Trimethylamine N-Oxide increases soluble fms-like tyrosine Kinase-1 in human placenta via NADPH oxidase dependent ROS accumulation.

BACKGROUNDS: Preeclampsia (PE) is characterized as placental vascular disturbance and excessive secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) into the maternal circulation. Trimethylamine N-oxide (TMAO, a gut microbe-derived metabolite) is strongly associated with various cardiovascular and cerebrovascular diseases. Recently, we observe that higher maternal circulating TMAO and sFlt-1 in patients with PE. The aims of the present study are to explore the effects of TMAO on placental sFlt-1 production and the underlying mechanism in human placenta. METHODS: Human placental explants, human placental primary trophoblasts and the extravillous trophoblasts (EVT) cell line (HRT-8/SVneo) were exposured to various concentrations of TMAO (100, 150, 300, and 600 µM). The mRNA expression and protein secretion of sFlt-1 in placental explants, primary trophoblasts and HRT-8/SVneo cells were determined with qPCR and ELISA, respectively. The levels of intracellular reactive oxygen species (ROS) production in primary trophoblasts and HRT-8/SVneo cells were measured by peroxide-sensitive fluorescent probe dichlorofluorescein diacetate. RESULTS: Exposure of placental explants, primary trophoblasts and HRT-8/SVneo cells to TMAO significantly enhanced sFlt-1 at both mRNA and protein levels in a dose dependent manner. Moreover, inhibition of NADPH oxidase with apocynin significantly attenuated TMAO-induced ROS production in primary trophoblasts and HRT-8/SVneo, and suppressed sFlt-1 secretion in placental explants, primary trophoblasts and HRT-8/SVneo. CONCLUSIONS: Our findings indicated the NADPH oxidase dependent ROS pathway played a critical role in mediating TMAO-induced sFlt-1 generation in human placenta. TMAO may become a potential novel target for pharmacological or dietary interventions to reduce the risk of developing PE.

A CdII -Based Metal-Organic Framework with pcu Topology as Turn-On Fluorescent Sensor for Al3.

A new metal-organic framework (MOF) {[Cd2 (bbib)2 (ndc)2 ]⋅2DMF}n (JXUST-1) (bbib=1,3-bis(benzimidazolyl)benzene, H2 ndc=1,4-naphthalenedicarboxylic acid, DMF=N,N-dimethylformamide) has been solvothermally synthesized and characterized by single-crystal X-ray diffraction, PXRD, TGA, IR and elemental analysis. JXUST-1 exhibits a three-dimensional 6-connected pcu topology with a Schläfli symbol {412 .63 } constructed by [Cd2 (CO2 )3 ] secondary building units. Fluorescence studies show that this MOF can sensitively and selectively recognize Al3+ via a fluorescence enhancement effect, and the detection limit is 0.048 ppm. Furthermore, JXUST-1 displays relatively good thermal and chemical stabilities as well as reusability. All these results suggest JXUST-1 to be a highly selective and recyclable luminescent sensing material for the detection of Al3+ .