Genetic variation in EYA4 on the risk of noise-induced hearing loss in Chinese steelworks firm sample.

OBJECTIVES: Noise-induced hearing loss is one of the most serious occupational diseases worldwide. It is caused by interactions between environmental and genetic factors. The purpose of this study was to examine the association between the genetic susceptibility of the eye absent homolog 4 (EYA4) gene and the risk of developing noise-induced hearing loss in China. METHODS: A case-control association study was carried out with 326 hearing loss cases and 326 controls matched with age and duration of noise exposure, drawn from a cohort of steel workers. Five single nucleotide polymorphisms (SNPs) in the EYA4 were selected and genotyped. Logistic regression was performed to analyse the main effect of genotypes and interactions between genotypes and individual/environmental factors adjusted for confounding factors. Moreover, generalised multiple dimensionality reduction was applied to further detect interaction among the 5 selected SNPs. RESULTS: Analysis revealed that locus polymorphism of rs3813346 was associated with the risk of developing noise-induced hearing loss in the dominance model, the codominance model and the addictive model (p=0.004, 0.009 and 0.003, respectively). A significant interaction between rs9321402 and cumulative noise exposure was found (p=0.002). A significant main effect p value (p=0.006) was obtained in the high-level exposure group (cumulative noise exposure ≥98 dB(A)). Generalised multiple dimensionality reduction indicated that the combined interaction of the 2 loci-rs3813346 and rs9493627-significantly affected the incidence of noise-induced hearing loss. CONCLUSIONS: The research suggests that EYA4 genetic variant and its interaction with noise levels may modify the susceptibility to develop noise-induced hearing loss in Chinese population.

A novel CpG ODN compound adjuvant enhances immune response to spike subunit vaccines of porcine epidemic diarrhea virus.

CpG oligodeoxynucleotides (CpG ODNs) boost the humoral and cellular immune responses to antigens through interaction with Toll-like receptor 9 (TLR9). These CpG ODNs have been extensively utilized in human vaccines. In our study, we evaluated five B-type CpG ODNs that have stimulatory effects on pigs by measuring the proliferation of porcine peripheral blood mononuclear cells (PBMCs) and assessing interferon gamma (IFN-γ) secretion. Furthermore, this study examined the immunoenhancing effects of the MF59 and CpG ODNs compound adjuvant in mouse and piglet models of porcine epidemic diarrhea virus (PEDV) subunit vaccine administration. The in vitro screening revealed that the CpG ODN named CpG5 significantly stimulated the proliferation of porcine PBMCs and elevated IFN-γ secretion levels. In the mouse vaccination model, CpG5 compound adjuvant significantly bolstered the humoral and cellular immune responses to the PEDV subunit vaccines, leading to Th1 immune responses characterized by increased IFN-γ and IgG2a levels. In piglets, the neutralizing antibody titer was significantly enhanced with CpG5 compound adjuvant, alongside a considerable increase in CD8+ T lymphocytes proportion. The combination of MF59 adjuvant and CpG5 exhibits a synergistic effect, resulting in an earlier, more intense, and long-lasting immune response in subunit vaccines for PEDV. This combination holds significant promise as a robust candidate for the development of vaccine adjuvant.

Global and MGMT promoter hypomethylation independently associated with genomic instability of lymphocytes in subjects exposed to high-dose polycyclic aromatic hydrocarbon.

Global hypomethylation, gene-specific methylation, and genome instability are common events in tumorigenesis. To date, few studies have examined the aberrant DNA methylation patterns in coke oven workers, who are highly at risk of lung cancer by occupational exposure to polycyclic aromatic hydrocarbons (PAHs). We recruited 82 PAH-exposed workers and 62 unexposed controls, assessed exposure levels by urinary 1-hydroxypyrene, and measured genetic damages by comet assay, bleomycin sensitivity, and micronucleus assay. The PAHs in coke oven emissions (COE) were estimated based on toxic equivalency factors. We used bisulfite-PCR pyrosequencing to quantitate DNA methylation in long interspersed nuclear element-1 (LINE-1) and O(6)-methylguanine-DNA methyltransferase (MGMT). Further, the methylation alteration was also investigated in COE-treated human bronchial epithelial (16HBE) cells. We found there are higher levels of PAHs in COE. Among PAH-exposed workers, LINE-1 and MGMT methylation levels (with CpG site specificity) were significantly lowered. LINE-1, MGMT, and its hot CpG site-specific methylation were negatively correlated with urinary 1-hydroxypyrene levels (r = -0.329, p < 0.001; r = -0.164, p = 0.049 and r = -0.176, p = 0.034, respectively). In addition, LINE-1 methylation was inversely associated with comet tail moment and micronucleus frequency, and a significant increase of micronucleus in low MGMT methylation group. In vitro study revealed that treatment of COE in 16HBE cells resulted in higher production of BPDE-DNA adducts, LINE-1 hypomethylation, hypomethylation, and suppression of MGMT expression. These findings suggest hypomethylation of LINE-1 and MGMT promoter could be used as markers for PAHs exposure and merit further investigation.

[Development of animal model for lung injury in rats caused by unknown polymer via intratracheal instillation].

OBJECTIVE: To establish an animal model of lung injury in SD rats using intratracheal instillation of unknown polymer and to provide the base for exploring the molecular mechanism of lung tissue injury induced by occupational exposure. METHODS: One hundred forty SD rats were randomly divided into seven groups, including the control group 1 which was exposed to normal solution, the control group 2 which was not exposed to any one and five treatment groups which were exposed to 1 ml unknown polymer (0.5 ml for each lung) at the doses of 40, 30, 20, 10 and 5 mg/ml, respectively by intratracheal instillation. The rats were sacrificed on the 1st, 3rd, 7th, 10th, 14th, 21th and 28th day after exposure, then the lung tissues were examined pathologically and the blood bio-chemical analysis was conducted. RESULTS: The results of blood biochemical analysis indicated that ALT and AST levels in rats exposed to 30 and 40 mg/ml unknown polymer were significantly higher than those in control groups. Intratracheal instillation of unknown polymer can causes PLF in experimental animals on the 14th days after exposure. The results of pathological examination exhibited that the lung tissue injury in rats exposed to unknown polymer for 14 days or more was found and the dose-effect relationship was observed. CONCLUSION: An animal model of lung injury in SD rats induced by unknown polymer with intratracheal instillation was established successfully. The results of pathological examination showed that the types of rat lung injury were similar to the clinical lung injury after exposure to unknown polymer, which provided a base for studying the mechanism of lung injury caused by occupational exposure to unknown polymer.

Inhaled tire-wear microplastic particles induced pulmonary fibrotic injury via epithelial cytoskeleton rearrangement.

Tire wear microplastic particles (TWMPs) are emerging microplastic pollutants that have gained increasing attention lately. However, the health effect of inhaled airborne TWMPs has never been explored before and may already be included in particulate matter morbidity and mortality. Here, we endeavored to address the preliminary study of TWMP inhalation-induced pulmonary toxic effects and its epigenetic mechanisms in C57BL/6 mice. As a result, restricted ventilatory dysfunction and fibrotic pathological changes were observed in TWMP-treaded mice. Further research found that attenuation of miR-1a-3p plays an important role in TWMP-induced lung injury. Results from in vitro study confirmed that cytoskeleton regulatory gene twinfilin-1 was one of the target genes of miR-1a-3p, and involved in cytoskeleton rearrangement caused by TWMP exposure. Mechanistically, miR-1a-3p inhibited the F-actin formation by targeting cytoskeletal regulatory proteins twinfilin-1, leading to TWMP-induced pulmonary fibrotic injury. While we are in the very early stages of explaining the role of epigenetics in TWMP-induced lung injury, the potential for the use of epigenetic marks as biomarkers is high and discoveries made in this field will likely bring us closer to better understanding this crucial mechanism.

Comparison of Polyethylene Wear before and after Hip Revision with Liner Exchange Fixed with the Original Locking Mechanism.

OBJECTIVE: To compare the wear of conventional ultra-high molecular weight polyethylene (CUHMWPE) and highly cross-linked polyethylene (HCLPE) in hip revision with liner exchange fixed with original locking mechanism using analysis of history medical data. METHODS: From Jan. 1, 2000, to Dec. 31, 2007, 26 patients (with 29 involved hips) underwent liner exchange revision fixed with the original locking mechanism due to wear of CUHMWPE and/or osteolysis. The mean age was 53 ± 9 years at the time of the primary total hip arthroplasty (THA) and 64 ± 9 years at the revision. The exchanged liners (Marathon, Depuy) were made of HCLPE. Annual X-rays were used to measure linear wear and osteolysis. The annual linear penetration was measured using PolyWare® software (Draftware Inc.). Annual Harris Hip Scores(HSS) were recorded. RESULTS: The mean follow-up time between the primary and revision THAs was 11 ± 2 years and 8 ± 2 years after revision. The mean Harris Hip Score(HHS) before primary THA, 1 year after primary THA, before revision and 1 year after revision was 43±5, 85±5, 71±6, 83±7 individually. The mean penetration of the CUHMWPE and HCLPE liners occurring in the first year were 0.44 ± 0.28 mm and 0.38 ± 0.14 mm, respectively (p = 0.211). The mean annual linear penetration of CUHMWPE and HCLPE from the second year onward were 0.29±0.09 mm and 0.08 ± 0.03 mm respectively (p <0.01). All THAs with CUHMWPE showed osteolysis on acetabular and/or femoral side before revision. No HCLPE liner showed osteolysis at the last follow-up. Conclusion: The CUHMWPE liner had a significantly higher wear rate than did the HCLPE liner. The HCLPE liner showed a satisfactory liner penetration rate after revision with isolated liner exchange fixed with the original locking mechanism.

Albumin adducts of naphthalene metabolites as biomarkers of exposure to polycyclic aromatic hydrocarbons.

We investigated the utility of adducts formed by the reaction of the naphthalene metabolites naphthalene-1,2-oxide, 1,2-naphthoquinone (1,2-NPQ), and 1,4-naphthoquinone (1,4-NPQ) with serum albumin (Alb) as biomarkers of exposure to polycyclic aromatic hydrocarbons. Cysteinyl serum Alb adducts of 1,2- and 1,4-NPQ (1,2-NPQ-Alb and 1,4-NPQ-Alb, respectively) but not of naphthalene-1,2-oxide were detected in 28 coke oven workers and 22 controls from the steel industry of northern China. The median level of 1,2-NPQ-Alb in coke oven workers (76.6 pmol/g) was significantly higher than that observed in controls (44.9 pmol/g; P = 0.0027). However, the median level of 1,4-NPQ-Alb in exposed subjects was not significantly different from that of controls (48.6 versus 44.2 pmol/g; P = 0.296). Levels of 1,2-NPQ-Alb were significantly correlated with exposure category (controls, side and bottom workers, and top-of-oven workers) as well as with previously measured levels of urinary naphthalene, 1- and 2-naphthol, and 1-pyrenol in these subjects. Multiple linear regression analysis revealed that 35% of the variation in 1,2-NPQ-Alb could be explained by the work category and age. A negative relationship between 1,2-NPQ-Alb and age was observed, suggesting that cytochrome P450 c metabolism diminished with age at approximately 3%/year of life.