Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis

Introduction: Increasing evidence indicates that microRNAs (miRNAs) play a critical role in the pathogenesis of inflammatory diseases. The aim of the study was to investigate the expression pattern and function of miRNAs in CD4 + T cells from patients with rheumatoid arthritis (RA).Methods: The expression profile of miRNAs in CD4 + T cells from synovial fluid (SF) and peripheral blood of 33 RA patients was determined by microarray assay and validated by qRT-PCR analysis. The correlation between altered expression of miRNAs and cytokine levels was determined by linear regression analysis. The role of miR-146a overexpression in regulating T cell apoptosis was evaluated by flow cytometry. A genome-wide gene expression analysis was further performed to identify miR-146a-regulated genes in T cells.Results: miRNA expression profile analysis revealed that miR-146a expression was significantly upregulated while miR-363 and miR-498 were downregulated in CD4 + T cells of RA patients. The level of miR-146a expression was positively correlated with levels of tumor necrosis factor-alpha (TNF-α), and in vitro studies showed TNF-α upregulated miR-146a expression in T cells. Moreover, miR-146a overexpression was found to suppress Jurkat T cell apoptosis. Finally, transcriptome analysis of miR-146a overexpression in T cells identified Fas associated factor 1 (FAF1) as a miR-146a-regulated gene, which was critically involved in modulating T cell apoptosis.Conclusions: We have detected increased miR-146a in CD4 + T cells of RA patients and its close correlation with TNF-α levels. Our findings that miR-146a overexpression suppresses T cell apoptosis indicate a role of miR-146a in RA pathogenesis and provide potential novel therapeutic targets. © 2010 Li et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.published_or_final_versio

Biomimetic Nanosilica-Collagen Scaffolds for In Situ Bone Regeneration: Toward a Cell-Free, One-Step Surgery.

Current approaches to fabrication of nSC composites for bone tissue engineering (BTE) have limited capacity to achieve uniform surface functionalization while replicating the complex architecture and bioactivity of native bone, compromising application of these nanocomposites for in situ bone regeneration. A robust biosilicification strategy is reported to impart a uniform and stable osteoinductive surface to porous collagen scaffolds. The resultant nSC composites possess a native-bone-like porous structure and a nanosilica coating. The osteoinductivity of the nSC scaffolds is strongly dependent on the surface roughness and silicon content in the silica coating. Notably, without the use of exogenous cells and growth factors (GFs), the nSC scaffolds induce successful repair of a critical-sized calvarium defect in a rabbit model. It is revealed that topographic and chemical cues presented by nSC scaffolds could synergistically activate multiple signaling pathways related to mesenchymal stem cell recruitment and bone regeneration. Thus, this facile surface biosilicification approach could be valuable by enabling production of BTE scaffolds with large sizes, complex porous structures, and varied osteoinductivity. The nanosilica-functionalized scaffolds can be implanted via a cell/GF-free, one-step surgery for in situ bone regeneration, thus demonstrating high potential for clinical translation in treatment of massive bone defects

Prevalence of prediabetes by the fasting plasma glucose and HbA1c screening criteria among the children and adolescents of Shenzhen, China

BackgroundPrediabetes is associated with an increased risk of cardiovascular diseases and all-cause mortality. Rare research in China has evaluated the prevalence of prediabetes among children and adolescents using the HbA1c criterion or the combined FPG-or-HbA1c diagnostic criterion, and researchers paid no attention to the distributions of blood glucose in Shenzhen, especially for juveniles.MethodsWe conducted a school-based cross-sectional study based on the first-year students from 17 primary, middle, and high schools. Prediabetes was defined as FPG of 5.6–6.9 mmol/L or HbA1c of 5.7%–6.4%. The crude and standardized prevalence of prediabetes with 95% confidence interval (95% CI) was estimated.ResultsA total of 7519 participants, aged 6 to 17 years, were included. For all subjects, the crude prevalence (95% CI) of prediabetes was 1.49% (1.21–1.77), 8.72% (8.08–9.36), and 9.80% (9.13–10.47) by the FPG-only, HbA1c-only, and FPG-or-HbA1c criteria, respectively. Based on the 2010 Shenzhen census population, the standardized prevalence was 1.56% (males 1.85%, females 1.19%), 11.05% (males 11.47%, females 10.53%), and 12.19% (males 13.01%, females 11.15%) by the corresponding criteria. The proportion of prediabetes was higher for males than females, and the prevalence decreased with grade for males but increased for females. The association of BMI and prediabetes was U-shaped curve, indicating higher rates of prediabetes for underweight and obesity people.ConclusionThe blood glucose status of children and adolescents in Shenzhen is worrisome, and the early detection and management of prediabetes are imperative

B-Cell Receptor-Associated Protein 31 Promotes Metastasis via AKT/β-Catenin/Snail Pathway in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most lethal cancer worldwide, characterized with high heterogeneity and inclination to metastasize. Emerging evidence suggests that BAP31 gets involved in cancer progression with different kinds. It still remains unknown whether and how BAP31 plays a role in HCC metastasis. Epithelial–mesenchymal transition (EMT) has been a common feature in tumor micro-environment, whose inducer TGF-β increased BAP31 expression in this research. Elevated expression of BAP31 was positively correlated with tumor size, vascular invasion and poor prognosis in human HCC. Ectopic expression of BAP31 promoted cell migration and invasion while BAP31 knockdown markedly attenuated metastatic potential in HCC cells and mice orthotopic xenografts. BAP31 induced EMT process, and enhanced the expression level of EMT-related factor Snail and decreased contents and membrane distribution of E-cadherin. BAP31 also activated AKT/β-catenin pathway, which mediated its promotional effects on HCC metastasis. AKT inhibitor further counteracted the activated AKT/β-catenin/Snail upon BAP31 over-expression. Moreover, silencing Snail in BAP31-overexpressed cells impaired enhanced migratory and invasive abilities of HCC cells. In HCC tissues, BAP31 expression was positively associated with Snail. In conclusion, BAP31 promotes HCC metastasis by activating AKT/β-catenin/Snail pathway. Thus, our study implicates BAP31 as potential prognostic biomarker, and provides valuable information for HCC prognosis and treatment

The dimer state of GyrB is an active form: implications for the initial complex assembly and processive strand passage

In a previous study, we presented the dimer structure of DNA gyrase B′ domain (GyrB C-terminal domain) from Mycobacterium tuberculosis and proposed a ‘sluice-like’ model for T-segment transport. However, the role of the dimer structure is still not well understood. Cross-linking and analytical ultracentrifugation experiments showed that the dimer structure exists both in the B′ protein and in the full-length GyrB in solution. The cross-linked dimer of GyrB bound GyrA very weakly, but bound dsDNA with a much higher affinity than that of the monomer state. Using cross-linking and far-western analyses, the dimer state of GyrB was found to be involved in the ternary GyrA–GyrB–DNA complex. The results of mutational studies reveal that the dimer structure represents a state before DNA cleavage. Additionally, these results suggest that the dimer might also be present between the cleavage and reunion steps during processive transport

The complete mitochondrial genome analysis of a stonefly, Acroneuria carolinensis (Plecoptera: Perlidae)

We sequenced and annotated the species of Acroneuria carolinensis which is the second species representative of the genus Acroneuria to provide mitochondrial genome data for order Plecoptera. The complete mitochondrial genome of A. carolinensis was 15,718 bp in length and possessed 22 transfer RNA (tRNA) genes, 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes and one control region. The A + T account of the whole genome, PCGs, tRNAs, rRNAs, and the control region was 64.6%, 62.7%, 67.8%, 68.6%, and 73.9%, respectively. Ten PCGs used the normal start codon except ND2, ND5, and ND1 used the exceptional GTG and TTG as start codon. All PCGs stopped with the terminal codon TAN, but only COII gene used the single T––. The phylogenetic tree was based on the PCG12R matrix (including PCGs first and second codons and two rRNAs) by Bayesian inference (BI) method and we found that the genus Acroneuria and Sinacroneuria were clustered in a clade

The complete mitochondrial genome of a Chinese endemic stonefly species, Sinacroneuria dabieshana (Plecoptera: Perlidae)

The complete mitochondrial genome of Sinacroneuria dabieshana Li & Murányi, the first representative of the genus Sinacroneuria, was sequenced and annotated. This mitogenome was 15,752 bp long and encoded 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes and a control region. The S. dabieshana mitogenome with an A + T content of 67.3% presented a positive AT-skew (0.058) and a negative GC-skew (−0.303). Ten PCGs started with a typical ATN codon, except ATP8, COI and ND1 initiated with GTG, CCG and TTG, respectively. Eleven PCGs use the typical stop codon TAA/TAG, except COII and ND5 gene terminated with a single T. The Bayesian (BI) and maximum-likelihood (ML) trees both showed that S. dabieshana and Acroneuria hainana are the sister group. Phylogenetic relationships among six genera within Perlidae were recovered as (Caroperla + ((Acroneuria + Sinacroneuria) + (Dinocras + (Togoperla + Kamimuria))))