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Glutathione S-transferases (GSTs) are involved in the metabolism of carcinogens and anticancer drugs. Functional polymorphisms exist in at least three genes that code for the GSTs, such as the GSTM1 and GSTT1 gene deletions or the A-G transition within the GSTP1 gene, which represents distinct GSTP1a and GSTP1b alleles. In the present case-control study, we aimed at estimation of the relationship between the GSTM1, GSTT1, and GSTP1 genotypes and the susceptibility to various types of childhood malignancies and the early relapses of diseases.', 'Using the polymerase chain reaction on the DNA extracted from peripheral blood leukocytes, we identified the GSTM1, GSTT1, and GSTP1 genotypes in 234 children at the initial stage of a childhood malignancy as well as in 460 age-and sex-matched healthy subjects who served as controls. The follow-up period for the effects of the anticancer therapy ranged from 11 to 43 months.', 'Compared to the controls, a significant increase in the frequency of the GSTP1b/GSTP1b genotype (odds ratio (OR) 5.7; 95% confidence limit (CL) from 2.4 to 13.8; Pearsons Chi-square P = 0.0001) was detected in the children with neoplasms. The GSTM1 and GSTT1 genotypes did not show any correlation with the risk of the de novo diagnosed neoplasms. During the observation, 62 children (26%) were found to be present with a local or disseminated recurrence of the diseases. The analysis indicated a trend in increasing risk of relapse for carriers of the GSTP1a allele (OR = 3.29; 95% CL from 0.73 to 14.67 P = 0.03).
Is polymorphism within the glutathione S-transferase P1 gene associated with increased susceptibility to childhood malignant diseases?

Cyclovirobuxinum D (CVB-D), an alkaloid isolated from the Chinese medicinal plant Buxus microphylla, has been found to be effective to treat cardiac insufficiency, arrhythmias and coronary heart disease. In the present study, we investigated the effects of CVB-D on the inflammatory responses in lipopolysaccharide (LPS)-stimulated murine macrophages in vitro and the underlying mechanisms.', 'Murine macrophage cell line RAW264.7 cells were incubated in the presence of LPS (0.1 μg/mL) for 24 h. The cell viability was measured using MTT assay. The release of NO and cytokines were detected using the Griess test and ELISA, respectively. The mRNA and protein levels were determined using RT-PCR and Western blot, respectively. Reporter gene assays were used to analyze the transcriptional activity of NF-κB.', 'Treatment of RAW264.7 cells with CVB-D (25-300 μmol/L) did not affect the cell viability. Pretreatment with CVB-D (50, 100 and 200 μmol/L) concentration-dependently decreased NO release and iNOS expression in LPS-treated RAW264.7 cells (its IC50 value in inhibition of NO production was 144 μmol/L). CVB-D also concentration-dependently inhibited the secretion and mRNA expression of IL-1β and IL-6 in LPS-treated RAW264.7 cells. Furthermore, CVB-D remarkably inhibited the phosphorylation of STAT1 and STAT3, as well as JAK2 in LPS-treated RAW264.7 cells, but did not affect the activation of NF-κB and MAPKs pathways. Pretreatment with the JAK2 specific inhibitor AG490 (30 μmol/L) produced similar effects on NO release and iNOS expression in LPS-treated RAW264.7 cells.
Does cyclovirobuxinum D suppress lipopolysaccharide-induced inflammatory responses in murine macrophages in vitro by blocking JAK-STAT signaling pathway?

Patients with type 2 diabetes have an increased risk of atherosclerosis and vascular disease. Vitamin D deficiency is associated with vascular disease and is prevalent in diabetes patients. We undertook this study to determine the association between 25-hydroxyvitamin D (25[OH]D) levels and prevalence of peripheral arterial disease (PAD) in type 2 diabetes patients.', 'A total of 1028 type 2 diabetes patients were recruited at Nanjing Medical University Affiliated Nanjing Hospital from November 2011 to October 2013. PAD was defined as an ankle-brachial index (ABI)\xa0<\xa00.9. Cardiovascular risk factors (blood pressure, HbA1c, lipid profile), comorbidities, carotid intima-media thickness (IMT) and 25(OH)D were assessed.', 'Overall prevalence of PAD and of decreased 25(OH)D (<30\xa0ng/mL) were 20.1% (207/1028) and 54.6% (561/1028), respectively. PAD prevalence was higher in participants with decreased (23.9%) than in those with normal (15.6%) 25(OH)D (≥30\xa0ng/mL, p\xa0<0.01). Decreased 25(OH)D was associated with increased risk of PAD (odds ratio [OR], 1.69, 95% CI: 1.17-2.44, p\xa0<0.001) and PAD was significantly more likely to occur in participants ≥65\xa0years of age (OR, 2.56, 95% CI: 1.51 -4.48, vs. 1.21, 95% CI: 0.80-1.83, p-interaction\xa0=\xa00.027). After adjusting for known cardiovascular risk factors and potential confounding variables, the association of decreased 25(OH)D and PAD remained significant in patients <65\xa0years of age (OR, 1.55; 95% CI: 1.14-2.12, p\xa0=\xa00.006).

Does low 25-Hydroxyvitamin D Level be Associated with Peripheral Arterial Disease in Type 2 Diabetes Patients?