Publications by authors named "Colley H"

Accurately predicting the permeation of chemicals through human epithelial tissues is crucial for pharmaceutical therapeutic design and toxicology. Current mathematical models of multi-layered stratified squamous epithelium such as those in the oral cavity use simplistic 'bricks and mortar' geometries that do not fully account for the complex cellular architecture that may affect chemical permeation in these tissues. Here we aimed to develop a new, advanced mechanistic mathematical model of the human epithelium that more accurately represents chemical tissue permeation.

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Approximately one in five individuals experience alveolar osteitis (AO) following wisdom tooth extraction. AO is characterised by loss of the blood clot from the tooth extraction socket leading to infection and pain, resulting in repeated hospital visits that impose a substantial burden on healthcare systems. Current treatments are sub-optimal; to address this we developed a novel drug-loaded mucoadhesive patch composed of dual electrospun polyvinyl pyrrolidone/Eudragit RS100 (PVP/RS100) and poly(N-isopropylacrylamide) (PNIPAM) fibres protected by a poly(ε-caprolactone) (PCL) backing layer.

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  • Scientists developed a tissue-engineered model of oral mucosa to study oral lichen planus (OLP) and its inflammatory properties, addressing the lack of experimental models for this condition.
  • They used activated T-cells to simulate OLP pathogenesis, resulting in increased secretion of inflammatory substances and tissue damage, which was assessed through histological analysis.
  • The study tested treatment options such as JAK inhibitors and clobetasol, showing potential for these methods to reduce cytokine release and prevent tissue damage, paving the way for future therapeutic research.
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Skin in vitro models offer much promise for research, testing drugs, cosmetics, and medical devices, reducing animal testing and extensive clinical trials. There are several in vitro approaches to mimicking human skin behavior, ranging from simple cell monolayer to complex organotypic and bioengineered 3-dimensional models. Some have been approved for preclinical studies in cosmetics, pharmaceuticals, and chemicals.

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Background: In 2017, a mumps outbreak occurred in a US military barracks. Serum collected at service entry was used to compare pre-exposure with presumptive vaccine-induced antibody levels from persons who developed mumps (cases) and potentially exposed persons who did not develop mumps (non-cases). Sufficient information to determine levels of exposure during the outbreak was not available.

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Protein-based biologics constitute a rapidly expanding category of therapeutic agents with high target specificity. Their clinical use has dramatically increased in recent years, but administration is largely via injection. Drug delivery across the oral mucosa is a promising alternative to injections, in order to avoid the gastrointestinal tract and first-pass metabolism.

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Fibrous mucoadhesive polymer membranes prepared using electrospinning demonstrate many advantages for mucosal drug delivery compared to other formulations. Previous electrospun membrane formulations have been developed mainly for the delivery of small molecule drugs. There remains great potential to further develop the technology for the delivery of vesicular vectors that allow administration of advanced therapeutic agents.

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  • Skin irritancy from topical chemicals is a widespread issue, requiring industry testing for safety using non-animal methods.
  • Current tests often fall short as they use simple cell cultures that don't mimic real skin, or complex human skin equivalents that are hard to manage.
  • This research highlights that irritant chemicals activate specific kinases (like c-Src) in human skin models, suggesting potential new rapid testing methods for irritants based on this activation.
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  • Laboratory confirmation of measles via measles-specific IgM detection in serum using ELISA is crucial for accurate surveillance.
  • The study compared a CDC-developed IgM capture assay with five commercial ELISA kits, revealing significant variability in their sensitivity (50-83%) and specificity (86.9-98%).
  • False-positive and false-negative results were common across the commercial kits, complicating the evaluation process in settings aiming for measles elimination.
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Chronic ulcerative oral mucosal inflammatory diseases, including oral lichen planus and recurrent aphthous stomatitis, are painful and highly prevalent, yet lack effective clinical management. In recent years, systemic biologic therapies, including monoclonal antibodies that block the activity of cytokines, have been increasingly used to treat a range of immune-mediated inflammatory conditions such as rheumatoid arthritis and psoriasis. The ability to deliver similar therapeutic agents locally to the oral epithelium could radically alter treatment options for oral mucosal inflammatory diseases, where pro-inflammatory cytokines, in particular tumour-necrosis factor-α (TNFα), are major drivers of pathogenesis.

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Oral lichen planus (OLP) is a T cell-mediated inflammatory disease of the oral mucosa that has been extensively researched over many years but as yet the mechanisms of pathogenesis are still not fully understood. Whilst the specific aetiological factors driving OLP remain ambiguous, evidence points to the development of a chronic, dysregulated immune response to OLP-mediating antigens presented by innate immune cells and oral keratinocytes leading to increased cytokine, chemokine and adhesion molecule expression. These molecules recruit T cells and mast cells to the diseased site and orchestrate a complex interplay between cells that culminates in keratinocyte cell death, mucosal basement membrane destruction and long-term chronicity of the disease.

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Mitochondria are unavoidably subject to organellar stress resulting from exposure to a range of reactive molecular species. Consequently, cells operate a poorly understood quality control programme of mitophagy to facilitate elimination of dysfunctional mitochondria. Here, we used a model stressor, deferiprone (DFP), to investigate the molecular basis for stress-induced mitophagy.

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There are no physical or visual manifestations that define skin sensitivity or irritation; a subjective diagnosis is made on the basis of the evaluation of clinical presentations, including burning, prickling, erythema, and itching. Adverse skin reaction in response to topically applied products is common and can limit the use of dermatological or cosmetic products. The purpose of this study was to evaluate the use of human skin equivalents based on immortalized skin keratinocytes and evaluate the potential of a 22-gene panel in combination with multivariate analysis to discriminate between chemicals known to act as irritants and those that do not.

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  • A significant measles outbreak in New York City involved cases among vaccinated individuals, revealing insights into vaccine failures and their effects on transmission.
  • Researchers measured measles IgG avidity in 62 people, finding that most had high avidity (53), indicating prior immunity, while 9 had low avidity, suggesting potential recent vaccination or lack of immunity.
  • The study shows that even with prior vaccination, people can still transmit measles during outbreaks, highlighting the importance of vigilance for measles cases regardless of vaccination history.
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Nanoparticles have the potential to increase the efficacy of anticancer drugs whilst reducing off-target side effects. However, there remain uncertainties regarding the cellular uptake kinetics of nanoparticles which could have implications for nanoparticle design and delivery. Polymersomes are nanoparticle candidates for cancer therapy which encapsulate chemotherapy drugs.

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Macrophages play a key role in orchestrating the host immune response toward invading organisms or non-self molecules in the oral mucosa. Three-dimensional (3D) oral mucosal equivalents (OME) containing oral fibroblasts and keratinocytes are used extensively to mimic the human oral mucosa where they have been employed to examine innate immune responses to both bacterial and fungal pathogens as well as to biomaterials. Although the presence of immune cells is critical in generating an immune response, very few studies have incorporated leukocytes into OME, and to date, none have contained primary human macrophages.

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Oral lichen planus (OLP) is an immune-mediated disease of the oral mucosa with idiopathic aetiology. It is frequently treated with topical corticosteroids (applied as gels, mouthwashes, or sprays); however, the mucosal exposure times of topical corticosteroids are short because of removal by the constant flow of saliva and mechanical forces. In this study we used cell monolayers, as well as oral mucosal equivalents (OMEs) containing activated T-cells, to examine corticosteroid potency and delivery of clobetasol-17-propionate from a novel electrospun mucoadhesive patch.

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Oral disease greatly affects quality of life, as the mouth is required for a wide range of activities including speech, food and liquid consumption. Treatment of oral disease is greatly limited by the dose forms that are currently available, which suffer from short contact times, poor site specificity, and sensitivity to mechanical stimulation. Mucoadhesive devices prepared using electrospinning offer the potential to address these challenges by allowing unidirectional site-specific drug delivery through intimate contact with the mucosa and with high surface areas to facilitate drug release.

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Current oral squamous cell carcinoma chemotherapies demonstrate off-target toxicity, which could be reduced by local delivery. Curcumin acts via many cellular targets to give anti-cancer properties; however the bioavailability is hindered by its physicochemical characteristics. The incorporation of curcumin into emulgel systems could be a promising approach for its solubilization and delivery.

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The delivery of biopharmaceuticals to the oral mucosa offers a range of potential applications including antimicrobial peptides to treat resistant infections, growth factors for tissue regeneration, or as an alternative to injections for systemic delivery. Existing formulations targeting this site are typically non-specific and provide little control over dose. To address this, an electrospun dual-layer mucoadhesive patch was investigated for protein delivery to the oral mucosa.

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  • The study evaluates the reliability of five commercially available tests for measuring measles virus-specific IgG antibodies to determine immunity in individuals with uncertain vaccination status.
  • False-negative results can lead to unnecessary quarantine or revaccination, while false-positive results may allow susceptible individuals to inadvertently spread the disease.
  • Discrepancies were found mainly in low-positive samples, but overall, the tests performed well for confirming negative IgG status and intermediate to high levels of IgG, with about 11% of low-antibody sera yielding false negatives.
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In early preclinical drug development, potential candidates are tested in the laboratory using isolated cells. These experiments traditionally involve cells cultured in a two-dimensional monolayer environment. However, cells cultured in three-dimensional spheroid systems have been shown to more closely resemble the functionality and morphology of cells .

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Mucoadhesive nanostructured systems comprising poloxamer 407 and Carbopol 974P have already demonstrated good mucoadhesion, as well as improved mechanical and rheological properties. Curcumin displays excellent biological activity, mainly in oral squamous cancer; however, its physicochemical characteristics hinder its application. Therefore, the aim of this study was to develop nanostructured formulations containing curcumin for oral cancer therapy.

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Herein, we describe a protocol for the preparation and analysis of primary isolated rat hepatocytes in a 3D cell culture format described as spheroids. The hepatocyte cells spontaneously self-aggregate into spheroids without the need for synthetic extracellular matrices or hydrogels. Primary rat hepatocytes (PRHs) are a readily available source of primary differentiated liver cells and therefore conserve many of the required liver-specific functional markers, and elicit the natural in vivo phenotype when compared with common hepatic cells lines.

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Many oral mucosal conditions cause considerable and prolonged pain that to date has been difficult to alleviate via topical delivery, and the use of injection causes many patients dental anxiety and needle-prick pain. Therefore, developing a noninjectable drug delivery system as an alternative administration procedure may vastly improve the health and wellbeing of these patients. Recent advances in the development of mucoadhesive electrospun patches for the direct delivery of therapeutics to the oral mucosa offer a potential solution, but as yet, the release of local anesthetics from this system and their uptake by oral tissue have not been demonstrated.

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