Lysine (K)-specific demethylase 5C regulates the incidence of severe preeclampsia by adjusting the expression of bone morphogenetic protein-7.

This study aimed to investigate the roles of the lysine (K)-specific demethylase 5C (KDM5C)-bone morphogenetic protein-7 (BMP-7) signaling pathway in the pathogenesis of severe preeclampsia (sPE). A total of 180 pregnant patients were enrolled in the study and classified into three groups: an early-onset sPE group (EOsPE) (n = 60), a late-onset sPE group (LOsPE) (n = 60), and a control group (normal pregnancy; n = 60). The messenger RNA (mRNA) and protein expression levels of bone morphogenetic protein receptor II (BMPRII), BMP-7, and KDM5C were detected in placenta samples from the two sPE groups, and their sites were evaluated using immunohistochemistry (IHC). The sPE groups showed an increased KDM5C mRNA expression, and the EOsPE group showed a decreased BMP-7 and BMPRII mRNA expression compared with the LOsPE group. However, contradictory results were discovered in terms of protein expression. Immunostaining of KDM5C, BMP-7, and BMPRII was observed in villous trophoblast and extravillous trophoblast cells. Compared with the control group, the staining intensity of KDM5C in the placental tissue trophoblast cell nucleus and vascular endothelial cells of the sPE groups was weaker, while that of BMP-7 and BMPRII was stronger, and the staining intensity was more subjective in the LOsPE group. Consistent findings were obtained by IHC and Western blot analysis. KDM5C nuclear-cytoplasmic translocation may regulate sPE through BMP-7 and its receptors. The KDM5C-BMP-7 signaling pathway may also lead to less invasion and increased apoptosis of the trophoblast cells, which is involved in the pathogenesis of sPE.

Resveratrol induces SIRT1-Dependent autophagy to prevent H2O2-Induced oxidative stress and apoptosis in HTR8/SVneo cells.

INTRODUCTION: Pre-eclampsia (PE) is a serious complication of pregnancy, and the likely pathogenic basis of early onset PE are placental dysfunction and increased oxidative stress. Resveratrol (RES) is a potent antioxidant which has shown beneficial effects in many diseases. The aim of this study was to investigate the protective effects of RES against oxidative stress-induced damage in trophoblasts, and elucidate the potential mechanisms. METHODS: We established an in vitro model of oxidative stress by exposing the human first-trimester extravillous trophoblast cell line HTR8/SVneo to H2O2. The level of oxidative stress was reflected by ROS, MDA and SOD. The viability of cells was determined by the MTS assay. Apoptosis was detected using Annexin V-FITC staining and flow cytometry. Levels of SIRT1(sirtuin 1) and autophagy-related proteins (LC3, Beclin-1, p62) were detected by western blot. Autophagosomes were observed by transmission electron microscopy (TEM). RESULTS: Pre-treatment with RES significantly ameliorated H2O2-induced cytotoxicity, morphological damage, oxidative stress and apoptosis. Mechanistically, RES restored the levels of SIRT1 and autophagy-related proteins including LC3-II, Beclin-1 and p62 that were dysregulated by H2O2. Blocking autophagy by 3-methyladenine (3-MA) completely abolished the protective effects of RES, as did knocking down SIRT1. CONCLUSION: RES may protect human trophoblasts against H2O2-induced oxidative stress by activating SIRT1-dependent autophagy, and therefore has therapeutic potential in PE.

[Effects of Environmental Factors on the Synergy of Functional Bacteria in Completely Autotrophic Granular Sludge].

To obtain experimental evidences for optimizing a completely autotrophic nitrogen removal process based on granules, the effects of dissolved oxygen (DO) concentration, temperature (t), initial ammonium (NH4+-N) concentration, and solution pH conditions on the synergy between the aerobic and anaerobic ammonium-oxidizing bacteria (AOB and AMX) were investigated using a single factor batch experiment, while the analysis of the microbial community structure within them was conducted using MiSeq high-throughput pyrosequencing. Results revealed that AOB (genus Nitrosomonas) and AMX (genus Candidatus Kuenenia) dominated in the granules, representing relative abundances of 32.9% and 9.8%, respectively. For the granules, the highest specific nitrogen removal rate of q(TN)=(17.7±1.0) mg·(g·h)-1 was obtained at a DO concentration of 2 mg·L-1, while the initial NH4+-N concentration was set at 100 mg·L-1. And a lower DO level resulted in partial nitritation became the rate-limiting step of process, otherwise, it would be the ANAMMOX reaction instead. According to the free energy of the reactions, the activity of AMX was more sensitive to low temperature than that of AOB. When the reaction temperature was lower than 30℃, nitrite accumulation could be observed in bulk liquid, with the significant decrease of q(TN) for the granules. Under the same oxygen supply conditions, an initial NH4+-N concentration lower than 100 mg·L-1 could inhibit the activity of AMX partly. However, with an initial NH4+-N concentration over 150 mg·L-1, either oxygen-limiting or high free ammonia concentration could lead to the dramatic decrease of q(TN). In addition, the effective synergy of the two types of ammonium oxidizers in granules was always achieved at solution pH in the range of 7.0-8.5.

Mutational spectrum of the phenylalanine hydroxylase gene in patients with phenylketonuria in the central region of China.

Phenylketonuria (PKU, OMIM 261600) caused by phenylalanine hydroxylase (PAH) deficiency is an autosomal recessive disease that is characterized by abnormalities of phenylalanine metabolism. In this study, a total of 77 patients, originating from the central region of China and who were diagnosed with PAH deficiency at the third affiliated hospital of Zhengzhou University, were enrolled in this study. The 13 exons and 12 flanking introns of the PAH gene were analyzed by Sanger sequencing and next generation sequencing. The sequencing data were aligned to the hg19, PAHvdb and HGMD databases to characterize the genotypes of PKU patients, and genotype-phenotype correlations and BH4 responsiveness predictions were performed using BIOPKUdb. In total, 149 alleles were characterized among the 154 PKU alleles. These mutations were located in exons 2-13, and intron 12 of the PAH gene, with a relative frequency of ≥5%, for EX6-96A>G, p.R241C, p.R243Q, p.V399V and p.R53H. Additionally, a novel variant, p.D84G, was identified. The genotype correlated with clinical symptoms in 33.3-100% of the cases, depending on the disease severity, and BH4 responsiveness predictions show that only five patients with MHP-PKU and one patient with Mild-PKU were predicted to be BH4 responsive. In conclusion, we have characterized the mutational spectrum of PAH in the central region of China and have identified a novel mutation. The hotspot mutation information might be useful for screening, diagnosis and treatment of PKU.

[Start-up of a High Performance Nitrosation Reactor Through Continuous Growth of Aerobic Granular Sludge].

In order to examine the continuous growth capacity of the nitrosation granular sludge (NGS), the sludge was inoculated to start up the columnar sequencing batch reactor (SBR). During 130 d, the concentration of mixed liquor suspended solids (MLSS) in SBR increased from 0.1 g·L-1 to 11.8 g·L-1, corresponding to the nitrite-nitrogen accumulation rate of 0.4-4.9 kg·(m3·d)-1, promoted by a higher ammonia-nitrogen loading rate (NLR) from 0.74 kg·(m3·d)-1 to 6.66 kg·(m3·d)-1in the influent. Because of the obvious increase in small granules (size<200 µm), the mean average diameter of NGS decreased significantly at NLR<4.44 kg·(m3·d)-1. At higher NLR values, the growth of the mean average diameter of NGS could be fitted well using a modified logistic model. The specific growth rate of the k value was 0.0229 d-1. In addition, the combined inhibition of nitrite oxidizing bacteria (NOB) was expected at relatively high concentrations of both free ammonia (FA) and free nitrite acid (FNA); thus, the nitrite accumulation ratio (NAR) in the effluent was always higher than 80%. These results provide a feasible approach to start up a high-performance NGS reactor at the industrial-scale.