eIF5A promotes +1 programmed ribosomal frameshifting in Euplotes octocarinatus.

Programmed ribosomal frameshifting (PRF) exists in all branches of life that regulate gene expression at the translational level. The single-celled eukaryote Euplotes exhibit high frequency of PRF. However, the molecular mechanism of modulating Euplotes PRF remains largely unknown. Here, we identified two novel eIF5A genes, eIF5A1 and eIF5A2, in Euplotes octocarinatus and found that the Eo-eIF5A2 gene requires a -1 PRF to produce complete protein product. Although both Eo-eIF5As showed significant structural similarity with yeast eIF5A, neither of them could functionally replace yeast eIF5A. Eo-eIF5A knockdown inhibited +1 PRF of the η-tubulin gene. Using an in vitro reconstituted translation system, we found that hypusinated Eo-eIF5A (Eo-eIF5AH) can promote +1 PRF at the canonical AAA_UAA frameshifting site of Euplotes. The results showed eIF5A is a novel trans-regulator of PRF in Euplotes and has an evolutionary conserved role in regulating +1 PRF in eukaryotes.

Protective effect of vitamin C against tetrachlorobenzoquinone-induced 5-hydroxymethylation-dependent apoptosis in HepG2 cells mainly via the mitochondrial apoptosis pathway.

Tetrachlorobenzoquinone (TCBQ) is an active metabolite of pentachlorophenol, and stimulates the accumulation of ROS to trigger apoptosis. The preventive effect of vitamin C (Vc) against TCBQ-induced apoptosis in HepG2 cells is unknown. And there is little known about TCBQ-triggered 5-hydromethylcytosine (5hmC)-dependent apoptosis. Here, we confirmed that Vc alleviated TCBQ-induced apoptosis. Through investigating the underlying mechanism, we found TCBQ downregulated 5hmC levels of genomic DNA in a Tet-dependent manner, with a particularly pronounced decrease in the promoter region, using UHPLC-MS-MS analysis and hydroxymethylated DNA immunoprecipitation sequencing. Notably, TCBQ exposure resulted in alterations of 5hmC abundance to ∼91% of key genes at promoters in the mitochondrial apoptosis pathway, along with changes of mRNA expression in 87% of genes. By contrast, 5hmC abundance of genes only exhibited slight changes in the death receptor/ligand pathway. Interestingly, the pretreatment with Vc, a positive stimulator of 5hmC generation, restored 5hmC in the genomic DNA to near-normal levels. More notably, Vc pretreatment further counter-regulated TCBQ-induced alteration of 5hmC abundance in the promoter with 100% of genes, accompanying the reverse modulation of mRNA expressions in 89% of genes. These data from Vc pretreatment supported the relationship between TCBQ-induced apoptosis and the altered 5hmC abundance. Additionally, Vc also suppressed TCBQ-stimulated generation of ROS, and further increased the stability of mitochondria. Our study illuminates a new mechanism of TCBQ-induced 5hmC-dependent apoptosis, and the dual mechanisms of Vc against TCBQ-stimulated apoptosis via reversely regulating 5hmC levels and scavenging ROS. The work also provided a possible strategy for the detoxification of TCBQ.

Association between long-term exposure to ambient particulate matter and pulmonary function among men and women in typical areas of South and North China.

Background: Studies comparing the effects of different sizes and concentrations of ambient particulate matter (PM) on pulmonary function in different regions and sexes remain sparse. Objectives: To investigate the associations of different sizes and levels of long-term ambient PM exposure with pulmonary function among people of different sexes in typical areas of South and North China. Methods: In 2021, a total of 1,592 participants aged 20-73 years were recruited to participate in the pulmonary function test from the baseline survey of the Diverse Life-Course Cohort (DLCC) in typical areas of Guangdong Province and Hebei Province. The three-year (2018-2020) average ambient PM concentrations were assessed from the ChinaHighPM1 dataset, ChinaHighPM2.5 dataset and ChinaHighPM10 dataset. Mean differences in pulmonary function were used in multilevel models for different regions and sexes. Results: We discovered significant associations of ambient PM exposure with reduced forced vital capacity (FVC) and increased forced expiratory volume in 1 s/forced vital capacity ratio (FEV1/FVC) among men and lower levels of FEV1 and FVC among women, such that a 5-µg/m3 concentration increase in PM1, PM2.5, and PM10 was associated with decreases in FVC of 122.1 ml (95% confidence interval (CI): 30.8, 213.4), 54.6 ml (95% CI: 15.8, 93.3) and 42.9 ml (95% CI: 12.7, 73.1) and increases in FEV1/FVC of 2.2% (95% CI: 0.6, 3.9), 1.1% (95% CI: 0.4, 1.9) and 0.9% (95% CI: 0.3, 1.5) among men and decreases in FEV1 of 51.1 ml (95% CI: 9.7, 92.4), 21.6 ml (95% CI: 4.3, 38.9) and 16.7 ml (95% CI: 3.3, 30.1) and in FVC of 77.8 ml (95% CI: 10.0, 145.6), 38.7 ml (95% CI: 9.0, 68.5) and 31.1 ml (95% CI: 8.1, 54.1) among women in Hebei Province. There was no association between ambient PM and pulmonary function in Guangdong Province. Conclusion: Long-term exposure to different sizes and concentrations of ambient PM were associated with FEV1 and FVC among men and women differently. The impact of ambient PM on FVC should be of greater concerned.

TCDD-induced antagonism of MEHP-mediated migration and invasion partly involves aryl hydrocarbon receptor in MCF7 breast cancer cells.

Evidence has shown that the activation of AhR (aryl hydrocarbon receptor) can promote cancer cell metastasis. However, limited studies have been carried out on mixed exposure to endocrine-disrupting chemicals (EDCs), especially in human breast cancer. Therefore, using MCF7 human breast cancer cells, we investigated the effects of coexposure to MEHP (mono 2-ethylhexyl phthalate) and TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) on cell migration and invasion, as well as the roles of AhR and the MMP/slug pathway. Our data suggest that MEHP or TCDD can induce migration and invasion in MCF7 cells, and the promotion is partly AhR dependent. We also observed that MEHP antagonized TCDD to reduce AhR-mediated CYP1A1 expression. Subsequently, we revealed that MEHP recruited AhR to dioxin response element (DRE) sequences and decreased TCDD-induced AhR-DRE binding in CYP1A1 genes. Overall, MEHP is a potential AHR agonist, capable of decreasing TCDD-induced AhR-DRE binding in CYP1A1 genes. The antagonizing effect of coexposure led to the inhibition of the epithelial-mesenchymal transition (EMT) in MCF7 cells. Our study provides new evidence for the potential mechanisms involved in EDCs exposure and their interactions in EMT.

Association between occupational stressors and type 2 diabetes among Chinese police officers: a 4-year follow-up study in Tianjin, China.

PURPOSE: To explore the relationship between occupational stressors and the incidence of type 2 diabetes mellitus among police officers. METHODS: Baseline data were collected from policemen who completed the Occupational Stress Inventory-Revised (OSI-R) questionnaire, a self-designed questionnaire, and underwent free clinical measurements at the Medical Center of Police Hospital in Tianjin, China, in April 2007. A total of 5811 policemen participated in follow-up with the dynamic observation of new-onset diabetes (NOD) events occurring annually between 2008 and 2011. Occupational stress was measured by the OSI-R questionnaire, which contains 14 different scales. Cox proportional hazards regression was used to calculate the hazard ratios (HR) of the incidence of type 2 diabetes mellitus (T2DM) by occupational stressors. RESULTS: A total of 3.1% of the participants (n = 179) developed NOD in the follow-up period from 2008 to 2011, and the incidence rates of NOD were 0.58% in 2008, 0.98% in 2009, 0.52% in 2010, and 1.01% in 2011. Role overload (RO), role boundary (RB), physical environment (PE), interpersonal strain (IS), and physical strain (PHS) were associated with the incidence of T2DM (RO: HR = 1.574, 95% CI = 1.071-2.372; RB: HR = 1.645, 95% CI = 1.144-2.365; PE: HR = 2.292, 95% CI = 1.545-3.400; IS: HR = 1.537, 95% CI = 1.079-2.191; and PHS: HR = 1.680, 95% CI = 1.167-2.006) after adjustment for confounding factors. A subgroup Cox regression analysis among traffic control police officers showed the specific work stressors remained robust except RO. CONCLUSIONS: Several aspects of stressors were independent predictors of T2DM in a prospective cohort study in Tianjin, China. This practical information can be applied to the development of psychological interventions against T2DM.