Aim:To examine the associations between fetal growth restriction (FGR) and DNA methylation of six growth-related genes in human placenta. Materials & methods: A total of 181 mother-newborn pairs (80 FGR cases and 101 controls) were enrolled in this case-control study. Placental DNA methylation was measured by bisulfite pyrosequencing. Results: DNA methylation levels of IGF2 and AHRR were positively associated with newborn birth weight and Quetelet's index, while DNA methylation levels of HSD11B2 and WNT2 were negatively associated with those fetal growth indicators. In addition, significantly elevated odds of FGR birth were associated with increasing DNA methylation of HSD11B2 and WNT2, and decreasing DNA methylation of IGF2. Conclusion: Our findings demonstrated that placental DNA methylation levels of IGF2, AHRR, HSD11B2 and WNT2 were associated with measures of fetal growth.

For a long time, skin was thought to be no more than the barrier of our body. However, in the last few decades, studies into the idea of skin as an independent functional organ have gradually deepened our understanding of skin and its functions. In this review, we gathered evidence that presented skin as a “trinity” of neuro–endocrine–immune function. From a neuro perspective, skin communicates through nerves and receptors, releasing neurotrophins and neuropeptides; from an endocrine perspective, skin is able to receive and secrete most hormones and has the cutaneous equivalent of the hypothalamic-pituitary-adrenal (HPA) axis; from an immune perspective, skin is protected not only by its physical barrier, but also immune cells and molecules, which can also cause inflammation. Together as an organ, skin works bidirectionally by operating peripheral neuro–endocrine–immune function and being regulated by the central nervous system, endocrine system and immune system at the same time, maintaining homeostasis. Additionally, to further explain the “trinity” of cutaneous neuro–endocrine–immune function and how it works in disease pathophysiology, a disease model of rosacea is presented.

Background/Aims Pigeon breeder’s lung (PBL) results from Th1/Th2 cell imbalance. B cells inhibit the immune activity of Th1, and EBF3 is a key B cell factor. This study explored the relationship between EBF3 and Th1/Th2 imbalance in chronic PBL cases complicated with pulmonary fibrosis (PF). Methods Twenty Uygur PBL+PF patients, 20 pigeon breeders without PBL or PF, and 20 healthy individuals without pigeon breeding history constituted the patient I, negative control, and normal control groups, respectively. Peripheral blood specimens and case backgrounds were collected between June 2016 and March 2017. EBF3 gene methylation was analyzed by matrix assisted laser desorption ionization-time of flight mass spectrometry. To compare different mechanisms of PF progression in PBL, samples from 20 Uygur PBL patients without PF (at acute and sub-acute stages) were collected between October 2017 and February 2018, constituting the patient II group. EBF3 mRNA expression was evaluated by real-time polymerase chain reaction. IFN-γ, IL-4 and IL-10 expression and Th1/Th2 imbalance in PBL were evaluated by enzyme-linked immunosorbent assay and flow cytometry. Results CpG-2 and general methylation rates in the patient I group were lower than those in the control groups (P˂0.017). The level of EBF3 mRNA expression in the patient I group was significantly higher than that in any other group. Compared with the control groups, the patient I group showed a significantly higher level of IL-4, whereas the patient II group showed a significantly lower level. IL-10 was also expressed more highly in the patient I group than in any other group (P< 0.01). Flow cytometry showed INF-γ dominance (Th1 cytokine) in PBL at the acute/sub-acute stage and IL-4 dominance (Th2 cytokine) at the chronic stage after PF occurred. The general methylation rate was negatively correlated with the mRNA level, with the latter being positively correlated with the IL-10 level and number of pigeons bred in the past 3 months. IL-4 expression was negatively correlated with INF-γ but positively correlated with PF area and duration of pigeon breeding history. Conclusions After PF occurs in chronic PBL, the inflammation type changes from Th1 dominance to Th2 dominance. During PBL development, IL-10 increases before IL-4 does, which may be associated with EBF3 hypomethylation and the involvement of B lymphocytes.

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