1,721,091 research outputs found
Recent developments and applications of smart nanoparticles in biomedicine
Full text linkOver the last decades, nanotechnology applied in medicine (nanomedicine) has sparked great interest from the scientific community, thanks to the possibility to engineer nanostructured materials, including nanoparticles (NPs), for a specific application. Their small size confers them unique properties because they are subject to physical laws in the middle between classical and quantum physics. This review is proposed to explain better how to design a specific NP and clarify the relationship between the type, size, and shape of NPs and the specific medical applications. NPs are classified into inorganic (metallic NPs, quantum dots, carbon-based nanostructures, mesoporous silica NPs) and organic (liposomes and micelles, dendrimers, and polymer NPs). Here, we report an accurate description of the potential of each NPs type focusing on their multiple areas of application, including theranostics drug delivery, imaging, tissue engineering, antimicrobial techniques, and nanovaccines. All these features make NPs a promise to revolutionize the new era of nanomedicine
Graphene nanosystems as supports in siRNA Delivery
No full textThe nature of graphene-based nanosystems, as well as the possibility to synthesize them at low cost, have made them in the last few years, an interesting proposition in tumour therapy as a drug delivery system. Here, a reduced form of graphene oxide (RGO) has been synthesized and conjugated with a specific antibody for active targeting against tumour cells (RGOY). Furthermore, its bi-dimensional nature permits also p- p stacking interactions with planar molecules like siRNA (RGOY-siRNA). All these nano-complexes were characterized by DLS and DSC analysis, TEM and Raman spectroscopy and their biocompatibility was demonstrated by viability assay on cell line ECV 304. The system is able to be internalized from cells, as demonstrated by uptake studies with confocal microscopy, performed using its red fluorescence variant (RGOY-AF). A high reduction of the stacking interactions between the graphene sheets was obtained by conjugating RGOY particles to polyvinylpyrrolidone (PVP) (RGOY-PVP). The addition of PVP did not alter the biocompatibility of the system, but limited the formation of aggregates due to the stacking interaction between the graphene sheets: the complexes appeared more dispersed and able to enter into the cells after only few minutes, and in higher amounts with respect to the complex without PVP. All obtained data indicate graphene nanosystems very good candidates as delivery system thanks to their specific properties that permit to link to both antibody and siRNA without any degradation effect
Cerebrospinal and Blood Biomarkers in Alzheimer's Disease: Did Mild Cognitive Impairment Definition Affect Their Clinical Usefulness?
Full text linkDespite Alzheimer's Disease (AD) being known from the times of Alois Alzheimer, who lived more than one century ago, many aspects of the disease are still obscure, including the pathogenesis, the clinical spectrum definition, and the therapeutic approach. Well-established biomarkers for AD come from the histopathological hallmarks of the disease, which are A beta and phosphorylated Tau protein aggregates. Consistently, cerebrospinal fluid (CSF) Amyloid beta (A beta) and phosphorylated Tau level measurements are currently used to detect AD presence. However, two central biases affect these biomarkers. Firstly, incomplete knowledge of the pathogenesis of diseases legitimates the search for novel molecules that, reasonably, could be expressed by neurons and microglia and could be detected in blood simpler and earlier than the classical markers and in a higher amount. Further, studies have been performed to evaluate whether CSF biomarkers can predict AD onset in Mild Cognitive Impairment (MCI) patients. However, the MCI definition has changed over time. Hence, the studies on MCI patients seem to be biased at the beginning due to the imprecise enrollment and heterogeneous composition of the miscellaneous MCI subgroup. Plasma biomarkers and novel candidate molecules, such as microglia biomarkers, have been tentatively investigated and could represent valuable targets for diagnosing and monitoring AD. Also, novel AD markers are urgently needed to identify molecular targets for treatment strategies. This review article summarizes the main CSF and blood AD biomarkers, underpins their advantages and flaws, and mentions novel molecules that can be used as potential biomarkers for AD
The Cytokine CX3CL1 and ADAMs/MMPs in Concerted Cross-Talk Influencing Neurodegenerative Diseases
Full text linkNeuroinflammation plays a fundamental role in the development and progression of neurodegenerative diseases. It could therefore be said that neuroinflammation in neurodegenerative pathologies is not a consequence but a cause of them and could represent a therapeutic target of neuronal degeneration. CX3CL1 and several proteases (ADAMs/MMPs) are strongly involved in the inflammatory pathways of these neurodegenerative pathologies with multiple effects. On the one hand, ADAMs have neuroprotective and anti-apoptotic effects; on the other hand, they target cytokines and chemokines, thus causing inflammatory processes and, consequently, neurodegeneration. CX3CL1 itself is a cytokine substrate for the ADAM, ADAM17, which cleaves and releases it in a soluble isoform (sCX3CL1). CX3CL1, as an adhesion molecule, on the one hand, plays an inhibiting role in the pro-inflammatory response in the central nervous system (CNS) and shows neuroprotective effects by binding its membrane receptor (CX3CR1) present into microglia cells and maintaining them in a quiescent state; on the other hand, the sCX3CL1 isoform seems to promote neurodegeneration. In this review, the dual roles of CX3CL1 and ADAMs/MMPs in different neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (MH), and multiple sclerosis (MS), are investigated
E-beam crosslinked nanogels conjugated with monoclonal antibodies in targeting strategies
No full textPoly(N-vinyl pyrrolidone)-based-nanogels (NGs), produced by e-beam irradiation, are conjugated with monoclonal antibodies (mAb) for the development of an effective targeting purposes. The uptake of immuno-functionalized nanogels is tested in an endothelial cell line, ECV 304, using confocal and epifluorescence microscopy. Intracellular localization studies reveal a faster uptake of the immuno-nanogel complex with respect to the “bare” nanogel. The specific internalization pathway of these immuno-nanogels is clarified by selective endocytosis inhibition experiments, flow cytometry and confocal microscopy. Active targeting ability is also verified by conjugating a monoclonal antibody which recognizes the αvβ3 integrin on activated endothelial cells. Epifluorescence images of the “wound healing assay” on ECV304 cells reveals an exclusive localization of nanogels in the target cells. Thus, the immuno-nanogels have the potential to recognize specific cell types in a heterogeneous system, which makes them suitable for targeted drug delivery applications
Production of Injectable Marine Collagen-Based Hydrogel for the Maintenance of Differentiated Chondrocytes in Tissue Engineering Applications
Full text linkCartilage is an avascular tissue with limited ability of self-repair. The use of autologous chondrocyte transplants represent an effective strategy for cell regeneration; however, preserving the differentiated state, which ensures the ability to regenerate damaged cartilage, represents the main challenge during in vitro culturing. For this purpose, we produced an injectable marine collagen-based hydrogel, by mixing native collagen from the jellyfish Rhizostoma pulmo with hydroxy-phenyl-propionic acid (HPA)-functionalized marine gelatin. This biocompatible hydrogel formulation, due to the ability of enzymatically reticulate using horseradish peroxidase (HPR) and H2O2, gives the possibility of trap cells inside, in the absence of cytotoxic effects, during the cross-linking process. Moreover, it enables the modulation of the hydrogel stiffness merely varying the concentration of H2O2 without changes in the concentration of polymer precursors. The maintenance of differentiated chondrocytes in culture was then evaluated via morphological analysis of cell phenotype, GAG production and cytoskeleton organization. Additionally, gene expression profiling of differentiation/dedifferentiation markers provided evidence for the promotion of the chondrogenic gene expression program. This, combined with the biochemical properties of marine collagen, represents a promising strategy for maintaining in vitro the cellular phenotype in the aim of the use of autologous chondrocytes in regenerative medicine practices
Preparation, characterization and in vitro test of composites poly-lactic acid/hydroxyapatite scaffolds for bone tissue engineering
No full textIn this work, the possibility to produce composite Poly-L-lactic acid (PLLA)/Hydroxyapatite (HA) porous scaffolds via Thermally Induced Phase Separation (TIPS) for bone tissue engineering applications was investigated. Several PLLA/HA wt/wt ratios (95/5, 90/10, 70/30, 50/50, 34/66) were tested and the as-obtained scaffolds were characterized via Scanning Electron Microscopy, Wide Angle X-Ray Diffraction, Thermogravimetric analysis, Gas Pycnometry, Differential Scanning Calorimetry and mechanical compression test. Morphological analysis revealed an open structure with interconnected pores and HA particles embedded in the polymer matrix. Finally, cell cultures were carried out into the composite scaffolds in order to evaluate the effect of HA on the proliferation and differentiation of osteoblastic cells, showing a higher alkaline phosphatase activity on composite scaffolds compared to neat PLLA ones
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
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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