Associations of early pregnancy serum uric acid levels with risk of gestational diabetes and birth outcomes: a retrospective cohort study.

BACKGROUND: Previous evidence suggests that higher blood uric acid (UA) levels are associated with adverse cardiovascular outcomes during pregnancy and subsequent birth outcomes. However, it has been relatively unclear whether these associations persist in normotensive pregnant women. METHODS: The study was based on a retrospective analysis of 18,250 mother-infant pairs in a large obstetric center in China. Serum UA concentrations in early pregnancy (median: 17.6, IQR: 16.3, 18.6 gestational weeks) were assessed. Hyperuricemia was defined as ≥ one standard deviation (SD) of the reference value for the corresponding gestational age. Outcomes of gestational diabetes mellitus (GDM), preterm birth (PB), low birth weight (LBW), macrosomia, small for gestational age (SGA) and large for gestational age (LGA) were extracted from the medical records. RESULTS: The mean maternal UA level was 0.22 ± 0.05 mmol/L, and 2,896 (15.9%) subjects had hyperuricemia. After adjustment for several covariates, UA was associated with several adverse outcomes. The ORs (95%CI) per one SD increase in serum UA concentration were 1.250 (1.136, 1.277) for GDM, 1.137 (1.060, 1.221) for PB, 1.134 (1.051, 1.223) for LBW, and 1.077 (1.020, 1.137) for SGA, respectively. Similar adverse associations were found between hyperuricemia and GDM, PB (ORs: 1.394 and 1.385, P < 0.001), but not for LBW, macrosomia, SGA, and LGA. Adverse associations tended to be more pronounced in subjects with higher BMI for outcomes including PB, LBW, and SGA (P interaction = 0.001-0.028). CONCLUSION: Higher UA levels in early pregnancy were associated with higher risk of GDM, PB, LBW, and SGA in normotensive Chinese women.

A novel derivative of evodiamine improves cognitive impairment and synaptic integrity in AD mice.

Alzheimer's disease (AD), the major cause of dementia, is a multifactoral progressive neurodegenerative disorder that currently affects over 43 million people worldwide. The interaction betweengenetic and environmental factors decides pathogenesis and pathological development. The chemical drugs designed for clinical applications on AD have not reached the expected preventive effect so far.Here, we obtained a new evodiamine (Evo) derivative, LE-42, which exhibited lower cytotoxicity in SH-SY5Y cells and HepaG2 cells than that of Evo. The LD50 of LE-42 in SH-SY5Y cells and HepaG2 cells was increased by 9 folds and 14 folds than Evo, respectively. The LE-42 also exhibited much more potent effects on anti-oxidation and anti-cytotoxicity of AßOs than Evo. The LE-42 significantly improved the working memory, spatial learning, and memory of the 3×Tg AD mice, and the pharmacodynamic dose of LE-42 on AD mice was increased by 500 folds than that of Evo. LE-42 significantly improved the Tau hyperphosphorylation, a typical pathological feature in 3×Tg AD mice. The LE-42 restored the JAK2/STAT3 pathway's dysfunction and upregulated the expression of GluN1, GluA2, SYN, and PSD95, subsequentially improving the synaptic integrity in 3×Tg mice. The activation of the JAK2/STAT3 axis by LE-42 was a possible mechanism for a therapeutic effect on the AD mice.

Establishment of appropriate conditions for the efficient determination of multiple mycotoxins in tea samples and assessment of their drinking risks.

Conditions were determined for rapid, convenient, and efficient determination of 16 common mycotoxins in tea samples. Mycotoxins in tea leaves and tea infusion samples were extracted using solid-liquid extraction/liquid-liquid extraction combined with ultrasonic-assisted extraction. The extraction solvent was 2-butanone/ethyl acetate (9/1 v/v) with 0.1 % formic acid. The established conditions enabled the analysis of these mycotoxins by ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) in 5.5 min. In addition, HPLC with a temperature-controlled fluorescence detector was able to simultaneously determine 8 mycotoxins with fluorescent properties in 10 min without derivatization. Aflatoxin M1 (2.15 and 3.01 µg/kg), fumonisin B2 (198.89 µg/kg), and zearalenone (87.54 µg/kg) could be detected in commercially available pu-erh tea, green tea, and black tea products, and their total transfer rates from the products to brewed tea infusions were 64.08-65.13 %, 90.59 %, and 25.99 %, respectively. The risks of drinking mycotoxins from these tea infusions mostly showed low levels of concern.

Optimization of QuEChERS and high performance liquid chromatography-fluorescence detection conditions to assess the impact of preparation procedures on EU priority PAHs in coffee samples and their PAHs consumption risk.

The good performance conditions for determination of EU priority PAHs in coffee samples were established to evaluate the effects of roasting degree on the PAHs in coffee beans and the brewing methods on the PAHs transfer from coffee beans to their brews. The consumption risk of the PAHs in coffee products was also assessed. The PAHs levels of the roasted coffee beans were in the order: 923.65 ng/g (dark roast) > 132.20 ng/g (medium roast) > 69.28 ng/g (light roast). Compared with general brewing with the drip bag (PAHs content, 0.30-0.62 ng/mL in coffee brews), the coffee machine brewing (set at 4 bar) induced higher PAHs release into coffee brews (PAHs content, 0.36-2.14 ng/g). The PAHs amounts of the commercial brewed and canned coffee products were 0.32-1.23 ng/g and 0.16-0.46 ng/g, respectively. The consumption risk of the PAHs in the coffee brews and products is a low level of concern.

[Retracted] MicroRNA­155 enhances the activation of Wnt/ß­catenin signaling in colorectal carcinoma by suppressing HMG­box transcription factor 1.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blot assay data shown in Figs. 1C and 6A were strikingly similar to data appearing in different form in another article written by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 13: 2221­2228, 2016; DOI: 10.3892/mmr.2016.4788].

MicroRNA-206 inhibition and activation of the AMPK/Nampt signalling pathway enhance sevoflurane post-conditioning-induced amelioration of myocardial ischaemia/reperfusion injury.

This study aimed to investigate the effect of miR-206 on apoptosis and autophagy of cardiomyocytes in ischaemia/reperfusion (I/R) injured rats treated with sevoflurane post-conditioning (SP) through the AMPK/Nampt signalling pathway. Rat models of myocardial I/R injury were established. The combination of SP, miR-206 inhibitor, AMPK activator AICAR and inhibitor Compound C was induced in rats, and their effects on I/R injury were determined with detection of malondialdehyde (MDA), hydroxyproline (HYP) and superoxide dismutase (SOD) levels in cardiomyocytes, autophagy, and apoptosis. We also conducted experiments to determine p62, Beclin1, Bax and Bcl-2 expression and the mRNA and expression pattern of AMPK/Nampt signalling pathway-related genes. Myocardial I/R injured rats revealed decreased SOD activity and elevated MDA content, autophagy and apoptosis. With the combined performance of SP, miR-206 inhibitor and AMPK activator AICAR, the rats presented higher SOD level and lower MDA and HYP levels, suppressed autophagy and apoptosis. Meanwhile, miR-206 inhibition also contributed to elevated expression of Nampt and the extent of AMPK phosphorylation, increased Bcl-2/Bax ratio, but degraded expression of p62 and Beclin1. Collectively, inhibition of miR-206 could activate the AMPK/Nampt signalling pathway, thus protecting against myocardial I/R injury on the basis of SP.

Rapid determination of neomycin in biological samples using fluorescent sensor based on quantum dots with doubly selective binding sites.

A new analytical method was developed to detect neomycin in complex biological samples using molecularly imprinted polymer to construct an optical sensor. Fluorescent neomycin-imprinted polymers (fMIPs) containing both imprinted cavity and boronate affinity site were synthesized on the surface of silica-modified quantum dots. The fMIPs exhibited high selectivity to neomycin by having two binding sites for the target analyte. Neomycin analogues (competing for imprinted cavity) and D-glucose (competing for the boronate affinity site) did not affect the selectivity of the fMIPs. When combined with a fluorescent microplate reader, the obtained fMIP sensor displayed a linear concentration-dependent fluorescence quenching in response to neomycin in the range of 2-1000 µg/L, with a limit of detection as 0.16 µg/L. The fMIP sensor was able to detect trace neomycin in biological samples accurately after simple sample pre-treatment. The sensitivity of the fMIP sensor was higher than HPLC equipped with a fluorescence detector. The fMIP sensor containing the doubly selective binding sites provides a selective, sensitive, accurate, and high through-put approach for neomycin monitoring.

Bio-inspired virus imprinted polymer for prevention of viral infections.

A novel virus-imprinted polymer for prevention of viral infection was prepared by anchoring molecularly imprinted polymer (MIP) on the surface of poly-dopamine (PDA)-coated silica particles. The imprinting reaction was carried out via self-polymerization of dopamine in the presence of a virus template. Plaque forming assay indicated that the MIP exhibited selective anti-viral infection properties for the template virus in complex media containing different interfering substances, and even other types of viruses. Remarkable dose-dependent and time-dependent inhibition of virus infection was observed due to the MIP's selective binding to the template virus. When the MIP was incubated with the virus and host cells together, rapid and selective adsorption of template viruses by the MIP prevented the viruses to infect the host cells in a period of 12h. The MIP was biocompatible and non-toxic, and had excellent stability and reusability. Furthermore, the MIPs prepared using different viruses as templates showed similar anti-viral infection properties. The MIP synthesized using dopamine as monomer and crude virus as template provided an attractive possibility for clinical applications in the field of antiviral therapy. STATEMENT OF SIGNIFICANCE: This is the first report to prepare artificial antibody (molecularly imprinted polymer, MIP) that can selectively prevent virus infection using dopamine self-polymerization system. Only MIP anchoring on the surface of poly-dopamine coated silica particles and polymerized using ammonium persulfate as radical initiator showed dose-dependent and time-dependent inhibition of template virus infection in complex media containing interferences and even other viruses. Viruses bond to MIP lost infectious capability. When incubated with virus and host cells, MIP rebond viruses rapidly and selectively to prevent viruses infecting host cells for 12h. The achieved MIPs were biocompatibility, non-toxicity with excellent stability and reusability, and can be used to different viruses. The bio-mimic MIPs provided an attractive prospect for clinical applications in antiviral therapy.

MicroRNA-155 enhances the activation of Wnt/ß-catenin signaling in colorectal carcinoma by suppressing HMG-box transcription factor 1.

Colorectal carcinoma (CRC) is a malignant solid tumor arising from the large intestine and is associated with an increasing incidence and poor prognosis. Further understanding of the molecular mechanisms underlying CRC may contribute to the development of novel effective therapeutic strategies. MicroRNAs (miRs), including miR­155, have been reported to be associated with the etiology and biology of CRC; however, the molecular mechanisms by which miR­155 affect CRC remain to be fully elucidated. The present study used a multidisciplinary approach, involving reverse transcription­quantitative polymerase chain reaction, northern blotting, MTT assay, cell cycle progression analysis, immunoblotting, and animal experiments, to determine the possible targets of miR­155 in CRC cells. miR­155 was found to be overexpressed in CRC tissue samples, compared with paired normal colon tissue samples. In addition, the inhibition of miR­155 induced a deceleration in CRC cell proliferation and inactivation of the Wnt/ß­catenin signaling pathway. miR­155 suppression also reduced the growth of CRC xenografts in an animal model. HMG­box transcription factor 1 (HBP1) was identified as a novel target of miR­155, which mediated its effect on CRC via the Wnt/ß­catenin pathway. Furthermore, patients with CRC exhibiting higher serum levels of miR­155 exhibited reduced survival rates. In conclusion, the present study demonstrated that miR­155 may contribute to the progression and growth of CRC by enhancing the Wnt/ß­catenin pathway in an HBP1­associated mechanism. Therefore, miR­155 may be considered a promising therapeutic target for the treatment of CRC.

MIPs in Aqueous Environments.

When organic solvent-compatible molecularly imprinted polymers (MIPs) are used in aqueous environment, how to reduce nonspecific binding is a major challenge. By modifying the binding solvents and introducing appropriate washing and elution steps, even relatively hydrophobic MIPs can gain optimal rebinding selectivity in aqueous conditions. Furthermore, water-compatible MIPs that can be used to treat aqueous samples directly have been prepared. The use of hydrophilic co-monomers, the controlled surface modification through controlled radical polymerization, and the new interfacial molecular imprinting methods are different strategies to prepare water-compatible MIPs. By combining MIPs with other techniques, both organic solvent-compatible and water-compatible MIPs can display better functional performances in aqueous conditions. Intensive studies on MIPs in aqueous conditions can provide new MIPs with much-improved compatibilities that will lead to more interesting applications in biomedicine and biotechnology.

Correlation between the cystathionine-γ-lyase (CES) and the severity of peptic ulcer disease.

BACKGROUND: The infection of Helicobacter pylori (H. pylori) is one of the most important causes of gastric ulcer disease. The role of hydrogen sulfide (H2S) production in H. pylori-induced gastric ulcer disease. AIM: The expression of cystathionine-γ-lyase (CSE) was determined, and correlated with the severity of gastric ulcer disease. METHODS: One hundred and eight patients were selected based on the determination of gastric ulcer and the infection of Helicobacter pylori (H. pylori), including 36 normal control, 36 patients with H. Pylori-negative gastric ulcer, and 36 patients with H. Pylori-positive gastric ulcer. RT-PCR determination was performed to determine the expression of CSE, NF-κB and IL-8. RESULTS: The expression of CSE, NF-κB and IL-8 was higher in the gastric ulcer group than control group (p<0.05). Compared with the H. pylori-negative gastric ulcer, the expression of CSE, NF-κB and IL-8 was higher than H. pylori-positive gastric ulcer group (p<0.05). For H. pylori-negative gastric ulcer group, the expression of CSE positively correlated with the expression of NF-κB (r=0.98, p<0.05) and IL-8 (r=0.95, p<0.05). For H. pylori-positive gastric ulcer group, the expression of CSE also positively correlated with the expression of NF-κB (r=0.99, p<0.05) and IL-8 (r=0.85, p<0.05). CONCLUSION: The expression of CSE was positively correlated with the severity of gastric ulcer.

Selective and simultaneous determination of trace bisphenol A and tebuconazole in vegetable and juice samples by membrane-based molecularly imprinted solid-phase extraction and HPLC.

Nanofibrous molecularly imprinted membranes (nano-MIMs) with multi-analyte selectivity were prepared by encapsulating two types of molecularly imprinted polymer nanoparticles (MIP-NPs) into electrospun polyvinyl alcohol nanofibers. The obtained nano-MIMs maintained high molecular selectivity offered by each of the MIP-NPs. Nano-MIM embedding BPA-imprinted nanoparticles and TBZ-imprinted nanoparticles together showed the highest binding selectivity for acid bisphenol A (BPA) and basic tebuconazole (TBZ). This nano-MIM was used as affinity material of membrane-based molecularly imprinted solid-phase extraction (m-MISPE) to extract trace BPA and TBZ in vegetables and juices simultaneously. The recoveries of BPA and TBZ from different samples were higher than 70.33% with RSDs lower than 9.57%. m-MISPE gave better HPLC separation efficiencies and higher recoveries than conventional SPE based on C18/SCX. Multi-analyte selective m-MISPE combined with HPLC realized selective and simultaneous determination of several trace analytes with opposite charges/polarities in different food samples.