ORCID Profile
0000-0002-0659-559X
Current Organisations
The Ohio State University
,
Queensland Health
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Publisher: Proceedings of the National Academy of Sciences
Date: 19-05-2022
Abstract: We report the discovery of fundamental roles for the noncanonical inflammasome molecule Caspase-4/11 in promoting pathological inflammatory and prothrombotic pathways in severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) infections. Our work demonstrates that Caspase-11 has a broader role in immune responses beyond its previously appreciated effects in bacterial infections. Further, we show that Caspase-11–deficient mice infected with SARS–CoV-2 fare significantly better in terms of overall illness, lung inflammation, and thrombosis than wild-type (WT) mice, thus implicating Caspase-11 as a new therapeutic target for preventing or treating COVID-19.
Publisher: Public Library of Science (PLoS)
Date: 29-04-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2019
DOI: 10.1097/CCM.0000000000003547
Abstract: To evaluate the effect of ICU diaries on posttraumatic stress disorder symptoms in ICU survivors and their relatives. Secondary objectives were to determine the effect on anxiety, depression, and health-related quality of life in patients and their relatives. We searched online databases, trial registries, and references of relevant articles. Studies were included if there was an ICU diary intervention group which was compared with a group without a diary. Titles, abstracts, and full-text articles were reviewed independently by two authors. Data was abstracted using a structured template. Our search identified 1,790 articles and retained eight studies for inclusion in the analysis. Pooled results found no significant reduction in patients’ posttraumatic stress disorder symptoms with ICU diaries (risk ratio, 0.75 [0.3–1.73] p = 0.5 n = 3 studies) however, there was a significant improvement in patients’ anxiety (risk ratio, 0.32 [0.12, 0.86] p = 0.02 n = 2 studies) and depression (risk ratio, 0.39 [0.17–0.87] p = 0.02 n = 2 studies) symptoms. Two studies reported significant improvement in posttraumatic stress disorder symptoms of relatives of ICU survivors however, these results could not be pooled due to reporting differences. One study reported no significant improvement in either anxiety (risk ratio, 0.94 95% [0.66–1.33] p = 0.72) or depression (risk ratio, 0.98 95% [0.5–1.9] p = 0.95) in relatives. There was a significant improvement in health-related quality of life of patients with a mean increase in the Short Form-36 general health score by 11.46 (95% CI, 5.87–17.05 p ≤ 0.0001 n = 2 studies). No studies addressed health-related quality of life of relatives. ICU diaries decrease anxiety and depression and improve health-related quality of life, but not posttraumatic stress disorder among ICU survivors and may result in less posttraumatic stress disorder among relatives of ICU patients. Multicenter trials with larger s le sizes are necessary to confirm these findings.
Publisher: American Physiological Society
Date: 02-2021
DOI: 10.1152/AJPLUNG.00452.2020
Abstract: Cigarette smoking is a risk factor for several lung diseases, including chronic obstructive pulmonary disease, cardiovascular disease, and lung cancer. The potential health effects of chronic use of electronic nicotine delivery systems (ENDS) is unclear. This study utilized fully differentiated primary normal human bronchial epithelial (NHBE) cultures in a repeat-dose exposure to evaluate and compare the effect of combustible cigarette and ENDS preparations. We show that 1-h daily exposure of NHBE cultures over a 10-day period to combustible cigarette whole smoke-conditioned media (WS-CM) increased expression of oxidative stress markers, cell proliferation, airway remodeling, and cellular transformation markers and decreased mucociliary function including ion channel function and airway surface liquid. Conversely, aerosol conditioned media (ACM) from ENDS with similar nicotine concentration (equivalent-nicotine units) as WS-CM and nicotine alone had no effect on those parameters. In conclusion, primary NHBE cultures in a repeat-dose exposure system represent a good model to assess the features of lung disease. This study also reveals that cigarette and ENDS preparations differentially elicit several key endpoints, some of which are potential biomarkers for lung cancer or chronic obstructive pulmonary disease (COPD).
Publisher: Springer Science and Business Media LLC
Date: 24-01-2019
DOI: 10.1038/S41598-018-36735-Z
Abstract: Robust in vitro lung models are required for risk assessment to measure key events leading to respiratory diseases. Primary normal human bronchial epithelial cells (NHBE) represent a good lung model but obtaining well-differentiated 3D cultures can be challenging. Here, we evaluated the ability to expand primary NHBE cells in different culture conditions while maintaining their 3D culture characteristics such as ciliated and goblet cells, and ion channel function. Differentiated cultures were optimally obtained with PneumaCult-Ex Plus (expansion medium)/PneumaCult-ALI (differentiation medium). Primary cells passaged up to four times maintained airway epithelial characteristics as evidenced by ciliated pseudostratified columnar epithelium with goblet cells, trans-epithelial electrical resistance (TEER) ( Ohms.cm 2 ), and cystic fibrosis transmembrane conductance regulator-mediated short-circuit currents ( µA/cm 2 ). No change in ciliary beat frequency (CBF) or airway surface liquid (ASL) meniscus length was observed up to passage six. For the first time, this study demonstrates that CFTR ion channel function and normal epithelial phenotypic characteristics are maintained in passaged primary NHBE cells. Furthermore, this study highlights the criticality of evaluating expansion and differentiation conditions for achieving optimal phenotypic and functional endpoints (CBF, ASL, ion channel function, presence of differentiated cells, TEER) when developing in vitro lung models.
Publisher: American Physiological Society
Date: 08-2019
DOI: 10.1152/AJPLUNG.00096.2019
Abstract: Cigarette smoking is known to disrupt the normal mucociliary function of the lungs, whereas the effect of electronic nicotine delivery systems (ENDS) is not completely understood. This study aimed to compare the effects of acute exposure of primary normal human bronchial epithelial (NHBE) 3D cultures at air-liquid interface to combustible cigarette and ENDS preparations on mucociliary function, including ion channel function, ciliary beat frequency (CBF), and airway surface liquid (ASL) height. Differentiated NHBE cultures were exposed to whole smoke-conditioned media (WS-CM) or total particulate matter (TPM) prepared from 3R4F reference cigarettes, whole aerosol-conditioned media (ACM) or e-TPM generated from a marketed ENDS product, or nicotine alone. We found that a dose of 7 μg/mL equi-nicotine units of cigarette TPM and WS-CM significantly decreased cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial sodium channel (ENaC) function, which regulates fluid homeostasis in the lung. Conversely, higher (56 µg/mL) equi-nicotine units of ENDS preparations or nicotine alone had no effect on CFTR and ENaC function. Despite a significant decrease in ion channel function, cigarette smoke preparations did not alter CBF and ASL. Similarly, ENDS preparations and nicotine alone had no effect on ASL and CBF. This study demonstrates that acute exposures of cigarette smoke preparations exert a notable inhibitory effect on CFTR and ENaC function compared with ENDS preparations. In summary, the functional assays described herein are potentially useful for tobacco product evaluations.
Publisher: Elsevier BV
Date: 2021
Publisher: Future Medicine Ltd
Date: 04-2015
DOI: 10.2217/FMB.14.153
Abstract: ABSTRACT Streptococcus pneumoniae is a potentially deadly human pathogen associated with high morbidity, mortality and global economic burden. The universally used bacterial genotyping methods are multilocus sequence typing and pulsed field gel electrophoresis. However, another highly discriminatory, rapid and less expensive genotyping technique, multilocus variable number of tandem repeat analysis (MLVA), has been developed. Unfortunately, no universal MLVA protocol exists, and some MLVA protocols do not lify certain loci for all pneumococcal serotypes, leaving genotyping profiles incomplete. A number of other genotyping or characterization methods have been developed and will be discussed. This review examines the various protocols for genotyping S. pneumoniae and highlights the current direction technology and research is heading to understand this bacterium.
Publisher: American Physiological Society
Date: 05-2023
DOI: 10.1152/AJPLUNG.00191.2022
Abstract: Respiratory viruses, such as influenza, decrease airway cilia function and expression, which leads to reduced mucociliary clearance and inhibited overall immune defense. Ubiquitination is a posttranslational modification using E3 ligases, which plays a role in the assembly and disassembly of cilia. We examined the role of membrane-associated RING-CH (MARCH) family of E3 ligases during influenza infection and determined that MARCH10, specifically expressed in ciliated epithelial cells, is significantly decreased during influenza infection in mice, human lung epithelial cells, and human lung tissue. Cellular depletion of MARCH10 in differentiated human bronchial epithelial cells (HBECs) using CRISPR/Cas9 showed a decrease in ciliary beat frequency. Furthermore, MARCH10 cellular knockdown in combination with influenza infection selectively decreased immunoreactive levels of the ciliary component, dynein axonemal intermediate chain 1. Cellular overexpression of MARCH10 significantly decreased influenza hemagglutinin protein levels in the differentiated HBECs and knockdown of MARCH10 increased IL-1β cytokine expression, whereas overexpression had the reciprocal effect. These findings suggest that MARCH10 may have a protective role in airway pulmonary host defense and innate immunity during influenza infection.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.BBAGEN.2018.06.008
Abstract: Marijuana consumption is on the rise in the US but the health benefits of cannabis smoking are controversial and the impact of cannabis components on lung homeostasis is not well-understood. Lung function requires a fine regulation of the ion channel CFTR, which is responsible for fluid homeostasis and mucocilliary clearance. The goal of this study was to assess the effect that exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive substance present in marijuana, has on CFTR expression and function. Cultures of human bronchial epithelial cell line 16HBE14o- and primary human airway epithelial cells were exposed to THC. The expression of CFTR protein was determined by immunoblotting and CFTR function was measured using Ussing chambers. We also used specific pharmacological inhibitors of EGFR and ERK to determine the role of this pathway in THC-induced regulation of CFTR. THC decreased CFTR protein expression in primary human bronchial epithelial cells. This decrease was associated with reduced CFTR-mediated short-circuit currents. THC also induced activation of the ERK MAPK pathway via activation of EGFR. Inhibition of EGFR or MEK/ERK prevented THC-induced down regulation of CFTR protein expression. THC negatively regulates CFTR and this is mediated through the EGFR/ERK axis. This study provides the first evidence that THC present in marijuana reduces the expression and function of CFTR in airway epithelial cells.
No related grants have been discovered for Rachael E Rayner.