Chronic microaspiration of bile acids induces lung fibrosis through multiple mechanisms in rats
In this study, a rat model of bile acid microaspiration was established by weekly intratracheal instillation of three major bile acids including chenodeoxycholic acid (CDCA), deoxycholic acid (DCA) and lithocholic acid (LCA) . Repeated microaspiration of CDCA, DCA and LCA caused fibrotic changes, including alveolar wall thickening and extensive collagen deposition, in rat lungs. Bile acid microaspiration also induced alveolar epithelial-mesenchymal transition (EMT), as indicated by upregulation of mesenchymal markers α-smooth muscle actin (α-SMA) and vimentin, as well as downregulaton of epithelial marke...
Source: Clinical Science - March 24, 2017 Category: Biomedical Science Authors: chen, B., You, W. J., Liu, X. Q., Xue, S., Qin, H., Jiang, H. D. Tags: PublishAheadOfPrint Source Type: research
The noncoding RNA linc-ADAMTS5 cooperates with RREB1 to protect from intervertebral disc degeneration through inhibiting ADAMTS5 expression
In this study, through mining computational algorithm programs, and public available data sets, we identified Ras responsive element binding protein 1 (RREB1) as a crucial transcription factor regulating the expression of ADAMTS5 in NP cells. RNA pull-down, RNA immunoprecipitation, in vitro binding assays, and gain- and loss-of-function studies indicated that a physical interaction between linc-ADAMTS5 and splicing factor proline/glutamine-rich (SFPQ) facilitated the recruitment of RREB1 to binding sites within the ADAMTS5 promoter to induce chromatin remodeling. This resulted in subdued ADAMTS5 levels in cultured NP cells...
Source: Clinical Science - March 24, 2017 Category: Biomedical Science Authors: Wang, K., Song, Y., Liu, W., Wu, X., Zhang, Y., Li, S., Kang, L., Tu, J., Zhao, k., Hua, W., Yang, C. Tags: PublishAheadOfPrint Source Type: research
Vascular endothelial growth factor-A165b ameliorates outer-retinal barrier and vascular dysfunction in the diabetic retina
Diabetic retinopathy (DR) is one of the leading causes of blindness in the developed world. Characteristic features of DR are retinal neurodegeneration, pathological angiogenesis and breakdown of both the inner and outer retinal barriers of the retinal vasculature and RPE-choroid respectively. Vascular endothelial growth factor-A (VEGF), a key regulator of angiogenesis and permeability, is the target of most pharmacological interventions of DR. VEGF-A can be alternatively spliced at exon 8 to form 2 families of isoforms, pro- and anti-angiogenic. VEGF-A165a is the most abundant pro-angiogenic isoform, is pro-inflammatory a...
Source: Clinical Science - March 24, 2017 Category: Biomedical Science Authors: Ved, N., Hulse, R. P., Bestall, S. M., Donaldson, L. F., Bainbridge, J. W., Bates, D. Tags: PublishAheadOfPrint Source Type: research
Pretreatment with ALDH2 agonist Alda-1 reduces intestinal injury induced by ischemia and reperfusion in mice
This study was to determine whether ALDH2 agonist, Alda-1, could alleviate intestinal injury after gut IR. In a mice model of intestinal IR injury, histological grading, proinflammatory cytokines, oxidative stress, cellular apoptosis, chemokine contents, ALDH2 activity, 4-HNE and MDA were evaluated. The results indicated that IR treatment conferred elevation in pathological scores, proinflammatory cytokines, oxidative stress, cellular apoptosis, chemokine levels, accompanied by accumulated 4-HNE and MDA. No significant changes in ALDH2 activity were observed after IR. However, Alda-1 pretreatment significantly decreased th...
Source: Clinical Science - March 21, 2017 Category: Biomedical Science Authors: Zhu, Q., He, G., Wang, J., Wang, Y., Chen, W. Tags: PublishAheadOfPrint Source Type: research
Diabetes confers in vitro calcific potential on serum which associates with in-vivo vascular calcification
Although vascular calcification (VC) is prevalent in type 2 diabetes (T2DM), underlying mechanisms remain unclear. Neither is it known whether T2DM confers calcific potential (CP) to serum, enabling it to induce VC outside the disease milieu. We therefore investigated the CP of serum from controls and subjects with T2DM with and without in vivo VC . Samples from 20 healthy controls and 45 age- and sex-matched patients with T2DM with MDRD-eGFR>60mL min-1 were analysed for CP using rat aortic smooth muscle cells in vitro . CT scans of femoral arteries identified individuals with in vivo calcification. Serum from sub...
Source: Clinical Science - March 19, 2017 Category: Biomedical Science Authors: Patidar, A., Singh, D. K., Thakur, S., Winocour, P., Farrington, K., Baydoun, A. Tags: PublishAheadOfPrint Source Type: research
