well as an early loss of the mitochondrial transmembrane potential. Moreover, intracellular iron was significantly decreased after exposure to sodium ascorbate. Apoptotic markers were reverted when the cells were pretreated with the iron donor ferric ammonium citrate (FAC), further confirming that iron depletion is responsible for the ascorbate-induced cell death in NB cells.</p> <p>Conclusion</p> <p>Sodium ascorbate is highly toxic to neuroblastoma cell lines and the specific mechanism of vitamin C-induced apoptosis is due to a perturbation of intracellular iron levels ensuing TfR-downregulation.</p

    Botanical and Genetic Identification Followed by Investigation of Chemical Composition and Biological Activities on the Scabiosa atropurpurea L. Stem from Tunisian Flora

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    Scarce information about the phenolic composition of Scabiosa atropurpurea L. is available, and no carotenoid compounds have been reported thus far. In this study the phenolic and carotenoid composition of this plant was both investigated and associated bioactivities were evaluated. Aiming to obtain extracts and volatile fractions of known medicinal plants to valorize them in the pharmaceutical or food industries, two techniques of extraction and five solvents were used to determine the biologically active compounds. Gas chromatography coupled to flame ionization and mass spectrometry and liquid chromatography coupled to photodiode array and atmospheric pressure chemical ionization/electrospray ionization mass spectrometry highlighted the presence of 15 volatiles, 19 phenolic, and 24 natural pigments in Scabiosa atropurpurea L. stem samples; among them, the most abundant were 1,8-cineole, chlorogenic acid, cynaroside, and lutein. Bioactivity was assessed by a set of in vitro tests checking for antioxidant, antibacterial, antifungal, and allelopathic (against Brassica oleracea L. and Lens culinaris Medik) effects. Scabiosa atropurpurea L. stem extracts presented a considerable antioxidant, antibacterial, and allelopathic potential, with less antifungal effectiveness. These results indicate that the volatile fractions and extracts from S. atropurpurea L. stem could be considered as a good source of bioactive agents, with possible applications in food-related, agriculture, and pharmaceutical fields. Genetic investigations showed 97% of similarity with Scabiosa tschiliensis, also called Japanese Scabiosa

    Polymeric nanoparticles for nonviral gene therapy extend brain tumor survival in vivo

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    Biodegradable polymeric nanoparticles have the potential to be safer alternatives to viruses for gene delivery; however, their use has been limited by poor efficacy in vivo. In this work, we synthesize and characterize polymeric gene delivery nanoparticles and evaluate their efficacy for DNA delivery of herpes simplex virus type I thymidine kinase (HSVtk) combined with the prodrug ganciclovir (GCV) in a malignant glioma model. We investigated polymer structure for gene delivery in two rat glioma cell lines, 9L and F98, to discover nanoparticle formulations more effective than the leading commercial reagent Lipofectamine 2000. The lead polymer structure, poly(1,4-butanediol diacrylate-co-4-amino-1-butanol) end-modified with 1-(3-aminopropyl)-4-methylpiperazine, is a poly(\u3b2-amino ester) (PBAE) and formed nanoparticles with HSVtk DNA that were 138 \ub1 4 nm in size and 13 \ub1 1 mV in zeta potential. These nanoparticles containing HSVtk DNA showed 100% cancer cell killing in vitro in the two glioma cell lines when combined with GCV exposure, while control nanoparticles encoding GFP maintained robust cell viability. For in vivo evaluation, tumor-bearing rats were treated with PBAE/HSVtk infusion via convection-enhanced delivery (CED) in combination with systemic administration of GCV. These treated animals showed a significant benefit in survival (p = 0.0012 vs control). Moreover, following a single CED infusion, labeled PBAE nanoparticles spread completely throughout the tumor. This study highlights a nanomedicine approach that is highly promising for the treatment of malignant glioma

    Design, construction, and test of the Gas Pixel Detectors for the IXPE mission

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    Due to be launched in late 2021, the Imaging X-Ray Polarimetry Explorer (IXPE) is a NASA Small Explorer mission designed to perform polarization measurements in the 2-8 keV band, complemented with imaging, spectroscopy and timing capabilities. At the heart of the focal plane is a set of three polarization-sensitive Gas Pixel Detectors (GPD), each based on a custom ASIC acting as a charge-collecting anode. In this paper we shall review the design, manufacturing, and test of the IXPE focal-plane detectors, with particular emphasis on the connection between the science drivers, the performance metrics and the operational aspects. We shall present a thorough characterization of the GPDs in terms of effective noise, trigger efficiency, dead time, uniformity of response, and spectral and polarimetric performance. In addition, we shall discuss in detail a number of instrumental effects that are relevant for high-level science analysis -- particularly as far as the response to unpolarized radiation and the stability in time are concerned.Comment: To be published in Astroparticle Physic

    Injection‐locked oscillator lock detector

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