Search

The relationship between brominated flame retardants (BFRs) exposure and the human liver was still not well understood. A total of 3108 participants (age > 12) from the National Health and Nutrition Examination Survey (NHANES) database spanning from 2005 to 2016 were included as the study population, with nine BFRs exhibiting a detection rate of over 70% serving as the exposure factor. The singular effects and combined effects of BFRs exposure on liver injury, non-alcoholic fatty liver disease (NAFLD), and advanced hepatic fibrosis (AHF) were evaluated separately. Finally, COX regression was employed to explore the hazard ratios associated with individual BFRs. In our analysis of individual exposures, we found significant positive association of PBB153 with alanine aminotransferase (ALT), PBB153 with aspartate aminotransferase (AST), PBDE47, PBDE85, PBDE99, PBDE100, and PBDE154 with alkaline phosphatase (ALP), PBDE28 and PBB153 with gamma-glutamyl transaminase (GGT), PBB153 with the risk of NAFLD and AHF; and significant negative association of PBB153 with ALP, PBDE28, PBDE47, PBDE99, PBDE100, PBDE85, PBDE209, and PBDE154 with albumin (ALB), PBB153 with AST/ALT. The nonlinear analysis results from Restricted Cubic Spline (RCS) further validated these associations (all P<0.05). In the mixed analysis combining Weighted Quantile Sum (WQS) regression and Quantile G-computation (QGC) analysis, BFRs were positively associated with ALT (β>0, P<0.001), GGT (β>0, P<0.001), and the risk of NAFLD (OR>1, P=0.007). Conversely, BFRs exhibited significant negative correlations with ALP (β<0, P<0.001), ALB (β<0, P<0.001), and AST/ALT (β<0, P<0.001). Furthermore, the COX regression analysis revealed that PBB153 had the highest hazard ratio among the BFRs. BFR exposure may increase the risk of liver injury and NAFLD, with no significant association with AHF risk. The impact of BFR exposure on liver health should not be overlooked, especially in individuals residing in impoverished areas. • BFRs exposure increases the risk of human liver injury and NAFLD. • BFRs exposure poses a greater threat to impoverished populations. • Among the 9 included BFRs, PBB153 exhibits the highest risk. • The mixture of BFRs was associated with the risk of human liver injury and NAFLD. [ABSTRACT FROM AUTHOR]

Discovering the regulatory relationships between microRNAs (miRNAs) and mRNAs is an important problem that interests many biologists and medical researchers. A number of computational methods have been proposed to infer miRNA–mRNA regulatory relationships, and are mostly based on the statistical associations between miRNAs and mRNAs discovered in observational data. The miRNA–mRNA regulatory relationships identified by these methods can be both direct and indirect regulations. However, differentiating direct regulatory relationships from indirect ones is important for biologists in experimental designs. In this paper, we present a causal discovery based framework (called DirectTarget) to infer direct miRNA–mRNA causal regulatory relationships in heterogeneous data, including expression profiles of miRNAs and mRNAs, and miRNA target information. DirectTarget is applied to the Epithelial to Mesenchymal Transition (EMT) datasets. The validation by experimentally confirmed target databases suggests that the proposed method can effectively identify direct miRNA–mRNA regulatory relationships. To explore the upstream regulators of miRNA regulation, we further identify the causal feedforward patterns (CFFPs) of TF–miRNA–mRNA to provide insights into the miRNA regulation in EMT. DirectTarget has the potential to be applied to other datasets to elucidate the direct miRNA–mRNA causal regulatory relationships and to explore the regulatory patterns. [ABSTRACT FROM AUTHOR]

High myopia has been continually increasing globally until now and often results in visual impairment. Scleral extracellular matrix (ECM) remodeling is considered a common factor contributing to progression of myopia. However, the role of microRNAs (miRNAs) in regulating scleral ECM organization is not well understood. We aimed to explore the effect and regulatory mechanism of hsa-miR-142-3p on collagen I in human scleral fibroblasts in high myopia. First, next-generation sequencing was conducted to identify 37 miRNAs differentially expressed in the aqueous humor of high myopia samples and control samples. Furthermore, hsa-miR-142-3p in the aqueous humor was found to positively relate to the ocular axial length. Besides, the results of immunofluorescence and Western blot assay indicated that hsa-miR-142-3p overexpression decreased collagen I expression in the human fetal scleral fibroblasts (HFSFs); while hsa-miR-142-3p downregulation increased collagen I. Moreover, hsa-miR-142-3p targets TGFβ-1 gene expression. Quantitative polymerase chain reaction (qPCR) and Western blot analysis showed that miRNA 142-3p reduced TGFβ-1 expression while an inhibitor had an opposite effect. Therefore, there is an inverse relationship between changes in miR-142-3p expression levels and those of collagen1a1 in human scleral fibroblasts. Such a dependence suggests that miR-142-3p may be a target to improve therapeutic management of this condition. • miRNAs expression profile in high myopia was detected by next-generation sequencing. • Hsa-miR-142-3p is positively associated with the ocular axial length. • Hsa-miR-142-3p decreases collagen I in HFSFs. • Hsa-miR-142-3p targets TGF-β1 in HFSFs. [ABSTRACT FROM AUTHOR]

Thyroid hormone disorders have long been linked to depression, but the causal relationship between them remains controversial. To address this question, we established rat models of hypothyroidism using 131 iodine ( 131 I) and hyperthyroidism using levothyroxine (LT 4 ). Serum free thyroxine (FT 4 ) and triiodothyronine (FT 3 ) significantly decreased in the hypothyroid of rats with single injections of 131 I (5 mCi/kg). These rats exhibited decreased depression-like behaviors in forced swimming test and sucrose preference tests, as well as decreased anxiety-like behaviors in an elevated plus maze. Diminished levels of brain serotonin (5-HT) and increased levels of hippocampal brain-derived neurotrophic factor (BDNF) were found in the hypothyroid rats compared to the control saline–vehicle administered rats. LT 4 treatment reversed the decrease in thyroid hormones and depression-like behaviors. In contrast, hyperthyroidism induced by weekly injections of LT 4 (15 μg/kg) caused a greater than 10-fold increase in serum FT 4 and FT 3 levels. The hyperthyroid rats exhibited higher anxiety- and depression-like behaviors, higher brain 5-HT level, and lower hippocampal BDNF levels than the controls. Treatment with the antidepressant imipramine (15 mg/kg) diminished serum FT 4 levels as well as anxiety- and depression-like behaviors in the hyperthyroid rats but led to a further increase in brain 5-HT levels, compared with the controls or the hypothyroid rats. Together, our results suggest that hypothyroidism and hyperthyroidism have bidirectional effects on anxiety- and depression-like behaviors in rats, possibly by modulating hippocampal BDNF levels. [ABSTRACT FROM AUTHOR]