Application of Serum Apelin and MMP-9 in Evaluation of Silicosis and Their Correlation with Lung Function

[Objectives]This study was conducted to explore the combination of serum Apelin and MMP-9 in the assessment of silicosis and their correlation with lung function. [Methods] From January 2020 to January 2021, eight patients with silicosis(including 3, 2 and 3 patients with silicosis in stages I, II and III respectively) were selected as the observation group, and eight persons frees of silicosis were selected as the control group during the same period. All patients were detected for serum APJ endogenous ligand(Apelin) of G protein-coupled receptor, matrix metalloproteinase-9(MMP-9) and pulmonary function indexes. The levels of serum Apelin and MMP-9 and lung function in the two groups were compared, and the correlation between serum Apelin and MMP-9 indexes and lung function was analyzed. [Results] The serum Apelin and lung function in the observation group were lower than those in the control group, and the level of MMP-9 in the observation group was higher than that in the control group, and the differences were statistically significant(P<0.05). The MMP-9 index in patients with silicosis in stage III was higher than those in patients with silicosis in stage II and stage I, and the MMP-9 index in patients with silicosis in stage II was higher than that in patients with silicosis in stage I, and the differences were statistically significant(P<0.05). The serum Apelin and lung function indexes of patients with silicosis in stage III were lower than those of patients with silicosis in stage II and stage I, and the serum Apelin and lung function indexes of patients with silicosis in stage II were lower than those of patients with silicosis in stage I, and the differences were statistically significant(P<0.05). The correlation analysis showed a positive correlation between serum Apelin and lung function indexes, and a negative correlation between MMP-9 and lung function indexes. [Conclusions] A lower serum Apelin and a higher MMP-9 value in patients with silicosis indicate severer lung function impairment, and the combined detection of serum Apelin and MMP-9 is conducive to effective evaluation of the disease of silicosis. The serum Apelin index was negatively correlated with silicosis, and the level of MMP-9 was positively correlated with silicosis, which could provide a scientific basis for clinical diagnosis and treatment.

Silicosis in Automobile Foundry Workers: A 29-Year Cohort Study

Objectives The purposes were to determine the relationship between silicosis among foundry workers and their cumulative exposure to silica dust, and to establish a regression model to predict the risk for developing silicosis by a given length of employment and air concentrations of silica at worksites. Methods A 29-year cohort study was conducted, including all those employed for more than one year during January 1, 1980 to December 31, 1996 and all members of the cohort were followed-up to December 3 1, 2008. In total, 2 009 workers of an automobile foundry in Shiyan, Hubei province were recruited in the study, 1 300 at eight worksites including sand preparation, cast shakeout, and finishing, melting, moulding, core-making, overhead crane operation and pouring as exposed group, and the other 709 auxiliary workers at the same factory, such as electricians, inspectors, fitters, and so on, as control group. Person-years of observation were calculated by persons observed and years followed-up for each of them. Person-year incidence of silicosis and its relative risk （RR） or odds ratio （OR） and 95% confidence intervals （CI） among the workers were estimated, adjusted for relevant factors with logistic regression model using SPSS version 15.0 software. Results Totally, 2 009 workers were followed-up for 37 151 person-years and 48 cases of silicosis were found, with an overall incidence of 1.34 per thousand, 2.02 per thousand in exposed group, and 0.15 per thousand in control one. Risk of silicosis was significantly higher in the exposed group than that in the control one （RR=13.13, 95% CI 3.18-54.13）, higher in men than that in women （RR=13.92, 95% CI 1.92-100.93）. Risks of silicosis varied by job, highest in those exposed to cast shakeout and finishing （RR=28.14, 95% CI 6.43-123.11）, followed by those exposed to pouring （RR-22.23, 95% CI 5.01-98.55） in the foundry. Average length of employment at onset of silicosis was 25.94 years, and silicosis incidence increased with length of employment. Average age at onset of silicosis was 47.83 years old. The risk of silicosis in workers with pulmonary tuberculosis was 2.57 folds as those without it （P〈0.01）. Ten deaths were recorded in those with silicosis, with a case-fatality rate of 20.83 percent three of them died of lung cancer, three of liver cancer, two of ischemic heart disease, and two of other diseases as their immediate causes of death. Incidence of silicosis in foundry workers positively correlated with their cumulative silica exposure （OR-3.00, 95% CI 2.34-3.83）. Risks of silicosis increased by 4.38 folds with an increase of 1 mg/m^3-year of cumulative silica exposure, and by 3.79 folds with smoking, respectively, adjusted for alcohol drinking and age. Based on a logistic regression model fitted, incidence of silicosis is expected to be 44.6 per thousand for those with daily exposure to silica of 4.18 mg/m^3 in average for 30 years, and if incidence of silicosis is expected to be less than 1 per thousand, daily exposure to silica should be controlled below 0.2 mg/m^3 for those with 20 years of employment, or below 0.1 mg/m^3 for those with 30 or 40 years of silica exposure. Conclusions At present, foundry workers in China still face high risk of developing silicosis. For lowering occurrence of silicosis in exposed workers, it seems necessary that current occupational exposure limits for silica at worksites in China should be reexamined and silica dust control measures be strengthend.

TNF-α and IL-1RA Polymorphisms and Silicosis Susceptibility in Chinese Workers Exposed to Silica Particles:A Case-Control Study

Abstract Objective To assess the association of TNF-α and IL-1RA SNPs with the risk of silicosis in Chinese workers exposed to silica particles. Methods Case-control study design was used to enroll 68 silicotic patients induced by silica particles and 68 healthy workers matched for length of silica particle exposure as controls. Both cases and controls were from the same company in southwest China, and each of them was requested to complete a questionnaire. Blood samples were drawn for genomic DNA extraction from each participant. The genotyping of TNF-α （-238 and -308） and IL-1RA （＋2018） was performed using polymerase chain reaction-based restriction fragment length polymorphism （PCR-RFLP） and SYBR green-based quantitative polymerase chain reaction {qPCR）, respectively. Unconditional logistic regression model was used to estimate odds ratios （ORs） and their 95% confidential intervals （Cl） for SNPs. Results No significant differences were found between cases and controls in particles exposure length, body mass index （BMI）, and status of smoking and alcohol consumption except for age （P=O.O01） and blood type （P=0.042）. The frequencies of TNF-c（（-238） and IL-1RA （＋2018） genotypes in cases were significantly different from those in controls, （P=O.O01 and P=0.O02, respectively）, while a borderline significant difference was found in the frequencies of TNF-α（-308） between cases and controls （P=0.063）. The variants of three SNPs increased the risk of silicosis in the Chinese workers exposed to silica particles. The adjusted ORs of TNFα（-308）, TNF-α（-238） and IL-1RA （＋2018） were 2.8 （95% Ch 2.1-7.5）, 20.9 （95% Ch 2.8-236.4） and 4.0 （95% CI： 2.6-10.2）, respectively. Conclusion It is suggested that cytokine polymorphisms of TNF-ct （-238, -308） and IL-1RA （＋2018） are associated with the risk of silicosis in the Chinese workers exposed to silica particles. Further independent studies on the interaction between SNPs and exposure to silica particles with a larger sample size are therefore warranted.

The Effects of Tetrandrine (TT) and Polyvinylpyridine-N-Oxide (PVNO) on Gene Expression of Type Ⅰand Type ⅢCollagens during Experimental Silicosis

In the screening tests of drugs for silicosis in our laboratory, we found that TT, a type of alkaloid isolated from Stephania tetrandra, could inhibit the development of experimental silicosis of rats and the synthesis of collagen in rat lung. Chest X-rays of silicotic patients treaied with TT for 1-3 years showed obvious changes. The silicotic nodules became smallel and shadows became clearer. PVNO was proved to have anti-silicotic effect on animal and clinically. This presentation reports the effect of them on collagen mRNA.Dot blot results showed that 1 (Ⅰ) and 1 (Ⅲ) mRNA levels increased significantly at 60 and 120 days after the rats were exposed to silica dust. The mRNA levels went down at 1 and 3 months after treated by TT and PVNO. In situ hybridization observation revealed that the silver grains of Type Ⅰand Type Ⅲ collagen were scattered within the fibroblasts in cellular nodules and in thickened interstitium of silicosis tissue. The amounts of mRNA silver grains decreased in the lung tissue treated by TT and PVNO. It was suggested that TT and PVNO may inhibil the gene expression of collagen during silicosis

Combined silicosis and mixed dust pneumoconiosis with rapid progression: A case report and literature review

BACKGROUND Rapidly progressive pneumoconiosis(RPP) occasionally occurs in coal workers, particularly those with high exposure to silica. Here, we report the case of a 64-year-old male miller with RPP. CASE SUMMARY The patient had a persistent cough for one month and had been clinically diagnosed with pulmonary tuberculosis in 2011. He worked in a stone processing factory from the ages of 20 through 37 and has owned his own mill for the past 25 years. His chest radiograph showed significant increases in the size and number of lung nodules since his last follow-up in 2013. By percutaneous needle lung biopsy, the nodular lesions showed diffuse infiltration of phagocytic macrophages and birefringent crystals by polarizing microscopy. He was finally diagnosed with RPP of mixed dust pneumoconiosis combined with silicosis. CONCLUSION In this case, mixed dust pneumoconiosis with silicosis might be accelerated by persistent exposure to graindust from working in a mill environment.

Modified Glasgow Prognostic Score, and Neutrophil/lymphocyte and Platelet/lymphocyte Ratios in Different Stages of Silicosis

Until now, although comprehensive management strategies have improved treatment, there are no treatments to alleviate symptoms and slow disease progression[1]. In the past few decades, there has been increasing evidence that inflammation plays a very important role in silicosis. Injury-induced inflammation is an effective strategy to remove harmful stimuli and initiate a healing process. However, it might be harmful to the organism and result in a permanent disease state if the inflammation is prolonged[2].

The Relationship between Polymorphisms of Interleukin-4 Gene and Silicosis

Objective To explore the relationship between polymorphisms of interleukin-4 （IL-4） gene （-33, ＋45, intron3, ＋429, ＋448） and the susceptibility of silicosis. Methods A case-control study was carried out. 101 silicosis patients were selected as cases. As strictly matching, 121 of non silicosis workers were selected as the controls. The polymophisms of IL-4 （five locus） were detected by the method of polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） techniques. Results The GA genotype in the IL-4＋429 locus and the CC genotype in the IL-4＋448 locus were found. The frequencies ofAA, GG and AG of IL-4＋45 locus in the cases were 55.4%, 10.9%, and 33.7% and in the controls were 62.0%, 12.6%, and 26.4%. The differences between cases and controls were not significant. The frequencies of B1B1, B2B2, and B1B2 of intron3 VNTR locus in the cases were 73.3%, 1.0%, and 25.7% and in the controls were 68.6%, 1.7%, and 29.8%. The differences were not significant. The frequencies of TT, CC, and CT in -33 locus in the cases were 55.4%, 11.9%, and 32.7% and in the controls were 69.4%, 4.1%, and 26.4%. The differences were significant （P=0.034）. Conclusion The relationship between genetic polymorphism of IL-4-33 site and silicosis has been found and -33TT is a protective genotype for silicosis.

Serum neuron-specific enolase:A promising biomarker of silicosis

BACKGROUND Silicosis is a type of chronic pulmonary fibrosis caused by long-term inhalation of silica dust particles.There has been no ideal biomarker for the diagnosis and differential diagnosis of silicosis until now.Studies have found that elevated neuron-specific enolase(NSE)concentration in the serum of silicosis patients is helpful for diagnosis and severity assessment of the disease.However,the number of cases in these studies was not enough to arouse attention.AIM To investigate the clinical significance of serum NSE in the diagnosis and staging of silicosis.METHODS From January 2017 to June 2019,326 cases of silicosis confirmed in Quanzhou First Hospital Affiliated to Fujian Medical University were included in the silicosis group.A total of 328 healthy individuals or medical patients without silicosis were included in the control group.Serum NSE concentrations of all subjects were determined by electrochemical luminescence.RESULTS There were no significant differences in sex,age,smoking index and complications between the silicosis and control groups.The mean serum NSE concentration was 26.57±20.95 ng/mL in the silicosis group and 12.42±2.68 ng/mL in the control group.The difference between the two groups was significant(U=15187,P=0.000).Among the 326 patients with silicosis,103 had stage I silicosis,and the mean serum NSE concentration was 15.55±6.23 ng/mL.The mean serum NSE concentration was 21.85±12.05 ng/mL in 70 patients with stage II silicosis.The mean serum NSE concentration was 36.14±25.72 ng/mL in 153 patients with stage III silicosis.Kruskal-Wallis H test suggested that the difference in serum NSE concentration in silicosis patients in the three groups was significant(H=130.196,P=0.000).Receiver operating characteristic curve analysis indicated that the area under the curve was 0.858(95%confidence interval:0.828-0.888;P=0.000).When the NSE concentration was 15.82 ng/mL,the Jorden index was the largest,the sensitivity was 72%,and the specificity was 90%.CONCLUSION Serum NSE concentration may be a promising biomarker for the diagnosis and assessment of severity of silicosis.

A Biochemical Study on Combined Treatment of Experimental Silicosis with Tetradrine-PVNO and Tetradrine-QOHP in Rats

A better understanding is needed to explain the mechanism of therapeutic effect of combined use of tetradrine-PVNO and tetradrine-QOHP which play very important roles in treatment of silicosis. Blood prolidase (PLD), monoamine oxidase (MAO) and plasminogen (PLG) in silicotic rats after treatment with tetradrine-PVNO or tetradrine-QOHP were measured. The values obtained were compared with the untreated silicotic rats. It was found that the silicotic rats that received tetradrine-PVNO showed significant increase in PLD and decrease in PLG, but no significant change in MAO. The PLD in plasma of silicotic rats that received tetradrine-QOHP were elevated significantly, but PLG and MAO did not change appreciably. These findings suggest that the combined use of tetradrine-PVNO and tetradrine-QOHP can accelerate the degradation of collagen in silicotic rats

Effects of respiratory rehabilitation training combined with Corbrin Capsule on the inflammatory response and pulmonary fibrosis in patients with silicosis complicated by COPD

Objective: To explore the effects of respiratory rehabilitation training combined with Corbrin Capsule on the inflammatory response and pulmonary fibrosis in patients with silicosis complicated by COPD. Methods: A total of 80 patients with silicosis complicated by COPD who were treated in our hospital between January 2013 and December 2016 were selected as the research subjects and randomly divided into control group (n=40) and observation group (n=40). Control group were treated with Corbrin Capsule on the basis of routine treatment, and observation group were treated with respiratory rehabilitation training combined with Corbrin Capsule on the basis of routine treatment. The differences in serum levels of inflammatory factors and pulmonary fibrosis indexes were compared between the two groups before intervention, after 6 months of intervention and after 1 year of intervention. Results: Before intervention, there was no statistically significant difference in serum levels of inflammatory factors and pulmonary fibrosis indexes between the two groups. After 6 months of intervention and after 1 year of intervention, serum inflammatory factors IL-6, IL-8, IL-12, IL-17, IL-18 and MCP-1 levels of observation group were lower than those of control group;serum pulmonary fibrosis indexes PCⅢ, LN, HA, ICAM-1 and HO-1 contents were lower than those of control group. Conclusion: Respiratory rehabilitation training combined with Corbrin Capsule therapy can effectively reduce the systemic inflammatory response and inhibit the pulmonary fibrosis process in patients with silicosis complicated by COPD.

Natural Course of Silicosis in Dust-exposed Workers

To provide a scientific basis for determining the health surveillance period of dust-exposed workers, data of a retrospective cohort study was re-analyzed with emphasis on natural course of silicosis. 33640 workers exposed to silica dust who were employed for at least 1 year from 1972 to 1974 in twenty Chinese mines or pottery factories were included as subjects, and were followed up till December 31, 1994. The cohort included subjects from 8 tungsten mines, 4 tin mines and 8 pottery factories. Our results showed that the mean latency of silicosis, for all the cases of the cohorts, was 22.9±9.8 y. 52.2 % of silicosis was diagnosed approximately 9.1±5.7 y after the dust exposure had ceased. The progression rates of silicosis from stage Ⅰ to Ⅱ and from stage Ⅱ to Ⅲ were 48.2 % and 18.5 %, and the duration was 4.1±0. 2 and 6.8±0.2 y, respectively. The survival times of silicosis stage Ⅰ , Ⅱ and Ⅲ, from the year of diagnosis to death, were 21.5, 15.8 and 6.8 years, respectively. There was 25 % of the silicosis patients whose survival time was beyond 33 y. The mean death age of all silicosis cases was 56.0 y. The death age inereased to 65.6 y in the middle of 1990s. Among dust-exposed workers, subjects who became suspected case （0^＋ ） accounted for 15.0 %. 48.7 % of the suspected silicosis cases developed to silicosis, and the average year from the time of being suspected of the disease to the first stage of silicosis was 5.1y. The natural characteristics, as mentioned above, varied with different mines and factories. We are led to conclude that silicosis is chronic in nature, but progress quickly. As a serious occupational disease it significantly reduces the life span of exposed workers. The study of its natural history is of importance for the development of health surveillance criteria for dust-exposed workers.

Studies on Structural Changes of Collagen in Silicosis

In order to provide scientific information on the prevention and treatment of silicosis,studies about changes of silicotic collagen in lungs were carried out. In this paper, we present experiments about the structural changes of collagen in silicotic lungs of rats and patients. These included electron microscopy, circular dichroism and infrared spectroscopy studies of collagen fibers. The results indicated that fibers of silicotic collagen were shorter in length, smaller in diameter and decreased in α-helix content. The -Si-O-R- group and -OH group were found increased and -C-C- backbone shortened. The increase of -Si-O-R-group indicated that silica formed linking bridges between collagens which may be the cause of progressive enlargement of nodules

Exploring the key pathways of tetrandrine in the treatment of early silicosis based on bioinformatics and in vitro experiments

Objective:Exploring the key pathways affecting the development of early silicosis based on bioinformatics and in vitro experiments.Method:Collecting differentially expressed genes in silicosis patients through literature mining;Collecting differentially expressed genes in silicon dioxide infusion mice by using a high-throughput gene expression database(GEO);Obtaining disease targets related to silicosis by means of online human Mendelian genetic database(OMIM),GeneCards and comparative toxicgenomics database(CTD);differentially expressed genes and disease targets were subjected to gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genome(KEGG)enrichment analysis via R-package and Metascape platforms,respectively.The Schrödinger and Pymol software were used for molecular docking and modification.Silicon dioxide-stimulated macrophages and epithelial cells were modeled and analyzed by PCR and western blot(WB).Result:2065 differentially expressed genes in silicosis patients,2291 differentially expressed genes in rat infused with silicon dioxide,and 803 targets for silicosis-related diseases were screened out.GO enrichment analysis mainly involves G protein-coupled receptor binding,the regulation of inflammatory response,and participation in immune response.The enrichment analysis of KEGG pathway mainly included ECM-receptor interaction,TNF signaling pathway,and IL-17 signaling pathway.IL-17 signaling pathway was screened out from different genes and disease targets,indicating that IL-17 signaling pathway might be the key pathway for the development of silicosis.Molecular docking results showed that the silicosis drug tetrandrine had good binding effect with the RAF/MEK/ERK pathway in the IL-17 signaling pathway.Cellular experiments showed that tetrandrine reduced the expression of inflammatory factors such as IL-6 and TGF-βin macrophages by regulating the RAF/MEK/ERKpathway,and inhibited the epithelialmesenchymal transition and expression of inflammatory factors in epithelial cells.Conclusion:Tetrandrine regulates the inflammatory response and epithelial-mesenchymal transition(EMT)through the RAF/MEK/ERK pathway and thus affects the early progression of silicosis.

Effect of oxidative stress on development of silicosis

AIM: To investigate the changes of oxidative stress indicators in the serum of silicosis patients and explore the mechanism of silicosis development.METHODS: Two hundred workers who were exposed to silica dust for more than one year were recruited as dust-exposed group, 100 non-dust-exposed subjects served as control group, 32 patients with suspected 0+ silicosis as observation group, and 130 silicosis patients were taken as the silicosis group. Indicators of oxidative stress, including superoxide dismutase(SOD), nitric oxide(NO), serum glutathione peroxidase(GSHPx), total antioxidant capacity(T-AOC), nitric oxide synthase(NOS), and lipid malondialdehyde(MDA), were determined in all the groups. RESULTS: Compared with the control group, NO and GSH-Px in dust-exposed group and silicosis group increased, and SOD decreased significantly(81.162± 35.176, 270.469 ± 39.228 and 68.209 ± 21.528, respectively, P = 0.004, P = 0.002, P = 0.005). Compared with the control and dust-exposed group, T-AOC, NOS and MDA in silicosis group increased significantly(13.048 ± 4.153, 36.201 ± 7.782 and 5.054 ± 1.204, respectively, P = 0.018, P = 0.022, P = 0.011). Compared with dust-exposed group, GSH-Px in the silicosis group increased significantly(270.469 ± 39.228, P = 0.002). GSH-Px in phase Ⅲ silicosis was significantly higher than in phase Ⅰsilicosis(290.750 ± 39.129, P = 0.021). Pearson correlation analysis showed that serum GSH-Px was positively correlated with silicosis staging, length of dust exposure and type of occupation(47.109 ± 8.015, P = 0.001).CONCLUSION: The imbalance of oxidative and antioxidation system is associated with the development of silicosis. The surveillance of oxidative stress indicators will benefit the prognosis of silicosis patients.

The Effects of N-acetyl-seryl-aspartyl-lysyl-proline on Expression of NF-κb and MCP-1 in Rats with Silicosis

In the present study, we developed silicosis of rat model by bronchial perfusion SiO2 dust, and intervenes with AcSDKP, immunohisto chemistry was used to detect NF-κb and MCP-1 expression in lung tissue, and positive cells were counted. We found that compared with silicotic model group, the positive cells of NF-κb and MCP-1 were decreased significantly in anti-fibrosis treatment of AcSDKP group. The findings suggest that AcSDKP could inhibit the expression of NF-κb and MCP-1 in lung tissue of silicosos, this may be related to AcSDKP inhibit of macrophage infiltration in lung tissue and reduced the degree of dust alveolitis.

The characteristics of plasma lipids in silicosis rat models were studied based on lipid metabolomics

Objective To screen the differential metabolites and metabolic pathways in silicosis model by analyzing plasma metabolomics of silicosis rats.Methods In May 2021,twenty male SD rats were randomly divided into control group(C),1-week silicosis group(S1W),2-week silicosis group(S2W)and 4-week silicosis group(S4W),with 5 rats in each group.

circPVT1 promotes silica-induced epithelial-mesenchymal transition by modulating the miR-497-5p/TCF3 axis

Epithelial-mesenchymal transition(EMT)is a vital pathological feature of silica-induced pulmonary fibrosis.However,whether circRNA is involved in the process remains unclear.The present study aimed to investigate the role of circPVT1 in the silica-induced EMT and the underlying mechanisms.We found that an elevated expression of circPVT1 promoted EMT and enhanced the migratory capacity of silica-treated epithelial cells.The isolation of cytoplasmic and nuclear separation assay showed that circPVT1 was predominantly expressed in the cytoplasm.RNA immunoprecipitation assay and RNA pull-down experiment indicated that cytoplasmic-localized circPVT1 was capable of binding to miR-497-5p.Furthermore,we found that miR-497-5p attenuated the silica-induced EMT process by targeting transcription factor 3(TCF3),an E-cadherin transcriptional repressor,in the silica-treated epithelial cells.Collectively,these results reveal a novel role of the circPVT1/miR-497-5p/TCF3 axis in the silica-induced EMT process in lung epithelial cells.Once validated,this finding may provide a potential theoretical basis for the development of interventions and treatments for pulmonary fibrosis.

Gefitinib and fostamatinib target EGFR and SYK to attenuate silicosis:a multi-omics study with drug exploration

Silicosis is the most prevalent and fatal occupational disease with no effective therapeutics,and currently used drugs cannot reverse the disease progress.Worse still,there are still challenges to be addressed to fully decipher the intricated pathogenesis.Thus,specifying the essential mechanisms and targets in silicosis progression then exploring anti-silicosis pharmacuticals are desperately needed.In this work,multi-omics atlas was constructed to depict the pivotal abnormalities of silicosis and develop targeted agents.By utilizing an unbiased and time-resolved analysis of the transcriptome,proteome and phosphoproteome of a silicosis mouse model,we have verified the significant differences in transcript,protein,kinase activity and signaling pathway level during silicosis progression,in which the importance of essential biological processes such as macrophage activation,chemotaxis,immune cell recruitment and chronic inflammation were emphasized.Notably,the phosphorylation of EGFR(p-EGFR)and SYK(pSYK)were identified as potential therapeutic targets in the progression of silicosis.To inhibit and validate these targets,we tested fostamatinib(targeting SYK)and Gefitinib(targeting EGFR),and both drugs effectively ameliorated pulmonary dysfunction and inhibited the progression of inflammation and fibrosis.Overall,our drug discovery with multi-omics approach provides novel and viable therapeutic strategies for the treatment of silicosis.

The study of the impact by atractylenolide-1 on inflammatory cytokine,autophagy and apoptosis in alveolar macrophages of silicosis patients

Objective To explore the effect of atractylenolide-1( ATL-Ⅰ) on alveolar macrophages in silicosis patients.Methods In December 2019,12 male silicosis patients treated in Beidaihe Sanatorium for Chinese Coal Miners from July to September 2019 were selected by random sampling.Their alveolar macrophages were collected and divided into control group,ATL-Ⅰ group( 100 μmol/L) and dimethyl sulfoxide( DMSO) group( 100 μmol/L).

Dynamic Variation of RAS on Silicotic Fibrosis Pathogenesis in Rats

The dynamic variation of renin-angiotensin system (RAS) in silicosis remains unclear.Seventy Wistar rats were divided into 7 groups including control group,silicosis groups (inhaling SiO2 for 2,4,8,16 and 24 weeks,respectively) and Captopril (Cap) group.Rat lung primary fibroblasts were divided into control group,SiO2-stimulated group (0,0.5,1,3,6,12,24 and 48 h) and Cap group.The silicotic nodules were formed and collagens were deposited gradually in silicosis group observed by haematoxylin and eosin (HE) staining and Van Gieson (VG) staining.Cap relieved the lung fibrosis and collagen deposition.Immunohistochemistry indicated the positive expression of α-smooth muscle actin α-SMA) was increased gradually in silicotic rat lung tissue.Western blotting revealed the expression of collagen type Ⅰ(Col Ⅰ) and α-SMA was up-regulated in silicotic rat lung tissue and fibroblasts stimulated by SiCh.Cap decreased the expression of Col Ⅰ and α-SMA in silicotic rat lung tissue and fibroblasts stimulated by SiCh.Western blotting also demonstrated the expression of angiotensin-converting enzyme (ACE) and angiotensin Ⅱ type 1 receptor (ATI) was increased,and the expression of ACE2 and Mas was decreased gradually in silicotic rat lung tissue and fibroblasts stimulated by SiCh.ELISA showed the serum levels of ACE and angiotensin Ⅱ(Ang Ⅱ) were also increased and ACE2 and Ang (1 -7) were decreased in the silicosis group.Treatment with Cap decreased the expression levels of ACE,Ang Ⅱ and ATI,and increased the expression levels of ACE2,Ang (1-7) and Mas.These findings suggested that an imbalance between ACE-Ang Ⅱ-AT1 axis and ACE2-Ang (l-7)-Mas axis may participate in the development of silicosis.