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Four endotypes were identified; endotypes 1, 2 and 3 had higher proportions of AD (67%), asthma (60%), and allergic march (75%), respectively, and endotype 4 had more control members (70%; Figure 1B, Table S1). AD, atopic dermatitis; As, asthma; AM, allergic march. gl Endotypes were classified clearly by the omics features showing different intensities (Figure 1D, Tables S3-S5). [Extracted from the article]

Background: The prevalence of atopic dermatitis (AD) is increasing worldwide. Prenatal particulate matter with an aerodynamic diameter <2.5 μm (PM2.5) and maternal anxiety during pregnancy has been suggested as a potential causes of AD. This study investigated the effects of prenatal PM2.5 and maternal anxiety on AD and identified the critical period of PM2.5 exposure for AD in infants. Methods: This study included 802 children from the COCOA birth cohort study with follow‐up data at 1 year of age. PM2.5 was estimated by land‐use regression models and prenatal anxiety was measured with a questionnaire. AD was diagnosed by doctor at 1 year of age. Logistic regression analysis and Bayesian distributed lag interaction models were applied. Results: Higher PM2.5 during the first trimester of pregnancy, higher prenatal maternal anxiety, and male gender were associated with AD at 1 year of age (adjusted odds ratio [aOR] and 95% confidence interval [CI]: 1.86 [1.08–3.19], 1.58 [1.01–2.47], and 1.54 [1.01–2.36], respectively). Higher PM2.5 during the first trimester and higher maternal anxiety during pregnancy showed an additive effect on the risk of AD (aOR: 3.13; 95% CI: 1.56–6.28). Among boys exposed to higher maternal anxiety during pregnancy, gestational weeks 5–8 were the critical period of PM2.5 exposure for the development of AD. Conclusions: Higher PM2.5 exposure during gestational weeks 5–8 increased the probability of AD in infancy, especially in boys with higher maternal anxiety. Avoiding PM2.5 exposure and maternal anxiety from the first trimester may prevent infant AD. [ABSTRACT FROM AUTHOR]

We previously demonstrated that the chronic consumption of a high-fat diet (HFD) promotes lung and liver metastases of 4T1 mammary carcinoma cells in obesity-resistant BALB/c mice. To examine early transcriptional responses to tumour progression in the liver and lungs of HFD-fed mice, 4-week-old female BALB/c mice were divided into four groups: sham-injected, control diet (CD)-fed; sham-injected, HFD-fed (SH); 4T1 cell-injected, CD-fed (TC); 4T1 cell-injected, HFD-fed (TH). Following 16 weeks of either a CD or HFD, 4T1 cells were injected into the mammary fat pads of mice in the TC and TH groups and all mice were continuously fed identical diets. At 14 d post-injection, RNA was isolated from hepatic and pulmonary tissues for microarray analysis of mRNA expression. Functional annotation and core network analyses were conducted for the TH/SH Unique gene set. Inflammation in hepatic tissues and cell mitosis in pulmonary tissues were the most significant biological functions in the TH/SH Unique gene set. The biological core networks of the hepatic TH/SH Unique gene set were characterised as those genes involved in the activation of acute inflammatory responses (Orm1, Lbp, Hp and Cfb), disordered lipid metabolism and deregulated cell cycle progression. Networks of the pulmonary Unique gene set displayed the deregulation of cell cycle progression (Cdc20, Cdk1 and Bub1b). These HFD-influenced alterations may have led to favourable conditions for the formation of both pro-inflammatory and pro-mitotic microenvironments in the target organs that promote immune cell infiltration and differentiation, as well as the infiltration and proliferation of metastatic tumour cells. [ABSTRACT FROM PUBLISHER]

Prolonged high-fat diet leads to the development of obesity and multiple comorbidities including non-alcoholic steatohepatitis (NASH), but the underlying molecular basis is not fully understood. We combine molecular networks and time course gene expression profiles to reveal the dynamic changes in molecular networks underlying diet-induced obesity and NASH. We also identify hub genes associated with the development of NASH. Core diet-induced obesity networks were constructed using Ingenuity pathway analysis (IPA) based on 332 high-fat diet responsive genes identified in liver by time course microarray analysis (8 time points over 24 weeks) of high-fat diet-fed mice compared to normal diet-fed mice. IPA identified five core diet-induced obesity networks with time-dependent gene expression changes in liver. These networks were associated with cell-to-cell signaling and interaction (Network 1), lipid metabolism (Network 2), hepatic system disease (Network 3 and 5), and inflammatory response (Network 4). When we merged these core diet-induced obesity networks, Tlr2, Cd14, and Ccnd1 emerged as hub genes associated with both liver steatosis and inflammation and were altered in a time-dependent manner. Further, protein-protein interaction network analysis revealed Tlr2, Cd14, and Ccnd1 were interrelated through the ErbB/insulin signaling pathway. Dynamic changes occur in molecular networks underlying diet-induced obesity. Tlr2, Cd14, and Ccnd1 appear to be hub genes integrating molecular interactions associated with the development of NASH. Therapeutics targeting hub genes and core diet-induced obesity networks may help ameliorate diet-induced obesity and NASH. [ABSTRACT FROM AUTHOR]

Background: Although the development of allergic rhinitis (AR) is associated with multiple genetic and hygienic environmental factors, previous studies have focused mostly on the effect of a single factor on the development of AR., Objective: This study aimed to investigate the combined effect of multiple genetic and hygienic environmental risk factors on AR development in school children., Methods: We conducted a cross-sectional study, comprising 1,797 children aged 9-12 years. Weighted environmental risk score (ERS) was calculated by using four hygienic environmental factors, including antibiotic use during infancy, cesarean section delivery, breast milk feeding, and having older siblings. Weighted polygenic risk score (PRS) was calculated by using four single nucleotide polymorphisms (SNPs), including interleukin-13 (rs20541), cluster of differentiation 14 (rs2569190), toll-like receptor 4 (rs1927911), and glutathione S-transferase P1 (rs1695). Multivariable logistic regression analysis was used., Results: More than three courses of antibiotic use during infancy increased the risk of current AR (adjusted odd ratio [aOR], 2.058; 95% confidence interval [CI]: 1.290-3.284). Having older siblings, especially > 2 (aOR, 0.526; 95%Cl: 0.303-0.913) had a protective effect. High ERS ( > median; aOR, 2.079; 95%Cl: 1.466-2.947) and PRS ( > median; aOR, 1.627; 95%Cl: 1.117-2.370) increased the risk of current AR independently. Furthermore, children who had both high ERS and PRS showed a higher risk of current AR (aOR, 3.176; 95%Cl: 1.787-5.645)., Conclusions: Exposure to multiple hygienic risk factors during infancy increases the risk of AR in genetically susceptible children.