[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 pat...[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.展开更多
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...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.展开更多
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 eviden...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].展开更多
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 no...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.展开更多
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 tot...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.展开更多
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 literat...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.展开更多
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 mor...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.展开更多
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...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.展开更多
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 ...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.展开更多
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 ...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.展开更多
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 full...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.展开更多
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 fr...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).展开更多
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,res...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.展开更多
Objective Silicosis, caused by inhalation of silica dust, is the most serious occupational disease in China and the aim of present study was to explore the protective effect of Ang (1-7) on silicotic fibrosis and myof...Objective Silicosis, caused by inhalation of silica dust, is the most serious occupational disease in China and the aim of present study was to explore the protective effect of Ang (1-7) on silicotic fibrosis and myofibroblast differentiation induced by Ang Ⅱ. Methods HOPE-MED 8050 exposure control apparatus was used to establish the rat silicosis model. Pathological changes and collagen deposition of the lung tissue were examined by H.E. and VG staining, respectively. The localizations of ACE2 and a-smooth muscle actin (a-SMA) in the lung were detected by immunohistochemistry. Expression levels of collagen type Ⅰ, a-SMA, ACE2, and Mas in the lung tissue and fibroblasts were examined by western blot. Levels of ACE2, Ang (1-7), and Ang Ⅱ in serum were determined by ELISA. Co-localization of ACE2 and a-SMA in fibroblasts was detected by immunofluorescenee. Results Ang (1-7) induced pathological changes and enhanced collagen deposition in vivo. Ang (1-7) decreased the expressions of collagen type Ⅰ and a-SMA and increased the expressions of ACE2 and Mas in the silicotic rat lung tissue and fibroblasts stimulated by Ang Ⅱ. Ang (1-7) in creased the levels of ACE2 and Ang (1-7) and decreased the level of Ang Ⅱ in silicotic rat serum. A779 enhanced the protective effect of Ang (1-7) in fibroblasts stimulated by Ang Ⅱ. Conclusion Ang (1-7) exerted protective effect on silicotic fibrosis and myofibroblast differentiation induced by Ang Ⅱ by regulating ACE2-Ang (l-7)-Mas axis.展开更多
Based on published investigations of other researchers, the authors have carriedout experimental research for 20 years, and proved that the mechanisms of ear acupuncture in diag-nosing and treating diseases involved n...Based on published investigations of other researchers, the authors have carriedout experimental research for 20 years, and proved that the mechanisms of ear acupuncture in diag-nosing and treating diseases involved not only a single system, but rather a comprehensive functionalrelative system at varrious levels through a number of approaches. Examples are given to analyze howthe theory is utilized to guide clinical practice and to explain various clinical phenomena.展开更多
Environmental exposure to crystalline silica particles can lead to silicosis, which is one of the most serious pulmonary interstitial fibrosis around the world. Unfortunately, the exact mechanism on silicosis is uncle...Environmental exposure to crystalline silica particles can lead to silicosis, which is one of the most serious pulmonary interstitial fibrosis around the world. Unfortunately, the exact mechanism on silicosis is unclear, and the effective treatments are lacking to date. In this study, we aim to explore the molecular mechanism by which interleukin-11(IL-11) affects silica particles-induced lung inflammation and fibrosis. We observed that IL-11 expressions in mouse lungs were significantly increased after silica exposure, and maintained at high levels across both inflammation and fibrosis phase. Immunofluorescent dual staining further revealed that the overexpression of IL-11 mainly located in mouse lung epithelial cells and fibroblasts. Using neutralizing anti-IL-11 antibody could effectively alleviate the overexpression of pro-inflammatory cytokines(i.e., interleukin-6 and tumor necrosis factor-α) and fibrotic proteins(i.e., collagen type I and matrix metalloproteinase-2) induced by silica particles. Most importantly, the expressions of IL-11 receptor subunit α(IL-11Rα), Glycoprotein130(GP130), and phosphorylated extracellular signal-regulated kinase(p-ERK) were significantly increased in response to silica, whereas blocking of IL-11 markedly reduced their levels. All findings suggested that the overexpression of IL-11 was involved in the pathological of silicosis, while neutralizing IL-11 antibody could effectively alleviate the silica-induced lung inflammation and fibrosis by inhibiting the IL-11Rα/GP130/ERK signaling pathway. IL-11 might be a promising therapeutic target for lung inflammation and fibrosis caused by silica particles exposure.展开更多
Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide,but the molecular basis underlying its development remains unclear.An accumulating body of evidence supports gasdermin D(G...Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide,but the molecular basis underlying its development remains unclear.An accumulating body of evidence supports gasdermin D(GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases.However,there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis.In this work,we investigated the role of GSDMD-mediated pyroptosis in silicosis.Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression.Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica.Measurement of interleukin-1βrelease,lactic dehydrogenase activity,and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages.Additionally,we verified that both canonical(caspase-1-mediated)and non-canonical(caspase-4/5/11-mediated)signaling pathways mediated silica-induced pyroptosis activation,in vivo and in vitro.Notably,Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes,which highlighted the pivotal role of pyroptosis in this disease.Taken together,our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.展开更多
基金Supported by Science and Technology Fund Project of Guizhou Provincial Health Commission (gzwjkj2020-1-184)。
文摘[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.
文摘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.
文摘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].
基金Supported by Quanzhou Science and Technology Bureau,No.2018N053S.
文摘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.
基金Hubei Provincial Natural Science Foundation Project(Grant No.2014CFB478).
文摘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.
基金National Natural Science Foundation of China(No.81971483)Anhui University Collaborative Innovation Project(No.GXXT‑2020‑058)Anhui University of Science and Technology Innovation and Entrepreneurship Project(No.2021CX2125,2021CX2126,2021CX2124)。
文摘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.
文摘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.
文摘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.
文摘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.
基金funded by the National Natural Science Foundation of China(Grant No.82073518).
文摘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.
基金funded by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS)(grant number:2021-I2M-1-049)National Key Research and Development Program of China Grants(grant numbers:2021YFC2500700)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(grant number:2021RC31002,2018RC31001).
文摘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.
文摘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).
基金This study was supported by grants from the National Natural Science Foundation of China (No.81472953)Natural Science Foundation of Hebei Province (No.H2016209170)+2 种基金Graduate Student Innovation Fund of Hebei Province (No.2016196)Graduate Student Innovation Fund of North China University of Science and Technology (No.2016B10)Undergraduate Innovative Project of North China University of Science and Technology (No.X2017354).
文摘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.
基金supported by the National Natural Science Foundation of China [grant no.81472953]Natural Science Foundation of Hebei Province [grant no.H2016209170]+2 种基金Graduate Student Innovation Fund of Hebei Province [grant no.2016196]Graduate Student Innovation Fund of North China University of Science and Technology [grant no.2016B10]undergraduate innovative project of North China University of Science and Technology [grant no.X2017354]
文摘Objective Silicosis, caused by inhalation of silica dust, is the most serious occupational disease in China and the aim of present study was to explore the protective effect of Ang (1-7) on silicotic fibrosis and myofibroblast differentiation induced by Ang Ⅱ. Methods HOPE-MED 8050 exposure control apparatus was used to establish the rat silicosis model. Pathological changes and collagen deposition of the lung tissue were examined by H.E. and VG staining, respectively. The localizations of ACE2 and a-smooth muscle actin (a-SMA) in the lung were detected by immunohistochemistry. Expression levels of collagen type Ⅰ, a-SMA, ACE2, and Mas in the lung tissue and fibroblasts were examined by western blot. Levels of ACE2, Ang (1-7), and Ang Ⅱ in serum were determined by ELISA. Co-localization of ACE2 and a-SMA in fibroblasts was detected by immunofluorescenee. Results Ang (1-7) induced pathological changes and enhanced collagen deposition in vivo. Ang (1-7) decreased the expressions of collagen type Ⅰ and a-SMA and increased the expressions of ACE2 and Mas in the silicotic rat lung tissue and fibroblasts stimulated by Ang Ⅱ. Ang (1-7) in creased the levels of ACE2 and Ang (1-7) and decreased the level of Ang Ⅱ in silicotic rat serum. A779 enhanced the protective effect of Ang (1-7) in fibroblasts stimulated by Ang Ⅱ. Conclusion Ang (1-7) exerted protective effect on silicotic fibrosis and myofibroblast differentiation induced by Ang Ⅱ by regulating ACE2-Ang (l-7)-Mas axis.
文摘Based on published investigations of other researchers, the authors have carriedout experimental research for 20 years, and proved that the mechanisms of ear acupuncture in diag-nosing and treating diseases involved not only a single system, but rather a comprehensive functionalrelative system at varrious levels through a number of approaches. Examples are given to analyze howthe theory is utilized to guide clinical practice and to explain various clinical phenomena.
基金supported by the National Natural Science Foundation of China (Nos. 81803205 and 81872593)the China Postdoctoral Science Foundation (No. 2019T120665)+2 种基金the Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology (No. OHIC_(2)020G01)the Fundamental Research Funds for the Central Universities (No. 2020kfy XJJS005)the Open Projects Program of Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment (No. 2017B030314152)。
文摘Environmental exposure to crystalline silica particles can lead to silicosis, which is one of the most serious pulmonary interstitial fibrosis around the world. Unfortunately, the exact mechanism on silicosis is unclear, and the effective treatments are lacking to date. In this study, we aim to explore the molecular mechanism by which interleukin-11(IL-11) affects silica particles-induced lung inflammation and fibrosis. We observed that IL-11 expressions in mouse lungs were significantly increased after silica exposure, and maintained at high levels across both inflammation and fibrosis phase. Immunofluorescent dual staining further revealed that the overexpression of IL-11 mainly located in mouse lung epithelial cells and fibroblasts. Using neutralizing anti-IL-11 antibody could effectively alleviate the overexpression of pro-inflammatory cytokines(i.e., interleukin-6 and tumor necrosis factor-α) and fibrotic proteins(i.e., collagen type I and matrix metalloproteinase-2) induced by silica particles. Most importantly, the expressions of IL-11 receptor subunit α(IL-11Rα), Glycoprotein130(GP130), and phosphorylated extracellular signal-regulated kinase(p-ERK) were significantly increased in response to silica, whereas blocking of IL-11 markedly reduced their levels. All findings suggested that the overexpression of IL-11 was involved in the pathological of silicosis, while neutralizing IL-11 antibody could effectively alleviate the silica-induced lung inflammation and fibrosis by inhibiting the IL-11Rα/GP130/ERK signaling pathway. IL-11 might be a promising therapeutic target for lung inflammation and fibrosis caused by silica particles exposure.
基金supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMSNos.2021-1-I2M-049 and 2018-I2M-1-001,China)+1 种基金the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(Nos.2019RC330001 and 2021RC310002,China)National Natural Science Foundation of China(No.82090010)。
文摘Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide,but the molecular basis underlying its development remains unclear.An accumulating body of evidence supports gasdermin D(GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases.However,there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis.In this work,we investigated the role of GSDMD-mediated pyroptosis in silicosis.Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression.Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica.Measurement of interleukin-1βrelease,lactic dehydrogenase activity,and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages.Additionally,we verified that both canonical(caspase-1-mediated)and non-canonical(caspase-4/5/11-mediated)signaling pathways mediated silica-induced pyroptosis activation,in vivo and in vitro.Notably,Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes,which highlighted the pivotal role of pyroptosis in this disease.Taken together,our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.
