Adolescent ; Adult ; Dust ; Female ; Humans ; Male ; Mental Health ; statistics & numerical data ; Middle Aged ; Occupational Exposure ; Steel ; Surveys and Questionnaires

Objective: The expression of WNT5A is associated with aggressive tumor biology and poor clinical outcomes of various types of cancer. However, its function in the cell migration of small cell lung cancer (SCLC) should be elucidated. Methods:The expres-sion of WNT5A in SCLC and normal lung tissues was detected by immunohistochemisty. The correlation between the expression and clinical characteristics of WNT5A was analyzed. The function of WNT5A in regulating cell migration was studied in DMS153 cell line in vitro. Small interfering RNA (SiRNA) was used to knock down WNT5A. Wound healing and Transwell tests were used to determine the migration rate of DMS153. The phosphorylated JNK expression was detected by Western blot analysis. Results:The WNT5A expression was higher in SCLC tissues than that of normal lung tissues. WNT5A was correlated with clinical stages, lymph nodes, and distance me-tastasis in SCLC. The high expression of WNT5A was accompanied by abnormal levels of NSE and Pro-GRP. The WNT5A phosphoryla-tion of JNK promoted cell migration in vitro. Conclusion:The expression of WNT5A in SCLC is high and correlated with tumor metasta-sis. The influence of WNT5A/JNK on the cell migration property of DMS153 supports the concept that WNT5A can initiate the cell mi-gration of SCLC, which suggested that WNT5A may be a marker and can be potentially used as an effective therapeutic target for the SCLC metastasis.

This study is to investigate the effects of ubenimex on tumor cell invasion and apoptosis, dose relationship and mechanism. Immunofluorescence staining was performed to detect the expression of CD13 in HT-1080 cells. MTT assay was used to analyze the effect of ubenimex on cell proliferation. Annexin V-EGFP/PI was used to detect apoptotic cells by flow cytometry. Cell cycle was analyzed using flow cytometry. Ala-pNA was used as substrate to evaluate the effect of ubenimex on the aminopeptidase activity. Transwell assay was used to analyze the effect of ubenimex on cell invasion and migration ability. Western blotting was used to detect the expression level of CD13. MMP activity was analyzed using gelatin zymography. The results showed that ubenimex at high concentration inhibited the proliferation of HT-1080 cells (IC50: 3.8 mg x mL(-1)), and induced cell apoptosis. Cell cycle was blocked at G1 phase. Ubenimex at low concentration inhibited the aminopeptidase activity of HT-1080 cells (IC50: 8.3 microg x mL(-1)) and inhibited cell invasion, but it had no effects on the cell migration and proliferation. Ubenimex had no effects on CD13 expression and MMP activity. In conclusion, ubenimex at low concentration can inhibit the invasion ability of tumor cells by directly inhibiting the aminopeptidase activity; ubenimex at high concentration can inhibit the proliferation of tumor cells and induce cell apoptosis by a CD13-independent pathway.
Antibiotics, Antineoplastic ; pharmacology ; Apoptosis ; drug effects ; CD13 Antigens ; metabolism ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Fibrosarcoma ; metabolism ; pathology ; Humans ; Leucine ; analogs & derivatives ; pharmacology ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Neoplasm Invasiveness

Ventricular fibroblasts were cultured using conditioned growth medium for ventricular fibroblasts (FCGM). The rate of the total collagen synthesis of ventricular fibroblasts was measured by assaying the incorporation rate of ［3H］-proline, whereas the proliferation of ventricular fibroblasts was assessed by determining the incorporation rate of ［3H］-TdR and the expression of c-fos genes. FCGM significantly increased the ［3H］-proline incorporation rate and ［3H］-TdR incorporation rate of fibroblasts in a dose-dependent manner. Furthermore, FCGM promoted the c-fos gene expression of fibroblasts, which attained its maximum in 1 h. BQ123, an ETA receptor antagonist, partially blocked the above effects of FCGM, but AT1 receptor antagonist CV11974 and α-adrenergic receptor antagoist regitin did not. It is suggested that the ventricular fibroblast has an autorine function in promotion of collagen synthesis and proliferation of fibroblasts by secreting endothelin and other bioactive substances.

Using cell culture, radioimmunoassay for endothelin and RT-PCR, the effect of aldosterone on the endothelin secretion of ventricular fibroblasts was studied. The results showed that aldosterone (1×10－7 mol/L) promoted the expression of ppET-1 mRNA, which began to increase in 2 hours and attained the highest level in 4 hours, thereafter decreased; aldosterone increased the endothelin level in ventricular fibroblasts and fibroblast conditioned growth medium (FCGM) as well, which was blocked by spironolactone (1×10－6 mol/L), an aldosterone receptor antagonist. The results suggest that aldosterone can increase endothelin secretion by ventricular fibroblasts, which can be inhibited by its receptor antagonist spironolactone.

The aim of this study was to examine the effects of L-arginine, a nitric oxide (NO) precursor, on protein expression of endothelial nitric oxide (eNOS), nitrite/nitrate content, protein expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) and the activity of mitogen-activated protein kinase (MAPK) in cardiac tissues in renovascular hypertensive rats (RHR). The Goldblatt renovascular hypertensive model was established by two-kidney one clip method. The rats were divided into four groups, respectively treated with 50, 150 and 450 mg/kg L-arginine and 150 mg/kg L-arginine plus 10 mg/kg L-NAME (an eNOS inhibitor) (ip). Another group did not receive specific treatment from the 5th week after renal artery constriction. Control group was sham-operated. Mean arterial blood pressure (MABP) and the ratio of left ventricular weight to body weight (LVW/BW) were measured 8 weeks after treatment. eNOS protein expression, nitrite/nitrate content, MKP-1 protein expression and MAPK activity in cardiac tissues were detected using Western blot analysis, enzyme-reduction method and substrate in-gel kinase assay, respectively. It was found that L-arginine significantly inhibited the increase of MABP and LVW/BW, attenuated the activity of MAPK, increased protein expression of eNOS and MKP-1 and potentiated production of NO in cardiac tissue with the most effective dosage of 150 mg/kg, and these effects of L-arginine could be inhibited by L-NAME. These results suggest that MKP-1 may play an important role in the NO-induced inhibition of myocardial hypertrophy. The anti-hypertrophic effects of L-arginine may involve increase of eNOS protein expression and NO production, poten- tiation of MKP-1 protein expression, and inhibition of MAPK activity in the cardiac tissue of RHR.

BACKGROUNDThe role of chronic hyperglycaemia as a coronary artery disease (CAD) risk factor is well-known, and the glycemic variability is still a matter of debate. The aim of this study was to investigate the association of admission glycemic excursion and hemoglobin A(1c) (HbA(1c)) with the presence and severity of CAD in patients with undiagnosed diabetes mellitus (DM).

METHODSWe studied 286 newly diagnosed DM patients without prior revascularization undergoing coronary angiography for suspected ischaemic chest pain. Patients were grouped into those with CAD and without CAD according to angiographic results. The severity of CAD was assessed using the Gensini score. Glycemic variability, indicated as the mean amplitude of glycemic excursions (MAGE), was determined by a continuous glucose monitoring system. Serum levels of HbA(1c) and high-sensitive C-reactive protein (hs-CRP) as well as plasma concentrations of fasting glucose, lipids and creatinine were measured in all patients. Predictors of CAD were determined using multivariate Logistic regression model and receiver-operating characteristic (ROC) curves.

RESULTSThe newly diagnosed DM patients with CAD were older, and more were male and current cigarette smokers compared with the patients without CAD. The CAD group had significantly higher levels of MAGE and HbA(1c). Individuals with high levels of HbA(1c) (≥ 7%) or MAGE (≥ 3.4 mmol/L) had also significantly higher CAD prevalence. Logistic regression analysis revealed that high MAGE level and high HbA(1c) level were independent predictors for CAD. The area under the receiver-operating characteristic curve for MAGE (0.606, P = 0.005) was superior to that for HbA(1c) (0.582, P = 0.028). Gensini score closely correlated with age, MAGE, HbA(1c), hs-CRP, creatinine and total cholesterol. Multivariate analysis indicated that age (P < 0.001), MAGE (P < 0.001), HbA(1c) (P = 0.022) and hs-CRP (P = 0.005) were independent determinants for Gensini score.

CONCLUSIONSBoth admission glycemic excursion and chronic hyperglycaemia are associated with the severity of CAD in newly diagnosed DM patients. MAGE displays a significant value in predicting CAD in patients with undiagnosed diabetes even more than HbA(1c).

Aged ; Blood Glucose ; metabolism ; Coronary Angiography ; Coronary Artery Disease ; blood ; diagnostic imaging ; etiology ; metabolism ; Diabetes Mellitus ; blood ; diagnostic imaging ; metabolism ; physiopathology ; Female ; Glycated Hemoglobin A ; metabolism ; Humans ; Logistic Models ; Male ; Middle Aged ; Risk Factors

ObjectiveTo study the epidemiological characteristics of diabetes mellitus and awareness rate in Zhejiang adults.MethodA total of 17 437 adults from 15 counties were randomly selected with stratified multi-stage cluster sampling method from July to November,2010.Each participant was required to complete a set of standardized questionnaire,physical examination,and blood specimen collection.ResultsThe overall standardized rate of diabetes mellitus was 5.94％ ( crude prevalence 8.80％ ).It was increased by 96.67％ during past 8 years,as compared with the prevalence 3.02％ in 2002.The standardized rate of diabetes mellitus of the urban and rural area were 7.52％ and 5.19％ ( crude prevalence 11.33％ and 7.09％ ),respectively.The standardized rate of diabetes mellitus in the urban was higher than rural ( u =6.58,P＜0.05 ).The standardized rate of diabetes mellitus of the male and the female were 5.74％ and 6.15％ ( crude prevalence 8.36％ and 9.13％ ),respectively,without significant difference ( u =1.39,P＞0.05 ).The awareness rate of diabetes mellitus was 59.19％ ( 56.66％ in male and 61.23 ％ in female,x2 =3.26,P＞0.05 ).The awareness rate of the urban was higher than the rural (63.47％ vs 54.69％,x2=12.20,P＜0.01 ).ConclusionThe prevalence of diabetes mellitus showed a rapidly rising trend in Zhejiang province.The effective intervention should be taken at its early stage.

Objective To access the prevalence of type 2 diabetes mellitus ( T2DM) and its associated risk factors among adults with obesity in Zhejiang province. Methods The enrolled subjects were selected among local residents aged≥18 years with body mass index≥28 kg/m2 from 15 counties by multi stage stratified cluster random sampling from July to November, 2010. Each participant was required to attend complete questionnaire, physical examination, and testing overnight fasting blood specimen. Results A total of 1 351 residents were enrolled, including 613 males and 738 females. The prevalence of T2DM in adult population with obesity was 15. 03%, being 14. 03% in male, and 15. 85% in female;and that in urban area was 16. 64%, and in rural area was 13. 93%. Data from multivariable logistic regression showed that factors such as ageing (OR=1. 473, 95% CI 1. 243-1. 747), a family history of T2DM(OR=8. 945, 95% CI 5. 481-14. 598), staple food intake (OR=1. 185, 95% CI 1. 017-1. 380), triglyceride(≥1. 7 mmol/L, OR=1. 542, 95%CI 1. 066-2. 232) were risk factors of T2DM;while annual income(OR=0. 695, 95%CI 0. 544-0. 888), and milk intake(OR=0. 750, 95%CI 0. 567-0. 993) were shown as protective factors. Conclusion The prevalence of T2DM in adults with obesity was raised, ageing, a family history of T2DM, staple food intake, and dyslipidemia appeared to be major risk factors for T2DM.

OBJECTIVETo investigate the chemical constituents from the tuber of the planted Cremastra appendiculata.

METHODThe compounds were isolated by column chromatography over silica gel, Sephadex LH-20 and RP-HPLC, and their structures were elucidated on the basis of spectroscopic analysis.

RESULTEight compounds were isolated, and identified as cirrhopetalanthrin (I), 7-hydroxy-4-methoxyphenanthrene-2-O-beta-D-glucoside (II), 4-(2-hydroxyethyl)-2-methoxyphenyl-1-O-beta-D-glucopyranoside (III), tyrosol 8-O-beta-D-gluco-pyranoside (IV), vanilloloside (V), p-hydroxybenzaldehyde (VI), sucrose (VII), adenosine (VIII).

CONCLUSIONThese compounds are isolated from this plant for the first time. All compounds were evaluated against human colon cancer (HCT-8), human hepatoma (Bel7402), human stomach cancer(BGC-823), human lung adenocarcinoma (A549), human breast cancer (MCF-7), and human ovarian cancer (A2780) cell lines, and cirrhopetalanthrin (I) showed non-selective moderate cytotoxicity with IC50 values of 8.4-13.3 micromol x L(-1), and other compounds were inactive.

Adenosine ; chemistry ; isolation & purification ; pharmacology ; Antineoplastic Agents, Phytogenic ; chemistry ; isolation & purification ; pharmacology ; Benzaldehydes ; chemistry ; isolation & purification ; pharmacology ; Cell Line, Tumor ; drug effects ; Humans ; Inhibitory Concentration 50 ; Orchidaceae ; chemistry ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Sucrose ; chemistry ; isolation & purification ; pharmacology