9,234 research outputs found

    Ruthenium metallotherapeutics: a targeted approach to combatting multidrug resistant pathogens

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    The discovery of antibiotics revolutionised healthcare practice. However due to overuse, inappropriate use, widespread prophylaxis therapy and the lack of new developments, the threat of antimicrobial resistance is now a major global threat to health. By 2050, it is estimated that mortality due to antimicrobial resistant infections will exceed 10 million people per annum, superseding cancer as the leading cause of global mortality. The use of drug repurposing to identify potential therapies which combat antimicrobial resistance is one potential solution. Metals have been used as antimicrobial agents throughout the history of medicine for a broad range of applications, including the use of Silver as an antimicrobial agent which dates back to antiquity. More recently, Ruthenium metallotherapeutic complexes have been shown to exhibit highly active antimicrobial properties by targeting a range of bacterial species, and in contrast to traditional antibiotics, these compounds are thought to elicit antibacterial activity at multiple sites within the bacterial cell, which may reduce the possibility of resistance evolution. This study aimed to evaluate the antimicrobial activity of a series of Ruthenium metallotherapeutic complexes against multidrug-resistant bacterial pathogens, with a focus on use within wound care applications. Antimicrobial susceptibility assays identified two lead candidates, Hexaammineruthenium (III) chloride and [Chlorido(η6-p-cymene)(N-(4-chlorophenyl)pyridine-2-carbothioamide) ruthenium (II)] chloride which demonstrated activity against Pseudomonas aeruginosa and Staphylococcus aureus respectively with MIC values ranging between 4 μg mL-1 and 16 μg mL-1. Furthermore, Hexaammineruthenium (III) chloride demonstrated antibiofilm activity in both a time and concentration-dependent manner. Synergy studies combining lead complexes with antibiotics demonstrated the potential for use as resistance breakers. Subsequent in vitro infection modelling using scratch assays with skin cell lines, coupled with a 3D full thickness skin wound infection model was used to determine potential applied applications of Hexaammineruthenium (III) chloride for use as topical antimicrobial agent against P. aeruginosa infections. Antimicrobial mechanistic studies demonstrated that Hexaammineruthenium (III) chloride targeted the bacterial cell ultrastructure of P. aeruginosa strain PAO1 as cell perturbations were observed when treated cells were analysed by scanning electron microscopy. Furthermore, exposure of P. aeruginosa PAO1 to Hexaammineruthenium (III) chloride also resulted in a concentration dependent membrane depolarisation, which further supported the antimicrobial mechanistic role. Finally, global changes in gene expression following exposure of P. aeruginosa strain PAO1 to Hexaammineruthenium (III) chloride were explored by RNA sequencing. Genes involved in ribosome function, cofactor biosynthesis and membrane fusion were downregulated, which provided a further insight into the wider mechanisms of antibacterial activity. The research conducted in the present study indicated the potential use of Hexaammineruthenium (III) chloride (and derivatives) as a potential treatment option for chronic wounds infected with P. aeruginosa, which could be applied as either a direct treatment or used within antimicrobial wound care applications

    A Three-Dimensional Model of Bacterial Biofilms and Its Use in Antimicrobial Susceptibility Testing

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    (1) Background: The discrepant antimicrobial susceptibility between planktonic and biofilm bacterial modes poses a problem for clinical microbiology laboratories and necessitates a relevant 3D experimental model allowing bacteria to grow in biofilm mode, in vitro, for use in anti-biofilm susceptibility testing. (2) Methods: This work develops a 3D biofilm model consisting of alginate beads containing S. aureus biofilm and encased within two thick layers of alginate matrix. The constructed model was placed on a thin Boyden chamber insert suspended on a 24-well culture plate containing the culture medium. The antibacterial activity of bacitracin and chlorhexidine digluconate (CD), either combined or separately, against 2D S. aureus culture was compared to that in the 3D biofilm model. Quantitative analysis and imaging analysis were performed by assessing the bacterial load within the matrix as well as measuring the optical density of the culture medium nourishing the matrix. (3) Results: The 3D biofilm model represented the typical complex characteristics of biofilm with greater insusceptibility to the tested antimicrobials than the 2D culture. Only bacitracin and CD in combination at 100Ă— the concentration found to be successful against 2D culture were able to completely eliminate the 3D biofilm matrix. (4) Conclusions: The 3D biofilm model, designed to be more clinically relevant, exhibits higher antimicrobial insusceptibility than the 2D culture, demonstrating that the model might be useful for testing and discovering new antimicrobial therapies. The data also support the view that combination therapy might be the optimal approach to combat biofilm infections

    Animal protein-based soft materials for tissue engineering applications

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    Proteins have long been used in coatings for cell culture plates and to supplement cell culture media. Due to their unmatched biocompatibility, biodegradability, bioactivity and immune-privilege, the interest in proteins rapidly advanced for the design and engineering of more complex substrates for biomedical applications. In this chapter, the proteins typically used in the design and fabrication of biomedical devices are presented and discussed, with particular focus in human-based platforms. However, restrictions in the use of protein-derived materials are associated with their limited processability and stability, but to overcome this, multiple bioconjugation techniques have been described and are herein presented. An overview of current protein-based materials that have found clinical application and that have been commercialized is also provided.publishe

    Recent Advances in Novel Materials and Techniques for Developing Transparent Wound Dressings

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    Optically transparent wound dressings offer a range of potential applications in the biomedical field, as they allow for the monitoring of wound healing progress without having to replace the dressing. These dressings must be impermeable to water and bacteria, yet permeable to moisture vapor and atmospheric gases in order to maintain a moist environment at the wound site. This review article provides a comprehensive overview of the types of wound dressings, novel wound dressing materials, advanced fabrication techniques for transparent wound dressing materials, and the key features and applications of transparent dressings for the healing process, as well as how it can improve healing outcomes. This review mainly focuses on representing specifications of transparent polymeric wound dressing materials, such as transparent electrospun nanofibers, transparent crosslinked hydrogels, and transparent composite films/membranes. Due to the advance properties of electrospun nanofiber such as large surface area, enable efficient incorporation of antibacterial molecules, a structure similar to the extracellular matrix, and high mechanical stability, is often used in wound dressing applications. We also highlight the hydrogels or films for wound healing applications, it's promote the healing process, provide a moisture environment, and offer pain relief with their cool, high-water content, excellent biocompatibility, and bio-biodegradability.Comment: N

    A closed-body preclinical model to investigate blast-induced spinal cord injury

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    Blast-induced spinal cord injuries (bSCI) are common and account for 75% of all combat-related spinal trauma. It remains unclear how the rapid change in pressure contributes to pathological outcomes resulting from these complex injuries. Further research is necessary to aid in specialized treatments for those affected. The purpose of this study was to develop a preclinical injury model to investigate the behavior and pathophysiology of blast exposure to the spine, which will bring further insight into outcomes and treatment decisions for complex spinal cord injuries (SCI). An Advanced Blast Simulator was used to study how blast exposure affects the spinal cord in a non-invasive manner. A custom fixture was designed to support the animal in a position that protects the vital organs while exposing the thoracolumbar region of the spine to the blast wave. The Tarlov Scale and Open Field Test (OFT) were used to detect changes in locomotion or anxiety, respectively, 72 h following bSCI. Spinal cords were then harvested and histological staining was performed to investigate markers of traumatic axonal injury (β-APP, NF-L) and neuroinflammation (GFAP, Iba1, S100β). Analysis of the blast dynamics demonstrated that this closed-body model for bSCI was found to be highly repeatable, administering consistent pressure pulses following a Friedlander waveform. There were no significant changes in acute behavior; however, expression of β-APP, Iba1, and GFAP significantly increased in the spinal cord following blast exposure (p < 0.05). Additional measures of cell count and area of positive signal provided evidence of increased inflammation and gliosis in the spinal cord at 72 h after blast injury. These findings indicated that pathophysiological responses from the blast alone are detectable, likely contributing to the combined effects. This novel injury model also demonstrated applications as a closed-body SCI model for neuroinflammation enhancing relevance of the preclinical model. Further investigation is necessary to assess the longitudinal pathological outcomes, combined effects from complex injuries, and minimally invasive treatment approaches

    A Novel Approach for the Treatment of Aerobic Vaginitis: Azithromycin Liposomes-in-Chitosan Hydrogel

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    Biocompatible mucoadhesive formulations that enable a sustained drug delivery at the site of action, while exhibiting inherent antimicrobial activity, are of great importance for improved local therapy of vaginal infections. The aim of this research was to prepare and evaluate the potential of the several types of azithromycin (AZM)-liposomes (180–250 nm) incorporated into chitosan hydrogel (AZM-liposomal hydrogels) for the treatment of aerobic vaginitis. AZM-liposomal hydrogels were characterized for in vitro release, and rheological, texture, and mucoadhesive properties under conditions simulating the vaginal site of application. The role of chitosan as a hydrogel-forming polymer with intrinsic antimicrobial properties was explored against several bacterial strains typical for aerobic vaginitis as well as its potential effect on the anti-staphylococcal activity of AZM-liposomes. Chitosan hydrogel prolonged the release of the liposomal drug and exhibited inherent antimicrobial activity. Additionally, it boosted the antibacterial effect of all tested AZM-liposomes. All AZM-liposomal hydrogels were biocompatible with the HeLa cells and demonstrated mechanical properties suitable for vaginal application, thus confirming their potential for enhanced local therapy of aerobic vaginitis

    Stem Cells in Domestic Animals

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    Stem cells are an attractive tool for cell-based therapies in regenerative medicine, both for humans and animals. The research and review articles published in this first book of the Collection “Stem Cells in Domestic Animals: Applications in Health and Production” are excellent examples of the recent advances made in the field of stem/stromal cell research in veterinary medicine. In this field, sophisticated and new treatments are now required for improving patients’ quality of life; in livestock animals, the goal of regenerative medicine is to improve not only animal welfare but also the quality of production, aiming to preserve human health. The contributions collected in this book concern both laboratory research and clinical applications of mesenchymal stem/stromal cells. The increasing knowledge of cell-based therapies may constitute an opportunity for researchers, veterinary practitioners, and animal owners to contribute to animal and human health and well-being

    Application of Cell-Based Therapies in Veterinary Dermatology

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    Stem cells have been extensively studied in the field of veterinary medicine due to their unique characteristics. The last are undifferentiated cells with self-renewal, anti-inflammatory, and immunomodulatory capacity. Mesenchymal stem cells (MSCs) are widely used due to its simple isolation and expansion, being collected from different sources such as adipose tissue, bone marrow, peripheral blood, and umbilical cord. For that reason, MSCs have been studied and used as innovative therapies in the treatment of several diseases, such as tendinitis, bone regeneration, osteoarthritis, neuromuscular diseases, heart diseases, respiratory diseases, kidney disorders, ophthalmology, oncology, and dermatology. Concerning dermatological problems, the number of skin diseases in animals has been increasing in recent years. Skin diseases may be related to genetic conditions, external aggressions, or immunological disorders. Many of these skin pathologies are chronic, reason why the animals are subjected to long-term therapies, which can have deleterious side effects. This review aims to highlight the importance of cell-based therapies, using MSCs from different origins and their secretome, in the field of veterinary dermatology and in immune-mediated diseases such as atopic dermatitis, furunculosis, anal vasculitis, and scar tissue regeneration. These approaches should be further explored, as they have revealed promising results in the search for novel therapies
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