No abstract

It has been reported that lysosomal proteases play important roles in ischemic and excitotoxic neuronal cell death. We have previously reported that cathepsin B expression increased remarkably after traumatic brain injury (TBI). The present study sought to investigate the effects of a selective cathepsin B inhibitor (CBI) [N-L-3-trans-prolcarbamoyloxirane-2-carbonyl)-L-isoleucyl-L-proline] on cell death and behavioral deficits in our model. We examined the levels of cathepsin B enzymatic activity and its expression by double labelling damaged cells in the brain slice with propidium iodide (PI) and anticathepsin B. The results showed an elevated enzymatic activity associated with TBI-induced increase in a mature form of cathepsin B, suggesting that cathepsin B may play a role in TBI-induced cell injury. PI was found to label cells positive for the neuronal-specific nuclear marker NeuN, whereas fewer GFAP-positive cells were labelled by PI, suggesting that neurons are more sensitive to cell death induced by TBI. Additionally, we found that pretreatment with CBI remarkably attenuated TBI-induced cell death, lesion volume, and motor and cognitive dysfunction. To analyze the mechanism of action of cathepsin B in the cell death signaling pathway, we assessed DNA fragmentation by electrophoresis, Bcl-2/Bax protein expression levels, Bid cleavage, cytochrome c release, and caspase-3 activation. The results imply that cathepsin B contributes to TBI-induced cell death through the present programmed cell necrosis and mitochondria-mediated apoptotic pathways.

Chitooligosaccharide (COS), which is acknowledged for possessing multiple functions, is a kind of low-molecular-weight polymer prepared by degrading chitosan via enzymatic, chemical methods, etc. COS has comprehensive applications in various fields including food, agriculture, pharmacy, clinical therapy, and environmental industries. Besides having excellent properties such as biodegradability, biocompatibility, adsorptive abilities and non-toxicity like chitin and chitosan, COS has better solubility. In addition, COS has strong biological functions including anti-inflammatory, antitumor, immunomodulatory, neuroprotective effects, etc. The present paper has summarized the preparation methods, analytical techniques and biological functions to provide an overall understanding of the application of COS.

No abstract

Our present study was conducted to investigate whether liquiritin (7-hydroxy-2-[4-[3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-yl] oxyphenyl]-chroman-4-one, 1), an active component of Glycyrrhiza uralensis Fisch., exerts a neuroprotective effect against focal cerebral ischemia/reperfusion (I/R) in male Institute of Cancer Research (ICR) mice. On the establishment of mice with middle cerebral artery occlusion (MCAO) for 2 h and reperfusion for 22 h, liquiritin at the doses of 40, 20, and 10 mg/kg was administered before MCAO once a day intragastrically for a subsequent 3 days. Neurological deficits and infarct volume were measured, respectively. The levels of malondialdehyde (MDA) and carbonyl, activities of superoxide anion (SOD), catalase (CAT) and glutathion peroxidase (GSH-Px) and reduced glutathione/oxidized disulfide (GSH/GSSG) ratio in brain were estimated spectrophotometrically. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and terminal deoxynucleotidyl transferase-mediated DuTP-biotin nick end labeling (TUNEL)-positive cells were detected by immunohistochemical analysis. Our results showed that the neurological deficits, infarct volume, and the levels of MDA and carbonyl decreased, the ratio of GSH/GSSG and the activities of SOD, CAT, and GSH-Px were compensatorily up-regulated, and 8-OHdG and TUNEL-positive cells decreased after 22 h of reperfusion in liquiritin-treated groups. These findings suggest that liquiritin might be a potential agent against cerebral I/R injury in mice by its antioxidant and antiapoptosis properties.