Prediction of shared gene signatures and biological mechanisms between polycystic ovary syndrome and asthma: Based on weighted gene coexpression network analysis.

OBJECTIVE: Several clinical studies have shown an association between polycystic ovary syndrome (PCOS) and asthma; however, the molecular link between these conditions remains unclear. In this study, we conducted a reanalysis and repurposing of existing databases in order to depict the common key genes, related signaling pathways, and similarity of the immune microenvironment between PCOS and asthma. METHODS: PCOS and asthma data sets were downloaded, and common signal pathways were identified by using gene set enrichment analysis. Identified common susceptibility genes were explored by intersecting the weighted gene coexpression network analysis module genes for both diseases. Then, we performed protein-protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses of the common susceptibility genes. Finally, we analyzed the immune environment of PCOS and asthma. RESULTS: We identified five hub genes, namely, MMP9, CDC42, CD44, CD19, and BCL2L1, and uncovered that these five hub genes showed a tendency to be upregulated in both PCOS and asthma and possessed good diagnostic ability. In addition, we revealed that both PCOS and asthma were significantly enriched in the FcεRI-mediated signaling pathway. Moreover, we found that both PCOS and asthma exhibited infiltration of similar types of immune cells, such as monocytes, suggesting that the two diseases have similar pathological features. CONCLUSION: PCOS and asthma share common causative genes with a similar immune environment. Taken together, we uncovered previously unsuspected traits for comprehensive diagnosis and treatment of PCOS and asthma in the future.

Machine learning and bioinformatics framework integration reveal potential characteristic genes related to immune cell infiltration in preeclampsia.

Introduction: Preeclampsia is a disease that affects both the mother and child, with serious consequences. Screening the characteristic genes of preeclampsia and studying the placental immune microenvironment are expected to explore specific methods for the treatment of preeclampsia and gain an in-depth understanding of the pathological mechanism of preeclampsia. Methods: We screened for differential genes in preeclampsia by using limma package. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, disease ontology enrichment, and gene set enrichment analyses were performed. Analysis and identification of preeclampsia biomarkers were performed by using the least absolute shrinkage and selection operator regression model, support vector machine recursive feature elimination, and random forest algorithm. The CIBERSORT algorithm was used to analyze immune cell infiltration. The characteristic genes were verified by RT-qPCR. Results: We identified 73 differential genes, which mainly involved in reproductive structure and system development, hormone transport, etc. KEGG analysis revealed emphasis on cytokine-cytokine receptor interactions and interleukin-17 signaling pathways. Differentially expressed genes were dominantly concentrated in endocrine system diseases and reproductive system diseases. Our findings suggest that LEP, SASH1, RAB6C, and FLT1 can be used as placental markers for preeclampsia and they are associated with various immune cells. Conclusion: The differentially expressed genes in preeclampsia are related to inflammatory response and other pathways. Characteristic genes, LEP, SASH1, RAB6C, and FLT1 can be used as diagnostic and therapeutic targets for preeclampsia, and they are associated with immune cell infiltration. Our findings contribute to the pathophysiological mechanism exploration of preeclampsia. In the future, the sample size needs to be expanded for data analysis and validation, and the immune cells need to be further validated.

Association of maternal triglyceride responses to thyroid function in early pregnancy with gestational diabetes mellitus.

Introduction: The prevalence of Gestational Diabetes Mellitus (GDM) is increasing globally, and high levels of triglyceride (TG) and low levels of free thyroxine (FT4) in early pregnancy are associated with an increased risk of GDM; however, the interaction and mediation effects remain unknown. The aim of the present study is to examine the impact of FT4 and TG combined effects on the prevalence of GDM and the corresponding casual paths among women in early pregnancy. Materials and methods: This study comprised 40,156 pregnant women for whom early pregnancy thyroid hormones, fasting blood glucose as well as triglyceride were available. GDM was diagnosed using a 2-hour 75-g oral glucose tolerance test (OGTT) according to the American Diabetes Association guidelines, and the pregnant women were grouped and compared according to the results. Results: An L-shaped association between FT4 and GDM was observed. The prevalence of GDM increased with increasing TG levels. After accounting for multiple covariables, the highest risk for GDM was found among pregnant women of lower FT4 with the highest TG concentrations (odds ratio, 2.44, 95% CI, 2.14 to 2.80; P<0.001) compared with mothers of higher FT4 with the TG levels in the lowest quartile (Q1). There was a significant interaction effect of maternal FT4 and TG levels on the risk for GDM (P for interaction = 0.036). The estimated proportion of the mediating effect of maternal TG levels was 21.3% (95% CI, 15.6% to 36.0%; P < 0.001). In the sensitivity analysis, the mediating effect of TG levels was stable across subgroups. Conclusion: This study demonstrated an L-shaped association between maternal FT4 levels and GDM and the benefit of low TG levels, in which maternal TG levels act as an important mediator in this association. Our findings suggested that pregnant women who treat hypothyroidism should also reduce triglycerides levels in early pregnancy to prevent GDM development.

Construction of a ceRNA network in polycystic ovary syndrome (PCOS) driven by exosomal lncRNA.

Polycystic ovary syndrome (PCOS), a common and frustrating syndrome in women of reproductive age, is characterized by symptoms including hyperandrogenemia, ovulation dysfunction, and polycystic ovaries. The role of competitive endogenous RNA (ceRNA) networks is receiving increasing attention and has been reported in multiple complicated diseases, such as various carcinomas, endometriosis, and tubal factor infertility. However, the association of ceRNA networks with the pathogenesis of PCOS remains unclear. This study aimed to construct a ceRNA network orchestrated by exosomal lnRNA and circRNA in PCOS. We screened RNA data of 34 samples from the Gene Expression Omnibus (GEO) database for differentially expressed lncRNAs (DELs), miRNAs (DEMs), mRNAs (DEGs), and circRNA associated with the progression of PCOS (PCOS, n = 17 vs. normal, n = 17). A protein-protein interaction (PPI) network, gene set enrichment analysis (GSEA), and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted. Importantly, the function of the ceRNA network was explored using GO and KEGG enrichment analyses. We identified 46 DELs (25 upregulated and 21 downregulated), 31 DEMs (20 upregulated and 11 downregulated), 165 DEGs (52 upregulated and 113 downregulated), and 1 differentially expressed circRNA. The PPI network had 79 nodes and 112 edges. The GSEA results showed that these genes were mainly related to oxidative phosphorylation; TNF signaling pathways; and valine, leucine, and isoleucine degradation. GO and KEGG analyses revealed that the DEGs were significantly enriched in lipid metabolism, peroxisome proliferator-activated receptor (PPAR) signaling pathways, and fatty acid metabolism. Additionally, we constructed a novel PCOS-associated lncRNA-miRNA-mRNA ceRNA triple network and a circRNA-related network. Thereafter, we described the potential roles played by follicular fluid exosomes in PCOS. Our present study describes the molecular pathogenesis of PCOS in human ovarian granulosa cells at the post-transcriptional level, which provides new insights for the clinical diagnosis and treatment of PCOS and further scientific research.

Integrative Single-Cell Transcriptomic Analysis of Human Fetal Thymocyte Development.

Intrathymic differentiation of T lymphocytes begins as early as intrauterine stage, yet the T cell lineage decisions of human fetal thymocytes at different gestational ages are not currently understood. Here, we performed integrative single-cell analyses of thymocytes across gestational ages. We identified conserved candidates underlying the selection of T cell receptor (TCR) lineages in different human fetal stages. The trajectory of early thymocyte commitment during fetal growth was also characterized. Comparisons with mouse data revealed conserved and species-specific transcriptional dynamics of thymocyte proliferation, apoptosis and selection. Genome-wide association study (GWAS) data associated with multiple autoimmune disorders were analyzed to characterize susceptibility genes that are highly expressed at specific stages during fetal thymocyte development. In summary, our integrative map describes previously underappreciated aspects of human thymocyte development, and provides a comprehensive reference for understanding T cell lymphopoiesis in a self-tolerant and functional adaptive immune system.