Association between diabetes mellitus and lung cancer: Meta-analysis.

BACKGROUND: This study aimed to summarize the association between diabetes mellitus (DM) and the incidence of lung cancer using a meta-analysis of cohort studies. MATERIALS AND METHODS: We systematically searched PubMed, Embase and the Cochrane Library to identify potential cohort studies. Relative risk (RR) was used to calculate the association between DM and the risk of lung cancer. Subgroup analysis, sensitivity analysis and test for publication bias were performed. Twenty cohort studies were selected. RESULTS: The participants with DM showed little or no significant effect on the risk of lung cancer (RR: 1.10; 95% CI: 0.99-1.23; P = .087). DM was not associated with the risk of lung cancer in men (RR: 1.11; 95%CI: 0.92-1.35; P = .270), but a significant association was observed in women (RR: 1.18; 95%CI: 1.10-1.28; P < .001). Subgroup analysis suggested that smoker status was confounding variables that could bias the relationship between DM and the incidence of lung cancer. CONCLUSIONS: This meta-analysis suggests that DM has no significant impact on the incidence of lung cancer in men but has a harmful effect on women.

The expression of protease-activated receptors in esophageal carcinoma cells: the relationship between changes in gene expression and cell proliferation, apoptosis in vitro and growing ability in vivo.

BACKGROUND: Protease-activated receptors (PARs) are a family of four G protein-coupled receptors expressed widely in many types of cells. PAR1, 2, and 4 have been shown to play an important role in many of the physiological activities of cells and many types of cancer cells. Esophageal carcinoma has become the fourth most common clinically diagnosed cancer and one of the top three leading causes of cancer-related deaths in China. The functions and expression patterns of PAR1, 2, and 4 in esophageal carcinoma have not published previously. METHODS: Here, we systematically studied the expression of PAR1, 2, and 4 in clinical esophageal carcinoma patients and determined their role in esophageal carcinoma in vivo and in vitro through the overexpression or knockdown of PAR1, 2, and 4. RESULTS: We found that the expression of PAR1 and 2 expressed higher in esophageal carcinoma than in the paracarcinoma tissues on clinical patients. PAR1 and 2 enhanced cell proliferation both in vivo and in vitro and reduced apoptosis to strengthen cancer cell vitality in TE-1 cells. In contrast, the expression of PAR4 expressed decreased in esophageal carcinoma, and its expression induced apoptosis in vivo and vitro. CONCLUSION: In our previous studies and the present study, we noted that the expression of PAR1, 2, and 4 was almost absent in different stages of esophageal carcinoma. PAR1 and 2 might be potential molecular markers for esophageal carcinoma, and PAR4 might be an effective treatment target for esophageal carcinoma prevention and treatment.

High Incidence of Malaria Along the Sino-Burmese Border Is Associated With Polymorphisms of CR1, IL-1A, IL-4R, IL-4, NOS, and TNF, But Not With G6PD Deficiency.

Malaria is highly endemic in Yunnan Province, China, with the incidence of malaria being highest along the Sino-Burmese border. The aim of our study was to determine whether genetic polymorphisms are associated with the prevalence of malaria among Chinese residents of the Sino-Burmese border region. Fourteen otherwise healthy people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, 50 malaria patients, and 67 healthy control subjects were included in our cross-sectional study. We analyzed the frequency of the G3093T and T520C single-nucleotide polymorphisms (SNPs) of CR1. Logistic regression was used to calculate the prevalence odds ratio (POR) and 95% confidence interval (CI) of malaria for the T520C SNP of CR1 and SNPs of G6PD, IL-4, IL-4R, IL-1A, NOS, CD40LG, TNF, and LUC7L. The frequency of the 3093T/3093T genotype of CR1 in the malaria group (0.16) was significantly higher than that in the control group (0.045, P < 0.05), and significantly lower than that in the G6PD deficiency group (0.43, P < 0.01). The frequency of the 520T/520T genotype of CR1 was significantly higher in the malaria patients (0.78) than that in the control group (0.67, P < 0.05) and G6PD-deficiency group (0.36, P < 0.05). The T allele of the T520C variant of CR1 was significantly associated with the prevalence of malaria (POR: 1.460; 95% CI: 0.703-3.034). Polymorphisms of G6PD did not significantly influence the prevalence malaria (P > 0.05). A GTGTGTC haplotype consisting of IL-1A (rs17561), IL-4 (rs2243250), TNF (rs1800750), IL-4R (rs1805015), NOS (rs8078340), CD40LG (rs1126535), and LUC7L (rs1211375) was significantly associated with the prevalence of malaria (POR: 1.822, 95% CI: 0.998-3.324). The 3093G/3093G and 520T/520T genotypes are the predominant genetic variants of CR1 among Chinese residents near the Sino-Burmese border, and the T allele of T520C is associated with the prevalence of malaria in this region. Although G6PD deficiency does not protect against malaria, it may diminish the association between malaria and the CR1 polymorphisms in this population. The GTGTGTC haplotype is also associated with the prevalence of malaria in this region.

Protease-activated receptor (PAR)1, PAR2 and PAR4 expressions in esophageal squamous cell carcinoma.

Here, we used reverse transcription-PCR (RT-PCR) and western blot to detect protease-activated receptor (PAR) 1, PAR 2 and PAR 4 expression in cancer tissues and cell lines of esophageal squamous cell carcinoma, and investigated the co-relationship between PAR expression and clinic-pathological data for esophageal cancer. The methylation of PAR4 gene promoter involved in esophageal carcinoma was also analyzed. By comparing the mRNA expressions of normal esophageal tissue and human esophageal epithelial cells (HEEpiC), we found that among the 28 cases of esophageal squamous cell carcinoma, PAR1 (60%) and PAR2 (71%) were elevated in 17 and 20 cases, respectively, and PAR4 (68%) expression was lowered in 19 cases. Whereas, in human esophageal squamous cells (TE-1 and TE-10), PAR1 and PAR2 expression was increased but PAR4 was decreased. Combined with clinical data, the expression of PAR1 in poorly differentiated (P=0.016) and middle and lower parts of the esophagus (P=0.016) was higher; expression of PAR4 in poorly differentiated carcinoma was lower (P=0.049). Regarding TE-1 and TE-10 protein expression, we found that in randomized esophageal carcinoma, PAR1 (P=0.027) and PAR2 (P=0.039) expressions were increased, but lowered for PAR4 (P=0.0001). In HEEpiC, TE-1, TE-10, esophageal and normal esophagus tissue samples (case No. 7), the frequency of methylation at the 19 CpG loci of PAR4 was 35.4%, 95.2%, 83.8%, 62.6% and 48.2%, respectively. Our results indicate that the expression of PAR1 and PAR2 in esophageal squamous cell carcinoma is increased but PAR4 is decreased. Hypermethylation of the promoter of the PAR4 gene may contribute to reduced expression of PAR4 in esophageal squamous cell carcinoma.

Enzyme kinetics and molecular modeling studies of G6PD(Mahidol) associated with acute hemolytic anemia.

G6PD(Mahidol) enzyme is the most common variant in the Achang Chinese ethnic group and clinically manifests as class II. In this study, G6PD(Mahidol) enzyme was characterized by molecular modeling to understand its kinetics. G6PD(Mahidol), G6PD(G487A) and G6PD(WT) proteins were heterologously expressed in the G6PD-deficient DF213 E. coli strain, purified and their steady-state kinetic parameters were determined. Compared with G6PD(WT), the Km, and Vmax of NADP+ with G6PD(G487A) were about 28-fold and 12-fold lower, respectively. The Ki values of dehydroepiandrosterone (DHEA), NADPH and ATP with G6PD(G487A) showed 29.5-fold, 2.36-fold reduction and 1.83-fold increase, respectively. A molecular modeling of G6PD(G487A) was performed based on the X-ray structure of human G6PD (PDB: 2BH9). It is suggested that Ser-163 might affect the stability of G6PD(G487A) alpha-helix d and beta-strand E, besides the conformation of beta-strand D. In conclusion, the biochemical and structural properties of G6PD(G487A) and G6PD(WT) enzymes are significantly different, which may be responsible for clinical diversity of G6PD deficiencies.

[Changes of the immune cells, cytokines and growth hormone in teenager drug addicts].

AIM: To investigate the effect of heroin on the immune function, growth and development in the teenager heroin addicts by measuring their T-lymphocyte subsets, Th1/Th2 cytokines and serum growth hormone. METHODS: Tlymphocyte subsets of peripheral blood from the teenager heroin addicts were measured by direct microvolume whole blood immunofluorescent staining technique by flow cytometer (FCM). Thl / Th2 cytokines were measured by BD cytometric bead array and serum growth hormone was assayed using the chemiluminescence method in the 20 teenager heroin addicts and 23 healthy teenagers. RESULTS: The levels of CD3(+), CD3(+) + CD4(+), CD3(+) + CD4(+)/CD3(+)+ CD8(+), Th1 cytokines(IL-2, TNF-alpha and IFN-gamma) and Th2 cytokines(IL-4 and IL-10) reduced significantly in the teenager heroin addicts compared with the healthy control group (P < 0.01 or P < 0.05). The level of Th1 cytokines(IL-2 + TNF-alpha+IFN-gamma) decreased more than that of Th2 cytokines(IL-4 + IL-5 + IL-10)(P < 0.05). The level of serum growth hormone from the teenager heroin addicts was remarkably higher than that in control group (P<0.01). CONCLUSION: Heroin can inhibit the immunofunction especially the celluar immunity of the teenager heroin addicts. Besides, it can increase the level of serum growth hormone of the teenager heroin addicts.

Oil A induces apoptosis of pancreatic cancer cells via caspase activation, redistribution of cell cycle and GADD expression.

AIM: To explore the mechanisms of effects of oil A on apoptosis of human pancreatic cancer cells. METHODS: Cellular DNA content was analyzed by flow cytometry. Western blotting was used for caspase-3 and PARP, caspase-7, caspase-9, cytochrome c, Bcl-2, Bax, Mcl-1, cyclinA, cyclin B1, cyclin D1, cyclin E, CDK2, CDK4, CDK6, P21, P27, GADD45, GADD153. RESULTS: The caspase-3, caspase-7, and caspase-9 activities were significantly increased as well as the cleavage of caspase-3, downstream substrate poly-ADP ribose polymerase (PARP) was induced. The amount of cytochrome c in the cytosolic fraction was increased, while the amount of cytochrome c in the mitochondrial fraction was decreased after oil A treatment. The anti-apoptosis proteins Bcl-2 and Mcl-1 were decreased in parallel and Bax increased, indicating that Bcl-2 family proteins-mitochondria-caspase cascade was responsible for oil-induced apoptosis. The proportion of cells in the G0/G1 decreased in MiaPaCa-2 and AsPC-1 cells after the treatment of oil A for 24 hours. The number of cells in S phase was increased in two cancer cell lines at 24 hours. Therefore, cells were significantly accumulated in G2/M phase. The cells with a sub-G0/G1 DNA content, a hallmark of apoptosis, were seen at 24 hours both in MiaPaCa-2 and AsPC-1 cells following exposure to oil A. The expression of cyclin A and cyclin B1 was slightly decreased and cyclin D1 levels were markedly lowered in MiaPaCa-2 cells. The expression of cyclin A and cyclin B1 was markedly decreased and cyclin D1 levels were slightly lowered in AsPC-1 cells, while cyclin E was not affected and the levels of CDK2, CDK4, and CDK6 were unchanged in MiaPaCa-2 and AsPC-1 cells. In response to oil A, P21 expression was increased, but P27 expression was not affected. The expression of both GADD45 and GADD153 was increased in two cell lines following oil A treatment. CONCLUSION: Oil A induces apoptosis of pancreatic cancer cells via activating caspase cascade, modifying cell cycle progress and changing cell cycle-regulating proteins and GADD expression.