1,721,077 research outputs found
Poly(Lactide-Co-Glycolide) Nanoparticles Co-Loaded with Chlorophyllin and Quantum Dots as Photodynamic Therapy Agents
No full textPhotodynamic therapy (PDT) is an approach to treating cancer and involves light-induced activation of a photosensitizer that triggers the formation of reactive oxygen species (ROS) in targeted cells and subsequent cell death. Examples of photosensitizers are porphyrins, including the natural compound chlorophyll. These molecules can be delivered alone or co-formulated with an agent, such as quantum dots (QDs), that is able to excite them through a fluorescence resonance energy transfer (FRET)-based mechanism. We encapsulated a chlorophyllin copper complex and CdSe/ZnS core-shell QDs into biodegradable nanoparticles (NPs) composed of poly(lactide-co-glycolide) (PLGA), that allow modification with specific targeting ligands. When excited at 365 nm, FRET occurs between co-encapsulated QDs and chlorophyllin to result in the formation of ROS. This chlorophyllin-QD coformulation allows generation of ROS both in an aqueous environment and in cells, thus confirming the potential of this formulation in PDT
Pyridine and Triphenylphosphine Oxide Activation of Sulfonyl Chlorides in the Syntheses of (E) Alk-1-enyl Sulfones
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Nanocarriers for protein delivery to the cytosol: Assessing the endosomal escape of poly(lactide-co-Glycolide)-poly(ethylene Imine) nanoparticles
No full textTherapeutic proteins and enzymes are a group of interesting candidates for the treatment of numerous diseases, but they often require a carrier to avoid degradation and rapid clearance in vivo. To this end, organic nanoparticles (NPs) represent an excellent choice due to their biocompatibility, and cross-linked enzyme aggregates (CLEAs)-loaded poly (lactide-co-glycolide) (PLGA) NPs have recently attracted attention as versatile tools for targeted enzyme delivery. However, PLGA NPs are taken up by cells via endocytosis and are typically trafficked into lysosomes, while many therapeutic proteins and enzymes should reach the cellular cytosol to perform their activity. Here, we designed a CLEAs-based system implemented with a cationic endosomal escape agent (poly(ethylene imine), PEI) to extend the use of CLEA NPs also to cytosolic enzymes. We demonstrated that our system can deliver protein payloads at cytoplasm level by two different mechanisms: Endosomal escape and direct translocation. Finally, we applied this system to the cytoplasmic delivery of a therapeutically relevant enzyme (superoxide dismutase, SOD) in vitro
Role of extracellular calcium and mitochondrial oxygen species in psychosine-induced oligodendrocyte cell death
Full text linkGloboid cell leukodystrophy (GLD) is a metabolic disease caused by mutations in the galactocerebrosidase (GALC) gene. GALC is a lysosomal enzyme whose function is to degrade galacto-lipids, including galactosyl-ceramide and galactosyl-sphingosine (psychosine, PSY). GALC loss of function causes progressive intracellular accumulation of PSY. It is widely held that PSY is the main trigger for the degeneration of myelinating cells and progressive white-matter loss. However, still little is known about the molecular mechanisms by which PSY imparts toxicity. Here, we address the role of calcium dynamics during PSY-induced cell death. Using the human oligodendrocyte cell line MO3.13, we report that cell death by PSY is accompanied by robust cytosolic and mitochondrial calcium (Ca2+) elevations, and by mitochondrial reactive oxygen species (ROS) production. Importantly, we demonstrate that the reduction of extracellular calcium content by the chelating agent ethylenediaminete-traacetic acid can decrease intra-mitochondrial ROS production and enhance cell viability. Antioxidant administration also reduces mitochondrial ROS production and cell loss, but this treatment does not synergize with Ca2+ chelation. Our results disclose novel intracellular pathways involved in PSY-induced death that may be exploited for therapeutic purposes to delay GLD onset and/or slow down its progression
Quantitative optical lock-in detection for quantitative imaging of switchable and non-switchable components
No full textReversible photoswitching has been proposed as a way to identify molecules that are present in small numbers over a large, non-switching, background. This approach, called optical-lock-indetection (OLID) requires the deterministic control of the fluorescence of a photochromic emitter through optical modulation between a bright (on) and a dark state (off). OLID yields a high-contrast map where the switching molecules are pinpointed, but the fractional intensities of the emitters are not returned. The present work presents a modified OLID approach (quantitative OLID or qOLID) that yields quantitative information of the switching (f(SW)) and non-switching (f(NS)) components. After the validation of the method with a sample dataset and image sequence, we apply qOLID to measurements in cells that transiently express the photochromic protein EYQ1. We show that qOLID is efficient in separating the modulated from the non-modulated signal, the latter deriving from background/autofluorescence or fluorophores emitting in the same spectral region. Finally, we apply qOLID to Forster (Fluorescence) Resonance Energy Transfer (FRET) imaging. We here demonstrate that qOLID is able to highlight the distribution of FRET intensity in a sample by using a photochromic donor and a non-photochromic acceptor
La libertà globale. Prospettive interculturali nell’antropologia filosofica di Max Scheler
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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