Chemical Space Charting of Different Parts of Inula nervosa Wall.: Upregulation of Expression of Nrf2 and Correlated Antioxidants Enzymes.

The edible and medicinal part of Inula nervosa Wall. (Xiaoheiyao) is confined to its root without sufficient phytochemical and biological investigation. In this study, the secondary metabolites of root, stem, leaf, and flower of I. nervosa Wall. were visualized using Global Natural Products Social Molecular Networking (GNPS), MolNetEnhancer, XCMS(xcmsonline.scripps.edu) analysis, and `ili mapping based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) data to reveal their chemical differences. Among the 11 kinds of chemical repertoires annotated by MolNetEnhancer and 16 hits against the GNPS library, 10-isobutyryloxy-8,9-epoxythymol isobutyrate (1) was revealed as the most dominant and responsible marker between the roots and the other parts. Moreover, a battery of unique MS features as well as differential markers were discovered from different parts of the plant. The chemical differences contribute to the bioactivity differences, which presented in the 2,2-diphenyl-1-picryl-hydrazyl (DPPH)assay and H2O2-insulted HepG2 cells and were in significant correlations with the contents of 1. real-time reverse transcription polymerase chain reaction (RT-PCR)results demonstrated that I. nervosa Wall. extracts upregulated the mRNA expression of nuclear factor E2-related factor 2(Nrf2), heme oxygenase 1(HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), manganese superoxide dismutase (MnSOD), and glutamate-cysteine ligase catalytic subunit (GCLC) actors involved in antioxidative response in H2O2-challenged HepG2 cells. These findings support the roots of I. nervosa Wall. as active parts of Xiaoheiyao, and also indicate the potential antioxidant activities of other parts.

Dietary Methionine Restriction Ameliorated Fat Accumulation, Systemic Inflammation, and Increased Energy Metabolism by Altering Gut Microbiota in Middle-Aged Mice Administered Different Fat Diets.

Diet greatly influences gut microbiota. Dietary methionine restriction (MR) prevents and ameliorates age-related or high-fat-induced diseases and prolongs life span. This study aimed to reveal the impact of MR on gut microbiota in middle-aged mice with low-, medium-, high-fat diets. C57BL/6J mice were randomly divided into six groups with different MR and fat-content diets. Multiple indicators of intestinal function, fat accumulation, energy consumption, and inflammation were measured. 16S rRNA gene sequencing was used to analyze cecal microbiota. Our results indicated that MR considerably reduced the concentrations of lipopolysaccharide (LPS) and increased short-chain fatty acids (SCFAs) by upregulating the abundance of Corynebacterium and SCFA-producing bacteria Bacteroides, Faecalibaculum, and Roseburia and downregulating the LPS-producing or proinflammatory bacteria Desulfovibrio and Escherichia-Shigella. The effect of MR on LPS and SCFAs further reduced fat accumulation and systemic inflammation, enhanced heat production, and mediated the LPS/LBP/CD14/ TLR4 pathway to strength the intestinal mucosal immunity barrier in middle-aged mice.

Dityrosine suppresses the cytoprotective action of thyroid hormone T3 via inhibiting thyroid hormone receptor-mediated transcriptional activation.

Dityrosine (Dityr) is the most common oxidized form of tyrosine. In the previous studies of mice treated with dityrosine, cell death in the pancreas, kidneys, and liver was detected in the presence of enhanced plasma triiodothyronine (T3) content. Due to its structural similarity with the thyroid hormone T3, we hypothesized that dityrosine might disrupt T3-dependent endocrine signaling. The cytotoxic effect of dityrosine was studied in C57BL/6 mice by gavage with a dityrosine dose of 320 µg per kg per day for 10 weeks. Cell death in the liver was detected in the presence of enhanced plasma thyroid hormone content in mice treated with dityrosine. The antagonistic effect of dityrosine on T3 biofunction was studied using HepG2 cells. Dityrosine incubation reduced T3 transport ability and attenuated the T3-mediated cell survival via regulation of the PI3k/Akt/MAPK pathway. Furthermore, dityrosine inhibited T3 binding to thyroid hormone receptors (TRs) and suppressed the TR-mediated transcription. Dityrosine also downregulated the expressions of T3 action-related factors. Taken together, this study demonstrates that dityrosine inhibits T3-dependent cytoprotection by competitive inhibition, resulting in downstream gene suppression. Our findings offer insights into how dityrosine acts as an antagonist of T3. These findings shed new light on cellular processes underlying the energy metabolism disorder caused by dietary oxidized protein, thus contributing to a better understanding of the diet-health axis at a cellular level.

Composition and immuno-stimulatory properties of extracellular DNA from mouse gut flora.

AIM: To demonstrate that specific bacteria might release bacterial extracellular DNA (eDNA) to exert immunomodulatory functions in the mouse small intestine. METHODS: Extracellular DNA was extracted using phosphate buffered saline with 0.5 mmol/L dithiothreitol combined with two phenol extractions. TOTO-1 iodide, a cell-impermeant and high-affinity nucleic acid stain, was used to confirm the existence of eDNA in the mucus layers of the small intestine and colon in healthy Male C57BL/6 mice. Composition difference of eDNA and intracellular DNA (iDNA) of the small intestinal mucus was studied by Illumina sequencing and terminal restriction fragment length polymorphism (T-RFLP). Stimulation of cytokine production by eDNA was studied in RAW264.7 cells in vitro. RESULTS: TOTO-1 iodide staining confirmed existence of eDNA in loose mucus layer of the mouse colon and thin surface mucus layer of the small intestine. Illumina sequencing analysis and T-RFLP revealed that the composition of the eDNA in the small intestinal mucus was significantly different from that of the iDNA of the small intestinal mucus bacteria. Illumina Miseq sequencing showed that the eDNA sequences came mainly from Gram-negative bacteria of Bacteroidales S24-7. By contrast, predominant bacteria of the small intestinal flora comprised Gram-positive bacteria. Both eDNA and iDNA were added to native or lipopolysaccharide-stimulated Raw267.4 macrophages, respectively. The eDNA induced significantly lower tumor necrosis factor-α/interleukin-10 (IL-10) and IL-6/IL-10 ratios than iDNA, suggesting the predominance for maintaining immune homeostasis of the gut. CONCLUSION: Our results indicated that degraded bacterial genomic DNA was mainly released by Gram-negative bacteria, especially Bacteroidales-S24-7 and Stenotrophomonas genus in gut mucus of mice. They decreased pro-inflammatory activity compared to total gut flora genomic DNA.

Role of miR-383 and miR-146b in different propensities to obesity in male mice.

The study was designed to investigate the possible mechanisms of hepatic microRNAs (miRs) in regulating local thyroid hormone (TH) action and ultimately different propensities to high-fat diet (HFD)-induced obesity. When obesity-prone (OP) and obesity-resistant (OR) mice were fed HFD for 7 weeks, OP mice showed apparent hepatic steatosis, with significantly higher body weight and lower hepatic TH receptor b (TRb) expression and type 1 deiodinase (DIO1) activity than OR mice. Next-generation sequencing technology revealed that 13 miRs in liver were dysregulated between the two phenotypes, of which 8 miRs were predicted to target on Dio1 or TRb When mice were fed for 17 weeks, OR mice had mild hepatic steatosis and increased Dio1 and TRb expression than OP mice, with downregulation of T3 target genes (including Srebp1c, Acc1, Scd1 and Fasn) and upregulation of Cpt1α, Atp5c1, Cox7c and Cyp7a1 A stem-loop qRT-PCR analysis confirmed that the levels of miR-383, miR-34a and miR-146b were inversely correlated with those of DIO1 or TRb. Down-regulated expression of miR-383 or miR-146b by miR-383 inhibitor (anti-miR-383) or miR-146b inhibitor (anti-miR-146b) in free fatty acid-treated primary mouse hepatocytes led to increased DIO1 and TRb expressions, respectively, and subsequently decreased cellular lipid accumulation, while miR-34a inhibitor (anti-miR-34a) transfection had on effects on TRb expression. Luciferase reporter assay illustrated that miR-146b could directly target TRb 3'untranslated region (3'UTR). These findings suggested that miR-383 and miR-146b might play critical roles in different propensities to diet-induced obesity via targeting on Dio1 and TRb, respectively.

Regressive Effect of Myricetin on Hepatic Steatosis in Mice Fed a High-Fat Diet.

Myricetin is an effective antioxidant in the treatment of obesity and obesity-related metabolic disorders. The objective of this study was to explore the regressive effect of myricetin on pre-existing hepatic steatosis induced by high-fat diet (HFD). C57BL/6 mice were fed either a standard diet or a HFD for 12 weeks and then half of the mice were treated with myricetin (0.12% in the diet, w/w) while on their respective diets for further 12 weeks. Myricetin treatment significantly alleviated HFD-induced steatosis, decreased hepatic lipid accumulation and thiobarbituric acid reactive substance (TBARS) levels, and increased antioxidative enzyme activities, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Microarray analysis of hepatic gene expression profiles showed that myricetin significantly altered the expression profiles of 177 genes which were involved in 12 biological pathways, including the peroxisome proliferator activated receptor (PPAR) signaling pathway and peroxisome. Further research indicated that myricetin elevated hepatic nuclear Nrf2 translocation, increased the protein expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1), reduced the protein expression of PPARγ, and normalized the expressions of genes that were involved in peroxisome and the PPAR signaling pathway. Our data indicated that myricetin might represent an effective therapeutic agent to treat HFD-induced hepatic steatosis via activating the Nrf2 pathway and the PPAR signaling pathway.

Isolation of lactobacillus reuteri from Peyer's patches and their effects on sIgA production and gut microbiota diversity.

SCOPE: We previously reported that specific Lactobacillus reuteri colonized within mouse Peyer's patches (PP) effectively prevented high fat diet induced obesity and low-grade chronic inflammation. We further investigated the role of PP Lactobacillus reuteri on sIgA production in rats in this study. METHODS AND RESULTS: Lactobacilli were isolated from rat PP. All isolates were L. reuteri and belonged to three phenotypes according to amplified fragment length polymorphism analysis. Typical strains of two main clusters, PP1 and PP2, were used to treat control and vitamin A deficient (VAD) rats, respectively. The feeding of PP1 and PP2 affected sIgA and Lactobacillus diversity by strain-specific manner. Free sIgA was significantly increased by PP1 (p = 0.069) and PP2 (p < 0.05) in the control rats but not in the VAD rats. Only PP1 significantly changed PP Lactobacillus diversity in the control rats (p < 0.05). However, PP2 specifically changed ileal Lactobacillus diversity in both control and VAD rats. Fecal sIgA was correlated with PP Lactobacillus diversity (R(2) = 0.7958, p = 0.011). CONCLUSION: Modulation of sIgA production by PP L. reuteri of rat is dependent on vitamin A and change of Lactobacillus diversity in PP.

Structure-based approach for the study of thyroid hormone receptor binding affinity and subtype selectivity.

Thyroid hormone (TH) possesses the ability to lower cholesterol and improve cardiac performance, which have prompted the efforts to design analogs that can utilize the cholesterol-lowering property without adversely affecting heart function. In order to gain insights into the interaction mechanism for agonists at the active site of thyroid hormone receptor ß (TRß), quantitative structure-activity relationship (QSAR) models have been developed on TRß agonists, significant statistical coefficients were obtained (CoMFA, R(2)cv, .732), (CoMSIA, R(2)cv, .853), indicating the internal consistency of the models, the obtained models were further validated using the test set, the acquired R(2)pred values .7054 and .7129 were in good agreement with the experimental results. The key amino acids affecting ligand binding were identified by molecular docking, and the detailed binding modes of the compounds with different activities were also determined. Furthermore, molecular dynamics (MD) simulations were conducted to assess the reliability of the derived models and the docking results. Moreover, TH exerts significant physiological effects through modulation of the two human thyroid hormone receptor subtypes. Because TRß and TRα locate in different target cells, selective TR ligands would target specific tissues regulated by one receptor without affecting the other. Thus, the 3D information was analyzed to reveal the most relevant structural features involved in selectivity. The findings serve as the basis for further investigation into selective TRß/TRα agonists.

High-fat-diet-induced obesity is associated with decreased antiinflammatory Lactobacillus reuteri sensitive to oxidative stress in mouse Peyer's patches.

OBJECTIVE: Diet-induced inflammation in the small intestine may represent an early event that precedes and predisposes to obesity and insulin resistance. This is related to decrease of lactobacilli in Peyer's patches (PP) revealed in our previous study. The present study aimed to clarify specific changes of PP Lactobacillus on the strain level and related biological activity. METHODS: C57 BL/6 J male mice were fed with either low-fat diet (control [CT]; 10% calories from fat) or high-fat diet (HFD; 50% calories from fat) for 25 wk, and the HFD-fed mice were classified into obesity prone (OP) or obesity resistant (OR) on the basis of their body weight gain. Lactobacillus was isolated from PP using a selective medium. Oxidative resistance and cytokine-inducing effect were analyzed in vitro. RESULTS: We obtained 52, 18, and 22 isolates from CT, OP, and OR mice, respectively. They belonged to 13 different types according to enterobacterial repetitive intergenic consensus sequence-PCR analysis. Lactobacillus reuteri was the most abundant strain, but its abundance in OP mice was much lower than that in CT and OR mice. This strain includes eight subgroups according to genotyping. L. reuteri L3 and L. reuteri L8 were the specific strains found in CT and OP mice, respectively. Oxidative-resistant L. reuteri was much higher in HFD-fed mice. When co-cultured with PP cells, L8 induced higher production of proinflammatory cytokines such as interleukin (IL)-6, IL-12, and tumor necrosis factor-α, whereas L3 induced higher production of an anti-inflammatory cytokine (IL-10). CONCLUSION: HFD may induce oxidative stress that drives strain selection of Lactobacillus strains, resulting in decreased anti-inflammatory response in PP.

In silico study on ß-aminoketone derivatives as thyroid hormone receptor inhibitors: a combined 3D-QSAR and molecular docking study.

In order to explore the structure-activity correlation of a series of ß-aminoketone analogs as inhibitors of thyroid hormone receptor (TR), a set of three-dimensional quantitative structure-activity relationship (3D-QSAR) models based on comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA), for the first time, were developed in the present work. The best CoMFA model with steric and electrostatic fields exhibited [Formula: see text], [Formula: see text] for TRß, and [Formula: see text], [Formula: see text] for TRα. 3D contour maps produced from the optimal models were further analyzed individually, which provide the areas in space where interactive fields would affect the inhibitory activity. In addition, the binding modes of inhibitors at the active site of TRs were examined using molecular docking, the results indicated that this series of inhibitors fit into the active site of TRs by forming hydrogen bonding and electrostatic interactions. The docking studies also revealed that Leu305, Val458 for TRß, and Asp407 for TRα are showing hydrogen bonds with the most active inhibitors. In any case, the 3D-QSAR models combined with the binding information will serve as a useful approach to explore the chemical space for improving the activity of TRß and TRα inhibitors.

Molecular determinants of thyroid hormone receptor selectivity in a series of phosphonic acid derivatives: 3D-QSAR analysis and molecular docking.

A mathematical study was performed on a set of phosphonic acid derivatives that are substrates for thyroid hormone receptor ß (TRß) and thyroid hormone receptor α (TRα), three-dimensional quantitative structure-activity relationship (3D-QSAR) models using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were employed to investigate the structural requirements for this series of compounds with improved activity. Some descriptors were also employed to significantly improve the performance of the derived models. The CoMFA model for TRß exhibited Rcv(2) of 0.612, Rpred(2) of 0.7218, whereas CoMSIA model showed Rcv(2) of 0.621, R(2)pred of 0.7358; the CoMFA model for TRα displayed Rcv(2) of 0.678, Rpred(2) of 0.6424, and the CoMSIA model had Rcv(2) of 0.671, Rpred(2) of 0.6932, which indicate that the constructed models are statistically significant. The derived contour maps further pointed out the regions where interactive fields may influence the activity. In order to validate the QSAR models and explore the origin of the selectivity at the amino acid level, molecular docking was developed, and the results indicate that Arg282, Arg320, Asn331, Gly332, Thr329 and His435 for TRß, but Ala225, Arg228, Met259, Arg262 and His381 for TRα, respectively are important residues. The information obtained from the QSAR models can be used in the design of more potent TR agonists.

Role of thyroid hormone homeostasis in obesity-prone and obesity-resistant mice fed a high-fat diet.

BACKGROUND: The exact mechanism for different propensities to obesity when consuming a high-fat diet (HFD) is largely unknown. Thyroid hormone (TH) is an important modulator of energy homeostasis and body weight. OBJECTIVE: The present study aimed to find the potential mechanisms of TH in the development of obesity-prone (OP) and obesity-resistant (OR) mice after short-term and long-term HFD feeding. METHODS: C57Bl/6 male mice were randomly divided into two groups: a low-fat diet (LFD) group and an HFD group. In the 7th week, HFD-fed mice were classified as OP or OR according to upper and lower tertiles of body weight. Half of the mice were sacrificed at this time point and the remaining mice were kept on feeding and sacrificed in the 27th week. Indirect calorimetry was performed. At harvest, serum was used for ELISA assays and oxidative stress biomarkers determination. Tissues were dissected for deiodinases activity and relative mRNA expression determination, as well as antioxidant capacity evaluation. RESULTS: In the 7th week, OP mice showed a significant body weight gain, decreased energy expenditure (EE), normal circulating TH levels, and activated HPT axis, whereas OR mice had normal body weight and maintained T(3) levels only through enhancing hepatic D1 activity. In the 27th week, OR mice gained more body weight than LFD mice accompanied by an activation of HPT axis and decreased hepatic deiodination. Genes involved in TH production were down-regulated in OP mice and up-regulated in OR mice. Changes in deiodinases activity and thyroid function were related with redox status in specific tissues. Furthermore, OP mice had more serious hepatic steatosis than OR mice, with up-regulation of T(3) target genes (e.g. Srebp1c, Acc1, Fasn) involved in lipid synthesis and down-regulation of Pgc1α, Cyp7a1 and Cpt1α. CONCLUSIONS: HPT axis function and deiodinases activity might be involved in different propensities to obesity and the ability of OR mice to resist obesity was limited.

Antioxidant and antibacterial activities of extracts from Conyza bonariensis growing in Yemen.

This study aims to examine the antioxidant and antibacterial activities and phenolic contents of Conyza bonariensis growing in Yemen. The whole plants of C. bonariensis were ultrasonically extracted by ethanol. The antioxidant activity of the extract was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ß-carotene bleaching (BCB). The effectiveness of the extract on the growth inhibition of some indicators of foodborne illness bacteria were investigated by agar well diffusion assay. The total phenols (TP), total flavonoids (TF), total tannins (TT), and total anthocyanins (TA) were determined by Folin-Ciocalteu method, aluminium chloride method, Folin and Ciocalteu method, and pH-differential method, respectively. The extract of C. bonariensis possessed TP 144.1 mg/g, TF 143 mg/g, TT 0.99mg/g, and TA 0.97mg 100g, with 94.57% inhibition of DPPH and 92.47% inhibition of BCB, and strong inhibitory effects against tested bacteria, which was approximate to those of peel extract of Punica granatum.

Association Between Thyroid Hormones, Lipids and Oxidative Stress Markers in Subclinical Hypothyroidism.

BACKGROUND: Oxidative stress plays a role in the pathogenesis of many chronic diseases. It is recognized in overt hypothyroidism while its existence in subclinical hypothyroidism (SCH) is not well established. The aim of this study was to determine whether there was increased oxidation of lipids and proteins in SCH, and examine their association with lipids and thyroid hormones. METHODS: Male adults (35-59 years) with SCH (n=467) and euthyroid controls (n=190) were studied. Anthropometric measurements, plasma lipids, thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total antioxidant capacity (T-AOC), lipid peroxidation products, malondialdehyde (MDA), advanced oxidation protein products (AOPP) and dityrosine concentrations were measured. RESULTS: Plasma concentrations of MDA were significantly higher (p<0.05) in SCH (8.11±1.39 nmol/mL) compared with euthyroid controls (7.34±1.31 nmol/mL) while AOPP, dityrosine and T-AOC levels were not different. MDA was not associated with TSH (ß=-0.019, P=0.759), FT4 (ß=-0.062, P=0.323) and FT3 (ß=-0.018, P=0.780) in SCH while levels increased with elevated total cholesterol (ß=0.229, P=0.001), LDL (ß=0.203, P=0.009) and triglycerides (ß=0.159, P=0.036) after adjustment for age and body mass index. T-AOC reduced (ß=-0.327, P=0.030) with increased MDA in euthyroid controls and not in SCH (ß=-0.068, P=0.349), while levels increased with elevated triglycerides in both groups. CONCLUSIONS: Oxidative stress was increased in subclinical hypothyroidism as evidenced by the elevated lipid peroxidation product, malondialdehyde, while protein oxidation was absent. Thus, reduction of oxidative stress may be beneficial in patients with subclinical hypothyroidism.

Differential effects of quercetin on hippocampus-dependent learning and memory in mice fed with different diets related with oxidative stress.

High fat diets induce oxidative stress which may be involved in neurodegenerative diseases. Quercetin is a kind of antioxidant that has neuroprotective effects and potent7ial pro-oxidant effects as well. In this study, we evaluated cognitive function in mice fed with high fat diets and basic diets with or without quercetin. Male Chinese Kunming (KM) mice were randomly assigned to five groups fed with basic diet (Control), basic diet with 0.005% (w/w) quercetin (CQ1), high fat diet (HFD), HFD with 0.005% (w/w) quercetin (HFDQ1) and 0.01% (w/w) quercetin (HFDQ2) for 13weeks. At the end of the study period, fasting blood glucose (FBG), plasma and hippocampal markers of oxidative stress, plasma lipid status, Morris water maze as well as hippocampal relative mRNA expression of akt, bdnf, camkII, creb, gsk-3ß, nrf2 and pi3k were examined. The results suggested that in comparison to the control group, the escape latency was increased and percent time spent in the target quadrant was decreased, with increased reactive carbonyls, malondialdehyde (MDA) and declined expression of pi3k, akt, nrf2, creb and bdnf in the hippocampus of HFD and CQ1 groups. Conversely, higher quercetin supplemented to HFD improved antioxidant capacity and reversed cognitive decline completely. Significant correlations between the redox status and cognition-related gene expression were observed as well (P<0.05). Thus, in the case of oxidative stress, an appropriate dose of quercetin can attenuate oxidative stress to improve hippocampus dependent cognition. But under a balanced situation, quercetin exerts pro-oxidant effects to impair cognition.

Elevated plasma dityrosine in patients with hyperlipidemia compared to healthy individuals.

BACKGROUND: Dityrosine, the modification of tyrosine residues, may contribute to metabolic disorders. This study was undertaken to investigate plasma dityrosine concentrations in patients with hyperlipidemia and to examine the correlation between dityrosine and lipid profiles. METHODS: Fluorescence spectrophotometry was used to measure dityrosine in the plasma of healthy subjects (n = 203) and dyslipidemic subjects, which included patients with mild hyperlipidemia (n = 246) and hyperlipidemia (n = 179). Advanced oxidation protein products (AOPP) and malondialdehyde (MDA) were also assayed in all subjects. RESULTS: Dityrosine levels were higher by 9.3 and 22.9% in mildly hyperlipidemic and hyperlipidemic patients, respectively, compared to controls after adjustment for age, gender, and BMI. AOPP and MDA levels showed similar trends. The levels of dityrosine related positively (p < 0.05) to total cholesterol (r = 0.362), triglycerides (r = 0.449), and low-density lipoprotein cholesterol (r = 0.359). Moreover, plasma dityrosine (r = 0.408), AOPP (r = 0.488), and MDA (r = 0.181) levels were elevated with an increase in the atherosclerosis index in the subjects. CONCLUSIONS: These findings suggest that dityrosine formation may be an early event in the pathological process of hyperlipidemia. Dityrosine as a biomarker detected by fluorescence spectrophotometry might be a useful tool to evaluate the plasma redox state in hyperlipidemia.

Disparities in the Prevalence of Metabolic Syndrome (MS) and its Components Among University Employees by Age, Gender and Occupation.

BACKGROUND: Metabolic Syndrome (MS), a known risk factor for Cardiovascular Disease (CVD) and type II diabetes is an emerging epidemic in China. Studies carried out on the general population indicate a varied clustering of cardiovascular risks in many parts of the country. However, there is limited data on its prevalence in the working population. Workplace can serve as an important place for prevention, control and management of CVD risks. The aim of this study was to investigate the prevalence of MS and its components among University workers, and determine how the prevalence varied according to sex and occupation. METHODS: This was a cross-sectional study of 2,428 University employees (22-60 years) who received an annual clinical examination at the University hospital. Anthropometric measurements, blood pressure, Fasting Plasma Glucose (FPG), and lipid profiles were measured. MS was defined according to the National Cholesterol Education Program Adult Treatment panel III modified criteria. RESULTS: Overall prevalence of MS was 6.1%, higher in males (5.1%) than females (1.1%), and increased with age. The most prevalent MS components in all workers were hypertension (37.9%) and hypertryglyceridemia (20.8%), corresponding rates in males were 28.3% and 16.1% while females had a prevalence of 9.6% and 4.7%. After adjustment for age, administrative work was associated (p<0.05) with increased hypertension (odds ratio (OR) =1.474; 95% confidence interval (CI), 1.146-1.896) and hyperglycemia (OR=1.469; 95% CI, 1.082-1.993) in male workers, and with hypertension (OR=1.492; 95% CI, 1.071-2.080) in females. However, prevalence of hypertryglyceridemia was lower (OR=0.390; 95% CI, 0.204-0.746) in female administrators compared to those in academics. Obesity, MS and reduced High Density Lipoprotein (HDL) cholesterol prevalence was not different (p>0.05) between the two occupations in both sexes. CONCLUSIONS: Prevalence of MS and its components was higher in male workers than in females, increased with age, and were more common in administrative workers. The findings support the need for gender and occupation specific health interventions to prevent CVDs and type II diabetes in the workplace.

[Molecular design, structural analysis and bactericidal activity of derivatives of antimicrobial peptide buforin II].

A novel peptide, named BF2-X, was designed based on the structure-activity analysis of an analogue of Buforin II, named BF2-A. The BF2-X was a hybrid peptide containing the N-terminal residues 5 to 13 of BF2-A and three repeats of the C-terminal regular alpha-helical motif RLLR, and the residues 8 valine were replaced by leucine. The results of bioinformatics analysis had showed that compared with BF2-A, the helicity, positive charge, hydrophobicity rate and C-terminal amphipathy of BF2-X had remarkably enhanced. Both peptides showed a random coil structure in an aqueous solution, while displaying a typical alpha-helical structure in 50% trifluoroethanol solution (a membrane mimic condition). BF2-X exhibited higher alpha-helical contents than BF2-A in hydrophobic environment. BF2-X displayed potent antimicrobial activities against a broad spectrum of microorganisms. And BF2-X showed stronger antimicrobial activities against bacteria tested than parent peptide BF2-A. These results suggest that the alpha-helical content was directly correlated with the enhanced antibacterial activity. Both peptides had no hemolytic action on mouse erythrocyte.

The intracellular mechanism of action on Escherichia coli of BF2-A/C, two analogues of the antimicrobial peptide Buforin 2.

In the present study, the antimicrobial peptides BF2-A and BF2-C, two analogues of Buforin 2, were chemically synthesized and the activities were assayed. To elucidate the bactericidal mechanism of BF2-A/C and their different antimicrobial activities, the influence of peptides to E. coli cell membrane and targets of intracellular action were researched. Obviously, BF2-A and BF2-C did not induce the influx of PI into the E. coli cells, indicating nonmemebrane permeabilizing killing action. The FITC-labeled BF2-A/C could penetrate the E. coli cell membrane and BF2-C penetrated the cells more efficiently. Furthermore, BF2-A/C could bind to DNA and RNA respectively, and the affinity of BF2-C to DNA was powerful at least over 4 times than that of BF2-A. The present results implied that BF2-A and BF2-C inhibited the cellular functions by binding to DNA and RNA of cells after penetrating the cell membranes, resulting in the rapid cell death. The structure-activity relationship analysis of BF2-A/C revealed that the cell-penetrating efficiency and the affinity ability to DNA were critical factors for determining the antimicrobial potency of both peptides. The more efficient cell-penetrating and stronger affinity to DNA caused that BF2-C displayed more excellent antimicrobial activity and rapid killing kinetics than BF2-A.

Inhibition of Fe-induced colon oxidative stress by lactobacilli in mice.

Iron (Fe) can promote hydrogen peroxide (H(2)O(2)) and hydroxyl radical generation in the colonic surface and promote growth of Fe-dependent bacteria. Some Lactobacillus strains are resistant to oxygen free-radicals, allowing them to survive in a Fe-modulated mucosal environment and influence colon microbial ecology and redox state. Here, we investigated the capacity of lactobacilli with different antioxidant abilities to modify the bacterial profile and prevent oxidative stress in the colon of Fe-overloaded mice. Survival time of Lactobacillus rhamnosus LGG (LGG) in the presence of H(2)O(2) and hydroxyl radical was significantly longer compared with the mid- and non-antioxidative strains, Lactobacillus paracasei Fn032 and Lactobacillus plantarum Fn001, respectively. Different Lactobacillus strains are specific in free-radical scavenging activities of their cell-free extracts, which increased to varying extent depending on strains when bacteria were exposed to simulated gastric and pancreatic juice. Fe-overloaded mice showed increased colonic luminal ferrous Fe content, Enterococcus and Escherichia coli concentrations, mucosal malondialdehyde and free-radicals, and decreased mucosal total antioxidative capacity and oxidative enzymatic activity. Translocation of endotoxin to the liver was also significantly increased (P < 0.05). Lactobacilli inhibited ferrous Fe accumulation, especially in LGG and Fn032. LGG significantly inhibited the increase of colonic mucosal free-radicals and malondialdehyde content (P < 0.05). Fn032 only inhibited malondialdehyde (P < 0.05). LGG and Fn032 significantly inhibited increases in colonic Enterococcus (P < 0.05). Fn001 showed no significant antioxidative ability in vivo. The difference of these effects in vivo were well agreed with scavenging activities against reactive oxygen species (ROS) of simulated gastrointestinals fluid pretreated cells in vitro. In conclusion, ROS scavenging activities was essential for Lactobacillus to prevent oxidative stress in vivo and inhibition of ROS-producing bacterial growth and mucosal barrier injury.