1,721,039 research outputs found

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

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    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

    Mucoadhesive chitosan-methylcellulose oral patches for the treatment of local mouth bacterial infections

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    : Mucoadhesive buccal patches are dosage forms promising for successful drug delivery. They show the distinctive advantages of long residence time on the oral mucosa and increased in situ drug bioavailability. In this context, electrophoretic deposition (EPD) of chitosan (CS) has been demonstrated as a simple and easily tunable technique to produce mucoadhesive buccal patches. However, CS-based buccal patches may suffer from weak mucoadhesion, which can impair their therapeutic effect. In this work, methylcellulose (MC), a widely investigated biopolymer in the biomedical area, was exploited to increase the mucoadhesive characteristic of pristine CS patches. CS-MC patches were obtained in a one-pot process via EPD, and the possibility of incorporating gentamicin sulfate (GS) as a model of a broad-spectrum antibiotic in the so-obtained patches was investigated. The resulting CS-MC patches showed high stability in a water environment and superior mucoadhesive characteristic (σadh = 0.85 ± 0.26 kPa, Wadh = 1192.28 ± 602.36 Pa mm) when compared with the CS control samples (σadh = 0.42 ± 0.22 kPa, Wadh = 343.13 ± 268.89 Pa mm), due to both the control of the patch porosity and the bioadhesive nature of MC. Furthermore, GS-loaded patches showed no in vitro cytotoxic effects by challenging L929 cells with material extracts and noteworthy antibacterial activity on both Gram-positive and Gram-negative bacterial strains

    Advancing nucleic acid delivery through cationic polymer design: non-cationic building blocks from the toolbox

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    Polymers used for the delivery of nucleic acids (NAs) typically possess ionizable, cationic moieties enabling their electrostatic interactions with negatively charged NAs and form stable polyplexes. However, non-cationic building blocks have been harnessed to design cationic polymers with enhanced delivery of DNA/RNA to tissues, cells, and subcellular compartments while remaining stable in biological fluids. By customizing the chemistry of these functional groups, we can improve cell targeting behavior, uptake, endosomal escape, non-toxicity, and transfection efficiency. Additionally, the physicochemical properties, such as the loading capacity, complexation ability, size and morphology, biodegradability, pH sensitivity, and amphiphilicity, can be adjusted based on the specific application. This review summarizes the role of non-cationic moieties in various biomedical contexts, from therapeutic interventions to gene editing. By unpacking and critically summarizing the existing literature, this review provides valuable insights into the rational integration of these building blocks for designing more effective nanovectors to deliver NAs.The rational integration of non-cationic building blocks into cationic polymers can be devised to enhance the performance of the resulting gene delivery vectors, improving cell targeting behavior, uptake, endosomal escape, toxicity, and transfection efficiency

    Demineralized dentin and enamel matrices as suitable substrates for bone regeneration

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    Background: In recent decades, tooth derivatives such as dentin (D) and enamel (E) have been considered as potential graft biomaterials to treat bone defects. This study aimed to investigate the effects of demineralization on the physical-chemical and biological behavior of D and E. Methods: Human D and E were minced into particles (à &lt;1 mm), demineralized and sterilized. Thorough physicalchemical and biochemical characterizations of native and demineralized materials were performed by SEM and EDS analysis and ELISA kits to determine mineral, collagen type I and BMP-2 contents. In addition, MG63 and SAOS-2 cells were seeded on tooth-derived materials and Bio-Oss®, and a comparison of cell responses in terms of adhesion and proliferation was carried out. Results: The sterilization process, as a combination of chemical and thermal treatments, was found to be effective for all materials. On the other hand, D demineralization allowed preserving the collagen content, while increasing BMP-2 bioavailability. D and demineralized D (dD) displayed excellent biocompatibility, even greater than Bio-Oss®. Conversely, the high mineral content displayed by E, as confirmed by EDS analysis, inhibited cell proliferation. Of note, even though the demineralization process was somehow less effective in E than in D, demineralized E (dE) displayed increased BMP-2 bioavailability and improved performance in vitro compared with native E. Conclusions: Our results substantiate the idea that the demineralization process lead to an increase of BMP-2 bioavailability, thus paving the way toward development of more effective, osteoinductive tooth-derived materials for bone regeneration and replacement

    Effect of UV Irradiation and TiO2-Photocatalysis on Airborne Bacteria and Viruses: An Overview

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    Current COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has put a spotlight on the spread of infectious diseases brought on by pathogenic airborne bacteria and viruses. In parallel with a relentless search for therapeutics and vaccines, considerable effort is being expended to develop ever more powerful technologies to restricting the spread of airborne microorganisms in indoor spaces through the minimization of health- and environment-related risks. In this context, UV-based and photocatalytic oxidation (PCO)-based technologies (i.e., the combined action of ultraviolet (UV) light and photocatalytic materials such as titanium dioxide (TiO2)) represent the most widely utilized approaches at present because they are cost-effective and ecofriendly. The virucidal and bactericidal effect relies on the synergy between the inherent ability of UV light to directly inactivate viral particles and bacteria through nucleic acid and protein damages, and the production of oxidative radicals generated through the irradiation of the TiO2 surface. In this literature survey, we draw attention to the most effective UV radiations and TiO2-based PCO technologies available and their underlying mechanisms of action on both bacteria and viral particles. Since the fine tuning of different parameters, namely the UV wavelength, the photocatalyst composition, and the UV dose (viz, the product of UV light intensity and the irradiation time), is required for the inactivation of microorganisms, we wrap up this review coming up with the most effective combination of them. Now more than ever, UV- and TiO2-based disinfection technologies may represent a valuable tool to mitigate the spread of airborne pathogens

    Perspectives in Amyotrophic Lateral Sclerosis: Biomarkers, Omics, and Gene Therapy Informing Disease and Treatment

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    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons, leading to muscle weakness, paralysis, and ultimately respiratory failure. Despite advances in understanding its genetic basis, particularly mutations in Chromosome 9 Open Reading Frame 72 (C9orf72), superoxide dismutase 1 (SOD1), TAR DNA-binding protein (TARDBP), and Fused in Sarcoma (FUS) gene, current diagnostic methods result in delayed intervention, and available treatments offer only modest benefits. This review examines innovative approaches transforming ALS research and clinical management. We explore emerging biomarkers, including the fluid-based markers such as neurofilament light chain, exosomes, and microRNAs in biological fluids, alongside the non-fluid-based biomarkers, including neuroimaging and electrophysiological markers, for early diagnosis and patient stratification. The integration of multi-omics data reveals complex molecular mechanisms underlying ALS heterogeneity, potentially identifying novel therapeutic targets. We highlight current gene therapy strategies, including antisense oligonucleotides (ASOs), RNA interference (RNAi), and CRISPR/Cas9 gene editing systems, alongside advanced delivery methods for crossing the blood&ndash;brain barrier. By bridging molecular neuroscience with bioengineering, these technologies promise to revolutionize ALS diagnosis and treatment, advancing toward truly disease-modifying interventions for this previously intractable condition

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Point-of-Care Nucleic Acid Detection: From Molecular Design to Clinical Reality

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    Point-of-Care (PoC) diagnostics are transforming healthcare by enabling rapid and accessible disease detection right at the patient’s bedside. This comprehensive review examines recent advances in nucleic acid (NA)-based PoC testing, revealing how these technologies are revolutionizing molecular diagnostics. Here, we critically analyze the three key components of NA-based PoC development: (i) probe design strategies, (ii) immobilization techniques, and (iii) detection methodologies. Our analysis uncovers the complex relationship between probe density, hybridization conditions, and detection sensitivity, challenging the conventional trial-and-error approaches currently dominating the field. The review introduces a novel classification of detection methods based on equipment requirements, offering valuable insights for developing truly accessible diagnostic solutions. Notably, we highlight that colorimetric and electrochemical detection methods show superior potential in meeting the REASSURED criteria (Affordable, Sensitive, Specific, User-friendly, Rapid and Robust, Equipment-free, Real-time connectivity, Ease of specimen collection, and Deliverable to end-users). These criteria are essential for global healthcare implementation. Despite major advances, significant gaps remain between laboratory innovations and practical, affordable diagnostic products. We suggest that prioritizing equipment-free detection methods and enhancing standardization could accelerate the translation of these PoC technologies into clinical practice. This review outlines a strategic roadmap for advancing NA-based PoC diagnostics, emphasizing the potential to transform healthcare delivery worldwide through accessible, rapid, and reliable molecular testing
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