PRKCDBP Methylation is a Potential and Promising Candidate Biomarker for Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#The occurrence and development of lung cancer are closely linked to epigenetic modification. Abnormal DNA methylation in the CpG island region of genes has been found in many cancers. Protein kinase C delta binding protein (PRKCDBP) is a potential tumor suppressor and its epigenetic changes are found in many human malignancies. This study investigated the possibility of PRKCDBP methylation as a potential biomarker for non-small cell lung cancer (NSCLC).@*METHODS@#We measured the methylation levels of PRKCDBP in the three groups of NSCLC tissues. Promoter activity was measured by the dual luciferase assay, with 5'-aza-deoxycytidine to examine the effect of demethylation on the expression level of PRKCDBP.@*RESULTS@#The methylation levels of PRKCDBP in tumor tissues and 3 cm para-tumor were higher than those of distant (>10 cm) non-tumor tissues. Receiver operating characteristic (ROC) curve analysis between tumor tissues and distant non-tumor tissues showed that the area under the line (AUC) was 0.717. Dual luciferase experiment confirmed that the promoter region was able to promote gene expression. Meanwhile, in vitro methylation of the fragment (PRKCDBP_Me) could significantly reduce the promoter activity of the fragment. Demethylation of 5'-aza-deoxycytidine in lung cancer cell lines A549 and H1299 showed a significant up-regulation of PRKCDBP mRNA levels.@*CONCLUSIONS@#PRKCDBP methylation is a potential and promising candidate biomarker for non-small cell lung cancer.

Preliminary study on the polymorphisms of some related genes and the methylation levels of BAX and ApoE genes in Alzheimer′s disease / 中华神经科杂志

Objective:To preliminarily explore the association between single nucleotide polymorphisms (SNP) of five candidate genes (APH1B, PRNP, HMGCR, SIRT1, ApoE) and Alzheimer′s disease (AD), and to analyze the methylation levels of BAX and ApoE promoters on the pathogenesis of AD.Methods:Seventeen cases who were admitted to the Department of Geriatrics of the First Affiliated Hospital of Xinjiang Medical University from 2014 to 2015 and diagnosed as likely to be AD by geriatrician and neurologists according to the AD diagnostic criteria in 4th Revised Edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association served AD group, with an age of (75.65±5.86) years, and 34 non-AD patients with matching baseline data such as age, gender, ethnicity, and education status among patients hospitalized during the same period were selected as control group, with an age of (77.59±7.41) years. Sanger sequencing method was used for SNP typing of candidate genes. Methylation-specific polymerase chain reaction was used to determine the DNA methylation level.Results:The distribution of ApoE ε4 allele was statistically different between the AD group and the control group (χ 2=9.718, P=0.002). Candidate genes (SIRT1 rs7895833, APH1B rs1047552, PRNP rs1799990, HMGCR rs3846662) SNP locus genotypes and alleles had no statistically significant differences in the distribution between the AD group and the control group ( P>0.05). After stratification according to whether they carried ApoE ε4, no statistically significant difference was found between the two groups ( P>0.05). The BAX promoter methylation level of the AD group (0.045±0.025) was lower than that of the control group (0.061±0.028) ( t=-2.078, P=0.045). After gender stratification, the BAX methylation level of the female AD group (0.044±0.021) was lower than that of the control group (0.065±0.275) ( t=-2.230, P=0.045). There was no statistically significant difference in the methylation level of ApoE promoter between the AD group and the control group ( P>0.05). After stratification according to whether they carry ApoE ε4 or not, the methylation level of AD patients with ApoE ε4 allele (1.553±0.291) was higher than that of non-carriers (1.221±0.261) ( t=2.480, P=0.025). Conclusions:ApoE ε4 allele may be a risk factor for the onset of AD. BAX promoter hypomethylation contributes to AD in the elderly in Xinjiang, especially in female. ApoE ε4 allele may cause AD through the interaction with ApoE methylation.

The role of institutional trust in preventive and treatment-seeking behaviors during the 2019 novel coronavirus (2019-nCoV) outbreak among residents in Hubei, China

BackgroundSince December 2019, pneumonia associated with the 2019 novel coronavirus (2019-nCoV) has emerged in Wuhan, China. The exponential increase of the confirmed number of cases of 2019n-CoV is of great concern to the global community. The fears and panic among residents in the epicenters have prompted diverse responses, which are understudied. During such a crisis, community trust and support for the government and health authorities are important to contain the outbreak. We aimed to investigate the influence of institutional trust on public responses to the 2019-nCoV outbreak. MethodsAn anonymous Internet-based, cross-sectional survey was administered on January 29, 2020. The study population comprised all residents currently residing or working in the province of Hubei, where Wuhan is the capital city. The level of trust in information provision and preventive instructions, individual preventive behaviors and treatment-seeking behaviors were queried. FindingsThe majority of the participants expressed a great extent of trust in the information and preventive instructions provided by the central government than by the local government. A high uptake of 2019-nCoV preventive measures was found, particularly among people who had been placed under quarantine. Being under quarantine (adjusted odds ratio [OR] = 2.35, 95% confidence interval [CI] 1.80 to 3.08) and having a high institutional trust score (OR = 2.23, 95% CI 1.96 to 2.53) were both strong and significant determinants of higher preventive behavior scores. The majority of study participants (85.7%, n = 3,640) reported that they would seek hospital treatment if they suspected themselves to have been infected with 2019 n-CoV. Few of the participants from Wuhan (16.6%, n = 475) and those participants who were under quarantine (13.8%, n = 550) expressed an unwillingness to seek hospital treatment. Similarly, being under quarantine (OR = 2.36, 95% CI 1.80 to 3.09) and having a high institutional trust score (OR = 2.20, 95% CI 1.96 to 2.49) were two strong significant determinants of hospital treatment-seeking. InterpretationThe results of this study suggest that institutional trust is an important factor influencing adequate preventive behavior and seeking formal medical care during an outbreak. In view of the 2019-nCoV being highly pathogenic and extremely contagious, our findings also underscore the importance of public health intervention to reach individuals with poor adherence to preventive measures and who are reluctant to seek treatment at formal health services. FundingNational Key R&D Program of China, Ningbo Health Branding Subject F und, Sanming Project of Medicine in Shenzhen, K.C. Wong Magna Fund in Ningbo University, National Natural Science Foundation of China, Fundamental Research Fu nds for the Central Universities, China Postdoctoral Science Foundation, and Natural Science Basic Research Program of Shanxi Province. Evidence before this studyWe searched PubMed on January 28, 2020, for articles that describe the trust, preventive practices and health-seeking behaviors related to the 2019 novel coronavirus (2019-nCoV) in China, using the search terms "novel coronavirus," "institutional trust," "behavioral change," "protective behaviors," and "treatment-seeking" with no language or publication time restrictions. Previously published research discussed the behavioral responses to the severe acute respiratory syndrome (SARS) epidemic and the 2009 pandemic influenza A (H1N1) in Hong Kong. The only report investigating the influence of institutional trust and public responses was published on March 27, 2019, on the Ebola outbreak in the Democratic Republic of the Congo. No previous studies have investigated how trust in the information provision and prevention instructions from the authorities during a disease outbreak has influenced the publics prevention practices and treatment-seeking in the epicenter of the 2019-nCoV.

The impact of traffic isolation in Wuhan on the spread of 2019-nCov

The 2019-nCoV outbreak occurred near the Chinese Spring Festival transport period in Wuhan. As an important transportation center, the migration of Wuhan accelerated the spread of 2019-nCoV across mainland China. Based on the cumulative Baidu migration index (CBMI), we first analyzed the proportion of Wuhans migrant population to other cities. Our results confirm that there is a significant correlation between the export population of Wuhan and reported cases in various regions. We subsequently found that the mortality rate in Hubei Province was much higher than that in other regions of mainland China, while the investigation of potential cases in Wuhan was far behind other provinces in Mainland China, which indicates the effectiveness of early isolation.

Correlation between methylation level of and genes and aging in healthy individuals / 南方医科大学学报

OBJECTIVE@#To analyze the relationship between and gene methylation with aging in the general population.@*METHODS@#We collected peripheral blood samples from 284 male and 246 female healthy subjects for detection of methylation levels of and genes using quantitative methylation-specific PCR (qMSP). The relationship between the methylation levels of and genes and aging was analyzed using Spearman or Pearson correlation test.@*RESULTS@#We found a significant positive correlation between the methylation levels of the two genes in these subjects ( < 0.05). In the overall population as well in the female subjects, methylation was found to be inversely correlated with age ( < 0.05). The methylation levels of and genes were inversely correlated with TG, ApoE, Lp(a) and AST in the overall population ( < 0.05). In both the female and male subjects, the methylation levels of the two genes were inversely correlated with Lp(a) ( < 0.05). In the male subjects, methylation was inversely correlated with AST ( < 0.05), while methylation was inversely correlated with HDL and ApoE ( < 0.05). In the female subjects, methylation was positively correlated with LDL and inversely correlated with ApoE and AST ( < 0.05).@*CONCLUSIONS@#The methylation levels of and are closely related to age and the levels of multiple proteins in healthy subjects.

Association between TLR2, MTR, MTRR, XPC, TP73, TP53 genetic polymorphisms and gastric cancer: a meta-analysis.

OBJECTIVE: The aim of our meta-analyses is to test the association between six genetic polymorphisms and gastric cancer. METHODS: A systematic search was performed for all the available candidate genes and gastric cancer among several online databases including PubMed, Embase, Web of Science, the Cochrane Library, CNKI and Wanfang online libraries. After a comprehensive screening, a total of six genes were harvested for the current meta-analyses. These genes include TLR2 (-196 to -174 ins>del), MTR (rs1805087), MTRR (rs1801394), XPC (rs2228001), TP73 (G4C14-A4T14), and TP53 (rs1042522). RESULTS: Altogether 49 comparative studies among 11 776 cases and 18 633 controls were involved in our meta-analyses. TP53 rs1042522 polymorphism was shown to be associated with gastric cancer risk under the dominant model (P=0.02, OR=1.03, 95% CI=1.00-1.05). A subgroup meta-analysis indicated a significant association under dominant model between TP53 rs1042522 and gastric cancer in the Eastern Asians (P=0.03, OR=1.17, 95%=1.02-1.34). CONCLUSIONS: These results suggest that TP53 rs1042522 polymorphism might contribute to the susceptibility of gastric cancer under the dominant model, especially in Eastern Asians.

Tumor necrosis factor alpha gene polymorphisms in ankylosing spondylitis: associations with clinical disease progression and disease susceptibility / 中国组织工程研究

BACKGROUND: The association of tumor necrosis factor alpha (TNF-α) gene polymorphisms with the onset and development of ankylosing spondylitis (AS) has been the focus of studies on AS in the field of genetics.OBJECTIVE: To explore the association of the polymophisms of TNF-α promoter gene at positions-308 and -238 with AS susceptibility and clinical pathological changes.DESIGN: A case-control study.SETTING:The Rheumatic Immunology Department of Changhai Hospital of the Second Military Medical University of Chinese PLA.PARTICIPANTS: Totally, 108 AS patients were recruited from Rheumatic Immunology Department of Changhai Hospital, Second Military Medical University of Chinese PLA from January 1999 to December 2003 ,they had no kinship. The ratio of men to women was 5.3: 1. They aged from 13 to 71 (30-± 12) years old, and AS was divided into Ⅰ- Ⅳ radiographic stages according to the sacro-iliac joint damage. A total of 100 healthy controls were randomly selected from the blood donators(Shanghai Hospital) who were aged from 19 -56 (33 ±9) years old, and the ratio of men to women was 4.9: 1. Informed consent was obtained from all the subjects.ti-coagulated with EDTA. Polymerase chain reaction amplification and purification of the TNF-α promoter region was made and the sequence of polymerase chain reaction products was examined and displayed by Chromas 1.62 softcorresponding radiographic stage of sacro-iliac joint damage was assessed to investigate the influence of gene polymorphisms on AS.MAIN OUTCOME MEASURES: DNA direct sequencing method was used to detect -238 and -308 allele phenotypes for investigating the association with clinical presentations.G and -238G/A allele was 98.1% (106 cases) and1. 9% (2 cases) respectively in AS group and 95.0% (95 cases) and 5.0% (5 cases) respecquency of TNF-α promoter gene at positions -308. 1.1(G/G) and - 308.1.2(G/A) alleles was 82.4% (89 cases) and 17.6% (192 cases) respectively in AS group, which was not significantly different compared respectively with 85.0% (85 cases) and 14.0% (14 cases) of the control of sacro-iliac joint damage and the frequency of TNF-α promoter gene at the position of - 308 (G/G) and (G/A): AS patients with(G/G) phenotype who were confirmed of radiographic stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ were observed in 3/35/40/11cases,compared with (G/A) phenotype of 1/12/6/0 cases.The difference was statistically significant (χ2GMH = 4.77, P ＜ 0.05 ).CONCLUSION: Our data suggest that the polymorphisms of TNF-α promoter gene at positions of - 238 and - 308 allele has no association with AS susceptibility, but the polymorphisms of TNF - α promoter gene at the position of -308 might exert great influence on AS according to the radiographic stage of sacro-iliac joint damage.