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  1. AU="Christopher D. Pascoe"
  2. AU="Imura, Satoshi"
  3. AU="Sutherland, Kate D"
  4. AU="Xiao Jian"
  5. AU="Littler, Dene R." AU="Littler, Dene R."
  6. AU="Yoo, Byeongjun"

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  1. Article ; Online: Characterization of sex-related differences in allergen house dust mite-challenged airway inflammation, in two different strains of mice

    Dina H. D. Mostafa / Mahadevappa Hemshekhar / Hadeesha Piyadasa / Anthony Altieri / Andrew J. Halayko / Christopher D. Pascoe / Neeloffer Mookherjee

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 12

    Abstract: Abstract Biological sex impacts disease prevalence, severity and response to therapy in asthma, however preclinical studies often use only one sex in murine models. Here, we detail sex-related differences in immune responses using a house dust mite (HDM)- ...

    Abstract Abstract Biological sex impacts disease prevalence, severity and response to therapy in asthma, however preclinical studies often use only one sex in murine models. Here, we detail sex-related differences in immune responses using a house dust mite (HDM)-challenge model of acute airway inflammation, in adult mice of two different strains (BALB/c and C57BL/6NJ). Female and male mice were challenged (intranasally) with HDM extract (~ 25 μg) for 2 weeks (N = 10 per group). Increase in serum HDM-specific IgE showed a female bias, which was statistically significant in BALB/c mice. We compared naïve and HDM-challenged mice to define immune responses in the lungs by assessing leukocyte accumulation in the bronchoalveolar lavage fluid (BALF), and profiling the abundance of 29 different cytokines in BALF and lung tissue lysates. Our results demonstrate specific sex-related and strain-dependent differences in airway inflammation. For example, HDM-driven accumulation of neutrophils, eosinophils and macrophages were significantly higher in females compared to males, in BALB/c mice. In contrast, HDM-mediated eosinophil accumulation was higher in males compared to females, in C57BL/6NJ mice. Differences in lung cytokine profiles indicated that HDM drives a T-helper (Th)17-biased response with higher IL-17 levels in female BALB/c mice compared to males, whereas female C57BL/6NJ mice elicit a mixed Th1/Th2-skewed response. Male mice of both strains showed higher levels of specific Th2-skewed cytokines, such as IL-21, IL-25 and IL-9, in response to HDM. Overall, this study details sex dimorphism in HDM-mediated airway inflammation in mice, which will be a valuable resource for preclinical studies in allergic airway inflammation and asthma.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Temporal and Spatial Patterns of Inflammation and Tissue Injury in Patients with Postoperative Respiratory Failure after Lung Resection Surgery

    Jay Kormish / Tejas Ghuman / Richard Y. Liu / Sadeesh K. Srinathan / Lawrence Tan / Kristen Graham / Stephanie Enns / Gordon Buduhan / Andrew J. Halayko / Christopher D. Pascoe / Biniam Kidane

    International Journal of Molecular Sciences, Vol 24, Iss 10051, p

    A Nested Case–Control Study

    2023  Volume 10051

    Abstract: Thoracic surgeries involving resection of lung tissue pose a risk of severe postoperative pulmonary complications, including acute respiratory distress syndrome (ARDS) and respiratory failure. Lung resections require one-lung ventilation (OLV) and, thus, ...

    Abstract Thoracic surgeries involving resection of lung tissue pose a risk of severe postoperative pulmonary complications, including acute respiratory distress syndrome (ARDS) and respiratory failure. Lung resections require one-lung ventilation (OLV) and, thus, are at higher risk of ventilator-induced lung injury (VILI) attributable to barotrauma and volutrauma in the one ventilated lung, as well as hypoxemia and reperfusion injury on the operated lung. Further, we also aimed to assess the differences in localized and systemic markers of tissue injury/inflammation in those who developed respiratory failure after lung surgery versus matched controls who did not develop respiratory failure. We aimed to assess the different inflammatory/injury marker patterns induced in the operated and ventilated lung and how this compared to the systemic circulating inflammatory/injury marker pattern. A case–control study nested within a prospective cohort study was performed. Patients with postoperative respiratory failure after lung surgery ( n = 5) were matched with control patients ( n = 6) who did not develop postoperative respiratory failure. Biospecimens (arterial plasma, bronchoalveolar lavage separately from ventilated and operated lungs) were obtained from patients undergoing lung surgery at two timepoints: (1) just prior to initiation of OLV and (2) after lung resection was completed and OLV stopped. Multiplex electrochemiluminescent immunoassays were performed for these biospecimen. We quantified 50 protein biomarkers of inflammation and tissue injury and identified significant differences between those who did and did not develop postoperative respiratory failure. The three biospecimen types also display unique biomarker patterns.
    Keywords one-lung ventilation (OLV) ; acute lung injury (ALI) ; ventilation-induced lung injury (VILI) ; acute respiratory distress syndrome (ARDS) ; postoperative pulmonary complications (PPCs) ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Integrating Proteomes for Lung Tissues and Lavage Reveals Pathways That Link Responses in Allergen-Challenged Mice

    Thomas H. Mahood / Christopher D. Pascoe / Tobias K. Karakach / Aruni Jha / Sujata Basu / Peyman Ezzati / Victor Spicer / Neeloffer Mookherjee / Andrew J. Halayko

    ACS Omega, Vol 6, Iss 2, Pp 1171-

    2021  Volume 1189

    Keywords Chemistry ; QD1-999
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher American Chemical Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics.

    Sonia R Rosner / Christopher D Pascoe / Elizabeth Blankman / Christopher C Jensen / Ramaswamy Krishnan / Alan L James / John G Elliot / Francis H Green / Jeffrey C Liu / Chun Y Seow / Jin-Ah Park / Mary C Beckerle / Peter D Paré / Jeffrey J Fredberg / Mark A Smith

    PLoS ONE, Vol 12, Iss 3, p e

    2017  Volume 0171728

    Abstract: Bronchospasm induced in non-asthmatic human subjects can be easily reversed by a deep inspiration (DI) whereas bronchospasm that occurs spontaneously in asthmatic subjects cannot. This physiological effect of a DI has been attributed to the manner in ... ...

    Abstract Bronchospasm induced in non-asthmatic human subjects can be easily reversed by a deep inspiration (DI) whereas bronchospasm that occurs spontaneously in asthmatic subjects cannot. This physiological effect of a DI has been attributed to the manner in which a DI causes airway smooth muscle (ASM) cells to stretch, but underlying molecular mechanisms-and their failure in asthma-remain obscure. Using cells and tissues from wild type and zyxin-/- mice we report responses to a transient stretch of physiologic magnitude and duration. At the level of the cytoskeleton, zyxin facilitated repair at sites of stress fiber fragmentation. At the level of the isolated ASM cell, zyxin facilitated recovery of contractile force. Finally, at the level of the small airway embedded with a precision cut lung slice, zyxin slowed airway dilation. Thus, at each level zyxin stabilized ASM structure and contractile properties at current muscle length. Furthermore, when we examined tissue samples from humans who died as the result of an asthma attack, we found increased accumulation of zyxin compared with non-asthmatics and asthmatics who died of other causes. Together, these data suggest a biophysical role for zyxin in fatal asthma.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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