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Nebivolol as a Potent TRPM8 Channel Blocker: A Drug-Screening Approach through Automated Patch Clamping and Ligand-Based Virtual Screening (2022)
Journal Article
Jahanfar, F., Sadofsky, L., Morice, A., & D’Amico, M. (2022). Nebivolol as a Potent TRPM8 Channel Blocker: A Drug-Screening Approach through Automated Patch Clamping and Ligand-Based Virtual Screening. Membranes, 12(10), Article 954. https://doi.org/10.3390/membranes12100954

Transient Receptor Potential Melastatin 8 (TRPM8) from the melastatin TRP channel subfamily is a non-selective Ca2+-permeable ion channel with multimodal gating which can be activated by low temperatures and cooling compounds, such as menthol and ici... Read More about Nebivolol as a Potent TRPM8 Channel Blocker: A Drug-Screening Approach through Automated Patch Clamping and Ligand-Based Virtual Screening.

ATP, an attractive target for the treatment of refractory chronic cough (2022)
Journal Article
Zhang, M., Sykes, D. L., Sadofsky, L. R., & Morice, A. H. (2022). ATP, an attractive target for the treatment of refractory chronic cough. Purinergic Signalling, 18, 289-305. https://doi.org/10.1007/s11302-022-09877-z

Chronic cough is the most common complaint in respiratory clinics. Most of them have identifiable causes and some may respond to common disease-modifying therapies. However, there are many patients whose cough lacks effective aetiologically targeted... Read More about ATP, an attractive target for the treatment of refractory chronic cough.

Rhinovirus-16 increases ATP release in A549 cells without concomitant increase in production (2020)
Journal Article
Atkinson, S. K., Morice, A. H., & Sadofsky, L. R. (2020). Rhinovirus-16 increases ATP release in A549 cells without concomitant increase in production. ERJ Open Research, 6(4), Article 00159-2020. https://doi.org/10.1183/23120541.00159-2020

Human rhinovirus (RV) is the most common cause of upper respiratory tract infection (URTI) and chronic airway disease exacerbation. Cough is present in 50–80% of URTI cases, accompanied by heightened airway hypersensitivity, yet no effective treatmen... Read More about Rhinovirus-16 increases ATP release in A549 cells without concomitant increase in production.

Azithromycin for sarcoidosis cough: an open label exploratory clinical trial (2020)
Journal Article
Fraser, S. D., Thackray-Nocera, S., Shepherd, M., Flockton, R., Wright, C., Sheedy, W., Brindle, K., Morice, A. H., Kaye, P. M., Crooks, M. G., & Hart, S. P. (2020). Azithromycin for sarcoidosis cough: an open label exploratory clinical trial. ERJ Open Research, 6(4), Article 00534. https://doi.org/10.1183/23120541.00534-2020

Background: Chronic cough is a distressing symptom for many people with pulmonary sarcoidosis. Continuous treatment with a macrolide antibiotic may improve cough. We aimed to assess the potential efficacy of azithromycin in patients with sarcoidosis... Read More about Azithromycin for sarcoidosis cough: an open label exploratory clinical trial.

Characterisation of a New Human Alveolar Macrophage-Like Cell Line (Daisy) (2019)
Journal Article
Sadofsky, L. R., Hayman, Y. A., Vance, J., Cervantes, J. L., Fraser, S. D., Wilkinson, H. N., Williamson, J. D., Hart, S. P., & Morice, A. H. (2019). Characterisation of a New Human Alveolar Macrophage-Like Cell Line (Daisy). Lung, 197(6), 687-698. https://doi.org/10.1007/s00408-019-00288-3

Purpose: There is currently no true macrophage cell line and in vitro experiments requiring these cells currently require mitogenic stimulation of a macrophage precursor cell line (THP-1) or ex vivo maturation of circulating primary monocytes. In thi... Read More about Characterisation of a New Human Alveolar Macrophage-Like Cell Line (Daisy).

N-cinnamoylanthranilates as human TRPA1 modulators: Structure-activity relationships and channel binding sites (2019)
Journal Article
Chandrabalan, A., McPhillie, M. J., Morice, A. H., Boa, A. N., & Sadofsky, L. R. (2019). N-cinnamoylanthranilates as human TRPA1 modulators: Structure-activity relationships and channel binding sites. European Journal of Medicinal Chemistry, 170, 141-156. https://doi.org/10.1016/j.ejmech.2019.02.074

The transient receptor potential ankyrin 1 (TRPA1) channel is a non-selective cation channel, which detects noxious stimuli leading to pain, itch and cough. However, the mechanism(s) of channel modulation by many of the known, non-reactive modulators... Read More about N-cinnamoylanthranilates as human TRPA1 modulators: Structure-activity relationships and channel binding sites.

Effect of high glucose on human alveolar macrophage phenotype and phagocytosis of mycobacteria (2018)
Journal Article
Vance, J., Santos, A., Sadofsky, L., Morice, A., & Cervantes, J. (2019). Effect of high glucose on human alveolar macrophage phenotype and phagocytosis of mycobacteria. Lung, 197(1), 89–94. https://doi.org/10.1007/s00408-018-0181-z

Purpose
Diabetes mellitus (DBM) reduces immunological activity and increases susceptibility to various infections, including tuberculosis (TB). Human alveolar macrophage (hAM) functions are altered in DBM.

Methods
To mimic hyperglycemic conditions i... Read More about Effect of high glucose on human alveolar macrophage phenotype and phagocytosis of mycobacteria.

Textural analysis demonstrates heterogeneous [18F]-fluorodeoxyglucose uptake in radiologically normal lung in patients with idiopathic pulmonary fibrosis (2018)
Journal Article
Aliyu, S. A., Avery, G., Cawthorne, C., Archibald, S. J., Kadir, T., Willaime, J. M., Morice, A. H., Hart, S. P., & Crooks, M. G. (2018). Textural analysis demonstrates heterogeneous [18F]-fluorodeoxyglucose uptake in radiologically normal lung in patients with idiopathic pulmonary fibrosis. European respiratory journal, 52(5), 1801138. https://doi.org/10.1183/13993003.01138-2018

Positron Emission Tomography (PET) scanning in idiopathic pulmonary fibrosis (IPF) has revealed increased [18F]-fluorodeoxyglucose ([18F]-FDG) uptake in areas of the lungs that appear normal on high resolution computed tomography (HRCT). We hypothesi... Read More about Textural analysis demonstrates heterogeneous [18F]-fluorodeoxyglucose uptake in radiologically normal lung in patients with idiopathic pulmonary fibrosis.

The effects of exogenous lipid on THP-1 cells : an in vitro model of airway aspiration? (2017)
Journal Article
Hayman, Y. A., Sadofsky, L. R., Williamson, J. D., Hart, S. P., & Morice, A. H. (2017). The effects of exogenous lipid on THP-1 cells : an in vitro model of airway aspiration?. Ers Monograph, 3(1), 00026-2016. https://doi.org/10.1183/23120541.00026-2016

Chronic inflammatory diseases of the airways are associated with gastro-oesophageal reflux (GOR) and aspiration events. The observation of lipid laden macrophages (LLM) within the airway may indicate aspiration secondary to GOR. The proposed mechanis... Read More about The effects of exogenous lipid on THP-1 cells : an in vitro model of airway aspiration?.

TRPV1 polymorphisms influence capsaicin cough sensitivity in men (2017)
Journal Article
Sadofsky, L. R., Cantero-Recasens, G., Wright, C., Valverde, M. A., & Morice, A. H. (2017). TRPV1 polymorphisms influence capsaicin cough sensitivity in men. Journal of thoracic disease, 9(3), 839-840. https://doi.org/10.21037/jtd.2017.03.50

Capsaicin, the hot component of chilli peppers, is a well-known tussive agent, which is regularly used as a tool to study cough and antitussives (1). Capsaicin is known to activate the transient receptor potential vanilloid 1 (TRPV1) cation channel w... Read More about TRPV1 polymorphisms influence capsaicin cough sensitivity in men.

TRPA1 mediates aromatase inhibitor-evoked pain by the aromatase substrate androstenedione (2016)
Journal Article
Morice, A. H., Sadofsky, L. R., Benemei, S., Coppi, E., De Logu, F., Di Tommaso, M., Fusi, C., Geppetti, P., Li Puma, S., Marone, I. M., Materazzi, S., Moneti, G., Nassini, R., Susini, T., Terreni, A., & Tonello, R. (2016). TRPA1 mediates aromatase inhibitor-evoked pain by the aromatase substrate androstenedione. Cancer Research, 76(23), 7024-7035. https://doi.org/10.1158/0008-5472.CAN-16-1492

Aromatase inhibitors (AI) induce painful musculoskeletal symptoms (AIMSS), which are dependent upon the pain transducing receptor TRPA1. However, as the AI concentrations required to engage TRPA1 in mice are higher than those found in the plasma of p... Read More about TRPA1 mediates aromatase inhibitor-evoked pain by the aromatase substrate androstenedione.

How does rhinovirus cause the common cold cough? (2016)
Journal Article
Atkinson, S. K., Sadofsky, L. R., & Morice, A. H. (2016). How does rhinovirus cause the common cold cough?. BMJ Open Respiratory Research, 3(1), Article e000118. https://doi.org/10.1136/bmjresp-2015-000118

© 2016, BMJ Publishing Group. All rights reserved. Cough is a protective reflex to prevent aspiration and can be triggered by a multitude of stimuli. The commonest form of cough is caused by upper respiratory tract infection and has no benefit to the... Read More about How does rhinovirus cause the common cold cough?.

Genetic variants affecting human TRPA1 or TRPM8 structure can be classified in vitro as 'well expressed', 'poorly expressed' or 'salvageable' (2015)
Journal Article
Morgan, K., Sadofsky, L. R., & Morice, A. H. (2015). Genetic variants affecting human TRPA1 or TRPM8 structure can be classified in vitro as 'well expressed', 'poorly expressed' or 'salvageable'. Bioscience Reports, 35(5), Article e00255. https://doi.org/10.1042/BSR20150108

© 2015 Authors. Multiple mis-sense variants of TRPA1 (transient receptor potential A1) and TRPM8 (transient receptor potential M8) are recorded in the human genome single nt polymorphism (SNP) database, but their potential impact on channel signallin... Read More about Genetic variants affecting human TRPA1 or TRPM8 structure can be classified in vitro as 'well expressed', 'poorly expressed' or 'salvageable'.

Human TRPM8 and TRPA1 pain channels, including a gene variant with increased sensitivity to agonists (TRPA1 R797T), exhibit differential regulation by SRC-tyrosine kinase inhibitor (2014)
Journal Article
Morgan, K., Sadofsky, L. R., Crow, C., & Morice, A. H. (2014). Human TRPM8 and TRPA1 pain channels, including a gene variant with increased sensitivity to agonists (TRPA1 R797T), exhibit differential regulation by SRC-tyrosine kinase inhibitor. Bioscience Reports, 34(4), 469-478. https://doi.org/10.1042/BSR20140061

TRPM8 (transient receptor potential M8) and TRPA1 (transient receptor potential A1) are cold-temperature-sensitive nociceptors expressed in sensory neurons but their behaviour in neuronal cells is poorly understood. Therefore DNA expression construct... Read More about Human TRPM8 and TRPA1 pain channels, including a gene variant with increased sensitivity to agonists (TRPA1 R797T), exhibit differential regulation by SRC-tyrosine kinase inhibitor.

Inflammatory stimuli up-regulate transient receptor potential vanilloid-1 expression in human bronchial fibroblasts (2012)
Journal Article
Sadofsky, L. R., Ramachandran, R., Crow, C., Cowen, M., Compton, S. J., & Morice, A. H. (2012). Inflammatory stimuli up-regulate transient receptor potential vanilloid-1 expression in human bronchial fibroblasts. Experimental Lung Research, 38(2), 75-81. https://doi.org/10.3109/01902148.2011.644027

Lung fibroblasts are involved in interstitial lung disease, chronic asthma, and chronic obstructive pulmonary disease (COPD). The expanded fibroblast population in airway disease leads to airway remodeling and contributes to the inflammatory process... Read More about Inflammatory stimuli up-regulate transient receptor potential vanilloid-1 expression in human bronchial fibroblasts.

Palmitoylation of human proteinase-activated receptor-2 differentially regulates receptor-triggered ERK1/2 activation, calcium signalling and endocytosis (2011)
Journal Article
Botham, A., Guo, X., Xiao, Y. P., Morice, A. H., Compton, S., & Sadofsky, L. R. (2011). Palmitoylation of human proteinase-activated receptor-2 differentially regulates receptor-triggered ERK1/2 activation, calcium signalling and endocytosis. Biochemical Journal, 438(2), 359-367. https://doi.org/10.1042/BJ20101958

hPAR2 (human proteinase-activated receptor-2) is a member of the novel family of proteolytically activated GPCRs (G-protein-coupled receptors) termed PARs (proteinase-activated receptors). Previous pharmacological studies have found that activation o... Read More about Palmitoylation of human proteinase-activated receptor-2 differentially regulates receptor-triggered ERK1/2 activation, calcium signalling and endocytosis.

N-linked glycosylation regulates human proteinase-activated receptor-1 cell surface expression and disarming via neutrophil proteinases and thermolysin (2011)
Journal Article
Xiao, Y. P., Morice, A. H., Compton, S. J., & Sadofsky, L. (2011). N-linked glycosylation regulates human proteinase-activated receptor-1 cell surface expression and disarming via neutrophil proteinases and thermolysin. Journal of Biological Chemistry, 286(26), 22991-23002. https://doi.org/10.1074/jbc.M110.204271

Proteinase-activated receptor 1 (PAR1) induces activation of platelet and vascular cells after proteolytic cleavage of its extracellular N terminus by thrombin. In pathological situations, other proteinases may be generated in the circulation and mig... Read More about N-linked glycosylation regulates human proteinase-activated receptor-1 cell surface expression and disarming via neutrophil proteinases and thermolysin.