The mitochondria-targeted antioxidant MitoQ ameliorates inorganic arsenic-induced DCs/Th1/Th2/Th17/Treg differentiation partially by activating PINK1-mediated mitophagy in murine liver.

Inorganic arsenic is a well-established environmental toxicant linked to acute liver injury, fibrosis, and cancer. While oxidative stress, pyroptosis, and ferroptosis are known contributors, the role of PTEN-induced kinase 1 (PINK1)-mediated mitophagy in arsenic-induced hepatic immunotoxicity remains underexplored. Our study revealed that acute arsenic exposure prompts differentiation of hepatic dendritic cells (DCs) and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cells, alongside increased transcription factors and cytokines. Inorganic arsenic triggered liver redox imbalance, leading to elevated alanine transaminase (ALT), hydrogen peroxide (H2O2), malondialdehyde (MDA), and activation of nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway. PINK1-mediated mitophagy was initiated, and its inhibition exacerbates H2O2 accumulation while promoting DCs/Th1/Th2/Treg differentiation in the liver of arsenic-exposed mice. Mitoquinone (MitoQ) pretreatment relieved arsenic-induced acute liver injury and immune imbalance by activating Nrf2/HO-1 and PINK1-mediated mitophagy. To our knowledge, this is the first report identifying PINK1-mediated mitophagy as a protective factor against inorganic arsenic-induced hepatic DCs/Th1/Th2 differentiation. This study has provided new insights on the immunotoxicity of inorganic arsenic and established a foundation for exploring preventive and therapeutic strategies targeting PINK1-mediated mitophagy in acute liver injury. Consequently, the application of mitochondrial antioxidant MitoQ may offer a promising treatment for the metalloid-induced acute liver injury.

PINK1/Parkin-Mediated Mitophagy Partially Protects against Inorganic Arsenic-Induced Hepatic Macrophage Polarization in Acute Arsenic-Exposed Mice.

Inorganic arsenic is a well-known environmental toxicant and carcinogen, and there is overwhelming evidence for an association between this metalloid poisoning and hepatic diseases. However, the biological mechanism involved is not well characterized. In the present study, we probed how inorganic arsenic modulates the hepatic polarization of macrophages, as well as roles of PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy participates in regulating the metalloid-mediated macrophage polarization. Our results indicate that acute arsenic exposure induced macrophage polarization with up-regulated gene expression of inducible nitric oxide synthase (Inos) and arginase-1 (Arg1), monocyte chemotactic protein-1 (Mcp-1) and macrophage inflammatory protein-2 (Mip-2), tumor necrosis factor (Tnf)-α, interleukin (Il)-1ß and Il-6, as well as anti-inflammatory factors Il-4 and Il-10. In parallel, we demonstrated the disrupted hepatic redox balance typically characterized by the up-regulation of hydrogen peroxide (H2O2) and glutathione (GSH), and activation of PINK1/Parkin-mediated mitophagy in the livers of acute arsenic-exposed mice. In addition, our results demonstrate that it might be the PINK1/Parkin-mediated mitophagy that renders hepatic macrophage refractory to arsenic-induced up-regulation of the genes Inos, Mcp-1, Mip-2, Tnf-α, Il-1ß, Il-6 and Il-4. In this regard, this is the first time the protective effects of PINK1/Parkin-mediated mitophagy in inorganic arsenic-induced hepatic macrophage polarization in vivo have been reported. These findings add novel insights into the arsenical immunotoxicity and provide a basis for the preve.ntive and therapeutic potential of PINK1/Parkin-mediated mitophagy in arsenic poisoning.

Comparison of properties of dust in alveolar of rats and the workplace.

OBJECTIVES: The purpose of this study was to analyze the α-SiO2 content, composition, dispersion, morphology, and free radical content of dust between the alveolar and the workplace, to explore the possible changes in the properties (especially the pathogenicity) of dust after it enters the lung. METHODS: We collected the dust in the workplace in HANDAN Coal mine. They were selected by a 400 mesh sieve and was made a suspension of 50 mg/ml, which would be used to perfuse into the trachea of rats. When one week, four weeks, eight weeks, fourteen weeks, twenty weeks after perfusing, we harvested dust in rats alveolar through lung lavage for further processing. RESULTS: In the animal test, typical fibrous nodules appeared 20 weeks after dust exposure. No inflammatory reaction was observed in the saline group. The results of animal experiments showed that there was no significant difference in the content of α-SiO2 between dust in the workplace and the lung lavage (P > 0.05). The content of the Fe element gradually increased with dust exposure time. The 12 elements of Al, Mg, Si, Pb, Mn, Ni, Zn, Cu, Cr, Sb, Cd, and AS were reduced in the experiment group compared with the workplace group. The shape of the dust in the workplace was mostly spherical. The shape of the dust extracted from the lung lavage fluid was mostly blocky and angular, and a few dust edges were sharp, and more than 80% of the particle size was smaller than 5 µm, while less than 1% of the particle size was larger than 10 µm. The amount of hydroxyl radical released by lung lavage dust in phosphate buffer was higher than that of the workplace dust. CONCLUSIONS: After the dust entered the alveoli, the content of α-SiO2 in the dust did not change with dust exposure time, while the content of elements in the dust, the morphology, and dispersion of the dust changed. The ability of dust in alveoli to produce hydroxyl radicals in phosphate buffer was higher than that in the workplace.

Silica dust exposure induces autophagy in alveolar macrophages through switching Beclin1 affinity from Bcl-2 to PIK3C3.

Increased deposition of silica dust in pulmonary interstitial tissues leads to silicosis, in which autophagy plays a defensive role in silica dust-associated stress response and cell death. Our previous studies revealed that silica dust exposure contributed to autophagy in pulmonary macrophages in vivo, while the specific regulatory mechanism is still unclear. This study aimed to figure out the regulatory mechanism as well as the role of autophagy in the pathogenesis of experimental silicosis. We used 3-methyladenine (3-MA) and ABT-737 to suppress the expression of phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) and B cell leukemia/lymphoma 2 (Bcl-2), two critical initiators of autophagy, and detected and evaluated the autophagy in NR8383 cells with or without silica dust exposure. We found that exposure of silica dust increased autophagy in NR8383 cells and elevated the expression of Beclin1 and PIK3C3, but it reduced the expression of Bcl-2. The relationship among Beclin1, PIK3C3, and Bcl-2 were then investigated using immunoprecipitation analysis, and we found that suppression of PIK3C3 and/or Bcl-2 using 3-MA and/or ABT-737 could alter the autophagy induced by silica dust in NR8383 cells, and the complexes of Beclin1/PIK3C3 and Beclin1/Bcl-2 were both downregulated, which may be that inhibition of PIK3C3 and Bcl-2 altered the affinity of Beclin1 with PIK3C3 and Bcl-2 and lead to the silence of PIK3C3 signaling. These findings indicate that silica dust exposure induces autophagy via changing the connectivity of Beclin1 from Bcl-2 to PIK3C3.

Bioinformatics analysis on differentially expressed genes of alveolar macrophage in IPF.

Objective: This study aimed to explore the differentially expressed genes (DEGs) of pulmonary macrophages in human idiopathic pulmonary fibrosis (IPF) by bioinformatics, and elaborate on IPF on the gene level. Methods: The gene expression profile GSE49072 was downloaded from the gene expression omnibus (GEO) database. Genes of alveolar macrophages between normal volunteers and patients diagnosed as IPF were analyzed by GEO2R tools. Gene ontology (GO) and pathway enrichment analyses of genes were performed in the database for annotation, visualization and integrated discovery (DAVID) database, followed by functional annotation and protein-protein interaction (PPI) network construction in String website. Finally, the results were analyzed in a comprehensive way. Results: A total of 551 DEGs, including 205 down-regulated and 346 up-regulated were identified. The expression of 209875_s_at (secreted phosphoprotein 1, SPP1) and 214146_s_at (pro-platelet basic protein, PPBP) genes are the most significant in upregulated genes. DEGs in the MAPK（mitogen-activated protein kinase） signaling pathway and chemokine signaling pathway play important roles in the development of IPF. Conclusions: The up-regulation of genes such as SPP1 and PPBP affect the secretion of alveolar macrophages, thereby speeding up the process of fibrosis.

Establishment and application of an index system for prevention of coal workers' pneumoconiosis: a Delphi and analytic hierarchy process study in four state-owned coal enterprises of China.

OBJECTIVE: To explore the difference of cumulative incidence rate of coal workers' pneumoconiosis (CWP) among four large state-owned coal enterprises in northern China, we created an index system for evaluating the quality of comprehensive measures against CWP and applied the system to evaluate and compare the measures of the four coal enterprises. METHODS: A two-round Delphi investigation was conducted to identify the indicators in the index system. The weight values of the indicators were calculated with analytic hierarchy process methods. Measures of CWP, mine annals, records and other information in each coal mine of the four enterprises were collected. The evaluation scores, which ranged from 0 to 100, were calculated and compared with. RESULTS: A three-grade index system with 3 first-grade indicators, 9 second-grade indicators and 44 tertiary-grade indicators was established. The expert authority coefficient (Cr ) was 0.75 and the Kendall's coefficient of concordance (Kendall's W) was 0.15 (χ2=193.30, P<0.001). The weight value of 'Geological conditions' was 0.43, equal to 'Dust control engineering technology', and that of 'Occupational health management' was 0.14. The medians and quartiles of the evaluation scores of comprehensive measures against CWP of the four enterprises were 58.38 (54.60~63.02), 64.63 (60.83~67.06), 72.99 (68.92~77.67) and 75.07 (70.73~79.20), respectively. CONCLUSIONS: The index system could be effectively used for evaluation and comparison of the comprehensive measures against CWP among different enterprises. The geological conditions and dust control engineering technology played an important role in preventing and controlling CWP.

Analysis of Hemogram of Radiation Workers in Tangshan, China.

OBJECTIVES: This study aimed to investigate changes in peripheral blood cells of radiation workers and explore the impact of long-term ionizing radiation (IR) on human peripheral hemogram. METHODS: With a cohort method, we selected 1,392 radiation workers (case group) and 1,430 non-health-ray-exposure history persons (control group) to detect and analyze their peripheral hemogram. FAITH3000 automatic biochemical analyzer was used for blood testing. Examination of peripheral hemogram includes the examination of white blood cells (WBCs), platelet (PLTs), red blood cells (RBCs), hemoglobin (Hb), lymphocytes (LYMs), and mononuclear cells (MOs). The data analysis was conducted with software SPSS19.0. RESULTS: All the peripheral hemogram indicators (WBCs, RBCs, Hb, PLTs, LYMs, and MOs) in the case group, in accordance with the order of radiology diagnostic medical group, industrial inspection group, petroleum logging group, and radiotherapy medical group, showed a significant decreasing trend and were lower than those in the control group (all P < 0.05). Besides, with the increase of radiation seniority and accumulative radiation dose, all the peripheral hemogram indicators (WBCs, RBCs, Hb, PLTs, LYMs, and MOs) in the case group dramatically decreased and were lower than those in the control group (all P < 0.05). Seniority was in negative association with the expressions of WBCs, PLTs, RBCs, Hb, LYMs, and MOs and radiation dose with Hb, LYMs, and MOs (all P < 0.05). CONCLUSION: Long-term IR has some effects on the health of radiation workers, thus protective measures should be further strengthened.

[Relationship between genetic polymorphisms of matrix metalloproteinase-2 and -3 and susceptibility to silicosis].

OBJECTIVE: To investigate the relationship between the genetic polymorphisms of matrix metalloproteinase-2 (MMP-2) (-735) and matrix metalloproteinase-3 (MMP-3) (-1171) and the susceptibility to silicosis. METHODS: A case-control study was conducted in 113 patients diagnosed with stage I silicosis (case group) and 115 dust-exposed workers without silicosis (control group); the two groups had the same sex, ethnic group, and type of dust and similar age and cumulative exposure time. Polymerase chain reaction-restriction fragment length polymorphism was used to determine the genotypes of MMP-2 (-735) and MMP-3 (-1171). RESULTS: No significant difference was observed in age, cumulative exposure time, or smoking rate between cases and controls (P > 0.05). The frequencies of genotypes C/C, C/T, and T/T at MMP-2 C-735T in the case group were 57.5% (65/113), 31.0% (35/113), and 11.5% (13/113), respectively, which were significantly different from those of the control group (69.6% (80/115), 26.9% (31/115), and 3.5% (4/115)), χ² = 6.542, P < 0.05). The frequencies of T allele in cases and controls were 27.0% and 17.0%, respectively, which were significantly different from each other χ² = 6.704, P < 0.05). Carriage of T allele at MMP-2 C-735T increased the risk of silicosis (OR = 1.811, 95% CI: 1.151-2.847). The frequencies of genotypes 6A/6A, 5A/6A, and 5A/5A at MMP-3 A-1171A were 67.2% (76/113), 24.8% (28/113), and 8.0% (9/113), respectively, in the case group, versus 59.1% (68/115), 37.4% (43/115), and 3.5% (4/115) in the control group (χ² = 5.519, P > 0.05). CONCLUSION: Genetic polymorphism at MMP-2 C-735T is significantly associated with the development of silicosis. Carriage of T allele increases the risk of silicosis among workers exposed to dust. No significant association was found between MMP-3 A-1171A polymorphism and silicosis in this study.

[Investigation on psychological stress of mine emergency rescue personnel].

OBJECTIVE: To investigate psychological stress and influence factors on the mine emergency rescue personnel. METHOD: 564 mine emergency rescue personnel from a rescue group were select as subjects, and 60 designers from a steel design institute were as controls. Self-made questionnaire and general job stress questionnaire were used to investigate the basic information, rescue history, psychosomatic symptoms, depression symptoms, daily job stress and negative emotions of emergency rescue personnel. SPSS17.0 software was used to analysis the psychological stress on the mine rescue personnel and its influence factors. RESULTS: The detection rate (41.94%) of depression symptoms in rescue team was higher than that of controls (24.90%). The score of daily job stress was higher than that of logistical support. The older age group with higher negative emotional and daily job stress than the younger. The highest negative emotion was in age group of more than 40 years old. The highest score of daily job stress was in ≤30 years old. The score of depression and psychosomatic symptoms were higher than those of the college and the above. The scores of depression in group of duration of rescue <10 years was higher than that of duration≥10 years. The score of daily job stress is the lowest in rescue for 1 to 2 times per year and the highest in group of simulation training once a week. The score of daily job stress and depressive symptoms were getting higher with the extension of combat duty time. Age, hours of combat duty, training times a week, education and life events were the main affecting fectors on mental health of mine rescuers. CONCLUSIONS: Mine rescuers have more psychological stress than generic population. The psychological stress of the mine crew is related to age, education, life events, training and combat readiness duty time.

A Differential Protein Study on Bronchoalveolar Lavage Fluid at Different Stages of Silicosis.

OBJECTIVES: In this study, by comparing the difference in protein expression in bronchoalveolar lavage fluid between silicosis patients in different stages and healthy controls, the pathogenesis of pneumoconiosis was discussed, and a new idea for the prevention and treatment of pneumoconiosis was provided. METHODS: The lung lavage fluid was pretreated by 10 K ultrafiltration tube, Agilent 1100 conventional liquid phase separation, strong cation exchange column (SCX) HPLC pre-separation, and C18 reverse phase chromatography desalting purification, and protein was labeled with isotope. GO, KEGG pathway, and PPI analysis of differential proteins were conducted by bioinformatics, and protein types and corresponding signal pathways were obtained. RESULTS: Thermo Q-Exactive mass spectrometry identified 943 proteins. T-test analysis was used to evaluate the different significance of the results, and the different protein of each group was obtained by screening with the Ratio≥1.2 or Ratio≤0.83 and P<0.05. We found that there are 16 kinds of protein throughout the process of silicosis. There are different expressions of protein in stages III/control, stages II/control, stage I/control, stages III/ stages II, stages III/ stage I and stages II/ stage I groups. The results of ontology enrichment analysis of total differential protein genes show that KEGG pathway enrichment analysis of differential protein suggested that there were nine pathways related to silicosis. CONCLUSION: The main biological changes in the early stage of silicosis are glycolysis or gluconeogenesis, autoimmunity, carbon metabolism, phagocytosis, etc., and microfibril-associated glycoprotein 4 may be involved in the early stage of silicosis. The main biological changes in the late stage of silicosis are autoimmunity, intercellular adhesion, etc. Calcium hippocampus binding protein may participate in the biological changes in the late stage of silicosis. It provides a new idea to understand the pathogenesis of silicosis and also raises new questions for follow-up research.

Evaluation and the mechanism of ShengXian and JinShuiLiuJun decoction in the treatment of silicotic fibrosis: An integrated network pharmacology, life omics, and experimental validation study.

BACKGROUND: Silicosis is a systemic disease characterized by extensive fibrosis due to prolonged exposure to silica dust, with rising incidence rates significantly impacting global public health. ShengXian and JinShuiLiuJun Decoction (SXD) is a Chinese medicinal preparation containing a variety of medicinal plants. It has shown notable clinical efficacy in treating silicotic fibrosis in China. However, the precise mechanisms underlying its therapeutic effects remain unclear. This study integrates network pharmacology, multi-omics analysis, and experimental validation to investigate the potential mechanisms by which SXD treats silicotic fibrosis. OBJECTIVE: The study aims to investigate the therapeutic efficacy of SXD in treating silicotic fibrosis and to elucidate its underlying molecular mechanisms. METHODS: HPLC-Q-TOF-MS was used to identify the active components of SXD, and combined with network pharmacology, metabolomics, and transcriptomics, the mechanism of SXD in treating silicotic fibrosis was explored from multiple perspectives. The therapeutic effect of SXD was assessed through HE staining, Masson staining, Micro CT imaging, pulmonary function tests, and hydroxyproline content in lung tissue. Finally, network pharmacology and multi-omics findings were validated using molecular docking. CETSA, immunofluorescence, SPR, and Western blotting were used to analyze key factors in the NF-κB pathway at the animal, cellular, and molecular levels. RESULTS: SXD treatment improved lung function in silicosis rats, reduced inflammatory cell infiltration, collagen deposition, fibrosis and other pathological changes, and inhibited the protein expression of TNF-α, IL-17A, and IL-1ß, and NF-κB in lung tissue. HPLC-Q-TOF-MS combined with network pharmacology identified key compounds such as Liquiritigenin, 3-Methoxynobiletin, Isomangiferin, Hesperidin, shogaol, and Ligustroflavone, which likely exert therapeutic effects through the TNF, IL-17, NF-κB, and TGF-ß signaling pathways. Transcriptomics and metabolomics results revealed that SXD up-regulated the expression of NF-κB pathway-related genes (NFKBIA, NFKBIZ) and key regulators of the retinol metabolism pathway, while down-regulating pro-inflammatory genes (IL1B, IL17A, IL6). Experimental findings confirmed that SXD suppressed the expression of NF-κB pathway-related proteins and upstream activators TNF-α, IL-17A, and IL-1ß, as well as their receptors, in both lung tissue and cellular models. Additionally, SXD-containing serum had a direct, non-toxic effect on MRC-5 cells, effectively inhibiting collagen expression and TGF-ß secretion. SXD also had a positive effect on collagen production and extracellular matrix (ECM) aggregation in fibroblasts. Molecular dynamics studies showed that SXD directly binds to NF-κB and IκB. CONCLUSION: SXD exerts therapeutic effects on silicotic fibrosis by inhibiting NF-κB signaling transduction mediated by TNF-α, IL-17A, and IL-1ß, and suppressing fibroblast activation.

Difference in Intestinal Flora and Characteristics of Plasma Metabonomics in Pneumoconiosis Patients.

From the two perspectives of intestinal flora and plasma metabolomics, the mechanism of occurrence and development of pneumoconiosis was explored to provide a new target for the prevention and treatment of pneumoconiosis. In this study, 16S ribosome DNA (16SrDNA) gene sequencing technology was used to analyze the differences in intestinal flora of each research group through operational taxonomic units (OUT) analysis, cluster analysis, principal component analysis (PCA), partial least square discriminant analysis (PLS-DA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and other analytical methods were used to analyze the differences in plasma metabolites between the study groups. Metabonomics analysis showed that the plasma metabolites of pneumoconiosis patients were significantly different from those of normal people. Fold change > 2; vip > 1; p < 0.05 were the screening criteria. In the positive and negative mode, we screened ten types of differential metabolites. These ten metabolites were upregulated to varying degrees in the pneumoconiosis patients. Seven metabolic pathways were obtained by analyzing the metabolic pathways of different metabolites. Among them, the aminoacyl tRNA biosynthesis pathway changed most obviously. The α diversity of two groups of intestinal flora was analyzed using the 16SrDNA technique. The results showed that there was no significant difference in ACE, Chao1, Shannon, or Simpson in the two groups (p > 0.05). Beta diversity analysis showed that there were differences in microbial communities. In pneumoconiosis patients, the abundance of Prevotellaceae increased, and the other nine species decreased. Compared to the control group, the abundance of Prevotellaceae in the intestinal flora of pneumoconiosis increased, and the abundance of the other nine species decreased. Compared to controls, ten substances in the plasma metabolites of pneumoconiosis patients were upregulated. Seven metabolic pathways were obtained by analyzing the metabolic pathways of different metabolites. Among them, the aminoacyl tRNA biosynthesis pathway changed most significantly. This provided a theoretical basis for further study on the pathogenesis, early prevention, and treatment of pneumoconiosis.

Fas/FasL pathway-mediated alveolar macrophage apoptosis involved in human silicosis.

In vitro and in vivo studies have demonstrated that lung cell apoptosis is associated with lung fibrosis; however the relationship between apoptosis of alveolar macrophages (AMs) and human silicosis has not been addressed. In the present study, AM apoptosis was determined in whole-lung lavage fluid from 48 male silicosis patients, 13 male observers, and 13 male healthy volunteers. The relationships between apoptosis index (AI) and silica exposure history, soluble Fas (sFas)/membrane-bound Fas (mFas), and caspase-3/caspase-8 were analyzed. AI, mFas, and caspase-3 were significantly higher in lung lavage fluids from silicosis patients than those of observers or healthy volunteers, but the level of sFas demonstrated a decreasing trend. AI was related to silica exposure, upregulation of mFas, and activation of caspase-3 and -8, as well as influenced by smoking status after adjusting for confounding factors. These results indicate that AM apoptosis could be used as a potential biomarker for human silicosis, and the Fas/FasL pathway may regulate this process. The present data from human lung lavage samples may help to understand the mechanism of silicosis and in turn lead to strategies for preventing or treating this disease.

[Case-control study of relationship between polymorphisms of interleukin-4 gene and susceptibility of silicosis].

OBJECTIVE: To explore the relationship between polymorphisms of interleukin-4 (IL-4) gene (-33, +45, VNTR, +429, +448) and the susceptibility of silicosis. METHODS: In a case-control study, the case group consisted of 101 patients with silicosis, and was matched with the control group (121 workers without silicosis), according to the age, sex, nationality, working place, exposure to dust. The polymorphisms of IL-4 (five locus) detected by the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques. RESULTS: There was no difference of age, exposure and smoking between case group and control group (P > 0.05). The two groups had good comparability. Only the GA genotype in the IL-4 (+429) locus was found, the genotypes of AA and GG were not found. The CC genotype in the IL-4 (+448) locus was found, the genotypes of CG and GG were not found. The frequencies of AA, GG and AG of IL-4 (+45) locus in the case and control groups were 55.4%, 10.9%, 33.7% and 62.0%, 11.6%, 26.4%, respectively, there was no the significant difference between case and control groups (P > 0.05). The frequencies of B1B1, B2B2 and B1B2 of IL-4 (VNTR) locus in the case and control groups were 73.3%, 1.0%, 25.7% and 68.6%, 1.7%, 29.8%, respectively, there was no the significant difference between case and control groups (P > 0.05). The frequencies of TT, CC and CT in IL-4 -33 locus in the case group were 55.4%, 11.9% and 32.7%, which were significantly higher than those (69.4%, 4.1%, 26.4%) in control group (P < 0.05). CONCLUSIONS: There was no relationship between IL-4 (+45, VNTR) genotypes and prevalence of silicosis in this study. The polymorphisms of IL-4 (+448) site were not found which may be related to the race. The relationship between genetic polymorphism of IL-4 (-33) locus and silicosis development was found, Workers with IL-4 (-33) allele C are susceptible to the silica.

[Investigation about prevention behavior for dust workers in machinery, ceramic, and metallurgy industry].

OBJECTIVE: The purposes of this thesis were to study the behavior about workers exposed to dust and provide scientific basis for health promotion. METHODS: We designed a questionnaire and carry it on the 746 dust workers in the 3 representative corporations of Machinery, Ceramic, and Metallurgy Industry. All data were input into computer. And a database was established with Excel. SPSS11.5 statistical analysis software was used to analyze the influence on protecting behavioral between the application of qualifications, different jobs, training or protection, and other aspects etc. RESULTS: The rates were 94.4% and 75.3% about the regular physical examination and requirements for protective equipment. The rate of choosing an effective way of protection was generally low (15.4%). There was significant difference for among different educational background workers (P < 0.01). The rates of choosing an effective way of protection (20.3%), the regular physical examination (98.3%) and requirements for protective equipment (86.4%) in the dust workers who participated in the training of dust protection were superior than those who did not participated in the training. There was the significant difference (P < 0.05, P < 0.01). There was the significant difference for the rate of effective way of protection, regular physical examination, and requirements for protective equipment among the different corporations (P < 0.05). CONCLUSIONS: Dust workers' using rate about the choosing an effective way of protection was generally low in Machinery, Ceramic, and Metallurgy Industry. Those who were not educated had a lower using rate about the protection behavior, regular physical examination, and requirements for protective equipment than those educated.

Silica nanoparticle induces pulmonary fibroblast transdifferentiation via macrophage route: Potential mechanism revealed by proteomic analysis.

Recently, more and more attention has been focused on silica nanoparticles (SiNPs) as they are increasingly used in various fields. Yet, their biological effects, especially on human beings, largely remain unknown. This study was implanted to assess the biological responses in vitro elicited by human macrophages exposed to the SiNPs and to explore its toxicity and fibrosis biomarker. We found that SiNPs suppressed the viability of THP-1 cells in a dose-dependent manner while they triggered apoptosis and promoted the secretion of inflammatory factors. Next, SiNPs-induced macrophage supernatant was used to act on fibroblast (MRC-5), indicating that the expression of hydroxyproline (Hyp), α-SMA, and collagonIin MRC-5 increased after SiNPs treatment. To further explore the biomarker of fibrosis, Liquid-mass spectrometry facilitated quantitative proteomics, identified 3247 proteins, of which 791 proteins were expressed differentially in human embryonic lung fibroblasts after treated with SiNPs. In conclusion, our observations suggest that SiNPs induced THP-1-derived macrophage damage and apoptosis. Moreover, SiNPs induced macrophages to secrete cytokines that promote fibroblasts' proliferation and differentiation and changed protein expression in MRC-5 cells, regulating biological processes such as apoptosis, protein synthesis, and cell growth. Among these results, our findings could provide a basis for determining fibrosis biomarkers of silica nanoparticle exposure.

Activation of MAPK and Cyclin D1/CDK4 in Malignant Transformation of Human Embryonic Lung Fibroblasts Induced by Silica and Benzopyrene.

OBJECTIVE: Silica and Benzo(a)pyrene are listed as carcinogens. This study aims to explore Cyclin D1, CDK4 and difference of cell cycle adjusted by MAPK signal transduction pathway in silica and B(a)P-induced malignant transformation of human embryonic lung fibroblasts. METHODS: Activity of the subfamily (ERK, p38 and JNK) of mitogen-activated protein kinase (MAPK), cyclin D1 and CDK4 (cyclin dependent kinase) were evaluated using Human embryonic lung fibroblast (HELF) purchased from the cell room, basic research institute, Chinese Academy of Medical Sciences. The expression of cyclin D1 and CDK4 (cyclin dependent kinase) were measured in silica and B(a)P induced malignant using Western blot (WB) assay. RESULT: P-ERK and P-JNK expression increased significantly (P<0.01), while CDK4 and P-p38 expression decreased (P<0.01, P<0.05) in silica-induced malignant transformation cells compared with the control group. P-ERK, P-JNK and Cyclin D1 expression increased (P<0.01, P<0.01, P<0.05) in B(a)P-induced group compared with the control group. P-ERK and P-JNK expression decreased (P<0.01), while P-p38, Cyclin D1 and CDK4 expression increased (P<0.05, P<0.05, P<0.01) in B(a)P-induced group compared with the silica-induced group. CONCLUSION: MAPK and cyclin D1/CDK4 activation expressed differently in human embryo lung fibroblasts malignant transformation induced by silica and benzopyrene.

Different patterns of cyclin D1/CDK4-E2F-1/4 pathways in human embryo lung fibroblasts treated by benzo[a]pyrene at different doses.

OBJECTIVE: To investigate the roles of the cyclin D1/CDK4 and E2F-1/4 pathways and compare their work patterns in cell cycle changes induced by different doses of B[a]P. METHODS: Human embryo lung fibroblasts (HELFs) were treated with 2 micromol/L or 100 micromol/L B[a]P which were provided with some characteristics of transformed cells (T-HELFs). Cyclin D1, CDK4 and E2F-1/4 expressions were determined by Western blotting. Flow cytometry was used to detect the distribution of cell cycle. RESULTS: After B[a]P treatment, the proportion of the first gap (G1) phase cells decreased. CDK4 and E2F-4 expression did not change significantly. In 2 micromol/L treated cells, a marked overexpression of cyclin D1 and E2F-1 was observed. However, in T-HELFs overexpression was limited to cyclin D1 only, and no overexpression of E2F-1 was observed. The decreases of G1 phase in response to B[a]P treatment were blocked in antisense cyclin D1 and antisense CDK4 transfected HELFs (A-D1 and A-K4) and T-HELFs (T-A-D1 and T-A-K4). After 2 micromol/L B[a]P treatment, overexpression of E2F-1 was attenuated in A-D1, and E2F-4 expression was decreased significantly in A-K4. In T-A-D1 and T-A-K4, E2F-4 expression was increased significantly, compared with T-HELFs. The E2F-1 expression remained unchanged in T-A-D1 and T-A-K4. CONCLUSIONS: Cyclin D1/CDK4-E2F-1/4 pathways work in different patterns in response to low dose and high dose B[a]P treatment. In HELFs treated with 2 micromol/L B[a]P, cyclin D1 positively regulates the E2F-1 expression while CDK4 negatively regulates the E2F-4 expression; however, in HELFs treated with 100 micromol/L B[a]P, both cyclin D1 and CDK4 negatively regulate the E2F-4 expression.

[Decrease of cyclin D1 and CDK4 protein and their related factors induced by quartz in human embryonic lung fibroblasts].

OBJECTIVE: To study the expression level of cyclin D1-CDK4 protein in human embryonic lung fibroblasts (HELF) induced by quartz, and to study whether the expression level of cyclin D1-CDK4 protein mediated by mitogen activated protein kinase (MAPK)/(AP-1) signaling pathways. METHODS: Cells were harvested after stimulation 2 h for the detection of cytokines. Cyclin D1 and CDK4 (cyclin dependent kinase 4) proteins was measured by immunocytochemistry (IC) and Western blot (WB). RESULTS: The exposure of HELF to crystalline quartz for 2 hours could cause the decrease of cyclin D1 and cyclin dependent kinase 4 (CDK4) protein expression level, (7.91 +/- 0.29) x 10(3) and (5.17 +/- 0.28) x 10(4) respectively, which was lower than that of the HELF group (P < 0.05). AG126 (chemical inhibitor of the extracellular signal regulated protein kinase (ERK) signaling pathway) and the dominant negative mutant of ERK2 (molecular inhibitor of ERK2), prevented the decrease of cyclin D1 and CDK4 protein expression level. The chemical inhibitor of c-Jun NH2-terminal amino kinase (JNK), SP600125, could prevent both cyclin D1 and CDK4 protein expression level decrease. But SB203580, the chemical inhibitor of p38, prevented neither cyclin D1 nor CDK4 protein expression level decrease. Curcumin could prevent CDK4 protein expression level decrease but not cyclin D1 protein. CONCLUSION: ERKs and JNKs, but not p38, are responsible for the decrease of cyclin D1 and CDK4 protein expression level in HELF induced by quartz. AP-1 is responsible for the decrease of CDK4 expression level but not that of cyclin D1.