Combined association of early exposure to long-chain n-3 polyunsaturated fatty acids, mercury and selenium with cognitive performance in 1-year-old infants.

BACKGROUND: Previous studies on long-chain n-3 polyunsaturated fatty acids (LCn3PUFAs) and infant neurodevelopment did not consider effect modifications of mercury (Hg) and selenium (Se). OBJECTIVES: To examine the joint association of prenatal LCn3PUFAs, Hg and Se with infant cognitive performance, and to explore whether DNA methylation may explain this potential association. METHODS: A total of 484 newborns were enrolled from the Shanghai Birth Cohort with available data on cord blood LCn3PUFA, nail Hg and Se during 2015-2016. Cord blood LCn3PUFA concentrations were assessed by gas chromatography, and nail Hg and Se concentrations were measured using clippings collected within 6 months of birth by inductively coupled plasma mass spectrometry. Five aspects of infant neurodevelopment (communication, gross motor, fine motor, problem-solving, and personal-social skills) were assessed using the Age and Stage Questionnaire (ASQ) at ages 6 and 12 months. Multivariable-adjusted generalized estimating equations models were performed to examine the associations between cord blood LCn3PUFA concentrations and ASQ test scores, and these associations were stratified by nail Hg and Se levels. Epigenome-wide DNA methylation in cord blood was compared in a random subgroup consisting of 19 infants from the highest and 21 from the lowest decile of LCn3PUFA concentrations. RESULTS: LCn3PUFAs were not significantly associated with any ASQ test scores. However, in the subgroup with lower Hg (

Early-life exposure to aluminum and fine motor performance in infants: a longitudinal study.

BACKGROUND: Aluminum (Al) is a well-established neurotoxicant. However, little is known about its effects on the neurodevelopment of infants. OBJECTIVES: To examine early-life exposure to Al in relation to neurodevelopment in healthy infants. METHODS: Nail Al concentrations were measured among 747 newborn babies within 6 months of delivery in the Shanghai Birth Cohort. Neurodevelopment was assessed using Ages and stages questionnaire (third edition, ASQ-3) at ages 6 and 12 months. General linear regression models were performed to estimate the associations between Al concentrations and ASQ-3 scores. RESULTS: After adjustment for potential confounders, early-life exposure to Al was not associated with any neurodevelopmental performance at age 6 months. However, Al level was associated with an increased risk of having a low fine motor score (quartile 4 vs. quartile 1, mean difference (MD): -1.63; 95% confidence interval (CI): -3.22, -0.05; P-trend < 0.01) at 12 months. No association was found for communication, gross motor, problem-solving, or personal-social score at 12 months. SIGNIFICANCE: Early-life exposure to Al may be associated with poor fine motor skills in a dose-response manner among apparently healthy infants at age 12 months.

Molecular interaction of cyanidin-3-O-glucoside with ovalbumin: insights from spectroscopic, molecular docking and in vitro digestive studies.

Anthocyanins bound with proteins have influence on the digestibility of proteins. In this study, the interaction between cyanidin-3-O-glucoside (C3G) and ovalbumin (OVA) was investigated through multi-spectroscopy and molecular docking. The interactive effect of C3G on OVA digestibility was estimated by an in vitro digestion model. Fluorescence studies indicated that C3G quenched the fluorescence of OVA in a static mode, where the binding constants (Ka) at 298, 308 and 318 K were above 105 M-1, indicating a strong binding affinity of C3G with OVA. The negative values of thermodynamic parameters (ΔG, ΔH and ΔS) revealed a spontaneous binding process, where hydrogen and van der Waals forces were involved in stabilizing the OVA-C3G complex. The secondary structure of OVA was modified by C3G binding, with augmented ß-sheet (21.5%-25.1%) and diminished α-helix (23.3%-21.6%). Besides, C3G substantially inhibited the digestion of OVA in pancreatin solution whereas it had negligible effect on pepsin. Furthermore, molecular docking and cleavage site prediction studies showed that the hydrogen binding sites of C3G are not near to the cleavage sites of pepsin but partially overlap trypsin cleavages sites in OVA, which might lead to an inhibited effect on pancreatic digestion. These results provide a better understanding of the anthocyanin-protein interactions and their effect on the protein digestibility.Communicated by Ramaswamy H. Sarma.

Microfluidic Device Directly Fabricated on Screen-Printed Electrodes for Ultrasensitive Electrochemical Sensing of PSA.

How to fabricate scale low-cost microfluidic device for detection of biomarkers owns a great requirement. Herein, it is for the first time reported that a new microfluidic device based on bonding polydimethylsiloxane microfluidic channels onto the substrate of a screen-printed electrode with coating glass solution was fabricated for electrochemical sensing of prostate-specific antigen (PSA). Compared to traditional microfabrication processes, this method is simple, fast, low cost, and also suitable for mass production. The prepared screen-printed electrode-based microfluidic device (CASPE-MFD) was used for the detection of the PSA in human serum. The prepared CASPE-MFD had a detection limit of 0.84 pg/mL (25.8 fM) and a good linearity with PSA concentration ranging from 0.001 to 10 ng/mL, which showed a great promise platform toward the development of miniaturized, low-cost electrochemical microfluidic device for use in human health, environmental monitoring, and other applications.

The cytotoxic effect of the NOS-mediated oxidative stress in MCF-7 cells after PbCl2 exposure.

The potential Pb-induced cytotoxicity in various tissues and biological systems has been reported. Some evidences also indicate that the Pb-caused cytotoxicity may be associated with the nitric oxide synthase (NOS). However, there remains uncertainty about the role of the NOS signaling pathway during the Pb-induced cytotoxicity. In this report, we provide data showing that PbCl2 treatment depresses the expressions of the three distinct NOS isoforms: neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) on both transcriptional and translational levels in MCF-7 cells. The down-regulation of NOSs expressions by PbCl2 exposure leads to reduced NOS activity and nitric oxide (NO) production. Meanwhile, the intracellular reactive oxygen species (ROS) level is elevated after PbCl2 exposure, which leads to the alpha subunit of eukaryotic initiation factor 2 (elF2α) phosphorylation. The reduction effects of the free radical scavenger N-acetyl-L-cysteine or the NOS substrate l-arginine on the Pb-induced ROS generation suggest that the NOS signaling pathway plays a key role in the Pb-induced oxidative stress, which further results in the elF2α phosphorylation and cytotoxicity.

The role of NOS-mediated ROS accumulation in an early phase Cu-induced acute cytotoxicity in MCF-7 cells.

Copper (Cu) ion is essential for the biological systems, however, high level of CuCl2 exposure causes detrimental effects, which leads to cell apoptosis. Nitric oxide (NO) is an efficient cell signal messenger, which plays an important role in cell apoptosis. However, the potential mechanism of an early phase Cu-induced acute cytotoxicity through the nitric oxide synthase (NOS) signaling pathway and its interaction has not been studied. In this report, we provide data showing that high level of CuCl2 could rapidly decrease the NO production with the release of Ca(2+) and Zn(2+), and then modulate the transcriptional and translational expression of NOSs in MCF-7 cells. The reactive oxygen species (ROS) level in cells was increased after high level of CuCl2 exposure, which led to the alpha subunit of eukaryotic initiation factor 2 phosphorylation. By using the free radical scavenger N-acetyl-L-cysteine or the NOS substrate L-arginine, it demonstrated that NOS played a critical role on the Cu-induced ROS generation, which further led to the oxidative stress and cell apoptosis. These results suggested that Cu-induced apoptosis was associated with the oxidative stress, and through the NOS-mediated signaling pathway.

The role of nitric oxide synthase in an early phase Cd-induced acute cytotoxicity in MCF-7 cells.

Literature to date has confirmed that cadmium (Cd) can accomplish its toxic effects via the free radical-induced damage, but Cd itself cannot generate free radicals directly. Nitric oxide (NO) is a fundamental molecule that interplays with reactive oxygen species (ROS), which may be associated with the Cd-induced cytotoxicity. However, the role of nitric oxide synthase (NOS) in an early phase Cd-induced acute cytotoxicity and its interaction has not been studied. In this report, we provide data showing that CdCl2 (10 µM, 100 µM, 1 mM) could modulate NOS activity in terms of NO production which was first suppressed with the release of Ca(2+) and Zn(2+), then induced with the transcriptional and translational activation of the three NOS isoforms in a possible feedback manner. The ROS level in cells was increased after CdCl2 exposure. By using the free radical scavenger N-acetyl-L-cysteine (LNAC) or the NOS activity inhibitor N(G)-methyl-L-arginine (LNMMA), it was demonstrated that NOS played a critical role on the Cd-induced ROS generation. The Cd-induced cytotoxicity was associated with the NOS-mediated oxidative stress in MCF-7 cells.

The role of nitric oxide synthase signaling pathway in the Zn-induced cellular responses in MCF-7 cells.

Trace amount zinc plays key roles in biological systems, while in excessive amount it causes toxic effects. Evidence shows that there exists a crosstalk between NO and Zn apoptotic signal transduction pathway. However, the potential mechanism of Zn-induced cellular responses through the NOS signaling pathway has not been determined yet. In this research, trace amount ZnCl2 (1nM) could induce the NO production, however it appears that this influence does not extend to genetic level in MCF-7 cells. Whereas, excess ZnCl2 (100µM, 1mM) could lead to a decreased NO production first with the release of Ca(2+), and then induce the NO production with the transcriptional and translational activation of NOSs. The ROS generation was also induced by excess ZnCl2, causing the elF2α phosphorylation. The alleviation effect of N-acetyl-l-cysteine or l-arginine on the Zn-induced ROS generation and apoptosis suggested that Zn-induced apoptosis was associated with the NOS-mediated oxidative stress.

Quantitative studies on structure-ORAC relationships of anthocyanins from eggplant and radish using 3D-QSAR.

The 3-dimensional quantitative structure activity relationship (3D-QSAR) models were established from 21 anthocyanins based on their oxygen radical absorbing capacity (ORAC) and were applied to predict anthocyanins in eggplant and radish for their ORAC values. The cross-validated q(2)=0.857/0.729, non-cross-validated r(2) = 0.958/0.856, standard error of estimate = 0.153/0.134, and F = 73.267/19.247 were for the best QSAR (CoMFA/CoMSIA) models, where the correlation coefficient r(2)pred = 0.998/0.997 (>0.6) indicated a high predictive ability for each. Additionally, the contour map results suggested that structural characteristics of anthocyanins favourable for the high ORAC. Four anthocyanins from eggplant and radish have been screened based on the QSAR models. Pelargonidin-3-[(6''-p-coumaroyl)-glucosyl(2 → 1)glucoside]-5-(6''-malonyl)-glucoside, delphinidin-3-rutinoside-5-glucoside, and delphinidin-3-[(4''-p-coumaroyl)-rhamnosyl(1 → 6)glucoside]-5-glucoside potential with high ORAC based the QSAR models were isolated and also confirmed for their relative high antioxidant ability, which might attribute to the bulky and/or electron-donating substituent at the 3-position in the C ring or/and hydrogen bond donor group/electron donating group on the R1 position in the B ring.