The effect and mechanism of 19S proteasome PSMD11/Rpn6 subunit in D-Galactose induced mimetic aging models.
Experimental cell research
Regulating proteasome activity is a potent therapeutic aspect of age-related hearing loss, which has been proven to protect neurons from age-related damaging. PSMD11, subunit of the 19S proteasome regulatory particle, is known to mainly up-regulate proteasome activity and prolong aging. However, the mechanism of PSMD11 in age-related hearing loss has not been deeply explored. In the present study, we explore the function and mechanism of PSMD11 protecting neurons in d-Galactose (D-Gal) mimetic aging models. Age-related pathologies were detected by Taq-PCR, ABR, Transmission electron microscopy, toluidine blue and beta-galactosidase staining. The relative expressions of the proteins were explored by Western blotting, oxyblot, immunoprecipitation and immunofluorescence. Flow cytometry was used to manifest the oxidative state. We discovered that proteasome activity was impaired with aging, and that ROS and toxic protein accumulated in D-Gal induced aging models. PSMD11 changed with aging, and was associated with the metabolism of proteasome activity in the D-Gal treated models. Moreover, the knockdown or overexpression of PSMD11 was sufficient to change the oxidative state caused by D-Gal. Our results also demonstrated that PSMD11 could bond to AMPKalpha1/2 in the auditory cortex and PC12 cells, and AMPKalpha2 but not AMPKalpha1 was efficient to regulate the function of PSMD11. Deeper insights into the mechanisms of regulating PSMD11 for the anti-aging process are needed, and may offer novel therapeutic methods for central presbycusis.
View details for DOI 10.1016/j.yexcr.2020.112093
View details for PubMedID 32450067
Prevalence of respiratory symptoms and spirometric changes among non-smoker male wood workers.
2020; 15 (3): e0224860
To assess the effects of workplace exposure to hardwood dust on lung function and determine a prevalence of respiratory symptoms among wood workers.Cross-sectional observational study.Tertiary referral center.Two hundred seventy-six, non-smoker male wood workers and equal number of non-smoker male office workers, referred to pulmonology clinic included in this study. Evaluation of study participants included completion of a questionnaire regarding respiratory symptoms and baseline spirometry was measured according to the actual recommendations.Respiratory symptoms including cough, phlegm, chest tightness, and wheezing were significantly higher in wood workers than office workers (40.2% versus 29.3% for cough, p = 0.0073; 40.6% versus 23.6% for phlegm, p<0.0001; 38.0% versus 23.1% for chest tightness, p = 0.0001; 25.3% versus 14.5% for wheezing, p = 0.0014). No statistically significant differences were observed for Dyspnea, and upper respiratory tract symptoms among wood workers compared to office workers. While wood workers were more likely to require spirometry test than office workers (21.4% versus 5.4%, p<0.001) the obstructive changes were more prevalent on spirometry test in wood workers (71.4% obstructive pattern versus 28.6% restrictive pattern). Spirometry test revealed the mean values of FEV1 and FEV1/FVC ratio were significantly lower in the wood workers, compared to their mean values in the control group.Respiratory symptoms associated with work, are more prevalent among wood workers than office workers. Our data revealed that workplace exposure to hardwood dust may compromise respiratory function, indicating the importance and the need for optimizing preventive measures in workplace to protect the respiratory health among exposed workers. Obstructive changes on pulmonary function test is a dominant pathologic pattern in pulmonary function test among wood workers. Further investigation is required by current available tools such as nasal cytology to detect influence of wood dust exposure on the upper respiratory airway.
View details for DOI 10.1371/journal.pone.0224860
View details for PubMedID 32187180
DNA methylation biomarkers for nasopharyngeal carcinoma.
2020; 15 (4): e0230524
Aberrant methylation of DNA plays an important role in the pathogenesis of nasopharyngeal carcinoma (NPC). In the current study, we aimed to integrate three cohorts profile datasets to identify abnormally methylated-differentially expressed genes and pathways associated with NPC.Data of gene expression microarrays (GSE53819, GSE412452) and gene methylation microarrays (GSE52068) obtained from the GEO database. Aberrantly methylated differentially expressed genes (DEGs) were obtained by GEO2R. The David database was utilized to perform enrichment and functional analysis regarding selected genes. To create a protein-protein interaction (PPI), STRING and Cytoscape software were utilized. The MCODE was used for module analysis of the PPI network.In total, 181 hypomethylation-high expression genes were identified, which were enriched in the biological mechanisms involved in the differentiation of endodermal cell, mitotic nuclear division, mitotic cell cycle process, chromosome segregation and cell cycle phase transition, etc. Pathway enrichment showed ECM-receptor interaction, PI3K-Akt signaling pathway, Focal adhesion, Protein digestion and absorption and Amoebiasis, etc. The top 3 hub genes of PPI network were FANCI, POSTN, and IFIH1. Additionally, 210 hypermethylation-low expression genes were identified, and our data revealed enrichment in biological processes including axoneme assembly, micro tubular formation, assembly of axonemal dynein complex, cilium movement and cilium organization, etc. Pathway analysis indicated enrichment in B cell receptor signaling pathway, Hematopoietic cell lineage, Leukocyte transendothelial migration, Complement and coagulation cascades and Fc gamma R-mediated phagocytosis, etc. The ZMYND10, PACRG and POU2AF1 were identified as the top three hub genes of PPI network. After validation in TCGA and GEPIA database, most hub genes remained significant. Patients with high expression of POSTN found to have shorter overall survival, while in patients with high expression of ZMYND10 and POU2AF1 longer overall survival was identified.The data revealed novel aberrantly methylated-differentially expressed genes and pathways in NPC by bioinformatics analysis, potentially providing novel insights for the molecular mechanisms governing NPC progression. Hub genes including FANCI, POSTN, IFIH1, ZMYND10, PACRG and POU2AF1 might serve as novel biomarkers for precision diagnosis and providing medical treatment for patient with NPC.
View details for DOI 10.1371/journal.pone.0230524
View details for PubMedID 32271791
Respiratory symptoms prevalence and spirometric changes among non-smoker male wood workers
SPRINGER WIEN. 2019: 523–24
View details for Web of Science ID 000490595300048
Correlation between mitochondrial DNA 4977 bp deletion and presbycusis: A system review and meta-analysis.
2019; 98 (27): e16302
OBJECTIVE: Researchers have evaluated the associations between mitochondrial DNA (mtDNA) 4977 bp deletion and presbycusis. This study aimed to assess the differences of mtDNA 4977 bp deletion between presbycusis patients and controls by conducting a meta-analysis of published studies.METHODS: Databases, including PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched to collect case-control studies on the correlation between mitochondrial DNA 4977 bp deletion and presbycusis. The research findings of related articles were collected according to the inclusion criteria. Pooled odds ratios (ORs) and corresponding confidence intervals (CIs) were calculated. Meanwhile, subgroup analysis was performed to examine the source of heterogeneity. Revman 5.3 and Stata 12.0 software were used for data synthesis.RESULTS: Eight English and Chinese studies were included in the meta-analysis, the results of which showed that mitochondrial DNA 4977 bp deletion could increase the risk of presbycusis (OR = 8.16, 95% CI: 3.51-18.99), and the difference was statistically significant (P <. 01). Analysis of the polled OR showed the incidence of mtDNA 4977 bp deletion was 8.50 times higher in Asians with presbycusis than in the control group. And the OR in the studies of occidentals was 7.24. Sample source analysis was also performed with the sample source divided by temporal bone source and other sources (hair and blood). The OR was 4.18 and 22.36 for the temporal bone and other sources, respectively.CONCLUSION: Mitochondrial DNA 4977 bp deletion could increase the risk of presbycusis.
View details for DOI 10.1097/MD.0000000000016302
View details for PubMedID 31277167
Association of polymorphisms in grainyhead-like-2 gene with the susceptibility to age-related hearing loss: A systematic review and meta-analysis.
2019; 98 (25): e16128
The grainyhead-like-2 (GRHL2) genetic variants were reported in age-related hearing impairment (ARHI) susceptibility in several case-control studies. However, their conclusions are conflicting; it is difficult to precisely assess the disease risk associated with the variants. Therefore we conduct the meta-analysis to discover the association of GRHL2 polymorphisms and the risk of ARHI.A related literature search was conducted in on-line databases, such as Wanfang database, China National Knowledge Infrastructure (CNKI), EMBASE, Web of Science, and PubMed (updated to August 30, 2018). We use Review Manager 5.0 and Stata SE 12.0 software to reckon the odds radio (OR), 95% confidence interval (CI) and P value in random- or fixed-effects model according to the I2 value in the heterogeneity test.2762 cases and 2321 controls in 5 articles were provided data to the meta-analysis. The pooled ORs (95% CI) of the rs10955255 polymorphism were 1.26 (1.05-1.50, P = .01), 1.33 (1.07-1.65, P = .01), and 1.32 (1.12-1.55, P = .0007) in the allele, homozygote and recessive model separately. Besides, a significant association was detected between rs1981361 in mixed population and the ARHI risk in the allele, heterozygote, and dominant genetic model respectively. Then subgroup analyses was performed by ethnicity, for rs10955255 meaningful associations were detected for the allele model, homozygote model, dominant model and recessive model in the Caucasian population but no relations in any of the 5 genetic models in Asian population.The meta-analysis indicated that the rs10955255 polymorphism could be an important risk factor for ARHI, especially in the Caucasians. The rs1981361 polymorphism may be a risk factor for ARHI in Asians. Larger scale researches are needed to further bring the consequences up to date.
View details for DOI 10.1097/MD.0000000000016128
View details for PubMedID 31232964