Pneumoconiosis refers to a spectrum of pulmonary diseases caused by inhalation of mineral dust, usually as the result of certain occupations. The main pathological features include chronic pulmonary inflammation and progressive pulmonary fibrosis, which can eventually lead to death caused by respiratory and/or heart failure. Pneumoconiosis is widespread globally, seriously threatening global public health. Its high incidence and mortality lie in improper occupational protection, and in the lack of early diagnostic methods and effective treatments. This article reviews the epidemiology, safeguard procedures, diagnosis, and treatment of pneumoconiosis, and summarizes recent research advances and future research prospects.

Clinical studies reveal changes in blood eosinophil counts and eosinophil cationic proteins that may serve as risk factors for human coronary heart diseases. Here we report an increase of blood or heart eosinophil counts in humans and mice after myocardial infarction (MI), mostly in the infarct region. Genetic or inducible depletion of eosinophils exacerbates cardiac dysfunction, cell death, and fibrosis post-MI, with concurrent acute increase of heart and chronic increase of splenic neutrophils and monocytes. Mechanistic studies reveal roles of eosinophil IL4 and cationic protein mEar1 in blocking H₂O₂- and hypoxia-induced mouse and human cardiomyocyte death, TGF-β-induced cardiac fibroblast Smad2/3 activation, and TNF-α-induced neutrophil adhesion on the heart endothelial cell monolayer. In vitro-cultured eosinophils from WT mice or recombinant mEar1 protein, but not eosinophils from IL4-deficient mice, effectively correct exacerbated cardiac dysfunctions in eosinophil-deficient ∆dblGATA mice. This study establishes a cardioprotective role of eosinophils in post-MI hearts.

Silicosis caused by inhalation of silica particles leads to more than ten thousand new occupational exposure-related deaths yearly. Exacerbating this issue, there are currently few drugs reported to effectively treat silicosis. Tetrandrine is the only drug approved for silicosis treatment in China, and despite more than decades of use, its efficacy and mechanisms of action remain largely unknown. Here, in this study, we established silicosis mouse models to investigate the effectiveness of tetrandrine of early and late therapeutic administration. To this end, we used multiple cardiopulmonary function test, as well as markers for inflammation and fibrosis. Moreover, using single cell RNA sequencing and transcriptomics of lung tissue and quantitative microarray analysis of serum from silicosis and control mice, our results provide a novel description of the target pathways for tetrandrine. Specifically, we found that tetrandrine attenuated silicosis by inhibiting both the canonical and non-canonical NLRP3 inflammasome pathways in lung macrophages. Taken together, our work showed that tetrandrine yielded promising results against silicosis-associated inflammation and fibrosis and further lied the groundwork for understanding its molecular targets. Our results also facilitated the wider adoption and development of tetrandirne, potentially accelerating a globally accepted therapeutic strategy for silicosis.

Silicosis is the most prevalent and fatal occupational disease with no effective therapeutics, and currently used drugs cannot reverse the disease progress. Worse still, there are still challenges to be addressed to fully decipher the intricated pathogenesis. Thus, specifying the essential mechanisms and targets in silicosis progression then exploring anti-silicosis pharmacuticals are desperately needed. In this work, multi-omics atlas was constructed to depict the pivotal abnormalities of silicosis and develop targeted agents. By utilizing an unbiased and time-resolved analysis of the transcriptome, proteome and phosphoproteome of a silicosis mouse model, we have verified the significant differences in transcript, protein, kinase activity and signaling pathway level during silicosis progression, in which the importance of essential biological processes such as macrophage activation, chemotaxis, immune cell recruitment and chronic inflammation were emphasized. Notably, the phosphorylation of EGFR (p-EGFR) and SYK (p-SYK) were identified as potential therapeutic targets in the progression of silicosis. To inhibit and validate these targets, we tested fostamatinib (targeting SYK) and Gefitinib (targeting EGFR), and both drugs effectively ameliorated pulmonary dysfunction and inhibited the progression of inflammation and fibrosis. Overall, our drug discovery with multi-omics approach provides novel and viable therapeutic strategies for the treatment of silicosis.

Heart failure (HF) patients often suffer from multiple comorbidities, such as diabetes, atrial fibrillation, depression, chronic obstructive pulmonary disease, and chronic kidney disease. The coexistance of comorbidities usually leads to multi morbidity and poor prognosis. Treatments for HF patients with multi morbidity are still an unmet clinical need, and finding an effective therapy strategy is of great value. HF can lead to comorbidity, and in return, comorbidity may promote the progression of HF, creating a vicious cycle. This reciprocal correlation indicates there may be some common causes and biological mechanisms. Metabolism remodeling and chronic inflammation play a vital role in the pathophysiological processes of HF and comorbidities, indicating metabolism and inflammation may be the links between HF and comorbidities. In this review, we comprehensively discuss the major underlying mechanisms and therapeutic implications for comorbidities of HF. We first summarize the potential role of metabolism and inflammation in HF. Then, we give an overview of the linkage between common comorbidities and HF, from the perspective of epidemiological evidence to the underlying metabolism and inflammation mechanisms. Moreover, with the help of bioinformatics, we summarize the shared risk factors, signal pathways, and therapeutic targets between HF and comorbidities. Metabolic syndrome, aging, deleterious lifestyles (sedentary behavior, poor dietary patterns, smoking, etc.), and other risk factors common to HF and comorbidities are all associated with common mechanisms. Impaired mitochondrial biogenesis, autophagy, insulin resistance, and oxidative stress, are among the major mechanisms of both HF and comorbidities. Gene enrichment analysis showed the PI3K/AKT pathway may probably play a central role in multi morbidity. Additionally, drug targets common to HF and several common comorbidities were found by network analysis. Such analysis has already been instrumental in drug repurposing to treat HF and comorbidity. And the result suggests sodium-glucose transporter-2 (SGLT-2) inhibitors, IL-1β inhibitors, and metformin may be promising drugs for repurposing to treat multi morbidity. We propose that targeting the metabolic and inflammatory pathways that are common to HF and comorbidities may provide a promising therapeutic strategy.