No abstract

Despite increasing evidence that long non-coding RNAs (lncRNAs) widely take part in human diseases, the role of lncRNAs in systemic lupus erythematosus (SLE) is largely unknown. In this study, we performed a two-stage study to explore the plasma levels of five lncRNAs (GAS5, linc0949, linc0597, HOTAIRM1 and lnc-DC) and their potential as SLE biomarkers. Compared with healthy controls, plasma levels of GAS5 and lnc-DC were significantly decreased (P < 0.001 and P = 0.002, respectively) while linc0597 were overexpressed in SLE patients (P < 0.001). When SLE patients were divided into SLE without nephritis and lupus nephritis (LN), the levels of lnc-DC were significantly higher in LN compared with SLE without nephritis (P = 0.018), but no significant difference in levels of GAS5 and linc0597 were found between LN and SLE without nephritis; plasma linc0949 level showed no significant difference in all comparisons. Further evaluation on potential biomarkers showed that GAS5, linc0597 and lnc-DC may specifically identify patients with SLE, the combination of GAS5 and linc0597 provided better diagnostic accuracy; lnc-DC may discriminate LN from SLE without nephritis. In summary, GAS5, linc0597 and lnc-DC in plasma could be potential biomarkers for SLE.

The observational association between gut microbiome and systemic lupus erythematosus (SLE) has been well documented. However, whether the association is causal remains unclear. The present study used publicly available genome-wide association study (GWAS) summary data to perform two-sample Mendelian randomization (MR), aiming to examine the causal links between gut microbiome and SLE. Two sets of MR analyses were conducted. A group of single nucleotide polymorphisms (SNPs) that less than the genome-wide statistical significance threshold (5 × 10-8) served as instrumental variables. To obtain a comprehensive conclusion, the other group where SNPs were smaller than the locus-wide significance level (1 × 10-5) were selected as instrumental variables. Based on the locus-wide significance level, the results indicated that there were causal effects of gut microbiome components on SLE risk. The inverse variance weighted (IVW) method suggested that Bacilli and Lactobacillales were positively correlated with the risk of SLE and Bacillales, Coprobacter and Lachnospira were negatively correlated with SLE risk. The results of weighted median method supported that Bacilli, Lactobacillales, and Eggerthella were risk factors for SLE and Bacillales and Coprobacter served as protective factors for SLE. The estimates of MR Egger suggested that genetically predicted Ruminiclostridium6 was negatively associated with SLE. Based on the genome-wide statistical significance threshold, the results showed that Actinobacteria might reduce the SLE risk. However, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) detected significant horizontal pleiotropy between the instrumental variables of Ruminiclostridium6 and outcome. This study support that there are beneficial or detrimental causal effects of gut microbiome components on SLE risk.

The triple-negative breast cancer (TNBC), with a particularly poor prognosis, is increasingly recognized as heterogeneous in molecular signatures. MicroRNA expression profiles have been used for the classification and prognostication of breast cancer, numerous significantly upregulated microRNAs, i.e. miR-21, have been verified oncogenic in non-TNBCs. In present study, we determined the miR-21 levels in TNBC specimens, and TNBC cell levels in vitro, and then identified the role of miR-21 on tumor cell proliferation, apoptosis, and then identified PTEN as the possible target of the microRNA. It was shown that miR-21 expression is upregulated generally, and heterogeneous in TNBC specimens, posing a correlation with poor prognosis for TNBC patients. Further results demonstrated that the upregulated miR-21 promoted the tumor proliferation and inhibited cell apoptosis in vitro. And pro-apoptotic PTEN had been shown being targeted and downregulated. Therefore, our finding emphasized the oncogenic role of miR-21 in TNBC.

We evaluated the differences in major markers of cardiovascular (CV) risk between inflammatory bowel diseases (IBDs) and controls by a systematic review and a meta-analysis. We searched PubMed, EMBASE, and Cochrane databases for literature comparing CV risk markers in IBDs and controls. The overall mean carotid intima-media thickness (CIMT), flow-mediated dilation (FMD%), and carotid-femoral pulse wave velocity (cfPWV) difference between patients with IBDs and control groups were calculated. Twenty-eight studies were included in the meta-analysis, including 16 studies with data on CIMT, 7 studies reporting FMD%, and 9 studies on cfPWV. Compared to controls, patients with IBDs showed significantly higher CIMT (standardized mean difference [ SMD]: 0.534 mm; 95% confidence interval [CI], 0.230 to 0.838; P = .001), significantly lower FMD% ( SMD, -0.721%; 95% CI, -1.020 to -0.421; P < .0001), and significantly increased cfPWV ( SMD, 0.849; 95% CI, 0.589 to 1.110; P < .0001). When analyzing subgroups with ulcerative colitis and Crohn disease (CD), all results were still significant except CIMT in CD. Our findings support the current evidence for an elevated CV burden in patients with IBD and support the clinical utility of markers of subclinical atherosclerosis in the management of these patients.