Bioinformatics-based dynamics of cuproptosis -related indicators in experimental silicosis.

Pneumoconiosis is one of the most serious occupational diseases worldwide. Silicosis due to prolonged inhalation of free silica dust during occupational activities is one of the main types. Cuproptosis is a newly discovered mode of programmed cell death characterized by the accumulation of free copper in the cell, which ultimately leads to cell death. Increased copper in the serum of silicosis patients, suggests that the development of silicosis is accompanied by changes in copper metabolism, but whether cuproptosis is involved in the progression of silicosis is actually to be determined. To test this hypothesis, we screened the genetic changes in patients with idiopathic fibrosis by bioinformatics methods and predicted and functionally annotated the cuproptosis-related genes among them. Subsequently, we established a mouse silicosis model and detected the concentration of copper ions and the activity of ceruloplasmin (CP) in serum, as well as changes of the concentration of copper and cuproptosis related genes in mouse lung tissues. We identified 9 cuproptosis-related genes among the differential genes in patients with IPF at different times and the tissue-specific expression levels of ferredoxin 1 (FDX1) and Lipoyl synthase (LIAS) proteins. Furthermore, serum CP activity and copper ion levels in silicosis mice were elevated on days 7th and 56th after silica exposure. The expression of CP in mouse lung tissue elevated at all stages after silica exposure. The mRNA level of FDX1 decreased on days 7th and 56th, and the protein level remained in accordance with the mRNA level on day 56th. LIAS and Dihydrolipoamide dehydrogenase (DLD) levels were downregulated at all times after silica exposure. In addition, Heatshockprotein70 (HSP70) expression was increased on day 56. In brief, our results demonstrate that there may be cellular cuproptosis during the development of experimental silicosis in mice and show synchronization with enhanced copper loading in mice.

Silica-exposed macrophages-secreted exosomal miR125a-5p induces Th1/Th2 and Treg/Th17 cell imbalance and promotes fibroblast transdifferentiation.

Until now, the specific pathogenesis of silicosis is not clear. Exosomal miRNAs, as a newly discovered intercellular communication medium, play an important role in many diseases. Our previous research found that serum exosomal miR125a-5p was increased in silicosis patients by miRNAs high-throughput sequencing. TRAF6, is a target gene of miR125a-5p, which is involved in T-cell differentiation. Furthermore, results from animal study indicate that knockdown of miR-125a-5p can regulate T lymphocyte subsets and significantly reduce pulmonary fibrosis by targeting TRAF6. However, the level of serum exosomal miR125a-5p in silicosis patients has not been reported, the role of macrophages-secreted exosomal miR-125a-5p in regulating T cell differentiation to promote fibroblast transdifferentiation (FMT) remains unknown. In this study, the levels of serum exosomal miR125a-5p and serum TGF-ß1, IL-17A, IL-4 cytokines in silicosis patients were elevated, with the progression of silicosis, the level of serum exosomal miR125a-5p and serum IL-4 were increased; thus, the serum level of IFN-γ was negatively correlated with the progression of silicosis. In vitro, the levels of miR125a-5p in macrophages, exosomes, and T cells stimulated by silica were significantly increased. When the mimic was transfected into T cells, which directly suppressed TRAF6 and caused the imbalance of T cells differentiation, induced FMT. To sum up, these results indicate that exosomal miR-125a-5p may by targeting TRAF6 of T cells, induces the activation and apoptosis of T cells and the remodeling of Th1/Th2 and Th17/Tregs distribution, ultimately promotes FMT. Suggesting that exosomal miR-125a-5p may be a potential therapeutic target for silicosis.

Exosomal miR-125a-5p regulates T lymphocyte subsets to promote silica-induced pulmonary fibrosis by targeting TRAF6.

Silicosis caused by long-term inhalation of crystalline silica during occupational activities seriously threatens the health of occupational populations. Imbalances in T helper 1(Th1), Th2, Th17, and regulatory T cells (Tregs) promote the development of pulmonary silicosis. Exosomes and their contents, especially microRNAs (miRNAs), represent a new type of intercellular signal transmission mediator related to various diseases including pulmonary fibrosis. However, whether exosomal miRNAs can affect the progression of silicosis by regulating T cell differentiation remains to be determined. To test this hypothesis, we established a miR-125a-5p antagomir mouse model and examined changes in miR-125a-5p levels and T cell subtypes. We found that miR-125a-5p levels were increased in lung tissues and serum exosomes in the silica group at 7 days and 28 days. Downregulation of miR-125a-5p attenuated α-smooth muscle actin (α-SMA), collagen I, fibronectin, p-p65, and p-inhibitor of nuclear factor kappa B (NF-κB) kinase (IKK) protein expression, while tumor necrosis factor receptor-associated factor 6 (TRAF6) and p-inhibitor of κBα (IKBα) expression were increased. MiR-125a-5p anta-miR treatment contributes to the maintenance of Th1/Th2 balance during the progression of pulmonary fibrosis. Our findings indicated that knockdown miR-125a-5p could regulate T lymphocyte subsets and significantly reduce pulmonary fibrosis by targeting TRAF6.

MALAT1-miR-30c-5p-CTGF/ATG5 axis regulates silica-induced experimental silicosis by mediating EMT in alveolar epithelial cells.

Epithelial-mesenchymal transdifferentiation of alveolar type Ⅱ epithelial cells is a vital source of pulmonary myofibroblasts, and myofibroblasts formation is recognized as an important phase in the pathological process of silicosis. miR-30c-5p has been determined to be relevant in the activation of the epithelial-mesenchymal transition (EMT) in numerous disease processes. However, elucidating the role played by miR-30c-5p in the silicosis-associated EMT process remains a great challenge. In this work, based on the establishment of mouse silicosis and A549 cells EMT models, miR-30c-5p was interfered with in vivo and in vitro models to reveal its effects on EMT and autophagy. Moreover, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), connective tissue growth factor (CTGF), autophagy-related gene 5 (ATG5), and autophagy were further interfered with in the A549 cells models to uncover the possible molecular mechanism through which miR-30c-5p inhibits silicosis associated EMT. The results demonstrated the targeted binding of miR-30c-5p to CTGF, ATG5, and MALAT1, and showed that miR-30c-5p could prevent EMT in lung epithelial cells by acting on CTGF and ATG5-associated autophagy, thereby inhibiting the silicosis fibrosis process. Furthermore, we also found that lncRNA MALAT1 might competitively absorb miR-30c-5p and affect the EMT of lung epithelial cells. In a word, interfering with miR-30c-5p and its related molecules (MALAT1, CTGF, and ATG5-associated autophagy) may provide a reference point for the application of silicosis intervention-related targets.

Dendritic cells activated by cimetidine induce Th1/Th17 polarization in vitro and in vivo.

Dendritic cells (DCs) are powerful antigen presentation cells and the initiator of adaptive immune response. Cimetidine, a widely used drug for gastric ulcers treatment, has significant immunomodulatory ability. However, the effects of cimetidine on DC-mediated T cell activation need to be further explored. In this study, we constructed the in vitro and in vivo model of cimetidine exposure, and our data showed that cimetidine stimulated the maturity of immature DCs, and further enhanced its T cell priming capacity. In vivo, the number of rat splenic CD103+ DC were not altered after cimetidine exposure, but the expression of surface markers CD54, CD11c, and MHC-II of which were up-regulated. Importantly, cimetidine interfered with DC-mediated T cell polarization, which was reflected in the up-regulation of Th1 and Th17 cells and the down-regulation of Th2 and Treg cells in vitro and in vivo. These results indicate that cimetidine can induce DC activation and promote DC mediated pro-inflammatory T cell response while weaken immunosuppressive T cell response.

Genetic polymorphisms of metabolic enzyme genes associated with leukocyte mitochondrial DNA copy number in PAHs exposure workers.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) exposure had been reported to be a risk factor of mtDNAcn in our early study. However, the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs-Exposure workers has not been fully evaluated. AIM: The aim of the study was to explore the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs-Exposure. METHODS AND RESULTS: We investigated the effects of metabolic enzymes' genetic polymorphisms on mtDNAcn among 544 coke oven workers and 238 office staffs. The mtDNAcn of peripheral blood leukocytes was measured using the Real-time quantitative polymerase chain reaction (PCR) method. PCR and restriction fragment length was used to detect five polymorphisms in GSTT1, GSTM1, GSTP1 rs1695, CYP2E1 rs6413432, and CYP2E1 rs3813867. The mtDNAcn in peripheral blood leukocytes was significantly lower in the exposure group than that in the control group (p < .001). The 1-OHPYR had an increasing trend with the genotypes AA→AG → GG of GSTP1 rs1695 in the control group. Generalized linear model indicated that the influencing factors of mtDNAcn were PAHs-exposure [ß (95% CI) = -0.420 (-0.469, -0.372), p < .001], male [ß (95% CI) = -0.058 (-0.103, -0.012), p = .013], and AA genotype for GSTP1 rs1695 [ß (95% CI) = -0.051 (-0.095, -0.008), p = .020]. CONCLUSION: The individuals carrying the AA genotype of GSTP1 rs1695 may have a lower mtDNAcn due to their weaker detoxification of PAHs.

Born-Oppenheimer molecular dynamics simulations on structures of high-density and low-density water: a comparison of the SCAN meta-GGA and PBE GGA functionals.

Using Born-Oppenheimer ab initio molecular dynamics (BOAIMD) simulations, the high-density water (HDW) and low-density water (LDW) structures based on SCAN meta-GGA are compared with those based on PBE GGA. Compared with Car-Parrinello ab initio molecular dynamics (CPAIMD) simulations, BOAIMD simulations can produce more accurate results because no fictitious electron mass is introduced. At each state point, our simulations continue for 100 ps after the system reached equilibrium, which is the longest ab initio simulations of liquid water reported so far and can ensure an accurate statistical average. The influence of the size effect and nuclear quantum effect on structure is not considered in the present work, but only that of two different functionals on the structure is discussed. It is found that, in HDW, just as shown using CPAIMD simulations, the SCAN-based hydrogen-bonds (HBs) are more flexible than the PBE-based ones, which makes the structure based on SCAN obviously closer to the experimental results than that based on PBE. However, it is not the case in LDW, and the difference between the results based on these two functionals is very small.

Comparative analysis of three data mining techniques in diagnosis of lung cancer.

There is a lot of abnormal information in the development of lung cancer, and how to extract useful knowledge is urgent from massive information. Data mining technology has become a popular tool for medical classification and prediction. However, each technology has its advantage and disadvantage, and several data mining methods will be applied to conduct the in-depth analysis step by step. And the prediction results of different models are compared. A total of 180 lung cancer patients and 243 lung benign individuals were collected from the First Affiliated Hospital of Zhengzhou University from October 2014 to March 2016, and the prediction models based on epidemiological data, clinical features and tumor markers were developed by artificial neural network (ANN), decision tree C5.0 and support vector machine (SVM). The results showed that there were significant differences between the lung cancer group and the lung benign group in terms of seven tumor markers and 10 epidemiological and clinical indicators. The accuracy rates of ANN, C5.0 and SVM were 76.47, 89.92 and 85.71%, respectively. The results of receiver operating characteristic curve (ROC) curve revealed the area under the ROC curve (AUC) of ANN was 0.811 (0.770-0.847), the AUC of C5.0 was 0.897 (0.864-0.924) and the AUC of SVM was 0.878 (0.843-0.908). It was shown that the decision tree C5.0 model has the least error rate and highest accuracy, and it could be used to diagnose lung cancer.

Association between genetic polymorphisms of telomere pathway genes and hydrogen peroxide level in omethoate exposure workers.

OBJECTIVE: The aim of this study was to explore the association between genetic variations in telomere pathway genes and the level of hydrogen peroxide (H2O2) in omethoate exposure workers. METHODS: A total of 180 omethoate exposure workers and 115 healthy controls were recruited. The level of H2O2 in plasma was determined with molybdenic acid colorimetry. Polymerase chain reaction and restriction fragment length was used to detect polymorphisms in POT1 rs1034794, POT1 rs10250202, TERF1 rs3863242, and TERT rs2736098. RESULTS: The level of H2O2 in exposure group (4.26 ± 0.71) was significantly higher than that in control group (3.29 ± 0.46). Generalized linear models indicated that risk factors for the increase H2O2 level were exposure [ß(95 % CI) = 0.951 (0.806, 1.096), P < 0.001] and AA + AT genotype in POT1 rs034794 [ß(95 % CI) = 0.397 (0.049, 0.745), P = 0.025]. CONCLUSION: The increase H2O2 level was associated with omethoate exposure and AA + AT genotypes in POT1 gene rs1034794. It provided a new idea that polymorphisms in telomere pathway genes may indirectly regulate telomere length by influencing oxidative stress.

Transcriptome analysis reveals a protective role of liver X receptor alpha against silica particle-induced experimental silicosis.

Silicosis, a severe and irreversible form of pulmonary fibrosis (PF) caused by long-term exposure to dust particles in production environments, is the biggest occupational health concern in China and most low-income countries. The transdifferentiation of pulmonary fibroblasts is the terminal event in silicosis, and specific transcription factors (TFs) play a crucial role in this condition. However, the relationship between TF-mediated regulation and silicosis remains unknown. We performed a transcriptomic analysis to elucidate this relationship, and our results revealed that two TFs, EGR2 and BHLHE40, were upregulated and five, i.e., TBX2, NR1H3 (LXRα), NR2F1, PPARG (PPARγ), and EPAS1, were downregulated in activated fibroblasts. Notably, PPARγ and LXRα expression was also decreased in an experimental mouse model of silicosis. The mechanism underlying these changes may involve TGF-ß1 secretion from silica-exposed alveolar macrophages, causing PPARγ and LXRα downregulation, which in turn would result in aberrant α-SMA transcription. Our results suggest that LXRα is a potential target for the prevention of silicosis and PF.

Human monocyte-derived dendritic cells as an in vitro alternative model cell to evaluate the immunotoxicity of 2, 4-Dinitrochlorobenzene.

Improvements in science and technology have led to the increasing threats of new chemicals to the public health. It is crucial to evaluate the toxicity, especially immunotoxicology. Dendritic cells (DCs) are believed to be more favorable choices in immunotoxicity evaluations. To obtain and evaluate the value of human monocyte-derived immature DCs (imDCs) in vitro applications in immunotoxicology, compared the results in vitro. DCs were obtained from enriched leukocytes of peripheral blood by using magnetic cell sorting and cytokine (rhGM-CSF + rhIL-4) co-induction. imDCs function in vitro and the surface antigens changes both in imDCs and THP-1 after 24 h of 2,4-dinitrochlorobenzene (DNCB) exposure were determined. The results were compared with those of DNCB-induced rats. The feasibility of imDCs applications in immunotoxicology was evaluated. In vivo, the splenic nodules, lymphocytes, and CD103+DC surface antigen expression were altered in the spleen of DNCB-induced rats. Moreover, DNCB exposure increased CD8+ T cell numbers both in peripheral blood and in the spleen of DNCB-induced rats. In vitro, DNCB exposure reduced the antigen uptake capacity and enhanced the T cell proliferative capacity of imDCs. The results are consistent with in vivo, but superior to that of the THP-1. Our results suggest that human monocyte-derived DCs may have potential applications as an attractive in vitro alternative cell model to evaluate the sensitization of DNCB.

PHTF2 regulates lipids metabolism in gastric cancer.

Identification of hub genes and key pathways of gastric cancer was recognized to be essential to elucidate the tumorigenesis of GC. This study was aimed to identify the differentially expressed genes (DEGs) in GC via bioinformatics methods and their related pathways involved in the pathological process of GC. Gene expression profile datasets acquired by microarray chips or RNA-seq were downloaded from GEO dataset and TCGA, and 298 differentially expressed genes was identified. The Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) pathways of DEGs were then analyzed by the DAVID database to elucidate the potential molecular functions of DEGs. The protein-protein interaction (PPI) network of DEGs was further analyzed with the STRING database and PHTF2 was identified as a hub gene in the PPI network. Subsequently, PHTF2 was found to be highly expressed in different subtypes of gastric cancer tissues obtained from TCGA database or clinical patients, resulting with a poor prognosis. By GSEA, PHTF2 was found to significantly enrich the fatty acid metabolism pathway in gastric cancer. Moreover, PHTF2-regulated lipids metabolism significantly affected the tumorigenesis of GC cells. In summary, this work identified a new mechanism by which PHTF2 precipitated in the pathological process of GC by regulating cellular lipid metabolism.

Silica particles disorganize the polarization of pulmonary macrophages in mice.

Silicosis is a fatal fibrotic lung disease caused by long-term silica particle exposure, in which pulmonary macrophages play an important role. However, the relationship between macrophage polarization and silicosis remains unclear. We established an experimental silicosis mouse model to investigate macrophage polarization during silicosis development. C57BL/c mice were exposed to silica by intra-tracheal instillation and sacrificed at different time points. Lung tissues and bronchoalveolar lavage fluid were collected for flow cytometry, quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assays, western blotting, and histology examinations. The polarization of pulmonary macrophages was dysregulated during silicosis development. In the early stage of silicosis, M1 macrophages were induced and played a leading role in eliciting inflammatory; in the late stage, M2 macrophages were induced to promote tissue repair. Levels of several cytokines in lung tissue microenvironment changed with macrophage polarization. Inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-1ß and IL-6 were upregulated in the inflammation stage, while the anti-inflammatory cytokine IL-10 was upregulated in the fibrosis stage. Furthermore, we found that STAT (signal transducer and activator of transcription) and IRF (interferon regulatory factor) signaling pathway were involved in the regulation of macrophage polarization in silicosis. In summary, macrophage polarization is closely related to the occurrence and development of silicosis and may be a key point for further elucidating silicosis pathogenesis.

Equation of state of water based on the SCAN meta-GGA density functional.

Based on the newly developed SCAN meta-GGA and the widely used PBE-GGA functionals, ab initio molecular dynamics are performed on water. It is proved that, although the SCAN meta-GGA is not as good as the TIP4P/2005 model potential in describing the equation of state of water, it is much better than the PBE-GGA, the ST2 model potential, and ab initio trained neural network potentials. Moreover, the SCAN meta-GGA predicts a first-order liquid-liquid transition from high- to low-density water at negative pressure, in which the structures are qualitatively consistent with experimental observations, and the spinodal point of high-density water is very close to Speedy's stability limit line.

Effect of TRF1 rs3863242 polymorphism on telomere length in omethoate-exposed workers.

Telomere length was found to be associated with omethoate exposure and polymorphisms in certain genes among occupational workers. However, whether the polymorphisms in telomere-binding protein genes influence telomere length remains unclear. To explore the correlation between telomere length and polymorphisms in telomere-binding protein genes, telomere length in peripheral blood leukocytes was determined by real-time quantitative polymerase chain reaction in 180 omethoate-exposed workers and 115 healthy controls. Polymorphisms in 10 pairs of alleles were detected using flight mass spectrometry or polymerase chain reaction-restriction fragment length polymorphism technique. The results showed that individuals with GG genotype in TRF1 rs3863242 had longer telomere lengths than those with AG + AA genotype in the control group (p = 0.005). The multiple regression analysis suggested that both omethoate exposure (b = 0.526, p < 0.001) and TRF1 rs3863242 GG (b = 0.220, p = 0.002) were related to a longer telomere length. In conclusion, GG genotype in TRF1 rs3863242 is linked to prolongation of telomere length, and individuals with GG genotype are recommended to strengthen health protection in a Chinese occupational omethoate-exposed population.

Dose-related telomere damage associated with the genetic polymorphisms of cGAS/STING signaling pathway in the workers exposed by PAHs.

Telomeres are located at the end of eukaryotic chromosomes and vulnerable to exogenous chemical compounds. Exposure to coke oven emissions (COEs) leads to a dose-related telomere damage, and such chromosomal damage might trigger the cGAS/STING signaling pathway which plays an important role in immune surveillance. However, the relationship between the genetic variations in the cGAS/STING signaling pathway and telomere damage in the COEs-exposure workers has not been investigated. Therefore, we recruited 544 coke oven workers and 238 healthy control participants, and determined the level of COEs exposure, concentration of urinary 1-hydroxypyrene (1-OHPYR), genetic polymorphisms and telomere length. The results showed that the telomere length significantly decreased from the control-to high-exposure groups as defined by the external exposure level (P < 0.05). The results also indicated that STING rs7447927 CC, cGAS rs34413328 AA, and cGAS rs610913 AA could inhibit telomere shortening in the exposure group (P < 0.05), and cGAS rs34413328, urine 1-OHPYR and cumulative exposure dose (CED) had a significant association with telomere length by generalized linear model. In conclusion, telomere shortening was a combined consequence of short-term exposure, long-term exposure, and genetic variations among the COEs-exposure workers.

Identification of Three Differentially Expressed miRNAs as Potential Biomarkers for Lung Adenocarcinoma Prognosis.

OBJECTIVE: The aim of this study areto screen MicroRNAs (miRNAs) related to the prognosis of lung adenocarcinoma (LUAD) and to explore the possible molecular mechanisms. METHODS: The data for a total of 535 patients with LUAD data were downloaded from The Cancer Genome Atlas (TCGA) database. The miRNAs for LUAD prognosis were screened by both Cox risk proportional regression model and Last Absolute Shrinkage and Selection Operator (LASSO) regression model. The performances of the models were verified by time-dependent Receiver Operating Characteristic (ROC) curve. The possible biological processes linked to the miRNAs' target genes were analyzed by Gene Ontology (GO), Kyoto gene and genome encyclopedia (KEGG). RESULTS: Among 127 differentially expressed miRNAs identified from the screening analysis, there are 111 up-regulated and 16 down-regulated miRNAs. Three of them, hsa-miR-1293, hsa-miR-490 and hsa-miR- 5571, were also significantly associated with the survival of the LUAD patients. The targets of the three miRNAs are significantly enriched in systemic lupus erythematosus pathways. CONCLUSION: Hsa-miR-1293, hsa-miR-490 and hsa-miR-5571 can be potentially used as novel biomarkers for the prognosis prediction of LUAD.

The association between polymorphisms in tankyrase gene and telomere length in omethoate-exposed workers.

Peripheral blood leukocyte telomere length in omethoate-exposed workers is related to environmental exposure and single nucleotide polymorphisms (SNPs) in genes including p21, GSTM1, miR-145, etc. However, the roles of SNPs in tankyrase (TNKS) gene in telomere length are still unknown. The aim of this study was to explore the association between SNPs in TNKS gene and telomere length in omethoate-exposed workers. Telomere length in peripheral blood leukocyte DNA from 180 omethoate-exposed workers and 115 healthy controls was measured using Real-time quantitative polymerase chain reaction (PCR). Genotyping of the selected functional and susceptible SNPs was performed by the flight mass spectrometry based on PCR and single-base extension. The analysis of covariance was performed to find effects of SNPs on telomere length. Generalized linear models were used to analyze the environment, gene, and interaction on telomere length. The results showed that telomere length in the CG + CC genotypes in rs1055328 in TNKS gene was significantly longer than that in the wild homozygous GG genotype both in exposure group (P = 0.017) and in control group (P = 0.038) after adjusting the covariates. The variables kept in the generalized linear models included omethoate-exposure (ß = 0.580, P = 0.001) and rs1055328 (CG + CC) in TNKS gene (ß = 0.339, P = 0.002). The study suggests that the prolongation of telomere length is associated with omethoate-exposure and the CG + CC genotypes in rs1055328 in TNKS gene.

Effects of polycyclic aromatic hydrocarbon exposure and miRNA variations on peripheral blood leukocyte DNA telomere length: A cross-sectional study in Henan Province, China.

Telomeres play a major role in human aging and disease, especially in most cancers. Telomere length was shortened in workers exposed to polycyclic aromatic hydrocarbons (PAHs) and influenced by individual genetic variations in telomere-binding proteins. MicroRNAs (miRNAs) can affect the progress of messenger RNA (mRNA) transcription; however, whether polymorphisms in miRNA can act on the telomere length is still unknown. Therefore, we aimed to explore the relationships between telomere damage and genetic polymorphisms in miRNA or environmental exposure. A total of 544 coke oven workers and 238 healthy controls were recruited. After collecting peripheral blood and extracting the genomic DNA of the study subjects, the telomere length (TL) in their leucocytes was detected by a real-time quantitative polymerase chain reaction (PCR), and polymorphisms in miRNAs were genotyped using the flight mass spectrometry technique. The concentrations of the four urine OH-PAHs were determined by high performance liquid chromatography (HPLC), and the Soxhlet extraction method was used to detect the concentration of coke oven emissions (COEs) in the air. We found that the peripheral blood leucocyte DNA TL was significantly shorter in the exposure group (0.75; 0.51, 1.08) than that in the control group (1.05; 0.76, 1.44) (Z = 7.692, P < 0.001). The total cumulative exposure dose (CED), 1-hydroxypyrene, 2-hydroxynaphthalene, and 3-hydroxyphenanthrene were significantly negatively correlated with TL (r = -0.307, P < 0.001; r = -0.212, P < 0.001; r = -0.110, P = 0.025; r = -0.251, P < 0.001, respectively). MiR-145 rs353291 GG, miR-30a rs2222722 CT/CC, and miR-197 rs1889470 AA could protect the telomere end in the exposed workers (P < 0.05). The interaction between miR-197 rs1889470 and the CED had an effect on TL (ß = 0.066, P = 0.034). This is the first study to evaluate gene-environmental interactions for miRNA polymorphisms and PAH exposure in coke oven workers.

Diagnostic Value of Plasma MicroRNAs for Lung Cancer Using Support Vector Machine Model.

Aim: Small single-stranded non-coding RNAs (miRNAs) play an important role in carcinogenesis through degrading target mRNAs. However, the diagnostic value of miRNAs was not explored in lung cancers. In this study, a support-vector-machine (SVM) model for diagnosis of lung cancer was established based on plasma miRNAs biomarkers, clinical symptoms and epidemiology material. Methods: The expressions of plasma miRNA were examined with SYBR Green-based quantitative real-time PCR. Results: We identified that the expressions of 10 plasma miRNAs (miR-21, miR-20a, miR-210, miR-145, miR-126, miR-223, miR-197, miR-30a, miR-30d, miR-25), smoking status, fever, cough, chest pain or tightness, bloody phlegm, haemoptysis, were significantly different between lung cancer and control groups (P<0.05). The accuracies of the combined SVM, miRNAs SVM, symptom SVM, combined Fisher, miRNAs Fisher and symptom Fisher were 96.34%, 80.49%, 84.15%, 84.15%, 75.61%, and 80.49%, respectively; AUC of these six model were 0.976, 0.841, 0.838, 0.865, 0.750, and 0.801, respectively. The accuracy and AUC of combined SVM were higher than the other 5 models (P<0.05). Conclusions: Our findings indicate that SVM model based on plasma miRNAs biomarkers may serve as a novel, accurate, noninvasive method for auxiliary diagnosis of lung cancer.