Investigation of the Relationship between CMYC Gene Polymorphisms and Glioma Susceptibility in Chinese Children.

Glioma is a common central nervous system tumors in children. CMYC has a range of functions that are disrupted in various tumor cells, and may contribute to the occurrence and development of glioma. Two CMYC single nucleotide polymorphisms (rs4645943C>T and rs2070583 A>G) were genotyped in 190 cases and 248 controls from Wenzhou and Guangzhou hospitals. After adjusting for age and sex, odds ratio and 95% confidence interval values were calculated by logistic regression to evaluate the correlation between CMYC gene polymorphisms and glioma risk; no significant associations were detected. These results require future validation in a larger sample cohort.

Association Between LIN28A Gene Polymorphisms and Glioma Susceptibility in Chinese Children.

Gliomas are the most prevalent brain tumors among children and adolescents. The occurrence and development of various malignant tumors is closely related with LIN28A gene, but its relationship with glioma susceptibility has not been widely discovered. In this case-control study, we conducted four single nucleotide polymorphisms (SNPs) (rs3811464 G>A, rs3811463 T>C, rs34787247 G>A, and rs11247957 G>A) of LIN28A gene to investigate whether they increase the risk of glioma. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate their relationship. There was no significant correlation between four SNPs and glioma risk in single polymorphism and conjoint analysis. However, in stratification analysis, we found that rs3811463 TC/CC may add to the risk of glioma with clinical stage III (adjusted OR = 3.16, 95% CI = 1.15-8.70, P = .026) or stage III+IV patients (adjusted OR = 2.05, 95% CI = 1.02-4.13, P = .044). Our research suggested that four SNPs of LIN28A gene have a weak relationship with the risk of glioma in Chinese children. LIN28A rs3811463 TC/CC may increase the possibility of glioma in clinical stage III or stage III+IV patients which need larger samples and further confirmation.

MYCN gene polymorphisms and Wilms tumor susceptibility in Chinese children.

BACKGROUND: Wilms tumor, derived from embryonic cells, accounts for a large proportion of pediatric renal tumors. MYCN encoded by MYCN proto-oncogene, a member of the MYC family, is a BHLH transcription factor. It plays a critical role in tumorigenesis and predicts poor clinical outcomes in various types of cancer. However, the role of MYCN remained unclarified in Wilms tumor. In this study, we investigated the association between MYCN gene polymorphisms and Wilms tumor susceptibility. METHODS: Four MYCN gene polymorphisms (rs57961569 G > A, rs9653226 T > C, rs13034994 A > G, and rs60226897 G > A) were genotyped in 183 cases and 603 controls. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated to evaluate the association between MYCN gene polymorphisms and Wilms tumor susceptibility. RESULTS: Overall, no significant association was found for any of the four MYCN gene polymorphisms. Interestingly, in the stratification analysis, the rs57961569 was found to be associated with decreased Wilms tumor susceptibility in the children older than 18 months (AOR = 0.65, 95% CI = 0.42-1.00, P = .050). Moreover, older children carrying 2-4 risk genotypes were at increased risk of Wilms tumor (OR = 1.55, 95% CI = 1.001-2.40, P = .0497). Haplotype GCAA was shown to significantly increased Wilms tumor risk (AOR = 2.40, 95% CI = 1.12-5.14, P = .024). CONCLUSION: Our study demonstrated that these MYCN gene polymorphisms might be low penetrant variants in Wilms tumor.

NCDN is a Potential Biomarker and Therapeutic Target for Glioblastoma.

Background: Glioblastoma (GBM) is a type of central nervous system malignancy. In our study, we determined the effect of NCDN in GBM patients through The Cancer Genome Atlas (TCGA) data analysis, and studied the effects of NCDN on GBM cell function to estimate its potential as a therapeutic target. Methods: Gene expression profiles of glioblastoma cohort were acquired from TCGA database and analyzed to look for central genes that may serve as GBM therapeutic targets. Then the cell function of NCDN in glioblastoma cell was explored through in vitro cell experiments. Results: Through gene ontology (GO) analysis, weighted gene co-expression network analysis (WGCNA), and survival analysis, we identified three key genes (NCDN, PAK1 and SPRYD3) associated with poor prognosis in glioblastoma. In vitro experiments showed impaired cell migration, apoptosis, and cell cycle arrest in NCDN knockdown cells. Conclusion: NCDN affects the progress and prognosis of glioblastoma by promoting cell migration and inhibiting apoptosis.

Genetic variants in XPD gene and glioma susceptibility in Chinese children: A multicenter case-control study.

Background: Glioma is one of the central nervous system (CNS) tumors in children, accounting for 80% of malignant brain tumors. Nucleotide excision repair (NER) is a vital pathway during DNA damage repair progression. Xeroderma pigmentosum group D (XPD) or excision repair cross-complementing group 2 (ERCC2) is a critical factor in the NER pathway, playing an indispensable role in the DNA repair process. Therefore, the genetic variants in XPD may be associated with carcinogenesis induced by defects in DNA repair. Methods: We are the first to conduct a multi-center case-control study to investigate the correlation between XPD gene polymorphisms and pediatric glioma risk. We chose three single nucleotide polymorphisms and genotyped them using the TaqMan assay. Results: Although there is no significant association of these genetic variations with glioma susceptibility, the stratified analysis revealed that in the subtype of astrocytic tumors, the rs13181 TG/GG genotype enhanced glioma risk than the TT genotype, and carriers with two to three genotypes also elevated the tumor risk than 0-1 genotypes. Conclusion: In conclusion, our findings provided an insight into the impact of XPD genetic variants on glioma risk.

CASC15 Gene Polymorphisms and Glioma Susceptibility in Chinese Children.

OBJECTIVE: Gliomas are the most common tumors in the central nervous system. The cancer susceptibility candidate 15 (CASC15) gene has been reported to be a susceptibility gene for several types of cancer. No studies have been carried out on the predisposing effect of CASC15 gene single nucleotide polymorphisms (SNPs) on glioma risk. METHODS: In order to determine whether CASC15 gene SNPs are involved in glioma susceptibility, the first association study in a relatively large sample, which consisted of 171 patients and 228 healthy controls recruited from China, was performed. The contribution of SNPs (rs6939340 A>G, rs4712653 T>C and rs9295536 C>A) to the risk of glioma was evaluated by multinomial logistic regression, based on the calculation of the odds ratio (OR) and 95% confidence interval (CI). RESULTS: In the single locus and combined analysis, it was revealed that the genetic risk score had no significant associations between CASC15 gene SNPs and glioma risk. However, in the stratified analysis, a significant decrease in risk of glioma was observed in subjects of <60 months old with the rs4712653 TT genotype, when compared to those with the CC/CT genotype (OR=0.12, 95% CI=0.02-0.91, P=0.041). CONCLUSION: The present study provides referential evidence on the association between the genetic predisposition of the CASC15 gene and glioma risk in Chinese children. However, more well-designed case-control studies and functional experiments are needed to further explore the role of CASC15 gene SNPs.

KRAS gene polymorphisms are associated with the risk of glioma: a two-center case-control study.

BACKGROUND: Glioma, also known as neuroglioma, is the most common primary tumors of the central nervous system. Many previous studies have reported associations between RAS gene polymorphisms and multiple tumors. However, the role of RAS gene polymorphisms on glioma risk has not been investigated. METHODS: We conducted a two-center case-control study to investigate whether the RAS gene polymorphisms predispose individuals to gliomas in 248 healthy controls and 191 glioma patients. RAS gene polymorphisms (rs12587 G>T, rs7973450 A>G, rs7312175 G>A in KRAS, rs2273267 A>T in NRAS) were genotyped by the TaqMan assay. The relationship between RAS gene functional single nucleotide polymorphisms (SNPs) and the risk of glioma was evaluated based on odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Individuals with KRAS rs7312175 GA genotype were more likely to develop glioma than those with GG genotype (adjusted OR =1.66, 95% CI: 1.05-2.64, P=0.030). However, the other three SNPs could not affect glioma risk. In stratified analysis of age, gender, subtypes, and clinical stages, rs7312175 GA carriers were more likely to develop glioma in the following subgroups: children less than 60 months, tumor derived from the astrocytic tumors, and clinical stages I. CONCLUSIONS: The study showed that polymorphism rs7312175 GA in the KRAS gene was associated with increased glioma susceptibility. Further investigation is warranted to confirm these findings and to better elucidate the involved biological pathways.

Association of HMGA2 Polymorphisms with Glioma Susceptibility in Chinese Children.

BACKGROUND: Glioma is a malignant central nervous system tumor in children, with poor outcomes and prognosis. HMGA2 is a proto-oncogene with increased expression in various malignancies. METHODS: We explored the association of HMGA2 polymorphisms with glioma susceptibility in Chinese children using a case-control study (191 cases, 248 controls). HMGA2 single nucleotide polymorphisms (rs6581658 A>G; rs8756 A>C; rs968697 T>C) were genotyped using PCR-based TaqMan. RESULTS: Increased glioma susceptibility was associated with rs6581658 A>G; AG (adjusted odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.13-2.58, P = 0.010) or GG (adjusted OR = 3.12, 95% CI = 1.26-7.74, P = 0.014) genotype carriers had significantly raised glioma risk compared with AA genotype carriers. The rs6581658 AG/GG (adjusted OR = 1.85, 95% CI = 1.25-2.73, P = 0.002) and AA/GG (adjusted OR = 2.58, 95% CI = 1.05-6.33, P = 0.038) genotypes were associated with an increased risk of glioma relative to the AA genotype. Subjects with 2-3 risk genotypes had a significantly elevated risk (adjusted OR = 1.93, 95% CI = 1.31-2.84, P = 0.001) relative to those with 0-1 risk genotype. CONCLUSION: HMGA2 rs6581658 A>G is associated with glioma susceptibility in Chinese children.

Efficient removal of acetochlor pesticide from water using magnetic activated carbon: Adsorption performance, mechanism, and regeneration exploration.

In this study, MnFe2O4 supported activated carbon magnetic adsorbent (MnFe2O4@AC) was successfully prepared by a simple one-pot solvothermal method and used for the adsorption and removal of acetochlor from aqueous media. Results showed that MnFe2O4@AC with a MnFe2O4/AC mass ratio of 1:2 was characterized by good magnetism and high acetochlor adsorption capacity over a wide ranging pH, ionic strength, and humic acid concentration in an aqueous solution. Acetochlor was adsorbed on MnFe2O4@AC mainly by hydrogen bonding, π-π interactions, and pore-filling via film, intraparticle, and pore diffusion steps. Adsorption reaction generally approached an equilibrium after 10 h, with the adsorption capacity being ca. 226 mg g-1 for 0.2 g L-1 adsorbent at 25 °C. Adsorbate (acetochlor) degradation and adsorbent regeneration were simultaneously achieved through heat-activated peroxymonosulfate (PMS) oxidation catalyzed by MnFe2O4 on the AC surface with >90% degradation efficiency at ≥9.6 mM PMS concentration at 70 °C within 12 h. However, the adsorption capacity of the regenerated adsorbent decreased by 50% of its original capacity. This needs to be addressed in future studies. MnFe2O4@AC adsorbent has the advantages of high adsorption capacity, good magnetism, and catalyzation, which are promising for adsorption, separation, and degradation for the effective removal and treatment of acetochlor as well as other organic contaminants in different types of waters.

Associations between LMO1 gene polymorphisms and central nervous system tumor susceptibility.

IMPORTANCE: LIM domain only 1 (LMO1) gene polymorphisms were previously found to be implicated in the risk of several cancers. No available studies were performed regarding the predisposing effect of LMO1 gene single nucleotide polymorphisms (SNPs) on central nervous system (CNS) tumor risk. OBJECTIVE: We aimed to determine whether the LMO1 gene SNPs were associated with the risk of CNS tumor by applying a case-control study with 191 cases and 248 controls in China. METHODS: The contributions of LMO1 gene SNPs to the risk of CNS tumor was evaluated by multinomial logistic regression. RESULTS: Based on the calculations of odds ratio (OR) and 95% confidence interval (CI), we failed to detect a significant relationship between each LMO1 gene SNP (rs110419 A>G, rs4758051 G>A, rs10840002 A>G, rs204938 A>G, and rs2168101 G>T) and CNS tumor risk, respectively. A negative association was also found in the combined effects on these five SNPs and CNS tumor risk. The stratification analysis further demonstrated the individuals with rs204938 AG/GG genotype confer to increased risk of CNS tumor compared with those with an AA genotype in males (OR: 1.74, 95% CI: 1.01-2.98, P = 0.046). INTERPRETATION: We concluded that LMO1 gene SNPs may not strong enough to influence the risk of CNS tumor in Chinese children. More studies are required to verify this association.

AURKA gene polymorphisms and central nervous system tumor susceptibility in Chinese children.

INTRODUCTION: Central nervous system (CNS) tumors comprise 15-20% of all malignancies occurring in childhood and adolescence. Previous researches have shown that overexpression and amplification of the AURKA gene could induce multiple human malignancies, with which the connection of CNS tumor susceptibility has not been extensively studied. MATERIAL AND METHODS: In this study, we assessed whether and to what extent AURKA gene single nucleotide polymorphisms (SNPs) (rs1047972 C > T, rs2273535 T > A, rs8173 G > C) were associated with CNS tumor susceptibility, based on a case-control analysis in 191 CNS tumor patients and 248 controls. We determined this correlation using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: AURKA gene rs8173 G > C exhibited a crucial function to CNS tumor susceptibility fall-off (GC/CC vs. GG: adjusted OR = 0.68, 95% CI = 0.46-0.998, P = 0.049). In addition, the combined effect of lowering the risk of developing CNS tumors was more pronounced in carriers with 3 protective genotypes than others (adjusted OR = 0.55, 95% CI = 0.31-0.98, P = 0.044). Further stratification analysis illustrated that the existence of rs8173 GC/CC and three protective genotypes lowered CNS tumor risk in some subgroups. CONCLUSIONS: Our research suggested that the AURKA gene rs8173 G > C could significantly reduce CNS tumor susceptibility in Chinese children. More functional experiments are needed to explore the role of the AURKA gene rs8173 G > C.

Neferine Protects against Hypoxic-Ischemic Brain Damage in Neonatal Rats by Suppressing NLRP3-Mediated Inflammasome Activation.

Hypoxic-ischemic encephalopathy (HIE) is recognized as the main cause of neonatal death, and efficient treatment strategies remain limited. Given the prevalence of HIE and the associated fatality, further studies on its pathogenesis are warranted. Oxidative stress and neuroinflammatory injury are two important factors leading to brain tissue injury and nerve cell loss in HIE. Neferine, an alkaloid extracted from lotus seed embryo, exerts considerable effects against several diseases such as cancers and myocardial injury. In this study, we demonstrated the neuroprotective effect of neferine on HIE and hypothesized that it involves the inhibition of neuronal pyroptosis, thereby ameliorating neurological inflammation and oxidative stress. We demonstrated that the mRNA levels of proteins associated with pyroptosis including caspase-1, the caspase adaptor ASC, gasdermin D, interleukin- (IL-) 18, IL-1ß, and some inflammatory factors were significantly increased in neonatal HIBD model rats compared to those in the control group. The increase in these factors was significantly suppressed by treatment with neferine. We stimulated PC12 cells with CoCl2 to induce neuronal HIBD in vitro and investigated the relationship between neferine and pyroptosis by altering the expression of the NLRP3 inflammasome. The overexpression of NLRP3 partially reversed the neuroprotective effect of neferine on HIBD, whereas NLRP3 knockdown further inhibited caspase-1 activation and IL-1ß and IL18 expression. In addition, simultaneous alteration of NLRP3 expression induced changes in intracellular oxidative stress levels after HIBD. These findings indicate that neferine ameliorates neuroinflammation and oxidative stress injury by inhibiting pyroptosis after HIBD. Our study provides valuable information for future studies on neferine with respect to neuroinflammation and pyroptosis.

A mixed thermal elastohydrodynamic lubrication model of rotary lip seal.

Rotary lip seal is used in various applications where the rotation shaft needs to be sealed, such as hydraulic pumps, fuel pumps, camshafts, crankshafts, and so on. Many thermal elastohydrodynamic lubrication models of rotary lip seal have been introduced, and most of these models neglect the asperity contact. This article proposes a mixed thermal elastohydrodynamic lubrication model of rotary lip seal, in which the microstructure of sealing lip surface, influence of temperature on fluid viscosity, and deformation of lip surface, as well as the asperity contact, are taken into consideration. Simulation study is carried out, and the results show that the asperity contact should not be neglected for analyzing the sealing performance of the rotary lip seal. The influence of speed on the sealing performance is also analyzed based on the proposed model.

The association of RAN and RANBP2 gene polymerphisms with Wilms tumor risk in Chinese children.

Wilms tumor is considered to be the most common renal malignancy among children. RAN, a member of RAS superfamily, and its binding partner RANBP2 are related to the progression of multiple tumors. Nevertheless, the effects of the RAN and RANBP2 gene polymorphisms on the tumorigenesis of Wilms tumor remain unclarified. In this study, three potentially functional polymorphisms (rs56109543 C>T, rs7132224 A>G, and rs14035 C>T) in the RAN and one (rs2462788 C>T) in the RANBP2 were chosen to investigate their association with Wilms tumor susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to assess the association of the selected polymorphisms with Wilms tumor susceptibility. Results shown that RAN rs7132224 AG/GG genotypes significantly increased Wilms tumor risk when compared to AA genotype (adjusted OR=1.40, 95% CI=1.01-1.95, P=0.047). Carriers of 1-3 risk genotypes have a significantly higher Wilms tumor risk than those without risk genotype (adjusted OR=1.49, 95% CI=1.07-2.07, P=0.020). Moreover, stratified analysis indicated that RAN rs56109543 CT/TT genotypes, RAN rs7132224 AG/GG genotypes and RANBP2 rs2462788 CT/TT genotypes remarkably increased Wilms tumor susceptibility among the subgroups. Our results indicated that RAN and RANBP2 polymorphisms were associated with Wilms tumor susceptibility in Chinese children. The role of RAN/RANBP2 in cancers deserves more attention.

The association of miR34b/c and TP53 gene polymorphisms with Wilms tumor risk in Chinese children.

Wilms tumor is the most common pediatric malignancy in the kidney. The miR34b/c is a downstream target gene of the transcription factor p53. The important role of TP53 mutations, the methylation of miR34b/c, and the interaction between these two molecules in tumorigenesis have been well documented. Due to the biological connection between p53 and miR34b/c, in the present study, we investigated the association between polymorphisms in these two molecules and Wilms tumor susceptibility through genotyping two important functional polymorphisms (miR34b/c rs4938723 T>C and TP53 rs1042522 C>G) in 183 cases and 603 controls. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) derived from the logistic regression analysis were used to assess the correlation of miR34b/c rs4938723 and TP53 rs1042522 polymorphisms with Wilms tumor risk. Our results indicated that the association of miR34b/c rs4938723 and TP53 rs1042522 polymorphisms with Wilms tumor susceptibility was not statistically significant. Stratified analysis by age, gender, and clinical stage, as well as combined effect analysis were also performed, yet, no significant association was found. In conclusion, our study indicated a lack of association between the two selected polymorphisms and Wilms tumor susceptibility. Our findings need to be verified in studies with larger sample size in the future.