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Ecotoxicology and Environmental Safety Jul 2024Oxidative stress and inflammation play a fundamental role in the beginning and advancement of silicosis. Hence, questing active phytocompounds (APCs) with anti-oxidative...
Oxidative stress and inflammation play a fundamental role in the beginning and advancement of silicosis. Hence, questing active phytocompounds (APCs) with anti-oxidative and anti-inflammatory properties such as diosgenin (DG) and emodin (ED) can be a therapeutic intervention targeting silica-induced pulmonary inflammation and fibrosis. Hydrophobicity and low bioavailability are the barriers that restrict the therapeutic efficacy of DG and ED against pulmonary defects. Encapsulating these APCs in polymeric nanoparticles can overcome this limitation. The present study has thus explored the anti-inflammatory and anti-fibrotic effects of polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) individually loaded with DG (DGn) or ED (EDn) and in combine DG+ED [(DG+ED)n] in respirable silica dust (RSD)-induced pulmonary fibrosis silicosis rat model. Our study found that individual and combined NPs revealed physiochemical characteristics appropriate for IV administration with sustained-drug release purposes. Physiological evaluations of RSD-induced silicosis rats suggested that no treatment could improve the body weight. Still, they reduced the lung coefficient by maintaining lung moisture. Only (DG+ED)n significantly cleared free lung silica. All interventions were found to attribute the increased per cent cell viability in BALF, reduce cytotoxicity via minimizing LDH levels, and balance the oxidant-antioxidant status in silicotic rats. The expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1, and TGF-β1) were efficiently down-regulated with NPs interventions compared to pure (DG+ED) treatment. All drug treatments significantly declined, the 8-HdG and HYP productions indicate that RSD-induced oxidative DNA damage and collagen deposition were successfully repaired. Moreover, histopathological investigations proposed that individual or combined drugs NPs interventions could decrease the fibrosis and alveolitis grades in RSD-induced silicosis rats. However, (DG+ED)n intervention significantly inhibited pulmonary fibrosis and alveolitis compared to pure (DG+ED) treatment. In conclusion, the RSD can induce oxidative stress and inflammation in rats, producing reactive oxygen species (ROS)-mediated cytotoxicity to pulmonary cells and leading to silicosis development. The IV administration of combined NP suppressed lung inflammation and collagen formation by maintaining oxidant-antioxidant status and effectively interrupting the fibrosis-silicosis progression. These results may be attributed to the improved bioavailability of DG and ED through their combined nano-encapsulation-mediated targeted drug delivery.
Topics: Animals; Diosgenin; Silicosis; Silicon Dioxide; Pulmonary Fibrosis; Rats; Emodin; Nanoparticles; Male; Dust; Oxidative Stress; Anti-Inflammatory Agents; Rats, Wistar; Lung; Polylactic Acid-Polyglycolic Acid Copolymer
PubMed: 38788565
DOI: 10.1016/j.ecoenv.2024.116483 -
Indian Journal of Occupational and... 2024Silicosis is a progressive pneumoconiosis caused by inhalation of crystalline silica dust commonly seen in workers of construction sites, flour mills, and mining....
Silicosis is a progressive pneumoconiosis caused by inhalation of crystalline silica dust commonly seen in workers of construction sites, flour mills, and mining. Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus antigens commonly encountered in patients with asthma and cystic fibrosis. We report a case of 60-year-old flour mill worker presented with clinico-radiological features of silicosis; further evaluation was found to have an overlap of ABPA in view of severe atopic symptoms. We describe a rare duet of silicosis with ABPA overlap.
PubMed: 38783879
DOI: 10.4103/ijoem.ijoem_170_23 -
Frontiers in Immunology 2024TAM receptor-mediated efferocytosis plays an important function in immune regulation and may contribute to antigen tolerance in the lungs, a site with continuous...
INTRODUCTION
TAM receptor-mediated efferocytosis plays an important function in immune regulation and may contribute to antigen tolerance in the lungs, a site with continuous cellular turnover and generation of apoptotic cells. Some studies have identified failures in efferocytosis as a common driver of inflammation and tissue destruction in lung diseases. Our study is the first to characterize the function of the TAM receptors, Axl and MerTk, in the innate immune cell compartment, cytokine and chemokine production, as well as the alveolar macrophage (AM) phenotype in different settings in the airways and lung parenchyma.
METHODS
We employed MerTk and Axl defective mice to induce acute silicosis by a single exposure to crystalline silica particles (20 mg/50 μL). Although both mRNA levels of Axl and MerTk receptors were constitutively expressed by lung cells and isolated AMs, we found that MerTk was critical for maintaining lung homeostasis, whereas Axl played a role in the regulation of silica-induced inflammation. Our findings imply that MerTk and Axl differently modulated inflammatory tone via AM and neutrophil recruitment, phenotype and function by flow cytometry, and TGF-β and CXCL1 protein levels, respectively. Finally, Axl expression was upregulated in both MerTk and WT AMs, confirming its importance during inflammation.
CONCLUSION
This study provides strong evidence that MerTk and Axl are specialized to orchestrate apoptotic cell clearance across different circumstances and may have important implications for the understanding of pulmonary inflammatory disorders as well as for the development of new approaches to therapy.
Topics: Animals; Mice; Axl Receptor Tyrosine Kinase; c-Mer Tyrosine Kinase; Cytokines; Disease Models, Animal; Homeostasis; Lung; Macrophages, Alveolar; Mice, Inbred C57BL; Mice, Knockout; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases; Silicosis; Male
PubMed: 38774866
DOI: 10.3389/fimmu.2024.1380628 -
Heliyon May 2024Silicosis is a progressive pulmonary fibrosis disease caused by long-term inhalation of silica. The early diagnosis and timely implementation of intervention measures...
Silicosis is a progressive pulmonary fibrosis disease caused by long-term inhalation of silica. The early diagnosis and timely implementation of intervention measures are crucial in preventing silicosis deterioration further. However, the lack of screening and diagnostic measures for early-stage silicosis remains a significant challenge. In this study, silicosis models of varying severity were established through a single exposure to silica with different doses (2.5mg/mice or 5mg/mice) and durations (4 weeks or 12 weeks). The diagnostic performance of computed tomography (CT) quantitative analysis was assessed using lung density biomarkers and the lung density distribution histogram, with a particular focus on non-aerated lung volume. Subsequently, we developed and evaluated a stacking learning model for early diagnosis of silicosis after extracting and selecting features from CT images. The CT quantitative analysis reveals that while the lung densitometric biomarkers and lung density distribution histogram, as traditional indicators, effectively differentiate severe fibrosis models, they are unable to distinguish early-stage silicosis. Furthermore, these findings remained consistent even when employing non-aerated areas, which is a more sensitive indicator. By establishing a radiomics stacking learning model based on non-aerated areas, we can achieve remarkable diagnostic performance to distinguish early-stage silicosis, which can provide a valuable tool for clinical assistant diagnosis. This study reveals the potential of using non-aerated lung areas as a region of interest in stacking learning for early diagnosis of silicosis, providing new insights into early detection of this disease.
PubMed: 38765063
DOI: 10.1016/j.heliyon.2024.e30651 -
Respiratory Medicine Case Reports 2024Extrapulmonary tuberculosis could affect many organs beside lung airway and parenchyma. The mycobacterium tuberculosis can invade area such as the pleural and...
Extrapulmonary tuberculosis could affect many organs beside lung airway and parenchyma. The mycobacterium tuberculosis can invade area such as the pleural and pericardium by lymphogenic, hematogenic, or direct infection. Patient with history exposure with silica (SiO2) have a high-risk factor developing tuberculosis or extrapulmonary tuberculosis. Therefore, this study presents a rare case of pulmonary silicosis in a 38 years-old-man with tuberculosis pericarditis and pleuritis. The amount of silica particle found in bronchoalveolar lavage (BAL) was 39,95 ppm SiO2, while the ADA test from the pericardium and pleural fluids was 35.4 U/L and 40.2 U/L, respectively. The patient underwent pericardiocentesis and thoracocentesis, received first-line anti-tuberculosis drugs, and resigned from work. After one month follow-up, the pericardial as well as pleural fluid totally disappeared. This disease can mimic any other disease. Early detection of risk factor for extrapulmonary tuberculosis and perform the right diagnostic and treatment will give a better outcome for the patient.
PubMed: 38764459
DOI: 10.1016/j.rmcr.2024.102030 -
BMJ Open Respiratory Research May 2024Many interstitial lung diseases (ILDs) have clear causal relationships with environmental and occupational exposures. Exposure identification can assist with diagnosis,... (Review)
Review
BACKGROUND
Many interstitial lung diseases (ILDs) have clear causal relationships with environmental and occupational exposures. Exposure identification can assist with diagnosis, understanding disease pathogenesis, prognostication and prevention of disease progression and occurrence in others at risk. Despite the importance of exposure identification in ILD, there is no standardised assessment approach. Many questionnaires are in clinical and research use, yet their utility, applicability, relevance and performance characteristics are unknown.
OBJECTIVES
This scoping review aimed to summarise the available evidence relating to ILD exposure assessment questionnaires, identify research gaps and inform the content for a future single evidence-based ILD questionnaire.
METHODS
A scoping review based on Arksey and O'Malley's methodological framework was conducted.
ELIGIBILITY CRITERIA
Any questionnaire that elicited exposures specific to ILD was included. A modified COSMIN Risk of Bias Framework was used to assess quality.
SOURCES OF EVIDENCE
Relevant articles were identified from MEDLINE and EMBASE up to 23 July 2023.
RESULTS
22 exposure questionnaires were identified, including 15 generally pertaining to ILD, along with several disease-specific questionnaires for hypersensitivity pneumonitis (n=4), chronic beryllium disease, sarcoidosis and silicosis (1 questionnaire each). For most questionnaires, quality was low, whereby the methods used to determine exposure inclusion and questionnaire validation were not reported or not performed. Collectively the questionnaires covered 158 unique exposures and at-risk occupations, most commonly birds, mould/water damage, wood dust, asbestos, farming, automotive mechanic and miners. Only five questionnaires also provided free-text fields, and 13 queried qualifiers such as temporality or respiratory protection.
CONCLUSIONS
Designing a robust ILD-specific questionnaire should include an evidence-based and relevance-based approach to exposure derivation, with clinicians and patients involved in its development and tested to ensure relevance and feasibility.
Topics: Humans; Lung Diseases, Interstitial; Surveys and Questionnaires; Occupational Exposure; Environmental Exposure
PubMed: 38754906
DOI: 10.1136/bmjresp-2023-002155 -
Association of smoking cessation with airflow obstruction in workers with silicosis: A cohort study.PloS One 2024Studies in general population reported a positive association between tobacco smoking and airflow obstruction (AFO), a hallmark of chronic obstructive pulmonary disease...
BACKGROUND
Studies in general population reported a positive association between tobacco smoking and airflow obstruction (AFO), a hallmark of chronic obstructive pulmonary disease (COPD). However, this attempt was less addressed in silica dust-exposed workers.
METHODS
This retrospective cohort study consisted of 4481 silicotic workers attending the Pneumoconiosis Clinic during 1981-2019. The lifelong work history and smoking habits of these workers were extracted from medical records. Spirometry was carried out at the diagnosis of silicosis (n = 4177) and reperformed after an average of 9.4 years of follow-up (n = 2648). AFO was defined as forced expiratory volume in one second (FEV1)/force vital capacity (FVC) less than lower limit of normal (LLN). The association of AFO with smoking status was determined using multivariate logistics regression, and the effect of smoking cessation on the development of AFO was evaluated Cox regression.
RESULTS
Smoking was significantly associated with AFO (current smokers: OR = 1.92, 95% CI 1.51-2.44; former smokers: OR = 2.09, 95% CI 1.65-2.66). The risk of AFO significantly increased in the first 3 years of quitting smoking (OR = 1.23, 95% CI 1.02-1.47) but decreased afterwards with increasing years of cessation. Smoking cessation reduced the risk of developing AFO no matter before or after the confirmation of silicosis (pre-silicosis cessation: HR = 0.58, 95% CI 0.46-0.74; post-silicosis cessation: HR = 0.62, 95% CI 0.48-0.79).
CONCLUSIONS
Smoking cessation significantly reduced the risk of AFO in the workers with silicosis, although the health benefit was not observed until 3 years of abstinence. These findings highlight the importance of early and long-term smoking cessation among silicotic or silica dust-exposed workers.
Topics: Humans; Silicosis; Male; Middle Aged; Smoking Cessation; Retrospective Studies; Adult; Pulmonary Disease, Chronic Obstructive; Female; Occupational Exposure; Forced Expiratory Volume; Smoking; Spirometry; Vital Capacity; Cohort Studies
PubMed: 38753732
DOI: 10.1371/journal.pone.0303743 -
Ecotoxicology and Environmental Safety Jun 2024Silicosis is a disease characterized by lung inflammation and fibrosis caused by long-term inhalation of free silicon dioxide (SiO). Recent studies have found that a...
Silicosis is a disease characterized by lung inflammation and fibrosis caused by long-term inhalation of free silicon dioxide (SiO). Recent studies have found that a large number of lymphatic hyperplasia occurs during the occurrence and development of silicosis. miRNAs play an important role in lymphangiogenesis. However, the regulation and mechanism of miRNAs on lymphangiogenesis in silicosis remain unclear. In this study, lymphangiogenesis was observed in silicosis rats, and VEGF-C-targeted miRNAs were screened, and the effect of miRNAs on the formation of human lymphatic endothelial cells (HLECs) tubular structure was investigated in vitro. The results showed that SiO promoted the expressions of Collagen Ι and α-SMA, TNF-α, IL-6 and VEGF-C increased first and then decreased, and promoted the formation of lymphatic vessels. Bioinformatics methods screened miR-455-3p for targeted binding to VEGF-C, and dual luciferase reporter genes confirmed VEGF-C as the target gene of miR-455-3p, and miR-455-3p was down-regulated in the lung tissue of silicosis rats. Transfection of miR-455-3p Inhibitors down-regulated the expression level of miR-455-3p and up-regulated the expression levels of VEGF-C and VEGFR-3 in HLECs, enhanced migration ability and increased tube formation. Transfection of miR-455-3p Mimics showed an opposite trend. These results suggest that miR-455-3p further regulates the tubular structure formation of HLECs by regulating VEGF-C/VEGFR3. Therefore, targeting miR-455-3p may provide a new therapeutic strategy for SiO-induced silicosis injury.
Topics: Animals; Humans; Male; Rats; Endothelial Cells; Lymphangiogenesis; MicroRNAs; Rats, Sprague-Dawley; Silicon Dioxide; Silicosis; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor Receptor-3
PubMed: 38728943
DOI: 10.1016/j.ecoenv.2024.116444 -
BMC Pulmonary Medicine May 2024Simvastatin (Sim), a hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in prevention and treatment of cardiovascular diseases....
BACKGROUND
Simvastatin (Sim), a hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in prevention and treatment of cardiovascular diseases. Studies have suggested that Sim exerts anti-fibrotic effects by interfering fibroblast proliferation and collagen synthesis. This study was to determine whether Sim could alleviate silica-induced pulmonary fibrosis and explore the underlying mechanisms.
METHODS
The rat model of silicosis was established by the tracheal perfusion method and treated with Sim (5 or 10 mg/kg), AICAR (an AMPK agonist), and apocynin (a NOX inhibitor) for 28 days. Lung tissues were collected for further analyses including pathological histology, inflammatory response, oxidative stress, epithelial mesenchymal transformation (EMT), and the AMPK-NOX pathway.
RESULTS
Sim significantly reduced silica-induced pulmonary inflammation and fibrosis at 28 days after administration. Sim could reduce the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α and transforming growth factor-β1 in lung tissues. The expressions of hydroxyproline, α-SMA and vimentin were down-regulated, while E-cad was increased in Sim-treated rats. In addition, NOX4, p22pox, p40phox, p-p47phox/p47phox expressions and ROS levels were all increased, whereas p-AMPK/AMPK was decreased in silica-induced rats. Sim or AICAR treatment could notably reverse the decrease of AMPK activity and increase of NOX activity induced by silica. Apocynin treatment exhibited similar protective effects to Sim, including down-regulating of oxidative stress and inhibition of the EMT process and inflammatory reactions.
CONCLUSIONS
Sim attenuates silica-induced pulmonary inflammation and fibrosis by downregulating EMT and oxidative stress through the AMPK-NOX pathway.
Topics: Animals; Male; Rats; Acetophenones; Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Disease Models, Animal; Epithelial-Mesenchymal Transition; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lung; NADPH Oxidase 4; NADPH Oxidases; Oxidative Stress; Pneumonia; Pulmonary Fibrosis; Ribonucleotides; Signal Transduction; Silicon Dioxide; Silicosis; Simvastatin; Transforming Growth Factor beta1
PubMed: 38720270
DOI: 10.1186/s12890-024-03014-9 -
Open Respiratory Archives 2024Asthma is a chronic inflammatory disease that affects about 5% of the world's population and generates high health and social costs. Proper management of the disease... (Review)
Review
Asthma is a chronic inflammatory disease that affects about 5% of the world's population and generates high health and social costs. Proper management of the disease requires a correct diagnosis, based on objective measures of functional impairment, as well as symptom control and assessment of the future risk of exacerbations.It has been estimated that 18% of asthma patients in Western Europe have severe asthma and approximately 50% of them have poor control. The severity of asthma is established based on the minimum maintenance treatment needs to achieve control. Asthma clinical practice guidelines recommend classifying severe patients into allergic asthma (T2); eosinophilic asthma (T2) and non-T2 asthma in order to establish the most appropriate treatment.In recent decades, new biological therapies have been developed that can be applied according to the phenotype and endotype of asthma, allowing for selective and personalized treatment. These phenotypes and endotypes can change over time and therefore, the identification of biomarkers capable of predicting the severity, the course of the disease and the response to a given treatment seems essential. A large number of biomarkers have been studied in asthma, but so far only a few can be readily used in routine clinical practice. The application of omics technologies (epigenomics, genomics, transcriptomics, proteomics, metabolomics, lipidomics, etc.) for this purpose is still in the research phase.
PubMed: 38707659
DOI: 10.1016/j.opresp.2024.100324