Evidence for genetic association of TBX21 and IFNG with systemic lupus erythematosus in a Chinese Han population

TBX21 recode T-bet which is an important transcription factor that drives the Th1 immune response primarily by promoting expression of the interferon-gamma (IFNG) gene. Recent studies have shown that genetic variants in TBX21 and IFNG are connected with risk of systemic lupus erythematosus (SLE). The aim of the present study was to replicate these genetic associations with SLE in Anhui Chinese population. Genotyping of 3 variants (rs4794067 in TBX21, rs2069705 and rs2069718 in IFNG) was performed. A total of 3732 subjects were included in the final analysis. The study only identified the association of rs2069705 with SLE susceptibility (T vs. C: odds ratio [OR] = 1.12, 95% confidence interval [CI] = 1.00-1.26, P = 0.046). Combined analysis with Hong Kong GWAS showed that the OR for rs2069705 was 1.10 (95% CI: 1.01-1.21, P = 0.027). Further pooled analysis with Korean populations involving 10498 subjects showed a more significant association between rs2069705 and SLE (T vs. C: OR = 1.11, 95%CI = 1.04-1.19, P = 0.002; TT + TC vs. CC: OR = 1.11, 95%CI = 1.02-1.21, P = 0.012; TT vs. TC + CC: OR = 1.28, 95%CI = 1.07-1.54, P = 0.008; TT vs. CC: OR = 1.33, 95%CI = 1.10-1.60, P = 0.003). In addition, we also identified a significant genetic interaction between rs2069705 and rs4794067 in Anhui Chinese population. Our study suggests that IFNG and IFNG-TBX21 interaction are involved in SLE susceptibility.published_or_final_versio

MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice

Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic steatosis. Male C57BL/6 wild-type (WT) and miR-155−/− mice were fed either normal chow or high fat diet (HFD) for 6 months then lipid levels, metabolic and inflammatory parameters were assessed in livers and serum of the mice. Mice lacking endogenous miR-155 that were fed HFD for 6 months developed increased hepatic steatosis compared to WT controls. This was associated with increased liver weight and serum VLDL/LDL cholesterol and alanine transaminase (ALT) levels, as well as increased hepatic expression of genes involved in glucose regulation (Pck1, Cebpa), fatty acid uptake (Cd36) and lipid metabolism (Fasn, Fabp4, Lpl, Abcd2, Pla2g7). Using miRNA target prediction algorithms and the microarray transcriptomic profile of miR-155−/− livers, we identified and validated that Nr1h3 (LXRα) as a direct miR-155 target gene that is potentially responsible for the liver phenotype of miR-155−/− mice. Together these data indicate that miR-155 plays a pivotal role regulating lipid metabolism in liver and that its deregulation may lead to hepatic steatosis in patients with diabetes

Role of MicroRNA Profile Modifications in Hepatitis C Virus-Related Mixed Cryoglobulinemia

Hepatitis C virus infection is closely related to lymphoproliferative disorders (LPDs), including mixed cryoglobulinemia (MC) and some lymphomas. Modification of the expression of specific microRNAs (miRNAs) has been associated with different autoimmune diseases and/or LPDs. No data exist about the modifications in miRNA expression in HCV-associated LPDs. The aim of this study was to analyze the expression levels of a panel of miRNAs previously associated with autoimmune/LPDs in a large population of HCV patients with and without MC or non-Hodgkin’s lymphoma (NHL), to identify potential markers of evolution of HCV infection. PBMC expression of miR-Let-7d, miR-16, miR-21, miR-26b, miR-146a and miR-155 was evaluated by real-time PCR in 167 HCV patients (75 with MC [MC-HCV], 11 with HCV-associated NHL [NHL-HCV], 81 without LPD [HCV]) and in 35 healthy subjects (HS). A significant increase in miR-21 (p<0.001), miR-16 (p<0.01) and miR-155 (p<0.01) expression was detected in PBMCs from only NHL patients whereas a significant decrease in miR-26b was detected in both MC and NHL subjects (p<0.01) when compared to HS and HCV groups. A restoration of miR-26b levels was observed in the post-treatment PBMCs of 35 HCV-MC patients experiencing complete virological and clinical response following antiviral therapy. This study, for the first time, shows that specific microRNAs in PBMC from HCV patients who developed MC and/or NHL are modulated differently. The specific, reversible downregulation of miR-26b strongly suggests the key role it plays in the pathogenesis of HCV-related LPDs and its usefulness as a biomarker of the evolution of HCV infection to these disorders

MicroRNA-210 and its theranostic potential

MicroRNAs (miRNAs) are a set of small single-stranded noncoding RNAs with diverse biological functions. As a prototypical hypoxamir, human microRNA-210 (hsa-miR-210) is one of the most widely studied miRNAs thus far. In addition to its involvement in sophisticated regulation of numerous biological processes, miR-210 has also been shown to be associated with the development of different human diseases including various types of cancers, cardiovascular and cerebrovascular diseases, and immunological diseases. Given its multi-faceted functions, miR-210 may serve as a novel and promising theranostic target for prevention and treatment of diseases. Areas covered: This review aims to provide a comprehensive overview of miR-210, the regulation of its expression, biological functions and molecular mechanisms, with particular emphasis on its diagnostic and therapeutic potential. Expert opinion: Although the exact roles of miR-210 in various diseases have not been fully clarified, targeting miR-210 may be a promising therapeutic strategy. Further investigations are also needed to facilitate therapeutic-clinical applications of miR-210 in human diseases

A novel pore-fracture dual network modeling method considering dynamic cracking and its applications

Unconventional reservoirs are normally characterized by dual porous media, which has both multi-scale pore and fracture structures, such as low permeability or tight oil reservoirs. The seepage characteristics of such reservoirs is mainly determined by micro-fractures, but conventional laboratory experimental methods are difficult to measure it, which is attribute to the dynamic cracking of these micro-fractures. The emerging digital core technology in recent years can solve this problem by developing an accurate pore network model and a rational simulation approach. In this study, a novel pore-fracture dual network model was established based on percolation theory. Fluid flow in the pore of two scales, micro-fracture and matrix pore, were considered, also with the impact of micro-fracture opening and closing during flow. Some seepage characteristic parameters, such as fluid saturations, capillary pressure, relative permeabilities, displacement efficiency in different flow stage, can be predicted by proposed calculating method. Through these work, seepage characteristics of dual porous media can be achieved. © 2019 Chinese Petroleum Societ