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

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

Latent tuberculosis infection and infection-associated risk factors for miner workers with silicosis in eastern China.

OBJECTIVES: Silicosis people are at high risk of developing pulmonary tuberculosis. Whether silica exposure increases the likelihood of latent tuberculosis infection (LTBI) was not well understood, and potential factors involved in LTBI risk among silicosis people were not evaluated before. Thus, LTBI among silicosis people and potential risk factors for LTBI among silicosis people were evaluated in this study. METHODS: A cross-sectional study was undertaken for 130 miner workers with silicosis. The QFT-GIT was performed for LTBI detection. RESULTS: The LTBI was high to 31.6% (36/114) for silicosis participants, and 13.1% (13/99) had a history of tuberculosis. Drinking was associated with LTBI risk (OR = 6.92, 95%CI, 1.47-32.66, P = 0.015). Meanwhile, tunneling work was associated with an increased risk of LTBI compared with other mining occupations (OR = 3.91,95%CI,1.20-12.70, P = 0.024). CONCLUSIONS: The LTBI rate of silicosis participants was high and more than 10% had a history of tuberculosis. Drinking alcohol and tunneling were independent risk factors for LTBI in silicosis participants.

[5 cases of silicosis complicated with connective tissue diseases].

Long-term inhalation of silica dust can cause silicosis, but also may induce autoimmune diseases, such as systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, anti-histidyl tRNA synthetase antibody (JO-1 antibody) syndrome. These two diseases can be isolated or combined. In this paper, the clinical characteristics of 5 cases of silicosis complicated with connective tissue diseases were analyzed and summarized to strengthen the clinical understanding of silicosis complicated with connective tissue diseases, so as to reduce its misdiagnosis and missed diagnosis, and provide reference for clinicians in diagnosis and treatment.

[A case of silicosis complicated with non-tuberculous mycobacterium pulmonary disease].

Non-tuberculosis mycobacterium (NTM) refers to a general term for a large group of mycobacteria, excluding the mycobacterium tuberculosis and mycobacterium leprae, which is an opportunistic pathogen. NTM pulmonary disease and pulmonary tuberculosis have very similar clinical and imaging manifestations. Ordinary sputum tests can not distinguish between mycobacterium tuberculosis and NTM accurately, and it needs to be differentiated through detection methods such as mycobacterium culture medium, high-performance liquid chromatography, and molecular biology. During the diagnosis of occupational pneumoconiosis, a sandblasting and polishing worker's lung CT showed dynamic changes in infiltrating shadows and cavities in the right lung. A sputum drug sensitivity test showed NTM infection, but the patient refused treatment. After 20 months, the CT examination of the lung showed further enlargement of infiltrating shadows and cavities, and NTM bacterial identification showed intracellular mycobacterial infection. Amikacin, moxifloxacin, azithromycin, and ethambutol combined antibacterial treatment were given. Currently, the patient is still under treatment.

Results from omic approaches in rat or mouse models exposed to inhaled crystalline silica: a systematic review.

BACKGROUND: Crystalline silica (cSiO2) is a mineral found in rocks; workers from the construction or denim industries are particularly exposed to cSiO2 through inhalation. cSiO2 inhalation increases the risk of silicosis and systemic autoimmune diseases. Inhaled cSiO2 microparticles can reach the alveoli where they induce inflammation, cell death, auto-immunity and fibrosis but the specific molecular pathways involved in these cSiO2 effects remain unclear. This systematic review aims to provide a comprehensive state of the art on omic approaches and exposure models used to study the effects of inhaled cSiO2 in mice and rats and to highlight key results from omic data in rodents also validated in human. METHODS: The protocol of systematic review follows PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Eligible articles were identified in PubMed, Embase and Web of Science. The search strategy included original articles published after 1990 and written in English which included mouse or rat models exposed to cSiO2 and utilized omic approaches to identify pathways modulated by cSiO2. Data were extracted and quality assessment was based on the SYRCLE's Risk of Bias tool for animal studies. RESULTS: Rats and male rodents were the more used models while female rodents and autoimmune prone models were less studied. Exposure of animals were both acute and chronic and the timing of outcome measurement through omics approaches were homogeneously distributed. Transcriptomic techniques were more commonly performed while proteomic, metabolomic and single-cell omic methods were less utilized. Immunity and inflammation were the main domains modified by cSiO2 exposure in lungs of mice and rats. Less than 20% of the results obtained in rodents were finally verified in humans. CONCLUSION: Omic technics offer new insights on the effects of cSiO2 exposure in mice and rats although the majority of data still need to be validated in humans. Autoimmune prone model should be better characterised and systemic effects of cSiO2 need to be further studied to better understand cSiO2-induced autoimmunity. Single-cell omics should be performed to inform on pathological processes induced by cSiO2 exposure.

Psychometric properties of the Perceived Stress Scale (PSS-10) in silica-exposed workers from diverse cultural and linguistic backgrounds.

BACKGROUND: The Perceived Stress Scale (PSS-10) has been used in a range of occupational cohorts, but only recently in stone benchtop workers undergoing screening for silicosis. The aim of this study was to compare psychometric properties of the PSS-10 in stone benchtop workers amongst those born overseas or who used an interpreter. METHODS: Stone benchtop workers in Melbourne, Australia completed the PSS-10 as part of their occupational screening for silicosis. Internal consistency was assessed with Cronbach's α for the total score and the positive and negative subscales. Validity was assessed using confirmatory factor analysis (CFA). Analysis was performed for the total group and for subgroups according to sex, interpreter use, overseas-born, and language spoken at home. RESULTS: The results of 682 workers with complete PSS-10 scores were included in analysis. Most participants were male (93%), with mean age 36.9 years (SD 11.4), with just over half (51.6%) born in Australia, 10.1% using an interpreter, and 17.5% using a language other than English at home. Cronbach's α for the overall group (α = 0.878) suggested good internal consistency. DISCUSSION: CFA analysis for validity testing suggested PSS-10 performance was good for both sexes, moderate for country of birth and language spoken at home categories, but poorer for those who used an interpreter. Whilst professional interpreters provide a range of benefits in the clinical setting, the use of translated and validated instruments are important, particularly in cohorts with large numbers of migrant workers. CONCLUSION: This study describes the psychometric properties of the PSS-10 in a population of stone benchtop workers, with good internal consistency, and mixed performance from validity testing across various subgroups.

TB and interstitial lung disease: a systematic review and meta-analysis.

To determine the frequency of TB among patients with interstitial lung diseases (ILDs).We performed a comprehensive search in the PubMed/Medline, EMBASE and Scopus databases up to 1 August 2023 of studies reporting on the prevalence of TB among patients with ILDs.Twelve studies comprising 3,817 patients with ILD were found: the pooled prevalence of TB among ILD patients was 11.0% (95% CI 5.4-21.0). In the subgroup analysis, the TB rate among patients with silicosis and idiopathic pulmonary fibrosis (IPF) was respectively 35.6% (95% CI 32.6-38.8) and 4.4% (95% CI 3.6-5.3) (P = 0.00). The frequency of TB among ILD patients was higher in high TB burden countries than in low/intermediate-burden countries: 26.3%, 95% CI 17.7-37.3 vs. 4.9%, 95% CI 3.3-7.2; P = 0.00.This study shows the frequency of TB among ILD patients. The meta-analysis reveals a significantly increased prevalence of TB among ILD patients with silicosis compared to IPF, and among individuals in high TB burden countries than in those with low/intermediate burden. The study results can help physicians and policymakers make efficient decisions for prompt screening and anti-TB treatment initiation in ILD patients..

Macrophage-derived exosomal HMGB3 regulates silica-induced pulmonary inflammation by promoting M1 macrophage polarization and recruitment.

BACKGROUND: Chronic inflammation and fibrosis are characteristics of silicosis, and the inflammatory mediators involved in silicosis have not been fully elucidated. Recently, macrophage-derived exosomes have been reported to be inflammatory modulators, but their role in silicosis has not been explored. The purpose of the present study was to investigate the role of macrophage-derived exosomal high mobility group box 3 (HMGB3) in silica-induced pulmonary inflammation. METHODS: The induction of the inflammatory response and the recruitment of monocytes/macrophages were evaluated by immunofluorescence, flow cytometry and transwell assays. The expression of inflammatory cytokines was examined by RT-PCR and ELISA, and the signalling pathways involved were examined by western blot analysis. RESULTS: HMGB3 expression was increased in exosomes derived from silica-exposed macrophages. Exosomal HMGB3 significantly upregulated the expression of inflammatory cytokines, activated the STAT3/MAPK (ERK1/2 and p38)/NF-κB pathways in monocytes/macrophages, and promoted the migration of these cells by CCR2. CONCLUSIONS: Exosomal HMGB3 is a proinflammatory modulator of silica-induced inflammation that promotes the inflammatory response and recruitment of monocytes/macrophages by regulating the activation of the STAT3/MAPK/NF-κB/CCR2 pathways.

Dose-response relationship between lung function and chest imaging response to silica exposures in artificial stone manufacturing workers.

BACKGROUND: Occupational exposure to artificial stone, a popular material used for countertops, can cause accelerated silicosis, but the precise relationship between silica dose and disease development is unclear. OBJECTIVES: This study evaluated the impact of silica exposure on lung function and chest imaging in artificial stone manufacturing workers. METHODS: Questionnaire and spirometry assessments were administered to workers in two plants. A high-exposure subset underwent further evaluation, including chest CT and DLco. Weighting factors, assigned as proxies for silica exposure, were based on work tasks. Individual cumulative exposures were estimated using area concentration measurements and time spent in specific areas. Exposure-response associations were analyzed using linear and logistic regression models. RESULTS: Among 65 participants, the mean cumulative silica exposure was 3.61 mg/m3-year (range 0.0001 to 44.4). Each 1 mg/m3-year increase was associated with a 0.46% reduction in FVC, a 0.45% reduction in FEV1, and increased lung function abnormality risk (aOR = 1.27, 95% CI = 1.03-1.56). Weighting factors correlated with cumulative exposures (Spearman correlation = 0.59, p < 0.0001), and weighted tenure was associated with lung function abnormalities (aOR = 1.04, 95% CI = 1.01-1.09). Of 37 high-exposure workers, 19 underwent chest CT, with 12 (63%) showing abnormal opacities. Combining respiratory symptoms, lung function, and chest X-ray achieved 91.7% sensitivity and 75% specificity for predicting chest CT abnormalities. CONCLUSION: Lung function and chest CT abnormalities occur commonly in artificial stone workers. For high-exposure individuals, abnormalities on health screening could prompt further chest CT examination to facilitate early silicosis detection.

Systemic inflammation indices as hematological biomarkers of inflammatory response in non-silicotic workers exposed to respirable silica dust.

This cross-sectional study was performed to assess whether systemic inflammatory indices, including systemic inflammation response index (SIRI), systemic immune­inflammation index (SII), and aggregate index of systemic inflammation (AISI), can be considered as possible inflammatory markers in silica-exposed workers with no diagnosis of silicosis. We studied 371 non-silicotic workers exposed to respirable silica dust (RSD) and 1422 reference workers. The workers' exposure to RSD were assessed and the inflammatory indices were compared between subgroups of the exposed workers based on the severity and duration of exposure. Correlations between inflammatory indices and the pulmonary function parameters were investigated. Also, the receiver operating characteristic (ROC) curve and Youden index were used to determine the cut-off values of the SII, SIRI, and AISI. Significant dose-response relationships were observed between duration of exposure and all indices except monocytes and LMR. No significant interaction was observed between duration of exposure to RSD and smoking. Borderline significant correlations were observed between AISI and SIRI with forced expiratory volume (FEV1) and FEV1 to forced vital capacity (FVC) ratio. Higher AUCs were obtained for SII and AISI, respectively. The cut-off values for these biomarkers to be considered abnormal were > 348.48 for SII, > 183.78 for AISI, and > 0.768 for SIRI. Overall, the present study showed for the first time, that SII, AISI, and SIRI might be considered as available, easy-to-obtain, and non-expensive markers of inflammation in non-silicotic workers with a long duration of exposure to RSD who are at risk of developing silicosis in subsequent years.

Lung cancer risk and occupational pulmonary fibrosis: systematic review and meta-analysis.

BACKGROUND: Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary fibrosis and lung cancer. RESEARCH QUESTION: Is pulmonary fibrosis from exposure to occupational carcinogens an independent risk factor for lung cancer? STUDY DESIGN AND METHODS: A comprehensive search of PubMed, Embase, Web of Science and Cochrane databases with over 100 search terms regarding occupational hazards causing pulmonary fibrosis was conducted. After screening and extraction, quality of evidence and eligibility criteria for meta-analysis were assessed. Meta-analysis was performed using a random-effects model. RESULTS: 52 studies were identified for systematic review. Meta-analysis of subgroups identified silicosis as a risk factor for lung cancer when investigating odds ratios for silicosis in autopsy studies (OR 1.47, 95% CI 1.13-1.90) and for lung cancer mortality in patients with silicosis (OR 3.21, 95% CI 2.67-3.87). Only considering studies with an adjustment for smoking as a confounder identified a significant increase in lung cancer risk (OR 1.58, 95% CI 1.34-1.87). However, due to a lack of studies including cumulative exposure, no adjustments could be included. In a qualitative review, no definitive conclusion could be reached for asbestosis and silicosis as independent risk factors for lung cancer, partly because the studies did not take cumulative exposure into account. INTERPRETATION: This systematic review confirms the current knowledge regarding asbestosis and silicosis, indicating a higher risk of lung cancer in exposed individuals compared to exposed workers without fibrosis. These individuals should be monitored for lung cancer, especially when asbestosis or silicosis is present.

[The role of NLRP3 inflammasome pathway in silicosis-induced pulmonary fibrosis and its prospect as a therapeutic target].

Inhalation of crystalline silicon dioxide particles can induce silicosis, and the development of silicosis is closely related to the occurrence and development of pulmonary inflammation and pulmonary fibrosis. NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome has been established as a major proinflammatory receptor for sensing environmental danger signals. Activation of NLRP3 inflammasomes after phagocytosis of silicon dioxide particles by pulmonary macrophages may be an important mechanism to induce oxidative stress and sustained inflammatory response in the lung. This article summarizes the role of NLRP3 inflammasome in the inflammatory response and pulmonary fibrosis in silicosis, and analyzes it as a potential target for silicosis treatment.

The interplay of Cxcl10+/Mmp14+ monocytes and Ccl3+ neutrophils proactively mediates silica-induced pulmonary fibrosis.

As a fatal occupational disease with limited therapeutic options, molecular mechanisms underpinning silicosis are still undefined. Herein, single-cell RNA sequencing of the lung tissue of silicosis mice identified two monocyte subsets, which were characterized by Cxcl10 and Mmp14 and enriched in fibrotic mouse lungs. Both Cxcl10+ and Mmp14+ monocyte subsets exhibited activation of inflammatory marker genes and positive regulation of cytokine production. Another fibrosis-unique neutrophil population characterized by Ccl3 appeared to be related to the pro-fibrotic process, specifically the "inflammatory response". Meanwhile, the proportion of monocytes and neutrophils was significantly higher in the serum of silicosis patients and slices of lung tissue from patients with silicosis further validated the over-expression of Cxcl10 and Mmp14 in monocytes, also Ccl3 in neutrophils, respectively. Mechanically, receptor-ligand interaction analysis identified the crosstalk of Cxcl10+/Mmp14+ monocytes with Ccl3+ neutrophils promoting fibrogenesis via coupling of HBEGF-CD44 and CSF1-CSF1R. In vivo, administration of clodronate liposomes, Cxcl10 or Mmp14 siRNA-loaded liposomes, Ccl3 receptor antagonist BX471, CD44 or CSF1R neutralizing antibodies significantly alleviated silica-induced lung fibrosis. Collectively, these results demonstrate that the newly defined Cxcl10+/Mmp14+ monocytes and Ccl3+ neutrophils participate in the silicosis process and highlight anti-receptor-ligand pair treatment as a potentially effective therapeutic strategy in managing silicosis.

Early experience of endobronchial ultrasound-guided transbronchial nodal cryobiopsy: a case series from Sabah, Malaysia.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an established minimally invasive method for the diagnosis of benign and malignant conditions. Continuous efforts are underway to improve the material adequacy of EBUS-TBNA, including the introduction of a new technique called EBUS-guided transbronchial nodal cryobiopsy (EBUS-TBNC). This method allows for the retrieval of larger and well-preserved histologic samples from the mediastinum. We present a case series of four patients who underwent combined EBUS-TBNA and EBUS-TBNC procedures in our centre. All procedures were performed under general anaesthesia using a convex probe EBUS scope (Pentax EB-1970UK). Two patients were diagnosed with malignancy and two with benign disorders (silicosis and tuberculosis). In the malignant cases, both EBUS-TBNA/cell block and cryobiopsy provided a diagnosis but cryobiopsy yielded more material for ancillary tests in one patient. However, in the benign cases, there was discordance between EBUS-TBNA/cell block and cryobiopsy. Only cryobiopsy detected granuloma in the patient with TB (tuberculosis), and in the patient with silicosis, TBNC provided a better overall histological evaluation, leading to a definitive diagnosis. No complications were observed. This case series supports the potential diagnostic value of combining EBUS-TBNA and EBUS-TBNC, particularly in benign mediastinal lesions (granulomatous diseases), and in cases requiring additional molecular tests in cancer diagnosis.

Exploring a new lymph node biopsy technique: case series from Sabah, MalaysiaWe explored a new technique for lung diagnosis called EBUS-guided transbronchial nodal cryobiopsy (EBUS-TBNC). This method helps get larger and well-preserved tissue samples from the chest area. In our study, we used this technique on four patients alongside the established method called EBUS-guided transbronchial needle aspiration (EBUS-TBNA). All procedures were done with the patient under general anesthesia using a specific type of scope. Two patients were found to have cancer, and two had non-cancerous conditions (silicosis and tuberculosis). In the cancer cases, both methods provided a diagnosis, but the cryobiopsy gave more material for additional tests in one patient. However, in non-cancer cases, there were differences between the two methods. Only the cryobiopsy detected granulomas in the tuberculosis patient, and in the silicosis patient, cryobiopsy gave a better overall tissue evaluation, leading to a clear diagnosis. No complications were seen in any of the cases. This study suggests that combining EBUS-TBNA and EBUS-TBNC can be valuable, especially for non-cancerous chest lesions (like granulomatous diseases) and when extra tests are needed for cancer diagnosis.

lncRNA Profiling of Exosomes and Its Communication Role in Regulating Silica-Stimulated Macrophage Apoptosis and Fibroblast Activation.

Long-term silica particle exposure leads to interstitial pulmonary inflammation and fibrosis, called silicosis. Silica-activated macrophages secrete a wide range of cytokines resulting in persistent inflammation. In addition, silica-stimulated activation of fibroblast is another checkpoint in the progression of silicosis. The pathogenesis after silica exposure is complex, involving intercellular communication and intracellular signaling pathway transduction, which was ignored previously. Exosomes are noteworthy because of their crucial role in intercellular communication by delivering bioactive substances, such as lncRNA. However, the expression profile of exosomal lncRNA in silicosis has not been reported yet. In this study, exosomes were isolated from the peripheral serum of silicosis patients or healthy donors. The exosomal lncRNAs were profiled using high-throughput sequencing technology. Target genes were predicted, and functional annotation was performed using differentially expressed lncRNAs. Eight aberrant expressed exosomal lncRNAs were considered to play a key role in the process of silicosis according to the OPLS-DA. Furthermore, the increased expression of lncRNA MSTRG.43085.16 was testified in vitro. Its target gene PARP1 was critical in regulating apoptosis based on bioinformatics analysis. In addition, the effects of exosomes on macrophage apoptosis and fibroblast activation were checked based on a co-cultured system. Our findings suggested that upregulation of lncRNA MSTRG.43085.16 could regulate silica-induced macrophage apoptosis through elevating PARP1 expression, and promote fibroblast activation, implying that the exosomal lncRNA MSTRG.43085.16 might have potential as a biomarker for the early diagnosis of silicosis.

Burden of silica-attributed pneumoconiosis and tracheal, bronchus & lung cancer for global and countries in the national program for the elimination of silicosis, 1990-2019: a comparative study.

BACKGROUND: In industries worldwide, crystalline silica is pervasive and poses risks of pneumoconiosis and respiratory malignancies, with the latter being a knowledge gap in disease burden research that this study aims to address. By integrating both diseases, we also seek to provide an in-depth depiction of the silica-attributed disease burden. METHODS: Data from the Global Burden of Disease 2019 were extracted to analyze the disease burden due to silica exposure. The trends of age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) from 1990 to 2019, as well as the age-specific number and rate of deaths and disability-adjusted life years (DALYs) in 1990 and 2019, were presented using GraphPad Prism software. The average annual percentage changes (AAPCs) on ASMR and ASDR were calculated using joinpoint regression models. RESULTS: The global trends of disease burden due to silica exposure from 1990 to 2019 showed a significant decrease, with AAPCs on ASMR and ASDR of -1.22 (-1.38, -1.06) and - 1.18 (-1.30, -1.05), respectively. Vietnam was an exception with an unprecedented climb in ASMR and ASDR in general over the years. The age-specific deaths and DALYs mainly peaked in the age group 60-64. In comparison to 1990, the number of deaths and DALYs became higher after 45 years old in 2019, while their rates stayed consistently lower in 2019. Males experienced an elevated age-specific burden than females. China's general age-standardized burden of pneumoconiosis and tracheal, bronchus & lung (TBL) cancer ranked at the forefront, along with the highest burden of pneumoconiosis in Chilean males and South African females, as well as the prominent burden of TBL cancer in Turkish males, Thai females, and overall Vietnamese. The age-specific burden of TBL cancer surpassed that of pneumoconiosis, and a delay was presented in the pneumoconiosis pinnacle burden compared to the TBL cancer. Besides, the burden of pneumoconiosis indicated a sluggish growth trend with advancing age. CONCLUSION: Our research highlights the cruciality of continuous enhancements in occupational health legislation for countries seriously suffering from industrial silica pollution and the necessity of prioritizing preventive measures for male workers and elderly retirees.

Whole transcriptome sequencing identifies key lncRNAs,circRNAs, and mRNAs for exploring the pathogenesis and therapeutic target of mouse pneumoconiosis.

BACKGROUND: Pneumoconiosis is a kind of lung dysfunction caused by the inhalation of mineral dust. However, the potential molecular mechanism of pneumoconiosis have not been fully elucidated. METHODS: In this study, the silica-treated pneumoconiosis mice model was constructed and the transcriptome sequencing data including lncRNA, circRNA, and mRNA were obtained. Firstly, differentially expressed lncRNA, circRNA, and mRNA (DElncRNA, DEcircRNA, DEGs) between control and pneumoconiosis/silicosis samples were screened, the target miRNAs (co-pre-miRNAs) were obtained by intersecting the miRNAs predicted by DElncRNA and DEcircRNA, respectively, and the target mRNAs (co-mRNA) were obtained by intersecting the mRNAs predicted by target miRNA and DEGs. Then, the lncRNA/circRNA-miRNA-mRNA networks were constructed by Cytoscape. Next, the key mRNAs were obtained by protein-protein interaction (PPI) analysis, and the key lncRNAs/circRNAs were selected by correlation analysis. Moreover, the expression of the key lncRNAs, circRNAs and mRNAs on chromosome were studied by the "circlize" package. Furthermore, the TFs-miRNA-mRNA network was constructed and the function of DEGs were explored by Ingenuity Pathway Analysis (IPA). To demonstrate the feasibility and value of the constructed ceRNA networks, we validated key genes and mmu-miR-682 pathway. Finally, We used the Drug-Gene Interaction database to predict potential drugs that could interfere with key genes,which may help to find promising treatment. RESULTS: There were 427 DElncRNAs, 107 DEcircRNAs and 1,597 DEGs between silicosis and control groups. Totals of 77 co-pre-miRNAs and 96 co-mRNA were screened, and the lncRNA/circRNA-miRNA-mRNA networks were constructed with 27 lncRNA/25 circRNAs, 74 miRNAs and 96 mRNAs. Then, 6 key mRNAs including Igf1, Klf4, Ptgs2, Epas1, Gnao1, and Il1a were obtained by PPI, and all of these key mRNAs and 10 key lncRNAs and 8 circRNAs were significantly different between the pneumoconiosis and normal groups, in which 10 lncRNAs and 9 circRNA that have not been previously studied in pneumoconiosis/silicosis can be used as new potential therapeutic targets. Moreover, the TFs-miRNA-mRNA network were constructed with 11 TFs, 1 key miRNA (mmu-miR-682) and 3 key mRNAs (Igf1, Epas1, Ptgs2). And the validation of key genes revealing by RNA-seq through experimental approaches shows the the predictive power of this study. Finally, IPA results indicated that 41 pathways were activated and 2 pathways were suppressed in pneumoconiosis/silicosis groups, and Pathogen Induced Cytokine Storm Signaling Pathway was the most significant pathway affected by pneumoconiosis/silicosis. In addition, 93 drugs were screened out by Drug-Gene Interaction database. Among them, Hydroxychloroquine was a kind of drug which associated with Il1a and Ptgs2, may be a promising treatment. CONCLUSION: This study constructed the lncRNA/circRNA-miRNA-mRNA and TFs-miRNA-mRNA networks, which could deepen the potential molecular regulatory mechanism of pneumoconiosis/silicosis.

Health Screening Strategies for Artisanal and Small-Scale Miners for Tuberculosis, Human Immunodeficiency Virus and Silicosis: A Case of the USAID-Supported Kunda Nqob'iTB Project in Zimbabwe.

Artisanal and small-scale mining is characterized by excessive exposure to physical, chemical, ergonomic, psychosocial and biological hazards. There is a high burden of tuberculosis (TB), human immunodeficiency virus (HIV) infections and silicosis among artisanal and small-scale miners (ASMs). The aim of this project report is to describe lessons learned from strategies implemented to reach ASMs with screening services for TB, HIV and silicosis in Zimbabwe through the Kunda-Nqob'i TB (KNTB) project supported by the United States Agency for International Development (USAID). The intervention package for screening ASMs for TB, HIV and silicosis included service provision through two occupational health clinics at two provincial hospitals and a mobile workplace-based screening (WBS) facility at the mining sites. From 1 October 2020 to 30 September 2023, 10,668 ASMs were screened, with a high number of cases of silicosis (21%) and TB (7.4%). There was a high burden of HIV (30%) in ASMs attending the occupational health clinics. The two occupational health clinics screened 3453 ASMs, while the mobile WBS activities screened 7215 ASMs during the period. A total of 370 healthcare workers (doctors/clinical officers, nurses, environmental health technicians and district tuberculosis and Leprosy control officers) were trained on TB and the fundamental diagnostic principles of silicosis. The KNTB project has been successful in reaching out to many ASMs operating in remote and hard-to-reach mining areas. The KNTB project has brought to light the positive health-seeking behavior of ASMs operating in remote areas. The project has brought to the fore the effectiveness of multi-stakeholder engagement and collaboration in reaching out to ASMs in remote areas with health screening services. There is a high burden of TB, HIV and silicosis in ASMs. Screening for TB, HIV and silicosis using workplace-based screening and occupational health clinics is an effective strategy and should be rolled out to all areas with high artisanal and small-scale mining activity.