Human S100A9 blocking peptide

Objective: Animal studies suggest that S100A8/S100A9 may be involved in the pathogenesis of osteoarthritis (OA); however, there has been no clinical study examining the associations between serum S100A8/S100A9 and knee symptoms, joint structures and cartilage degradation enzymes in knee OA patients so far. Therefore, this study was designed to investigate the cross-sectional associations between serum levels of S100A8/S100A9 and the outcomes in patients with knee OA. Design: A total of 141 subjects with clinical knee OA were included. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was used to assess joint symptoms. Magnetic resonance imaging (MRI) was used to measure knee structural abnormalities including cartilage defects. Knee radiography was used to assess joint space narrowing (JSN), osteophytes and the radiographic severity of OA. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of S100A8/S100A9, matrix metalloproteinase (MMP)-3, MMP10 and MMP13. Results: In multivariable analyses, serum S100A8/S100A9 were positively associated with total WOMAC score (beta: 0.111 per 10 ng/ml, P = 0.021), WOMAC weight-bearing pain (beta: 0.015 per 10 ng/ml, P = 0.043) and WOMAC physical dysfunction (beta: 0.091 per 10 ng/ml, P = 0.010), and had positive associations with total cartilage defects and cartilage defects at lateral femoral, lateral tibial and medial femoral sites (ORs: 1.006-1.008 per 10 ng/ml, all P < 0.05) and serum levels of MMP3 (beta: 0.002 per 10 ng/ml, P = 0.032) in patients with clinical knee OA. Conclusions: Serum levels of S100A8/S100A9 were positively associated with increased knee symptoms, cartilage defects and serum cartilage degradation enzymes in patients with knee OA, suggesting that S100A8/S100A9 may have a role to play in knee OA. Future longitudinal studies are required to confirm these findings. (c) 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Background Solid predominant lung adenocarcinomas (LUAD) have distinct histopathological and clinical characteristics compared with nonsolid subtypes. A comprehensive comparison of altered genes found in solid and nonsolid subtypes has not previously been performed. In this study, we analyzed differences in gene expression, genetic mutations, and DNA methylation to better understand the risk factors for these two subtypes of LUAD. Methods Differentially expressed genes (DEGs) and differentially mutated genes (DMGs) were analyzed from RNA-seq data downloaded from The Cancer Genome Atlas (TCGA) and Broad Institute database. To understand the functional significance of molecular changes, we examined the DEGs and DMGs with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Results A total of 184 patients in the TCGA cohort and 140 patients in the Broad Institute cohort were included in this study. We identified 75 DEGs, of which 15 were upregulated and 56 downregulated in the solid group relative to the nonsolid group. The DEGs were mainly involved in the regulation of water and fluid transport. We discovered 38 significantly differentially expressed genes that overlapped in the two groups. The DMGs were mainly enriched for pathways involved in cell-cell adhesion, cell adhesion, biological adhesion, and hemophilic cell adhesion. We additionally discovered nine significantly methylated genes between solid and nonsolid LUAD. Conclusions Our study identified distinct DEGs, DMGs, and methylation genes for solid and nonsolid LUAD subtypes. These findings improve our understanding of the different carcinogenesis mechanisms in LUAD and will help to develop new therapeutic strategies.