Analysis of serum metabolome of laborers exposure to welding fume.

OBJECTIVE: Welding fume exposure is inevitable of welding workers and poses a severe hazard to their health since welding is a necessary industrial process. Thus, preclinical diagnostic symptoms of worker exposure are of great importance. The aim of this study was to screen serum differential metabolites of welding fume exposure based on UPLC-QTOF-MS/MS. METHODS: In 2019, 49 participants were recruited at a machinery manufacturing factory. The non-target metabolomics technique was used to clarify serum metabolic signatures in people exposed to welding fume. Differential metabolites were screened by OPLS-DA analysis and Student's t-test. The receiver operating characteristic curve evaluated the discriminatory power of differential metabolites. And the correlations between differential metabolites and metal concentrations in urine and whole blood were analyzed utilizing Pearson correlation analysis. RESULTS: Thirty metabolites were increased significantly, and 5 metabolites were decreased. The differential metabolites are mainly enriched in the metabolism of arachidonic acid, glycero phospholipid, linoleic acid, and thiamine. These results observed that lysophosphatidylcholine (20:1/0:0) and phosphatidylglycerol(PGF1α/16:0) had a tremendous anticipating power with relatively increased AUC values (AUC > 0.9), and they also presented a significant correlation of Mo concentrations in whole blood and Cu concentrations in urine, respectively. CONCLUSION: The serum metabolism was changed significantly after exposure to welding fume. Lysophosphatidylcholine (20:1/0:0) and phosphatidylglycerol (PGF1α/16:0) may be a potential biological mediator and biomarker for laborers exposure to welding fume.

Determination of protein-bound α-amanitin in mouse plasma: A potential new indicator of poisoning with the mushroom toxin α-amanitin.

Approximately 70%∼90% of mushroom poisoning deaths are caused by the class of mushroom toxins known as amatoxins. However, the rapid elimination of amatoxins from plasma within 48 h after mushroom ingestion limits the practical value of plasma amatoxin analysis as a diagnostic indicator of Amanita mushroom poisoning. To increase the positive detection rate and extend the detection window of amatoxin poisoning, we developed a new method to detect protein-bound α-amanitin based on the hypothesis that RNAP II-bound α-amanitin released from the tissue into the plasma could be degraded by trypsin hydrolysis and then detected by conventional liquid chromatography-mass spectrometry (LC‒MS). Toxicokinetic studies on mice intraperitoneally injected with 0.33 mg/kg α-amanitin were conducted to obtain and compare the concentration trends, detection rates, and detection windows of both free α-amanitin and protein-bound α-amanitin. By comparing detection results with and without trypsin hydrolysis in the liver and plasma of α-amanitin-poisoned mice, we verified the credibility of this method and the existence of protein-bound α-amanitin in plasma. Under the optimized trypsin hydrolysis conditions, we obtained a time-dependent trend of protein-bound α-amanitin in mouse plasma at 1-12 days postexposure. In contrast to the short detection window (0-4 h) of free α-amanitin in mouse plasma, the detection window of protein-bound α-amanitin was extended to 10 days postexposure, with a total detection rate of 53.33%, ranging from the limit of detection to 23.94 µg/L. In conclusion, protein-bound α-amanitin had a higher positive detection rate and a longer detection window than free α-amanitin in mice.

Liver transcriptome analyses of acute poisoning and recovery of male ICR mice exposed to the mushroom toxin α-amanitin.

Approximately 70-90% of mushroom poisoning deaths are caused by α-amanitin-induced liver injury resulting from RNA polymerase II (RNAP II) inhibition. Liver regeneration ability may contribute greatly to individual survival after α-amanitin poisoning. However, it is unclear what cellular pathways are activated to stimulate regeneration. We conducted dose-effect and time-effect studies in mice that were intraperitoneally injected with 0.33-0.66 mg/kg α-amanitin to establish a poisoning model. The liver/body weight ratio, serological indices, and pathology were evaluated to characterize the liver injury. In the time-effect study, the liver transcriptome was analyzed to explore the mRNA changes resulting from RNAP II inhibition and the underlying pathways associated with recovery. Based on the two animal studies, we established a poisoning model with three sequential liver states: early injury, regulation, and recovery. The mRNA changes reflected by the differentially expressed genes (DEGs) in the transcriptome could be used to illustrate the inhibition of RNAP II by α-amanitin. DEGs at four key time points were well matched with the three liver states, including 8-h downregulated genes in the early injury state, 16-h and 72-h upregulated genes in the regulation state, and 96-h upregulated/downregulated genes in the recovery state. By clustering analysis, the mTOR signaling pathway was screened out as the most promising potential pathway promoting recovery. The results of our investigations of the pathways and events downstream of the mTOR pathway indicated that the activation of mTOR probably contributes crucially to liver regeneration, which could be a promising basis for drug development.

Prevalence of latent tuberculosis infection among coal workers' pneumoconiosis patients in China: a cross-sectional study.

BACKGROUND: Little is known about the prevalence of latent tuberculosis infection (LTBI) among coal workers' pneumoconiosis (CWP) patients. To estimate the prevalence of LTBI and identify its associated risk factors among CWP patients. METHODS: A cross-sectional study was conducted to assess the prevalence of LTBI. Participants were screened for active TB or a history of TB by X-ray and those that underwent QuantiFERON-TB Gold In-Tube (QFT) test. A standardized questionnaire was completed and risk factors were assessed for acquiring TB. Log-binomial regression was used to estimate the LTBI prevalence ratio (PR) in relation to risk factors. RESULTS: Of 244 individuals with CWP (median age 67 years; all male), 162 (66.4%) were QFT positive. In Multivariate analysis, poor workplace ventilation (adjusted prevalence ratio [APR] = 1.26) and intake of fruits regularly (≥4 days of every week) (APR = 0.81) (all p < 0.05) were associated with a decreased risk of QFT. CONCLUSIONS: This study showed a high prevalence of LTBI among individuals with CWP in China. Poor workplace ventilation may be an important contributing factor for LTBI. Regular monitoring and dust control measures need to be improved in workplaces to ensure the safety of workers. Moreover, intake of fruits regularly may be a protective factor for LTBI. However, the effect of fruits should be further studied.

[Inhibitory mechanisms of three compounds for chrysotile-induced biological activities].

OBJECTIVE: To study the effects of aluminum citrate (AC), rare earth compounds (REC) and sodium selenite (SS) on the surface elements of chrysotile fibers and the inhibitory mechanisms of three compounds for chrysotile-induced biological activities. METHODS: After being soaked in 250, 500 and 1000 microg/ml aluminum citrate solutions, 125, 250, 500 and 1000 microg/ml mixed rare earths solutions or 125, 250, 500 and 1000 microg/ml sodium selenite solutions for 10 min or 1 hour, the fabrication and the levels of surface elements of chrysotile fibers were determined. RESULTS: Aluminum citrate, mixed rare earths or sodium selenite all could be adsorbed by chrysotile fibers. After pretreatment of chrysotile fibers with aluminum citrate, mixed rare earths or sodium selenite solutions for 10 min or 1 hour, the corresponding elements or ion on the surface of chrysotile fibers increased with the increase of concentration of the solutions. CONCLUSION: Pretreatment of chrysotile with aluminum citrate, mixed rare earths or sodium selenite solutions can change the fabrication and the levels of surface elements of chrysotile fibers, and inhibit the biological activities of chrysotile by "sealing" some "active sites" on the surface of chrysotile fibers.