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Silica particles can cause silicosis, a disease characterized by diffuse fibrosis of the lungs. Various signaling pathways composed of different types of cells and cytokines are involved in the development of silicosis. Exosomes have become a research hotspot recently. However, the role of exosomal microRNA (miRNA) in silicosis remains unclear. In this study, we generated exosomal miRNA sequences from exosomes isolated from bronchoalveolar lavage fluid (BALF) of silicosis patients and the control group by high-throughput sequencing. Functional annotation and analysis of miRNA identified key target miRNAs. Levels of target miRNAs were analyzed in patient and animal samples and cells. Effects of increased miRNA were assessed through protein levels in target signaling pathways in cells treated with silica, miRNA mimics, and inhibitors. Our study identified 40 up-regulated and 70 down-regulated miRNAs, with miR-552–3p and its putative target gene Caveolin 1 (CAV1) as targets for further research. We found that the levels of exosomal miR-552–3p increased in silicosis patients' BALF samples, silicosis model mice, and A549 cells exposed to silica. Inhibition of miR-552–3p suppressed the expression of fibrosis markers. The increased miR-552–3p leads to the up-regulation of fibronectin and α-smooth muscle actin (α-SMA) and the suppression of caveolin 1 in fibroblast cells. Mitogen-activated protein kinase (MAPK) signaling pathways are activated in cells treated with silica and miR-552–3p mimics. These results help to understand exosomal miRNA-mediated intercellular communication and its key role in fibroblast activation and silicosis. [Display omitted] • This study identifies exosome-induced fibroblast proliferation in silicosis BALF. • The pro-fibrosis impact of epithelial cell-derived exosomes on fibroblasts is documented. • Observations show elevated miR-552-3p expression in silica-exposed A549, HPAEpiC cells, and their exosomes. • Study associates miR-552-3p upregulation with silicosis, confirms CAV 1 binding. • Exosome transport of epithelial miR-552-3p to fibroblasts results in phenotype transdifferentiation. [ABSTRACT FROM AUTHOR]

Background: Silicosis has always been a serious global occupational health problem. Oral microbiota plays important roles in the development of lung disease. However, few studies have investigated the relationship between periodontal conditions, oral bacteria and silicosis disease. Method: A single-center and cross-sectional study was conducted in 2019 in Sichuan Province, China, including a small sample of silicosis patient group and healthy control group. Demographic data and periodontal examinations measured by clinical attachment loss (CAL), bleeding on probing (BOP) and periodontal pocket (PD) were collected from each participant. Phenotypic changes were detected by histopathological staining. Next-generation sequencing targeting 16S ribosomal RNA was targeted to decipher the salivary microbiome of the two groups. Random forest, Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression and multivariable logistic regression analysis were conducted to find potential indicators to distinguish silicosis. Results: In general, 29 male healthy controls and 24 male silicosis patients were included. The proportion of CAL ≥ 3 mm in silicosis group was greater than control group, while the proportion of BOP (+) and PD ≥ 4 mm was reduced in silicosis group. The α-smooth muscle actin and fibronectin expression increased in gingiva of patients. The composition of salivary microbiota exhibited significant differences between the two groups, with silicosis patients demonstrating a lower diversity of salivary microbiota. Genus of Aggregatibacter [odds ratio (OR) = 0.000, p = 0.003] and Catonella (OR = 0.000, p = 0.049) were identified as biomarkers to distinguish silicosis. Conclusions: The silicosis group exhibited worse CAL, improved BOP and PD, which may be related to the gingival fibrosis found in this study. The composition of the oral microbiota underwent significant changes, accompanied by a decrease in diversity, in patients with silicosis. Our study indicates that respirable crystalline silica exposure affects oral health, and alterations of oral microbiota might be implicated in silicosis. We primarily identified Aggregatibacter and Catonella as the potential indicators to distinguish silicosis patients from healthy controls. [ABSTRACT FROM AUTHOR]

Background: India, with the highest global burden of tuberculosis (TB) and drug-resistant TB, aims to eliminate TB by 2025. Yet, limited evidence exists on drug resistance patterns and retreatment among patients with silico-tuberculosis. This study explores these patterns and assesses the impact of silicosis on TB retreatment in India. Methods: This secondary data analysis stems from a larger retrospective cohort study conducted in Khambhat, Gujarat, between January 2006 and February 2022. It included 138 patients with silico-tuberculosis and 2,610 TB patients without silicosis. Data from the Nikshay TB information portal were linked with silicosis diagnosis reports from the Pneumoconiosis Board using the unique Nikshay ID as the linking variable. Drug-resistant TB was defined as resistance to any anti-TB drug recorded in Nikshay. Retreatment refers to TB patients who have previously undergone anti-TB treatment for one month or more and need further treatment. Recurrent TB denotes patients who were previously declared cured or had completed treatment but later tested positive for microbiologically confirmed TB. Multivariable logistic regression was used to determine the impact of co-prevalent silicosis on drug resistance and retreatment. Results: Patients with silico-tuberculosis showed a higher proportion of retreatment compared to those without silicosis (55% vs. 23%, p < 0.001). Notably, 28% of patients with silico-tuberculosis were recurrent TB cases, compared to 11% among those without silicosis. Regarding drug resistance, the silico-tuberculosis group exhibited a higher rate (6% vs. 3%), largely due to rifampicin resistance (5% vs. 2%, p = 0.022). Co-prevalent silicosis was associated with a 2.5 times greater risk of drug-resistant TB (adjusted OR 2.5, 95% CI, 1.1–5.3; p = 0.021). Additionally, patients with silico-tuberculosis had a fourfold increased risk of retreatment for TB (adjusted OR 4, 95% CI, 3–6; p < 0.001). Conclusions: Co-prevalent silicosis significantly elevates the risk of drug resistance, recurrence, and retreatment among TB patients in India. This study indicates a need for improved treatment protocols and suggests that future research should focus on randomized controlled trials to evaluate appropriate anti-TB regimen and duration of therapy for this high-risk group. Given India's goal to eliminate TB by 2025, addressing the challenges posed by silico-tuberculosis is critical. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs play a key role in silicosis, a fatal fibrotic lung disease, and there is an urgent need to develop new treatment targets. Long intergenic non-protein-coding RNA 3047 (LINC03047) is associated with cancer, but its role and mechanism in the progression of silicosis require further elucidation. This study investigated the function of LINC03047 in the epithelial-mesenchymal transition (EMT) during silicosis progression. LINC03047 expression was upregulated in SiO 2 -treated BEAS-2B and A549 cells, promoting SiO 2 -induced ferroptosis and subsequent EMT. Moreover, knockdown of LINC03047 significantly decreased the expression of solute carrier family 39 member 14 (SLC39A14), a ferrous iron transporter, and inhibition of SLC39A14 alleviated the ferroptosis and EMT caused by LINC03047 overexpression. We further investigated that NF-κB p65 (RELA) was critical for LINC03047 transcription in SiO 2 -treated BEAS-2B and A549 cells. In vivo experiments showed that SLC39A14 deficiency improved SiO 2 -induced lipid peroxidation and EMT. Collectively, our study reveals the function of the RELA/LINC03047/SLC39A14 axis in SiO 2 -induced ferroptosis and EMT, thereby contributing to the identification of novel drug targets for silicosis therapy. [Display omitted] • Silicosis is a lethal lung disease urgently requiring new treatment targets. • High expression of LINC03047 was related with silica-induced ferroptosis and EMT. • Inhibition of SLC39A14 alleviated silica-induced ferroptosis and EMT. • LINC03047 regulated silica-induced ferroptosis and EMT via SLC39A14. • RELA was critical for LINC03047 transcription in SiO2-treated cells. [ABSTRACT FROM AUTHOR]

Engineered stone‐associated silicosis is characterised by a rapid progression of fibrosis linked to a shorter duration of exposure. To date, there is lack of information about molecular pathways that regulates disease development and the aggressiveness of this form of silicosis. Therefore, we compared transcriptome responses to different engineered stone samples and standard silica. We then identified and further tested a stone dust specific pathway (aryl hydrocarbon receptor [AhR]) in relation to mitigation of adverse lung cell responses. Cells (epithelial cells, A549; macrophages, THP‐1) were exposed to two different benchtop stone samples, standard silica and vehicle control, followed by RNA sequencing analysis. Bioinformatics analyses were conducted, and the expression of dysregulated AhR pathway genes resulting from engineered stone exposure was then correlated with cytokine responses. Finally, we inhibited AhR pathway in cells pretreated with AhR antagonist and observed how this impacted cell cytotoxicity and inflammation. Through transcriptome analysis, we identified the AhR pathway genes (CYP1A1, CYP1B1 and TIPARP) that showed differential expression that was unique to engineered stones and common between both cell types. The expression of these genes was positively correlated with interleukin‐8 production in A549 and THP‐1 cells. However, we only observed a mild effect of AhR pathway inhibition on engineered stone dust induced cytokine responses. Given the dual roles of AhR pathway in physiological and pathological processes, our data showed that expression of AhR target genes could be markers for assessing toxicity of engineered stones; however, AhR pathway might not play a significant pathologic role in engineered stone‐associated silicosis. By comparing transcriptome responses of lung cells to engineered stone and standard silica, we have identified a specific pathway (aryl hydrocarbon receptor, AhR) potentially associated with development of engineered stone‐associated silicosis. However, our further study only shows mild effect of AhR pathway inhibition on engineered stone dust induced cytokine responses. Taken together, we conclude that AhR pathway is a marker of lung cell activation, but does not play a central pathologic role in engineered stone‐associated silicosis. [ABSTRACT FROM AUTHOR]

Objective: Interstitial lung diseases (ILDs) are diverse pulmonary disorders marked by diffuse lung inflammation and fibrosis. The variability in characteristics and treatment approaches complicates diagnosis and management. In advanced cases requiring transplantation, determining indications and selecting suitable candidates presents additional challenges. Methods: Of all patients with non-IPF ILD between December 2016 to December 2022 were analyzed retrospectively. Patients were categorized into two groups: transplanted patients and deceased patients on the waiting list. Clinical data and survival outcomes were compared between groups. Results: Of the 43 patients, 20 underwent lung transplantation while 23 died awaiting transplantation. Waiting list mortality was 53.4%, with median waiting times similar between groups (3 months for transplant patients and 6 months for those on the waiting list). There were no significant differences between groups in age, gender, height, BMI, 6-minute walk test (6MWT), or forced vital capacity (FVC). The prevalence of pulmonary hypertension (PH) was 76.7% in right heart catheterizations, similar in both groups. One single and 19 bilateral lung transplants were performed. Overall, 13 of the 20 patients survived to discharge from the hospital. One-year mortality was 7/20 (35%). The median follow-up was 34 months, with a 1-year conditional survival of 90.9% at 3 years and 70.7% at 5 years. Conclusions: This study underscores the importance of further research into non-IPF ILDs. Lung transplantation remains a viable option that can significantly enhance both the quality and longevity of life for patients with advanced ILD. [ABSTRACT FROM AUTHOR]

Tetrandrine (TET) has been traditionally used in China as a medication to treat silicosis and has recently demonstrated anti-SARS-CoV-2 potential in vitro. By recognizing the disparity between in vitro findings and in vivo performance, we aimed to estimate the free lung concentration of TET using a physiologically based pharmacokinetic (PBPK) model to link in vitro activity with in vivo efficacy. Comparative pharmacokinetic studies of TET were performed in rats and dogs to elucidate the pharmacokinetic mechanisms as well as discern interspecies variations. These insights facilitated the creation of an animal-specific PBPK model, which was subsequently translated to a human model following thorough validation. Following validation of the pharmacokinetic profile from a literature report on single oral dosing of TET in humans, the plasma and lung concentrations were predicted after TET administration at approved dosage levels. Finally, the antiviral efficacy of TET in humans was assessed from the free drug concentration in the lungs. Both in vivo and in vitro experiments thus confirmed that the systemic clearance of TET was primarily through hepatic metabolism. Additionally, the lysosomal capture of basic TET was identified as a pivotal factor in its vast distribution volume and heterogeneous tissue distribution, which could modulate the absorption dynamics of TET in the gastrointestinal tract. Notably, the PBPK-model-based unbound lung concentration of TET (1.67-1.74 μg/mL) at the recommended clinical dosage surpassed the in vitro threshold for anti-SARS-CoV-2 activity (EC90 = 1.52 μg/mL). Thus, a PBPK model was successfully developed to bridge the in vitro activity and in vivo target exposure of TET to facilitate its repurposing. [ABSTRACT FROM AUTHOR]

AbstractAlveolar macrophages (AMs), the first line against the invasion of foreign invaders, play a predominant role in the pathogenesis of silicosis. Studies have shown that inhaled silica dust is recognized and engulfed by AMs, resulting in the production of large amounts of silica-induced reactive oxygen species (ROS), including particle-derived ROS and macrophage-derived ROS. These ROS change the microenvironment of the AMs where the macrophage phenotype is stimulated to swift from M0 to M1 and/or M2, and ultimately emerge as the M2 phenotype to trigger silicosis. This is a complex process accompanied by various molecular biological events. Unfortunately, the detailed processes and mechanisms have not been systematically described. In this review, we first systematically introduce the process of ROS induced by silica in AMs. Then, describe the role and molecular mechanism of M2-type macrophage polarization caused by silica-induced ROS. Finally, we review the mechanism of pulmonary fibrosis induced by M2 polarized AMs. We conclude that silica-induced ROS initiate the fibrotic process of silicosis by inducing macrophage into M2 phenotype, and that targeted intervention of silica-induced ROS in AMs can reprogram the macrophage polarization and ameliorate the pathogenesis of silicosis. [ABSTRACT FROM AUTHOR]

Assessing the association between candidate single-nucleotide polymorphisms (SNPs) identified by multi-omics approaches and susceptibility to silicosis. RNA-seq analysis was performed to screen the differentially expressed mRNAs in the fibrotic lung tissues of mice exposed to silica particles. Following this, we integrated the SNPs located in the above human homologenes with the silicosis-related genome-wide association study (GWAS) data to select the candidate SNPs. Then, expression quantitative trait locus (eQTL)-SNPs were identified by the GTEx database. Next, we validated the associations between the functional eQTL-SNPs and silicosis susceptibility by additional case–control study. And the contribution of the identified SNP and its host gene in the fibrosis process was further validated by functional experiments. A total of 12 eQTL-SNPs were identified in the screening stage. The results of the validation stage suggested that the variant T allele of rs419540 located in IL12RB1 significantly increased the risk of developing silicosis [additive model: odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.11–2.85, P = 0.017]. Furthermore, the combination of GWAS and the results of validation stage also indicated that the variant T allele of rs419540 in IL12RB1 was associated with increased silicosis risk (additive model: OR = 2.07, 95% CI 1.38–3.12, P < 0.001). Additionally, after knockdown or overexpression of IL12RB1, the levels of pro-inflammatory factors, such as IL-12, IFN-γ, and other pro-inflammatory factors, were correspondingly decreased or increased. The novel eQTL-SNP, rs419540, might increase the risk of silicosis by modulating the expression levels of IL12RB1. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the incidence rates of mycobacterial infections in silicosis patients with systemic autoimmune rheumatic disease (ARD). Methods: This was a retrospective cohort of silicosis patients between January of 1999 and December of 2023. We compared the incidence of tuberculosis and nontuberculous mycobacterial disease (NTM) in patients with silicosis with and without ARD. We also compared the tuberculosis incidence in the overall cohort with general Brazilian population estimates. Results: The study comprised 369 silicosis patients, of whom 35 (9.5%) had ARD. Having ARD did not affect the cumulative incidence of mycobacterial diseases. The risk of tuberculosis was higher in the cohort when compared with that in the adult Brazilian male population (age-adjusted incidence rate ratio = 20.46; 95% CI 14.89-28.13). Conclusions: In this cohort of patients with silicosis, ARD was not associated with the incidence of mycobacterial diseases. [ABSTRACT FROM AUTHOR]

Silicosis typically has been classified as a chronic disease that develops after at least 10 years of exposure to silica dust, and often is associated with miners and stone workers. As industries have changed over time, other types of workers (including those in artificial stonework, jewelry polishing, and denim production) have become exposed to high levels of silica, leading to the development of acute and accelerated silicosis. Acute silicosis can develop in as little as a few months, and accelerated silicosis can develop in as little as 2 years. No cure exists for any form of silicosis, and lung transplantation is the only lifesaving treatment. Primary care clinicians must understand when patients are at risk for developing silicosis and not assume that a short time of exposure precludes the development of silicosis. [ABSTRACT FROM AUTHOR]

Exposure to respirable crystalline silica dust is one of the most common and severe risks due to the associated health outcomes among workers and results in many occupational-related lung diseases, such as silicosis and lung cancer. The study aimed to determine knowledge, attitudes, and practices on occupation health and safety among mine workers exposed to crystalline silica dust in Lesotho. A descriptive retrospective cross-sectional study design was used in the study. A record review guide was used to retrieve secondary data from the Southern Africa Tuberculosis and Health Systems Support (SATBHSS) project, which were thereafter entered into STATA software, version 17 for descriptive and inferential analysis. The study participants were purposively selected. Most participants were between the ages of 31 to 40 years of age and there was a significant difference between the genders with 35 (9%) females and 350 (91%) males. The majority of the participants had a high school level of education (305, 79%). The knowledge was generally positive in the study with a knowledge score mean of 13.43 (standard deviation: 2.99). The miners agreed with most attitude statements except for A1 (25%), A2 (35%), A3 (18%), and A4 (31%). The practice of exposed mine workers in the study was influenced by working in a dolerite mine (p = 0.003), knowledge score (p ˂ 0.001), and having an attitude about health and safety rules at the mine (p ˂ 0.001; 95% CI: 0.92 to 0.79), while age was a protective factor in the study. The findings of this study highlighted positive knowledge, attitudes, and practices toward occupational health and safety among mine workers. However, more educational programs can be implemented to ensure all mine workers understand the importance of good knowledge, positive attitude, and appropriate practices towards occupational health and safety in their environment. [ABSTRACT FROM AUTHOR]

Abstract Background Silicosis has always been a serious global occupational health problem. Oral microbiota plays important roles in the development of lung disease. However, few studies have investigated the relationship between periodontal conditions, oral bacteria and silicosis disease. Method A single-center and cross-sectional study was conducted in 2019 in Sichuan Province, China, including a small sample of silicosis patient group and healthy control group. Demographic data and periodontal examinations measured by clinical attachment loss (CAL), bleeding on probing (BOP) and periodontal pocket (PD) were collected from each participant. Phenotypic changes were detected by histopathological staining. Next-generation sequencing targeting 16S ribosomal RNA was targeted to decipher the salivary microbiome of the two groups. Random forest, Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression and multivariable logistic regression analysis were conducted to find potential indicators to distinguish silicosis. Results In general, 29 male healthy controls and 24 male silicosis patients were included. The proportion of CAL ≥ 3 mm in silicosis group was greater than control group, while the proportion of BOP (+) and PD ≥ 4 mm was reduced in silicosis group. The α-smooth muscle actin and fibronectin expression increased in gingiva of patients. The composition of salivary microbiota exhibited significant differences between the two groups, with silicosis patients demonstrating a lower diversity of salivary microbiota. Genus of Aggregatibacter [odds ratio (OR) = 0.000, p = 0.003] and Catonella (OR = 0.000, p = 0.049) were identified as biomarkers to distinguish silicosis. Conclusions The silicosis group exhibited worse CAL, improved BOP and PD, which may be related to the gingival fibrosis found in this study. The composition of the oral microbiota underwent significant changes, accompanied by a decrease in diversity, in patients with silicosis. Our study indicates that respirable crystalline silica exposure affects oral health, and alterations of oral microbiota might be implicated in silicosis. We primarily identified Aggregatibacter and Catonella as the potential indicators to distinguish silicosis patients from healthy controls.

Abstract Background India, with the highest global burden of tuberculosis (TB) and drug-resistant TB, aims to eliminate TB by 2025. Yet, limited evidence exists on drug resistance patterns and retreatment among patients with silico-tuberculosis. This study explores these patterns and assesses the impact of silicosis on TB retreatment in India. Methods This secondary data analysis stems from a larger retrospective cohort study conducted in Khambhat, Gujarat, between January 2006 and February 2022. It included 138 patients with silico-tuberculosis and 2,610 TB patients without silicosis. Data from the Nikshay TB information portal were linked with silicosis diagnosis reports from the Pneumoconiosis Board using the unique Nikshay ID as the linking variable. Drug-resistant TB was defined as resistance to any anti-TB drug recorded in Nikshay. Retreatment refers to TB patients who have previously undergone anti-TB treatment for one month or more and need further treatment. Recurrent TB denotes patients who were previously declared cured or had completed treatment but later tested positive for microbiologically confirmed TB. Multivariable logistic regression was used to determine the impact of co-prevalent silicosis on drug resistance and retreatment. Results Patients with silico-tuberculosis showed a higher proportion of retreatment compared to those without silicosis (55% vs. 23%, p

Abstract Objective Interstitial lung diseases (ILDs) are diverse pulmonary disorders marked by diffuse lung inflammation and fibrosis. The variability in characteristics and treatment approaches complicates diagnosis and management. In advanced cases requiring transplantation, determining indications and selecting suitable candidates presents additional challenges. Methods Of all patients with non-IPF ILD between December 2016 to December 2022 were analyzed retrospectively. Patients were categorized into two groups: transplanted patients and deceased patients on the waiting list. Clinical data and survival outcomes were compared between groups. Results Of the 43 patients, 20 underwent lung transplantation while 23 died awaiting transplantation. Waiting list mortality was 53.4%, with median waiting times similar between groups (3 months for transplant patients and 6 months for those on the waiting list). There were no significant differences between groups in age, gender, height, BMI, 6-minute walk test (6MWT), or forced vital capacity (FVC). The prevalence of pulmonary hypertension (PH) was 76.7% in right heart catheterizations, similar in both groups. One single and 19 bilateral lung transplants were performed. Overall, 13 of the 20 patients survived to discharge from the hospital. One-year mortality was 7/20 (35%). The median follow-up was 34 months, with a 1-year conditional survival of 90.9% at 3 years and 70.7% at 5 years. Conclusions This study underscores the importance of further research into non-IPF ILDs. Lung transplantation remains a viable option that can significantly enhance both the quality and longevity of life for patients with advanced ILD.

BackgroundThe senescence of alveolar type II epithelial cells is an important driving factor for the progression of silicotic fibrosis, and the regulatory effects of oxamate on the senescence of alveolar type II epithelial cells is still unclear.ObjectiveTo explore whether lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting senescence of alveolar type II epithelial cellsMethodsThis study was divided into two parts: in vivo experiments and in vitro experiments. In the first part, forty SPF C57BL/6J male mice were randomly divided into four groups with 10 in each group: control group, silicosis model group, low-dose oxamate treatment group, and high-dose oxamate treatment group. The silicotic mouse model was established by intratracheal instillation of 50 μL SiO2 suspension (100 mg·mL−1). The treatment models were prepared by intraperitoneal injection of 100 μL oxamate (225 mmol·L−1 and 1125 mmol·L−1). In the second part, induction of MLE-12 mouse alveolar type II epithelial cells was conducted with SiO2. The in vitro experimental groups were ① SiO2 induction groups: control group, 50 μg·mL−1 SiO2 group, 100 μg·mL−1 SiO2 group, and 200 μg·mL−1 SiO2 group, and ② oxamate treatment groups: control group, SiO2 group (100 μg·mL−1), low-dose oxamate (25 mmol·L−1) treatment group, and high-dose oxamate (50 mmol·L−1) treatment group. Pathological morphology of lung tissues was evaluated after hematoxylin-eosin (HE) staining; deposition of collagen in lung tissues was evaluated after sirius red staining; positive co-expression of prosurfactant protein C (Pro-SPC) and β-galactosidase was detected by immunofluorescence staining; positive expression of β-galactosidase in MLE-12 cells was detected by immunofluorescence staining. The protein expression levels of collagen type I (CoL I), fibronectin1 (FN1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), lactate dehydrogenase A (LDHA), p-ataxia telangiectasia and Rad3-related kinase (ATR), and cyclin-dependent kinase inhibitors p21, and p16 were detected by Western blotting.ResultsCompared with the control group, the protein expression levels of HK2, PKM2, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group and the SiO2-induced MLE-12 cells (P＜0.05). The in vivo studies showed that, compared with the control group, the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the protein expression levels of CoL I, FN1, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group (P＜0.05). Compared with the silicosis model group, the oxamate treatment groups showed significant downregulation of the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the the CoL I, FN1, LDHA, p-ATR, p21, and p16 protein expression levels, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05). The in vitro studies showed that, compared with the control group, the proportion of β-galactosidase positive cells and the protein expression levels of p-ATR, p21, and p16 were significantly upregulated in the SiO2-induced group (P＜0.05). Compared with the SiO2 group, the proportion of β-galactosidase positive cells and the LDHA, p-ATR, p21 and p16 protein expression levels were significantly downregulated in the oxamate treatment groups, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05).ConclusionLactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting the senescence of alveolar type II epithelial cells.

Abstract Background Silicosis is an irreversible fibrotic disease of the lung caused by chronic exposure to silica dust, which manifests as infiltration of inflammatory cells, excessive secretion of pro-inflammatory cytokines, and pulmonary diffuse fibrosis. As the disease progresses, lung function further deteriorates, leading to poorer quality of life of patients. Currently, few effective drugs are available for the treatment of silicosis. Bicyclol (BIC) is a compound widely employed to treat chronic viral hepatitis and drug-induced liver injury. While recent studies have demonstrated anti-fibrosis effects of BIC on multiple organs, including liver, lung, and kidney, its therapeutic benefit against silicosis remains unclear. In this study, we established a rat model of silicosis, with the aim of evaluating the potential therapeutic effects of BIC. Methods We constructed a silicotic rat model and administered BIC after injury. The FlexiVent instrument with a forced oscillation system was used to detect the pulmonary function of rats. HE and Masson staining were used to assess the effect of BIC on silica-induced rats. Macrophages-inflammatory model of RAW264.7 cells, fibroblast-myofibroblast transition (FMT) model of NIH-3T3 cells, and epithelial-mesenchymal transition (EMT) model of TC-1 cells were established in vitro. And the levels of inflammatory mediators and fibrosis-related proteins were evaluated in vivo and in vitro after BIC treatment by Western Blot analysis, RT-PCR, ELISA, and flow cytometry experiments. Results BIC significantly improved static compliance of lung and expiratory and inspiratory capacity of silica-induced rats. Moreover, BIC reduced number of inflammatory cells and cytokines as well as collagen deposition in lungs, leading to delayed fibrosis progression in the silicosis rat model. Further exploration of the underlying molecular mechanisms revealed that BIC suppressed the activation, polarization, and apoptosis of RAW264.7 macrophages induced by SiO2. Additionally, BIC inhibited SiO2-mediated secretion of the inflammatory cytokines IL-1β, IL-6, TNF-α, and TGF-β1 in macrophages. BIC inhibited FMT of NIH-3T3 as well as EMT of TC-1 in the in vitro silicosis model, resulting in reduced proliferation and migration capability of NIH-3T3 cells. Further investigation of the cytokines secreted by macrophages revealed suppression of both FMT and EMT by BIC through targeting of TGF-β1. Notably, BIC blocked the activation of JAK2/STAT3 in NIH-3T3 cells required for FMT while preventing both phosphorylation and nuclear translocation of SMAD2/3 in TC-1 cells necessary for the EMT process. Conclusion The collective data suggest that BIC prevents both FMT and EMT processes, in turn, reducing aberrant collagen deposition. Our findings demonstrate for the first time that BIC ameliorates inflammatory cytokine secretion, in particular, TGF-β1, and consequently inhibits FMT and EMT via TGF-β1 canonical and non-canonical pathways, ultimately resulting in reduction of aberrant collagen deposition and slower progression of silicosis, supporting its potential as a novel therapeutic agent.

Background Silicosis is an occupational respiratory disease linked to silica dust inhalation. The main driver was traditional coal mining, but in recent decades, new sources of exposure have emerged. Our aim in this study was to assess the temporal and spatial distribution of mortality due to this disease over a 22-year period in Spain. Methods Silicosis records, as an Underlying Cause of Death, were extracted from the National Institute of Statistics from 1999 to 2020 using the International Classification of Diseases 10th revision (code J62.8). Age- and sex-adjusted mortality rates per 1,000,000 inhabitants were calculated for the territory and by province. A geographic analysis was performed, and clusters of deaths were identified at the municipal level, and then the outcomes were compared in two periods of 11 years. Results There were 2618 deaths due to silicosis in Spain. The mean age of death increased significantly by 0.66% annually from 1999 to 2013. The age-adjusted mortality rate decreased by 7.30% per year, falling from 3.00 to 0.65 per 1,000,000 inhabitants. The temporal pattern showed a significant decrease of mortality rate in 31% of the provinces (16 out of 52), while it increased in Pontevedra. Regarding the spatial analysis, 11 clusters were found in both periods, but some variations were observed in terms of their distribution in the Spanish territory, as well as in the affected municipalities. Conclusions The decrease in mortality due to Silicosis could be related to less exposure to silica dust over the years and an improvement in the survival of those affected. It is thus essential to analyze the role of preventive measures for this occupational disease.

Abstract Background Extended contact with silica particles can lead to Silicosis, a chronic lung condition lacking established treatment protocols or clear mechanisms of development. The urgency for innovative treatments arises from the unavailability of effective treatment methodologies. The origin of silica-induced pulmonary fibrosis includes essential processes such as macrophage activation and the conversion of fibroblasts into myofibroblasts, with oxidative stress playing a pivotal role. Shionone (SHI), a triterpenoid extracted from the Aster tataricus plant, is recognized for its extensive health benefits. This study explores the capability of SHI to alleviate the effects of silica-induced lung fibrosis in mice. Methods This investigation explored the impact of SHI on lung inflammation and fibrosis at different stages (early and late) triggered by silica in mice, focusing specifically on the initial and more developed phases. It comprised an analysis of isolated peritoneal macrophages and fibroblasts extracted from mice to elucidate SHI's therapeutic potential and its underlying mechanism. The methodology employed encompassed quantitative PCR, immunofluorescence, flow cytometry, and western blotting to examine macrophage activity and their transition into myofibroblasts. The activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by SHI was confirmed via immunofluorescence and western blot studies. SHI's antioxidative properties were evidenced by the measurement of reactive oxygen species (ROS) and mitochondrial ROS within both macrophages and fibroblasts, using 2′, 7′-dichlorodihydrofluorescein diacetate and MitoSOX, respectively. The relevance of SHI was further underscored by applying ML385 and Nrf2 siRNA to gauge its effectiveness. Results Starting SHI treatment early countered the harmful effects of lung inflammation and fibrosis caused by silica, while initiating SHI at a later phase decelerated the advancement of fibrosis. SHI's action was linked to the activation of the Nrf2 signaling pathway, a boost in antioxidant enzyme levels, and a decrease in oxidative stress and inflammation in macrophages affected by silica. Furthermore, SHI prevented the conversion of fibroblasts into myofibroblasts prompted by TGF-β, along with the resultant oxidative stress. The beneficial outcomes of SHI were negated when ML385 and Nrf2 siRNA were applied, highlighting the pivotal role of the Nrf2 pathway in SHI's efficacy. Conclusion SHI plays a significant role in stimulating the Nrf2 pathway, thereby defending against silica-induced oxidative stress and inflammatory reactions in macrophages, and inhibiting the conversion of fibroblasts to myofibroblasts due to TGF-β. This suggests that SHI is a viable option for treating lung inflammation and fibrosis in mice suffering from silicosis.

Abstract The 2021 tuberculosis (TB) preventive treatment guidelines in India included silicosis as a screening group, yet latent TB infection (LTBI) testing for silica-dust-exposed individuals is underemphasized. Focusing on an estimated 52 million silica-dust-exposed workers, particularly agate-stone workers in Khambhat, Gujarat, our study aims to estimate LTBI prevalence, identify predictors, and gather insights from TB and silicosis experts. Employing a sequential explanatory mixed-methods approach, a cross-sectional study involved 463 agate-stone workers aged ≥ 20 years in Khambhat, using IGRA kits for LTBI testing. In-depth interviews with experts complemented quantitative findings. Among agate-stone workers, 58% tested positive for LTBI, with predictors including longer exposure, type of work, and BCG vaccination. Our findings reveal a nearly double burden of LTBI compared to the general population, particularly in occupations with higher silica dust exposure. Experts advocate for including silica-dust-exposed individuals in high-risk groups for LTBI testing, exploring cost-effective alternatives like improved skin sensitivity tests, and shorter TB preventive treatment regimens to enhance compliance. Future research should explore upfront TB preventive treatment for silica-dust-exposed individuals with high LTBI prevalence and optimal exposure duration. This study underscores the urgent need for policy changes and innovative approaches to TB prevention among silica-dust-exposed populations, impacting global occupational health strategies.

Abstract Background Silicosis represents a paramount occupational health hazard globally, with its incidence, morbidity, and mortality on an upward trajectory, posing substantial clinical dilemmas due to limited effective treatment options available. Trigonelline (Trig), a plant alkaloid extracted mainly from coffee and fenugreek, have diverse biological properties such as protecting dermal fibroblasts against ultraviolet radiation and has the potential to inhibit collagen synthesis. However, it’s unclear whether Trig inhibits fibroblast activation to attenuate silicosis-induced pulmonary fibrosis is unclear. Methods To evaluate the therapeutic efficacy of Trig in the context of silicosis-related pulmonary fibrosis, a mouse model of silicosis was utilized. The investigation seeks to elucidated Trig's impact on the progression of silica-induced pulmonary fibrosis by evaluating protein expression, mRNA levels and employing Hematoxylin and Eosin (H&E), Masson's trichrome, and Sirius Red staining. Subsequently, we explored the mechanism underlying of its functions. Results In vivo experiment, Trig has been demonstrated the significant efficacy in mitigating SiO2-induced silicosis and BLM-induced pulmonary fibrosis, as evidenced by improved histochemical staining and reduced fibrotic marker expressions. Additionally, we showed that the differentiation of fibroblast to myofibroblast was imped in Trig + SiO2 group. In terms of mechanism, we obtained in vitro evidence that Trig inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-β/Smad signaling according to the in vitro evidence. Notably, our finding indicated that Trig seemed to be safe in mice and fibroblasts. Conclusion In summary, Trig attenuated the severity of silicosis-related pulmonary fibrosis by alleviating the differentiation of myofibroblasts, indicating the development of novel therapeutic approaches for silicosis fibrosis.

Occupational lung disease remains one of the most common work-related illnesses and accounts for most deaths from occupational illness. Occupational lung diseases often have delayed manifestation over decades and nonspecific clinical presentations, making it challenging for clinicians to promptly identify the disease and implement preventive measures. Radiologists play a crucial role in identifying and diagnosing occupational lung diseases, allowing for removal of the exposure and early medical intervention. In this review, we share our clinical and radiologic approach to diagnosing occupational lung disease and its subtypes. A collection of sample cases of occupational lung diseases commonly encountered in the modern era at a large Canadian university hospital is included to facilitate understanding. This review will provide radiologists with valuable insights into recognizing and diagnosing occupational lung diseases. [ABSTRACT FROM AUTHOR]

Occupational crystalline silica (CS) particle exposure leads to silicosis. The burden of CS-associated disease remains high, and treatment options are limited due to vague mechanisms. Here we show that pulmonary CD4+ tissue-resident memory T cells (TRM) accumulate in response to CS particles, mediating the pathogenesis of silicosis. The TRM cells are derived from peripheral lymphocyte recruitment and in situ expansion. Specifically, CD69+CD103+ TRM-Tregs depend more on circulating T cell replenishment. CD69 and CD103 can divide the TRM cells into functionally distinct subsets, mirroring the immuno-balance within CD4+ TRM cells. However, targeting CD103+ TRM-Tregs do not mitigate disease phenotype since the TRM subsets exert immunosuppressive but not pro-fibrotic roles. After identifying pathogenic CD69+CD103- subsets, we highlight IL-7 for their maintenance and function, that present a promising avenue for mitigating silicosis. Together, our findings highlight the distinct role of CD4+ TRM cells in mediating CS-induced fibrosis and provide potential therapeutic strategies. Crystalline silica exposure led to CD4+ tissue-resident memory T-cell accumulation. The imbalance of pulmonary TRM-Teffs and TRM-Tregs promoted silicosis progression. Neutralizing IL-7 alleviated silicosis by disrupting TRM-Teff maintenance. [ABSTRACT FROM AUTHOR]

Aims: In addition to reducing the respiratory function, crystalline silica (SiO2) disturbs the immune response by affecting immune cells during the progression of silicosis. Regulatory T cell (Treg) differentiation may play a key role in the abnormal polarization of T helper cell (Th)1 and Th2 cells in the development of silicosis-induced fibrosis. Alpha-lipoic acid (ALA) has immunomodulatory effects by promoting Tregs differentiation. Thus, ALA may have a therapeutic potential for treating autoimmune disorders in patients with silicosis. However, little is known regarding whether ALA regulates the immune system during silicosis development. Results: We found that the expression levels of collagen increased, and the antioxidant capacity was lower in the Lias−/−+SiO2 group than in the Lias+/++SiO2 group. The proportion of Tregs decreased in the peripheral blood and spleen tissue in mice exposed to SiO2. The proportion of Tregs in the Lias−/−+SiO2 group was significantly lower than that in the Lias+/++SiO2 group. Supplementary exogenous ALA attenuates the accumulation of inflammatory cells and extracellular matrix in lung tissues. ALA promotes the immunological balance between Th17 and Treg responses during the development of silicosis-induced fibrosis. Innovation and Conclusion: Our findings confirmed that low expression of lipoic acid synthase aggravates SiO2-induced silicosis, and that supplementary exogenous ALA has therapeutic potential by improving Tregs in silicosis fibrosis. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of Haihuang Bufei Formula on inflammatory factors and T lymphocyte subsets in silicotic rats, and to further explore the therapeutic effects of Haihuang Bufei Formula. Methods The silicotic rat models were constructed by intratracheal instillation of silicon dioxide (SiO2) suspension. After 24 hours of modeling, the rats were randomly divided into normal control group, model group, positive drug control group, and low, medium, high dose group of Haihuang Bufei Formula. Each group contained 10 rats, which were administered once daily for one month. One hour after the last administration, the rats were sacrificed. Lung index, serum tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), hydroxyproline (HYP), superoxide dismutase (SOD), and malondialdehyde (MDA) contents in lung tissue were measured. Hematoxylin-eosin (HE) and Masson staining methods were used to observe the pathological changes in lung tissues. Flow cytometry was used to detect the T lymphocyte subsets in the peripheral blood of rats. Results Compared with the model group, the lung index, serum IL-1β, lung tissue HYP, and MDA contents in the middle and high dose groups of Haihuang Bufei Formula treatment were significantly reduced (P<0.05). In the high-dose group, the serum TNF-α content decreased to (238.64±51.80) ng/L, and the lung tissue SOD content increased to (55.30±13.77) pg/mL (P<0.05). HE and Masson's staining results indicated that the medium and high doses of Haihuang Bufei Formula could alleviate pathological damage of silicosis and fibrosis in lung tissue. Flow cytometer analysis showed that the percentage of CD8+T cells in the high-dose group of Haihuang Bufei Formula was significantly decreased (P<0.05). The ratio of CD4+/CD8+ increased to (1.44±0.19) (P<0.01), and the percentage of CD4+T cells showed no statistically significant change among groups (P>0.05). Conclusions Haihuang Bufei Formula has a protective effect on silicotic rats by reducing collagen content, alleviating pathological damage and fibrosis of lung tissue, which may be related to inhibiting the expression of inflammatory factors, reducing oxidative stress, and regulating the immune system. [ABSTRACT FROM AUTHOR]

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Background: Silicosis is an irreversible fibrotic disease of the lung caused by chronic exposure to silica dust, which manifests as infiltration of inflammatory cells, excessive secretion of pro-inflammatory cytokines, and pulmonary diffuse fibrosis. As the disease progresses, lung function further deteriorates, leading to poorer quality of life of patients. Currently, few effective drugs are available for the treatment of silicosis. Bicyclol (BIC) is a compound widely employed to treat chronic viral hepatitis and drug-induced liver injury. While recent studies have demonstrated anti-fibrosis effects of BIC on multiple organs, including liver, lung, and kidney, its therapeutic benefit against silicosis remains unclear. In this study, we established a rat model of silicosis, with the aim of evaluating the potential therapeutic effects of BIC. Methods: We constructed a silicotic rat model and administered BIC after injury. The FlexiVent instrument with a forced oscillation system was used to detect the pulmonary function of rats. HE and Masson staining were used to assess the effect of BIC on silica-induced rats. Macrophages-inflammatory model of RAW264.7 cells, fibroblast-myofibroblast transition (FMT) model of NIH-3T3 cells, and epithelial-mesenchymal transition (EMT) model of TC-1 cells were established in vitro. And the levels of inflammatory mediators and fibrosis-related proteins were evaluated in vivo and in vitro after BIC treatment by Western Blot analysis, RT-PCR, ELISA, and flow cytometry experiments. Results: BIC significantly improved static compliance of lung and expiratory and inspiratory capacity of silica-induced rats. Moreover, BIC reduced number of inflammatory cells and cytokines as well as collagen deposition in lungs, leading to delayed fibrosis progression in the silicosis rat model. Further exploration of the underlying molecular mechanisms revealed that BIC suppressed the activation, polarization, and apoptosis of RAW264.7 macrophages induced by SiO2. Additionally, BIC inhibited SiO2-mediated secretion of the inflammatory cytokines IL-1β, IL-6, TNF-α, and TGF-β1 in macrophages. BIC inhibited FMT of NIH-3T3 as well as EMT of TC-1 in the in vitro silicosis model, resulting in reduced proliferation and migration capability of NIH-3T3 cells. Further investigation of the cytokines secreted by macrophages revealed suppression of both FMT and EMT by BIC through targeting of TGF-β1. Notably, BIC blocked the activation of JAK2/STAT3 in NIH-3T3 cells required for FMT while preventing both phosphorylation and nuclear translocation of SMAD2/3 in TC-1 cells necessary for the EMT process. Conclusion: The collective data suggest that BIC prevents both FMT and EMT processes, in turn, reducing aberrant collagen deposition. Our findings demonstrate for the first time that BIC ameliorates inflammatory cytokine secretion, in particular, TGF-β1, and consequently inhibits FMT and EMT via TGF-β1 canonical and non-canonical pathways, ultimately resulting in reduction of aberrant collagen deposition and slower progression of silicosis, supporting its potential as a novel therapeutic agent. [ABSTRACT FROM AUTHOR]

The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored mechanisms of silica-induced pulmonary fibrosis in human lung samples collected from patients with occupational exposure to silica and in a longitudinal mouse model of silicosis using multiple modalities including whole-lung single-cell RNA sequencing and histological, biochemical, and physiologic assessments. In addition to pulmonary inflammation and fibrosis, intratracheal silica challenge induced osteoclast-like differentiation of alveolar macrophages and recruited monocytes, driven by induction of the osteoclastogenic cytokine, receptor activator of nuclear factor κB ligand (RANKL) in pulmonary lymphocytes, and alveolar type II cells. Anti-RANKL monoclonal antibody treatment suppressed silica-induced osteoclast-like differentiation in the lung and attenuated pulmonary fibrosis. We conclude that silica induces differentiation of pulmonary osteoclast-like cells leading to progressive lung injury, likely due to sustained elaboration of boneresorbing proteases and hydrochloric acid. Interrupting osteoclast-like differentiation may therefore constitute a promising avenue for moderating lung damage in silicosis. [ABSTRACT FROM AUTHOR]

Background: Silicosis is an occupational respiratory disease linked to silica dust inhalation. The main driver was traditional coal mining, but in recent decades, new sources of exposure have emerged. Our aim in this study was to assess the temporal and spatial distribution of mortality due to this disease over a 22-year period in Spain. Methods: Silicosis records, as an Underlying Cause of Death, were extracted from the National Institute of Statistics from 1999 to 2020 using the International Classification of Diseases 10th revision (code J62.8). Age - and sex-adjusted mortality rates per 1,000,000 inhabitants were calculated for the territory and by province. A geographic analysis was performed, and clusters of deaths were identified at the municipal level, and then the outcomes were compared in two periods of 11 years. Results: There were 2618 deaths due to silicosis in Spain. The mean age of death increased significantly by 0.66% annually from 1999 to 2013. The age-adjusted mortality rate decreased by 7.30% per year, falling from 3.00 to 0.65 per 1,000,000 inhabitants. The temporal pattern showed a significant decrease of mortality rate in 31% of the provinces (16 out of 52), while it increased in Pontevedra. Regarding the spatial analysis, 11 clusters were found in both periods, but some variations were observed in terms of their distribution in the Spanish territory, as well as in the affected municipalities. Conclusions: The decrease in mortality due to Silicosis could be related to less exposure to silica dust over the years and an improvement in the survival of those affected. It is thus essential to analyze the role of preventive measures for this occupational disease. [ABSTRACT FROM AUTHOR]

To explore the association between apaQTL/eQTL-SNPs and the susceptibility to silicosis. A silicosis-related GWAS was initially conducted to screen for single nucleotide polymorphisms (SNPs) associated with the risk of silicosis. Candidate SNPs with apaQTL and eQTL functions were then obtained from the 3′aQTL-atlas and GTEx databases. Subsequently, additional case–control studies were performed to validate the relationship between the candidate apaQTL/eQTL-SNPs and the risk of silicosis. Finally, experiments were conducted to illustrate APA events occurring at different alleles of the identified apaQTL/eQTL-SNPs. The combined results of the GWAS and iMLDR validations indicate that the variant T allele of the rs2974341 located on SMIM19 (additive model: OR = 0.66, the 95% CI = 0.53–0.84, P = 0.001) and the variant T allele of the rs2390488 located on TMTC4 (additive model: OR = 0.72, 95% CI = 0.57–0.90, P = 0.005) were significantly associated with decreased risk of developing silicosis susceptibility. Furthermore, 3′RACE experiments verified the presence of two poly (A) sites (proximal and distal) in SMIM19, rs2974341 may remotely regulate the binding between miRNA-3646 and SMIM19 with its high LD locus rs2974353 to affect the expression level of SMIM19. The rs2974341 variant T allele may contribute to the generation of the shorter 3′UTR transcript of SMIM19 and affect the binding of miRNA-3646 to the target gene SMIM19. The apaQTL/eQTL-SNPs may provide new perspectives for evaluating the regulatory function of SNPs in the development of silicosis. [ABSTRACT FROM AUTHOR]

Engineered stone silicosis (ESS), primarily caused by inhaling respirable crystalline silica, poses a significant occupational health risk globally. ESS has no effective treatment and presents a rapid progression from simple silicosis (SS) to progressive massive fibrosis (PMF), with respiratory failure and death. Despite the use of diagnostic methods like chest x‐rays and high‐resolution computed tomography, early detection of silicosis remains challenging. Since routine blood tests have shown promise in detecting inflammatory markers associated with the disease, this study aims to assess whether routine blood biomarkers, coupled with machine learning techniques, can effectively differentiate between healthy individuals, subjects with SS, and PMF. To this end, 107 men diagnosed with silicosis, ex‐workers in the engineered stone (ES) sector, and 22 healthy male volunteers as controls not exposed to ES dust were recruited. Twenty‐one primary biochemical markers derived from peripheral blood extraction were obtained retrospectively from clinical hospital records. Relief‐F features selection technique was applied, and the resulting subset of 11 biomarkers was used to build five machine learning models, demonstrating high performance with sensitivities and specificities in the best case greater than 82% and 89%, respectively. The percentage of lymphocytes, the angiotensin‐converting enzyme, and lactate dehydrogenase indexes were revealed, among others, as blood biomarkers with significant cumulative importance for the machine learning models. Our study reveals that these biomarkers could detect a chronic inflammatory status and potentially serve as a supportive tool for the diagnosis, monitoring, and early detection of the progression of silicosis. [ABSTRACT FROM AUTHOR]

Objective: To understand the prevalence rate of obstructive pulmonary dysfunction in workers exposed to silica dust and analyze its risk factors, so as to provide reference for the formulation of diagnostic criteria for chronic obstructive pulmonary disease caused by occupational dust. Methods: Data collection and structured questionnaire were used to collect the data of 2064 workers exposed to silica dust who underwent health examination in Hunan Occupational Disease Prevention and Control Hospital and Yuanling Second People's Hospital from January 1, 2021 to June 30, 2022. The prevalence rate of obstructive pulmonary ventilation dysfunction was analyzed and the risk factors were analyzed. Results: The prevalence rate of obstructive pulmonary ventilation dysfunction (FEV1/FVC < 70%) was 2.3% in 2064 silica dust exposed workers. The prevalence of restrictive pulmonary ventilation dysfunction (FVC/Pre < 80%) was 8.1%. The prevalence of obstructive pulmonary ventilation dysfunction in the high level exposure group was higher than that in the low level exposure group, 8.2 vs0.9% (P < 0.05). The rate of obstructive pulmonary ventilation dysfunction in female group was higher than that in male group (5.3% vs. 1.7%, p = 0.00). Workers with obstructive pulmonary dysfunction were older and worked longer than workers without obstructive pulmonary dysfunction, but there was no statistical difference. Multivariate regression analysis showed that high exposure level was a risk factor for obstructive pulmonary ventilation dysfunction in silica dust exposed workers (P < 0.05). Females were the risk factors for obstructive pulmonary ventilation dysfunction (P < 0.05). Conclusion: Silica dust exposure can cause obstructive pulmonary ventilation dysfunction and lead to chronic obstructive pulmonary disease. High level of exposure is a risk factor for obstructive pulmonary ventilation dysfunction. Women exposed to dust are more prone to obstructive pulmonary ventilation dysfunction than men. Early diagnosis of chronic obstructive pulmonary disease caused by silica dust and timely intervention measures are very important to delay the decline of lung function and protect the health of workers. [ABSTRACT FROM AUTHOR]

Background: Extended contact with silica particles can lead to Silicosis, a chronic lung condition lacking established treatment protocols or clear mechanisms of development. The urgency for innovative treatments arises from the unavailability of effective treatment methodologies. The origin of silica-induced pulmonary fibrosis includes essential processes such as macrophage activation and the conversion of fibroblasts into myofibroblasts, with oxidative stress playing a pivotal role. Shionone (SHI), a triterpenoid extracted from the Aster tataricus plant, is recognized for its extensive health benefits. This study explores the capability of SHI to alleviate the effects of silica-induced lung fibrosis in mice. Methods: This investigation explored the impact of SHI on lung inflammation and fibrosis at different stages (early and late) triggered by silica in mice, focusing specifically on the initial and more developed phases. It comprised an analysis of isolated peritoneal macrophages and fibroblasts extracted from mice to elucidate SHI's therapeutic potential and its underlying mechanism. The methodology employed encompassed quantitative PCR, immunofluorescence, flow cytometry, and western blotting to examine macrophage activity and their transition into myofibroblasts. The activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by SHI was confirmed via immunofluorescence and western blot studies. SHI's antioxidative properties were evidenced by the measurement of reactive oxygen species (ROS) and mitochondrial ROS within both macrophages and fibroblasts, using 2′, 7′-dichlorodihydrofluorescein diacetate and MitoSOX, respectively. The relevance of SHI was further underscored by applying ML385 and Nrf2 siRNA to gauge its effectiveness. Results: Starting SHI treatment early countered the harmful effects of lung inflammation and fibrosis caused by silica, while initiating SHI at a later phase decelerated the advancement of fibrosis. SHI's action was linked to the activation of the Nrf2 signaling pathway, a boost in antioxidant enzyme levels, and a decrease in oxidative stress and inflammation in macrophages affected by silica. Furthermore, SHI prevented the conversion of fibroblasts into myofibroblasts prompted by TGF-β, along with the resultant oxidative stress. The beneficial outcomes of SHI were negated when ML385 and Nrf2 siRNA were applied, highlighting the pivotal role of the Nrf2 pathway in SHI's efficacy. Conclusion: SHI plays a significant role in stimulating the Nrf2 pathway, thereby defending against silica-induced oxidative stress and inflammatory reactions in macrophages, and inhibiting the conversion of fibroblasts to myofibroblasts due to TGF-β. This suggests that SHI is a viable option for treating lung inflammation and fibrosis in mice suffering from silicosis. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) treatment is more challenging for patients with silicosis, as it complicates the diagnosis of both diseases and increases mortality risk. Silicosis, an incurable occupational disease, confounds the diagnosis of TB and vice versa, making it more difficult to accurately identify and treat either condition. Moreover, TB appears to accelerate the progression of silicosis. Exposure to silica dust, a common cause of silicosis, can also trigger latent TB to become active TB. This correspondence outlines a proposed framework for implementing collaborative TB-silicosis activities in India, aimed at improving early diagnosis and management for both diseases. An expert panel of medical professionals developed this framework through online consultations in October and November 2022. The panel's goal was to establish a consensus on integrating TB-silicosis activities, with a focus on early detection and proper management. The framework suggests testing all patients with silicosis for active TB and screening workers exposed to silica dust for latent TB infection. It also recommends that patients with TB who have a history of occupational exposure to silica dust should be tested for silicosis. Reliable diagnostic tools, such as chest X-rays, are emphasized, providing guidance on their use for both diseases. The proposed collaborative TB-silicosis framework offers a structured approach to identifying and managing these two diseases, contributing to the global goal of eliminating silicosis by 2030 and aligning with the World Health Organization's targets for reducing TB incidence and mortality. It recommends specific strategies for implementation, including testing, referral systems, and workplace-based interventions. The framework also underscores the need for coordinated efforts among stakeholders, including the ministries of health, labor, industry, and environment. This correspondence provides valuable insights into how India can successfully implement collaborative TB-silicosis activities, serving as a model for other regions with similar challenges. [ABSTRACT FROM AUTHOR]

The 2021 tuberculosis (TB) preventive treatment guidelines in India included silicosis as a screening group, yet latent TB infection (LTBI) testing for silica-dust-exposed individuals is underemphasized. Focusing on an estimated 52 million silica-dust-exposed workers, particularly agate-stone workers in Khambhat, Gujarat, our study aims to estimate LTBI prevalence, identify predictors, and gather insights from TB and silicosis experts. Employing a sequential explanatory mixed-methods approach, a cross-sectional study involved 463 agate-stone workers aged ≥ 20 years in Khambhat, using IGRA kits for LTBI testing. In-depth interviews with experts complemented quantitative findings. Among agate-stone workers, 58% tested positive for LTBI, with predictors including longer exposure, type of work, and BCG vaccination. Our findings reveal a nearly double burden of LTBI compared to the general population, particularly in occupations with higher silica dust exposure. Experts advocate for including silica-dust-exposed individuals in high-risk groups for LTBI testing, exploring cost-effective alternatives like improved skin sensitivity tests, and shorter TB preventive treatment regimens to enhance compliance. Future research should explore upfront TB preventive treatment for silica-dust-exposed individuals with high LTBI prevalence and optimal exposure duration. This study underscores the urgent need for policy changes and innovative approaches to TB prevention among silica-dust-exposed populations, impacting global occupational health strategies. [ABSTRACT FROM AUTHOR]

Background: Silicosis represents a paramount occupational health hazard globally, with its incidence, morbidity, and mortality on an upward trajectory, posing substantial clinical dilemmas due to limited effective treatment options available. Trigonelline (Trig), a plant alkaloid extracted mainly from coffee and fenugreek, have diverse biological properties such as protecting dermal fibroblasts against ultraviolet radiation and has the potential to inhibit collagen synthesis. However, it's unclear whether Trig inhibits fibroblast activation to attenuate silicosis-induced pulmonary fibrosis is unclear. Methods: To evaluate the therapeutic efficacy of Trig in the context of silicosis-related pulmonary fibrosis, a mouse model of silicosis was utilized. The investigation seeks to elucidated Trig's impact on the progression of silica-induced pulmonary fibrosis by evaluating protein expression, mRNA levels and employing Hematoxylin and Eosin (H&E), Masson's trichrome, and Sirius Red staining. Subsequently, we explored the mechanism underlying of its functions. Results: In vivo experiment, Trig has been demonstrated the significant efficacy in mitigating SiO2-induced silicosis and BLM-induced pulmonary fibrosis, as evidenced by improved histochemical staining and reduced fibrotic marker expressions. Additionally, we showed that the differentiation of fibroblast to myofibroblast was imped in Trig + SiO2 group. In terms of mechanism, we obtained in vitro evidence that Trig inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-β/Smad signaling according to the in vitro evidence. Notably, our finding indicated that Trig seemed to be safe in mice and fibroblasts. Conclusion: In summary, Trig attenuated the severity of silicosis-related pulmonary fibrosis by alleviating the differentiation of myofibroblasts, indicating the development of novel therapeutic approaches for silicosis fibrosis. [ABSTRACT FROM AUTHOR]

Synthetically produced silicon dioxide used as a food additive exhibits nanoparticle size and shape during the early stages of manufacturing. Even when processed into food products, these nanoparticles are detected. Although processing food ingredients into nanoparticles can improve absorption rates or enhance texture, there are concerns about the specific biological effects of nanoparticles. In this study, three types of silica particles, including nanosized particles, were repetitively administered to the stomach using a gastric tube or exposed to a single injection into the submucosal layer of the stomach. Macroscopic and microscopic examinations did not reveal acute toxicity. However, when silica particles were administered to the stomach during the healing and regeneration process of gastric ulcers (induced by injecting the alkylating agent of N-Methyl-N′-Nitro-N-Nitrosoguanidine into the submucosal layer), silica particles with a diameter of 70 nm (SiNPs-70) delayed regeneration more strongly than microsized silica particles with diameters of 300 nm or 1000 nm (SiMPs-300, -1000). Furthermore, fibrosis for tissue regeneration spread throughout the entire mucosa of the stomach, resulting in hypertrophic gastritis-like symptoms. The frequency of this symptom was over 50% with SiNPs-70, 20% with SiMPs-300, and 0% with SiMPs-1000. Although the silica particles used in this study differ from actual samples found in food, the impact of particle size, particularly the effects unique to nanosize, was identified as toxicity in the stomach healing process. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to compare the interventional effects of polydatin given by different administration modes on experimental silicosis rats. Methods Fifty SPF SD rats were randomly divided into five groups, namely the control group, silica model group, polydatin inhalation group, polydatin gavage group, and polydatin intraperitoneal injection group. There were 10 rats in each group. Among them, the control group did not have any treatment, the model group was only treated with silica molding, and the other 3 groups were treated with polydatin via different administration methods after silica molding. The general condition of rats in each group and the lung coefficient of each group were observed at 28 days and 56 days after dust treatment. Paraffin sections of rat lung tissue were stained with hematoxylin-eosin (HE) and Masson staining. The kit was used to detect the content of hydroxyproline (HYP) and malondialdehyde (MDA) in the lung tissue of rats in each group, and the degree of lung inflammation and pulmonary fibrosis in each group of rats was evaluated. Results At day 56 after dust exposure, the lung coefficient of rats in the model group was significantly increased (P < 0.001) compared with the control group; compared with the model group, the lung coefficient of rats in the intraperitoneal injection group was decreased (P < 0.05). The results of HE staining of lung tissue of rats in each group showed that the alveolar wall was thin and the alveolar structure was normal in the control group on the 28th and 56th days, and no collapse was seen; compared with the control group on the 28th day, the alveolar wall of the rats in the 28th day model group was significantly thickened, the alveolar septum was widened, and a large number of inflammatory cells infiltrated the alveolar cavity; compared with the 28th day model group, the alveolar structure of each intervention group of polydatin was relatively normal. At day 56, compared with the control group, the alveolar wall of fibroblasts and fibroblast hyperplasia were further thickened in the model group; compared with the model group, the alveolar spacing in the intraperitoneal injection group, gavage group, and nebulized inhalation group was reduced. The Masson staining examination of rat lung tissue showed that, compared with the control group, the lung tissue of the model groups on the 28th and 56th days had blue cord -like collagen fiber hyperplasia. The results of collagen volume analysis showed that on the 28th and 56th days, the collagen volume integration number of the model group increased significantly compared with the control group; compared with the model group, the collagen volume fraction of all three groups of polydatin -treated rats decreased (P < 0.01). Such effects were observed to be more pronounced in rats with the intraperitoneal injection compared to those of the other two groups. On the 56th day after treatment, the content of HYP in the lung tissues in all treated groups increased compared with the control group (P < 0.05); compared with the model group, the content of hydroxyproline decreased in the intraperitoneal injection group, gavage group, and nebulized inhalation group (P < 0.05). On the 28th day after treatment, there was no significant difference in the concentration of malondialdehyde in the serum of each group (P = 0.140). On the 56th day after treatment, compared with the control group, the levels of MDA in the serum of the model group, the gavage group, and the aerosol inhalation group increased (P < 0.05); the content of MDA in the intraperitoneal injection group, gavage group, and nebulized inhalation group decreased (P < 0.05) compared with the model group, among which the MDA content in the intraperitoneal injection group had the best amelioration effect. Conclusions Polydatin, optimally administered by intraperitoneal injection, could effectively decelerate silicosis progression in SD rats, possibly via its anti-inflammatory and anti-fibrotic effects. [ABSTRACT FROM AUTHOR]

Silicosis caused by engineered stone (ES-silicosis) is an emerging worldwide issue characterized by inflammation and fibrosis in the lungs. To our knowledge, only a few reports have investigated leukocyte/lymphocyte subsets in ES-silicosis patients. The present study was designed to explore the proportions of the main lymphocyte subsets in ES-silicosis patients stratified into two groups, one with simple silicosis (SS) and the other with a more advanced state of the disease, defined as progressive massive fibrosis (PMF). The proportions of B (memory and plasmablasts) cells, T (helper, cytotoxic, regulatory) cells, and natural killer (NK) (regulatory and cytotoxic) cells were investigated by multiparameter flow cytometry in 91 ES-silicosis patients (53 SS patients and 38 PMF patients) and 22 healthy controls (HC). Although the total number of leukocytes did not differ between the groups studied, lymphopenia was observed in patients compared to healthy controls. Compared with those in healthy controls, the proportions of memory B cells, naïve helper T cells, and the CD4+/CD8+ T cells' ratio in the peripheral blood of patients with silicosis were significantly decreased, while the percentages of plasma cells, memory helper T cells, and regulatory T cells were significantly increased. For the NK cell subsets, no significant differences were found between the groups studied. These results revealed altered cellular immune processes in the peripheral blood of patients with ES-silicosis and provided further insight into silicosis pathogenesis. [ABSTRACT FROM AUTHOR]

We study the dynamics about equilibria of an infinite dimensional system of ordinary differential equations of coagulation–fragmentation–death type that was introduced recently by da Costa et al. (Eur J Appl Math 31(6):950–967, 2020) as a model for the silicosis disease mechanism. For a class of piecewise constant rate coefficients an appropriate change of variables allows for the appearance of a closed finite dimensional subsystem of the infinite-dimensional system and the analysis of the eigenvalues of the linearizations of this finite dimensional subsystem about the equilibria is then used to obtain the results on the stability of the equilibria in the original infinite dimensional model. [ABSTRACT FROM AUTHOR]

Union activism, medical lobbying and occupational health and safety prosecutions led to a major public health initiative in Australia - the banning from 1 July 2024 of work with engineered/artificial stone, including manufacturing, supplying, processing and installing it. This editorial contextualises within the history of regulation of workers' exposure to risks of contracting silicosis the growing international awareness of the dangers posed by working with engineered stone, particularly in relation to making and installing kitchen and bathroom benchtops made from engineered stone. It argues that the Australian initiative is an important public health decision that has a sound justification, is likely to save many lives and should be emulated internationally. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the role and mechanism of ferroptosis in SiO 2 -induced cardiac injury using a mouse model. Male C57BL/6 mice were intratracheally instilled with SiO 2 to create a silicosis model. Ferrostatin-1 (Fer-1) and deferoxamine (DFO) were used to suppress ferroptosis. Serum biomarkers, oxidative stress markers, histopathology, iron content, and the expression of ferroptosis-related proteins were assessed. SiO 2 altered serum cardiac injury biomarkers, oxidative stress, iron accumulation, and ferroptosis markers in myocardial tissue. Fer-1 and DFO reduced lipid peroxidation and iron overload, and alleviated SiO 2 -induced mitochondrial damage and myocardial injury. SiO 2 inhibited Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes, while Fer-1 more potently reactivated Nrf2 compared to DFO. Iron overload-induced ferroptosis contributes to SiO 2 -induced cardiac injury. Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO 2 cardiotoxicity, potentially via modulation of the Nrf2 pathway. [ABSTRACT FROM AUTHOR]

Silicosis is a systemic disease caused by long‐term inhalation of free SiO2 and retention in the lungs. At present, it is still the most important occupational health hazard disease in the world. Existing studies have shown that non‐coding RNA can also participate in complex fibrosis regulatory networks. However, its role in regulating silicotic fibrosis is still unclear. In this study, we constructed a NR8383/RLE‐6TN co‐culture system to simulate the pathogenesis of silicosis in vitro. Design of miR‐204‐3p mimics and inhibitors to overexpress or downregulate miR‐204‐3p in RLE‐6TN cells. Design of short hairpin RNA (sh‐RNA) to downregulate MRAK052509 in RLE‐6TN cells. The regulatory mechanism of miR‐204‐3p and LncRNA MRAK052509 on EMT process was studied by Quantitative real‐time PCR, Western blotting, Immunofluorescence and Cell scratch test. The results revealed that miR‐204‐3p affects the occurrence of silica dust‐induced cellular EMT process mainly through regulating TGF‐βRΙ, a key molecule of TGF‐β signaling pathway. In contrast, Lnc MRAK052509 promotes the EMT process in epithelial cells by competitively adsorbing miR‐204‐3p and reducing its inhibitory effect on the target gene TGF‐βRΙ, which may influence the development of silicosis fibrosis. This study perfects the targeted regulation relationship between LncRNA MRAK052509, miR‐204‐3p and TGF‐βRΙ, and may provide a new strategy for the study of the pathogenesis and treatment of silicosis. [ABSTRACT FROM AUTHOR]