1,721,253 research outputs found

    Gene therapy: the state of the art and future directions

    No full text
    Gene therapy, because of its aim to eradicate the causes rather than the symptoms of diseases, is believed by many to be the therapy of the future. The problems of developing clinically viable gene therapeutic approaches and designing safe and efficient gene delivery reagents are inseparable: shortcomings in one are going to affect adversely the success of the other. It is generally accepted that the major impediment to the successful application of gene therapy for the treatment of a range of dis-eases is not a paucity of therapeutic genes, but the lack of efficient non-toxic gene delivery systems. Transfection vectors com-monly used in gene therapy are mainly of two types: viral and non-viral. Non-viral gene delivery is currently the subject of increasing attention because of its relative safety and its simplicity of use; however, its use is still far from being ideal due to its comparatively low efficiency. The purpose of this review is to give an overview of the current knowledge concerning the assembly of lipoplexes and the trafficking of lipoplexes into cells, as well as to underscore the advantages and disadvantages of lipidic gene carriers among non-viral gene delivery systems

    BMP-2 and type I collagen preservation in human deciduous teeth after demineralization

    Full text link
    Background: Great interest has recently been focused on tooth and tooth derivatives as suitable substrates for the treatment of alveolar bone defects. Here, we propose the use of demineralized baby teeth (BT) as potential grafting materials for bone augmentation procedures. Methods: Particles of human BT (Ø < 1 mm) were demineralized by means of a chemical/thermal treatment. Demineralized BT particles were thoroughly characterized by scanning electron microscopy/energy dispersive X-ray analyses to evaluate the effects of the demineralization on BT topography and mineral phase composition, and by enzyme-linked immunosorbent assays (ELISA) to quantify collagen and bone morphogenetic protein-2 (BMP-2) protein contents. The response of SAOS-2 cells to exogenous BMP-2 stimulation was evaluated to identify the minimum BMP-2 concentration able to induce osteodifferentiation in vitro (alkaline phosphatase (ALP) activity). Results: The demineralization treatment led to a dramatic decrease in relative Ca and P content (%) of ≈75% with respect to the native BT particles, while preserving native protein conformation and activity. Interestingly, the demineralization process led to a rise in the bioavailability of BMP-2 in BT particles, as compared to the untreated counterparts. The BMP-2 content found in demineralized BT was also proved to be very effective in enhancing ALP activity, thus in the osteodifferentiation of SAOS-2 cells in vitro, as confirmed by cell experiments performed upon exogenously added BMP-2. Conclusions: In this study we demonstrate that the BMP-2 content found in demineralized BT is very effective in inducing cell osteodifferentiation, and strengthens the idea that BTs are very attractive bioactive materials for bone-grafting procedures

    Improving indoor air quality by using the new generation of corrugated cardboard-based filters

    No full text
    Purpose: Indoor Air Quality (IAQ) is strictly affected by the concentration of total suspended particulate matter (TSP). Air filtration is by far the most feasible suggestion to improve IAQ. Unfortunately, highly effective HEPA filters also have a few major weaknesses that have hindered their widespread use. There is therefore a renewed interest in developing novel, cost-effective filtration systems. We have recently reported the development of cardboard-based filters for bacterial removal that were further implemented and tested herein.
Methods: A parallelepiped filter manufactured by aligning strips of corrugated cardboard and surrounded by a cardboard frame was specifically designed with an internal pocket holding a partially cut antistatic pleated fabric (HP). This filter, together with its parent version (CTRL) and a commercially sourced specimen (CAF), were assessed comparatively in a long-time test to assess their effectiveness on TSP removal.
Results: We found that the TSP abatement efficiency (E%) of the HP filter was relatively high and invariable over the 93 days of test and the pressure drop (PD%) decrease because of filter clogging was moderate. Most important, the HP filter was the most effective if assessed in terms of overall yield (Y%) and its performance was quite constant over the entire period considered.
Conclusions: This work disclosed this novel class of corrugated cardboard-based filters as promising tools to ameliorate IAQ in light of their good TSP removal properties that endure over time. Moreover, cardboard is a lightweight, inexpensive, and eco-friendly material and corrugated cardboard-based air filters are very easy to shape and mount on and/or replace in existing ventilation systems

    A Stepwise Approach for the Isolation and the Identification of Chemically Reactive Exofacial Protein Thiols

    No full text
    The plasma membrane controls the selective internalization of (macro)molecules through different mechanisms, often relaying on specialized outward-facing carriers such as exofacial proteins thiols (EPTs). Although the interchange of critical thiols and disulphides between EPTs and exogenous cargoes is the first critical event, the identification of specific cell interactors remains to be thoroughly explored. Besides, it is likewise evident that only the relatively little suite of EPTs truly reactive can be considered theranostic targets

    Non-viral gene delivery strategies for gene therapy: a “ménage à trois” among nucleic acids, materials, and the biological environment

    No full text
    Gene delivery is the science of transferring genetic material into cells by means of a vector to alter cellular function or structure at a molecular level. In this context, a number of nucleic acid-based drugs have been proposed and experimented so far and, as they act on distinct steps along the gene transcription-translation pathway, specific delivery strategies are required to elicit the desired outcome. Cationic lipids and polymers, collectively known as non-viral delivery systems, have thus made their breakthrough in basic and medical research. Albeit they are promising alternatives to viral vectors, their therapeutic application is still rather limited as high transfection efficiencies are normally associated to adverse cytotoxic side effects. In this scenario, drawing inspiration from processes naturally occurring in vivo, major strides forward have been made in the development of more effective materials for gene delivery applications. Specifically, smart vectors sensitive to a variety of physiological stimuli such as cell enzymes, redox status, and pH are substantially changing the landscape of gene delivery by helping to overcome some of the systemic and intracellular barriers that viral vectors naturally evade. Herein, after summarizing the state-of-the-art information regarding the use of nucleic acids as drugs, we review the main bottlenecks still limiting the overall effectiveness of non-viral gene delivery systems. Finally, we provide a critical outline of emerging stimuli-responsive strategies and discuss challenges still existing on the road toward conceiving more efficient and safer multifunctional vectors
    corecore