The present meta-analysis revealed that 16 stress-related miRNAs were significantly dysregulated in T2DM. MiR-148b, miR-223, miR-130a, miR-19a, miR-26b and miR-27b were selected as potential circulating biomarkers of T2DM. In addition, miR-146a and miR-21 were identified as potential tissue biomarkers of T2DM.
Hypertrophic cardiomyopathy (HCM) is a complex inherited cardiovascular disease. The present study investigated the long noncoding (lnc)RNA/microRNA (mi)RNA/mRNA expression pattern of patients with HCM and aimed to identify key molecules involved in the development of this condition. An integrated strategy was conducted to identify differentially expressed miRNAs (DEmiRs), differentially expressed lncRNAs (DElncs) and differentially expressed genes (DEGs) based on the GSE36961 (mRNA), GSE36946 (miRNA), GSE68316 (lncRNA/mRNA) and GSE32453 (mRNA) expression profiles downloaded from the Gene Expression Omnibus datasets. Bioinformatics tools were employed to perform function and pathway enrichment analysis, protein-protein interaction, lncRNA-miRNA-mRNA and hub gene networks. Subsequently, DEGs were used as targets to predict drugs. The results indicated that a total of 2,234 DElncs (1,120 upregulated and 1,114 downregulated), 5 DEmiRs (2 upregulated and 3 downregulated) and 42 DEGs (35 upregulated and 7 downregulated) were identified in 4 microarray profiles. Gene ontology analysis revealed that DEGs were mainly involved in actin filament and stress fiber formation and in calcium ion binding, whereas Kyoto Encyclopedia of Genes and Genomes pathway analysis identified the hypoxia inducible factor-1, transforming growth factor-β and tumor necrosis factor signaling pathways as the main pathways involved in these processes. The hub genes were screened using cytoHubba. A total of 1,086 lncRNA-miRNA-mRNA interactions including 67 lncRNAs, 5 miRNAs and 25 mRNAs were mined in the present study based on prediction websites. Drug prediction indicated that the targeted drugs mainly included angiotensin converting enzyme inhibitors or β-blockers. A comprehensive bioinformatics analysis of the molecular regulatory lncRNA-miRNA-mRNA network was performed and potential therapeutic applications of drugs were predicted in HCM patients. The data may unravel the future molecular mechanism of HCM.
Interactions between climate change and anthropogenic activities result in increasing numbers of open fires, which have been shown to harm maternal health. However, few studies have examined the association between open fire and pregnancy loss. We conduct a self-comparison case-control study including 24,876 mothers from South Asia, the region with the heaviest pregnancy-loss burden in the world. Exposure is assessed using a chemical transport model as the concentrations of fire-sourced PM2.5 (i.e., fire PM2.5). The adjusted odds ratio (OR) of pregnancy loss for a 1-μg/m3 increment in averaged concentration of fire PM2.5 during pregnancy is estimated as 1.051 (95% confidence intervals [CI]: 1.035, 1.067). Because fire PM2.5 is more strongly linked with pregnancy loss than non-fire PM2.5 (OR: 1.014; 95% CI: 1.011, 1.016), it contributes to a non-neglectable fraction (13%) of PM2.5-associated pregnancy loss. Here, we show maternal health is threaten by gestational exposure to fire smoke in South Asia.
Background The prevalence of landscape fires has increased, particularly in low-income and middle-income countries (LMICs). We aimed to assess the impact of exposure to landscape fire smoke (LFS) on the health of children.
MethodsWe conducted a sibling-matched case-control study and selected 552 155 children (aged <18 years) from Demographic and Health Surveys in 55 LMICs from 2000 to 2014. Each deceased child was matched with their sibling(s). The exposure indicators were fire-sourced PM 2•5 and dry-matter emissions. We associated these exposure indicators with child mortality using conditional regressions, and derived an exposure-response function using a non-linear model. Based on the association, we quantified the global burden of fire-attributable child deaths in LMICs from 2000 to 2014. Findings Each 1 µg/m³ increment of fire-sourced PM 2•5 was associated with a 2•31% (95% CI 1•50-3•13) increased risk of child mortality. The association was robust to different models. The exposure-response function was superlinear and suggested per-unit exposure to larger fires was more toxic. Based on our non-linear exposureresponse function, we estimated that between 2000 and 2014, the five countries with the largest number of child deaths associated with fire-sourced PM 2•5 were Nigeria (164 000 [126 000 to 209 000] annual deaths), Democratic Republic of the Congo (126 000 [95% CI 114 000 to 139 000] annual deaths), India (65 900 [−22 200 to 147 000] annual deaths), Uganda (30 200 [24 500 to 36 300] annual deaths), and Indonesia (28 900 [19 100 to 38 400]).Interpretation Exposure to landscape fire smoke contributes substantially to the global burden of child mortality.
Circular RNAs (circRNAs) are stable and abundantly expressed in vivo but are abnormally expressed in several diseases. This study aimed to identify circRNAs acting as potential biomarkers for cardiovascular disease (CVD). Research were retrieved from the articles published by September 2018 in eight databases to compare circRNA expression profiles between CVD and non-CVD in human and animal models. Meta-analysis under a random effects model was conducted.Subgroup analysis of tissue, species, and disease-specific circRNAs was examined.Sensitivity analysis was performed to explain the uncertainty among all studies.Diagnostic accuracy of circRNAs in CVD was analyzed to testify the discriminative ability. Bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was conducted. Among 6,284 differentially expressed circRNAs from 32 original studies, only 322 circRNAs were reported in three or more studies. The meta-analysis identified 63 significantly dysregulated circRNAs, 44 upregulated and 19 downregulated. Among the tissuespecific or disease-specific circRNAs identified in the subgroup analysis, two circRNAs (circCDKN2BAS and circMACF1) showed the potential to be circulating biomarkers for CVD. Sensitivity analysis demonstrated 69% of circRNAs were in conformity with the overall analysis. The pooled diagnostic odds ratio was 2.94 (95% confidence interval [CI], 2.35-3.58), and the overall area under the curve value was 0.86 (95% CI, 0.83-0.89). GO and KEGG enrichment analyses indicated that the target genes of circRNAs participate in cardiogenesis-related processes and pathways. This study demonstrates circRNAs have a high diagnostic value as potential biomarkers for CVD, and two candidate circRNAs, circCDKN2BAS and circMACF1, are potential circulating biomarkers for CVD diagnosis and treatment.
Landscape fire smoke (LFS) has been associated with reduced birthweight, but evidence from low- and middle-income countries (LMICs) is rare. Here, we present a sibling-matched case-control study of 227,948 newborns to identify an association between fire-sourced fine particulate matter (PM2.5) and birthweight in 54 LMICs from 2000 to 2014. We selected mothers from the geocoded Demographic and Health Survey with at least two children and valid birthweight records. Newborns affiliated with the same mother were defined as a family group. Gestational exposure to LFS was assessed in each newborn using the concentration of fire-sourced PM2.5. We determined the associations of the within-group variations in LFS exposure with birthweight differences between matched siblings using a fixed-effects regression model. Additionally, we analyzed the binary outcomes of low birthweight (LBW) or very low birthweight (VLBW). According to fully adjusted models, a 1 µg/m3 increase in the concentration of fire-sourced PM2.5 was significantly associated with a 2.17 g (95% confidence interval [CI]: 0.56-3.77) reduction in birthweight, a 2.80% (95% CI: 0.97-4.66) increase in LBW risk, and an 11.68% (95% CI: 3.59-20.40) increase in VLBW risk. Our findings indicate that gestational exposure to LFS harms fetal health.
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