Immunoregulatory role of AC007278.3 and HOTAIR long non-coding RNAs in lupus nephritis: potential biomarkers and therapeutic targets.

Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various biological processes, including immune regulation and autoimmune pathologies. However, their specific significance in modulating the cytokine network in systemic lupus erythematosus (SLE) remains largely unexplored. This study assessed the expression patterns of immune-related lncRNAs, HOTAIR, and AC007278.3, along with their related protein-coding genes, TNF-α and IL18RAP, in nephritic SLE patients. Additionally, the potential of selected genes as diagnostic biomarkers for SLE was evaluated. Blood samples were obtained from SLE patients (n = 30) and age-sex-matched healthy controls (HCs) (n = 60). Subsequently, RNA was isolated from peripheral blood mononuclear cells (PBMCs), and cDNA was synthesized to analyze the expression levels of the target genes using real-time PCR. The correlation analysis between the relative expressions of different genes was examined in both the patient and HC groups. The diagnostic potential of the lncRNAs was determined by calculating the Area Under the Curve of the Receiver Operating Characteristics (AUC of ROC), Cut-off, sensitivity, and specificity. Our results indicated a significant upregulation of lncRNAs AC007278.3 (fold change [FC] = 14.13, p-value < 0.0001) and HOTAIR (FC = 14.1, p-value < 0.0001). Correspondingly, their associated target genes, TNF-α and IL18RAP, were also overexpressed in patients (FC = 2.66 and FC = 5.18, respectively, p-value < 0.001). Notably, a strong positive correlation was observed between IL18RAP and AC007278.3 in SLE patients. Moreover, the AUC of ROC analyses underscored the diagnostic efficacy of AC007278.3 alone and combined with HOTAIR, yielding values of 0.89 and 0.86, respectively. These findings highlight the potential immunoregulatory roles of lncRNAs AC007278.3 and HOTAIR, emphasizing their significance as promising diagnostic biomarkers and potential therapeutic targets for SLE. Additionally, they provide valuable insights into the molecular mechanisms underpinning the disease's pathogenesis.

Rasuli E ，Javidi-Aghdam K ，Akbarzadeh-Khiavi M ，Abdshah A ，Gadakchi L ，Jafarpour M ，Khabbazi A ，Farajnia S ，Safary A ，Shaykh-Baygloo N ... -  《-》

Role of NEAT1 and HOTAIR long non-coding RNAs in Behcet's Disease pathogenesis and their correlation with target inflammatory cytokines.

Recent studies have highlighted the potential role of several long non-coding RNAs (lncRNAs) in the pathogenesis of Behçet's disease (BD). This study investigated the expression profiles of lncRNA NEAT1 and lncRNA HOTAIR, and their target cytokine genes, IL-6 and TNF-α, in active and inactive BD patients. This cross-sectional study was conducted on peripheral blood mononuclear cells (PBMCs) obtained from 25 BD patients and 25 age-sex-matched healthy controls (HCs). BD activity was evaluated using the BDCAF (Behcet's Disease Current Activity Form) score. Correlation analysis assessed the relationship between BD activity and the expression levels of lncRNAs and their target cytokine genes. The diagnostic potential of the genes was evaluated using Receiver Operating Characteristic (ROC) curve analysis. The expression levels of NEAT1, HOTAIR, IL-6, and TNF-α were significantly higher in the BD group compared to the HCs. However, there was no significant correlation between the expression levels of these genes and BD activity or the involvement of various organs. A positive correlation was observed between HOTAIR gene expression and IL-6 (R = 0.594, P-value = 0.009) in the BD group. In contrast, no significant correlation was found between HOTAIR and TNF-α or between NEAT1 and TNF-α or IL-6. The ROC curve analysis indicated strong diagnostic potential for the lncRNAs, with area under the curve (AUC) values of 0.90 for NEAT1 and 0.86 for HOTAIR. The elevated expression levels of NEAT1 and HOTAIR in BD patients suggest their potential involvement in the disease's pathogenesis, indicating promising targets for future diagnostic and therapeutic strategies in BD.

Javidi-Aghdam K ，Faghfouri A ，Jafarpour M ，Akbarzadeh-Khiavi M ，Safary A ，Pourbagherian O ，Khabbazi A ... -  《-》

The diagnostic and predictive potential of lncRNA CASC2 targeting miR-155 in systemic lupus erythematosus patients with nephritis complication.

Lupus nephritis (LN) is a serious problem that results from systemic lupus erythematosus (SLE) complications. Recent studies have highlighted that non-coding RNA (ncRNA) dysregulation is a notable feature in patients with SLE. As a result, this research was designed to investigate lncRNA CASC2 and miR-155 levels as non-invasive diagnostic biomarkers in SLE patients, including those with and without nephritis, and to investigate their effectiveness in assessing disease severity and predicting LN. Our study included 60 patients with SLE who were subclassified into (30 non-LN and 30 LN groups), along with 30 control subjects. Quantification of lncRNA CASC2 and miR-155 in serum samples from the Egyptian population was carried out with real-time polymerase chain reaction (RT-PCR). The disease activity index (SLEDAI) for SLE was evaluated, and the analysis of the receiver operating characteristic (ROC) curve was implemented. Increased levels of lncRNA CASC2 were observed in SLE patients compared to healthy controls, with even higher levels observed in the LN group versus the non-LN patients' group. Conversely, miR-155 was noted to be down-regulated in SLE patients relative to controls, and its levels were lower in the LN group relative to the non-LN patients' group. The elevated expression of lncRNA CASC2 and reduced expression of miR-155 were both correlated to the severity of the disease. The current study illustrated that both lncRNA CASC2 and miR-155 could act as valuable non-invasive diagnostic biomarkers for SLE and predicting LN among SLE patients, as well as their abilities to detect the disease severity and progression.

Mohamed NR ，El-Fattah ALA ，Shaker O ，Sayed GA ... -  《Scientific Reports》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》

Urinary microbiome profiling as a non-invasive tool for identifying biomarkers in systemic lupus erythematosus and lupus nephritis.

Bacteriome alterations have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). However, the relationship between SLE and the urinary microbiome remains underexplored. This study aimed to characterize the urinary microbiome of SLE patients using 16S rRNA sequencing and to investigate its correlations with clinical parameters through integrative analyses. Urine sediment samples were collected from individuals with SLE and lupus nephritis (LN) (n = 20), SLE without LN (n = 22), and healthy controls (HCs) (n = 23). DNA was extracted and subjected to 16S rRNA sequencing to profile the urinary microbiome. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic efficacy of urinary microbiota, while Spearman's correlation analysis was employed to identify links between specific microbial taxa and clinical parameters. Functional predictions of bacterial roles were performed using Picrust2. The urinary microbiota diagnostic model exhibited excellent performance in distinguishing SLE patients from HCs. Spearman's analysis revealed significant correlations between the urinary microbiome and clinical parameters. Specifically, Sphingomonas and Lachnospiraceae genera showed positive correlations with vitamin D levels, cylinderuria, and proteinuria, while Pedobacter, Aquabacterium, Delftia, and Achromobacter displayed negative correlations with proteinuria and albumin-to-creatinine ratio (ACR). Functional predictions indicated that the urinary microbiome might influence immune regulation through modulation of signaling pathways and metabolic processes. Our study is the first to reveal dysbiosis in the urinary microbiome of patients with SLE. Certain bacterial taxa in the urinary microbiome were identified as potential diagnostic biomarkers for SLE. Furthermore, the functional implications of these bacterial communities suggest their involvement in immune modulation, highlighting the potential for further investigation into their roles in SLE pathogenesis and diagnosis.

Shi B ，Chen F ，Gong J ，Khan A ，Qian X ，Xu Z ，Yang P ... -  《Frontiers in Cellular and Infection Microbiology》