ORCID Profile
0000-0002-8178-5641
Current Organisations
Curtin University
,
University of Tasmania
,
Murdoch University
,
University of Western Australia
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Wiley
Date: 20-03-2022
DOI: 10.1111/RESP.14246
Abstract: Coal mine dust has a complex and heterogeneous chemical composition. It has been suggested that coal particle chemistry plays a critical role in determining the pathogenesis of coal workers' pneumoconiosis (CWP). In this study, we aimed to establish the association between the detrimental cellular response and the chemical composition of coal particles. We sourced 19 real‐world coal s les. S les were crushed prior to use to minimize the impact of particle size on the response and to ensure the particles were respirable. Key chemical components and inorganic compounds were quantified in the coal s les. The cytotoxic, inflammatory and pro‐fibrotic responses in epithelial cells, macrophages and fibroblasts were assessed following 24 h of exposure to coal particles. Principal component analysis (PCA) and stepwise regression were used to determine which chemical components of the coal particles were associated with the cell response. The cytotoxic, inflammatory and pro‐fibrotic response varied considerably between coal s les. There was a high level of collinearity in the cell responses and between the chemical compounds within the coal s les. PCA identified three factors that explained 75% of the variance in the cell response. Stepwise multiple regression analysis identified K 2 O ( p .001) and Fe 2 O 3 ( p = 0.011) as significant predictors of cytotoxicity and cytokine production, respectively. Our data clearly demonstrate that the detrimental cellular effects of exposure to coal mine dusts are highly dependent on particle chemistry. This has implications for understanding the pathogenesis of CWP.
Publisher: American Physiological Society
Date: 10-2020
DOI: 10.1152/JAPPLPHYSIOL.00097.2020
Abstract: This study provides novel insights into the regional response to mechanical ventilation in the setting of acid-induced lung injury and highlights the complex interaction between tidal stretch and low end-expiratory lung volumes both of which caused altered regulation of different injury pathways.
Publisher: Springer Science and Business Media LLC
Date: 04-2011
Publisher: American Physiological Society
Date: 10-2023
DOI: 10.1152/JAPPLPHYSIOL.00693.2022
Abstract: How the heterogeneous distribution of lung volumes changes in response to different mechanical ventilation (MV) strategies is unclear. Using our well-developed four-dimensional computed tomography (4DCT) high resolution imaging technique, we aimed to assess the effect of different MV strategies on the distribution and heterogeneity of regional lung volumes. Healthy adult female BALB/c mice received either 2h of "injurious" MV (n=6, HPZP) with a peak inspiratory pressure (PIP) of 20cmH 2 O and zero positive end-expiratory pressure (PEEP), or 2h of "protective" MV (n=8, LPP) with PIP=12cmH 2 O and PEEP=2cmH 2 O. 4DCT images were obtained at baseline (0h) and after 2h of MV. Tidal volume (Vt) and end-expiratory lung volume (EEV) were measured throughout the whole lung on a voxel-by-voxel basis. Heterogeneity of ventilation was determined by the coefficient of variation (COV) of Vt and EEV. Our data showed that MV had minimal impact on global Vt but decreased EEV in the HPZP group ( p .05). Both ventilation modes decreased the COV of Vt (39.4% for HPZP and 9.7% for LPP) but increased the COV in EEV (36.4% for HPZP and 29.2% for LPP). This was consistent with the redistribution index which was significantly higher in the HVZP group than the LPP group ( p .001). We concluded that regional assessment of the change in EEV showed different patterns in progression between LPP and HPZP strategies. Both ventilation strategies decreased heterogeneity in Vt after 2h of MV but increased heterogeneity in EEV. Further work is required to determine the link between these effects and ventilator induced lung injury.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.EXPPARA.2013.06.014
Abstract: Cryptosporidium is an enteric protozoan parasite that is resistant to inactivation by commonly used drinking water disinfectants. Between 2004 and 2010, it was responsible for 60% of all waterborne protozoan parasitic outbreaks reported worldwide. Most sporadic infections in humans and almost all outbreaks are caused by Cryptosporidium parvum and Cryptosporidium hominis. We report the development and validation of a quantitative qPCR assay using minor groove binder (MGB)-probes targeting a unique Cryptosporidium specific protein-coding gene, that directly detects, quantitates and identifies C. hominis and C. parvum in environmental and faecal s les. An internal lification control (IAC) was also developed and included in this assay. The qPCR assay was compared with an 18S nested PCR assay for sensitivity and specificity. The analytical sensitivity for the qPCR assay was 1 oocyst and 1-10 oocysts for the 18S assay. Evaluation of analytical specificity of the qPCR assay revealed no cross-reactions with other genera and detected all C. parvum and C. hominis isolates correctly. The diagnostic sensitivity and specificity of the qPCR was 100% compared to 96.9% and 98.4%, respectively for the 18S assay. The qPCR assay was also highly reproducible with RSD (relative standard deviation) values of 1.4-9.4%, when the assay was performed by four different technicians. When tested on water s les, the qPCR assay was more sensitive than the 18S assay, detecting positives in 37 of 138 water s les compared to 35 for the 18S locus. This qPCR assay should be a valuable tool for the detection and differentiation of C. hominis and C. parvum in both clinical and environmental s les.
Publisher: MDPI AG
Date: 09-01-2023
Abstract: Emerging evidence suggests that inhalation of particulate matter (PM) can have direct adverse effects on liver function. Early life is a time of particular vulnerability to the effects of air pollution. On that basis, we tested whether in utero exposure to residential PM has an impact on the developing liver. Pregnant mice (C57BL/6J) were intranasally administered 100 µg of PM s led from residential roof spaces (~5 mg/kg) on gestational days 13.5, 15.5, and 17.5. The pups were euthanized at two weeks of age, and liver tissue was collected to analyse hepatic metabolism (glycogen storage and lipid level), cellular responses (oxidative stress, inflammation, and fibrosis), and genotoxicity using a range of biochemical assays, histological staining, ELISA, and qPCR. We did not observe pronounced effects of environmentally s led PM on the developing liver when examining hepatic metabolism and cellular response. However, we did find evidence of liver genomic DNA damage in response to in utero exposure to PM. This effect varied depending on the PM s le. These data suggest that in utero exposure to real-world PM during mid-late pregnancy has limited impacts on post-natal liver development.
Publisher: Springer Science and Business Media LLC
Date: 2012
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.TVJL.2015.08.021
Abstract: Brachyspira hyodysenteriae is an anaerobic spirochaete that can induce swine dysentery (SD), a severe mucohaemorrhagic colitis in grower and fattener pigs. The aim of this study was to develop a serological ELISA for use as a screening method to detect evidence of herd infection. Bioinformatic analysis of the complete genome sequence of strain WA1 was used to identify genes predicted to encode outer membrane proteins. Twenty candidate genes were expressed in an Escherichia coli mediated system, and purified as histidine-tagged recombinant proteins. Selection of optimal antigens under different conditions was conducted using Western blot and ELISA with a range of pig sera from infected and uninfected pigs. From this analysis, three recombinant proteins were selected as being most suitable for use as antigens. These antigens then were tested under optimized conditions in an indirect ELISA detecting IgG2 using 1551 sera from healthy pigs at slaughter, comprising 896 from 18 herds considered to be free from SD and 655 from 12 infected herds. Using a cut-off value for positivity of the mean plus five standard deviations of the mean for the negative sera, the best overall results were obtained with the ELISA using antigen H114, which was 100% specific and 91.7% sensitive at detecting the reported status of the herds. This new ELISA should be a useful adjunct for detecting and monitoring the status of herds with respect to the presence of B. hyodysenteriae, and should prove useful for understanding the dynamics of infection in herds where the spirochaete is present.
Publisher: Springer Science and Business Media LLC
Date: 27-02-2018
Publisher: S. Karger AG
Date: 2012
DOI: 10.1159/000334828
Abstract: i Background: /i Conventional mechanical ventilator (CMV) breaths during high-frequency jet ventilation (HFJV) are advocated to recruit and stabilize alveoli. i Objectives: /i To establish if CMV breath duration delivered during HFJV influences gas exchange, lung mechanics and lung injury. i Methods: /i Preterm lambs at 128 days gestational age were studied. HFJV (7 Hz, PEEP 8 cm H sub /sub O, PIP sub HFJV /sub 40 cm H sub /sub O, FiO sub /sub 0.4) with superimposed CMV breaths (PIP sub CMV /sub 25 cm H sub /sub O, rate 5 breaths/min) was commenced after delivery and continued for 2 h. CMV breath inspiratory time ( i t /i sub I /sub ) was either 0.5 s (HFJV+CMV sub .5 /sub n = 8) or 2.0 s (HFJV+CMV sub .0 /sub n = 8). Age-matched unventilated controls (UVC) were included for comparison. i Results: /i Serial arterial blood gas analyses were performed. PIP sub HFJV /sub was adjusted to target a i P /i aCO sub /sub of 45–55 mm Hg. FiO sub /sub was adjusted to target SpO sub /sub 90–95%. Pressure-volume curves, broncho-alveolar lavage (BAL) and lung tissue s les were obtained postmortem. Gas exchange, ventilation parameters, static lung compliance and BAL inflammatory markers were not different between HFJV+CMV sub .5 /sub and HFJV+CMV sub .0 /sub . Both ventilation groups had higher BAL inflammatory markers and increased iNOS-positive cells on histology compared to UVC, whilst lung tissue IL-1β and IL-6 mRNA expression was higher in the HFJV+CMV sub .0 /sub group compared to the UVC group. i Conclusions: /i Preterm lambs were ventilated effectively with HFJV and 5 CMV breaths/min. CMV breath duration did not alter blood gas exchange, ventilation parameters, ex vivo static lung mechanics or markers of lung injury over a 2-hour study, although consistent trends towards increased inflammatory markers with the longer i t /i sub I /sub suggest greater risk of injury.
Publisher: Springer Science and Business Media LLC
Date: 15-02-2014
Abstract: Sustained inflations (SI) are advocated for the rapid establishment of FRC after birth in preterm and term infants requiring resuscitation. However, the most appropriate way to deliver a SI is poorly understood. We investigated whether a volume-limited SI improved the establishment of FRC and ventilation homogeneity and reduced lung inflammation/injury compared to a pressure-limited SI. 131 d gestation lambs were resuscitated with either: i) pressure-limited SI (PressSI: 0-40 cmH 2 O over 5 s, maintained until 20 s) or ii) volume-limited SI (VolSI: 0-15 mL/kg over 5 s, maintained until 20 s). Following the SI, all lambs were ventilated using volume-controlled ventilation (7 mL/kg tidal volume) for 15 min. Lung mechanics, regional ventilation distribution (electrical impedance tomography), cerebral tissue oxygenation index (near infrared spectroscopy), arterial pressures and blood gas values were recorded regularly. Pressure-volume curves were performed in-situ post-mortem and early markers of lung injury were assessed. Compared to a pressure-limited SI, a volume-limited SI had increased pressure variability but reduced volume variability. Each SI strategy achieved similar end-inflation lung volumes and regional ventilation homogeneity. Volume-limited SI increased heart-rate and arterial pressure faster than pressure-limited SI lambs, but no differences were observed after 30 s. Volume-limited SI had increased arterial-alveolar oxygen difference due to higher FiO 2 at 15 min (p = 0.01 and p = 0.02 respectively). No other inter-group differences in arterial or cerebral oxygenation, blood pressures or early markers of lung injury were evident. With the exception of inferior oxygenation, a sustained inflation targeting delivery to preterm lambs of 15 mL/kg volume by 5 s did not influence physiological variables or early markers of lung inflammation and injury at 15 min compared to a standard pressure-limited sustained inflation.
Publisher: Hindawi Limited
Date: 2017
DOI: 10.1155/2017/1379430
Abstract: Isoliquiritigenin (ISL), a natural antioxidant, has antitumor activity in different types of cancer cells . However the antitumor effect of ISL on human tongue squamous carcinoma cells (TSCC) is not clear. Here we aimed to investigate the effects of synthetic isoliquiritigenin (S-ISL) on TSCC and elucidate the underlying mechanisms. S-ISL was synthesized and elucidated from its nuclear magnetic resonance spectrum and examined using high performance liquid chromatography. The effects of S-ISL on TSCC cells (Tca8113) were evaluated in relation to cell proliferation, apoptosis and adhesion, migration, and invasion using sulforhodamine B assay, fluorescence microscopy technique, flow cytometry (FCM) analysis, and Boyden chamber assay. The associated regulatory mechanisms were examined using FCM and fluorescence microscopy for intracellular reactive oxygen species (ROS) generation, Gelatin zymography assay for matrix metalloproteinase (MMP) activities, and Western blot for apoptosis regulatory proteins (Bcl-2 and Bax). Our data indicated that S-ISL inhibited Tca8113 cell proliferation, adhesion, migration, and invasion while promoting the cell apoptosis. Such effects were accompanied by downregulation of Bcl-2 and upregulation of Bax, reduction of MMP-2 and MMP-9 activities, and decreased ROS production. We conclude that S-ISL is a promising agent targeting TSCC through multiple anticancer effects, regulated by its antioxidant mechanism.
Publisher: Wiley
Date: 08-02-2013
DOI: 10.1002/PPUL.22762
Abstract: The preterm diaphragm is structurally and functionally immature, potentially contributing to an increased risk of respiratory distress and failure. We investigated developmental changes in contractile function and susceptibility to fatigue of the costal diaphragm in the fetal lamb to understand factors contributing to the risk of developing diaphragm dysfunction and respiratory disorders. We hypothesized that the functional capacity of the diaphragm will vary with maturational stage as will its susceptibility to fatigue. Lambs were studied at 75, 100, 125, 145, 154, 168, and 200 days postconceptional age (term = 147 days). Lambs were euthanized (sodium pentobarbitone, 100 mg/kg) either at delivery or immediately prior to post-mortem for postnatal lambs. Contractile function was assessed on longitudinal strips of intact muscle fibers and the remaining tissue frozen in liquid nitrogen for analysis of myosin heavy chain (MHC) mRNA expression and protein content. Fetal development of diaphragm function was characterized by a significant increase in maximum specific force, increased susceptibility to fatigue, reduced twitch contraction times, and a progressive increase in MHCI and MHCII protein content. Postnatally, there was a progressive decrease in the susceptibility to fatigue that coincided with an increase in the MHC I:II protein ratio. These data indicate that the functional capacity of the diaphragm varies with maturational age and may be an important determinant of the susceptibility to preterm respiratory failure.
Publisher: Wiley
Date: 07-03-2012
DOI: 10.1002/AR.22436
Publisher: Public Library of Science (PLoS)
Date: 06-09-2013
Publisher: Elsevier BV
Date: 05-2009
DOI: 10.1016/J.VETMIC.2008.12.018
Abstract: Swine dysentery (SD) is a mucohaemorrhagic colitis of pigs resulting from infection of the large intestine with the anaerobic intestinal spirochaete Brachyspira hyodysenteriae. Whole-cell bacterin vaccines are available to help control SD, but their performance has been inconsistent. This study aimed to use a reverse vaccinology approach to identify B. hyodysenteriae proteins for use as recombinant vaccine components. Nineteen open reading frames (ORFs) predicted to encode potential vaccine candidate molecules were identified from in silico analysis of partial genomic sequence data. The distribution of these ORFs among strains of B. hyodysenteriae was investigated by PCR, and widely distributed ORFs were cloned. The products were screened with a panel of immune pig sera, and from these a subset of conserved, immunogenic proteins was selected. Mice immunized intramuscularly with these recombinant proteins developed specific systemic antibody responses to them, and their sera agglutinated B. hyodysenteriae cells in vitro. In a pilot experiment, eight pigs were vaccinated twice intramuscularly with a combination of four of the proteins. The pigs developed antibodies to the proteins, and following experimental challenge only one developed SD compared to five of nine non-vaccinated control pigs. Although these differences in incidence were not significant, they indicated a trend towards protection using the recombinant proteins as immunogens. This study demonstrates that the reverse vaccinology approach has considerable potential for use in developing novel recombinant vaccines for SD.
Publisher: Public Library of Science (PLoS)
Date: 28-03-2014
Publisher: American Physiological Society
Date: 04-2015
DOI: 10.1152/JAPPLPHYSIOL.00985.2014
Abstract: Support of the mechanically complex preterm lung needs to facilitate aeration while avoiding ventilation heterogeneities: whether to achieve this gradually or quickly remains unclear. We compared the effect of gradual vs. constant tidal inflations and a pressure-limited sustained inflation (SI) at birth on gas exchange, lung mechanics, gravity-dependent lung volume distribution, and lung injury in 131-day gestation preterm lambs. Lambs were resuscitated with either 1) a 20-s, 40-cmH 2 O pressure-limited SI (PressSI), 2) a gradual increase in tidal volume (Vt) over 5-min from 3 ml/kg to 7 ml/kg (IncrVt), or 3) 7 ml/kg Vt from birth. All lambs were subsequently ventilated for 15 min with 7 ml/kg Vt with the same end-expiratory pressure. Lung mechanics, gas exchange and spatial distribution of end-expiratory volume (EEV), and tidal ventilation (electrical impedance tomography) were recorded regularly. At 15 min, early mRNA tissue markers of lung injury were assessed. The IncrVt group resulted in greater tissue hysteresivity at 5 min ( P = 0.017 two-way ANOVA), higher alveolar-arterial oxygen difference from 10 min ( P 0.01), and least uniform gravity-dependent distribution of EEV. There were no other differences in lung mechanics between groups, and the PressSI and 7 ml/kg Vt groups behaved similarly throughout. EEV was more uniformly distributed, but Vt least so, in the PressSI group. There were no differences in mRNA markers of lung injury. A gradual increase in Vt from birth resulted in less recruitment of the gravity-dependent lung with worse oxygenation. There was no benefit of a SI at birth over mechanical ventilation with 7 ml/kg Vt.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 07-2020
Publisher: Public Library of Science (PLoS)
Date: 10-04-2015
Publisher: Wiley
Date: 26-08-2015
DOI: 10.1111/RESP.12615
Abstract: In utero infection may critically influence diaphragm development and predispose preterm infants to postnatal respiratory failure. We aimed to determine how frequency and gestational age (GA) at time of intra-amniotic (IA) lipopolysaccharide (LPS) exposure affects preterm diaphragm function. Pregnant ewes received IA injections of saline or 10-mg LPS at 7 days or 21 days or weekly injections 21, 14 and 7 days before delivery at 121-day GA. Foetal lambs were killed with pentobarbitone (150 mg/kg intravenous). Diaphragm contractile function was measured in vitro. Muscle fibre type, activation of protein synthesis and degradation pathways, pro-inflammatory signalling and oxidative stress were evaluated using immunofluorescence staining, RT-qPCR, ELISA, Western blotting and biochemical assay. In utero LPS exposure significantly impaired diaphragm contractile function. LPS exposure 7 days before delivery caused maximum specific twitch and tetanic forces 30% lower than controls. When the initial LPS exposure occurred 21 days before delivery maximum specific forces were 40% lower than controls. Earlier LPS exposure also prolonged twitch contraction time, increased fatigue resistance and elevated protein carbonyl content. Despite increased white blood cell counts and interleukin-6 mRNA expression following weekly LPS exposure, there were no significant differences in contractile properties between exposure 21 days before delivery and repeated LPS groups suggesting that frequency of inflammatory exposure does not influence the severity of contractile dysfunction. GA at time of initial LPS exposure, rather than frequency of exposure, determines the extent of inflammation-induced diaphragm dysfunction.
Publisher: Elsevier BV
Date: 05-2009
DOI: 10.1016/J.VETMIC.2008.12.020
Abstract: Anaerobic intestinal spirochaetes of the genus Brachyspira include several important pathogenic species, particularly those infecting pigs and chickens. In this study a multiplex-quantitative polymerase chain reaction (M-qPCR) assay was developed based on lification of a 198 base pair portion of the NADH oxidase gene, using TaqMan probes for detecting and quantifying the three main pathogenic species, B. hyodysenteriae, B. pilosicoli and B. intermedia. The specificity of the assay was validated using 130 spirochaete strains belonging to members of the seven officially named and two provisionally named Brachyspira species. The detection limit for all three targeted species was 1-10 viable cells and 10 fg DNA per reaction. Further detection limit testing was conducted on porcine and chicken faecal specimens that were spiked with spirochaete cells before DNA extraction. The assay could detect 10(2) to 10(3)cells per 0.2g of s le, giving an improved detection threshold compared to standard PCRs. The M-qPCR was further developed by incorporating a novel internal control (IC) that employed host cells as template DNA. This adaptation allowed monitoring of the quality of the extracted DNA and ensured that there was no inhibition of the PCR reaction. Use of the IC further improved the detection limits of the assay and increased confidence in being able to detect low numbers of pathogens in faecal s les. Taken together, the results indicate that the new M-qPCR assay is a valuable tool for detecting and quantifying low numbers of pathogenic intestinal spirochaetes in the faeces of pigs and chickens, and potentially other species.
Publisher: SAGE Publications
Date: 04-07-2013
Abstract: Structural and functional immaturity of the preterm diaphragm predisposes the preterm baby to respiratory muscle weakness and consequent impaired efficiency of spontaneous respiration, potentially necessitating mechanical respiratory support. The ontogeny of several proteolytic genes (calpain, caspase-3, MAFbx and MuRF-1) changes dynamically with gestational and early postnatal development. We aimed to define the molecular signal cascades and triggers responsible for the dynamic changes in the proteolytic pathways during in utero and early postnatal development. Costal diaphragm was obtained immediately following euthanasia of fetal and newborn lambs from 75 to 200 days postconceptional age (term = 150 days). Gene expression of insulin-like growth factor 1 (IGF-1), tumour necrosis factor α (TNF-α) and myostatin decreased steadily in utero from 75 to 145 days ( P 0.05) and the transcripts increased again after birth except of myostatin. Rapid activation of the fork-head transcriptional factors of the O class (FOXO1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways was observed at 24 h of postnatal age. Diaphragm reactive oxygen species (ROS) production increased over 29-fold at 24 h postnatal age, compared with the 145 days fetus ( P 0.01). Local (diaphragmatic) ROS accumulation occurred earlier and was more predominant than systemic (plasma) ROS. There were positive correlations between signalling transduction molecules (FOXO1 and NF-κB) and antioxidant gene expression (superoxide dismutase and glutathione peroxidase 1). We conclude that anabolic (IGF-1) and catabolic (TNF-α and myostatin) factors have a similar developmental pattern with a decreasing trend toward full term. This may reflect in utero integration of cellular events into low protein metabolism as the diaphragm matures in late gestation. On initiation of spontaneous breathing, ROS accumulated and potentially activated cascade of FOXO and NF-κB signal transduction. The finding provides new insights into developmental regulation of protein metabolism within development. The implication of these postnatal events for diaphragm adaptation to the ex utero environment needs further investigation.
Publisher: American Thoracic Society
Date: 11-2013
Publisher: Public Library of Science (PLoS)
Date: 17-12-2009
No related grants have been discovered for Yong Song.