المؤلفون: Jannatul Ferdoush Tuli, Mahnaz Ramezanpour, Clare Cooksley, George Spyro Bouras, Kazuhiro Ogi, Sholeh Feizi, Roshan Nepal, Alkis James Psaltis, Peter‐John Wormald, Sarah Vreugde

المصدر: Laryngoscope Investigative Otolaryngology, Vol 9, Iss 3, Pp n/a-n/a (2024)

مصطلحات موضوعية: anaerobic conditions, antibiotic, chronic rhinosinusitis, pseudomonas aeruginosa, resistance, Otorhinolaryngology, RF1-547, Surgery, RD1-811

الوصف: Abstract Introduction In chronic rhinosinusitis (CRS), the congestion and blockage of the nose can cause anaerobic conditions within the sinus cavities which may promote the expression of virulence and antibiotic resistance genes in invading pathogens. Pseudomonas aeruginosa is a facultative anaerobic bacteria and causes severe recalcitrant CRS. In this study, we aimed to evaluate the antimicrobial resistance of P. aeruginosa isolates of CRS patients in planktonic and biofilm form grown in aerobic and anaerobic conditions. Methods P. aeruginosa clinical isolates of CRS patients (n = 25) were grown in planktonic and biofilm form in aerobic and anaerobic conditions. Minimum inhibitory concentrations (MIC) of planktonic forms and minimum biofilm eradication concentrations (MBEC) were determined. Additionally, metabolic activity by fluorescein diacetate assay, biofilm biomass by crystal violet assay and eDNA concentration were assessed in both conditions. Results P. aeruginosa planktonic cells grown in anaerobic condition exhibited increased gentamicin resistance (p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2378-8038Test

الوصول الحر: https://doaj.org/article/34c27f1a644040178b54f0e1f3f193e3Test

المؤلفون: Anna Megow, George Bouras, Yazeed Alsuliman, Clare Cooksley, Erich Vyskocil, William Murphy, Sarah Vreugde, Peter-John Wormald

المصدر: Frontiers in Surgery, Vol 11 (2024)

مصطلحات موضوعية: endoscopic sinus surgery, chronic rhinosinusitis (CRS), wound healing, microbiome, chitosan–dextran gel, deferiprone, Surgery, RD1-811

الوصف: BackgroundAdhesion formation, sinus ostial narrowing, and presence of pathogenic bacteria are associated with poor outcomes following endoscopic sinus surgery (ESS) for chronic rhinosinusitis. Chitogel has been shown to improve wound healing, restore a healthier microbiome, and reduce post-operative infections post ESS. Deferiprone has antibacterial properties and has been shown to reduce adhesion formation. The aim of the study was to assess whether the addition of low concentration deferiprone to Chitogel further improves surgical outcomes following ESS compared with Chitogel alone.MethodsIn this double-blinded trial, 45 patients undergoing ESS were prospectively recruited. At the end of the surgery, patients were randomised to receive Chitogel alone, Chitogel with 1 mM of deferiprone, or Chitogel with 5 mM of deferiprone to one side of the sinuses (allowing the other side to serve as control). Patients underwent routine follow-ups with symptom questionnaires and nasoendoscopies performed at 2, 6, and 12 weeks post-operatively. Sinus ostial measurements, microbiology, and microbiome swabs from bilateral middle meatuses were collected intraoperatively and at 12 weeks post-operatively.ResultsA significant improvement in the endoscopic appearance of the sinuses and frontal ostial patency was noted at 12 weeks post-operatively (p

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fsurg.2024.1338209/fullTest; https://doaj.org/toc/2296-875XTest

الوصول الحر: https://doaj.org/article/4a6685efa6b345eeb5ef1ab9c99e0418Test

المؤلفون: William Murphy, Sha Liu, Karen Hon, John Finnie, George Spyro Bouras, Sholeh Feizi, Ghais Houtak, Gohar Shaghayegh, Erich Vyskocil, Peter-John Wormald, Sarah Vreugde, Alkis J. Psaltis

المصدر: International Journal of Molecular Sciences, Vol 25, Iss 6, p 3336 (2024)

مصطلحات موضوعية: Staphylococcus aureus, chronic rhinosinusitis, lymphoplasmacytic inflammatory response, rodent model, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Chronic rhinosinusitis (CRS) is characterized by sinonasal mucosal inflammation. Staphylococcus aureus (S. aureus) is associated with severe CRS phenotypes. Different animal models have been proposed to study the association of CRS and S. aureus. However, current animal models are expensive due to the use of large animals, have high barriers to ethics approval, or require invasive surgical intervention, necessitating a need for a model that can overcome these limitations. This study aimed at establishing a reliable and efficient rat lymphoplasmacytic inflammatory model for rhinosinusitis. Sprague Dawley rats received a daily intranasal application of 20 μL of saline, S. aureus CI-182 exoprotein (250 μg/mL), or exoprotein CI-182 in combination with S. aureus clinical isolate (CI-908 or CI-913) 108 colony-forming unit (CFU)/mL. The rats’ sinuses were harvested at 1 and 2 weeks post-intervention. The CFU and histopathologic examination of inflammation were evaluated. S. aureus clinical isolates CI-908 or CI-913 in combination with the exoprotein (CI-182) had higher CFUs and caused persistently higher inflammation at both the 1 and 2-week post-intervention compared to the exoprotein and saline group. The observed inflammatory cell type was lymphoplasmacytic. This study provided evidence that the combination of a S. aureus exoprotein with S. aureus induces inflammation that persists for a minimum of two weeks post-intervention. This model is the first known animal model to create the lymphoplasmacytic inflammation subtype seen in CRS patients. This offers a cost-effective, accessible, non-invasive, and easy-to-replicate model to study the causes and treatment of such inflammation.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/25/6/3336Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/759d1b6a5ece4cd6842e00b72a631083Test

المؤلفون: Ghais Houtak, Roshan Nepal, George Bouras, Gohar Shaghayegh, Catherine Bennett, John Finnie, Kevin Fenix, Alkis James Psaltis, Peter-John Wormald, Sarah Vreugde

المصدر: International Journal of Molecular Sciences, Vol 25, Iss 6, p 3402 (2024)

مصطلحات موضوعية: Chronic rhinosinusitis, Staphylococcus aureus, biofilm, eosinophilic, IgE, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Chronic rhinosinusitis (CRS) is an inflammatory condition of the sinonasal mucosa. Despite being a common health issue, the exact cause of CRS is yet to be understood. However, research suggests that Staphylococcus aureus, particularly in its biofilm form, is associated with the disease. This study aimed to investigate the impact of long-term exposure to secreted factors of Staphylococcus aureus biofilm (SABSFs), harvested from clinical isolates of non-CRS carrier and CRS patients, on the nasal mucosa in a rat model. Animals were randomised (n = 5/group) to receive daily intranasal instillations of 40 μL (200 μg/μL) SABSFs for 28 days or vehicle control. The sinonasal samples were analysed through histopathology and transcriptome profiling. The results showed that all three intervention groups displayed significant lymphocytic infiltration (p ≤ 0.05). However, only the SABSFs collected from the CRSwNP patient caused significant mucosal damage, mast cell infiltration, and goblet cell hyperplasia compared to the control. The transcriptomics results indicated that SABSFs significantly enriched multiple inflammatory pathways and showed distinct transcriptional expression differences between the control group and the SABSFs collected from CRS patients (p ≤ 0.05). Additionally, the SABSF challenges induced the expression of IgA and IgG but not IgE. This in vivo study indicates that long-term exposure to SABSFs leads to an inflammatory response in the nasal mucosa with increased severity for S. aureus isolated from a CRSwNP patient. Moreover, exposure to SABSFs does not induce local production of IgE.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/25/6/3402Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/cec553a105f0487c8514c63f2e4f2abbTest

المؤلفون: William Murphy, Sha Liu, Shari Javadiyan, Erich Vyskocil, Sholeh Feizi, Claudio Callejas, Peter-John Wormald, Sarah Vreugde, Alkis J. Psaltis

المصدر: International Journal of Molecular Sciences, Vol 25, Iss 5, p 2796 (2024)

مصطلحات موضوعية: chronic rhinosinusitis, IL-6, inflammation, mesalazine, TNF-α, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Chronic rhinosinusitis (CRS) is a disease characterised by the inflammation of the nasal and paranasal cavities. It is a widespread condition with considerable morbidity for patients. Current treatment for chronic rhinosinusitis consists of appropriate medical therapy followed by surgery in medically resistant patients. Although oral steroids are effective, they are associated with significant morbidity, and disease recurrence is common when discontinued. The development of additional steroid sparing therapies is therefore needed. Mesalazine is a commonly used therapeutic in inflammatory bowel disease, which shares a similar disease profile with chronic rhinosinusitis. This exploratory in vitro study aims to investigate whether mesalazine could be repurposed to a nasal wash, which is safe on human nasoepithelial cells, and retains its anti-inflammatory effects. CRS patients’ human nasal epithelial cells (HNECs) were collected. HNECs were grown at an air-liquid interface (ALIs) and in a monolayer and challenged with mesalazine or a non-medicated control. Transepithelial electrical resistance, paracellular permeability, and toxicity were measured to assess epithelial integrity and safety. The anti-inflammatory effects of mesalazine on the release of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) were analysed using human leukemia monocytic cell line (THP-1). mesalazine did not impact the barrier function of HNEC-ALIs and was not toxic when applied to HNECs or THP-1 cells at concentrations up to 20 mM. mesalazine at 0.5 and 1 mM concentrations significantly inhibited TNF-α release by THP-1 cells. mesalazine effectively decreases TNF-α secretion from THP-1 cells, indicating the possibility of its anti-inflammatory properties. The safety profile of mesalazine at doses up to 20 mM suggests that it is safe when applied topically on HNECs.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/25/5/2796Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/263d6c7c4cea4bbaa574f032e7ccfa9fTest

المؤلفون: Tahlia L. Kennewell, Hanif Haidari, Suzanne Mashtoub, Gordon S. Howarth, Catherine Bennett, Clare M. Cooksley, Peter John Wormald, Allison J. Cowin, Sarah Vreugde, Zlatko Kopecki

المصدر: Materials, Vol 17, Iss 4, p 793 (2024)

مصطلحات موضوعية: Pseudomonas aeruginosa, wound infection, biofilms, Technology, Electrical engineering. Electronics. Nuclear engineering, TK1-9971, Engineering (General). Civil engineering (General), TA1-2040, Microscopy, QH201-278.5, Descriptive and experimental mechanics, QC120-168.85

الوصف: Pseudomonas aeruginosa is one of the most common pathogens encountered in clinical wound infections. Clinical studies have shown that P. aeruginosa infection results in a larger wound area, inhibiting healing, and a high prevalence of antimicrobial resistance. Hydroxypyridinone-derived iron chelator Deferiprone (Def) and heme analogue Gallium-Protoporphyrin (GaPP) in a chitosan-dextran hydrogel (Chitogel) have previously been demonstrated to be effective against PAO1 and clinical isolates of P. aeruginosa in vitro. Moreover, this combination of these two agents has been shown to improve sinus surgery outcomes by quickly reducing bleeding and preventing adhesions. In this study, the efficacy of Def-GaPP Chitogel was investigated in a P. aeruginosa biofilm-infected wound murine model over 6 days. Two concentrations of Def-GaPP Chitogel were investigated: Def-GaPP high dose (10 mM Def + 500 µg/mL GaPP) and Def-GaPP low dose (5 mM Def + 200 µg/mL GaPP). The high-dose Def-GaPP treatment reduced bacterial burden in vivo from day 2, without delaying wound closure. Additionally, Def-GaPP treatment decreased wound inflammation, as demonstrated by reduced neutrophil infiltration and increased anti-inflammatory M2 macrophage presence within the wound bed to drive wound healing progression. Def-GaPP Chitogel treatment shows promising potential in reducing P. aeruginosa cutaneous infection with positive effects observed in the progression of wound healing.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1996-1944/17/4/793Test; https://doaj.org/toc/1996-1944Test

الوصول الحر: https://doaj.org/article/c40e2dbdb2a04446a2dbfb9bf8cf4e7cTest

المؤلفون: Shuman Huang, Karen Hon, Catherine Bennett, Hua Hu, Martha Menberu, Peter-John Wormald, Yulin Zhao, Sarah Vreugde, Sha Liu

المصدر: Frontiers in Microbiology, Vol 14 (2023)

مصطلحات موضوعية: Corynebacterium accolens, Staphylococcus aureus, planktonic, biofilm, TER, cell-free culture supernatants, Microbiology, QR1-502

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmicb.2023.1279422/fullTest; https://doaj.org/toc/1664-302XTest

الوصول الحر: https://doaj.org/article/e4249bf76b7449d6ba38cad3f69eb85aTest

المؤلفون: Bimala Dhakal, Celine Man Ying Li, Mahnaz Ramezanpour, Ghais Houtak, Runhao Li, George Bouras, Alex Collela, Nusha Chegeni, Tim Kennion Chataway, Paul Drew, Benedetta C. Sallustio, Sarah Vreugde, Eric Smith, Guy Maddern, Giovanni Licari, Kevin Fenix

المصدر: Frontiers in Immunology, Vol 14 (2023)

مصطلحات موضوعية: M1 macrolphage, perhexiline, quantitative proteomics, THP-1 derived macrophages, macrophage polarisation, Immunologic diseases. Allergy, RC581-607

الوصف: BackgroundDysregulated inflammation is important in the pathogenesis of many diseases including cancer, allergy, and autoimmunity. Macrophage activation and polarisation are commonly involved in the initiation, maintenance and resolution of inflammation. Perhexiline (PHX), an antianginal drug, has been suggested to modulate macrophage function, but the molecular effects of PHX on macrophages are unknown. In this study we investigated the effect of PHX treatment on macrophage activation and polarization and reveal the underlying proteomic changes induced.MethodsWe used an established protocol to differentiate human THP-1 monocytes into M1 or M2 macrophages involving three distinct, sequential stages (priming, rest, and differentiation). We examined the effect of PHX treatment at each stage on the polarization into either M1 or M2 macrophages using flow cytometry, quantitative polymerase chain reaction (qPCR) and enzyme linked immunosorbent assay (ELISA). Quantitative changes in the proteome were investigated using data independent acquisition mass spectrometry (DIA MS).ResultsPHX treatment promoted M1 macrophage polarization, including increased STAT1 and CCL2 expression and IL-1β secretion. This effect occurred when PHX was added at the differentiation stage of the M1 cultures. Proteomic profiling of PHX treated M1 cultures identified changes in metabolic (fatty acid metabolism, cholesterol homeostasis and oxidative phosphorylation) and immune signalling (Receptor Tyrosine Kinase, Rho GTPase and interferon) pathways.ConclusionThis is the first study to report on the action of PHX on THP-1 macrophage polarization and the associated changes in the proteome of these cells.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1054588/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/01e53bbe66d247dfb4f326e58ef38816Test

المؤلفون: Ahad Sabab, Sha Liu, Shari Javadiyan, C. John McAdam, Lyall R. Hanton, Alistair Jukes, Sarah Vreugde, Peter-John Wormald

المصدر: Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract Beta-chitin patch has previously been proven to be an effective haemostat, but whether modifying the patch affects its efficacy and safety, remains unanswered. In this study, the patch was modified using polyethylene oxide, Pluronic-F127, calcium, increased thickness or polyphosphate, and their effect on the process of haemostasis and cytotoxicity was tested and compared with standard-of-care, Surgicel and FloSeal. Whole blood collected from volunteers was applied to the patches to test their whole blood clotting and thrombin generation capacities, whilst platelet isolates were used to test their platelet aggregation ability. The fluid absorption capacity of the patches was tested using simulated body fluid. Cytotoxicity of the patches was tested using AlamarBlue assays and PC12 cells and the results were compared with the standard-of-care. In this study, beta-chitin patch modifications failed to improve its whole blood clotting, platelet aggregation and thrombin generation capacity. Compared to non-modified patch, modifications with polyethylene oxide or calcium reduced platelet aggregation and thrombin generation capacity, while increasing the thickness or adding polyphosphate decreased platelet aggregation capacity. The cytotoxicity assays demonstrated that the beta-chitin patches were non-toxic to cells. In vivo research is required to evaluate the safety and efficacy of the beta-chitin patches in a clinical setting.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/8e8cc96d708a4eb0af32510973ec0355Test

المؤلفون: Shuman Huang, Karen Hon, Catherine Bennett, Hua Hu, Martha Menberu, Peter-John Wormald, Yulin Zhao, Sarah Vreugde, Sha Liu

المصدر: Frontiers in Microbiology, Vol 13 (2022)

مصطلحات موضوعية: Corynebacterium accolens, Staphylococcus aureus, planktonic, biofilm, TER, cell-free culture supernatants, Microbiology, QR1-502

الوصف: BackgroundCorynebacterium accolens (C. accolens) is a common nasal colonizer, whereas Staphylococcus aureus (S. aureus) is typically regarded a pathogenic organism in patients with chronic rhinosinusitis (CRS). This study aims to evaluate the interaction of the two bacteria in vitro.MethodsClinical isolates of C. accolens and S. aureus from sinonasal swabs, as well as primary human nasal epithelial cells (HNECs) cultured from cellular brushings of both healthy and CRS patients were used for this study. The cell-free culture supernatants of all isolates grown alone and in co-cultures were tested for their effects on transepithelial electrical resistance (TER), FITC-Dextran permeability, lactate dehydrogenase (LDH), and IL-6 and IL-8 secretion of HNECs. Confocal scanning laser microscopy and immunofluorescence were also used to visualize the apical junctional complexes. C. accolens cell-free culture supernatants were also tested for antimicrobial activity and growth on planktonic and biofilm S. aureus growth.ResultsThe cell-free culture supernatants of 3\C. accolens strains (at 60% for S. aureus reference strain and 30% concentration for S. aureus clinical strains) inhibited the growth of both the planktonic S. aureus reference and clinical strains significantly. The C. accolens cell-free culture supernatants caused no change in the TER or FITC-Dextran permeability of the HNEC-ALI cultures, while the cell-free culture supernatants of S. aureus strains had a detrimental effect. Cell-free culture supernatants of C. accolens co-cultured with both the clinical and reference strains of S. aureus delayed the S. aureus-dependent mucosal barrier damage in a dose-dependent manner.ConclusionCorynebacterium accolens cell-free culture supernatants appear to inhibit the growth of the S. aureus planktonic bacteria, and may reduce the mucosal barrier damage caused by S. aureus.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmicb.2022.984741/fullTest; https://doaj.org/toc/1664-302XTest

الوصول الحر: https://doaj.org/article/90086cc18a774703ab179822e615e622Test