Potential risk of hyperuricemia: leading cardiomyocyte hypertrophy by inducing autophagy.

BACKGROUND: Clinical studies have shown that hyperuricemia is associated with many cardiovascular diseases; however, the mechanisms involved remain unclear. In this study, we investigated the effect of uric acid on cardiomyocytes and the underlying mechanism. METHODS AND RESULTS: H9c2 cardiomyocytes were treated with various concentrations of uric acid. 3-Methyladenine (3-MA) or Compound C was added before treatment with uric acid. The expression of myocardial hypertrophy-related genes was measured using polymerase chain reaction (PCR). The cell surface area was calculated using ImageJ Software. Western blotting was used to measure the protein levels. Uric acid increased the gene expression of Nppa, Nppb, and Myh5, which are involved in myocardial hypertrophy, and the relative cell surface area of cardiomyocytes in a dose-dependent manner. Consistently, the ratio of LC3II/I, which is a biomarker of autophagy, increased dose-dependently, whereas the protein level of p62, a protein that is degraded by autophagy, decreased. 3-MA, an autophagy inhibitor, rescued uric acid-induced myocardial hypertrophy. Treatment with uric acid increased the level of phosphorylated adenosine monophosphate kinase (AMPK), as well as its downstream effector unc-51-like kinase (ULK1). Pharmacological inhibition of AMPK by Compound C attenuated the uric acid-induced activation of autophagy and myocardial hypertrophy. CONCLUSIONS: Uric acid induces myocardial hypertrophy by activating autophagy via the AMPK-ULK1 signaling pathway. Decreasing the serum uric acid level may therefore be clinically beneficial in alleviating cardiac hypertrophy.

Serum uric acid and its relationship with cardiovascular risk profile in Chinese patients with early-onset coronary artery disease.

The prevalence of coronary artery disease (CAD) is growing in the young population. We aimed to investigate the association between serum uric acid (SUA) levels and cardiovascular involvement in individuals under 45 years old diagnosed with early-onset CAD (EOCAD). Seven hundred eighty-six EOCAD patients were recruited and stratified into four groups by SUA levels. General information, serum indicators, and results of coronary angiography and echocardiography were recorded. The associations between SUA levels were explored by univariate and multivariate logistic regressions. With the increasing of SUA levels, the prevalence of hypertension and hyperlipidemia, triple branches involved, heart failure, and cardiac enlargement of left ventricle (LV), left atrium (LA), and right ventricle (RV) were significantly higher (all P < 0.05). The fourth group (SUA >8 mg/dl) had the highest proportions than other groups (all P < 0.05). After controlling potential confounders, multiple logistic regression analysis showed that odds ratios of SUA >8 mg/dl were 2.345 for triple branches involved (95 % confidence interval (CI) 1.335-4.119), 4.168 for heart failure (95 % CI 1.599-10.862), and 4.122 for LV enlargement (95 % CI 1.874-9.065) (P < 0.05). SUA >8 mg/dl was independently associated with triple branches involvement, heart failure and LV enlargement in Chinese EOCAD patients. Higher SUA level might play an important role in cardiac dysfunction and severity of EOCAD.

Assessment of lead bioaccessibility in soils around lead battery plants in East China.

Soil ingestion is an important human exposure pathway for lead (Pb). A modified physiologically based extraction test was applied to 70 soil samples from five battery plants in East China. The mean values for soil pH, soil organic matter, Fe and Mn concentrations ranged from 5.9% to 8.1, 0.37% to 2.2%, 2.78% to 3.75%, and 507-577 mg kg(-1), respectively, while Pb concentrations ranged widely in 14.3-2000 mg kg(-1). The isotopic ratios of 14 soils from one of the five battery plants formed a straight line in the plot of (208)Pb/(206)Pb vs. (207)Pb/(206)Pb, indicating Pb emissions from the lead battery plant as the dominant anthropogenic source within 200 m. Lead bioaccessibility in the soils ranged from 4.1% to 66.9% in the gastric phase and from 0.28% to 9.29% in the gastrointestinal phase. Multiple step regressions identified modes as BAgastric=-106.8+0.627[Pb]+19.1[Fe]+11.3[SOM], and BAgastrointestinal=-2.852+0.078[Pb].

Macrophage-secreted IL-8 induces epithelial-mesenchymal transition in hepatocellular carcinoma cells by activating the JAK2/STAT3/Snail pathway.

Macrophages are a major component of the leukocyte infiltrate of tumors and play a pivotal role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanisms by which macrophages promote HCC invasion are poorly understood. The present study was undertaken to investigate the relationship between macrophages and epithelial-mesenchymal transition (EMT) of HCC. Double-staining immunohistochemistry was used to observe the association between macrophages and EMT markers in clinical HCC samples and it showed that EMT primarily occurred at the edge of the tumor nest, in which infiltrating macrophages were always observed. This indicated that CD68 which is a marker of macrophages, was correlated with EMT marker levels. In addition, after being cultured with macrophages for 24 h, the ability of HCC cells to migrate and invade increased, Snail and N-Cadherin expression was upregulated, and E-Cadherin was downregulated. An antibody array assay was applied to analyze the supernatant of these cultures and it demonstrated IL-8 increased significantly in the macrophage co-culture system. Finally, the role of macrophage-derived IL-8 in the invasion of HCC cells was assayed, and downstream signaling pathways were also investigated. We found that IL-8: i) may induce EMT and promote HCC cell migration and invasion and ii) is associated with the JAK2/STAT3/Snail signaling pathway. Taking together, these findings revealed that macrophages that have infiltrated tumors may induce epithelial-mesenchymal transition of HCC cells via the IL-8 activated JAK2/STAT3/Snail pathway. Thus, this may offer a potential target for developing new HCC therapies.

[Variation of maternal milk adiponectin and its correlation with infant growth].

OBJECTIVE: To investigate the variation of human breast milk adiponectin (APN) concentration during lactation, analyze the relationship of APN concentrations in human breast milk with APN in infant serum, determine the association between maternal milk APN and infant body proportionality in the first year of life, and the period of greatest human milk exposure. METHOD: Subjects included 73 mother-infant pairs from Shanghai International Peace Maternity & Child Health Hospital. Maternal milk was collected at 2, 4, 13, 26 weeks and infant serum was collected at 26 weeks. The concentration of APN in maternal milk and infant serum were measured with commercially available ELISAs (R&D Systems). Weight-for-age Z-scores (WAZ), length-for-age Z-scores (LAZ), weight-for-length Z-scores (WLZ) and body mass index Z-scores (zBMI) of infants up to 1 year of age were calculated using World Health Organization (WHO) standards. Then the variation of maternal milk APN was investigated, the correlation between maternal milk APN and infant serum APN was analyzed; multivariate regression analysis was used to analyze covariates correlated with infant body proportionality, meanwhile determined the association between maternal milk APN and infant anthropometrics. RESULT: The concentration of APN in maternal milk at 2, 4, 13, 26 weeks was respectively (14.62 µg/L, 5.93 - 140.40 µg/L), (7.32 µg/L, 2.04 - 29.35 µg/L), (6.84 µg/L, 2.72 - 15.65 µg/L) and (4.88 µg/L, 1.12 - 13.38 µg/L). Higher milk APN in postpartum 2 weeks was associated with lower infant WAZ at 13, 26 and 52 weeks (P < 0.05). Milk APN in postpartum 4 weeks was inversely related to infant WAZ, WLZ, zBMI at 13, 26 and 52 weeks (all P < 0.05). Meanwhile, milk APN in postpartum 13 weeks had significantly negative correlation with infant WAZ, WLZ, zBMI at 13, 26 and 52 weeks (P < 0.01). Milk APN in postpartum 26 weeks also was inversely associated with infant WAZ, WLZ and zBMI at 52 weeks (P < 0.05). After adjusting covariates like birth weight using multivariate regression analysis, milk APN level is the most important influence factor to infant WAZ, WLZ, zBMI at 13, 26 and 52 weeks. There was a positive correlation between maternal milk APN and infant serum APN at 13, 26 weeks. CONCLUSION: Milk APN concentration declines throughout lactation. Maternal milk APN may play a vital role in the growth and development of breastfed infants, particularly closely associated with infant weight. Infant serum APN clearly correlated with maternal milk APN.

[Morphology of lymph vessels in human gastric carcinoma tissues and its association with cancer metastasis].

OBJECTIVE: To investigate the morphology of the lymph vessels in human gastric carcinoma tissues and the relationship to cancer metastasis. METHODS: Morphological changes of the lymph vessels and capillaries in 32 cases of gastric carcinoma tissues and adjacent tissue of the tumor. RESULTS: Numerous lymph vessels and capillaries were seen with opened lumen in the adjacent tissues of the tumor, and fasciculated lymph capillaries were most frequent in gastric carcinoma. The maximal lumen area, perimeter and diameter of lymph vessels and capillaries in gastric carcinoma and the adjacent tissues were significantly different between metastatic group and non-metastatic group (P<0.05). CONCLUSIONS: Dilation of lymph vessels and capillaries due to interstitial edema of the adjacent tissues of gastric carcinoma facilitates tumor metastasis, and lymph metastasis of carcinoma cells occurs through mature lymph capillaries in the adjacent tissues.