The Silencing of RECK Gene is Associated with Promoter Hypermethylation and Poor Survival in Hepatocellular Carcinoma

Background: To evaluate the promoter methylation status of RECK gene and mRNA expression in patients with hepatocellular carcinoma (HCC)

Low LPA gene kringle IV-2 repeat copy number association with elevated lipoprotein (a) concentration as an independent risk factor of coronary atherosclerotic heart disease in the Chinese Han population

Abstract Background Lipoprotein (a) [Lp(a)], which is genetically determined by the LPA gene kringle IV type 2 (KIV-2) repeat copy number, has previously been reported in different populations. However, it is uncertain if the same occurs in the Chinese Han population. This study explored the correlation of Lp(a) mass or particle concentration with KIV-2 repeat copy number and application for coronary atherosclerotic heart disease (CAHD) risk assessment. Methods A cross-sectional study including 884 subjects was conducted. The Lp(a) level and routine risk factors of CAHD were compared. The KIV-2 copy number distribution, relationship with Lp(a), and assessment for CAHD risk were explored. Results The mean of Lp(a) mass or particle concentration in the CAHD group was higher than that in the non-CAHD group, while the KIV-2 copy number in the CAHD group was lower. Lp(a) had auxiliary values in gauging the type of plaque and was significantly higher in the soft-plaque group than that in the other two groups (200 mg/L [21.5 nmol/L], 166 mg/L [18.6 nmol/L], 149 mg/L [17.1 nmol/L], respectively, P < 0.05). Kappa test indicated divergence for the same individual using two Lp(a) concentrations (kappa value was 0.536 [< 0.75]). Elevated Lp(a) was an independent CAHD risk factor, whatever mass or particle concentration, and large KIV-2 copy number was a protective factor. Conclusion Lp(a) level and small KIV-2 copy number are risk factors for CAHD in the Chinese Han population; furthermore, elevated Lp(a) may gauge the type of coronary plaque

Hypoxia Inhibits Osteogenesis and Promotes Adipogenesis of Fibroblast-like Synoviocytes via Upregulation of Leptin in Patients with Rheumatoid Arthritis

Hypoxia is associated with the pathogenesis of rheumatoid arthritis (RA). RA fibroblast-like synoviocytes (FLSs) are able to differentiate into osteoblasts and adipocytes. In this study, we aimed to investigate the role of hypoxia in the osteogenesis or adipogenesis of RA-FLSs. Bioinformatics analysis was performed to profile gene expression in the datasets of GSE21959, GSE32006, and GSE55875, and flow cytometry was performed for FLS characterization, while Alizarin Redand Oil Red O staining for osteogenic or adipogenic differentiation of FLSs, respectively. RNA interference leptin knockdown was used to determine the role of leptin in the osteogenesis and adipogenesis of RA-FLSs, and the expression of osteogenic and adipogenic markers was quantified by RT-qPCR and Western blotting. FLSs exhibited a mesenchymal stem cell (MSC)-like phenotype and we observed a limited self-renewal capacity in RA-FLSs compared to that in MSCs, but it was still greater than osteoarthritis (OA)-FLSs. Hypoxia did not change the RA-FLS MSC-like phenotype but inhibited the osteogenic differentiation and promoted the adipogenic differentiation of RA-FLSs. From the bioinformatics analysis ofGSE21959, GSE32006, and GSE55875 datasets, we found leptin, the only perturbed hypoxia-mediated upregulated gene across the three profiled datasets. Leptin knockdown in RA-FLSs reversed the hypoxia-mediated reduction of osteogenesis and hypoxia-mediated enhancement of adipogenesis by elevated expression of osteogenic markers and reduced expression of adipogenic markers, respectively. Therefore, hypoxia-leptin regulation of the osteogenic and adipogenic differentiation of RA-FLSs advances our understanding of RA pathogenesis, meanwhile also provides opportunities for future therapeutic intervention of RA