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China CDC Weekly Oct 2023
Review
PubMed: 37970069
DOI: 10.46234/ccdcw2023.162 -
International Journal of Biological... 2023Silicosis is a common and ultimately fatal occupational disease, yet the limited therapeutic option remains the major clinical challenge. Apelin, an endogenous ligand of...
Silicosis is a common and ultimately fatal occupational disease, yet the limited therapeutic option remains the major clinical challenge. Apelin, an endogenous ligand of the G-protein-coupled receptor (APJ), is abundantly expressed in diverse organs. The apelin-APJ axis helps to control pathological and physiological processes in lung. The role of apelin in the pathological process and its possible therapeutic effects on silicosis have not been elucidated. In this study, we found that lung expression and circulating levels of apelin were markedly decreased in silicosis patients and silica-induced fibrotic mice and associated with the severity. Furthermore, data demonstrated that pre-treatment from day 3 and post-treatment from day 15 with apelin could both alleviate silica-induced pulmonary fibrosis in mice. Besides, apelin inhibited pulmonary fibroblast activation via transforming growth factor beta 1 (TGF-β1) signaling. Our study suggested that apelin could prevent and reverse silica-induced pulmonary fibrosis by inhibiting the fibroblast activation through TGF-β1 signaling pathway, thus providing a new potential therapeutic strategy for silicosis and other pulmonary fibrosis.
Topics: Animals; Mice; Apelin; Fibroblasts; Pulmonary Fibrosis; Silicon Dioxide; Silicosis; Transforming Growth Factor beta1
PubMed: 37705751
DOI: 10.7150/ijbs.81436 -
CMAJ : Canadian Medical Association... Dec 2023
Topics: Humans; Middle Aged; Berylliosis; Metal Workers
PubMed: 38049163
DOI: 10.1503/cmaj.221680 -
International Immunopharmacology Dec 2023Silicosis, a highly lethal occupational respiratory disease characterized by irreversible pulmonary fibrosis, remains challenging to treat due to its unclear...
Silicosis, a highly lethal occupational respiratory disease characterized by irreversible pulmonary fibrosis, remains challenging to treat due to its unclear pathogenesis. In this study, bioinformatics, network pharmacology, and experimental validation were combined to explore potential mechanisms and therapeutic drugs for silicosis. First, the differentially expressed genes(DEGs)and pathway enrichment in pulmonary fibrosis were identified by GO and KEGG analysis. Next, the differential genes were submitted to cMap database for drug prediction and celastrol stood out as the most promising candidate drug. Then, network pharmacology analysis identified pharmacological targets of celastrol and demonstrated that celastrol could regulate JAK-STAT, MAPK, and Toll-like receptor signaling pathways. Finally, we verified the therapeutic role and mechanism of celastrol on silicosis. In vivo, celastrol significantly ameliorated CS-induced inflammation and fibrosis in silicosis mice, including inflammatory cell infiltration, collagen fiber and extracellular matrix deposition, fibroblast activation and related factor expression. Moreover, it dramatically improved lung respiratory function of silicosis mice. In vitro, celastrol suppressed CS-induced cytokine expression, apoptosis of macrophages and activation of Stat3 and Erk1/2 signals. Overall, our research identified and verified celastrol as a novel and promising candidate drug for silicosis.
Topics: Mice; Animals; Pulmonary Fibrosis; Network Pharmacology; Silicosis; Computational Biology
PubMed: 37948856
DOI: 10.1016/j.intimp.2023.111068 -
Journal of Fungi (Basel, Switzerland) Jul 2023The increasing morbidity and mortality of life-threatening pneumonia (PCP) in immunocompromised people poses a global concern, prompting the World Health Organization... (Review)
Review
The increasing morbidity and mortality of life-threatening pneumonia (PCP) in immunocompromised people poses a global concern, prompting the World Health Organization to list it as one of the 19 priority invasive fungal diseases, calling for increased research and public health action. In response to this initiative, we provide this review on the epidemiology of PCP in non-HIV patients with various immunodeficient conditions, including the use of immunosuppressive agents, cancer therapies, solid organ and stem cell transplantation, autoimmune and inflammatory diseases, inherited or primary immunodeficiencies, and COVID-19. Special attention is given to the molecular epidemiology of PCP outbreaks in solid organ transplant recipients; the risk of PCP associated with the increasing use of immunodepleting monoclonal antibodies and a wide range of genetic defects causing primary immunodeficiency; the trend of concurrent infection of PCP in COVID-19; the prevalence of colonization; and the rising evidence supporting de novo infection rather than reactivation of latent infection in the pathogenesis of PCP. Additionally, we provide a concise discussion of the varying effects of different immunodeficient conditions on distinct components of the immune system. The objective of this review is to increase awareness and knowledge of PCP in non-HIV patients, thereby improving the early identification and treatment of patients susceptible to PCP.
PubMed: 37623583
DOI: 10.3390/jof9080812 -
Toxicology Dec 2023Silicosis is a severe worldwide occupational hazard, characterized with lung tissue inflammation and irreversible fibrosis caused by crystalline silicon dioxide. As the...
Silicosis is a severe worldwide occupational hazard, characterized with lung tissue inflammation and irreversible fibrosis caused by crystalline silicon dioxide. As the most common and abundant internal modification of messenger RNAs or noncoding RNAs, N6-methyladenosine (m6A) methylation is dysregulated in the chromic period of silicosis. However, whether m6A modification is involved in the early phase of silica-induced pulmonary inflammation and fibrosis and its specific effector cells remains unknown. In this study, we established a pulmonary inflammation and fibrosis mouse model by silica particles on day 7 and day 28. Then, we examined the global m6A modification level by m6A dot blot and m6A RNA methylation quantification kits. The key m6A regulatory factors were analyzed by RTqPCR, Western blot, and immunohistochemistry (IHC) in normal and silicosis mice. The results showed that the global m6A modification level was upregulated in silicosis lung tissues with the demethylase FTO suppression after silica exposure for 7 days and 28 days. METTL3, METTL14, ALKBH5, and other m6A readers had no obvious differences between the control and silicosis groups. Then, single-cell sequencing analysis revealed that thirteen kinds of cells were recognized in silicosis lung tissues, and the mRNA expression of FTO was downregulated in epithelial cells, endothelial cells, fibroblasts, and monocytes. These results were further confirmed in mouse lung epithelial cells (MLE-12) exposed to silica and in the peripheral blood mononuclear cells of silicosis patients. In conclusion, the high level of global m6A modification in the early stage of silicosis is induced by the downregulation of the demethylase FTO, which may provide a novel target for the diagnosis and treatment of silicosis.
Topics: Animals; Humans; Mice; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Endothelial Cells; Leukocytes, Mononuclear; Methyltransferases; Pneumonia; Pulmonary Fibrosis; RNA Methylation; Silicon Dioxide; Silicosis
PubMed: 37979906
DOI: 10.1016/j.tox.2023.153673 -
European Respiratory Review : An... Jan 2024Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary fibrosis and lung cancer.
RESEARCH QUESTION
Is pulmonary fibrosis from exposure to occupational carcinogens an independent risk factor for lung cancer?
STUDY DESIGN AND METHODS
A comprehensive search of PubMed, Embase, Web of Science and Cochrane databases with over 100 search terms regarding occupational hazards causing pulmonary fibrosis was conducted. After screening and extraction, quality of evidence and eligibility criteria for meta-analysis were assessed. Meta-analysis was performed using a random-effects model.
RESULTS
52 studies were identified for systematic review. Meta-analysis of subgroups identified silicosis as a risk factor for lung cancer when investigating odds ratios for silicosis in autopsy studies (OR 1.47, 95% CI 1.13-1.90) and for lung cancer mortality in patients with silicosis (OR 3.21, 95% CI 2.67-3.87). Only considering studies with an adjustment for smoking as a confounder identified a significant increase in lung cancer risk (OR 1.58, 95% CI 1.34-1.87). However, due to a lack of studies including cumulative exposure, no adjustments could be included. In a qualitative review, no definitive conclusion could be reached for asbestosis and silicosis as independent risk factors for lung cancer, partly because the studies did not take cumulative exposure into account.
INTERPRETATION
This systematic review confirms the current knowledge regarding asbestosis and silicosis, indicating a higher risk of lung cancer in exposed individuals compared to exposed workers without fibrosis. These individuals should be monitored for lung cancer, especially when asbestosis or silicosis is present.
Topics: Humans; Silicon Dioxide; Lung Neoplasms; Pulmonary Fibrosis; Asbestosis; Silicosis; Occupational Exposure
PubMed: 38355151
DOI: 10.1183/16000617.0224-2023 -
Frontiers in Cellular and Infection... 2023Pneumoconiosis patients have a high prevalence of pulmonary infections, which can complicate diagnosis and treatment. And there is no comprehensive study of the...
BACKGROUND
Pneumoconiosis patients have a high prevalence of pulmonary infections, which can complicate diagnosis and treatment. And there is no comprehensive study of the microbiome of patients with pneumoconiosis. The application of metagenomic next-generation sequencing (mNGS) fills the gap to some extent by analyzing the lung microbiota of pneumoconiosis population while achieving accurate diagnosis.
METHODS
We retrospectively analyzed 44 patients with suspected pneumoconiosis complicated with pulmonary infection between Jan 2020 and Nov 2022. Bronchoalveolar lavage fluid (BALF) specimens from 44 patients were collected and tested using the mNGS technology.
RESULTS
Among the lung microbiome of pneumoconiosis patients with complicated pulmonary infection (P group), the most frequently detected bacteria and fungi at the genus level were and , at the species level were and , respectively, and the most frequently detected DNA virus was . There was no significant difference in α diversity between the P group and the non-pneumoconiosis patients complicated with pulmonary infection group (Non-P group) in pulmonary flora, while 0.01 for β diversity analysis, and the differential species between the two groups were and . In addition, we monitored a high distribution of and in the P group, while herpes virus was detected in the majority of samples.
CONCLUSIONS
Overall, we not only revealed a comprehensive lung microbiome profile of pneumoconiosis patients, but also compared the differences between their microbiome and that of non-pneumoconiosis complicated with pulmonary infection patients. This provides a good basis for a better understanding of the relationship between pneumoconiosis and microorganisms, and for the search of potential biomarkers.
Topics: Humans; Retrospective Studies; Pneumonia; Microbiota; High-Throughput Nucleotide Sequencing; Biomarkers; Lung; Sensitivity and Specificity; Metagenomics
PubMed: 37545858
DOI: 10.3389/fcimb.2023.1200157 -
Gene Apr 2024Pneumoconiosis is a kind of lung dysfunction caused by the inhalation of mineral dust. However, the potential molecular mechanism of pneumoconiosis have not been fully...
BACKGROUND
Pneumoconiosis is a kind of lung dysfunction caused by the inhalation of mineral dust. However, the potential molecular mechanism of pneumoconiosis have not been fully elucidated.
METHODS
In this study, the silica-treated pneumoconiosis mice model was constructed and the transcriptome sequencing data including lncRNA, circRNA, and mRNA were obtained. Firstly, differentially expressed lncRNA, circRNA, and mRNA (DElncRNA, DEcircRNA, DEGs) between control and pneumoconiosis/silicosis samples were screened, the target miRNAs (co-pre-miRNAs) were obtained by intersecting the miRNAs predicted by DElncRNA and DEcircRNA, respectively, and the target mRNAs (co-mRNA) were obtained by intersecting the mRNAs predicted by target miRNA and DEGs. Then, the lncRNA/circRNA-miRNA-mRNA networks were constructed by Cytoscape. Next, the key mRNAs were obtained by protein-protein interaction (PPI) analysis, and the key lncRNAs/circRNAs were selected by correlation analysis. Moreover, the expression of the key lncRNAs, circRNAs and mRNAs on chromosome were studied by the "circlize" package. Furthermore, the TFs-miRNA-mRNA network was constructed and the function of DEGs were explored by Ingenuity Pathway Analysis (IPA). To demonstrate the feasibility and value of the constructed ceRNA networks, we validated key genes and mmu-miR-682 pathway. Finally, We used the Drug-Gene Interaction database to predict potential drugs that could interfere with key genes,which may help to find promising treatment.
RESULTS
There were 427 DElncRNAs, 107 DEcircRNAs and 1,597 DEGs between silicosis and control groups. Totals of 77 co-pre-miRNAs and 96 co-mRNA were screened, and the lncRNA/circRNA-miRNA-mRNA networks were constructed with 27 lncRNA/25 circRNAs, 74 miRNAs and 96 mRNAs. Then, 6 key mRNAs including Igf1, Klf4, Ptgs2, Epas1, Gnao1, and Il1a were obtained by PPI, and all of these key mRNAs and 10 key lncRNAs and 8 circRNAs were significantly different between the pneumoconiosis and normal groups, in which 10 lncRNAs and 9 circRNA that have not been previously studied in pneumoconiosis/silicosis can be used as new potential therapeutic targets. Moreover, the TFs-miRNA-mRNA network were constructed with 11 TFs, 1 key miRNA (mmu-miR-682) and 3 key mRNAs (Igf1, Epas1, Ptgs2). And the validation of key genes revealing by RNA-seq through experimental approaches shows the the predictive power of this study. Finally, IPA results indicated that 41 pathways were activated and 2 pathways were suppressed in pneumoconiosis/silicosis groups, and Pathogen Induced Cytokine Storm Signaling Pathway was the most significant pathway affected by pneumoconiosis/silicosis. In addition, 93 drugs were screened out by Drug-Gene Interaction database. Among them, Hydroxychloroquine was a kind of drug which associated with Il1a and Ptgs2, may be a promising treatment.
CONCLUSION
This study constructed the lncRNA/circRNA-miRNA-mRNA and TFs-miRNA-mRNA networks, which could deepen the potential molecular regulatory mechanism of pneumoconiosis/silicosis.
Topics: Animals; Mice; RNA, Long Noncoding; RNA, Circular; Cyclooxygenase 2; Exome Sequencing; Pneumoconiosis; Silicosis; MicroRNAs; RNA, Messenger; Gene Regulatory Networks
PubMed: 38242381
DOI: 10.1016/j.gene.2024.148169 -
The Science of the Total Environment Dec 2023Asbestosis is a common pneumoconiosis caused by long-term asbestos exposure. Analysis of the burden of asbestosis would help in creating informed public health...
BACKGROUND
Asbestosis is a common pneumoconiosis caused by long-term asbestos exposure. Analysis of the burden of asbestosis would help in creating informed public health strategies.
METHODS
Data on asbestosis were analyzed using the Global Burden of Disease study 2019. The estimated annual percentage change (EAPC) was calculated to demonstrate temporal trends in the age-standardized rate (ASR) of asbestosis from 1990 to 2019.
RESULTS
Globally, 36,339 incident cases of asbestosis, led to 3572 deaths and 71,225 disability adjusted life years (DALYs) in 2019. During 1990-2019, the overall ASRs of incidence and DALYs declined by an annual average of 0.29 % and 0.27 %, with the respective EAPCs being -0.29 (95 % confidence interval [CI]: -0.43, -0.14) and -0.27 (95%CI: -0.53, -0.01). The ASRs of mortality increased with EAPC of 0.65 (95%CI: 0.34, 0.96). Trends in incidence and prevalence rose in females, but declined in males. The asbestosis burden was heterogeneous across regions and countries. The heaviest burden of asbestosis was observed in the United States, India, and China. Trends in ASRs of asbestosis varied across countries/territories. Pronounced increasing trends in incidence and prevalence occurred in Georgia, Iran, and Croatia.
CONCLUSIONS
Decreasing incident trend of asbestosis was observed globally over the past three decades. However, the ongoing asbestosis burden highlighted that asbestosis remained a challenge to public health, and cost-effective measures were required to reduce the asbestosis burden.
Topics: Female; Male; Humans; Asbestosis; China; Cluster Analysis; Croatia; Georgia; Quality-Adjusted Life Years; Incidence
PubMed: 37591378
DOI: 10.1016/j.scitotenv.2023.166346