Circulating miR-30e-3p induces disruption of neurite development in SH-SY5Y cells by targeting ABI1, a novel biomarker for schizophrenia.

Schizophrenia (SCZ) represents a set of enduring mental illnesses whose underlying etiology remains elusive, posing a significant challenge to public health. Previous studies have shown that the neurodevelopmental process involving small molecules such as miRNA and mRNA is one of the etiological hypotheses of SCZ. We identified and verified that miR-30e-3p and ABI1 can be used as biomarkers in peripheral blood transcriptome sequencing data of patients with SCZ, and confirmed the regulatory relationship between them. To further explore their involvement, we employed retinoic acid (RA)-treated SH-SY5Y differentiated cells as a model system. Our findings indicate that in RA-induced SH-SY5Y cells, ABI1 expression is up-regulated, while miR-30e-3p expression is down-regulated. Functionally, both miR-30e-3p down-regulation and ABI1 up-regulation promote apoptosis and inhibit the proliferation of SH-SY5Y cells. Subsequently, the immunofluorescence assay detected the expression location and abundance of the neuron-specific protein ß-tubulinIII. The expression levels of neuronal marker genes MAPT, TUBB3 and SYP were detected by RT-qPCR. We observed that these changes of miR-30e-3p and ABI1 inhibit the neurite growth of SH-SY5Y cells. Rescue experiments further support that ABI1 silencing can correct miR-30e-3p down-regulation-induced SH-SY5Y neurodevelopmental defects. Collectively, our results establish that miR-30e-3p's regulation of neurite development in SH-SY5Y cells is mediated through ABI1, highlighting a potential mechanism in SCZ pathogenesis.

Causal association of gastroesophageal reflux disease with chronic sinusitis and chronic disease of the tonsils and adenoids.

BACKGROUND: Exploring bidirectional causal associations between gastroesophageal reflux disease (GERD) and chronic disease of the tonsils and adenoids and chronic sinusitis, respectively. METHODS: We first conducted a TSMR (two-sample mendelian randomization) study using the results of the inverse variance weighting method as the primary basis and bidirectional MR to rule out reverse causation. Subsequently, MVMR (multivariate MR) analysis was performed to identify phenotypes associated with SNPs and to explore the independent effect of GERD on two outcomes. Finally, we calculated MR-Egger intercepts to assess horizontal polytropy and Cochran's Q statistic to assess heterogeneity and ensure the robustness of the study. RESULTS: For each standard deviation increase in genetically predicted GERD rate, there was an increased risk of chronic disease of the tonsils and adenoids (OR 1.162, 95% CI 1.036-1.304, P: 1.06E-02) and of developing chronic sinusitis (OR 1.365, 95% CI 1.185-1.572, P: 1.52E-05), and there was no reverse causality. Causality for TSMR was obtained on the basis of IVW (inverse variance weighting) and appeared to be reliable in almost all sensitivity analyses, whereas body mass index may be a potential mediator of causality between GERD and chronic sinusitis. CONCLUSION: There is a causal association between GERD and chronic disease of the tonsils and adenoids and chronic sinusitis, respectively, and the occurrence of GERD increases the risk of developing chronic disease of the tonsils and adenoids and chronic sinusitis.

Exploration of Positive and Negative Schizophrenia Symptom Heterogeneity and Establishment of Symptom-Related miRNA-mRNA Regulatory Network: Based on Transcriptome Sequencing Data.

Schizophrenia (SCZ) symptoms can be classified as positive and negative ones, each of which has distinct traits and possibly differences in gene expression and regulation. The co-expression networks linked to PANSS (Positive and Negative Syndrome Scale) scores were identified by weighted gene co-expression network analysis (WGCNA) using the expression profiles of miRNA and mRNA in the peripheral blood of first-episode SCZ patients. The heterogeneity between positive and negative symptoms was demonstrated using gene functional enrichment, gene-medication interaction, and immune cell composition analysis. Then, target gene prediction and correlation analysis of miRNA and mRNA constructed a symptom-related miRNA-mRNA regulatory network, screened regulatory pairs, and predicted binding sites. A total of six mRNA co-expression modules, two miRNA co-expression modules, and ten hub genes were screened to be significantly associated with positive symptoms; five mRNA co-expression modules and eight hub genes were correlated with negative symptoms. Positive symptom-related modules were significantly enriched in axon guidance, actin skeleton regulation, and sphingolipid signaling pathway, while negative symptom-related modules were significantly enriched in adaptive immune response, leukocyte migration, dopaminergic synapses, etc. The development of positive symptoms may have been influenced by potential regulatory pairings such as miR-98-5p-EIF3J, miR-98-5p-SOCS4, let-7b-5p-CLUH, miR-454-3p-GTF2H1, and let-7b-5p-SNX17. Additionally, immune cells were substantially connected with several hub genes for symptoms. Positive and negative symptoms in SCZ individuals were heterogeneous to some extent. miRNAs such as let-7b-5p and miR-98-5p might contribute to the incidence of positive symptoms by targeting mRNAs, while the immune system's role in developing negative symptoms may be more nuanced.

The causal effect of schizophrenia on fractures and bone mineral density: a comprehensive two-sample Mendelian randomization study of European ancestry.

BACKGROUND: Schizophrenia was clinically documented to co-occur with fractures and aberrant bone mineral density (BMD), but the potential causal relationship remained unclear. This study aimed to test the causal effects between schizophrenia and fractures as well as aberrant BMD by conducting Mendelian randomization (MR) analyses. METHODS: Two-sample MR was utilized, based on instrumental variables from large genome-wide association studies (GWAS) of schizophrenia as exposure, to identify the causal association of schizophrenia with mixed fractures, fractures at different body sites (including skull and facial bones, shoulder and upper arm, wrist and hand, and femur) and BMDs of forearm (FA), femoral neck (FN), lumbar spine (LS) and estimated BMD (eBMD). Multivariable Mendelian randomization (MVMR) analysis was performed to minimize the confounding effect of body mass index (BMI). RESULTS: Result from inverse variance weighting (IVW) method provided evidence schizophrenia increased the risk of fractures of skull and facial bones [odds ratio (OR) = 1.0006, 95% confidence interval (CI): 1.0003 to 1.0010] and femur [OR =1.0007, 95% CI: 1.0003 to 1.0011], whereas, decreased the level of eBMD [ß (95%CI): -0.013 (-0.021, -0.004)]. These causal effects still existed after adjusting for BMI. Sensitivity analyses showed similar results. However, no causal effect of schizophrenia on fracture or BMD in other parts was detected. CONCLUSION: The current finding confirmed that schizophrenia was causally associated with the fractures of skull, face and femur as well as eBMD, which might remind psychiatrists to pay close attention to the fracture risk in schizophrenic patients when formulating their treatment strategies.

Assessment of causal relationships between omega-3 and omega-6 polyunsaturated fatty acids in bipolar disorder: a 2-sample bidirectional mendelian randomization study.

Omega-3 fatty acids may be protective against bipolar disorder (BD), whereas omega-6 fatty acids and an increased omega-6:omega-3 ratio may increase the risk of BD. This causal relationship has not yet been established. We attempted to prove the existence of these causal relationships in this study. Datasets on omega-3, omega-6, and omega-6:omega-3 ratios were obtained from the UK Biobank. The EBI database was used to obtain the BD dataset. SNPs associated with fatty acids were identified as instrumental variables (IVs) that met the criteria of P < 5 × 10-8, LD (R2 > 0.01), and kb < 10 000. The main analytical method in this study was the inverse variance weighted (IVW) method. Furthermore, we employ a variety of methods for sensitivity analysis. According to the IVW analysis, higher omega-3 levels were associated with a lower risk of BD (OR = 0.884, 95%CI: 0.796-0.982, P < 0.05). An increase in the omega-6:omega-3 ratio was associated with an increased risk of BD (OR = 1.172, 95%CI: 1.046-1.314, P < 0.05), but no causal relationship between omega-6 levels and BD risk was unearthed. Our MR findings suggest that the ratio of omega-3, omega-6:omega-3 is associated with the risk of BD. It is important to be concerned about the risk of BD in individuals with low serum omega-3 intake and a high omega-6:omega-3 ratio.