Tag SNPs in complement receptor-1 contribute to the susceptibility to non-small cell lung cancer.

BACKGROUND: Complement receptor 1 (CR1), the receptor for C3b/C4b complement peptides, plays a crucial role in carcinogenesis. However, the association of genetic variants of CR1 with susceptibility to lung cancer remains unexplored. METHODS: This case-control study included 470 non-small cell lung cancer (NSCLC) patients and 470 cancer-free controls. Based on the Chinese population data from HapMap database, we used Haploview 4.2 program to select candidate tag SNPs. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed by logistic regression to evaluate the association of each tag SNP with NSCLC. RESULTS: Multivariate regression analysis indicated that the rs7525160 CC genotype was associated with an increased risk of developing NSCLC (OR = 1.52, 95% CI = 1.02-2.28; P = 0.028) compared with the GG genotype. When stratified by smoking status, the risk of NSCLC was associated with the rs7525160 C allele carriers in smokers with OR (95% CI) of 1.72 (1.15-2.79), but not in non-smokers with OR (95% CI) of 1.15 (0.81-1.65). When the interaction between smoking status and rs7525160 G > C variant was analyzed with cumulative smoking dose (pack-year). Similarly, GC or CC genotype carriers have increased risk of NSCLC among heavy smokers (pack-year ≥ 25) with OR (95% CI) of 2.01 (1.26-3.20), but not among light smokers (pack-year <25) with OR (95% CI) of 1.32 (0.81-2.16). CONCLUSION: CR1 rs7525160 G > C polymorphism was associated with an increased risk of developing NSCLC in Chinese population. The association displays a manner of gene-environmental interaction between CR1 rs7525160 tagSNP and smoking status.

A regulatory variant in CYP2E1 affects the risk of lung squamous cell carcinoma.

Cytochrome P450 2E1 (CYP2E1), an ethanol-inducible enzyme, has been shown to metabolically activate various carcinogens, which is critical for the development of cancers. It has been demonstrated that CYP2E1 polymorphisms alter the transcriptional activity. However, studies on the association between CYP2E1 -1239G>C polymorphism and non-small cell lung cancer have reported conflicting results. Thus, the gain of the present study was to investigate whether CYP2E1 -1239G>C polymorphism is associated with the development of non-small cell lung cancer in Chinese population. A case-control study was conducted in which CYP2E1 -1239G>C polymorphism was analyzed in 526 Chinese patients with non-small cell lung cancer and 526 age-matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism. Odds ratios were estimated by multivariate logistic regression. A meta-analysis was conducted to evaluate the association of CYP2E1 -1239G>C polymorphism with the risk of lung cancer in Chinese population by calculating pooled odds ratio (OR). For CYP2E1 -1239G>C polymorphism, -1239C allele carriers (OR = 0.67; 95% confidence interval (CI) = 0.51-0.87; P = 0.002) were associated with a decreased risk of non-small cell lung cancer when compared with -1239GG homozygotes. In the group analyses by pathological types, for lung squamous cell carcinoma and other types, the ORs of the C allele carriers were 0.60 (95% CI = 0.41-0.88; P = 0.009) and 0.54 (95% CI = 0.30-0.99; P = 0.045). In the group analysis of smoking status, the OR for the -1239C allele-containing genotype was higher than that for -1239GG genotype (OR = 0.57; 95% CI = 0.40-0.81; P = 0.002) among smokers, but not among nonsmokers. Moreover, when the risk associated with CYP2E1 polymorphism was further evaluated within strata of <25 and ≥25 pack-years smoked, this effect between susceptible genotypes and smoking was mostly evident among light smokers (<25 pack-years) with OR of 0.42 (95% CI 0.23-0.79), but not among heavy smokers with OR of 0.87 (95% CI 0.53-1.43). In the group analyses by TNM stage, there was no significant difference between CYP2E1 -1239G>C polymorphism and the risk of non-small cell lung cancer. Meta-analysis data also showed that the carriers of CYP2E1 -1239C allele had a protect effect on the risk of lung cancer in Chinese with overall OR of 0.77 (95% CI 0.66-0.90). CYP2E1 -1239G>C polymorphism was associated with a decreased risk of development of non-small cell lung cancer in Chinese patients. The association displays a manner of gene-environment interaction between this polymorphism and smoking status.

[Association of CYP1A1 Ile462Val polymorphisms with susceptibility to small cell lung cancer].

OBJECTIVE: To investigate the association of Ile462Val polymorphisms of cytochrome P450 1A1 (CYP1A1) gene with small cell lung cancer susceptibility. METHODS: A case-control study was done in 275 patients with small cell lung cancer and 406 control subjects. Genotypes of CYP1A1 Ile462Val were determined by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Logistic regression analysis was performed to estimate odd ratios (ORs) and 95% confidence intervals (95% CI) associated with genetic variants of CYP1A1. RESULTS: A case-control analysis showed ORs of 0.65 (95% CI 0.48 - 0.91) and 0.60 (95% CI 0.32 - 0.97) for small cell lung cancer in the CYP1A1 462 Ile/Val and 462 Val/Val genotype carriers respectively, compared with 462 Ile/Ile carriers. When stratified by smoking status, the ORs of 462 Ile/Val or Val/Val genotype for nonsmokers and smokers were 0.99 (95% CI 0.62 - 1.51) and 0.42 (95% CI 0.26 - 0.65), respectively. Furthermore, for light and heavy smokers, the ORs of 462 Ile/ Val or Val/Val genotype were 0.42 (95% CI 0.21 - 0.85) and 0.44 (95% CI 0.24 - 0.82), respectively. CONCLUSION: CYP1A1 Ile462Val polymorphisms may contribute to the decreased susceptibility of small cell lung cancer.

Age of Bilingual Onset Shapes the Dynamics of Functional Connectivity and Laterality in the Resting-State.

Bilingualism is known to enhance cognitive function and flexibility of the brain. However, it is not clear how bilingual experience affects the time-varying functional network and whether these changes depend on the age of bilingual onset. This study intended to investigate the bilingual-related dynamic functional connectivity (dFC) based on the resting-state functional magnetic resonance images, including 23 early bilinguals (EBs), 30 late bilinguals (LBs), and 31 English monolinguals. The analysis identified two dFC states, and LBs showed more transitions between these states than monolinguals. Moreover, more frequent left-right switches were found in functional laterality in prefrontal, lateral temporal, lateral occipital, and inferior parietal cortices in EBs compared with LB and monolingual cohorts, and the laterality changes in the anterior superior temporal cortex were negatively correlated with L2 proficiency. These findings highlight how the age of L2 acquisition affects cortico-cortical dFC pattern and provide insight into the neural mechanisms of bilingualism.

Construction of Resource Ecological Compensation Mechanism Model under Rural Leisure Sports Environment.

In order to solve the problem of resource ecological compensation, this paper proposed a model of resource ecological compensation mechanism based on a rural leisure sports environment. The model is carried out in many places in China. The survey data involves 31 provinces, 10 years, and 43 indicators, with a total of 43 × 10 × 31 = 13,330 data. The preliminary basis of mechanism construction is summarized from four aspects. Finally, make full use of modern information technology to improve the network platform of the compensation mechanism, promote the efficient allocation and comprehensive utilization of ecotourism resources, and lay a solid foundation for establishing a reasonable and perfect resource ecological compensation mechanism and ensuring the long-term and stable operation of the mechanism. Through the experiment, it is found that the timely and effective publication of information can eliminate the inner estrangement between the two sides, so as to make the behavior of both sides more rational. A special information feedback department is established to deal with the opinions put forward by all compensation parties in tourism development, extract effective information, summarize and publish reasonable guidance information, and guide the compensation of both sides to an ideal balance through the feedback of this information. The effectiveness of the experiment is verified.

Neural Basis of the Emotional Conflict Processing in Major Depression: ERPs and Source Localization Analysis on the N450 and P300 Components.

Objects: Effective psychological function requires that cognition is not affected by task-irrelevant emotional stimuli in emotional conflict. Depression is mainly characterized as an emotional disorder. The object of this study is to reveal the behavioral and electrophysiological signature of emotional conflict processing in major depressive disorder (MDD) using event-related potentials (ERPs) and standardized low-resolution brain electromagnetic tomography (sLORETA) analysis. Method: We used a face-word Stroop task involving emotional faces while recording EEG (electroencephalography) in 20 patients with MDD and 20 healthy controls (HCs). And then ERPs were extracted and the corresponding brain sources were reconstructed using sLORETA. Results: Behaviorally, subjects with MDDs manifested significantly increased Stroop effect when examining the RT difference between happy incongruent trials and happy congruent trials, compared with HC subjects. ERP results exhibited that MDDs were characterized by the attenuated difference between P300 amplitude to sad congruent stimuli and sad incongruent stimuli, as electrophysiological evidence of impaired conflict processing in subjects with MDD. The sLORETA results showed that MDD patients had a higher current density in rostral anterior cingulate cortex (rostral ACC) within N450 time window in response to happy incongruent trials than happy congruent stimuli. Moreover, HC subjects had stronger activity in right inferior frontal gyrus (rIFG) region in response to incongruent stimuli than congruent stimuli, revealing successful inhibition of emotional distraction in HCs, which was absent in MDDs. Conclusion: Our results indicated that rostral ACC was implicated in the processing of negative emotional distraction in MDDs, as well as impaired inhibition of task-irrelevant emotional stimuli, relative to HCs. This work furnishes novel behavioral and neurophysiological evidence that are closely related to emotional conflict among MDD patients.

Emotion Regulating Attentional Control Abnormalities In Major Depressive Disorder: An Event-Related Potential Study.

Major depressive disorders (MDD) exhibit cognitive dysfunction with respect to attention. The deficiencies in cognitive control of emotional information are associated with MDD as compared to healthy controls (HC). However, the brain mechanism underlying emotion that influences the attentional control in MDD necessitates further research. The present study explores the emotion-regulated cognitive competence in MDD at a dynamic attentional stage. Event-Related Potentials (ERPs) were recorded from 35 clinical MDD outpatients and matched HCs by applying a modified affective priming dot-probe paradigm, which consisted of various emotional facial expression pairs. From a dynamic perspective, ERPs combined with sLORETA results showed significant differences among the groups. In compared to HC, 100 ms MDD group exhibited a greater interior-prefrontal N100, sensitive to negative-neutral faces. 200 ms MDD showed an activated parietal-occipital P200 linked to sad face, suggesting that the attentional control ability concentrated on sad mood-congruent cognition. 300 ms, a distinct P300 was observed at dorsolateral parietal cortex, representing a sustained attentional control. Our findings suggested that a negatively sad emotion influenced cognitive attentional control in MDD in the early and late attentional stages of cognition. P200 and P300 might be predictors of potential neurocognitive mechanism underlying the dysregulated attentional control of MDD.

Matrine promotes oligodendrocyte development in CNS autoimmunity through the PI3K/Akt signaling pathway.

AIMS: Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, has been recently found to be beneficial in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mainly through its anti-inflammatory effect. In the present study, we tested the effect of MAT on ongoing EAE and defined possible mechanisms underlying its effects on myelination and oligodendrocytes. MAIN METHODS: EAE was induced in C57BL/6 mice and MAT treatment was started at disease onset. Clinical scores were monitored daily; spinal cords and the corpus callosum brain region of mice were harvested on day 23 p.i. for inflammatory infiltration and demyelination of the central nervous system. Myelin content and the development of oligodendrocytes and their precursors were determined by immunostaining, and expression of p-Akt, p-mTOR, p-PI3K, and p-P70S6 was determined by Western blot. KEY FINDINGS: MAT effectively suppressed EAE severity and increased the expression of proteolipid protein, a myelin protein that is a marker of CNS myelin. MAT treatment largely increased the number of mature oligodendrocytes, and significantly activated the PI3K/Akt/mTOR signaling pathway, which is required for oligodendrocyte survival and axon myelination. SIGNIFICANCE: These findings demonstrate a beneficial effect of MAT on oligodendrocyte differentiation and myelination during EAE, most likely through activating the PI3K/Akt/mTOR signaling pathway.

XPF-673C>T polymorphism effect on the susceptibility to esophageal cancer in Chinese population.

PURPOSE: Xeroderma pigmentsum group F (XPF) plays a pivotal role in DNA nucleotide excision repair and has been linked to the development of various cancers. This study aims to assess the association of XPF genetic variants with the susceptibility to esophageal squamous cell carcinoma (ESCC) in Chinese population. METHODS: This two-stage case-control study was conducted in a total of 1524 patients with ESCC and 1524 controls. Genotype of XPF -673C>T and 11985A>G variants were determined by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Logistic regression analysis was performed to estimate odd ratios (ORs) and 95% confidence intervals (95% CI). RESULTS: Our case-control study showed that XPF -673TT genotype was associated with a decreased risk of ESCC compared with CC genotype in both case-control sets (Tangshan set: OR = 0.58; 95%CI = 0.34-0.99, P = 0.040; Beijing set: OR = 0.66; 95%CI = 0.46-0.95, P = 0.027). Stratified analyses revealed that a multiplicative interaction between -673C>T variant and age, sex or smoking status was evident (Gene-age: Pinteraction = 0.002; Gene-sex: Pinteraction = 0.002; Gene-smoking: Pinteraction = 0.002). For XPF 11985A>G polymorphism, there was no significant difference of genotype distribution between ESCC cases and controls. CONCLUSION: These findings indicated that genetic variants in XPF might contribute to the susceptibility to ESCC.

Functional genetic variants of TNFSF15 and their association with gastric adenocarcinoma: a case-control study.

The purpose of this study was to identify functional genetic variants in the promoter of tumor necrosis factor superfamily member 15 (TNFSF15) and evaluate their effects on the risk of developing gastric adenocarcinoma. Forty DNA samples from healthy volunteers were sequenced to identify single nucleotide polymorphisms (SNPs) in the TNFSF15 promoter. Two TNFSF15 SNPs (-358 T > C and -638 A > G) were identified by direct sequencing. Next, genotypes and haplotypes of 470 gastric adenocarcinoma patients and 470 cancer-free controls were analyzed. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Serologic tests for Helicobacter pylori infection were measured by enzyme-linked immuno-sorbent assay (ELISA). Subjects carrying the TNFSF15 -358 CC genotype were at an elevated risk for developing gastric adenocarcinoma, compared with those with the -358 TT genotype (OR 1.42, 95% CI, 1.10 to 2.03). H. pylori infection was a risk factor for developing gastric adenocarcinoma (OR 2.31, 95% CI, 1.76 to 3.04). In the H. pylori infected group, subjects with TNFSF15 -358 CC genotype were at higher risks for gastric adenocarcinoma compared with those carrying -358 TT genotype (OR: 2.01, 95%CI: 1.65 to 4.25), indicating that H. pylori infection further influenced gastric adenocarcinoma susceptibility. The -358 T>C polymorphism eliminates a nuclear factor Y (NF-Y) binding site and the -358 C containing haplotypes showed significantly decreased luciferase expression compared with -358 T containing haplotypes. Collectively these findings indicate that functional genetic variants in TNFSF15 may play a role in increasing susceptibility to gastric adenocarcinoma.

CYP1A1 Ile462Val polymorphism and the risk of non-small cell lung cancer in a Chinese population.

AIMS AND BACKGROUND: Cytochrome P450 (CYP) 1A1 enzyme plays an important role in the metabolism of carcinogens, such as polycyclic aromatic hydrocarbons, nitroaromatics and arylamines. METHODS: The study examined the association of CYP1A1 Ile462Val polymorphism with the risk of developing non-small cell lung cancer in a Chinese population. We conducted a case-control study including 526 non-small cell lung cancer cases and 526 cancer-free controls. The odds ratios and 95％ confidence intervals were calculated by logistic regression models. RESULTS: Compared with 462Ile/Ile genotype carriers, subjects with CYP1A1 462Ile/Val or Val/Val genotype had a decreased risk of developing non-small cell lung cancer with odds ratios of 0.57 (95% CI, 0.44-0.75) and 0.54 (95% CI, 0.36-0.81), respectively. When stratified by smoking status, the decreased risk of non-small cell lung cancer associated with CYP1A1 462Ile/Val or Val/Val genotype was observed among non-smokers (OR = 0.62, 95% CI, 0.45-0.87) and among smokers (OR = 0.54, 95% CI, 0.37-0.78). When stratified by smoking-dose, the correlation between CYP1A1 genotypes and the risk of non-small cell lung cancer was detected among light smokers (OR = 0.30, 95% CI, 0.19-0.48) but not among heavy smokers (OR = 0.93, 95% CI, 0.61-1.43). CONCLUSIONS: The CYP1A1 Ile462Val variant was associated with a low risk of developing non-small cell lung cancer in a Chinese population.