Serum Levels of IL-1 ß , IL-6, TGF- ß , and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting.

Inflammation plays an important role in the pathophysiological process after carotid artery stenting (CAS). Monocyte is a significant source of inflammatory cytokines in vascular remodeling. Telmisartan could reduce inflammation. In our study, we first found that, after CAS, the serum IL-1ß, IL-6, TGF-ß, and MMP-9 levels were significantly increased, but only MMP-9 level was elevated no less than 3 months. Second, we established a new in vitro model, where THP-1 monocytes were treated with the supernatants of human umbilical vein endothelial cells (HUVECs) that were scratched by pipette tips, which mimics monocytes activated by mechanical injury of stenting. The treatment enhanced THP-1 cell adhesion, migration and invasion ability, and the phosphorylation of ERK1/2 and Elk-1 and MMP-9 expression were significantly increased. THP-1 cells pretreated with PD98095 (ERK1/2 inhibitor) attenuated the phosphorylation of ERK1/2 and Elk-1 and upregulation of MMP-9, while pretreatment with telmisartan merely decreased the phosphorylation of Elk-1 and MMP-9 expression. These results suggested that IL-1ß, IL-6, TGF-ß, and MMP-9 participate in the pathophysiological process after CAS. Our new in vitro model mimics monocytes activated by stenting. MMP-9 expression could be regulated through ERK1/2/Elk-1 pathway, and the protective effects of telmisartan after stenting are partly attributed to its MMP-9 inhibition effects via suppression of Elk-1.

Overexpression of Fibulin-5 Attenuates Ischemia/Reperfusion Injury After Middle Cerebral Artery Occlusion in Rats.

Ischemia/reperfusion (I/R) injury after middle cerebral artery occlusion (MCAO) induces detrimental processes such as oxidative stress, inflammation, and apoptosis. All parts of the neurovascular unit are involved in these pathological processes. Fibulin-5 is a 66-kD glycoprotein secreted by various vascular cells, including vascular smooth muscle cells (SMCs), fibroblasts, and endothelial cells. As an extracellular matrix protein involved in cell adhesion, fibulin-5 has been widely studied in tumor growth and invasion. However, the effects of fibulin-5 on brain injury following ischemia/reperfusion have not been reported. In this study, we examined the effect of overexpressed fibulin-5 on reactive oxygen species (ROS) production. Fibulin-5 overexpression attenuated ROS expression, which in turn decreased apoptosis and blood-brain barrier (BBB) permeability following MCAO and reperfusion. Fibulin-5 also improved neurological deficits but had no effect on infarction volume. T2-weighted MRI and electron microscopy further confirmed brain edema reduction and decreased BBB disruption in fibulin-5 overexpression recombinant adenovirus (Ad-FBLN) treated rats. In addition, tight junction protein occludin was significantly degraded and matrix metalloproteinase 9 (MMP-9) immunoreactivity was significantly increased. Fibulin-5-mediated ROS decrease was not due to increased total superoxide dismutase levels but was instead correlated with the activation of Rac-1 pathway. The findings highlight the importance of antioxidant mechanism underlying cerebral ischemia/reperfusion.

Curcumin inhibits mitochondrial injury and apoptosis from the early stage in EAE mice.

The exact pathophysiological change concerning mitochondrial injury and oligodendrocyte apoptosis in MS and EAE model is still unknown. Whether curcumin is able to inhibit mitochondrial injury and suppress the apoptosis in the early stages of MS/EAE is still unclear. We first explored mitochondrial injury and apoptosis at different time points p.i. in C57 BL/6 EAE mice. We then explored the effects of curcumin on mitochondria and apoptosis. Results showed that mitochondrial injury can be observed 3 days p.i. Apoptosis in the spinal cord occurred 3 days p.i. and the apoptotic cells were shown to be oligodendrocytes and neuronal cells. Curcumin significantly reduced the number of apoptotic cells and inhibited the upregulation of cyt-c, caspase-9, and caspase-3 at 7 days p.i. in the EAE mice. These observations demonstrate that mitochondrial injury and oligodendrocyte/neuronal apoptosis occur in the early stages of EAE. Curcumin can inhibit apoptosis in EAE mice which maybe act through protection of mitochondrial injury and inhibition of the intrinsic apoptotic pathway.

Systematic review of clinical practice guidelines related to multiple sclerosis.

BACKGROUND: High quality clinical practice guidelines (CPGs) can provide clinicians with explicit recommendations on how to manage health conditions and bridge the gap between research and clinical practice. Unfortunately, the quality of CPGs for multiple sclerosis (MS) has not been evaluated. OBJECTIVE: To evaluate the methodological quality of CPGs on MS using the AGREE II instrument. METHODS: According to the inclusion and exclusion criteria, we searched four databases and two websites related to CPGs, including the Cochrane library, PubMed, EMBASE, DynaMed, the National Guideline Clearinghouse (NGC), and Chinese Biomedical Literature database (CBM). The searches were performed on September 20th 2013. All CPGs on MS were evaluated by the AGREE II instrument. The software used for analysis was SPSS 17.0. RESULTS: A total of 27 CPGs on MS met inclusion criteria. The overall agreement among reviews was good or substantial (ICC was above 0.70). The mean scores for each of all six domains were presented as follows: scope and purpose (mean ± SD: 59.05 ± 16.13), stakeholder involvement (mean ± SD: 29.53 ± 17.67), rigor of development (mean ± SD: 31.52 ± 21.50), clarity of presentation (mean ± SD: 60.39 ± 13.73), applicability (mean ± SD: 27.08 ± 17.66), editorial independence (mean ± SD: 28.70 ± 22.03). CONCLUSIONS: The methodological quality of CPGs for MS was acceptable for scope, purpose and clarity of presentation. The developers of CPGs need to pay more attention to editorial independence, applicability, rigor of development and stakeholder involvement during the development process. The AGREE II instrument should be adopted by guideline developers.