RESUMO
Pneumoconiosis is the most common occupational disease among coal miners, which is a lung disease caused by long-term inhalation of coal dust and retention in the lungs. The early stage of this disease is highly insidious, and pulmonary fibrosis may occur in the middle and late stages, leading to an increase in patient pain index and mortality rate. Currently, there is a lack of effective treatment methods. The pathogenesis of pneumoconiosis is complex and has many influencing factors. Although the characteristics of coal dust have been considered the main cause of different mechanisms of pneumoconiosis, the effects of coal dust composition, particle size and shape, and coal dust concentration on the pathogenesis of pneumoconiosis have not been systematically elucidated. Meanwhile, considering the irreversibility of pneumoconiosis progression, early prediction for pneumoconiosis patients is particularly important. However, there is no early prediction standard for pneumoconiosis among coal miners. This review summarizes the relevant research on the pathogenesis and prediction of pneumoconiosis in coal miners in recent years. Firstly, the pathogenesis of coal worker pneumoconiosis and silicosis was discussed, and the impact of coal dust characteristics on pneumoconiosis was analyzed. Then, the early diagnostic methods for pneumoconiosis have been systematically introduced, with a focus on image collaborative computer-aided diagnosis analysis and biomarker detection. Finally, the challenge of early screening technology for miners with pneumoconiosis was proposed.
Assuntos
Minas de Carvão , Poeira , Humanos , Pneumoconiose , Antracose/epidemiologia , Exposição Ocupacional/efeitos adversos , Biomarcadores , Carvão Mineral , Doenças Profissionais/etiologia , Doenças Profissionais/epidemiologiaRESUMO
BACKGROUND: Nintedanib and pirfenidone are preferred pharmacological therapies for patients with idiopathic pulmonary fibrosis (IPF). However, evidence favoring antifibrotic therapy in patients with non-IPF fibrosing interstitial lung diseases (ILD) is limited. OBJECTIVE: To investigate the effects of antifibrotic therapy on disease progression, all-cause mortality, and acute exacerbation (AE) risk in patients with non-IPF fibrosing ILDs. DESIGN: Meta-analysis. DATA SOURCES AND METHODS: Electronic databases were searched for articles published before 28 February 2023. Studies that evaluated the efficacy of antifibrotic agents in patients with fibrosing ILDs were selected. The primary outcome was the disease progression risk, and the secondary outcomes included all-cause mortality and AE risk. The GRADE criteria were used for the certainty of evidence assessment. RESULTS: Nine studies with 1990 participants were included. Antifibrotic therapy reduced the rate of patients with disease progression (five trials with 1741 subjects; relative risk (RR), 0.56; 95% CI, 0.42-0.75; p < 0.0001; I2 = 0; high-certainty evidence). Antifibrotic therapy did not significantly decrease all-cause mortality (nine trials with 1990 subjects; RR, 0.76; 95% CI, 0.55-1.03; p = 0.08; I2 = 0; low-certainty evidence). However, in patients with progressive fibrosing ILDs (PF-ILD), antifibrotic therapy decreased all-cause mortality (four trials with 1100 subjects; RR, 0.69; 95% CI, 0.48-0.98; p = 0.04; I2 = 0; low-certainty evidence). CONCLUSION: Our study supports the use of antifibrotic agents in patients with PF-ILDs, which could slow disease progression and decrease all-cause mortality. TRIAL REGISTRATION: This study protocol was registered with PROSPERO (registration number: CRD42023411272).
Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Humanos , Antifibróticos , Estudos Prospectivos , Progressão da Doença , Ensaios Clínicos Controlados Aleatórios como Assunto , Doenças Pulmonares Intersticiais/tratamento farmacológico , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/complicações , FibroseRESUMO
Introduction: Lung adenocarcinoma (LUAD) is a prevalent form of lung cancer originating from lung glandular cells with low survival rates despite recent therapeutic advances due to its diverse and complex nature. Recent evidence suggests a link between ferroptosis and the effectiveness of anti-PD-L1 therapy, with potential synergistic effects. Methods: Our study comprehensively analyzed the expression patterns of ferroptosis regulators in LUAD and their association with prognosis and PD-L1 expression. Furthermore, we identified two distinct subtypes of LUAD through consensus clustering of ferroptosis regulators, revealing significant tumor heterogeneity, divergent PD-L1 expression, and varying prognoses between the subtypes. Results: Among the selected ferroptosis regulators, SLC7A11 emerged as an independent prognostic marker for LUAD patients and exhibited a negative correlation with PD-L1 expression. Subsequent investigations revealed high expression of SLC7A11 in the LUAD population. In vitro experiments demonstrated that overexpression of SLC7A11 led to reduced PD-L1 expression and inhibited ferroptosis in A549 cells, underscoring the significant role of SLC7A11 in LUAD. Additionally, pan-cancer analyses indicated an association between SLC7A11 and the expression of immune checkpoint genes across multiple cancer types with poor prognoses. Discussion: From a clinical standpoint, these findings offer a foundation for identifying and optimizing potential combination strategies to enhance the therapeutic effectiveness of immune checkpoint inhibitors and improve the prognosis of patients with LUAD.
Assuntos
Adenocarcinoma de Pulmão , Sistema y+ de Transporte de Aminoácidos , Antígeno B7-H1 , Ferroptose , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Ferroptose/genética , Humanos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Prognóstico , Regulação para Baixo , Células A549 , Biomarcadores Tumorais/genética , Masculino , Feminino , Linhagem Celular TumoralRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is considered related to chronic systemic inflammation. Renin angiotensin system (RAS) inhibitor, exerting an anti-inflammatory action in many systems, has been demonstrated relevant to the pathogenesis of COPD. However, the association between RAS inhibitor use and prognosis of patients with COPD remains controversial. Therefore, we conducted a meta-analysis and systematic review to summarise current evidence. MATERIAL AND METHODS: Databases, including Medline, Embase, Web of Science and Cochran Library, were searched for eligible studies by the end of 30 September 2022. Observational studies or randomised controlled trials (RCTs) that investigated the association of RAS inhibitor use with prognosis of COPD (mortality or risk of acute exacerbation) were selected. The Newcastle-Ottawa Scale was used for quality assessment of observational studies, while the Cochrane risk-of-bias tool was used to assess the quality of RCTs. Statistical analyses were performed using Stata V.15. We selected relative risk (RR) with 95% CI as the effect measure. Heterogeneity was assessed by I-squared (I2) statistics. The funnel plot was used for visual assessment of publication bias. RESULTS: A total of 20 studies with 5 51 649 subjects were included in the meta-analysis. The overall analysis indicated that RAS inhibitor use decreased the risk of death in patients with COPD (RR: 0.69, 95% CI: 0.61 to 0.78). Subgroup analyses were conducted according to comorbidities, race and type of RAS inhibitors, and the results kept consistent. However, in the pooled analysis of prospective studies, RAS inhibitor use did not significantly decrease the mortality (RR: 0.89, 95% CI: 0.78 to 1.02). Additionally, the risk of exacerbations of COPD did not decrease in patients who were prescribed RAS inhibitors (RR: 0.99, 95% CI: 0.80 to 1.23). The funnel plot indicated significant publication bias. CONCLUSION: RAS inhibitor use seemed to be associated with a reduction of mortality in patients with COPD. However, the available evidence is weak due to potential biases from retrospective studies and the heterogeneity across included studies.
Assuntos
Doença Pulmonar Obstrutiva Crônica , Sistema Renina-Angiotensina , Humanos , Inibidores EnzimáticosRESUMO
BACKGROUND: Silicosis is a public health issue in developing countries for long and cannot be completely cured. OBJECTIVE: To study the changes of ion content with TNF-α and TGF-ß expression in alveolar lavage fluid (BALF) at different time points in rats exposed to silica and to investigate their correlation with pulmonary fibrosis. METHODS: 42 rats were randomly divided into control group (n = 12) and exposure group (n = 30). Tissues of right lower lungs were collected and fixed for further Hematoxylin-eosin (HE) and Masson staining. We collected the BALF to examine the inflammatory cytokines of TNF-α and TGF-ß and measured the ion contents in BALF. RESULTS: The increase of TNF-α level was earlier than TGF-ß. The content of silica in BALF was significantly increased after exposure and reached the maximum at 7th day, similar to the curve of cytokine TGF-ß level. However, phosphorus ions increased quickly after gradual decline of silicon ion and roughly proportional to the curve of degree of fibrosis. CONCLUSIONS: Crystalline silica exposure can cause changes in TGF-ß and TNF-α in BALF and accompanied with fibrosis and ions content variation. The abnormal expression of phosphorus ion may have significance in the occurrence and development of silicosis.
Assuntos
Exposição Ambiental/efeitos adversos , Fósforo/análise , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/fisiopatologia , Dióxido de Silício/efeitos adversos , Silício/análise , Silicose/diagnóstico , Adulto , Animais , Biomarcadores/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/diagnóstico , Doenças Profissionais/fisiopatologia , Ratos , Ratos Sprague-Dawley , Silicose/fisiopatologiaRESUMO
The incidence of pulmonary fibrosis (PF), a progressively fatal disease, has increased in recent years. However, there are no effective medicines available. Previous results have shown that sinensetin probably has some curative effects on PF. Therefore, this paper aims to predict the targets of sinensetin using a network pharmacology method and to confirm its effects and functional targets in PF using a mouse PF model. First, network pharmacology analysis showed that sinensetin has 105 functional targets, and 1,698 gene targets closely relate to PF. The intersection of the functional targets and gene targets produced 52 targets for the treatment of PF with sinensetin. The PPIs (protein-protein interactions) led to several potential key target genes, including MAPK1, EGFR, SRC, and PTGS2. The results of GO and KEGG analyses suggested the crucial function of apoptosis in PF and its involvement in the PI3K signaling pathway. Subsequently, we tested the molecular docking of sinensetin with the PI3K protein using the AutoDock4 software. The results showed that sinensetin could fit well into several binding sites of the PI3K protein. Furthermore, we constructed a PF mouse model through one-off intratracheal instillation of bleomycin and then intragastrically administered different concentrations of sinensetin to the model mice. Twenty-eight days later, the mice were sacrificed, and the lung tissues, serum, and bronchoalveolar lavage fluid (BALF) were collected. The in vivo tests showed that the body weight of model mice increased slightly compared with that of PF mice after intragastric sinensetin. HE and Masson staining suggested a certain extent of reduction in the pathology of lung tissues. The expression of collagens I and III, as well as hydroxyproline in the lung tissues, was reduced to a certain extent. IL-6 levels in the serum and BALF decreased markedly. The expression of vimentin and α-SMA in pulmonary tissues decreased. Cell apoptosis, as well as P-PI3K and P-AKT levels, in lung tissues also reduced. In summary, network pharmacology and in vivo test results suggest sinensetin causes an effective delay in the progression of pulmonary fibrosis, and the functional mechanism is likely related to PI3K-AKT signaling.