Heparin fragments as a potential therapeutic for bronchiectasis and chronic obstructive pulmonary disease

The 67th Harden - Decoding the Biology of Heparan Suphate Proteoglycans, Cambridgeshire, U.K., 29 March-2 April 2009

Shed syndecan-1 restricts neutrophil elastase from α1- antitrypsin in neutrophilic airway inflammation

Persistent proteolytic imbalance in chronic inflammatory diseases has been ascribed to neutrophil elastase (NE)/antielastase imbalance in wound fluids. In sputum sols of patients with bronchiectasis, we found unopposed NE activity, despite overwhelming excess of the physiological antielastase, α1-antitrypsin (α1-AT). Western blot analysis found NE in a supramolecular complex with shed ectodomains of syndecan (Syn)-1 in sputum sol samples and, as such, inhibition of NE activity was incomplete, even with addition of exogenous α1-AT. To confirm that NE binding to heparan sulfate (HS) components of Syn-1 limits the antielastase effect, recombinant human Syn-1 was recovered from stable Syn-1 transfectants of a human B-lymphoid cell line (ARH-77). Western ligand blot confirmed that NE bound to HS moieties and α1-AT to the core protein of the recombinant product. Inhibition of NE activity by standard additions of α1-AT was incomplete unless Syn-1 had been deglycanated by heparitinase treatment. Surface plasmon resonance analysis revealed that NE binding to HS (equilibrium dissociation constant, ∼14 nM) could be outcompeted by heparin variants. We conclude that the HS moiety of shed Syn-1 binds and restricts NE from inhibition by α1-AT.link_to_OA_fulltex

Sulfated maltoheptaose reduces neutrophilic airway inflammation in a smoking rat model of chronic obstructive pulmonary disease

Conference Theme: Is Aging a Disease?The 5th International Symposium on Healthy Aging: Is Aging a Disease?, Hong Kong, China, 6-7 March 2010

Sulfated maltoheptaose is a potential therapeutic in reducing neutrophilic inflammation in a cigarette smoke-induced rat model of chronic obstructive pulmonary disease

Poster Session 1 - Proteases and Inhibitors: B2

Long non-coding RNA expression profiles predict clinical phenotypes in glioma

Glioma is the commonest form of primary brain tumor in adults with varying malignancy grades and histological subtypes. Long non-coding RNAs (lncRNAs) are a novel class of non-protein-coding transcripts that have been shown to play important roles in cancer development. To discover novel tumor-related lncRNAs and determine their associations with glioma subtypes, we first applied a lncRNA classification pipeline to identify 1970 lncRNAs that were represented on Affymetrix HG-U133 Plus 2.0 array. We then analyzed the lncRNA expression patterns in a set of previously published glioma gene expression profiles of 268 clinical specimens, and identified sets of lncRNAs that were unique to different histological subtypes (astrocytic versus oligodendroglial tumors) and malignancy grades. These lncRNAs signatures were then subject to validation in another non-overlapping, independent data set that contained 157 glioma samples. This is the first reported study that correlates lncRNA expression profiles with malignancy grade and histological differentiation in human gliomas. Our findings indicate the potential roles of lncRNAs in the biogenesis, development and differentiation of gliomas, and provide an important platform for future studies. © 2012 Elsevier Inc.link_to_subscribed_fulltex