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  1. Article ; Online: LKB1 depletion-mediated epithelial–mesenchymal transition induces fibroblast activation in lung fibrosis

    Zijian Xu / Elizabeth R. Davies / Liudi Yao / Yilu Zhou / Juanjuan Li / Aiman Alzetani / Ben G. Marshall / David Hancock / Tim Wallis / Julian Downward / Rob M. Ewing / Donna E. Davies / Mark G. Jones / Yihua Wang

    Genes and Diseases, Vol 11, Iss 3, Pp 101065- (2024)

    2024  

    Abstract: The factors that determine fibrosis progression or normal tissue repair are largely unknown. We previously demonstrated that autophagy inhibition-mediated epithelial–mesenchymal transition (EMT) in human alveolar epithelial type II (ATII) cells augments ... ...

    Abstract The factors that determine fibrosis progression or normal tissue repair are largely unknown. We previously demonstrated that autophagy inhibition-mediated epithelial–mesenchymal transition (EMT) in human alveolar epithelial type II (ATII) cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine signaling. Here, we report that liver kinase B1 (LKB1) inactivation in ATII cells inhibits autophagy and induces EMT as a consequence. In IPF lungs, this is caused by the down-regulation of CAB39L, a key subunit within the LKB1 complex. 3D co-cultures of ATII cells and MRC5 lung fibroblasts coupled with RNA sequencing (RNA-seq) confirmed that paracrine signaling between LKB1-depleted ATII cells and fibroblasts augmented myofibroblast differentiation. Together, these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATII cells and contribute to fibrosis via aberrant epithelial–fibroblast crosstalk.
    Keywords LKB1 ; CAB39L ; EMT ; Crosstalk ; Pulmonary fibrosis ; Medicine (General) ; R5-920 ; Genetics ; QH426-470
    Subject code 571
    Language English
    Publishing date 2024-05-01T00:00:00Z
    Publisher KeAi Communications Co., Ltd.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article: Transient characteristics of fine powder flows within fluidized dense phase pneumatic conveying systems

    Alkassar, Yassin / Mark G. Jones / Niranjana Behera / R.K. Pandey / Vijay K. Agarwal

    Elsevier B.V. Powder technology. 2019 Feb. 01, v. 343

    2019  

    Abstract: The objective of this paper is to report the experimental findings related to the pressure fluctuations in the fluidized dense phase pneumatic conveying of fine powders in the pipeline. Investigation has also been carried out to understand the relation ... ...

    Abstract The objective of this paper is to report the experimental findings related to the pressure fluctuations in the fluidized dense phase pneumatic conveying of fine powders in the pipeline. Investigation has also been carried out to understand the relation between pressure pulse characteristics and specific power consumption and pneumatic conveying parameters. In addition, the transition in mode of flow along the downstream of flow of fine powders has been assessed and discussed. The wavelet analysis (Daubechies db4 wavelet) of signals of air pulses revealed that the moving bed flow possesses the transient feature and pulsatile phenomenon characterized by multiple amplitudes and random frequencies. Variations of pulse structures along the length of pipeline have been observed due to occurring of frequent aeration and de-aeration of dunes during the conveying. Substantial variations in pulse structures have also been found with different types of bulk materials. Pulse velocities of air between two data points are found higher at high solid loading ratios leading to low voidage in case of dense phase flow.
    Keywords aeration ; air ; conveyors ; dunes ; energy use and consumption ; powders ; wavelet
    Language English
    Dates of publication 2019-0201
    Size p. 629-643.
    Publishing place Elsevier B.V.
    Document type Article
    ISSN 0032-5910
    DOI 10.1016/j.powtec.2018.11.081
    Database NAL-Catalogue (AGRICOLA)

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  3. Article: A model of solids friction factor for fluidized dense phase pneumatic conveying

    Behera, Niranjana / Mark G. Jones / Vijay K. Agarwal

    Powder technology. 2015 Nov., v. 284

    2015  

    Abstract: Solids friction factor is a parameter required for predicting the pressure drop in a process of pneumatic conveying. It depends upon a number of non-dimensional parameters. In this paper, experimental data for a 2m long section of a 173m long pipeline ... ...

    Abstract Solids friction factor is a parameter required for predicting the pressure drop in a process of pneumatic conveying. It depends upon a number of non-dimensional parameters. In this paper, experimental data for a 2m long section of a 173m long pipeline has been used to develop a mathematical model for solids friction factor. The model predicts the pressure drop with a low error margin for the 2m long pipeline. Although the model has been developed for a 2m long straight pipeline with fly ash as the conveying material, it has also been scaled-up for a 173m long straight pipeline. By scaling-up, the predicted pressure drop lies within an acceptable error margin. Since the model seems to be having less dependence upon the parameter of particle density, it predicts the pressure drop with less error margin for the experimental data of other conveying materials such as alumina and cement. The model shows high error in predicting pressure drop for the experimental data for a different pipeline configuration.
    Keywords aluminum oxide ; cement ; fly ash ; friction ; mathematical models ; powders ; prediction
    Language English
    Dates of publication 2015-11
    Size p. 403-410.
    Publishing place Elsevier B.V.
    Document type Article
    ISSN 0032-5910
    DOI 10.1016/j.powtec.2015.07.010
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Quantitative Proteomic Analysis in Alveolar Type II Cells Reveals the Different Capacities of RAS and TGF-β to Induce Epithelial–Mesenchymal Transition

    Yilu Zhou / Charlotte Hill / Liudi Yao / Juanjuan Li / David Hancock / Julian Downward / Mark G. Jones / Donna E. Davies / Rob M. Ewing / Paul Skipp / Yihua Wang

    Frontiers in Molecular Biosciences, Vol

    2021  Volume 8

    Abstract: Alveolar type II (ATII) epithelial cells function as stem cells, contributing to alveolar renewal, repair and cancer. Therefore, they are a highly relevant model for studying a number of lung diseases, including acute injury, fibrosis and cancer, in ... ...

    Abstract Alveolar type II (ATII) epithelial cells function as stem cells, contributing to alveolar renewal, repair and cancer. Therefore, they are a highly relevant model for studying a number of lung diseases, including acute injury, fibrosis and cancer, in which signals transduced by RAS and transforming growth factor (TGF)-β play critical roles. To identify downstream molecular events following RAS and/or TGF-β activation, we performed proteomic analysis using a quantitative label-free approach (LC-HDMSE) to provide in-depth proteome coverage and estimates of protein concentration in absolute amounts. Data are available via ProteomeXchange with identifier PXD023720. We chose ATIIER:KRASV12 as an experimental cell line in which RAS is activated by adding 4-hydroxytamoxifen (4-OHT). Proteomic analysis of ATII cells treated with 4-OHT or TGF-β demonstrated that RAS activation induces an epithelial–mesenchymal transition (EMT) signature. In contrast, under the same conditions, activation of TGF-β signaling alone only induces a partial EMT. EMT is a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell–cell adhesion to gain migratory properties, and is involved in embryonic development, wound healing, fibrosis and cancer metastasis. Thus, these results could help to focus research on the identification of processes that are potentially driving EMT-related human disease.
    Keywords epithelial-mesenchymal transition (EMT) ; RAS ; TGF-β ; lung disease ; fibrosis ; proteomics ; Biology (General) ; QH301-705.5
    Subject code 610 ; 500
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Deconvolution of RNA-Seq Analysis of Hyperbaric Oxygen-Treated Mice Lungs Reveals Mesenchymal Cell Subtype Changes

    Yuan Yuan / Yilu Zhou / Yali Li / Charlotte Hill / Rob M. Ewing / Mark G. Jones / Donna E. Davies / Zhenglin Jiang / Yihua Wang

    International Journal of Molecular Sciences, Vol 21, Iss 4, p

    2020  Volume 1371

    Abstract: Hyperbaric oxygen (HBO) is widely applied to treat several hypoxia-related diseases. Previous studies have focused on the immediate effect of HBO-exposure induced oxidative stress on the lungs, but knowledge regarding the chronic effects from repetitive ... ...

    Abstract Hyperbaric oxygen (HBO) is widely applied to treat several hypoxia-related diseases. Previous studies have focused on the immediate effect of HBO-exposure induced oxidative stress on the lungs, but knowledge regarding the chronic effects from repetitive HBO exposure is limited, especially at the gene expression level. We found that repetitive HBO exposure did not alter the morphology of murine lungs. However, by deconvolution of RNA-seq from those mice lungs using CIBERSORTx and the expression profile matrices of 8 mesenchymal cell subtypes obtained from bleomycin-treated mouse lungs, we identify several mesenchymal cell subtype changes. These include increases in Col13a1 matrix fibroblasts, mesenchymal progenitors and mesothelial cell populations and decreases in lipofibroblasts, endothelial and Pdgfrb high cell populations. Our data suggest that repetitive HBO exposure may affect biological processes in the lungs such as response to wounding, extracellular matrix, vasculature development and immune response.
    Keywords hyperbaric oxygen ; lung ; rna-seq ; cibersortx ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 612
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Delineating associations of progressive pleuroparenchymal fibroelastosis in patients with pulmonary fibrosis

    Eyjolfur Gudmundsson / An Zhao / Nesrin Mogulkoc / Frouke van Beek / Tinne Goos / Christopher J. Brereton / Marcel Veltkamp / Robert Chapman / Hendrik W. van Es / Helen Garthwaite / Bahareh Gholipour / Melissa Heightman / Arjun Nair / Katarina Pontoppidan / Recep Savas / Asia Ahmed / Marie Vermant / Omer Unat / Alex Procter /
    Laurens De Sadeleer / Emma Denneny / Timothy Wallis / Mark Duncan / Magali Taylor / Stijn Verleden / Sam M. Janes / Daniel C. Alexander / Athol U. Wells / Joanna Porter / Mark G. Jones / Iain Stewart / Coline H.M. van Moorsel / Wim Wuyts / Joseph Jacob

    ERJ Open Research, Vol 9, Iss

    2023  Volume 2

    Abstract: Background Computer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in ... ...

    Abstract Background Computer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in computer-quantified PPFE-like lesions in IPF and fibrotic hypersensitivity pneumonitis (FHP). Methods Two CT scans 6–36 months apart were retrospectively examined in one IPF (n=414) and one FHP population (n=98). Annualised change in computerised upper-zone pleural surface area comprising radiological PPFE-like lesions (Δ-PPFE) was calculated. Δ-PPFE >1.25% defined progressive PPFE above scan noise. Mixed-effects models evaluated Δ-PPFE against change in visual CT interstitial lung disease (ILD) extent and annualised forced vital capacity (FVC) decline. Multivariable models were adjusted for age, sex, smoking history, baseline emphysema presence, antifibrotic use and diffusion capacity of the lung for carbon monoxide. Mortality analyses further adjusted for baseline presence of clinically important PPFE-like lesions and ILD change. Results Δ-PPFE associated weakly with ILD and FVC change. 22–26% of IPF and FHP cohorts demonstrated progressive PPFE-like lesions which independently associated with mortality in the IPF cohort (hazard ratio 1.25, 95% CI 1.16–1.34, p<0.0001) and the FHP cohort (hazard ratio 1.16, 95% CI 1.00–1.35, p=0.045). Interpretation Progression of PPFE-like lesions independently associates with mortality in IPF and FHP but does not associate strongly with measures of fibrosis progression.
    Keywords Medicine ; R
    Subject code 310
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher European Respiratory Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Time taken from primary care referral to a specialist centre diagnosis of idiopathic pulmonary fibrosis

    Christopher J. Brereton / Timothy Wallis / Michelle Casey / Lynn Fox / Katarina Pontopiddan / Diane Laws / Jennifer Graves / Vanessa Titmuss / Sarah Kearney / Sian Evans / Alison Grove / Samreen Hamid / Luca Richeldi / Katherine M.A. O'Reilly / Sophie V. Fletcher / Mark G. Jones

    ERJ Open Research, Vol 6, Iss

    an opportunity to improve patient outcomes?

    2020  Volume 2

    Keywords Medicine ; R
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher European Respiratory Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Pseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis

    Christopher J Brereton / Liudi Yao / Elizabeth R Davies / Yilu Zhou / Milica Vukmirovic / Joseph A Bell / Siyuan Wang / Robert A Ridley / Lareb SN Dean / Orestis G Andriotis / Franco Conforti / Lennart Brewitz / Soran Mohammed / Timothy Wallis / Ali Tavassoli / Rob M Ewing / Aiman Alzetani / Benjamin G Marshall / Sophie V Fletcher /
    Philipp J Thurner / Aurelie Fabre / Naftali Kaminski / Luca Richeldi / Atul Bhaskar / Christopher J Schofield / Matthew Loxham / Donna E Davies / Yihua Wang / Mark G Jones

    eLife, Vol

    2022  Volume 11

    Abstract: Extracellular matrix (ECM) stiffening with downstream activation of mechanosensitive pathways is strongly implicated in fibrosis. We previously reported that altered collagen nanoarchitecture is a key determinant of pathogenetic ECM structure-function in ...

    Abstract Extracellular matrix (ECM) stiffening with downstream activation of mechanosensitive pathways is strongly implicated in fibrosis. We previously reported that altered collagen nanoarchitecture is a key determinant of pathogenetic ECM structure-function in human fibrosis (Jones et al., 2018). Here, through human tissue, bioinformatic and ex vivo studies we provide evidence that hypoxia-inducible factor (HIF) pathway activation is a critical pathway for this process regardless of the oxygen status (pseudohypoxia). Whilst TGFβ increased the rate of fibrillar collagen synthesis, HIF pathway activation was required to dysregulate post-translational modification of fibrillar collagen, promoting pyridinoline cross-linking, altering collagen nanostructure, and increasing tissue stiffness. In vitro, knockdown of Factor Inhibiting HIF (FIH), which modulates HIF activity, or oxidative stress caused pseudohypoxic HIF activation in the normal fibroblasts. By contrast, endogenous FIH activity was reduced in fibroblasts from patients with lung fibrosis in association with significantly increased normoxic HIF pathway activation. In human lung fibrosis tissue, HIF-mediated signalling was increased at sites of active fibrogenesis whilst subpopulations of human lung fibrosis mesenchymal cells had increases in both HIF and oxidative stress scores. Our data demonstrate that oxidative stress can drive pseudohypoxic HIF pathway activation which is a critical regulator of pathogenetic collagen structure-function in fibrosis.
    Keywords fibrosis ; Collagen ; Lung ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Mortality in combined pulmonary fibrosis and emphysema patients is determined by the sum of pulmonary fibrosis and emphysema

    An Zhao / Eyjolfur Gudmundsson / Nesrin Mogulkoc / Mark G. Jones / Coline van Moorsel / Tamera J. Corte / Chiara Romei / Recep Savas / Christopher J. Brereton / Hendrik W. van Es / Helen Jo / Annalisa De Liperi / Omer Unat / Katarina Pontoppidan / Frouke van Beek / Marcel Veltkamp / Peter Hopkins / Yuben Moodley / Alessandro Taliani /
    Laura Tavanti / Bahareh Gholipour / Arjun Nair / Sam Janes / Iain Stewart / David Barber / Daniel C. Alexander / Athol U. Wells / Joseph Jacob

    ERJ Open Research, Vol 7, Iss

    2021  Volume 3

    Keywords Medicine ; R
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher European Respiratory Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Safety and tolerability of nintedanib for the treatment of idiopathic pulmonary fibrosis in routine UK clinical practice

    Sophie V. Fletcher / Mark G. Jones / Elizabeth A. Renzoni / Helen Parfrey / Rachel K. Hoyles / Katherine Spinks / Maria Kokosi / Apollinaris Kwok / Chris Warburton / Vanessa Titmuss / Muhunthan Thillai / Nicola Simler / Toby M. Maher / Christopher J. Brereton / Felix Chua / Athol U. Wells / Luca Richeldi / Lisa G. Spencer

    ERJ Open Research, Vol 4, Iss

    2018  Volume 4

    Keywords Medicine ; R
    Language English
    Publishing date 2018-10-01T00:00:00Z
    Publisher European Respiratory Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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