Osteopontin Predicts Three-Month Outcome in Stroke Patients Treated by Reperfusion Therapies.

Establishing a prognosis at hospital admission after stroke is a major challenge. Inflammatory processes, hemostasis, vascular injury, and tissue remodeling are all involved in the early response to stroke. This study analyzes whether 22 selected biomarkers, sampled at admission, predict clinical outcomes in 153 stroke patients treated by thrombolysis and mechanical endovascular treatment (MET). Biomarkers were related to hemostasis (u-plasminogen activator/urokinase (uPA/urokinase), serpin E1/PAI-1, serpin C1/antithrombin-III, kallikrein 6/neurosin, alpha 2-macroglobulin), inflammation[myloperoxidase (MPO), chemokine ligand 2/monocyte chemoattractant protein-1 chemokine (CCL2/MCP-1), adiponectin, resistin, cell-free DNA (cDNA), CD40 Ligand (CD40L)], endothelium activation (Vascular cell adhesion protein 1 (VCAM-1) intercellular adhesion molecule 1 (ICAM-1), platelet endothelial cell adhesion molecule 1 (CD31/PECAM-1)], and tissue remodeling (total cathepsin S, osteopontin, cystatin C, neuropilin-1, matrix metallopeptidase 2 (MMP-2), matrix metallopeptidase 3 (MMP-3), matrix metallopeptidase 9 (MMP-9), matrix metallopeptidase 13 (MMP-13)]. Correlations between their levels and excellent neurological improvement (ENI) at 24 h and good outcomes (mRS 0-2) at three months were tested. Osteopontin and favorable outcomes reached the significance level (p = 0.008); the adjusted OR per SD increase in log-transformed osteopontin was 0.34 (95%CI, 0.18-0.62). The relationship between total cathepsin S and MPO with ENI, was borderline of significance (p = 0.064); the adjusted OR per SD increase in log-transformed of total cathepsin S and MPO was 0.54 (95%CI, 0.35-0.81) and 0.51 (95%CI, 0.32-0.80), respectively. In conclusion, osteopontin levels predicted three-month favorable outcomes, supporting the use of this biomarker as a complement of clinical and radiological parameters for predicting stroke prognosis.

Silver Nanoparticles Impair Retinoic Acid-Inducible Gene I-Mediated Mitochondrial Antiviral Immunity by Blocking the Autophagic Flux in Lung Epithelial Cells.

Silver nanoparticles (AgNPs) are microbicidal agents which could be potentially used as an alternative to antivirals to treat human infectious diseases, especially influenza virus infections where antivirals have generally proven unsuccessful. However, concerns about the use of AgNPs on humans arise from their potential toxicity, although mechanisms are not well-understood. We show here, in the context of an influenza virus infection of lung epithelial cells, that AgNPs down-regulated influenza induced CCL-5 and -IFN-ß release (two cytokines important in antiviral immunity) through RIG-I inhibition, while enhancing IL-8 production, a cytokine important for mobilizing host antibacterial responses. AgNPs activity was independent of coating and was not observed with gold nanoparticles. Down-stream analysis indicated that AgNPs disorganized the mitochondrial network and prevented the antiviral IRF-7 transcription factor influx into the nucleus. Importantly, we showed that the modulation of RIG-I-IRF-7 pathway was concomitant with inhibition of either classical or alternative autophagy (ATG-5- and Rab-9 dependent, respectively), depending on the epithelial cell type used. Altogether, this demonstration of a AgNPs-mediated functional dichotomy (down-regulation of IFN-dependent antiviral responses and up-regulation of IL-8-dependent antibacterial responses) may have practical implications for their use in the clinic.

Salivary proteome modifications associated with periodontitis in obese patients.

AIM: To identify changes in the salivary protein/peptide profiles by differential proteomics in obese patients with or without periodontitis. MATERIAL AND METHODS: Periodontal examinations and whole saliva samples were obtained from 38 obese patients (mean age: 45.1 ± 7.3 years, mean BMI: 49.3 ± 9 kg/m(2) ) including 13 periodontitis and 25 non-periodontitis subjects, and 19 healthy controls (mean age: 44.2 ± 6.4 years, mean BMI: 21.5 ± 2.1 kg/m(2) ). Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS) was used to compare the whole saliva polypeptide profiles. RESULTS: The SELDI-TOF-MS analysis detected eight putative markers. Six of them were increased and identified in obese subjects versus controls (albumin, α and ß haemoglobin chains, α-defensins 1, 2 and 3). Alpha-defensins were less abundant in saliva of periodontitis obese patients (36.47 ± 19.84 µA) versus non-periodontitis obese patients (43.44 ± 30.34  µA), whereas α-defensins were more abundant in obese patients (40.99 ± 26.66  µA) versus controls (27.1 ± 23.98  µA). CONCLUSIONS: Periodontal status modifies the salivary proteome in obese patients. Alpha-defensins may play a role in gingival inflammation, and be involved in the higher susceptibility of obese patients to periodontal diseases.