Association between fine particulate matter and fecundability in Henan, China: A prospective cohort study.

OBJECTIVE: To investigate the relationship between ambient fine particulate matter (PM2.5) exposure and fecundability. METHODS: This study included 751,270 female residents from Henan Province who participated in the National Free Pre-conception Check-up Projects during 2015-2017. Ambient cycle-specific PM2.5 exposure was assessed at the county level for each participant using satellite-based PM2.5 concentration data at 1-km resolution. Cox proportional hazards models with time-varying exposure were used to estimate the association between fecundability and PM2.5 exposure, adjusted for potential individual risk factors. RESULTS: During the study period, 568,713 participants were pregnant, monthly mean PM2.5 concentrations varied from 25.5 to 114.0 µg/m3 across study areas. For each 10 µg/m3 increase in cycle-specific PM2.5, the hazard ratio for fecundability was 0.951 (95 % confidence interval: 0.950-0.953). The association was more pronounced in women who were older, with urban household registration, history of pregnancy, higher body mass index (BMI), hypertension, without exposure to tobacco, or whose male partners were older, with higher BMI, or hypertension. CONCLUSION: In this population-based prospective cohort, ambient cycle-specific PM2.5 exposure was associated with reduced fecundability. These findings may support the adverse implications of severe air pollution on reproductive health.

RNF213 gene silencing upregulates transforming growth factor ß1 expression in bone marrow-derived mesenchymal stem cells and is involved in the onset of Moyamoya disease.

Moyamoya disease (MMD) is a chronic and progressive cerebrovascular occlusion disease, the precise etiology of which is poorly understood. Ring finger protein 213 (RNF213) has been previously identified as a susceptibility gene that serves an important role in angiogenesis, where it has been shown to be closely associated with the onset of MMD. Patients with MMD exhibit increased expression levels of various pro-inflammatory molecules and angiogenic factors. Under certain conditions, bone marrow mesenchymal stem cells (BMSCs) have the ability to differentiate to form neuron-like and microglia-like cells. In the present study, a total of 40 MMD patients and 40 healthy individuals were enrolled. ELISA assays revealed that the expression of serum vascular endothelial growth factor (VEGF) and transforming growth factor ß1 (TGF-ß1) were higher than that in healthy controls. Furthermore, rat BMSCs (rBMSCs) were isolated and cultured using the whole bone marrow adherence method, which were then phenotyped using flow cytometry. Osteogenic and adipogenic differentiation were determined by using Alizarin red and oil red O staining, respectively. RNF213 was knocked-down using a lentivirus-mediated short hairpin RNA system in passage three rBMSCs, and successful transfection of the RNF213 was confirmed by RT-qPCR and fluorescence imaging. The expression levels of VEGF and TGF-ß1 in these rBMSCs were measured on days 7 and 14, respectively. The results demonstrated that RNF213 knockdown upregulated TGF-ß1 at both protein and mRNA levels, but did not exert any effect on VEGF gene expression. In conclusion, these findings suggested that that RNF213 knockdown may contribute to aberrant TGF-ß1 expression via a pathway that remains to be unidentified, indicating that quantitative changes in RNF213 gene expression may serve an important role in the pathogenesis of MMD.

Analysis of Cyclooxygenase 2, Programmed Cell Death Ligand 1, and Arginase 1 Expression in Human Pituitary Adenoma.

BACKGROUND: Cyclooxygenase 2 (COX-2) is a key enzyme in the synthesis of prostaglandins. Recent studies have shown that overexpression of COX-2 can reduce the antitumor effect of the immune system by inhibiting the proliferation of B and T lymphocytes. Programmed cell death ligand 1 (PD-L1) was the first functionally characterized ligand of programmed cell death protein 1. It plays an important role in maintaining peripheral and central immune tolerance by combining with programmed cell death protein 1. Arginase 1 (ARG1) can process L-arginine in the local microenvironment and affect the function of T cells, resulting in immune escape. In this study, COX-2, PD-L1, and ARG1 expression in human pituitary adenoma (PA) and their relationship were investigated, which provided an initial theoretic basis for further study of the immune escape mechanism in PA in cellular and animal experiments. METHODS: The protein expression of COX-2, PD-L1, and ARG1 in 55 PA samples was detected by immunohistochemistry, with 10 normal brain tissues as the control group. The location of COX-2, PD-L1, and ARG1 in PA cells was studied by double immunofluorescence colocalization. The results of immunohistochemistry were further verified by Western blot. RESULTS: The expression of COX-2, PD-L1, and ARG1 in PA was significantly higher than that in normal brain tissue. In functional PA (FPA) and nonfunctional PA (NFPA), there was no significant difference in the expression of COX-2 and PD-L1, whereas ARG1 was higher in NFPA. Moreover, the protein expression level of COX-2 was positively correlated with that of PD-L1 and ARG1, and the expression of PD-L1 was positively correlated with that of ARG1. Immunofluorescence confocal imaging showed that COX-2, PD-L1, and ARG1 were all expressed in the cytoplasm of PA cells, and the physical positions of COX-2, PD-L1, and ARG1 were partially coincident. CONCLUSIONS: These findings indicate that overexpression of COX-2, PD-L1, and ARG1 may be involved in the pathogenesis of PA. ARG1 plays a more important role in the development of NFPA. By upregulating the expression of PD-L1, COX-2 may promote the expression of ARG1, forming the COX-2/PD-L1/ARG1 signal pathway in promoting the occurrence and development of PA. Perhaps further study of the pathogenesis of PA can start with the mechanism of immune escape.