Objective This study aims to investigate the expression, phenotypic changes, and mechanisms of action of guanylate-binding protein 2 (GBP2) in the process of silica-induced pulmonary fibrosis. Methods The expression and localization of GBP2 in silicotic lung tissue were detected by immunohistochemical staining and immunofluorescence. An in vitro cell model was constructed, and methods such as Western blot and real-time quantitative reverse transcription polymerasechain reaction were utilized to investigate the function of GBP2 in different cell lines following silica stimulation. The mechanism of action of GBP2 in various cell lines was elucidated using Western blot analysis. Results GBP2 was highly expressed in the lung tissue of patients with silicosis. Immunohistochemical staining and immunofluorescence have revealed that GBP2 was localized in macrophages and epithelial cells. In vitro cell experiments demonstrated that silicon dioxide stimulated THP-1 cells to activate the c-Jun pathway through GBP2, promoting the secretion of inflammatory factors and facilitating the occurrence of M2 macrophage polarization. In epithelial cells, GBP2 promoted the occurrence of epithelial to mesenchymal transition (EMT) by upregulating Krueppel-like factor 8 (KLF8). Conclusion GBP2 not only activates c-Jun in macrophages to promote the production of inflammatory factors and the occurrence of M2 macrophage polarization, but also activates the transcription factor KLF8 in epithelial cells to induce EMT, collectively promoting the progression of silicosis.
Humans ; Silicosis/genetics* ; Macrophages/cytology* ; Epithelial Cells/pathology* ; GTP-Binding Proteins/physiology* ; Epithelial-Mesenchymal Transition ; Disease Progression ; Cell Line ; Male

BACKGROUND: Indonesia is among countries with a high incidence of multi drug-resistant tuberculosis (MDR-TB) globally. In this study, we aim to determine the prevalence of silico-tuberculosis among TB patients and to investigate the association of radiographic silicosis and the role of drug supervisor as well as other socio-clinical factors, in the development of MDR-TB in Indonesia. METHODS: A hospital-based study in West Java among 148 MDR-TB patients (case) and 164 drug-sensitive/DS-TB patients (control) was conducted. Chest x-rays were evaluated by two radiologists and one NIOSH B reader according to the ILO Classification. Face-to-face interviews were conducted using structured questionnaires to collect patients' information, including the task of drug supervisor. RESULTS: Findings indicate that supportive drug supervisor reduces the risk of developing MDR-TB, but silicosis showed no significant association. Nevertheless, in this study we found that 17 cases (5.4%) had silico-tuberculosis mostly exhibited as ILO profusion 3; predominated by q shape, 52.9% with large opacities and dominated by size A. Other factors significantly associated with the risk of developing MDR-TB were marital status, low income, longer traveling time to hospital, unsuccessful previous treatment and suffering drug side effects. CONCLUSION This study reveals that one of preventive healthcare strategy to protect TB patients from developing MDR-TB is supportive drug supervisor. While, the development of MDR-TB was not significantly influenced by silicosis; however, there is a notable prevalence of silicosis as determined by chest radiography, highlighting the critical need for dust control, occupational hygiene, and health screening for high-risk populations.
Indonesia/epidemiology* ; Humans ; Silicosis/diagnostic imaging* ; Male ; Tuberculosis, Multidrug-Resistant/etiology* ; Middle Aged ; Adult ; Female ; Prevalence ; Risk Factors ; Aged ; Antitubercular Agents/therapeutic use*

OBJECTIVE: Recent studies have overturned the traditional concept of the lung as a "sterile organ" revealing that pulmonary microbiota dysbiosis and abnormal surfactant proteins (SPs) expression are involved in the progression of silicosis. This study aimed to investigate the relationship between abnormal SPs expression and dysbiosis of lung microbiota in silica-induced lung fibrosis, providing insights into mechanisms of silicosis. METHODS: Lung pathology, SPs expression, and microbiota composition were evaluated in silica-exposed mice. A mouse model of antibiotic-induced microbiota depletion was established, and alveolar structure and SPs expression were assessed. The roles of the lung microbiota and SPs in silicosis progression were further evaluated in mice with antibiotic-induced microbiota depletion, both with and without silica exposure. RESULTS: Silica exposure induced lung inflammation and fibrosis, along with increased expression of SP-A expression. Antibiotics (Abx)-induced microbiota depletion elevated SP-A and SP-D expression. Furthermore, silica exposure altered lung microbiota composition, enriching potentially pathogenic taxa. However, antibiotic-induced microbiota depletion prior to silica exposure reduced silica-mediated lung fibrosis and inflammation. CONCLUSION Lung microbiota is associated with silica-induced lung injury. Overproduction of SP-A and SP-D, induced by Abx-induced microbiota depletion, may enhance the resistance of mouse lung tissue to silica-induced injury.
Animals ; Silicosis/prevention & control* ; Lung/metabolism* ; Mice ; Anti-Bacterial Agents/pharmacology* ; Microbiota/drug effects* ; Silicon Dioxide/toxicity* ; Mice, Inbred C57BL ; Male ; Pulmonary Surfactant-Associated Proteins/genetics*

Humans ; Nutrition Assessment ; Prognosis ; Silicosis/prevention & control* ; Occupational Diseases ; China/epidemiology* ; Occupational Exposure ; Silicon Dioxide

OBJECTIVES: The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is one of the main signaling pathways related to autophagy. Autophagy plays a key role in the formation of silicosis fibrosis. The phenotypic transformation of lung fibroblasts into myofibroblasts is a hallmark of the transition from the inflammatory phase to the fibrotic phase in silicosis. This study aims to investigate whether the PI3K/Akt/mTOR pathway affects the phenotypic transformation of silicosis-induced lung fibroblasts into myofibroblasts via mediating macrophage autophagy. METHODS: The human monocytic leukemia cell line THP-1 cells were differentiated into macrophages by treating with 100 ng/mL of phorbol ester for 24 h. Macrophages were exposed to different concentrations (0, 25, 50, 100, 200, 400 μg/mL) and different times (0, 6, 12, 24, 48 h) of SiO₂ dust suspension. The survival rate of macrophages was measured by cell counting kit-8 (CCK-8) method. Enzyme linked immunosorbent assay (ELISA) was used to measure the contents of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) in the cell supernatant. The co-culture system of macrophages and HFL-1 cells was established by transwell. A blank control group, a SiO₂ group, a LY294002 group, a SC79 group, a LY294002+SiO₂ group, and a SC79+SiO₂ group were set up in this experiment. Macrophages in the LY294002+SiO₂ group were pretreated with LY294002 (PI3K inhibitor) for 18 hours, and macrophages in the SC79+SiO₂ group were pretreated with SC79 (Akt activator) for 24 hours, and then exposed to SiO₂ (100 μg/mL) dust suspension for 12 hours. The expression of microtubule-associated protein 1 light chain 3 (LC3) protein in macrophages was detected by the immunofluorescence method. The protein expressions of PI3K, Akt, mTOR, Beclin-1, LC3 in macrophages, and collagen III (Col III), α-smooth muscle actin (α-SMA), fibronectin (FN), matrix metalloproteinase-1 (MMP-1), tissue metalloproteinase inhibitor-1 (TIMP-1) in HFL-1 cells were measured by Western blotting. RESULTS: After the macrophages were exposed to SiO₂ dust suspension of different concentrations for 12 h, the survival rates of macrophages were gradually decreased with the increase of SiO₂ concentration. Compared with the 0 μg/mL group, the survival rates of macrophages in the 100, 200, and 400 μg/mL groups were significantly decreased, and the concentrations of TGF-β1 and TNF-α in the cell supernatant were obviously increased (all P<0.05). When 100 μg/mL SiO₂ dust suspension was applied to macrophages, the survival rates of macrophages were decreased with the prolonged exposure time. Compared with the 0 h group, the survival rates of macrophages were significantly decreased (all P<0.05), the concentrations of TGF-β1 and TNF-α in the cell supernatant were significantly increased, and the protein expression levels of Beclin-1 and LC3II were increased markedly in the 6, 12, 24, and 48 h groups (all P<0.05). Immunofluorescence results demonstrated that after exposure to SiO₂ (100 μg/mL) dust for 12 h, LC3 exhibited punctate aggregation and significantly higher fluorescence intensity compared to the blank control group (P<0.05). Compared with the blank control group, the protein expressions of Col III, FN, α-SMA, MMP-1, and TIMP-1 in HFL-1 cells were up-regulated in the SiO₂ group (all P<0.05). Compared with the SiO₂ group, the protein expressions of PI3K, Akt, and mTOR were down-regulated and the protein expressions of LC3II and Beclin-1 were up-regulated in macrophages (all P<0.05), the contents of TNF-α and TGF-β1 in the cell supernatant were decreased (both P<0.01), and the protein expressions of Col III, FN, α-SMA, MMP-1, and TIMP-1 in HFL-1 cells were down-regulated (all P<0.05) in the LY294002+SiO₂ group. Compared with the SiO₂ group, the protein expressions of PI3K, Akt, and mTOR were up-regulated and the protein expressions of LC3II and Beclin-1 were down-regulated in macrophages (all P<0.05), the contents of TNF-α and TGF-β1 in the cell supernatant were increased (both P<0.01), and the protein expressions of Col III, FN, α-SMA, MMP-1, and TIMP-1 in HFL-1 cells were up-regulated (all P<0.05) in the SC79+SiO₂ group. CONCLUSIONS Silica dust exposure inhibits the PI3K/Akt/mTOR pathway, increases autophagy and concentration of inflammatory factors in macrophages, and promotes the phenotype transformation of HFL-1 cells into myofibroblasts. The regulation of the PI3K/Akt/mTOR pathway can affect the autophagy induction and the concentration of inflammatory factors of macrophages by silica dust exposure, and then affect the phenotype transformation of HFL-1 cells into myofibroblasts induced by silica dust exposure.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Silicon Dioxide/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Matrix Metalloproteinase 1/metabolism* ; Tissue Inhibitor of Metalloproteinase-1 ; Sirolimus ; Beclin-1/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Dust ; TOR Serine-Threonine Kinases/metabolism* ; Lung/metabolism* ; Fibroblasts/metabolism* ; Silicosis/metabolism* ; Macrophages/metabolism* ; Autophagy

Objective: To understand the social security situation of current cases of pneumoconiosis in non-coal mine industries in Jiangsu Province, and to provide reference for the treatment and security work of pneumoconiosis patients. Methods: From January to October 2020, a follow-up survey was conducted on 4038 cases of pneumoconiosis in non-coal mine industries of the province from October 1949 to December 2019. The age, type of pneumoconiosis, industry type, and social security status of the patients were collected. Namely, work-related injury insurance, employer compensation, basic medical insurance for urban and rural residents, major illness insurance, etc. SPSS 19.0 was used for statistical description and analysis. Results: The cases of pneumoconiosis in non-coal mine industries in Jiangsu Province ranged in age from 36 to 105 (70.78±8.43) years old, and had been exposed to dust for 1 to 55 (19.27±9.29) years. Silicosis was the main form (3875 cases, 95.96%), and non-metallic mining and dressing industry was the main form (2618 cases, 64.83%). A total of 3991 cases (98.84%) of pneumoconiosis patients enjoyed social security, most of them were urban and rural residents with basic medical insurance (3624 cases, 89.75%), but there were still 47 patients without any social security. 15 cases (0.37%) enjoyed the subsistence allowance, with the monthly allowance amount ranging from 104 to 3960 yuan, with the average amount of 954.87 yuan/month. Conclusion: In Jiangsu Province, the proportion of pneumoconiosis patients in non-coal mine industries enjoying social security is relatively high, but there are still patients who do not enjoy any social security, and the difference in the amount of subsistence allowance is slightly larger. It is necessary to further improve the medical security of pneumoconiosis patients and improve their quality of life.
Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Social Security ; Prevalence ; Quality of Life ; Pneumoconiosis/epidemiology* ; Silicosis/epidemiology* ; Etoposide ; Ifosfamide ; Mesna ; Coal Mining ; China/epidemiology*

Objective: Through comparative analysis of the disease burden of occupational pneumoconiosis in Gansu Province from 2010 to 2020, the main influencing factors are screened, and scientific basis is provided for rational allocation of limited health resources, precise management and policy implementation. Methods: In August 2021, survey and collect information on surviving occupational pneumoconiosis patients and dead occupational pneumoconiosis patients diagnosed in Gansu Province from 2010 to 2020, and analyze and calculate indicators such as morbidity, mortality, and disability adjusted of life years (DALY). Analyzing the influencing factors of disease burden usirrg multiple linear regression. Results: From 2010 to 2020, the average annual incidence of occupational pneumoconiosis in Gansu Province was 0.9992/100000, the average annual mortality was 0.897/100000, the cumulative case fatality rate was 25.75%, and the cumulative DALY was 28932.96 person-years. The first stage of occupational pneumoconiosis was the highest among DALY loss (19920.14 person-years), and the DALY loss was positively correlated with the stage of occupational pneumoconiosis. Among occupational pneumoconiosis in Gansu Province, silicosis (13753.66 person-years) and coal worker's pneumoconiosis (13414.73 person-years) caused the highest disease burden, followed by cement pneumoconiosis and asbestos lung. Period, length of service, type of disease, and region are all influencing factors of DALY loss (P<0.05). Conclusion: From 2010 to 2020, the DALY losses caused by occupational pneumoconiosis in Gansu Province showed a fluctuating decrease, with the composition of DALY mainly changing from the loss of life years due to premature death to the loss of years due to injury and disability.
Humans ; Pneumoconiosis/epidemiology* ; Silicosis/epidemiology* ; Anthracosis/epidemiology* ; Asbestos ; Cost of Illness ; China/epidemiology*

Objective: To evaluate the right ventricular function using two-dimensional speckle tracking echocardiography (2-D STE) and analyze the associated risk factors of right ventricular dysfunction in patients with silicosis. Methods: All 104 patients with silicosis treated in the Department of Occupational Medicine and Toxicology in Beijing Chao-Yang Hospital, Capital Medical University from May 2021 to September 2022 were enrolled in this study in October 2022. The clinical information of patients such as general data, arterial blood gas analysis and pulmonary function test were collected. The right ventricular function of patients was evaluated by 2-D STE-derived right ventricular free wall longitudinal strain (RVFWLS) and conventional echocardiographic-derived parameters, including right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE) and doppler tissue imaging-derived tricuspid lateral annular systolic velocity (S'), respectively. Based on their RVFWLS, the patients were divided into right ventricular dysfunction group and normal right ventricular function group. Risk factors for right ventricular dysfunction in patients with silicosis were analyzed using binary logistic regression analysis. Results: A total of 104 silicosis patients were enrolled, with aneverage age (65.52±11.18) years old, among whom including 57 cases diagnosed with stage Ⅰ/Ⅱ silicosis and 47 cases diagnosed with stage Ⅲ silicosis. 26 (25.00%) patients concurrent right ventricular dysfunction. The abnormal rates of RVFAC, TAPSE and S' in patients were 16.35% (17 cases), 21.15% (22 cases) and 6.73% (7 cases), respectively. The RVFAC and TAPSE in right ventricular dysfunction group were lower than those in normal right ventricular function group, and the incidence of pulmonary arterial systolic pressure ≥36 mmHg was higher than that in normal right ventricular function group (P<0.05). Logistic regression analysis showed that arterial partial pressure of oxygen (OR=0.932, 95%CI: 0.885-0.981, P=0.007) was the protective factor, and the forced expiratory volume in 1 second (FEV(1)) /forced vital capacity (FVC) ratio<70% (OR=5.484, 95%CI: 1.049-28.662, P=0.044) and stage Ⅲ silicosis (OR=6.343, 95%CI: 1.698-23.697, P=0.007) were the risk factors for silicosis patients concurrent right ventricular dysfunction. Conclusion: The incidence of right ventricular dysfunction is higher in patients with stage Ⅲ silicosis than that in patients with stage Ⅰ/Ⅱ silicosis. Using 2-D STE can help the early detection of silicosis with right ventricular dysfunction. Hypoxemia, airflow limitation and the stage Ⅲ silicosis are the risk factors for silicosis patients concurrent right ventricular dysfunction.
Humans ; Middle Aged ; Aged ; Ventricular Dysfunction, Right/etiology* ; Ventricular Function, Right ; Echocardiography ; Risk Factors ; Silicosis/diagnostic imaging*

Objective: To analyze the clinical diagnostic characteristics of pneumoconiosis patients of migrant workers in Hunan Province, and to provide scientific basis for the prevention and treatment of pneumoconiosis. Methods: In February 2022, through the Hunan Provincial Medical Treatment and Assistance Information Platform for Pneumoconiosis Migrant Workers, the cases of irresponsible subjects with pneumoconiosis that were first diagnosed clinically in Hunan Province from January 2017 to December 2021 were collected, and analyzed their gender, age, length of service, types of pneumoconiosis, stages of pneumoconiosis, and comorbidities. Results: From January 2017 to December 2021, there were a total of 26131 cases of irresponsible pneumoconiosis patients diagnosed clinically in Hunan Province, with males accounting for 99.8% (26072 cases) and an average age of (60.66±8.04) years old. Among the 26131 patients, coal workers' pneumoconiosis and silicosis were the main causes, with 16816 and 9078 cases respectively, accounting for 99.1% of the diagnosed cases. There were 8640 cases (33.1%) of stageⅠpneumoconiosis, 6601 cases (25.2%) of stage Ⅱ pneumoconiosis, and 10890 cases (41.7%) of stage Ⅲ pneumoconiosis. 2051 patients experienced complications. The average age of exposure to dust of 26131 patients was (17.81±9.69) years, and the age of exposure to dust in silicosis patients was (14.60±9.62) years. The working age of coal worker's pneumoconiosis was (19.60±9.26) years. Compared with coal workers' pneumoconiosis patients, silicosis patients had a shorter working time exposed to dust, and the difference was statistically significant (P<0.05) . Conclusion: Coal workers' pneumoconiosis and silicosis are mainly diagnosed for the first time in migrant workers' pneumoconiosis patients in Hunan Province. Pneumoconiosis patients should be diagnosed in time, which is conducive to treatment and rehabilitation.
Male ; Humans ; Middle Aged ; Aged ; Child ; Adolescent ; Young Adult ; Adult ; Child, Preschool ; Coal Mining ; Pneumoconiosis/epidemiology* ; Silicosis ; Anthracosis/epidemiology* ; Dust ; Coal ; China/epidemiology*

Objective: To investigate the epidemiological characteristics of pneumoconiosis deaths in Putuo District of Shanghai, and to provide evidence for prevention and management of pneumoconiosis in the future. Methods: In June 2021, the data of 263 patients with pneumoconiosis who died from January 1961 to December 2020 in Putuo District of Shanghai were retrospectively analyzed. Trend χ(2) test, analysis of variance and Spearman rank correlation methods were used to analyze the basic information, age of exposure to dust, promotion period, course of disease and direct cause of death of patients with pneumoconiosis. Results: Among the 263 cases of pneumoconiosis patients who died in Putuo District of Shanghai from 1961 to 2020, 260 cases (98.86%) were male. The main types of pneumoconiosis were foundry worker pneumoconiosis (53.23%, 140/263) and silicosis (43.73%, 115/263). The main types of pneumoconiosis were sand cleaner (36.50%, 96/263). The age of onset was (53.42±10.13) years old, the age of death was (76.14±9.12) years old, and the age of exposure to dust was (20.91±8.99) years. The duration of dust exposure was negatively correlated with the duration of disease (r(s)=-0.24, P<0.001). With the increase of pneumoconiosis stage, the mortality of silicosis and foundry worker pneumoconiosis also showed an increasing trend (χ(2)(trend)=4.22, 3.87, P=0.040, 0.049). 31.94% (84/263) of pneumoconiosis patients died directly from pneumoconiosis, ranking first among the direct causes of death. Conclusion: The death cases of pneumoconiosis in Putuo District of Shanghai are mainly foundry worker pneumoconiosis and silicosis, and pneumoconiosis is the main cause of death.
Humans ; Male ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Child ; Adolescent ; Young Adult ; Female ; Retrospective Studies ; China/epidemiology* ; Pneumoconiosis/epidemiology* ; Silicosis/epidemiology* ; Dust