Silicosis is a global problem, and it has brought about great burdens to society and patients’ families. The etiology of silicosis is clear, preventable, and controllable, but the onset is hidden and the duration is long. Thus, it is difficult to diagnose it early and treat it effectively, leaving workers unaware of the consequences of dust exposure. As such, a lack of details in the work history and a slow progression of lung disease contribute to the deterioration of patients until silicosis has advanced to fibrosis. These issues are the key factors impeding the diagnosis and the treatment of silicosis. This article reviews the literature on the early identification, diagnosis, and treatment of silicosis as well as analyzes the difficulties in the diagnosis and the treatment of silicosis and discusses its direction of future development.

Silicosis is a common occupational disease and represents a significant contributor to respiratory morbidity and mortality worldwide. Lipid-laden macrophages, or foam cells, are observed in the lungs of patients with silicosis but the mechanisms mediating their formation remain poorly understood. In this study, we sought to elucidate the mechanisms by which silica promotes foam cell formation in the lung, and to determine whether uptake of lipids alone is sufficient to drive TGF-β production by alveolar macrophages. Consistent with previous reports, we found that foam cells were markedly increased in the lungs of patients with silicosis and that these findings associated with both higher levels of intracellular lipid levels (oxidized LDL, ox-LDL) and elevated transcript levels for the lipid scavenger receptor CD36 and the nuclear receptor PPARγ. Employing a rat alveolar macrophage cell line, we found that exposure to silica dust or ox-LDL alone had a modest effect on the induction of foam cell formation and only silica was capable of inducing the production of TGF-β. In contrast, foam cell formation and TGF-β production were both dramatically increased when cells were exposed to a combination of silica dust and ox-LDL. Moreover, we found that these endpoints were markedly attenuated by either blocking CD36 or inhibiting the activity of PPARγ. Altogether, our findings suggest that foam cell formation and TGF-β production are driven by the simultaneous uptake of silica and lipids in alveolar macrophages and that strategies aimed at blocking lipid uptake by alveolar macrophages might be effective in ameliorating fibrotic responses to silica in the lung.

Glycolytic reprogramming is an important metabolic feature in the development of pulmonary fibrosis. However, the specific mechanism of glycolysis in silicosis is still not clear. In this study, silicotic models and silica-induced macrophage were used to elucidate the mechanism of glycolysis induced by silica. Expression levels of the key enzymes in glycolysis and macrophage activation indicators were analyzed by Western blot, qRT-PCR, IHC, and IF analyses, and by using a lactate assay kit. We found that silica promotes the expression of the key glycolysis enzymes HK2, PKM2, LDHA, and macrophage activation factors iNOS, TNF-α, Arg-1, IL-10, and MCP1 in silicotic rats and silica-induced NR8383 macrophages. The enhancement of glycolysis and macrophage activation induced by silica was reduced by Ac-SDKP or siRNA-Ldha treatment. This study suggests that Ac-SDKP treatment can inhibit glycolytic reprogramming in silica-induced lung macrophages and silicosis.

Rosacea is a chronic inflammatory skin disease whose late manifestations have not yet been clearly reported in animal models. The objective of this study is to describe the skin lesions and major histopathological changes in a rosacea-like phenotype in mice induced by prolonged LL-37 administration and furthermore, to assess the potential of long-term LL-37 administration in inducing irreversible rosacea-like skin lesion models. Balb/c mice were continuously injected intradermally with LL-37 every 12 h to induce a rosacea-like phenotype. After LL-37 injections were administered for 20 consecutive days, the area of rosacea-like lesions gradually expanded in the first 13 days, then entered a stable phase. Haematoxylin and eosin (H&E) and Van Gieson’s staining showed a high degree of inflammatory cell aggregation, thickening of the epidermis and dermis, and collagen deposition in large quantities. The results of immunofluorescence staining and Western blotting showed that the expression of α-SMA, TNF-α, vimentin, and COL1 in the skin of mice was significantly upregulated. Short-term LL-37 administration induced rosacea-like lesions that only featured the aggregation of inflammatory factors and thickening of the epidermis, whereas no collagen hyperplasia was observed, and a full recovery was noticed. However, rosacea-like skin lesions induced by long-term LL-37 administration did not completely recover. Our study compares rosacea-like lesions induced by short-term versus long-term LL-37 administration, and the results suggest that irreversible rosacea-like lesions can be induced by long-term LL-37 administration.

From the two perspectives of intestinal flora and plasma metabolomics, the mechanism of occurrence and development of pneumoconiosis was explored to provide a new target for the prevention and treatment of pneumoconiosis. In this study, 16S ribosome DNA (16SrDNA) gene sequencing technology was used to analyze the differences in intestinal flora of each research group through operational taxonomic units (OUT) analysis, cluster analysis, principal component analysis (PCA), partial least square discriminant analysis (PLS-DA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and other analytical methods were used to analyze the differences in plasma metabolites between the study groups. Metabonomics analysis showed that the plasma metabolites of pneumoconiosis patients were significantly different from those of normal people. Fold change > 2; vip > 1; p < 0.05 were the screening criteria. In the positive and negative mode, we screened ten types of differential metabolites. These ten metabolites were upregulated to varying degrees in the pneumoconiosis patients. Seven metabolic pathways were obtained by analyzing the metabolic pathways of different metabolites. Among them, the aminoacyl tRNA biosynthesis pathway changed most obviously. The α diversity of two groups of intestinal flora was analyzed using the 16SrDNA technique. The results showed that there was no significant difference in ACE, Chao1, Shannon, or Simpson in the two groups (p > 0.05). Beta diversity analysis showed that there were differences in microbial communities. In pneumoconiosis patients, the abundance of Prevotellaceae increased, and the other nine species decreased. Compared to the control group, the abundance of Prevotellaceae in the intestinal flora of pneumoconiosis increased, and the abundance of the other nine species decreased. Compared to controls, ten substances in the plasma metabolites of pneumoconiosis patients were upregulated. Seven metabolic pathways were obtained by analyzing the metabolic pathways of different metabolites. Among them, the aminoacyl tRNA biosynthesis pathway changed most significantly. This provided a theoretical basis for further study on the pathogenesis, early prevention, and treatment of pneumoconiosis.

Glycolysis and ER stress have been considered important drivers of pulmonary fibrosis. However, it is not clear whether glycolysis and ER stress are interconnected and if those interconnections regulate the development of pulmonary fibrosis. Our previous studies found that the expression of LDHA, a key enzyme involved in glycolysis, was increased in silica-induced macrophages and silicotic models, and it was closely related to silicosis fibrosis by participating in inflammatory response. However, whether pharmacological inhibition of LDHA is beneficial to the amelioration of silicosis fibrosis remains unclear. In this study, we investigated the effects of oxamate, a potent inhibitor of LDHA, on the regulation of glycolysis and ER stress in alveolar macrophages and silicotic mice. We found that silica induced the upregulation of glycolysis and the expression of key enzymes directly involved in ER stress in NR8383 macrophages. However, treatment of the macrophages and silicotic mice with oxamate attenuated glycolysis and ER stress by inhibiting LDHA, causing a decrease in the production of lactate. Therefore, oxamate demonstrated an anti-fibrotic role by reducing glycolysis and ER stress in silicotic mice.