Genetic analyses of the bidirectional associations between common mental disorders and asthma.

Objective: Although extensive research has explored the link between mental disorders and asthma, the characteristics and patterns of this association are still unclear. Our study aims to examine the genetic causal links between common mental disorders (specifically, anxiety and depression) and asthma. Methods: We conducted genetic analyses including linkage disequilibrium score regression (LDSC) and bidirectional two-sample Mendelian randomization (MR) analyses, and utilized summary statistics from recent large-scale Genome-Wide Association Studies (GWASs) in European populations, covering sensation of anxiety or depression, anxiety sensation, depression sensation, anxiety disorders, major depression disorder (MDD), and asthma. Results: LDSC revealed significant genetic correlations among sensation of anxiety or depression, MDD and asthma (P < 0.017), highlighting potential genetic correlation between anxiety disorders and asthma (P < 0.05 yet > 0.017). In bidirectional two-sample MR, inverse-variance weighted (IVW) analyses suggested that genetic liability to asthma was significantly associated with an increased risk of sensation of anxiety or depression (OR = 4.760, 95%CI: 1.645-13.777), and MDD (OR = 1.658, 95%CI: 1.477-1.860). Conversely, IVW analyses indicated that genetic liability to anxiety disorders was not associated with an increased risk of asthma (P > 0.01), nor was genetic liability to asthma associated with an increased risk of anxiety disorders (P > 0.01). Furthermore, no significant genetic causal relationships were observed for other studied traits. Multivariate MR, after adjusting for body mass index and alcohol consumption, further corroborated the independent causal effect of genetic predisposition to MDD on the risk of asthma (OR = 1.460, 95% CI: 1.285-1.660). Conclusion: Our study establishes MDD as a predisposing factor for asthma. Meanwhile, anxiety disorders are not causal risk factors for asthma, nor is the reverse true. It is recommended to closely monitor asthma symptoms in patients with MDD.

Transition from Flat-Band Localization to Anderson Localization in a One-Dimensional Tasaki Lattice.

We report an extensive experimental investigation on the transition from flat-band localization (FBL) to Anderson localization (AL) in a one-dimensional synthetic lattice in the momentum dimension. By driving multiple Bragg processes between designated momentum states, an effective one-dimensional Tasaki lattice is implemented with highly tunable parameters, including nearest-neighbor and next-nearest-neighbor coupling coefficients and onsite energy potentials. With that, a flat-band localization phase is realized and demonstrated via the evolution dynamics of the particle population over different momentum states. The localization effect is undermined when a moderate disorder is introduced to the onsite potential and restored under a strong disorder. We find clear signatures of the FBL-AL transition in the density profile evolution, the inverse participation ratio, and the von Neumann entropy, where good agreement is obtained with theoretical predictions.

[Systematic review and Meta-analysis of efficacy and safety of Shufeng Jiedu Capsules in treatment of influenza].

This study aims to systematically review the efficacy and safety of Shufeng Jiedu Capsules in the treatment of influenza. The randomized controlled trial(RCT) of Shufeng Jiedu Capsules alone or in combination with conventional western medicine for treating influenza were retrieved from PubMed, EMbase, Cochrane Library, Web of Science, SinoMed, CNKI, VIP, Wanfang, and ClinicalTrails.gov. The data analysis was performed in RevMan 5.4.1. The Cochrane risk of bias assessment tool was used to evaluate the quality of the involved RCT, and GRADEpro GDT to assess the quality of the evidence. A total of 11 RCTs involving 1 836 patients were included in this study. Compared with conventional western medicine, Shufeng Jiedu Capsules/Shufeng Jiedu Capsules + conventional western medicine improved the response rate(RR=1.09, 95%CI[1.03, 1.15], P=0.002), shortened the time to relief of cough, and increased the 3-day sore throat relief rate, whereas there was no significant difference in the time to fever abatement, the time to relief of sore throat, 3-day cough relief rate, or 3-day runny nose relief rate. Subgroup-analysis showed that Shufeng Jiedu Capsules + conventional western medicine improved the response rate(RR=1.11, 95%CI[1.08, 1.15], P<0.000 01), shortened the time to relief of cough, and increased the 3-day relief rate of symptoms(cough, sore throat, and runny nose) compared with conventional western medicine alone, while there was no significant difference in the time to fever abatement or the time to relief of sore throat. Shufeng Jiedu Capsules alone could not improve the response rate(RR=0.97, 95%CI[0.93, 1.02], P=0.19). In addition, Shufeng Jiedu Capsules/Shufeng Jiedu Capsules + conventional western medicine vs conventional western medicine were no significant difference in adverse reactions(RR=0.98, 95%CI[0.57, 1.69], P=0.95). The available evidence suggests that Shufeng Jiedu Capsules is effective and safe in the treatment of influenza, and the combination of Shufeng Jiedu Capsules with conventional western medicine can accelerate the relief of symptoms. However, since the number and quality of the included studies were low, the above findings remained to be further verified by multicenter RCT with large sample sizes.

Endothelial PAS domain protein 1 gene hypomethylation is associated with colorectal cancer in Han Chinese.

Endothelial PAS domain-containing protein 1 (EPAS1) serves a role in angiogenesis, which is important for the development of tumors, including colorectal cancer (CRC). The current study aimed to estimate whether EPAS1 methylation was associated with CRC. A two-stage association study of EPAS1 methylation and CRC was conducted. In the first phase, EPAS1 methylation was evaluated in the tumor and adjacent non-tumor tissue samples from 41 patients with sporadic CRC in Jiangsu province, China. The diagnostic value of methylation of EPAS1 for CRC in the second phase was evaluated in 79 patients with sporadic CRC and 22 normal individuals in Zhejiang province, China. The methylation assay was performed using a quantitative methylation-specific polymerase chain reaction (qMSP) method. The percentage of methylated reference (PMR) was used to quantify the methylation level. The first-stage results indicated that EPAS1 promoter methylation was significantly lower in CRC tumor tissues compared with 5-cm-para-tumor tissues (median PMR, 0.59 vs. 1.22%; P=0.027) and 10-cm-para-tumor tissues (median PMR, 0.59 vs. 1.89%; P=0.001). In addition, the second-stage results indicated that EPAS1 promoter methylation was significantly lower in tumor tissues compared with 5-cm-para-tumor tissues (median PMR, 1.91 vs. 6.25%; P=3×10-7) and normal intestinal tissues from healthy controls (median PMR, 1.91 vs. 28.4%; P=5×10-7). Receiver Operating Characteristic curve analysis of the second-stage data indicated that the highest area under the curve of EPAS1 hypomethylation was 0.851 between Zhejiang CRC tissues and Zhejiang normal intestinal tissues (sensitivity, 95.5%; specificity, 60.8%).

TNFRSF10C methylation is a new epigenetic biomarker for colorectal cancer.

BACKGROUND: Abnormal methylation of TNFRSF10C was found to be associated with different types of cancers, excluding colorectal cancer (CRC). In this paper, the performance of TNFRSF10C methylation in CRC was studied in two stages. METHOD: The discovery stage was involved with 38 pairs of CRC tumor and paired adjacent non-tumor tissues, and 69 pairs of CRC tumor and paired adjacent non-tumor tissues were used for the validation stage. Quantitative methylation specific PCR (qMSP) method and percentage of methylated reference (PMR) were used to test and represent the methylation level of TNFRSF10C, respectively. A dual-luciferase reporter gene experiment was conducted to evaluate the promoter activity of TNFRSF10C fragment. RESULTS: A significant association of TNFRSF10C promoter hypermethylation with CRC was found and validated (discovery stage: 24.67 ± 7.52 vs. 3.36 ± 0.89; P = 0.003; validation stage: 31.21 ± 12.48 vs. 4.52 ± 1.47; P = 0.0005). Subsequent analyses of TCGA data among 46 pairs of CRC samples further confirmed our findings (cg23965061: P = 4E - 6; cg14015044: P = 1E - 7). Dual-luciferase reporter gene assay revealed that TNFRSF10C fragment was able to significantly promote gene expression (Fold change = 2.375, P = 0.013). Our data confirmed that TNFRSF10C promoter hypermethylation can predict shorter overall survival of CRC patients (P = 0.032). Additionally, bioinformatics analyses indicated that TNFRSF10C hypermethylation was significantly associated with lower TNFRSF10C expression. CONCLUSION: Our work suggested that TNFRSF10C hypermethylation was significantly associated with the risk of CRC.

Diagnostic value of RASSF1A hypermethylation in colorectal cancer: a meta-analysis.

PURPOSE: Ras association domain family 1 isoform A (RASSF1A), a member of Ras association domain family, plays an important role in tumorigenesis. The goal of our meta-analysis was to assess the diagnostic value of RASSF1A hypermethylation in colorectal cancer (CRC). METHODS: PubMed, Embase, CNKI and Wanfang databases were used to conduct literature selection. The association between RASSF1A methylation and CRC risk was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). Summary receiver operating characteristics (SROC) test was used to estimate the diagnostic value of RASSF1A methylation for CRC. RESULTS: A total of 22 articles among 1736 CRC and 811 non-tumor samples were included in the current meta-analysis. Our results showed that RASSF1A hypermethylation was found more frequently in CRC than non-tumor samples (OR = 6.02, 95% CI = 4.57-7.93, P <  0.001). Our SROC test showed that RASSF1A hypermethylation had an area under the curve (AUC) of 0.71 with a pooled sensitivity of 0.33 (95% CI = 0.31-0.36), a pooled specificity of 0.86 (95% CI = 0.84-0.89), a positive-likelihood ratio of 3.18 (95% CI = 1.99-5.09), a negative-likelihood ratio of 0.71 (95% CI = 0.63-0.80), and a diagnostic odds ratio of 5.53 (95% CI = 3.40-9.00). Data mining study indicated that a trend of increased RASSF1A expression was found in the CRC cell line C2C12 after 5-AZA treatment. CONCLUSIONS: Our study established that RASSF1A hypermethylation might have a potential value in the clinical diagnosis of CRC.

SMYD3 promoter hypomethylation is associated with the risk of colorectal cancer.

AIM: SMYD3 encodes histone lysine methyltransferase. The goal of our study was to investigate the association between SMYD3 methylation and colorectal cancer (CRC). MATERIALS & METHODS: SMYD3 methylation was measured by quantitative methylation-specific PCR method in 117 pairs of CRC tumor and para-tumor tissues. RESULTS: Significantly lower SMYD3 methylation was observed in CRC tumor tissues than para-tumor tissues (p = 0.002). Further subgroup analysis by clinical features showed that significantly lower SMYD3 methylation were only observed in the CRC patients with tumors of moderately and well differentiation, positive lymph node metastasis, and stage III + IV. CONCLUSION: Our work reported for the first time that SMYD3 promoter hypomethylation was associated with CRC.

Significant association of PRMT6 hypomethylation with colorectal cancer.

BACKGROUND: Protein arginine N-methyltransferase 6 (PRMT6) was deemed to be indispensable in the variety of biological processes. Upregulated PRMT6 was found in various human diseases including cancer. Herein, we investigated the performance of PRMT6 methylation in the diagnosis for CRC. METHODS: A quantitative methylation-specific polymerase chain reaction (qMSP) method was used to measure PRMT6 promoter methylation. The percentage of methylated reference (PMR) was applied to represent gene methylation level. RESULTS: Our data indicated that PRMT6 promoter methylation levels were significantly lower in CRC tissues than those in paired nontumor tissues (median PMR: 36.93% vs 63.12%, P = 1E-6) and normal intestinal tissues (median PMR: 36.93% vs 506.55%, P = 8E-12). We further examined the potential role of PRMT6 hypomethylation by the receiver operating characteristic (ROC) curve. Our results showed that the area under the curve (AUC) was 0.644 (95% CI = 0.596-0.733) between CRC tissues and paired nontumor tissues, 0.958 (95% CI = 0.919-0.998) between CRC tissues and normal intestinal tissues, and 0.899 (95% CI = 0.825-0.972) between paired nontumor tissues and normal intestinal tissues. CONCLUSION: Our study firstly indicated that the hypomethylation of PRMT6 promoter could be a novel diagnostic biomarker for CRC.

Aberrant methylation of mutL homolog 1 is associated with increased risk of non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a common malignant tumor. DNA hypermethylation in the promoter region has been served as a potential molecular marker for several tumors. The goal of the current study was to assess the diagnostic ability of mutL homolog 1 (MLH1) promoter methylation in NSCLC. METHODS: A total of 111 NSCLC patients' paired tissue samples were obtained to explore the association between MLH1 promoter methylation and NSCLC by methylation-specific polymerase chain reaction (MSP) method. Public databases including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used to verify our findings. RESULTS: Our results showed a significantly higher MLH1 methylation frequency in tumor tissue samples than their paired adjacent tissues (P = .008). ROC curve indicated that MLH1MSP assay was a sensitive but not a specific method in the diagnosis for NSCLC (sensitivity = 0.964, specificity = 0.135, AUC = 0.550). And the association between the methylation level and clinical characteristics has no statistical significance. TCGA cohort evinced a higher methylation probability in tumor group compared with nontumor group (the mean ß value: -0.449 [-0.467, -0.437] vs -0.466 [-0.472, -0.437], P = .011), which was consistent with our results. Meanwhile, an inverse correlation between MLH1 methylation and MLH1 expression was detected in TCGA and GEO databases. CONCLUSIONS: The MSP method for MLH1 methylation was a sensitive but not a specific diagnostic method for NSCLC.

Elevated UMOD methylation level in peripheral blood is associated with gout risk.

Uromodulin (UMOD) encodes an uromodulin glycoprotein, and its mutation results in uromodulin glycoprotein dysfunction and the occurrence of gout. The aim of our study was to assess whether UMOD methylation could predict the risk of gout. A total of 89 sporadic gout cases and 103 age and gender-matched healthy controls were recruited in this study. UMOD methylation level was determined by quantitative methylation-specific PCR (qMSP) in peripheral blood, and the percentage of methylated reference (PMR) was described to represent the methylation level. Our results showed that UMOD methylation was significantly higher in gout cases than controls (median: 1.45 versus 0.75, P < 0.001). The area under curve (AUC) of UMOD methylation in gout was 0.764 (P = 2.90E-10) with a sensitivity of 65.2% and a specificity of 88.3%. UMOD methylation level was shown to be significantly correlated with the serum level of uric acid (UA) (r = -0.208, P = 0.035). Besides, the luciferase reporter assay showed that UMOD CpG island region was able to upregulate gene expression (fold change = 2, P = 0.004). In conclusion, UMOD methylation assessment might be used to predict the occurrence of gout.