Identification of competing endogenous RNA networks associated with circRNA and lncRNA in TCDD-induced cleft palate development.

2,3,7,8 -tetrachlorodibenzo-p-dioxin (TCDD) is a teratogen that can induce cleft palate formation, a common birth defect. Competing endogenous RNAs (ceRNAs), including circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), indirectly regulate gene expression via sharing microRNAs (miRNAs). Nevertheless, the mechanism by which they act as ceRNAs to regulate palatal development remains to be explored in greater detail. Here, the cleft palate model of C57BL/6 N pregnant mice was constructed by gavage of TCDD (64 ug/kg) on gestation day (GD) 10.5, and the palatal shelves were taken on gestation day (GD) 14.5 for whole-transcriptome sequencing to investigate the underlying mechanisms of the roles of circRNAs and lncRNAs as ceRNAs in cleft palate. Sequencing results revealed that 293 lncRNA, 589 circRNA, 47 miRNA, and 138 messenger RNA (mRNA) were significantly dysregulated, and the cytochrome P450 (CYP) enzymes and the aryl hydrocarbon receptor (AhR) pathway play key roles in the induction of cleft palate upon exposure to TCDD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed the function of TCDD function was mainly related to the metabolic processes of intracellular compounds, including the metabolic processes of cellular aromatic compounds and the metabolism of exogenous drugs by cytochrome P450, etc. Furthermore, quantitative reverse transcription polymerase chain reaction (qRT-PCR) indicated that the circRNA_1781/miR-30c-1-3p/PKIB and XR_380026.2/miR-1249-3p/DNAH10 ceRNA networks were hypothesized to be a hub involved in palatal development suggesting that the circRNA_1781/miR-30c-1-3p/PKIB and XR_380026.2/miR-1249-3p/DNAH10 ceRNA networks may be critical for palatogenesis, setting the foundation for the investigation of cleft palate.

Upregulated LncRNA-Meg3 modulates the proliferation and survival of MEPM cells via interacting with Smad signaling in TCDD-induced cleft palate.

Exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in utero can result in high rates of cleft palate (CP) formation, yet the underlying mechanisms remain to be characterized. In vivo, the lncRNA Meg3 was upregulated following TCDD treatment in CP-associated murine embryonic palatal tissue, with concomitant changes in proliferative and apoptotic activity in these murine embryonic palatal mesenchymal (MEPM) cells. Meg3 can modulate the TGF-ß/Smad to control the proliferation, survival, and differentiation of cells. Accordingly, TCCD and TGF-ß1 were herein used to treat MEPM cells in vitro, revealing that while TCDD exposure altered the proliferative activity and apoptotic death of these cells, exogenous TGF-ß1 exposure antagonized these effects via TGF-ß/Smad signaling. TCDD promoted Meg3 upregulation, whereas TGF-ß1 suppressed TCDD-driven upregulation of this lncRNA. Meg3 was additionally determined to directly interact with Smad2, with significant Meg3 enrichment in Smad2-immunoprecipitates following TCDD treatment. When Meg3 was silenced, the impact of TCDD on Smad signaling, proliferative activity, and apoptosis were ablated, while the effects of exogenous TGF-ß1 were unchanged. This supports a model wherein Meg3 is upregulated in TCDD-exposed palatal tissue whereupon it can interact with Smad2 to suppress Smad-dependent signaling, thus controlling MEPM cell proliferation and apoptosis, contributing to TCDD-induced CP, which provides a theoretical support for the precautions of cleft palate induced by TCDD.

Associations between the proliferation of palatal mesenchymal cells, Tgfß2 promoter methylation, Meg3 expression, and Smad signaling in atRA-induced cleft palate.

All-trans retinoic acid (atRA) is a teratogen that can induce cleft palate formation. During palatal development, murine embryonic palate mesenchymal (MEPM) cell proliferation is required for the appropriate development of the palatal frame, with Meg3 serving as a key regulator of the proliferative activity of these cells and the associated epithelial-mesenchymal transition process. DNA methylation and signaling via the TGFß/Smad pathway are key in regulating embryonic development. Here, the impact of atRA on MEPM cell proliferation and associations between Tgfß2 promoter methylation, Meg3, and signaling via the Smad pathway were explored using C57BL/6 N mice treated with atRA (100 mg/kg) to induce fetal cleft palate formation. Immunohistochemistry and BrdU assays were used to detect MEPM proliferation and DNA methylation assays were performed to detect Tgfß2 promoter expression. These analyses revealed that atRA suppressed MEPM cell proliferation, promoted the upregulation of Meg3, and reduced the levels of Smad2 and Tgfß2 expression phosphorylation, whereas Tgfß2 promoter methylation was unaffected. RNA immunoprecipitation experiments indicated that the TgfßI receptor is directly targeted by Meg3, suggesting that the ability of atRA to induce cleft palate may be mediated through the Tgfß/Smad signaling pathway.

Association of greenspace with hypertension in adult: a systematic review and meta-analysis of epidemiological studies.

BACKGROUND: Several studies have investigated the relationship of greenspace with blood pressure (BP) and hypertension, but the results were inconsistent. We aimed to assess the relationship of greenspace with BP/hypertension. METHODS: We searched PubMed, Embase and Web of Science on greenspace and BP/hypertension published before 5 April 2023. The methodological quality and risk of bias were evaluated. RESULTS: Twenty-seven articles were included. Our results suggested that higher normalized difference vegetation index (NDVI) was associated with lower odds of hypertension and levels of SBP [for every 10% increase of NDVI 500-m and NDVI 1000-m, the ORs were 0.95 (95% CI: 0.90-0.99) and 0.95 (95% CI: 0.90-0.99), the ꞵwas -1.32 (95% CI: -2.18, -0.45) and -1.41 (95% CI: -2.57, -0.25), respectively]. CONCLUSION: This study indicated that higher exposure to greenspace might be associated with lower levels of BP and risk of hypertension. Increase green spaces should be regarded as an important public health intervention..

Sex Specificity in the Mixed Effects of Blood Heavy Metals and Cognitive Function on Elderly: Evidence from NHANES.

The way that males and females react to environmental exposures and negative impacts on their neurological systems is often different. Although previous research has examined the cognitively impairing effects of solitary metal exposures, the relationship between metal mixtures and cognitive function, particularly when considering an individual's sex, remains elusive. This study aimed to investigate the sex differences in the association between multiple metal combinations and cognitive function in older Americans. This research employed the 2011-2014 NHANES survey of elderly Americans. The association between five mixed metals and four cognitive tests (the animal fluency test (AFT), the digit symbol substitution test (DSST), the instant recall test (IRT), and the delayed recall test (DRT)) were investigated with generalized linear regression model (GLM), Bayesian kernel machine regression model (BKMR), weighted quantile sum regression model (WQS), and quantile g-computation regression model (Qgcomp). A total of 1833 people, including 883 males and 950 females, enrolled in this cross-sectional study. We discovered that blood lead and blood cadmium were negatively associated with cognitive performance, while blood selenium demonstrated a positive association with cognitive function in older people. The negative relationship of heavy metal combinations on cognitive function might be somewhat reduced or even reversed via selenium. The IRT, AFT, and DSST are three of the four cognitive tests where men had more dramatic positive or negative results. There was a sex-specific connection between blood metal ratios and cognitive function among older Americans, as evidenced by the more significant relationship between mixed metals and cognitive performance in men (either positively or negatively). These results emphasize the impacts of ambient heavy metal exposure on cognitive function by employing sex-specific methods.

Ambient fine particulate matter and pregnancy outcomes: An umbrella review.

The available evidence on the effects of ambient fine particulate matter (PM2.5) and pregnancy outcomes (birth outcomes and pregnancy complications) has increased substantially. The purpose of this umbrella review is to refine the evidence of the association between birth outcome (birth defects) and PM2.5; and summarize the credibility of existing research on the association between pregnancy complications and PM2.5. We searched PubMed, Web of Science, Embase, and Cochrane databases for relevant systematic reviews and meta-analyses up to March 16, 2022 in accordance with PRISMA guidelines. Two independent investigators conducted data extraction. AMSTAR 2 and GRADE assessment criteria were used to evaluate the methodological and evidence quality. We performed subgroup analyses by trimesters of pregnancy. The review protocol for this study has been registered in PROSPERO (CRD42022325550). This umbrella review identified a total of 41 systematic reviews, including 28 articles evaluating the influence of PM2.5 on birth outcomes and 13 on pregnancy complications. Positive associations between perinatal PM2.5 exposure and adverse birth outcomes were found, including low birth weight, preterm birth, stillbirth, small for gestational age, and birth defects. Pregnant women exposed to PM2.5 had a significantly higher risk of developing hypertensive disorder of pregnancy, gestational diabetes mellitus, gestational hypertension, and preeclampsia. The findings of subgroup analysis demonstrated that the effects of ambient PM2.5 exposure on pregnancy outcomes varied by trimesters. The findings of this extensive umbrella review provide convincing proof that exposure to ambient PM2.5 raises the risks of unfavorable birth outcomes and pregnancy complications. Some associations show considerable disparity between trimesters. These findings have implications for strengthen perinatal health care on air pollution and improving intergenerational equity.

The mechanisms governing mouse embryonic palate mesenchymal cells' proliferation associated with atRA-induced cleft palate in mice: insights from integrated transcriptomic and metabolomic analyses.

While exposure to high levels of all-trans retinoic acid (atRA) during pregnancy is known to suppress murine embryonic palate mesenchymal (MEPM) cells proliferation and to result in cleft palate (CP) development, the underlying mechanisms are poorly understood. Accordingly, this study was designed with the goal of clarifying the etiological basis for atRA-induced CP. A murine model of CP was established via the oral administration of atRA to pregnant mice on gestational day (GD) 10.5, after which transcriptomic and metabolomic analyses were performed with the goal of clarifying the critical genes and metabolites associated with CP development through an integrated multi-omics approach. MEPM cells proliferation was altered by atRA exposure as expected, contributing to CP incidence. In total, 110 genes were differentially expressed in the atRA treatment groups, suggesting that atRA may influence key biological processes including stimulus, adhesion, and signaling-related activities. In addition, 133 differentially abundant metabolites were identified including molecules associated with ABC transporters, protein digestion and absorption, mTOR signaling pathway, and the TCA cycle, suggesting a link between these mechanisms and CP. Overall, combined analyses of these transcriptomic and metabolomic results suggested that the MAPK, calcium, PI3K-Akt, Wnt, and mTOR signaling pathways are particularly important pathways enriched in the palatal cleft under conditions of atRA exposure. Together, these integrated transcriptomic and metabolomic approaches provided new evidence with respect to the mechanisms underlying altered MEPM cells proliferation and signal transduction associated with atRA-induced CP, revealing a possible link between oxidative stress and these pathological changes.

Interaction effects of night-time temperature and PM2.5 on preterm birth in Huai River Basin, China.

Nocturnal temperature is observed increasing with global warming. However, evidence on night-time non-optimal temperature on the risk of preterm birth (PTB) is limited, and the potential interactions with air pollution on PTB has not been well clarified. We therefore conducted a population-based retrospective cohort study to evaluate the effect of night-time temperature extremes on the risk of PTB and its interaction with air pollution. Records of 196,780 singleton births from 4 counties in Huai River Basin (2013-2018) were obtained. Gridded data on night-time temperature were collected from a high-quality Chinese Air Quality Reanalysis dataset. We used a multivariate logistic regression to evaluate the effects of night-time heat and cold exposure on the risk of PTB as well as its subtypes. Potential interactions between night-time temperature extremes and fine particulate matter < 2.5 µm (PM2.5) were examined using the relative excess risk due to interaction (RERI). We found that the risk of PTB was positively associated with third trimester night-time extremely heat and cold exposure, with adjusted OR of 1.898 (95 %CI: 1.655-2.177) and 2.044 (95 %CI: 1.786-2.339). Similar effects were observed for PTB subtypes, moderately PTB (mPTB) and very PTB (vPTB). Synergistic effects (RERI greater than 0) of each trimester night-time temperature extremes exposure and PM2.5 on PTB were observed. We identified consistent positive interactions between night-time temperature extremes and PM2.5 on mPTB. No significant interaction of night-time temperature extremes and PM2.5 on vPTB was found. In conclusion, this large retrospective cohort study found that third trimester night-time heat and cold exposure significantly increased the risk of PTB and its subtypes. There is a synergistic effect between night-time temperature extremes and high PM2.5 levels on PTB and mPTB. In the context of climate warming, our results add new evidence to the current understanding of night-time non-optimal temperature exposure on PTB.