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Nosch D.S.,University of Cardiff | Nosch D.S.,University of Applied Sciences and Arts Northwestern Switzerland | Pult H.,University of Cardiff | Pult H.,Dr Heiko Pult Optometry And Vision Research | And 6 more authors.
Optometry and Vision Science | Year: 2016

Purpose To examine the possible role of corneal sensitivity and tear film quality in triggering a blink by investigating the relationship between blink rate, central corneal sensitivity threshold (CST), ocular surface temperature (OST), tear meniscus height (TMH), tear film quality (noninvasive tear break-up time [NIBUT]), and tear film lipid pattern under normal conditions. Methods Forty-two volunteers (average age, 27.76 ± 5.36 years; 11 males) with good ocular health (Ocular Surface Disease Index, <15.0) were recruited for this cross-sectional cohort study. Blink rate, CST (noncontact corneal air gas aesthesiometry, NCCA), minimum and maximum OST in the central and inferior cornea between blinks (thermal infrared camera), TMH, NIBUT, and lipid pattern of the tear film (Keeler Tearscope Plus) were recorded on the right eye only. Results Median blink rate was 11 blinks/min (interquartile range [IR], 6.95 to 17.05), CST was 0.35 mbars (IR, 0.30 to 0.40), minimum OST in the central cornea was 35.15°C (IR, 34.58 to 35.50), and NIBUT was 34.55 s (IR, 12.45 to 53.80). Moderate but statistically significant correlations were observed between CST and NIBUT (r = 0.535, p < 0.001), CST and blink rate (r = -0.398, p < 0.001), lipid pattern and OST (r = 0.556, p < 0.001), and between CST and OST (r = 0.371, p = 0.008). The correlations between blink rate and NIBUT (r = -0.696, p < 0.001) and between OST and NIBUT (r = 0.639, p < 0.001; Spearman test) achieved higher significance; this was highlighted by the linear regression model where NIBUT and minimum central and inferior OST were identified as significant predictor variables. Conclusions There is strong evidence for significant interactions between corneal sensitivity, NIBUT, OST, and blink frequency, emphasizing that ocular surface conditions represent a possible important trigger for the initiation of a blink. However, the mechanisms involved in the initiation of a blink are complex, with local ocular sensory input as only one trigger, along with other external influences and internal factors under cortical control.


Jenkins R.H.,University of Cardiff | Martin J.,Cardiff Institute of Tissue Engineering and Repair | Phillips A.O.,Cardiff Institute of Tissue Engineering and Repair | Bowen T.,Cardiff Institute of Tissue Engineering and Repair | Fraser D.J.,Cardiff Institute of Tissue Engineering and Repair
Biochemical Society Transactions | Year: 2012

Diverse aetiologies result in significant deviation from homoeostasis in the kidney, leading to CKD (chronic kidney disease). CKD progresses to end-stage renal disease principally as a result of renal fibrosis, although the molecular mechanisms underlying this fibrotic process are still poorly understood. miRNAs (microRNAs) are a recently discovered family of endogenous short single-stranded RNAs that regulate global gene expression at the post-transcriptional level. The recent findings from our laboratory and others discussed in the present review outline pleiotropic roles for miR-192 in renal homoeostasis and in the fibrotic kidney. We describe miR-192-driven anti-and pro-fibrotic effects via the repression of ZEB1 and ZEB2 (zinc finger E-box-binding homeobox proteins 1 and 2), resulting in changes in extracellular matrix deposition and cell differentiation. ©The Authors Journal compilation ©2012 Biochemical Society.


Beltrami C.,University of Cardiff | Beltrami C.,Cardiff Institute of Tissue Engineering and Repair | Clayton A.,University of Cardiff | Phillips A.O.,University of Cardiff | And 5 more authors.
Biochemical Society Transactions | Year: 2012

Kidney biopsy is the gold-standard diagnostic test for intrinsic renal disease, but requires hospital admission and carries a 3% risk of major complications. Current non-invasive prognostic indicators such as urine protein quantification have limited predictive value. Better diagnostic and prognostic tests for chronic kidney disease patients are a major focus for industry and academia, with efforts to date directed largely at urinary proteomic approaches. microRNAs constitute a recently identified class of endogenous short non-coding single-stranded RNA oligonucleotides that regulate gene expression post-transcriptionally. Quantification of urinary microRNAs offers an alternative approach to the identification of chronic kidney disease biomarkers. ©The Authors Journal compilation ©2012 Biochemical Society.


Chen L.,University of Cardiff | Chen L.,Nanjing Southeast University | Neville R.D.,University of Cardiff | Neville R.D.,Cardiff Institute of Tissue Engineering and Repair | And 10 more authors.
Matrix Biology | Year: 2012

The ubiquitous mammalian extracellular matrix glycosaminoglycan hyaluronan (HA) plays a pivotal role in the regulation of cell phenotype in fibrosis and scarring. Transforming growth factor-beta 1 (TGF-β1) and interleukin-1 beta (IL-1β) up-regulate hyaluronan synthase (HAS) 1 and HAS2 in dermal fibroblasts and renal proximal tubular epithelial cells, and subsequent HA synthesis regulates cell phenotype. In the present study, we investigated the mechanism of HAS1 transcriptional up-regulation in response to these cytokines. We used 5'-rapid amplification of cDNA ends analysis to identify the 5' end of HAS1 transcripts, resulting in an increase of 26 nucleotides to the HAS1 exon 1 sequence of reference sequence NM_001523. Constitutive luciferase activity of upstream DNA sequences was shown in luciferase reporter assays, but our reporter vector signals were refractory to the addition of TGF-β1 and IL-1β. Using siRNAs to knockdown transcription factor mRNAs, we showed that TGF-β1 up-regulation of HAS1 transcription was mediated via Smad3 but not Smad2, while HAS1 induction by IL-1[U+F020]β was Sp3, not Sp1, dependent. © 2012 Elsevier B.V.


Michael D.R.,University of Cardiff | Phillips A.O.,University of Cardiff | Phillips A.O.,Cardiff Institute of Tissue Engineering and Repair | Krupa A.,University of Cardiff | And 10 more authors.
Journal of Biological Chemistry | Year: 2011

Aberrant expression of the human hyaluronan synthase 2 (HAS2) gene has been implicated in the pathology of malignancy, pulmonary arterial hypertension, osteoarthritis, asthma, thyroid dysfunction, and large organ fibrosis. Renal fibrosis is associated with increased cortical synthesis of hyaluronan (HA), an extracellular matrix glycosaminoglycan, and we have shown that HA is a correlate of interstitial fibrosis in vivo. Our previous in vitro data have suggested that both HAS2 transcriptional induction and subsequent HAS2-driven HA synthesis may contribute to kidney fibrosis via phenotypic modulation of the renal proximal tubular epithelial cell (PTC). Post-transcriptional regulation of HAS2 mRNA synthesis by the natural antisense RNA HAS2-AS1 has recently been described in osteosarcoma cells, but the antisense transcript was not detected in kidney. In this study, PTC stimulation with IL-1β or TGF-β1 induced coordinated temporal profiles of HAS2-AS1 and HAS2 transcription. Constitutive activity of the putative HAS2-AS1 promoter was demonstrated, and transcription factor-binding sequence motifs were identified. Knockdown of Sp1/Sp3 expression by siRNA blunted IL-1β induction of both HAS2-AS1 and HAS2, and Smad2/Smad3 knockdown similarly attenuated TGF-β1 stimulation. Inhibition of IL-1β-stimulated HAS2-AS1 RNA induction using HAS2-AS1-specific siRNAs also suppressed upregulation of HAS2 mRNA transcription. The thermodynamic feasibility of HAS2-AS1/HAS2 heterodimer formation was demonstrated in silico, and locus-specific cytoplasmic double-stranded RNA was detected in vitro. In summary, our data show that transcriptional induction of HAS2-AS1 and HAS2 occurs simultaneously in PTCs and suggest that transcription of the antisense RNA stabilizes or augments HAS2 mRNA expression in these cells via RNA/mRNA heteroduplex formation. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.


Peake M.A.,Cardiff Institute of Tissue Engineering and Repair | Peake M.A.,Northumbria University | Caley M.,Cardiff Institute of Tissue Engineering and Repair | Caley M.,Blizard Institute | And 10 more authors.
Wound Repair and Regeneration | Year: 2014

There is a spectrum/continuum of adult human wound healing outcomes ranging from the enhanced (nearly scarless) healing observed in oral mucosa to scarring within skin and the nonhealing of chronic skin wounds. Central to these outcomes is the role of the fibroblast. Global gene expression profiling utilizing microarrays is starting to give insight into the role of such cells during the healing process, but no studies to date have produced a gene signature for this wound healing continuum. Microarray analysis of adult oral mucosal fibroblast (OMF), normal skin fibroblast (NF), and chronic wound fibroblast (CWF) at 0 and 6 hours post-serum stimulation was performed. Genes whose expression increases following serum exposure in the order OMF

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