Chronic exposure to parabens promotes non-alcoholic fatty liver disease in association with the changes of the gut microbiota and lipid metabolism.

Non-alcoholic fatty liver disease (NAFLD) has become a serious public health issue due to changing dietary patterns and composition. However, the relationship between NAFLD occurrence and food additives, such as preservatives, remains unknown. This study aimed to evaluate the toxicity of parabens, namely methylparaben (MeP) and ethylparaben (EtP), in relation to NAFLD occurrence in mice under different dietary conditions. Exposure to MeP and EtP exacerbated high-fat diet (HFD)-induced obesity, glucose intolerance, higher serum lipid concentrations, and fat accumulation by upregulating genes involved in lipid metabolism. Untargeted metabolomics revealed that arachidonic acid (AA) metabolism was the top enriched pathway upon MeP and EtP exposure in the presence of HFD. 11,12-Epoxyeicosatrienoic acid (11,12-EET) was the most abundant AA metabolite and was significantly reduced upon exposure to MeP or EtP. Moreover, an integrative analysis of differential fecal taxa at the genus level and serum AA metabolites revealed significant associations. In addition, MeP and EtP enhanced lipid accumulation in AML12 cells and HepG2 cells cultured with oleic acid. 11,12-EET supplementation could significantly alleviate lipid accumulation by suppressing the expression of lipid metabolism-related genes and proteins. The present study suggests that chronic exposure to MeP and EtP promoted NAFLD via gut microbiota-dependent AA metabolism. These results highlight the need for reducing oral exposure to synthetic preservatives to improve metabolic disturbance under HFD conditions.

A G-quadruplex-assisted target-responsive dual-mode aptasensor based on copper nanoclusters synthesized in situ in a DNA hydrogel for ultrasensitive detection of ochratoxin A.

Developing ultrasensitive sensing platforms for trace ochratoxin A (OTA) in food safety is still challenging. Herein, we presented a novel dual-mode sensing strategy for fluorescence and colorimetric detection of OTA by combining the target-responsive hemin-encapsulated and copper nanoclusters (CuNCs) functionalized DNA hydrogel. Through simple assembly and in situ synthesis methods, fluorescence CuNCs are synthesized and modified on the 3D hydrophilic network structure of DNA cross-linked. OTA specifically recognized by Apt-linker can control the collapse of hydrogel, resulting in the fluorescence quenching of CuNCs and release of coated hemin. Interestingly, OTA could trigger Apt-linker conformational changes to form G-quadruplex structures, allowing the released hemin to form G-quadruplex/hemin DNAzyme via self-assembly. Fluorescence signal amplification could be achieved through further fluorescence quenching of CuNCs caused by DNAzyme-catalyzed hydrogen peroxide (H2O2) because of the peroxidase activity of DNAzyme. Simultaneously, DNAzyme could catalyze the H2O2-mediated oxidation of TMB to provide colorimetric signal. Thereafter, the DNA-CuNCs hydrogel exhibited low detection limits of 3.49 pg/mL in fluorescence mode and 0.25 ng/mL in colorimetric modality. Real sample analyses of foodstuffs showed satisfactory results, providing prospective potential for monitoring mycotoxin contaminant.

5-Methyltetrahydrofolate Alleviates Memory Impairment in a Rat Model of Alzheimer's Disease Induced by D-Galactose and Aluminum Chloride.

The effects of 5-methyltetrahydrofolate (5-MTHF) on a rat model of Alzheimer's disease (AD) induced by D-galactose (D-gal) and aluminum chloride (AlCl3) were investigated. Wistar rats were given an i.p. injection of 60 mg/kg D-gal and 10 mg/kg AlCl3 to induce AD and three doses of 1 mg/kg, 5 mg/kg or 10 mg/kg 5-MTHF by oral gavage. A positive control group was treated with 1 mg/kg donepezil by gavage. Morris water maze performance showed that 5 and 10 mg/kg 5-MTHF significantly decreased escape latency and increased the number of platform crossings and time spent in the target quadrant for AD rats. The administration of 10 mg/kg 5-MTHF decreased the brain content of amyloid ß-protein 1-42 (Aß1-42) and phosphorylated Tau protein (p-Tau) and decreased acetylcholinesterase and nitric oxide synthase activities. Superoxide dismutase activity, vascular endothelial growth factor level and glutamate concentration were increased, and malondialdehyde, endothelin-1, interleukin-6, tumor necrosis factor-alpha and nitric oxide decreased. The administration of 10 mg/kg 5-MTHF also increased the expression of disintegrin and metallopeptidase domain 10 mRNA and decreased the expression of ß-site amyloid precursor protein cleavage enzyme 1 mRNA. In summary, 5-MTHF alleviates memory impairment in a D-gal- and AlCl3-exposed rat model of AD. The inhibition of Aß1-42 and p-Tau release, reduced oxidative stress, the regulation of amyloid precursor protein processing and the release of excitatory amino acids and cytokines may be responsible.

Investigation into the Properties of L-5-Methyltetrahydrofolate and Seal Oil as a Potential Atherosclerosis Intervention in Rats.

Atherosclerosis is a chronic inflammatory disease that leads to tissue ischemia. As the biologically active form of folic acid, L-5-methyltetrahydrofolate (L-5-MTHF) can improve endothelial function. And Seal oil plays a beneficial role in the progression of atherosclerosis. The study aims to evaluate beneficial effects of L-5-MTHF alone or in combination with Seal oil on atherosclerosis. Seventy-two male Wistar rats were randomly divided into 6 groups: control (normal diet), atherosclerosis (high-fat diet), folic acid (high-fat+3 mg/kg folic acid), low-dose L-5-MTHF (high-fat+3 mg/kg L-5-MTHF), low-dose L-5-MTHF+Seal oil (high-fat+3 mg/kg L-5-MTHF+0.5 g/kg Seal oil), high-dose L-5-MTHF (high-fat+10 mg/kg L-5-MTHF). After 13 wk, rats were sacrificed. Rats exhibiting atherosclerosis had dyslipidemia and serious aortic lesions. Supplementation with low-dose L-5-MTHF+Seal oil or use of high-dose L-5-MTHF increased serum folate concentrations, decreased homocysteine levels, improved the serum lipid profile, up-regulated expression of NO and NOS, enhancement of the antioxidant properties of GSH-Px activity and reduction in the concentration of MDA, levels of Olr1 and RelA mRNA decreased in aortic tissues, and expression of inflammatory factors, TNF-α, IL-6, IL-1ß and endothelial cell injury factors ET-1 and sICAM-1, were also down-regulated. In addition, HD-L-5-MTHF increased the antioxidant activity of serum SOD. We conclude that L-5-MTHF has obvious anti-inflammatory and antioxidant effects on diseased blood vessels. The intervention of L-5-MTHF alone or in combination with Seal oil can improve atherosclerosis in rats and reduce the occurrence of aortic lesions. The anti-atherosclerotic mechanism may be related to down-regulation of Olr1 and RelA expression.

Cross-sectional study: Relationship between serum trace elements and hypertension.

BACKGROUND: A balanced intake of trace elements is beneficial for chronic diseases such as hypertension. However, the available information regarding trace elements that may be independently associated with hypertension is limited, and the relationship between this disorder and element ratios also remains unclear. METHODS: A total of 6,754 subjects from rural China were selected, after exclusion of patients who were under 18, had incomplete data or had additional related disorders, by multi-stage simple random and cluster sampling (participation rate: 95.22 %). Subjects were divided into a hypertensive (H) and a control (C) group. Data were collected on blood pressure and 12 serum trace elements were measured by flame atomic absorption spectrometry and inductively coupled plasma-mass spectrometry. Other basic information was collated from questionnaires and biochemical indicators were measured via kits. RESULTS: Differences in serum levels of magnesium (Mg(mg/l): H: 27.43 ± 12.72; C: 26.33 ± 12.16), iron (Fe(mg/l): H: 1.99 ± 1.24; C: 1.84 ± 1.16), copper (Cu(mg/l): H: 1.19 ± 0.37; C: 1.10 ± 0.36), boron (B(µg/l): H: 50.00 ± 25.21; C: 47.57 ± 26.25), selenium (Se(µg/l): H: 125.12 ± 32.81; C: 118.80 ± 29.72) and chromium (Cr(µg/l): H: 8.77 ± 10.12; C: 10.12 ± 10.72) between the hypertensive and control groups were found. There were no differences in serum contents of calcium (Ca(mg/l): H: 112.43 ± 58.25; C: 111.00 ± 59.49), zinc (Zn(mg/l): H: 1.50 ± 1.97; C: 1.44 ± 1.88), arsenic (As(µg/l): H: 4.17 ± 3.94; C: 4.10 ± 4.00), manganese (Mn(µg/l): H: 4.15 ± 4.03; C: 4.07 ± 4.05), cadmium (Cd(µg/l): H: 1.14 ± 1.11; C: 1.18 ± 1.12) or lead (Pb(µg/l): H: 4.22 ± 8.90; C: 4.26 ± 10.25). The serum Cr and Cd concentrations of hypertensive men were lower than that of male controls while Mg, Cu, Ca and Se concentrations in male controls were lower. Further differences were apparent and Fe, B, Se, Mg and Cu all showed higher levels in hypertensive females whereas Cr concentrations were higher in female controls. Serum Zn and B levels showed age-related variations among hypertensive patients and concentrations of serum Cu, Zn, Se and B showed age-related variations among control subjects. For hypertensive patients, the odds ratio (OR) and 95 % confidence interval (CI) for the association of serum Cu, Se and Cr levels with hypertension were Cu: 1.36 (1.12-1.66); Se: 1.03 (1.01-1.05); Cr: 0.89 (0.83-0.96). Moreover, when the participants in the grouping with the highest copper/zinc (Cu/Zn) and magnesium/manganese (Mg/Mn) ratios were compared with the reference group, the OR and 95 % CI for hypertension were 1.22 (1.04-1.44) and 1.20 (1.01-1.42), respectively. CONCLUSIONS: Levels of serum trace elements showed age- and sex-related differences in a group of rural Chinese adults with hypertension and healthy participants. Serum concentrations of Cu, Se and Cr may be independently associated with hypertension. Higher serum ratios of Cu:Zn and Mg:Mn may also be associated with hypertension. Further randomized trials are necessary to elucidate the true relationship between levels of Cu, Se, Cr, Cu:Zn, Mg:Mn and hypertension.