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International Immunopharmacology Jun 2024Silicosis is a progressive disease characterized by interstitial fibrosis resulting from inhalation of silica particles, and currently lacks specific treatment. Hydrogen...
Hydrogen combined with tetrandrine attenuates silica-induced pulmonary fibrosis via suppressing NF-kappaB/NLRP3 signaling pathway-mediated epithelial mesenchymal transition and inflammation.
Silicosis is a progressive disease characterized by interstitial fibrosis resulting from inhalation of silica particles, and currently lacks specific treatment. Hydrogen (H) has demonstrated antioxidative, anti-inflammatory, and anti-fibrotic properties, yet its efficacy in treating silicosis remains unexplored. In this study, rats exposed to silica were administered interventions of H combined with tetrandrine, and euthanized at 14, 28, and 56 days post-intervention. Lung tissues and serum samples were collected for analysis. Histological examination, MDA assay, enzyme-linked immunosorbent assay, hydroxyproline assay, and Western blotting were employed to assess the impact of H combined with tetrandrine on pulmonary fibrosis. The results revealed that this combination significantly alleviated inflammation in silicosis-afflicted rats, effectively suppressed levels of MDA, TNF-α, and IL-1β expression, and inhibited epithelial-mesenchymal transition (EMT), thereby ameliorating pulmonary fibrosis. Notably, protein expression level of E-cadherin was increased,however protein expression levels of vimentin and α-SMA were reduced, and TGF-β were reduced, alongside a significant decrease in hydroxyproline content. Furthermore, H combined with tetrandrine downregulated protein expression of NF-κB p65, NF-κB p-p65, Caspase-1, ASC, and NLRP3. These findings substantiate the hypothesis that H combined with tetrandrine mitigates inflammation associated with silicosis and suppresses the EMT process to ameliorate fibrosis via the NF-κB/NLRP3 signaling pathway. However, the pressure of airway opening was not assessed in this study and dynamic readings of lung physiological function were not obtained, which is a major limitation of this study.
PubMed: 38943976
DOI: 10.1016/j.intimp.2024.112563 -
International Journal of Environmental... May 2024Engineered stone (ES) is a popular building product, due to its architectural versatility and generally lower cost. However, the fabrication of organic resin-based ES... (Review)
Review
Engineered stone (ES) is a popular building product, due to its architectural versatility and generally lower cost. However, the fabrication of organic resin-based ES kitchen benchtops from slabs has been associated with alarming rates of silicosis among workers. In 2024, fifteen years after the first reported ES-related cases in the world, Australia became the first country to ban the use and importation of ES. A range of interacting factors are relevant for ES-associated silicosis, including ES material composition, characteristics of dust exposure and lung cell-particle response. In turn, these are influenced by consumer demand, work practices, particle size and chemistry, dust control measures, industry regulation and worker-related characteristics. This literature review provides an evidence synthesis using a narrative approach, with the themes of product, exposure and host. Exposure pathways and pathogenesis are explored. Apart from crystalline silica content, consideration is given to non-siliceous ES components such as resins and metals that may modify chemical interactions and disease risk. Preventive effort can be aligned with each theme and associated evidence.
Topics: Silicosis; Humans; Occupational Exposure; Construction Materials; Dust
PubMed: 38928930
DOI: 10.3390/ijerph21060683 -
Cureus May 2024In a periodical medical checkup, a 39-year-old Mongolian underground miner was diagnosed with silicosis based on chest radiography, computed tomography (CT), and work...
In a periodical medical checkup, a 39-year-old Mongolian underground miner was diagnosed with silicosis based on chest radiography, computed tomography (CT), and work history. Chest radiography showed diffuse bilateral rounded nodules in both lung fields, with upper lobe dominance and large opacities in the right upper zone. Chest CT presented conglomerated massive changes in the right upper lobe and the coalescence of small nodules in the left upper lung. In the blood test, serum levels of the lung cancer marker neuron-specific enolase (NSE) were elevated (24.58 ng/mL). Carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) levels were within the reference range. Subsequent to the suspicion of a tumour in the right upper lobe, a right upper lobectomy was performed. The histopathological examination of the lung specimen revealed the coalescence of numerous silica nodules, accompanied by indications of associated sarcoidosis. The histological features suggested the presence of two concurrent pathological processes: silicosis and sarcoidosis. This case demonstrated the combination of three clinical conditions diagnosed in one patient, including complicated silicosis associated with sarcoidosis and elevated serum NSE levels. This case report may serve as a foundation for future investigations exploring the potential of NSE as a marker for silicosis.
PubMed: 38919222
DOI: 10.7759/cureus.61130 -
Biomedicine & Pharmacotherapy =... Jun 2024This study examines the involvement of TRIM59 in silica-induced pulmonary fibrosis and explores the therapeutic efficacy of Tanshinone IIA (Tan IIA). In vivo experiments...
This study examines the involvement of TRIM59 in silica-induced pulmonary fibrosis and explores the therapeutic efficacy of Tanshinone IIA (Tan IIA). In vivo experiments conducted on rats with silica-induced pulmonary fibrosis unveiled an increase in TRIM59 levels and a decrease in PPM1A levels. Subsequent investigations using in vitro silicosis cell models demonstrated that modulation of TRIM59 expression significantly impacts silicosis fibrosis, influencing the levels of PPM1A and activation of the Smad2/3 signaling pathway. Immunofluorescence and co-immunoprecipitation assays confirmed the interaction between TRIM59 and PPM1A in fibroblasts, wherein TRIM59 facilitated the degradation of PPM1A protein via proteasomal and ubiquitin-mediated pathways. Furthermore, employing a rat model of silica-induced pulmonary fibrosis, Tan IIA exhibited efficacy in mitigating lung tissue damage and fibrosis. Immunohistochemical analysis validated the upregulation of TRIM59 and downregulation of PPM1A in silica-induced pulmonary fibrosis, which Tan IIA alleviated. In vitro studies elucidated the mechanism by which Tan IIA regulates the Smad2/3 signaling pathway through TRIM59-mediated modulation of PPM1A. Treatment with Tan IIA in silica-induced fibrosis cell models resulted in concentration-dependent reductions in fibrotic markers and attenuation of relevant protein expressions. Tan IIA intervention in silica-induced fibrosis cell models mitigated the TRIM59-induced upregulation of fibrotic markers and enhanced PPM1A expression, thereby partially reversing Smad2/3 activation. Overall, the findings indicate that while overexpression of TRIM59 may activate the Smads pathway by suppressing PPM1A expression, treatment with Tan IIA holds promise in counteracting these effects by inhibiting TRIM59 expression.
PubMed: 38908195
DOI: 10.1016/j.biopha.2024.117014 -
Occupational and Environmental Medicine Jun 2024Respirable crystalline silica is a well-known cause of silicosis but may also be associated with other types of interstitial lung disease. We examined the associations...
BACKGROUND
Respirable crystalline silica is a well-known cause of silicosis but may also be associated with other types of interstitial lung disease. We examined the associations between occupational exposure to respirable crystalline silica and the risk of idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis.
METHODS
The total Danish working population was followed 1977-2015. Annual individual exposure to respirable crystalline silica was estimated using a quantitative job exposure matrix. Cases were identified in the Danish National Patient Register. We conducted adjusted analyses of exposure-response relations between cumulative silica exposure and other exposure metrics and idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis.
RESULTS
Mean cumulative exposure was 125 µg/m-years among exposed workers. We observed increasing incidence rate ratios with increasing cumulative silica exposure for idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. For idiopathic interstitial pneumonias and pulmonary sarcoidosis, trends per 50 µg/m-years were 1.03 (95% CI 1.02 to 1.03) and 1.06 (95% CI 1.04 to 1.07), respectively. For silicosis, we observed the well-known exposure-response relation with a trend per 50 µg/m-years of 1.20 (95% CI 1.17 to 1.23).
CONCLUSION
This study suggests that silica inhalation may be related to pulmonary sarcoidosis and idiopathic interstitial pneumonias, though these findings may to some extent be explained by diagnostic misclassification. The observed exposure-response relations for silicosis at lower cumulative exposure levels than previously reported need to be corroborated in analyses that address the limitations of this study.
PubMed: 38902031
DOI: 10.1136/oemed-2023-108964 -
Chinese Medicine Jun 2024Extended contact with silica particles can lead to Silicosis, a chronic lung condition lacking established treatment protocols or clear mechanisms of development. The...
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.
PubMed: 38898509
DOI: 10.1186/s13020-024-00947-5 -
International Journal of Molecular... May 2024Silicosis 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...
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.
Topics: Humans; Male; Silicosis; Middle Aged; Female; Silicon Dioxide; Adult; Killer Cells, Natural; Lymphocyte Subsets; Pneumonia; Aged; Case-Control Studies
PubMed: 38891910
DOI: 10.3390/ijms25115722 -
Archives of Public Health = Archives... Jun 2024Tuberculosis (TB) treatment is more challenging for patients with silicosis, as it complicates the diagnosis of both diseases and increases mortality risk. Silicosis, an...
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.
PubMed: 38890764
DOI: 10.1186/s13690-024-01325-1 -
Mediastinum (Hong Kong, China) 2024Endobronchial ultrasound (EBUS)-guided mediastinal cryobiopsy is a novel technique that increases the accuracy of diagnosing most pathologies that affect the... (Review)
Review
Endobronchial ultrasound (EBUS)-guided mediastinal cryobiopsy is a novel technique that increases the accuracy of diagnosing most pathologies that affect the mediastinum. Although EBUS-guided transbronchial needle aspiration (EBUS-TBNA) is the first choice in the diagnosis of mediastinal pathology, mediastinal cryobiopsy offers a larger and higher quality biopsy with minimal artifacts and no crushing when compared to conventional cytological samples obtained through EBUS-TBNA. It is particularly valuable in pathologies where EBUS-TBNA has diagnostic limitations, such as lymphoproliferative diseases, benign granulomatous conditions like sarcoidosis and silicosis, some rare infectious processes, metastases from rare non-pulmonary tumors, and in advanced stages of non-small cell lung cancer (NSCLC) where immunohistochemistry and molecular analysis are essential for personalized treatment. Therefore, mediastinal cryobiopsy seems to play a crucial role in these challenging scenarios. However, there is ongoing debate in the field of interventional pulmonology regarding the best approach for obtaining a mediastinal cryobiopsy. Some interventional pulmonologists use a high-frequency needle knife to create an incision in the tracheobronchial wall adjacent to the mediastinal lesion before inserting the cryoprobe, while others use a needle to create a pathway to the target area. There are also variations in the use of endoscopic or ultrasound imaging for guidance. In this article, we aim to review the current literature on different methods of performing mediastinal cryobiopsy and share our own clinical experience and methodology in a systematic way for its implementation in a safe, fast, and effective way.
PubMed: 38881814
DOI: 10.21037/med-23-65 -
Redox Biology Jun 2024Silicosis is the most common type of pneumoconiosis, having a high incidence in workers chronically exposed to crystalline silica (CS). No specific medication exists for...
Silicosis is the most common type of pneumoconiosis, having a high incidence in workers chronically exposed to crystalline silica (CS). No specific medication exists for this condition. GHK, a tripeptide naturally occurring in human blood and urine, has antioxidant effects. We aimed to investigate the therapeutic effect of GHK-Cu on silicosis and its potential underlying molecular mechanism. An experimental silicosis mouse model was established to observe the effects of GHK-Cu on lung inflammation and fibrosis. Moreover, the effects of GHK-Cu on the alveolar macrophages (AM) were examined using the RAW264.7 cell line. Its molecular target, peroxiredoxin 6 (PRDX6), has been identified, and GHK-Cu can bind to PRDX6, thus attenuating lung inflammation and fibrosis in silicosis mice without significant systemic toxicity. These effects were partly related to the inhibition of the CS-induced oxidative stress in AM induced by GHK-Cu. Thus, our results suggest that GHK-Cu acts as a potential drug by attenuating alveolar macrophage oxidative stress. This, in turn, attenuates the progression of pulmonary inflammation and fibrosis, which provides a reference for the treatment of silicosis.
PubMed: 38879894
DOI: 10.1016/j.redox.2024.103237