Objective To identify the expression of DLK1 protein in different types of renal cell carcinomas and its correlations with pathological characteristics and metastasis. Methods Immunohistochemistry analysis was performed to evaluate the expression of DLK1 protein in 94 cases of primary clear cell renal cell carcinoma, 76 cases of papillary renal cell carcinoma, 45 cases of chromophobe renal cell carcinoma, 71 cases of distal metastatic and 24 cases of lymph node metastatic clear cell renal cell carcinoma, as well as 18 cases of normal renal tissue. The correlations of DLK1 protein expression with pathological characteristics were analyzed. Results DLK1 protein was expressed in proximal and distal renal tubular epithelial cells in all the normal renal cases. In contrast, DLK1 protein expression was lower in different types of renal cell carcinoma. The low or negative expression of DLK1 protein in clear cell renal cell carcinoma, papillary renal cell carcinoma and chromophobe renal cell carcinoma was 33.0% (31/94), 27.6% (21/76) and 33.3% (15/45), respectively. Compared to normal renal tissue, DLK1 protein expression was significantly down-regulated in renal cell carcinomas (P＞0.05), whereas there was no significant difference on DLK1 protein expressions among the different types (P＞0.05) of renal cell carcinomas. DLK1 protein expression was not correlated with sex (60 male and 34 female cases), age (≥55, 50 cases and 55, 44 cases), grade (41 cases in grade I, 9 cases in grade II, 21 cases in grade III and 23 cases in grade Ⅳ respectively) and lymph node metastasis (76 cases with and 18 cases without lymph node metastasis) in clear cell renal cell carcinoma (P＞0.05). There was also no significant difference among primary, lymph node and distal metastatic lesions of clear cell carcinoma (P＞0.05). Conclusions DLK1 protein expression is commonly down-regulated in different types of renal cell carcinomas. Down-regulation of DLK1 protein expression is not associated with pathological characteristics and metastasis in clear cell renal cell carcinoma.

OBJECTIVETo evaluate associations between carbon constituents of fine particulate matter (PM2.5) and atherogenic index of plasma (AIP).

METHODSWe collected subjects from two communities by a system sampling, and 112 people aged over 60 years old without cardiovascular disease were recruited. The levels of cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) of objects, and personal exposure to PM2.5 were measured on December, 2011. Total carbon (TC), organic carbon (OC) and elemental carbon (EC) of PM2.5 were detected and AIP was calculated according to its definition.

RESULTSThe value of AIP among the 112 subjects was 0.05 ± 0.26. Personal exposure concentration of PM2.5 and its carbon components (TC,OC and EC) were (164.75 ± 110.67), (53.86 ± 29.65), (44.93 ± 26.37) and (9.49 ± 5.75) µg/m(3), respectively. The Pearson analysis showed the linear relationship between TC,OC,EC and AIP, all significant positive correlations. The correlation coefficients were TC (r = 0.307, P < 0.05),OC (r = 0.287, P < 0.05) and EC (r = 0.252, P < 0.05), respectively. The multiple logistic regression analysis showed that when the AIP risk categories were selected as dependent variable and low risk group as reference group, the regression coefficient of TC,OC and EC was separately 1.03 (95%CI:1.01-1.05), 1.03 (95%CI:1.01-1.05), 1.12 (95%CI:1.02-1.22) in the high risk group; while there was no statistical significance of the regression coefficient and OR in the middle risk group.

CONCLUSIONThere was stable associations between the carbon constituents (TC,OC and EC) of fine Particulate Matter (PM2.5) and AIP. The findings suggested that carbon components of PM2.5 should be considered as risk factors of atherogenic.

Aged ; Air Pollutants ; analysis ; Air Pollution ; adverse effects ; Atherosclerosis ; diagnosis ; epidemiology ; Carbon ; analysis ; Cholesterol ; blood ; Environmental Exposure ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Particle Size ; Particulate Matter ; analysis ; Risk Assessment ; Triglycerides ; blood

OBJECTIVETo screen out serum differential proteins between vinyl chloride monomer (VCM)-exposed workers and healthy controls by proteomics and analyze the functions of differential proteins, and to provide a basis for elucidating the pathogenesis of diseases caused by VCM exposure and searching for the protein biomarkers.

METHODSFasting venous blood was collected from 125 VCM-exposed workers and 40 healthy controls according to accumulated exposure doses. Proteins were precipitated by acetone precipitation. These proteins were identified by 2D-nano LC-ESI-TOF/MS and quantified by isobaric tags for relative and absolute quantitation. The functions of differential proteins were analyzed by gene ontology.

RESULTSA total of 596 proteins were identified, including 194 quantified proteins. There were 21 differential proteins according to the screening criteria (19 upregulated proteins and 2 downregulated proteins), including complement, apolipoprotein, and glycoprotein. The functions of these differential proteins were binding, enzyme regulator activity, catalytic activity, and transporter activity, and they were involved in the biological processes including immune system process and response to stimulus.

CONCLUSIONThe complement, apolipoprotein, and glycoprotein identified in the proteomics may be related to liver injury caused by VCM exposure, and they could be used as candidate protein biomarkers of diseases caused by VCM exposure.

Biomarkers ; blood ; Blood Proteins ; analysis ; Humans ; Liver ; injuries ; Occupational Exposure ; Proteins ; metabolism ; Proteomics ; Vinyl Chloride ; toxicity

BACKGROUND: Congenital heart disease (CHD) is one of the most common congenital malformations in humans. Inconsistent results emerged in the existed studies on associations between air pollution and congenital heart disease. The purpose of this study was to evaluate the association of gestational exposure to air pollutants with congenital heart disease, and to explore the critical exposure windows for congenital heart disease. METHODS: The nested case-control study collected birth records and the following health data in Tianjin Women and Children's Health Center, China. All of the cases of congenital heart disease from 2013 to 2015 were selected matching five healthy controls for each case. Inverse distance weighting was used to estimate individual exposure based on daily air pollution data. Furthermore, the conditional logistic regression with distributed lag non-linear model was performed to identify the association between gestational exposure to air pollution and congenital heart disease. RESULTS: A total of 8,748 mother-infant pairs were entered into the analysis, of which 1,458 infants suffered from congenital heart disease. For each 10 µg/m³ increase of gestational exposure to PM_2.5, the ORs (95% confidence interval, 95%CI) ranged from 1.008 (1.001-1.016) to 1.013 (1.001-1.024) during the 1^st-2^nd gestation weeks. Similar weak but increased risks of congenital heart disease were associated with O₃ exposure during the 1^st week and SO₂ exposure during 6^th-7^th weeks in the first trimester, while no significant findings for other air pollutants. CONCLUSIONS This study highlighted that gestational exposure to PM_2.5, O₃, and SO₂ had lag effects on congenital heart disease. Our results support potential benefits for pregnancy women to the mitigation of air pollution exposure in the early stage, especially when a critical exposure time window of air pollutants may precede heart development.
Infant ; Pregnancy ; Child ; Humans ; Female ; Air Pollutants/analysis* ; Case-Control Studies ; Prenatal Exposure Delayed Effects/epidemiology* ; Heart Defects, Congenital/etiology* ; China/epidemiology* ; Particulate Matter/adverse effects* ; Maternal Exposure/adverse effects*

ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10^-3 g·kg^-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg^-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β₁/drosophila mothers against decapentaplegic protein2/3（TGF-β₁/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β₁ proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.