A LncRNA-miRNA-mRNA ceRNA regulatory network based tuberculosis prediction model.

The high incidence of tuberculosis (TB) has brought serious social burdens and it is urgent to explore the mechanism of TB development. This study was conducted to analyze the role of lncRNA-miRNA-mRNA regulatory network and its contained nodes involved in TB to identify crucial biomarkers for early diagnosis of TB. Long-noncoding RNAs (lncRNAs), messenger RNA (mRNAs) and microRNAs (miRNAs) expression profiles of TB patients and healthy individuals were downloaded from the GSE34608 dataset. Weighted gene co-expression network analysis (WGCNA) was performed to identified the key modules related to TB and the highly related mRNA-lncRNA pair in the module. Based on highly related mRNAs and lncRNAs in greenyellow module, lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network was constructed. The DE-mRNAs in the network were functionally enriched with Gene ontology (GO) and Gene set enrichment analysis (GSEA). Least absolute shrinkage and selection operator (LASSO) algorithm and receiver operating characteristic curve (ROC) were used to construct and evaluate the prediction model of TB. We identified 3267 DE-mRNAs, 484 DE-lncRNAs and 69 DE-miRNAs between the TB and healthy subjects, from which 8 DE-mRNAs, 14 DE-lncRNAs and 3 DE-miRNAs were used to construct the ceRNA network. The genes contained in the ceRNA network were mainly enriched in neutrophil mediated immune response, including neutrophil activation, degradation and signal transduction. ROC analysis revealed that has-miR-140-5p, has-miR-142-3p and the LASSO cox prediction model based on HMGA1 and CAPN1 have potential value for forecasting TB (AUC > 0.7). Hence, our study provides a new perspective from the lncRNA-miRNA-mRNA ceRNA regulatory network for TB diagnosis and treatment.

Incidence of death from kidney diseases among cancer patients: a US population-based analysis.

BACKGROUND: The purpose of our study was to retrospectively analyze the characteristic of death from kidney diseases among cancer patients and to screen the risk factors associated with nephrotic death using data from the surveillance, epidemiology, and end results (SEER) database. METHODS: The information on cancer patients dying of kidney diseases was retrieved from the SEER database. Standardized mortality ratios (SMRs) were calculated using the US general population as reference. Univariate and multivariate Cox regression analyses were conducted to screen potential risk factors of death from kidney diseases. RESULTS: Data of 7,167,808 patients diagnosed with malignant tumors between 2000 and 2016 were collected. Of these, 25,903 patients died of kidney diseases. Compared to the general population, cancer patients were at an elevated risk of nephrotic death with an SMR of 3.17, and this risk continues to increase in recent years. The majority of deaths from kidney diseases occur in patients > 45-year-old diagnosed with cancer of prostate, colorectum, and breast. Additionally, cancer patients with diagnosis in recent years, older age at diagnosis, black race, higher grade, and poorer disease stage were more likely to die of kidney diseases are at higher risk of nephrotic death compared to other cancer survivors. CONCLUSION: The risk of death from kidney diseases is increasing among cancer survivors recently. Nephrologists should be actively involved in certain facets of cancer treatment, and provide effective nephrology care, especially for elderly patients with black race, higher grade, and poorer disease stage.

The effects of HIF-1α overexpression on renal injury, immune disorders and mitochondrial apoptotic pathways in renal ischemia/reperfusion rats.

BACKGROUND: Renal ischemia/reperfusion (RI/R) injury are a common pathogenesis of acute kidney injury, which may cause renal parenchyma damage clinically. Hypoxia-inducible factor-1α (HIF-1α) has protective effects on cells in regulating the metabolism, angiogenesis, erythropoiesis, and anti-apoptosis of RI/R injury. However, the specific mechanisms for HIF-1α on RI/R injury are still unclear. This study aims to investigate the effects of HIF-1α overexpression on renal function injury, immune disorder, and mitochondrial apoptosis in RI/R rats. METHODS: The rat model of RI/R injury was set up. The lentivirus (LV) vector of HIF-1α overexpression was constructed, and then the LV was transfected to the model rats. The rats were randomly divided into four groups: the control group, RI/R group, RI/R + LV group, and RI/R + LV-HIF-1α group for later experiments. The mRNA levels of HIF-1α were detected by RT-PCR. Proteinuria, urea nitrogen, and serum creatinine levels were detected using the relative kit. Pathological damage was detected by HE staining. Apoptosis was detected by TUNEL staining. Levels of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α) and interleukin-10 (IL-10) were detected by ELISA. Western blotting was used to detect the protein levels of HIF-1α, caspase-3, caspase-9, Bax, Bcl-2, and other proteins. RESULTS: Compared with the control group, the mRNA and protein levels of HIF-1α in the RI/R group were increased significantly (P<0.05). Proteinuria, urea nitrogen, serum creatinine levels were increased significantly (P<0.05). The levels of IL-6, IL-1 beta, TNF-α were increased significantly (P<0.05). The ratios of cleaved caspase-3/caspase-3, cleaved caspase-9/caspase-9, and Bax/Bcl-2 were increased significantly (P<0.05). There was a significant increase in apoptosis rate and renal pathological tissue damage (P<0.05). Compared with RI/R+LV group, the mRNA and protein levels of HIF-1α in the RI/R+LV-HIF-1α group were increased significantly (P<0.05). Proteinuria, urea nitrogen, serum creatinine levels were decreased significantly (P<0.05). IL-6, IL-1 beta, TNF-α levels were significantly decreased (P<0.05). IL-10 level was significantly increased (P<0.05). The ratios of cleaved caspase-3/caspase-3, cleaved caspase-9/caspase-9, and Bax/Bcl-2 were significantly reduced (P<0.05), showing that the pathological damage degree and the apoptosis rate was significantly lower. CONCLUSIONS: HIF-1α overexpression has protective effects on renal ischemia-reperfusion rats by improving pathological injury and immune function, reducing the release of inflammatory factors, and the expression of apoptotic proteins.

Levels of tetrabromobisphenol A, hexabromocyclododecanes and polybrominated diphenyl ethers in human milk from the general population in Beijing, China.

Three brominated flame retardants (BFRs), tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD) and polybrominated diphenyl ethers (PBDEs), were measured in 103 human milk samples collected from Beijing in 2011. The donors' personal information, such as dietary habit and socioeconomic and lifestyle factors, was obtained by questionnaires. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) analysis indicated that the levels of TBBPA ranged from

Soy isoflavone attenuates brain mitochondrial oxidative stress induced by ß-amyloid peptides 1-42 injection in lateral cerebral ventricle.

The aim of this study is to investigate whether soy isoflavone (SIF) reduces oxidative stress and improves the antioxidant ability in mitochondria of rat brain damaged by injection of beta-amyloid peptides 1-42 (Aß1-42). Forty Wistar rats were randomly divided into control, Aß1-42, SIF + Aß1-42, and SIF groups according to body weight. The rats in the SIF + Aß1-42 group and SIF group were intragastrically administered SIF suspension in 0.5% CMC-Na for 28 days, whereas the rats in control group and Aß1-42 group were administered the same volume of 0.5% CMC-Na. On day 14, the rats in the Aß1-42 group and SIF + Aß1-42 group were injected with Aß1-42 into the lateral cerebral ventricle with physiological saline. The rat brains were then sampled, and brain mitochondria were isolated. After this, the mitochondrial membrane potential (MMP) and mitochondrial redox state were measured. The contents of brain nuclear factor E2-related factor (Nrf2) and heme oxygenase-1 (HO-1) protein in brain tissue were quantitated by Western blot. The results showed that SIF maintained the MMP, elevated the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, and increased glutathione peroxidase (GPx) and manganese superoxide dismutase (MnSOD) protein expression in brain mitochondria. Additionally, SIF reversed the Aß1-42-induced downregulation of the protein expression of Nrf2 and HO-1 in brain tissue. These results indicated that SIF could alleviate the oxidative damage and maintain the redox imbalance in brain mitochondria damaged by Aß1-42. This might result from regulation of the Nrf2/HO-1 pathway.

Antagonizing effects of soybean isoflavones on ß-amyloid peptide-induced oxidative damage in neuron mitochondria of rats.

Soybean isoflavone (SIF) has been demonstrated to have neuroprotective effects induced by ß-amyloid peptides (Aß) through suppressing oxidative stress; however, the explicit mechanisms still remain uncovered. In the present study, 32 Wistar rats were randomly divided into four groups: an Aß1-42-treated group, a SIF + Aß1-42 group, a SIF-treated group and a control group. We measured the protein content of 8-hydroxydeoxyguanosine (8-OhdG) and mRNA expression of 8-oxoguanine DNA glycosylase (OGG1). The protein expression of OGG1, Bcl-xl, Bad, beta subunit of ATP synthase (ATPB) and pyruvate dehydrogenase (PDH) in brain was also measured. The results showed that the level of 8-OHdG in both SIF groups was significantly decreased compared to the Aß1-42-treated group (p < 0.05), while the mRNA and protein expression of OGG1 in the SIF + Aß1-42 groups were up-regulated compared with the Aß1-42-treated groups (p < 0.05). The expression of Bcl-xl was up-regulated in the SIF-treated group compared with the Aß1-42-treated groups (p < 0.05), while the expression of Bad was down-regulated in the two SIF-treated groups (p < 0.05). Aß1-42 significantly down-regulated the expression of ATPase and PDH proteins compared with the control group (p < 0.05). SIF reversed the down-regulation effects on the mitochondrial energy metabolic enzymes induced by Aß1-42 (p < 0.05) in the rats. These results suggest that SIF alleviate the oxidative stress in neurons and mitochondria of rat brains mediated by Aß1-42, and these protective effects might be associated with the regulation of OGG1, Bad, Bcl-xl, ATPB and PDH.

Flavonoids protect cerebrovascular endothelial cells through Nrf2 and PI3K from ß-amyloid peptide-induced oxidative damage.

ß-amyloid peptides (Aß) induced cerebrovascular dysfunction has been recognized as a vital factor involved in the pathogenesis of neurodegeneration. Genistein, a flavonoid, has antioxidative properties to prevent neurodegeneration induced by ß-amyloid peptides. In this study, we were investigating whether genistein could antagonize oxidative damage induced by ß-amyloid peptide 25-35 (Aß25-35) in bEND.3 cells, and also identifying the potential neuroprotective targets of genistein. Vitamin E was used as the positive control. The bEND.3 cells were pre-incubated with/out genistein or vitamin E for 2 h followed by the incubation with 25 µM A 25-35 for another 24 h. The reactive oxygen species (ROS), nitrotyrosine, cell redox state, mRNA or protein expressions of the factors on Nrf2 signaling pathway were measured after Aß25-35 treatment. The results showed that genistein alleviated the increase of ROS and nitrotyrosine production induced by Aß25-35, and maintained bEND.3 cell redox state by increasing GSH level and GSH/GSSG. Genistein could reverse the down-regulation of total protein and mRNA expression of NF-E2-related factor 2 (Nrf2), nuclear Nrf2, γ-glutamylcysteine synthetase (γ-GCS), phosphatidylinositol 3-kinase (PI3K) induced by Aß25-35; while PI3K inhibitor LY294002 could attenuate the activation effects of genistein on Nrf2, especially for the promotion of nuclear translocation. These results suggested that genistein could protect cerebrovascular endothelial cells from Aß25-35-induced oxidative damage. The potential mechanisms might be associated with the activation of Nrf2 signaling pathway by modulating PI3K activity.

The role of glutathione S-transferase M1 and T1 gene polymorphisms and fruit and vegetable consumption in antioxidant parameters in healthy subjects.

The correlation of glutathione S-transferase (GST) M1/T1 genetic polymorphisms with oxidative stress-related chronic diseases was proved recently. The aim of the present study was to investigate the association of GSTM1/T1 genetic polymorphisms with antioxidant biomarkers and consumption of fruits and vegetables (F&V) in healthy subjects. In this study, for conducting a 3 d dietary survey, 190 healthy adults were recruited. After DNA extraction, a multiple PCR method was used for GSTM1/T1 genotyping. A spectrophotometer method was applied for the determination of plasma total antioxidant capacity (T-AOC), vitamin C level and erythrocyte GST enzyme activity. A general linear model was used to compare the mean values of antioxidant parameters for different GSTM1/T1 genotypes and consumption of F&V. Polymorphisms of GSTM1/T1 had no effects on plasma T-AOC and vitamin C levels. Deletion of the GSTM1 gene decreased the erythrocyte GST activity. There was correlation between plasma T-AOC and consumption of F&V in the GSTM1⁻ or GSTT1⁺ subjects. A similar pattern was evident for erythrocyte GST activity in the GSTM1⁻ subjects. No association was found among consumption of F&V and GSTM1/T1 genotypes and plasma vitamin C level. Different consumption of F&V had no impact on plasma T-AOC and vitamin C levels in the GSTM1⁻/GSTT1⁺ or GSTM1⁻/GSTT1⁻ subjects. The erythrocyte GST activity was more sensitive to consumption of F&V in the individuals with the GSTM1⁻/GSTT1⁺ genotype. Association was found among GSTM1/T1 genotypes, antioxidant parameters and consumption of F&V. Large-scale and multiple ethnic studies are needed to further evaluate the relationship.

[Determination of polybrominated diphenyl ethers and dechlorane plus in fish and fish oil supplements by gel permeation hromatography coupled with gas chromatography-negative chemical ionization mass spectrometry].

Polybrominated diphenyl ethers (PBDEs) and dechlorane plus (DP) are two kinds of widely used organic flame retardants, and PBDE and DP residues have been found in both environment and biota. A method for the determination of 8 PBDEs and 2 DPs in fish and fish oil supplements was developed using auto gel permeation chromatography (GPC) coupled with gas chromatography-negative chemical ionization/mass spectrometry (GC-NCI/MS) in the selected ion-monitoring (SIM) mode on a 15 m capillary column. The sample added with BDE-77 and 13C12-BDE-209 as the internal standards was extracted using a Soxhlet extractor, and further purified by auto GPC and a multilayer silica gel column. The sample preparation procedure was optimized, and the characteristic ions and fragmentations of the analytes in NCI/MS were studied. The limits of detection (LODs, S/N = 3) ranged from 2.2 to 39.8 ng/kg. The average recoveries were between 71.1% and 121.4% at two spiked levels of 2 and 20 ng/g for both BDE-209 and DP and 0.2 and 2 ng/g for others with the relative standard deviations between 2.96% and 13.31%. The developed method has been successfully applied in the determination of PBDEs and DPs in several fish and fish oil supplements samples. The total PBDEs found ranged from 2.18 to 15.93 ng/g, and DP was not found. This method was validated to be accurate and sensitive for the trace analysis of PBDEs and DPs in the samples with fat.

Genistein inhibits mitochondrial-targeted oxidative damage induced by beta-amyloid peptide 25-35 in PC12 cells.

The antioxidative properties of genistein (Gen) have been demonstrated by our previous studies and others, but its potential mechanism was not very clear. Because of the key role of mitochondria in oxidant production, we wondered if mitochondria were one of Gen's neuroprotective targets. In the present study we investigated whether Gen has protective effects on mitochondria damaged by Aß25-35. PC12 cells were pre-incubated with or without Gen for 2 h followed by the incubation with 20 µM Aß25-35 for another 24 h before mitochondrial membrane fluidity (MMF), mitochondrial membrane potential (MMP) , and mitochondrial redox state were measured. The results showed that Gen alleviated the decrease of MMF induced by Aß25-35, and maintained the MMP. Additionally, Gen promoted the mitochondrial antioxidative capability through increasing the GSH/GSSG ratio, GPx activity and MnSOD protein expression in mitochondria. Moreover, Gen reversed the changes of ChAT mRNA and AChE mRNA expression in cells induced by Aß25-35. These results suggested that Gen can protect the mitochondrial membrane and maintain redox state in mitochondria damaged by Aß25-35.

Genistein and folic acid prevent oxidative injury induced by ß-amyloid peptide.

To explore the mechanism(s) of the neuroprotective effects of genistein (GEN) and folic acid (FA) on neurons treated with beta amyloid 31-35 (Aß31-35), the primary cultured cortical neurons were treated with GEN and/or FA for 2 hr prior to exposure to Aß31-35. Cell viability and fluidity of cell membrane were measured by 3-[4,5-dimethylthiazol-2]-2,5 diphenyltetrazolium bromide and fluorescence polarization, respectively. Intracellular reactive oxygen species (ROS) and Ca(2+) concentrations were measured by laser scanning confocal microscope. Glutataione (GSH) and Glutathione disulfide (GSSG) in mitochondria were measured by enzymatic method. Flow cytometry technique was used to measure mitochondrial membrane potential. The expression of HCY-2 and p38-MAPK mRNA in neurons was analysed by reverse transcription-polymerase chain reaction (RT-PCR). The results showed that GEN and/or FA increased cell viability and reduced concentration of Ca(2+) and generation of ROS in neurons compared with Aß31-35-treated cells. Furthermore, the ratio of GSH/GSSG in mitochondria and mitochondrial membrane potential was increased after GEN and/or FA treatment. RT-PCR results showed that GEN and/or FA down-regulated expression of HCY-2 and p38-MAPK mRNA. We conclude that GEN and/or FA had neuroprotective effects in Aß31-35-treated neurons. The mechanisms might be associated with multiple factors such as maintaining redox balance, stabilizing mitochondrial membrane integrity and modulating the signal pathways related to oxidation and apoptosis.

[Determination of three brominated flame retardants in human serum using solid-phase extraction coupled with ultra-performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry].

A solid-phase extraction (SPE) method for the simultaneous extraction of hexabromocyclododecanes (HBCDs)/tetrabromobisphenol A (TBBPA) and polybrominated diphenyl ethers (PBDEs) in human serum was developed. The extracts of HBCDs/TBBPA and PBDEs were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-negative chemical ionization/mass spectrometry (GC-NCI/MS), respectively. The samples with the spiked internal standards, 13C(12)-HBCD, 13C(12)-TBBPA, 3, 3', 4, 4'-tetrabromodiphenyl ether (BDE-77) and 13C(12)-decabromodiphenyl ether (BDE-209), were extracted using the mixture of methyl tert-butyl ether (MTBE) and hexane (1:1, v/v). Then the co-extracted lipid was removed by sulfuric acid treatment. The newly obtained extract was purified using SPE with an LC-Si column and two fractions of HBCDs/TBBPA and PBDEs were finally got. The determination of HBCDs/TBBPA was performed on a 50 mm BEH C18 column in the multi-reaction monitoring (MRM) mode and the determination of PBDEs was on a 15 m capillary column in the selected ion-monitoring (SIM) mode. The limits of detection (LODs, S/N = 3) ranged from 1.81 to 42.16 pg/g. The average recoveries were from 80.3% to 108.8% at two spiked levels of 0.5 and 5 ng/g for HBCDs, 0.05 and 0.5 ng/g for TBBPA and BDE-209 with the relative standard deviations between 1.02% and 11.42% (n = 5). The developed method has been successfully applied to the determination of the 12 analytes in 42 pooled human serum samples. The levels of TBBPA in the samples ranged from < LOD to 6.58 ng/g, that of alpha-HBCD diastereoisomer ranged from < LOD to 7.22 ng/g, which was the most abundant isomer comparing with beta- and gamma-HBCD. The total PBDEs found ranged from 2.90 to 89.69 ng/g. This method was validated to be accurate and sensitive for the analysis of HBCDs, TBBPA and PBDEs in serum samples.

[Effects of genistein and folic acid on neuronal membrane and mitochondrial membrane damaged by ß-amyloid peptides 31-35].

OBJECTIVE: To observe the neuro-protective effects of genistein (Gen) and folic acid (FA) on neurons membrane and mitochondrial membrane damaged by ß-amyloid peptides 31-35 (Aß31-35). METHODS: The primary cultured rat cerebral cortical neurons were randomly divided into DMEM (control), Aß31-35 (25 µmol/L), Gen (Gen 27 µg/ml), FA (FA 40 µg/ml) and Gen + FA (Gen 27 µg/ml + FA 40 µg/ml). Gen and/or FA were added two hours before Aß31-35 addition. After twenty four hours, MTT assay was performed to measure the viability of cultured neurons. Fluorescence polarization was performed to observe the neuron cell membrane fluidity. The mitochondrial membrane potential (MMP) was determined to investigate the alteration of mitochondrial structure and function of neurons by laser scanning confocal microscope and a flow cytometer was used to investigate the activation of mitochondrial permeability transition pore (MPTP). Each experiment was repeated three times. RESULTS: Compared with group Aß31-35 (0.845 ± 0.050, F = 4.931, P < 0.05), the absorbance was significantly higher in group Gen (0.982 ± 0.110, t = 3.523, P < 0.01), FA (0.947 ± 0.061, t = 2.745, P < 0.01) and Gen + FA (0.996 ± 0.090, t = 3.966, P < 0.01). The viscosity of cell neuron membrane in group Gen (1.75 ± 0.28, t = 2.085, P < 0.05), FA (1.66 ± 0.37, t = 2.357, P < 0.05) and Gen + FA (1.50 ± 0.20, t = 3.784, P < 0.05) was significantly lower than that in group Aß31-35 (2.11 ± 0.44, F = 5.529, P < 0.01), which indicated the cell membrane fluidity was significantly higher in group Gen and/or FA than that in group Aß31-35. MMP was significantly decreased by Aß31-35 (3.364 ± 1.140, t = 3.949, P < 0.01) when comparing to control group (6.383 ± 1.683), while it was significantly increased by Gen (5.286 ± 1.792, t = 2.406, P < 0.05), FA (5.884 ± 2.022, t = 2.887, P < 0.01) and Gen + FA (6.120 ± 2.124, t = 3.304, P < 0.01) when comparing to group Aß31-35 (F = 7.585, P < 0.01). MPTP was activated by Aß31-35 and Gen and/or FA could reverse this progress. CONCLUSION: Gen and/or FA could protect the neuronal and mitochondrial membrane from the impairment induced by Aß31-35.

Genistein as a neuroprotective antioxidant attenuates redox imbalance induced by beta-amyloid peptides 25-35 in PC12 cells.

OBJECTIVE: Genistein (GEN), a principal component of soybean isoflavones, might possess the neuroprotective role through its antioxidant activity. However, the detailed mechanisms are unknown yet. The purpose of this study was to investigate whether GEN could alleviate oxidative damage induced by beta-amyloid peptides 25-35 (Abeta25-35) in PC12 cells. METHODS: The PC12 cells were pre-incubated with or without GEN for 2h following incubation with Abeta25-35 for another 24h. MTT was used to assess the cell viability. Hoechst 33342 staining was applied to determine the apoptotic cells. Confocal laser scanning microscopy was implemented to examine the reactive oxygen species (ROS) levels. Mitochondrial membrane potential (MMP) was measured by flow cytometry. Reduced and oxidized glutathione (GSH/GSSG) ratio was analyzed by using assay kits. Western blot analysis was performed to assess the proteins expression of NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and gamma-glutamylcysteine synthetase (gamma-GCS). RESULTS: GEN attenuated the cytotoxicity and partially prevented apoptosis induced by Abeta25-35. GEN dramatically attenuated ROS levels induced by Abeta25-35 in PC12 cells. In addition, GEN significantly reversed the reduction of MMP caused by Abeta25-35 to maintain the normal levels of the cells. The GSH/GSSG ratio in GEN pretreated groups significantly increased compared to the groups without GEN pretreatment. GEN reversed Abeta25-35 induced down regulation of the protein expression of gamma-GCS, Nrf2 and HO-1. CONCLUSION: GEN could alleviate the oxidative stress caused by Abeta25-35 treatment and maintain redox balance in PC12 cells, which might be associated with the regulation of Nrf2/HO-1 signal pathway.

Long-term effects of high lipid and high energy diet on serum lipid, brain fatty acid composition, and memory and learning ability in mice.

OBJECTIVE: It is well known that high lipid and high energy diet is harmful to health. But the different effects of high lipid diet composed of either saturated fatty acids or unsaturated fatty acids have not been distinguished. METHOD: Eighteen pregnant C57BL/6j (22-25g) mice were randomly divided into three groups of six each and fed with chow or high lipid diet composed of either flaxseed oil (chow diet 84%, cholesterol 0.2%, flaxseed oil 15.8%) or lard fat (chow diet 84%, cholesterol 0.2%, lard fat 15.8%). After weaning, the offspring were fed the same diet as their mothers were fed during the experiment, and their spatial memory and learning ability were evaluated by Morris water maze when they were 8 weeks old. Next, the blood and tissues were sampled when they were 9 weeks old. Serum lipids were determined using kits, and brain fatty acids were measured using a gas chromatograph. RESULTS: Compared to chow diet (control), high flaxseed oil diet (HFO) increased high density lipoprotein cholesterol level (HDL-C) in the mothers but not in offspring; high lard fat diet (HLF) increased serum total cholesterol level (TC) and low density lipoprotein cholesterol level (LDL-C) both in mothers and offspring. Brain fatty acids profile was altered by HLF compared with chow diet. Polyunsaturated fatty acids and long-chain polyunsaturated fatty acids content were significantly lower in the HLF group than in the control group, but saturated fatty acids content were significantly higher in HLF group than those in control group. The changed fatty acids composition affected the spatial memory and learning ability of adult offspring. CONCLUSIONS: A long-term high lard diet increased offspring serum TC and LDL-C levels and affected the brain's fatty acid composition, and memory and learning ability. The polyunsaturated fatty acid content of the brain may be correlated with serum cholesterol levels.

Dietary exposure assessment of Chinese adults and nursing infants to tetrabromobisphenol-A and hexabromocyclododecanes: occurrence measurements in foods and human milk.

Tetrabromobisphenol A(TBBPA) and hexabromocyclododecane diastereoisomers (alpha, beta, and gamma-HBCD) were determined in 24 pooled human milk samples and 48 Chinese total diet study (TDS) samples collected in 2007. On the basis of ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) analysis, levels of TBBPA ranged from < LOD to 5124 pg/g lipid weight (lw) in human milk and from < LOD to 2044 pg/g lw in TDS samples. The alpha-HBCD diastereoisomer, which ranged from < LOD to 2776 pg/g lw in human milk and from < LOD to 2224 pg/g lw in TDS samples, was generally the most abundant isomer comparing with beta- and gamma-HBCD. The average estimated daily intake (EDI) of TBBPA via human milk for nursing infants with a range 320-37240 pg/kg bodyweight (bw)/day was 5094 pg/kg bw/day, while that of sigmaHBCD was 5837 pg/kg bw/day with a range 670-17320 pg/kg bw/day. The medium bound (< LOD = 1/2LOD) EDI(TBBPA) for a "reference" man via animal origin foods was 256 pg/kg bw/day and EDI(sigmaHBCD) was 432 pg/kg bw/day. Meat and meat products were the main source in the total dietary intake of TBBPA and sigmaHBCD. Our research on the estimated daily intake of TBBPA and sigmaHBCD by the Chinese population indicated large variations in TBBPA and sigmaHBCD levels between provinces. Overall, our data indicate the Chinese EDI was lowerthan the EDI from similar studies in Europe.

Neuroprotective effects of genistein and folic acid on apoptosis of rat cultured cortical neurons induced by beta-amyloid 31-35.

Genistein and folic acid have been reported respectively to protect against the development of cognitive dysfunction; however, the underlying mechanism(s) for this protection remain unknown. In this report, the mechanism(s) contributing to the neuroprotective effects of genistein and folic acid were explored using rat cortical neuron cultures. We found that genistein and folic acid, both separately and collaboratively, increased cell viability and mitochondrial membrane potential in beta-amyloid (Abeta) 31-35-treated neurons. Furthermore, reduced percentage of comet cells and shortened tail length were observed in the neurons treated with genistein or folic acid. A more significant reduction in tail length of the comet neurons was observed in the co-administered neurons. RT-PCR analysis of the cultured cortical neurons showed down-regulated expression of p53, bax and caspase-3, but up-regulated expression of bcl-2 in the three neuroprotective treatment groups compared with neurons from the Abeta31-35 solo-treated group. In a nuclear dyeing experiment using Hoechst 33342, we found that both genistein and folic acid prevent neuronal apoptosis. Collectively, these findings suggest that the mechanism underlying the neuroprotection of genistein and folic acid singly or in combination observed in cultured cortical neuron studies might be related to their anti-apoptotic properties.

[Analysis of hexabromocyclododecane diastereoisomers in foods of animal origin using ultra performance liquid chromatography-mass spectgrometry and isotope dilution].

A method for the detection of the alpha, beta and gamma-diastereoisomers of hexabromocyclododecane (HBCDs) in foods of animal origin, such as fish, chick, milk, butter etc., was developed using ultra performance liquid chromatography-electrospray ionization mass spectrometry (UPLC-ESI-MS) and isotope dilution. The HBCDs with the spiked isotopic 13C-HBCDs, the internal standards, were extracted using Soxhiet extraction, and further purified using acidic silica treatment and solid phase extraction. The separation of HBCDs was performed on Waters ACQUITY UPLC system with the column of BEH C8 and the gradient elution solvent of methanol-acetonitrile and water at a flow rate of 0.2 mL/min. The HBCDs were identified on the basis of the retention times and precursor ions, and quantitatively determined under the selected ion recording mode, m/z 640.7 for the [M-H]-ion. The limits of detection (LODs) of HBCDs ranged from 0.1 to 0.4 ng/g; and the limits of quantification (LOQs) ranged from 0.4 to 1.2 ng/g. The average recoveries ranged from 92.9% to 99.3% for the spiked levels of 0.6, 2.0 and 6.0 ng/g. with the relative standard deviations (RSDs) between 3.1% and 8.0%.

[Lead and cadmium pollution in edible fungus sold in Beijing].

OBJECTIVE: To investigate the lead and cadmium pollution in edible mushrooms sold in Beijing. METHODS: 146 samples of 14 species were collected form 25 markets during the period of Mar. through May, 2007 in Beijing. The pollution of lead and cadmium were analyzed respectively according to the standard of GB/T5009. 12-2003 and GB 7096-2003. RESULTS: The content of lead and cadmium in edible mushrooms was ND--1.592 mg/kg, ND--0.550 mg/kg, respectively, both lower than the allowable content prescribed by The National Ministry of Health. CONCLUSION: The contents of lead and cadmium in the mushrooms marketed in Beijing are in safe ranges. It is worthy of mentioning the variation coefficients of heavy metal concentrations existing in edible mushrooms.

[Contamination source identification study of organochlorines pesticides in 2000 Chinese total diet study].

The third Chinese total diet study to estimate dietary intake of contaminants was carried out in 2000. The levels of HCH and DDT residues were less significant in most of foodstuffs, but the level of HCH residues of aquatic foods in South 2 and in North 1 is respectively 75.99microg/kg and 170.72microg/kg, and the ratio of gamma-HCH is 90% of the total HCHs residues. To identify the contamination source of gamma-HCH, the individual province composite samples and the individual samples of aquatic foods from individual province were further analyzed. The level of gamma-HCH in bream (Megalobrama amblycephala) sample in Hubei province is 546.4microg/kg, which is 98.3% of all HCHs (exceeding the 0.1mg/kg HCHs EMRL in fish), the level of gamma-HCH in carp (Cyprinus carpio Linnaeus) sample in Heilongjiang province is 602.4microg/kg, which is 98.5% of all HCHs. The two samples polluted by Lindane were confirmed by GC-MS. The result suggests that Lindane has been used irregularly in some areas in China.