6 results on '"Simon Keely"'
Search Results
2. Does postoperative inflammation or sepsis generate neutrophil extracellular traps that influence colorectal cancer progression? A systematic review
- Author
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Georgia M. Carroll, BMed, PGDip, Grace L. Burns, BBiomed, Sci (Hons), Joel A. Petit, BSc, MBBS, MMed, Marjorie M. Walker, BMBS, FRCPA, Andrea Mathe, PhD, Stephen R. Smith, MBBS, BSc, FRACS, MS, PhD, Simon Keely, PhD, and Peter G. Pockney, DM, MBBS, BSc, FRCS, FRACS
- Subjects
Surgery ,RD1-811 - Abstract
Background: Colorectal cancer is the third most common cancer worldwide. Almost half of those that have a potentially curative resection go on to develop metastatic disease. A recognized risk for recurrence is perioperative systemic inflammation and sepsis. Neutrophil extracellular traps have been implicated as promotors of tumor progression. We aimed to examine the evidence in the literature for an association between neutrophil extracellular traps and postoperative metastasis in colorectal cancer. Materials and methods: Studies published between 2000 and December 2018 that examined the role of neutrophil extracellular traps in sepsis and inflammation in colorectal cancer and in relation to tumor-related outcomes were identified through a database search of Cochrane, CINAHL, and MEDLINE. Quality and bias assessment was carried out by 2 reviewers. Results: Of 8,940 screened and of the 30 studies included, 21 were observational, 5 were in vivo experimental, 1 was in vitro, and 3 used a combination of these approaches. Conclusion: There is clear evidence from the literature that presence of a preoperative systemic inflammatory response predicts cancer recurrence following potentially curative resection, but the evidence for association of sepsis and progression is lacking. There is robust experimental evidence in murine models showing that neutrophil extracellular traps are present in sepsis and are associated with cancer progression. Some human observational studies corroborate the prognostic significance of neutrophil extracellular traps in progression of colorectal cancer. Further human studies are needed to translate the experimental evidence and to definitively associate sepsis and neutrophil extracellular traps with poor colorectal cancer-specific outcomes.
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- 2020
- Full Text
- View/download PDF
3. Interactions between taste receptors and the gastrointestinal microbiome in inflammatory bowel disease
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Alexandria Turner, Eileen Chijoff, Martin Veysey, Simon Keely, Christopher J. Scarlett, Mark Lucock, and Emma L. Beckett
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Nutrition. Foods and food supply ,TX341-641 ,Biochemistry ,QD415-436 - Abstract
Incidence rates of inflammatory bowel disease (IBD) are increasing worldwide. This correlates with increased consumption of red meats, alcohol, refined sugars, oils and animal fats, typical of a “Western” diet. Poor dietary habits are the most ubiquitous environmental factor implicated in IBD, along with gastrointestinal dysbiosis. Taste genetics and oral receptor expression levels determine dietary preferences and therefore, nutritional intake. Taste receptors (TRs) are also expressed throughout the gastrointestinal tract, where they are involved in modulating metabolic processes and gastrointestinal function. Importantly, these receptors are known to be involved in the modulation of inflammatory processes in the respiratory tract. In this system, TRs detect and respond to bacteria and bacterial signalling molecules and initiate protective responses. We propose that TRs play a similar role in the gastrointestinal tract, thereby modulating risk for IBD. TRs may indirectly affect risk for IBD by altering dietary intake, and therefore microbial composition and function. Alternatively, TRs may directly detect and respond to gastrointestinal bacterial components. Overall, there is evidence to suggest an emerging role for TRs in the aetiology of IBD. Furthermore, targeting these receptors via dietary modulation may have therapeutic potential. Keywords: Taste receptors, Nutrition, Microbiome, Inflammatory bowel disease, Diet
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- 2019
- Full Text
- View/download PDF
4. Interactions between taste receptors and the gastrointestinal microbiome in inflammatory bowel disease
- Author
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Mark Lucock, Christopher J. Scarlett, Emma L. Beckett, Alexandria Turner, Martin Veysey, Simon Keely, and Eileen Chijoff
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0301 basic medicine ,Gastrointestinal tract ,Nutrition and Dietetics ,business.industry ,Endocrinology, Diabetes and Metabolism ,Receptor expression ,Gastrointestinal Microbiome ,lcsh:TX341-641 ,medicine.disease ,Inflammatory bowel disease ,lcsh:Biochemistry ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Taste receptor ,Immunology ,medicine ,030211 gastroenterology & hepatology ,lcsh:QD415-436 ,Gastrointestinal function ,business ,Receptor ,Dysbiosis ,lcsh:Nutrition. Foods and food supply ,Food Science - Abstract
Incidence rates of inflammatory bowel disease (IBD) are increasing worldwide. This correlates with increased consumption of red meats, alcohol, refined sugars, oils and animal fats, typical of a “Western” diet. Poor dietary habits are the most ubiquitous environmental factor implicated in IBD, along with gastrointestinal dysbiosis. Taste genetics and oral receptor expression levels determine dietary preferences and therefore, nutritional intake. Taste receptors (TRs) are also expressed throughout the gastrointestinal tract, where they are involved in modulating metabolic processes and gastrointestinal function. Importantly, these receptors are known to be involved in the modulation of inflammatory processes in the respiratory tract. In this system, TRs detect and respond to bacteria and bacterial signalling molecules and initiate protective responses. We propose that TRs play a similar role in the gastrointestinal tract, thereby modulating risk for IBD. TRs may indirectly affect risk for IBD by altering dietary intake, and therefore microbial composition and function. Alternatively, TRs may directly detect and respond to gastrointestinal bacterial components. Overall, there is evidence to suggest an emerging role for TRs in the aetiology of IBD. Furthermore, targeting these receptors via dietary modulation may have therapeutic potential. Keywords: Taste receptors, Nutrition, Microbiome, Inflammatory bowel disease, Diet
- Published
- 2019
5. MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase–mediated suppression of histone deacetylase 2
- Author
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Richard Kim, Joerg Mattes, Tatt Jhong Haw, Andrew G. Jarnicki, James W. Pinkerton, Bernadette Jones, Paul S. Foster, Philip M. Hansbro, Jay C. Horvat, Malcolm R. Starkey, Ian M. Adcock, Jemma R. Mayall, Krishna P. Sunkara, Prema M. Nair, Simon Keely, Nicole G. Hansbro, Ama Tawiah Essilfie, Thi Hiep Nguyen, Medical Research Council (MRC), and Commission of the European Communities
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0301 basic medicine ,Severe asthma ,Allergy ,respiratory syncytial virus ,Drug Resistance ,species ,Histone Deacetylase 2 ,TENSIN HOMOLOG ,Dexamethasone ,corticosteroids ,chemistry.chemical_compound ,Mice ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Influenza A Virus, H1N1 Subtype ,PI3 kinase ,Immunology and Allergy ,Tensin ,IMMUNE-RESPONSE ,LY294002 ,Chlamydia ,Phosphorylation ,Respiratory Tract Infections ,INFLUENZA-VIRUS INFECTION ,Mice, Inbred BALB C ,Histone deacetylase 2 ,Respiratory Syncytial Viruses ,BACTERIAL-INFECTION ,1107 Immunology ,miR-21 ,medicine.symptom ,influenza ,Life Sciences & Biomedicine ,ALLERGIC AIRWAYS DISEASE ,RESPIRATORY-INFECTION ,Chlamydia muridarum ,Immunology ,Inflammation ,NEUTROPHILIC ASTHMA ,Biology ,OBSTRUCTIVE PULMONARY-DISEASE ,03 medical and health sciences ,medicine ,Animals ,Humans ,Antagomir ,REGULATORY T-CELLS ,Chlamydia species ,PI3K/AKT/mTOR pathway ,Asthma ,Science & Technology ,airway hyperresponsiveness ,PTEN Phosphohydrolase ,Antagomirs ,Pneumonia ,medicine.disease ,Haemophilus influenzae ,Disease Models, Animal ,MicroRNAs ,030104 developmental biology ,030228 respiratory system ,chemistry ,Gene Expression Regulation ,INFLAMMATORY RESPONSES ,Histone deacetylase ,Proto-Oncogene Proteins c-akt - Abstract
© 2016 American Academy of Allergy, Asthma & Immunology Background Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. However, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. The mechanisms that underpin infection-induced, severe steroid-insensitive asthma can be elucidated by using mouse models of disease. Objective We sought to develop representative mouse models of severe, steroid-insensitive asthma and to use them to identify pathogenic mechanisms and investigate new treatment approaches. Methods Novel mouse models of Chlamydia, Haemophilus influenzae, influenza, and respiratory syncytial virus respiratory tract infections and ovalbumin-induced, severe, steroid-insensitive allergic airway disease (SSIAAD) in BALB/c mice were developed and interrogated. Results Infection induced increases in the levels of microRNA (miRNA)-21 (miR-21) expression in the lung during SSIAAD, whereas expression of the miR-21 target phosphatase and tensin homolog was reduced. This was associated with an increase in levels of phosphorylated Akt, an indicator of phosphoinositide 3-kinase (PI3K) activity, and decreased nuclear histone deacetylase (HDAC)2 levels. Treatment with an miR-21–specific antagomir (Ant-21) increased phosphatase and tensin homolog levels. Treatment with Ant-21, or the pan-PI3K inhibitor LY294002, reduced PI3K activity and restored HDAC2 levels. This led to suppression of airway hyperresponsiveness and restored steroid sensitivity to allergic airway disease. These observations were replicated with SSIAAD associated with 4 different pathogens. Conclusion We identify a previously unrecognized role for an miR-21/PI3K/HDAC2 axis in SSIAAD. Our data highlight miR-21 as a novel therapeutic target for the treatment of this form of asthma.
- Published
- 2016
6. Fluorescently tagged star polymers by living radical polymerisation for mucoadhesion and bioadhesion
- Author
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Atvinder K. Rullay, Adam Limer, Verónica Miguel, E. Fitzpatrick, David J. Brayden, Simon Keely, Carmen Peinado, Stephen D. Carrington, and David M. Haddleton
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Polymers and Plastics ,General Chemical Engineering ,Dispersity ,ATRP ,Mucoadhesion ,Star polymers ,Methacrylate ,Biochemistry ,chemistry.chemical_compound ,Polymer chemistry ,Materials Chemistry ,Environmental Chemistry ,Methyl methacrylate ,chemistry.chemical_classification ,Bioadhesion ,Materiales ,Chemistry ,General Chemistry ,Polymer ,Fluorescent polymer ,Química ,Fluorescence ,Polyelectrolyte ,Polymerization ,Living radical polymerisation - Abstract
The synthesis of 3-, 5- and 8-arm dimethylaminoethyl methacrylate star polymers are reported, final Mn (PDI) = 12.2 K (1.09), 18.9K (1.10) and 38.4 K (1.11), respectively. The synthesis of 3-arm methyl methacrylate and dimethylaminoethyl methacrylate block co-polymer stars is also described. Living polymerisation occurred in all cases providing well defined stars with predictable molecular weights and narrow polydispersity. A fluorescent tag, 2-(8-methacryloyloy-3,6-dioxaoctyl)thioxantheno[2,1,9-dej]isoquinoline-1,3-dione, derived from a commercially available pigment, was incorporated into the star polymers. The fluorescence spectra of the polymers prepared were recorded over a range of pH and the peak emission frequency and intensity have been reported, λex = 462 nm. All of the multi-arm polymers exhibit fluorescence across a broad pH range with maximum emission at pH 4. A 3-arm star polymer has been demonstrated to show good bioadhesion in rat tissue. A reduced adhesion in epithelial tissues not covered by a viscoelastic mucus gel indicates an increased tendency for mucoadhesion over bioadhesion. We thank Clariant for the kind donation of the hostasol precursor and Genzyme for part funding this work. D.M. Haddleton would also like to thank Professor John Ebdon for all of his encouragement and support throughout his academic career.
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- 2015
- Full Text
- View/download PDF
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