The effects of selenium on GPX4-mediated lipid peroxidation and apoptosis in germ cells.

Emerging evidence suggests that selenium plays an essential role in sperm maturation. However, the specific signaling pathway by which selenium exerts effect has not been elucidated. To evaluate the effect of selenium on GPX4-mediated lipid peroxidation and apoptosis in germ cells, selenium deficiency was modeled by culturing GC2-spd cells in serum-free medium. Treatment with 0.5-µM sodium selenite (NaSe) or 5.0-µM selenomethionine (SeMet) significantly improved the proliferation rate and GPX4 protein expression after selenium deficiency. Moreover, NaSe and SeMet decreased the MDA content and lipid peroxidation. When adenovirus was used to knockdown the expression of the GPX4 gene (shRNA-GPX4), the early apoptosis rate of the shRNA-GPX4 cells was significantly higher than that of the EGFP cells. Increased expression of Caspase3 and Bax, as well as MDA content were observed in the shRNA-GPX4 cells compared with EGFP cells. In further, overexpression of the GPX4 gene (ORF-GPX4) cells exhibited increased cell proliferation and decreased MDA content. However, there was no significant difference in 12/15-lox expression both in ORF-GPX4 cells and shRNA-GPX4 cells. Conclusively, GPX4 was involved in the regulation of lipid peroxidation and apoptosis in GC2-spd cells. Selenium played a role in promoting cell proliferation by mediating GPX4. The regulation of GPX4 may occur independently of 12/15-Lox. These findings confirmed the effect of selenium on spermatogenesis and offered a potential target for treating abnormal semen quality in men.

Obesity-related genetic polymorphisms are associated with the risk of early puberty in Han Chinese girls.

OBJECTIVE: To explore the association between obesity and precocious puberty from the perspective of genetic polymorphism. DESIGN: Two hundred and ninety-eight pairs of girls in early puberty and age-matched controls (±3 months) were recruited. The genotypes of four obesity-related single-nucleotide polymorphism (SNP) loci (rs10968576, rs12935153, rs4674340 and rs7635103) were determined and the effect of variation on early puberty in Chinese Han girls was evaluated. The unstimulated luteinizing hormone (LH), follicle-stimulating hormone and estradiol levels were also measured to determine the relationship with SNP polymorphisms. RESULTS: The effect allele A of rs12935153 was associated with early puberty (odds ratio [OR] = 1.256, 95% confidence interval [CI]: 1.010-1.585), but the significance disappeared after multiple comparisons. After adjusting for body mass index, rs12935153 variation increased the risk of early puberty in additive (OR = 1.589, 95% CI: 1.222-2.066), dominant (OR = 1.788, 95% CI: 1.210-2.642) and recessive (OR = 1.915, 95% CI: 1.207-3.038) models of inheritance. Individuals harbouring AA genotype in rs12935153 had a risk of higher LH levels than that of wild type (OR = 1.668, 95% CI: 1.093-2.546). CONCLUSIONS: The association between obesity and precocity can be explained from a genetic perspective. Our study suggests that variations in rs12935153 increase the risk of early puberty in Chinese girls. Further studies are needed to verify our findings.

Association of Gut Microbiota-Dependent Metabolite Trimethylamine N-Oxide with First Ischemic Stroke.

AIM: We aimed to investigate the relationship of trimethylamine N-oxide (TMAO) concentrations with ischemic stroke in a large-scale case-control study conducted among the hospital-based general population. METHODS: We recruited 953 case-control sex- and age-matched pairs, and cases were confined to first acute ischemic stroke in this study. Fasting plasma TMAO was measured using high-performance liquid chromatography-tandem mass spectroscopy. Conditional logistic regression analysis was conducted to calculate odds ratios (OR) for the association of plasma TMAO with ischemic stroke. RESULTS: We found that plasma TMAO concentrations in patients with ischemic stroke were significantly higher than that in the control group (median: 2.85 µmol/L vs. 2.33 µmol/L, P＜0.001). In multivariable conditional logistic regression models, higher plasma TMAO concentrations were associated with increased odds of ischemic stroke [fully adjusted OR for highest vs. lowest TMAO quartile: 1.81; 95% confidence interval (CI): 1.27, 2.59; P for trend ＜0.001]. The multivariable-adjusted OR for ischemic stroke per 1 µmol/L increment of plasma TMAO was 1.05 (95% CI: 1.02, 1.08). Additionally, the positive association also persisted in subgroups stratified by age, sex, body mass index, smoking status, alcohol habits, history of diabetes, and history of hypertension. CONCLUSIONS: This study suggested a positive association between plasma TMAO and ischemic stroke. Further studies are required to explore the role of plasma TMAO concentrations in predicting stroke risk.

The Research Progress of Vascular Macrophages and Atherosclerosis.

MATERIALS: We made a minireview on the association of vascular macrophages with AS based on recent research studies systematically, from the mechanisms of macrophages accumulating in the walls of blood vessels, and the role of macrophages in AS as well as microenvironmental determinants of macrophage function in AS. The discovery of these mechanisms could reveal the pathogenesis of AS comprehensively and is crucial to provide scientific evidence for formulating the related measures of prevention and treatment for AS. Discussion. Vascular macrophages play important roles in the development of AS, and the vascular macrophages may become new targets for the prevention and treatment of AS. Effective regulation of host genes may help prevent or even treat AS. CONCLUSION: This minireview focuses on the association of vascular macrophages with the development of AS, which may supply some clues for future therapies and novel drug targets for AS.

Association of Polymorphisms in the Kisspeptin/GPR54 Pathway Genes With Risk of Early Puberty in Chinese Girls.

CONTEXT AND OBJECTIVE: This case control study was designed to investigate the association between mutation of 10 single nucleotide polymorphism (SNP) loci (rs1132506, rs5780218, rs192636495, rs4889, rs184749, rs12985070, rs708910, rs932491, rs8074995, and rs2306877) in all 5 genes (KISS1, GPR54, PLCB1, PRKCA, and ITPR1) in the kisspeptin/GPR54 pathway and the risk of early puberty in Chinese Han girls. DESIGN AND PARTICIPANTS: A total of 314 pairs of early puberty girls on their first visit to hospital and age-matched controls (± 3 months) were recruited. The genotypes of each SNP were determined and the effect of loci variation on early puberty was investigated. RESULTS: rs5780218 was significantly associated with early puberty in additive, dominant, and recessive models of inheritance after adjusting for confounding factors (Pr < .05). After stratification, rs5780218 variation (odds ratio [OR], 1.650, 95% confidence interval [CI], 1.155-2.355 in additive models and OR, 2.116; 95% CI, 1.187-3.770 in recessive models) increased the risk of central precocious puberty (CPP); mutation in rs708910 (OR, 2.768; 95% CI, 1.305-5.872 in recessive model) had a positive association with the risk of CPP; and rs932491 variation was negatively associated with early and fast puberty (EFP) (OR, 0.309; 95% CI, 0.144-0.661 in additive models and OR, 0.317; 95% CI, 0.141-0.713 in dominant models). CONCLUSIONS: Our study suggests that mutation in rs5780218 and rs708910 increases the risk of CPP. rs932491 variation may have a protective effect on the risk of EFP. Further studies in larger populations or with people from different regions are needed to verify our findings.

Liver function monitoring: a prospective nested case-control study of Salvia miltiorrhiza polyphenol injection.

Instructions for Salvia miltiorrhiza polyphenol injections indicate abnormal liver function as an occasional adverse reaction, but the incidence of this adverse drug reaction (ADR) has increased in recent years. We assessed S. miltiorrhiza polyphenol ADRs by performing a nested case-control study(NCCS) and meta-analysis. In the NCCS, 2633 patients receiving this treatment in the First Affiliated Hospital of Bengbu Medical College were enrolled. Logistic regression models found that in 58 (2.2%) patients experiencing abnormal liver function, the risk for liver dysfunction was associated with sulfa drug allergy (OR = 7.874, 95%CI (1.280, 48.447), P = 0.026), payment methods (OR = 0.106, 95%CI (0.012, 0.934), P = 0.043), duration of administration (OR = 0.922, 95%CI (0.862, 0.986), P = 0.017), cefathiamidine (OR = 0.441, 95%CI (0.216, 0.900), P = 0.025), human serum albumin (OR = 1.958, 95%CI (1.011, 3.789), P = 0.046), Dazhu Rhodiola injection (OR = 2.599, 95%CI (1.112, 6.070), P = 0.027), or reduced glutathione (OR = 0.394, 95%CI (0.188, 0.826), P = 0.014). Meta-analysis of reports on S. miltiorrhiza polyphenol ADRs in controlled trials and other observational studies included 676 patients, of which 17 (2.17%; 95%CI (0.0105, 0.0358)) presented with liver dysfunction; associated ADR risk factors included co-administration of other drugs. Our NCCS and meta-analysis had similar ADR incidence rates, which were higher than the rate in the drug instructions. This study provides guidance for assessing liver dysfunction risks associated with S. miltiorrhiza polyphenol injections.

Cellular metabolomics reveals glutamate and pyrimidine metabolism pathway alterations induced by BDE-47 in human neuroblastoma SK-N-SH cells.

Polybrominated diphenyl ethers (PBDEs) as potential neurotoxicants in environment may possess hazards to human health. Previous studies have reported that PBDEs exposure could induce oxidative stress and disturb mitochondrial functions in mammalian cells. However, the toxicological mechanism remains to be clarified. In this work, the neurotoxic effect and underlying mechanism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) was investigated by using human neuroblastoma SK-N-SH cells as an effective model. A liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach combined with cell viability assay was applied to elucidate the metabolic perturbations and relevant toxicological pathways upon BDE-47 exposure. Our results shown that the SK-N-SH cell viability decreased in a dose-dependent manner after exposure to BDE-47 at 24 h within the concentration range of 5-250 µM, and an IC50 value of 88.8 µM was obtained. Based on the dose-response curve and cell morphological observation, the 5 and 10 µM BDE-47 doses (equal to IC5 and IC10, respectively) were used for metabolomics study to capture the sensitive metabolic response following BDE-47 exposure. After BDE-47 treatment, nine metabolites were identified as potential biomarkers, and the most disturbed metabolic pathways were mainly involved in alanine, aspartate and glutamate metabolism, glutathione metabolism, tyrosine and phenylalanine metabolism, and pyrimidine metabolism, which imply that metabolic changes related to neurotransmitters, oxidative stress, and nucleotide-mediated signal transduction systems were the sensitive pathways mostly influenced. Our findings reported here may provide potential neurotoxic effect biomarkers and prompt deep understanding of the molecular and metabolic mechanisms triggered by BDE-47 exposure.

Inhibition of S-Adenosylhomocysteine Hydrolase Induces Endothelial Dysfunction via Epigenetic Regulation of p66shc-Mediated Oxidative Stress Pathway.

BACKGROUND: Elevated levels of S-adenosylhomocysteine (SAH), the precursor of homocysteine, are positively associated with the risk of cardiovascular disease and with the development and progression of atherosclerosis. However, the role of SAH in endothelial dysfunction is unclear. METHODS: Apolipoprotein E-deficient ( apoE-/-) mice received dietary supplementation with the SAH hydrolase (SAHH) inhibitor adenosine dialdehyde or were intravenously injected with a retrovirus expressing SAHH shRNA. These 2 approaches, along with the heterozygous SAHH gene knockout ( SAHH+/-) mouse model, were used to elevate plasma SAH levels and to examine the role of SAH in aortic endothelial dysfunction. The relationship between plasma SAH levels and endothelial dysfunction was also investigated in human patients with coronary artery disease and healthy control subjects. RESULTS: Plasma SAH levels were increased in SAHH+/- mice and in apoE-/- mice after dietary administration of adenosine dialdehyde or intravenous injection with SAHH shRNA. SAHH+/- mice or apoE-/- mice with SAHH inhibition showed impaired endothelium-dependent vascular relaxation and decreased nitric oxide bioavailability after treatment with acetylcholine; this was completely abolished by the administration of the endothelial nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester. Furthermore, SAHH inhibition induced production of reactive oxygen species and p66shc expression in the mouse aorta and human aortic endothelial cells. Antioxidants and p66shc siRNA prevented SAHH inhibition-induced generation of reactive oxygen species and attenuated the impaired endothelial vasomotor responses in high-SAH mice. Moreover, inhibition of SAHH induced hypomethylation in the p66shc gene promoter and inhibited expression of DNA methyltransferase 1. Overexpression of DNA methyltransferase 1, induced by transduction of an adenovirus, was sufficient to abrogate SAHH inhibition-induced upregulation of p66shc expression. Finally, plasma SAH levels were inversely associated with flow-mediated dilation and hypomethylation of the p66shc gene promoter and positively associated with oxidative stress levels in patients with coronary artery disease and healthy control subjects. CONCLUSIONS: Our findings indicate that inhibition of SAHH results in elevated plasma SAH levels and induces endothelial dysfunction via epigenetic upregulation of the p66shc-mediated oxidative stress pathway. Our study provides novel molecular insight into mechanisms of SAH-associated endothelial injury that may contribute to the development of atherosclerosis. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03345927.

Plasma alkylresorcinol metabolite, a biomarker of whole-grain wheat and rye intake, and risk of ischemic stroke: a case-control study.

Background: Epidemiologic studies on whole grains and risk of stroke have reported inconsistent results, with some suggesting a protective effect but others showing a null association. Objectives: The aim of this study was to examine whether plasma 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, is associated with risk of ischemic stroke. Methods: A hospital-based case-control study was conducted between March 2011 and May 2016. Cases (n = 990) with first ischemic stroke were matched to controls (n = 990) by sex and age. Concentrations of plasma DHPPA were determined by high-performance liquid chromatography-tandem mass spectrometry. We calculated ORs for the association of plasma DHPPA concentrations with ischemic stroke risk through the use of logistic regression. Results: Plasma DHPPA was inversely associated with ischemic stroke risk. After adjustment for potential confounding factors, the ORs for ischemic stroke across increasing quartiles of plasma DHPPA concentrations were 1 (referent), 0.76 (95% CI: 0.58, 0.99), 0.71 (95% CI: 0.54, 0.92), and 0.59 (95% CI: 0.45, 0.77), respectively (P-trend = 0.001). The inverse association was also observed in all subgroups of participants according to sex, age, body mass index, smoking status, alcohol consumption, history of hypertension, and history of diabetes. Conclusions: Our study showed that higher plasma DHPPA concentrations were associated with lower risk of ischemic stroke. This finding provides further evidence to support the health benefits of whole-grain consumption.

Associations between dietary patterns and the risk of breast cancer: a systematic review and meta-analysis of observational studies.

BACKGROUND: Epidemiologic evidence suggests that certain dietary patterns were associated with breast cancer risk, but the results have been inconclusive. We assessed the associations between different dietary patterns and the risk of breast cancer by conducting a meta-analysis of observational studies. METHODS: Relevant articles were searched in PubMed, Embase, and Cochrane library databases through September 2017. Multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs) comparing the highest and lowest categories of Western and prudent dietary patterns were combined by using the random-effects meta-analyses. RESULTS: We identified 32 eligible articles including 14 cohort and 18 case-control studies (34 Western and 35 prudent studies). The pooled analyses found that a Western dietary pattern was associated with a 14% increased risk (RR 1.14, 95% CI 1.02, 1.28), whereas a prudent dietary pattern was associated with an 18% reduced risk of breast cancer (RR 0.82, 95% CI 0.75, 0.89). In addition, sub-group analyses showed that the positive association between a Western dietary pattern and breast cancer risk was significant among postmenopausal (RR 1.20, 95% CI 1.06, 1.35), but not premenopausal women (RR 1.18, 95% CI 0.99, 1.40), and significant for hormone receptor-positive tumors (RR 1.18, 95% CI 1.04, 1.33), but not receptor-negative tumors (RR 0.97, 95% CI 0.83, 1.12). In contrast, the inverse association between a prudent dietary pattern and breast cancer was significant in premenopausal (RR 0.77, 95% CI 0.61, 0.98), but not postmenopausal women (RR 0.88, 95% CI 0.74, 1.03), and significant for both hormone receptor-positive and receptor-negative tumors. CONCLUSIONS: The results of the current meta-analysis suggest a possible increased risk of breast cancer associated with a Western dietary pattern and a reduced risk with a prudent dietary pattern. Large-scale cohort studies with a high quality need to be conducted to further confirm the findings of the current meta-analysis. As dietary patterns are modifiable, these findings may provide viable strategies for breast cancer prevention through changes in dietary intake.

Plasma Alkylresorcinol Metabolite, a Biomarker of Whole-Grain Wheat and Rye Intake, and Risk of Type 2 Diabetes and Impaired Glucose Regulation in a Chinese Population.

OBJECTIVE: To examine the association of plasma alkylresorcinol metabolite 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, with type 2 diabetes (T2D) and impaired glucose regulation (IGR) in a Chinese population. RESEARCH DESIGN AND METHODS: A total of 1,060 newly diagnosed T2D patients, 736 newly diagnosed IGR patients, and 1,443 control subjects with normal glucose tolerance were recruited in the case-control study. Plasma DHPPA concentrations were determined by high-performance liquid chromatography-tandem mass spectroscopy. Multivariate logistic regression analysis was used to evaluate the independent association of plasma DHPPA concentrations with the likelihood of T2D and IGR. RESULTS: After adjustment for age, sex, BMI, and family history of diabetes, the odds ratios (95% CI) of T2D and IGR were 0.57 (0.45, 0.73) and 0.66 (0.50, 0.85), respectively, comparing the lowest with the highest quartile of plasma DHPPA concentrations. Further adjustment for current smoking status, current alcohol consumption, physical activity, history of hypertension, and educational level did not change the observed association materially. Similar results were also obtained in T2D and IGR groups combined. The inverse association of plasma DHPPA with T2D persisted in stratified analyses according to age, sex, BMI, current smoking status, current alcohol consumption, physical activity, family history of diabetes, and history of hypertension. CONCLUSIONS: These findings suggested that higher plasma DHPPA concentrations were associated with lower odds of T2D and IGR. Further studies are warranted to confirm these findings in prospective cohorts.

ARRDC4 regulates enterovirus 71-induced innate immune response by promoting K63 polyubiquitination of MDA5 through TRIM65.

Enterovirus 71 (EV71) is the main causative agent of hand, foot and mouth disease (HFMD), which induces significantly elevated levels of cytokines and chemokines, leading to local or system inflammation and severe complications, whereas the underlying regulatory mechanisms and the inflammatory pathogenesis remain elusive. ARRDC4 is one member of arrestins family, having important roles in glucose metabolism and G-protein-coupled receptors (GPCRs) related physiological and pathological processes, however, the function of ARRDC4 in innate immune system is largely unknown. Here we identified that ARRDC4 expression was increased after EV71 infection in THP-1-derived macrophages and verified in EV71-infected HFMD patients and the healthy candidates. The expression level of ARRDC4 was positively correlated with the serum concentration of IL-6, TNF-α and CCL3 in clinical specimens. ARRDC4 interacted with MDA5 via the arrestin-like N domain, and further recruited TRIM65 to enhance the K63 ubiquitination of MDA5, resulting in activation of the downstream innate signaling pathway and transcription of proinflammatory cytokines during EV71 infection. Our data highlight new function of ARRDC4 in innate immunity, contributing to the better understanding about regulation of MDA5 activation after EV71 infection, and also suggest ARRDC4 may serve as a potential target for intervention of EV71-induced inflammatory response.

Circulating miR-31 as an effective biomarker for detection and prognosis of human cancer: a meta-analysis.

PURPOSE: Circulating miR-31 was found to be associated with cancers detection and prognosis. The present meta-analysis aimed to explore the effect of circulating miR-31 on cancer detection and prognosis. METHOD: The studies were accessed using multiple databases. RevMan5.3, Meta-DiSc 1.4, and STATA14.0 were used to estimate the pooled effects, heterogeneity among studies, and publication bias. RESULTS: A total of 14 studies with 1397 cancer patients and 1039 controls were included. For the 12 prognostic tests, the adjusted pooled-AUC was 0.79 (95% CI: 0.73-0.86) as the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odd ratio (DOR) from 10 tests was 0.79 (95% CI: 0.76-0.82), 0.79 (95% CI: 0.76-0.82), 3.81 (95% CI: 2.90-5.01), 0.26 (95% CI: 0.20-0.35), and 16.81 (95% CI: 9.67-29.25), respectively. For the 5 prognosis analyses, the pooled HR (hazard ratio) of overall survival (OS) was 1.55 (95% CI 1.30-1.86) for high versus low circulating miR-31 expression. However, high expression of circulating miR-31 did not significantly increase the risk of poor differentiation (pooled OR=1.39, 95% CI: 0.56-3.47) and LNM (pooled OR=3.46, 95% CI: 0.96-12.42) in lung cancer. CONCLUSION: Circulating miR-31 is an effective biomarker and could be used as a component of miRs signature for cancer detection and prognosis surveillance.

AlncRNA HULC as an effective biomarker for surveillance of the outcome of cancer: A meta-analysis.

PURPOSE: High expression of highly upregulated in iver cancer (HULC) has been found associated with increased metastasis and poor prognosis with cancer. This meta-analysis aimed to determine the pooled effect of HULC on metastasis and prognosis of cancers. METHOD: The studies were accessed using multiple databases. RevMan5.3 and STATA14.0 were used to estimate pooled effects, the heterogeneity among studies, and publication bias for the association of HULC and overall survival (OS). RESULTS: A total of 9 studies of 966 cancer patients were included. Risk of lymph node metastasis was increased with high versus low HULC expression (pooled odds ratio [OR] = 4.83, 95% confidence interval [CI] 1.59-14.63) as was distant metastasis (pooled OR = 5.44, 95% CI 2.33-12.74). Furthermore, OS time was shortened with high HULC expression (pooled hazard ratio [HR] = 1.48, 95% CI 1.03-2.12), especially in Chinese patients (pooled HR = 2.04, 95% CI 1.55-2.68), and risk of recurrence was increased (pooled OR = 6.68, 95% CI 2.77-16.13). CONCLUSION: HULC might be a potential biomarker for therapy and prognosis surveillance in cancers.

The Effects of Occupational Exposure of Carbon Disulfide on Sexual Hormones and Semen Quality of Male Workers From a Chemical Fiber Factory.

OBJECTIVE: This study is aimed to analyze the relationship between occupational CS2 exposure and reproductive impairments. METHODS: Seventy-six CS2-exposed (9.73 ±â€Š2.76 mg/m(3)) male workers and 94 unexposed workers were selected for study. Worker demographics were assessed with a customized questionnaire. Sexual hormones and sperm-related parameters were measured by biochemical or morphological analysis. RESULTS: The CS2-exposed workers had significantly higher serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and lower levels of testosterone (T). Significant decrements were also identified in sperm viability and motility, chromatin, antioxidant capacity, mitochondrial membrane potential, mitochondrial membrane permeability transition pore (MPTP), and respiratory chain Complexes II and IV. CONCLUSIONS: Our data indicated that occupational CS2 exposure can exert deleterious effects on male sexual hormones and sperm quality, and mitochondrial dysfunction may play a vital role in this process.

Preliminary Proteomic Analysis of A549 Cells Infected with Avian Influenza Virus H7N9 and Influenza A Virus H1N1.

A newly emerged H7N9 influenza virus poses high risk to human beings. However, the pathogenic mechanism of the virus remains unclear. The temporal response of primary human alveolar adenocarcinoma epithelial cells (A549) infected with H7N9 influenza virus and H1N1 influenza A virus (H1N1, pdm09) were evaluated using the proteomics approaches (2D-DIGE combined with MALDI-TOF-MS/MS) at 24, 48 and 72 hours post of the infection (hpi). There were 11, 12 and 33 proteins with significant different expressions (P<0.05) at 24, 48 and 72hpi, especially F-actin-capping protein subunit alpha-1 (CAPZA1), Ornithine aminotransferase (OAT), Poly(rC)-binding protein 1 (PCBP1), Eukaryotic translation initiation factor 5A-1 (EIF5A) and Platelet-activating factor acetylhydrolaseⅠb subunit beta (PAFAH1B2) were validated by western-blot analysis. The functional analysis revealed that the differential proteins in A549 cells involved in regulating cytopathic effect. Among them, the down-regulation of CAPZA1, OAT, PCBP1, EIF5A are related to the death of cells infected by H7N9 influenza virus. This is the first time show that the down-regulation of PAFAH1B2 is related to the later clinical symptoms of patients infected by H7N9 influenza virus. These findings may improve our understanding of pathogenic mechanism of H7N9 influenza virus in proteomics.

Polycyclic Aromatic Hydrocarbons-Associated MicroRNAs and Heart Rate Variability in Coke Oven Workers.

OBJECTIVE: We aimed to evaluate the association between polycyclic aromatic hydrocarbons (PAHs)-related microRNAs (miRNAs) and heart rate variability indices in coke oven workers. METHODS: We recruited 365 male coke oven workers and measured urinary PAH metabolites by gas chromatography-mass spectrometry. Five heart rate variability indices were measured using three-channel Holter monitor. Six miRNAs were detected by TaqMan miRNA assays (Life Technologies, Foster City, CA). RESULTS: miR-24-3p, miR-27a-3p, miR-142-5p, and miR-320b were negatively associated with the root mean of square of successive differences between adjacent normal NN intervals (RMSSD) (P(trend) = 0.006, 0.047, 0.019, 0.011, respectively). miR-142-5p and miR-320b were also negatively associated with standard deviation of all normal to normal NN intervals (SDNN) (P(trend) = 0.01 and 0.035). miR-24-3p, miR-27a-3p, and miR-320b were significantly interacted with multiple PAH metabolites and influenced heart rate variability indices, whereas miR-24-3p also significantly interacted with smoking to influence low frequency (P(interaction) < 0.05 for all). CONCLUSIONS: Plasma miRNAs might act as potential biomarkers for the adverse effect of PAH exposure on the cardiovascular system.

Cdc42 induces EGF receptor protein accumulation and promotes EGF receptor nuclear transport and cellular transformation.

Cdc42 is a Ras-related small GTP-binding protein. A previous study has shown that Cdc42 binding to the γ subunit of the coatomer protein complex (γCOP) is essential for Cdc42-regulated cellular transformation, but the molecular mechanism involved is not well understood. Here, we demonstrate that constitutively-active Cdc42 binding to γCOP induced the accumulation of epithelial growth factor receptor (EGFR) in the cells, sustained EGF-stimulated extracellular signal-regulated kinase (ERK), JUN amino-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K) signaling and promoted cell division. Moreover, constitutive Cdc42 activity facilitated the nuclear translocation of EGFR, and this indicates a novel mechanism through which Cdc42 might promote cellular transformation.

Time trends and age-period-cohort analyses on incidence rates of thyroid cancer in Shanghai and Hong Kong.

BACKGROUND: Increasing incidence rates of thyroid cancer have been noted worldwide, while the underlying reasons remain unclear. METHODS: Using data from population-based cancer registries, we examined the time trends of thyroid cancer incidence in two largest cities in China, Shanghai and Hong Kong, during the periods 1973-2009 and 1983-2011, respectively. We further performed age-period-cohort analyses to address the possible underlying reasons for the observed temporal trends. RESULTS: We observed continuous increases in the incidence rates of thyroid cancer in Shanghai and Hong Kong, since the 1980s, in addition to higher incidence rates in the 1970s in both sexes in Shanghai. The age-standardized incidence rate of thyroid cancer increased by 3.1% [95% confidence interval (CI): 1.0%, 5.1%] and 3.8% (95% CI: 1.9%, 5.7%) per year on average, respectively, in Shanghai men and women during the period 1973-2009, while it increased by 2.2% (95% CI: 1.5%, 2.8%) and 2.7% (1.6%, 3.8%) per year on average, respectively, in Hong Kong men and women during the period 1983-2011. We observed global changes in trends across all age groups in similar ways, in addition to varied trends across different generations (birth cohorts). CONCLUSIONS: The increased incidence rates of thyroid cancer in these two Chinese populations during recent decades may be contributable to a combination of the introduction of more sensitive diagnostic techniques and the increasing prevalence of environmental exposures in the populations.

Serum amyloid A and clusterin as potential predictive biomarkers for severe hand, foot and mouth disease by 2D-DIGE proteomics analysis.

Hand, foot, and mouth disease (HFMD) affects more than one million children, is responsible for several hundred child deaths every year in China and is the cause of widespread concerns in society. Only a small fraction of HFMD cases will develop further into severe HFMD with neurologic complications. A timely and accurate diagnosis of severe HFMD is essential for assessing the risk of progression and planning the appropriate treatment. Human serum can reflect the physiological or pathological states, which is expected to be an excellent source of disease-specific biomarkers. In the present study, a comparative serological proteome analysis between severe HFMD patients and healthy controls was performed via a two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) strategy. Fifteen proteins were identified as differentially expressed in the sera of the severe HFMD patients compared with the controls. The identified proteins were classified into different groups according to their molecular functions, biological processes, protein classes and physiological pathways by bioinformatics analysis. The up-regulations of two identified proteins, serum amyloid A (SAA) and clusterin (CLU), were confirmed in the sera of the HFMD patients by ELISA assay. This study not only increases our background knowledge about and scientific insight into the mechanisms of HFMD, but also reveals novel potential biomarkers for the clinical diagnosis of severe HFMD.