Preeclampsia (PE) is the leading cause of maternal and neonatal morbidity and mortality. Defects in trophoblast invasion, differentiation of endovascular extravillous trophoblasts (enEVTs), and spiral artery remodeling are key factors in PE development. There are no markers clinically available to predict PE, leaving expedited delivery as the only effective therapy. Dysregulation of miRNA in clinical tissues and maternal circulation have opened a new avenue for biomarker discovery. In this study, we investigated the role of miR-218-5p in PE development. miR-218-5p was highly expressed in EVTs and significantly downregulated in PE placentas. Using first-trimester trophoblast cell lines and human placental explants, we found that miR-218-5p overexpression promoted, whereas anti-miR-218-5p suppressed, trophoblast invasion, EVT outgrowth, and enEVT differentiation. Furthermore, miR-218-5p accelerated spiral artery remodeling in a decidua-placenta co-culture. The effect of miR-218-5p was mediated by the suppression of transforming growth factor (TGF)-β2 signaling. Silencing of TGFB2 mimicked, whereas treatment with TGF-β2 partially reversed, the effects of miR-218-5p. Taken together, these findings demonstrate that miR-218-5p promotes trophoblast invasion and enEVT differentiation through a novel miR-218-5p-TGF-β2 pathway. This study elucidates the role of an miRNA in enEVT differentiation and spiral artery remodeling and suggests that downregulation of miR-218-5p contributes to PE development.
T HE PRESENT study focuses on the efficiency of a suggested innovative system for the treatment of the sand filter backwashing water (SFBW) in the Drinking water treatment plant (DWTP). Usually, the DWTP is consumes between 15 to 20% of their clean treated drinking water to backwashing their sand filter. Such sand filter backwashing water (SFBW) is, usually, discharged as waste. Presently, the suggested innovative system as pilot plant (PP) was employed for the treatment of SFBW. Physical and chemical characteristics of the raw Canal fresh water and the treated drinking water were extensively determined via sampling program. Meanwhile, the inlet SFBW and the treated outlet of the suggested PP were also sampled and subjected to the physical and chemical analysis. The settled particles as sludge of the PP were sand filtered. The filtered water was also evaluated in terms of the physical and chemical characteristics.The suggested PP was operated continuously where it proved efficient removal of TSS, turbidity, and aluminum at 74.1, 84.2 and 71.4%, respectively. Removal of total residue, and alkalinity reached 30.1 and 29.1%, successively. The residual Al 3+ was 3.0 mg/l. Correlation between the physical and chemical characteristics of Canal water in one hand and the treated SFBW and the filtered water of the sludge on the other hand indicated that both later waters were at better quality than the former. Therefore, it was suggested to reuse this treated effluents as an additional fresh water resource to the DWTP. The advantages are: saving this wasted water, save the intial supply of water to the DWTP, and to decrease the amount of added alum to the water treatment system while protecting the Canal water from the dischrge of the SFBW that contained residual of Al 3+ .
miRNAs play important roles in gene regulation, and their dysregulation is associated with many diseases, including epithelial ovarian cancer (EOC). In this study, we determined the expression and function of miR-590-3p in EOC. miR-590-3p levels were higher in high-grade carcinoma when compared with low-grade or tumors with low malignant potential. Interestingly, plasma levels of miR-590-3p were significantly higher in patients with EOC than in subjects with benign gynecologic disorders. Transient transfection of miR-590-3p mimics or stable transfection of mir-590 increased cell proliferation, migration, and invasion. studies revealed that mir-590 accelerated tumor growth and metastasis. Using a cDNA microarray, we identified forkhead box A2 (FOXA2) and versican (VCAN) as top downregulated and upregulated genes by mir-590, respectively. miR-590-3p targeted FOXA2 3' UTR to suppress its expression. In addition, knockdown or knockout of FOXA2 enhanced cell proliferation, migration, and invasion. Overexpression of FOXA2 decreased, whereas knockout of FOXA2 increased VCAN mRNA and protein levels, which was due to direct binding and regulation of the VCAN gene by FOXA2. Interrogation of the TCGA ovarian cancer database revealed a negative relationship between FOXA2 and VCAN mRNA levels in EOC tumors, and high FOXA2/low VCAN mRNA levels in tumors positively correlated with patient survival. Finally, overexpression of FOXA2 or silencing of VCAN reversed the effects of mir-590. These findings demonstrate that miR-590-3p promotes EOC development via a novel FOXA2-VCAN pathway. Low FOXA2/high VCAN levels mediate the tumor-promoting effects of miR-590-3p and negatively correlate with ovarian cancer survival. .
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