[Diffuse interstitial lung disease of possible occupational origin treated at the Navarra Health Service. Navarra, Spain, 2017-2022]. / Enfermedad pulmonar intersticial difusa de posible origen laboral atendida en el Servicio Navarro de Salud. Navarra, España, 2017-2022.

INTRODUCTION: Diffuse interstitial lung disease (ILD) describes a broad group of pulmonary inflammatory and fibrosis disorders. Asbestosis and silicosis are the main causes linked to occupational exposure. The aim of this study was to estimate the proportion of cases with possible occupational origin and describe their exposure, clinical, and occupational status. METHOD: We conducted a retrospective longitudinal study of ILD cases between 2017 - 2022 at the University Hospital of Navarra was conducted. Information was supplemented with interviews of cases with possible occupational origin. The occupational proportion was calculated, labor and clinical characteristics analyzed, by statistical comparison of percentages and means. RESULTS: Out of 1067 ILD cases, 56 had a possible occupational origin 5,2% (95% CI 3,9-6,6%). 36 (64,3%) corresponded to asbestosis, 15 (26,8%) to silicosis, and 5 (8,9%) to unspecified pneumoconiosis. The most frequent activities in silicosis were "stone cutting-carving" and in asbestosis "manufacture of iron products". The average age of asbestosis cases was higher than that of silicosis cases (78,2 vs. 67,3 years), as well as their clinical manifestation. Five cases (8,9%) had been recognized as occupational diseases. CONCLUSIONS: The implementation of a computer tool in medical records has made it possible to estimate the magnitude and assess the evolution of occupational ILD treated in the Public Health Service. Economic activities reflect the economic risk structure of the region. However, there is a lack of recognition of these diseases as occupational illnesses and they represent a preventable burden of respiratory disease.

Introducción: La enfermedad pulmonar intersticial difusa (EPID) describe un amplio grupo de trastornos con inflamación y fibrosis pulmonar. La asbestosis y la silicosis son las principales causas por exposición laboral. El objetivo de este trabajo fue estimar la proporción de casos de posible origen laboral y describir la exposición, situación clínica y laboral.  Método: Estudio longitudinal retrospectivo de los casos de EPID, en el período 2017-2022 en el Hospital Universitario de Navarra. Se completó la información con entrevista a los casos de posible origen laboral.  Resultados: De un total de 1067 casos de EPID, 56 tuvieron un posible origen laboral, 5,2% (3,9-6,6 IC 95%) 36 (64,3%) correspondieron a asbestosis, 15 (26,8%) a silicosis y 5 (8,9%) a neumoconiosis no especificada. Las actividades más frecuentes en silicosis fueron "corte-tallado de piedra" y para asbestosis "fabricación productos hierro". La media de edad de los casos de asbestosis fue superior a los de silicosis (78,2 vs. 67,3 años), así como su afectación clínica. Cinco casos (8,9%) habían sido reconocidos como enfermedad profesional  Conclusiones: La implementación de una herramienta informática en historia clínica ha hecho posible estimar la magnitud y valorar la evolución de las EPID laborales atendidas en el servicio nacional de salud. Las actividades económicas reflejan la estructura económica de riesgo de la región. Sin embargo, existe una falta de su reconocimiento como enfermedad profesional y suponen una carga de enfermedad respiratoria evitable.

Unraveling the mechanism of tetrandrine combined with Buyang Huanwu Decoction against silicosis using network pharmacology and molecular docking analyses.

Silicosis is an incurable chronic disease characterized by lung fibrosis and inflammation. The combination of tetrandrine and Buyang Huanwu Decoction (BYHWD) has a curative effect on silicosis. However, the mechanism of action and the key active constituent in BYHWD are still unclear. The present study employed network pharmacology and molecular docking to determine the mechanism of action and the key active components of BYHWD of Tetrandrine in combination with BYHWD for silicosis. The primary elements and targets of BYHWD were obtained from the Traditional Chinese Medicine Systems Pharmacology and analysis platform. The targets associated with tetrandrine and silicosis were identified and extracted from the Comparative Toxicogenomics Database and GeneCards database. The potential targets for the treatment of silicosis using a combination of Tetrandrine and BYHWD were identified by considering the overlapping targets between compound drugs and silicosis. These targets were then utilized to construct protein-protein interaction networks, compound drug-ingredient-target networks, and perform enrichment analyses. The top 5 active ingredients present in the compound drug-ingredient-target network are tetrandrine, quercetin, luteolin, kaempferol, and beta-carotene. Similarly, the top 6 hub genes in the protein-protein interaction network are FGF2, MMP-9, MMP-1, IL-10, IL-17A, and IL-6. The molecular docking suggested that the active components may easily access the active pocket of the hub gene. The in-silico investigation suggested that quercetin might be the active component in BYHWD responsible for therapeutic effectiveness against silicosis. This study identified the active compound and potential molecular mechanism underlying the therapeutic effects of BYHWD in combination with tetrandrine for treating silicosis. Notably, we found that quercetin may serve as the key compound in BYHWD for the treatment of silicosis.

Mitochondrial folate pathway regulates myofibroblast differentiation and silica-induced pulmonary fibrosis.

BACKGROUND: Silica-induced pulmonary fibrosis (silicosis) is a diffuse interstitial fibrotic disease characterized by the massive deposition of extracellular matrix in lung tissue. Fibroblast to myofibroblast differentiation is crucial for the disease progression. Inhibiting myofibroblast differentiation may be an effective way for pulmonary fibrosis treatment. METHODS: The experiments were conducted in TGF-ß treated human lung fibroblasts to induce myofibroblast differentiation in vitro and silica treated mice to induce pulmonary fibrosis in vivo. RESULTS: By quantitative mass spectrometry, we revealed that proteins involved in mitochondrial folate metabolism were specifically upregulated during myofibroblast differentiation following TGF-ß stimulation. The expression level of proteins in mitochondrial folate pathway, MTHFD2 and SLC25A32, negatively regulated myofibroblast differentiation. Moreover, plasma folate concentration was significantly reduced in patients and mice with silicosis. Folate supplementation elevated the expression of MTHFD2 and SLC25A32, alleviated oxidative stress and effectively suppressed myofibroblast differentiation and silica-induced pulmonary fibrosis in mice. CONCLUSION: Our study suggests that mitochondrial folate pathway regulates myofibroblast differentiation and could serve as a potential target for ameliorating silica-induced pulmonary fibrosis.

Uncovering mechanisms of Baojin Chenfei formula treatment for silicosis by inhibiting inflammation and fibrosis based on serum pharmacochemistry and network analysis.

BACKGROUND: Baojin Chenfei formula (BCF), a Chinese herbal formula, has significant effects on improving the clinical symptoms of patients with silicosis. However, its active compounds and the underlying mechanisms have not yet fully been elucidated. PURPOSE: This study aimed to explore the underlying mechanisms of BCF in treating silicosis. METHODS: The rat model of silicosis was developed via a single intratracheal instillation of SiO2 suspension to examine the therapeutic impacts of BCF on silicosis. Subsequently, the active compounds, targets, and mechanisms of BCF were analyzed based on serum pharmacochemistry and network analysis. Finally, the underlying mechanisms of representative compounds of BCF were validated in vitro experiments. RESULTS: BCF significantly alleviated SiO2-induced silicosis in rats, evidenced by improved lung function, decreased pathological injury, and reduced inflammatory response and fibrosis. 19 active compounds were identified from the rat serum samples after BCF gavage. Subsequently, 299 targets for these 19 compounds in BCF and 257 genes related to silicosis were collected. 26 overlapping targets, including AKT1, TNF, IL6, MAPK3, EGFR, and others, were obtained from the intersection of the 299 BCF-related targets and 257 silicosis-associated genes. These overlapping targets mainly corresponded to glycyrrhetic acid and paeoniflorin and were mainly associated with positive regulation of smooth muscle cell proliferation, positive regulation of MAP kinase activity, and inflammatory response. In vitro experiments also demonstrated that the representative compounds of BCF (glycyrrhetic acid and paeoniflorin) could suppress inflammatory response by the MAPK pathway, and also inhibited fibroblast activation by the EGFR-PI3K-AKT pathway. CONCLUSION: Active compounds of BCF, such as glycyrrhetic acid and paeoniflorin, could suppress inflammatory response by the MAPK pathway and suppress fibroblast activation by the EGFR-PI3K-AKT pathway. These might be the mechanisms of BCF in treating silicosis.

Baicalin alleviates silica-induced lung inflammation and fibrosis by inhibiting TLR4/NF-?B pathway in rats.

Silicosis is an occupational lung disease caused by inhaling silica dust. The disease is characterized by early lung inflammation and late irreversible pulmonary fibrosis. Here we report the effect of Baicalin, a main flavonoid compound from the roots of Chinese herbal medicine Huang Qin on silicosis in a rat model. Results showed Baicalin (50 or 100 mg/kg/day) can mitigate the silica-induced lung inflammation and reduce the harm of alveolar structure and the blue region of collagen fibers in rat lung at 28 days after administration. At the same time, Baicalin also diminished the level of interleukin-1beta (IL-1beta, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) in lung tissues. The protein expression of collagen I (Col-1), alpha-smooth muscle actin (alpha-SMA) and vimentin were down-regulated while E-cadherin (E-cad) was increased in Baicalin-treated rats. In addition, the Toll Like Receptor 4 (TLR4)/ nuclear factor kappaB (NF-kappaB) pathway was enabled at 28 days after silica infusion, and the treatment of Baicalin diminished the expression of TLR4 and NF-?B in the lungs of rat with silicosis. These results suggested that Baicalin inhibited the pulmonary inflammatory and fibrosis in a rat model of silicosis, which could be attributed to inhibition of the TLR4/NF-kappaB pathway.

Enhancement of suppression oxidative stress and inflammation of quercetin by nano-decoration for ameliorating silica-induced pulmonary fibrosis.

Silicosis is a life-threatening lung fibrotic disease caused by excessive inhalation of environmental exposure to crystalline silica-containing dust, whereas achieving therapeutic cures are constrained. Antioxidation and anti-inflammation are currently recognized as effective strategies to counteract organ fibrosis. Using naturally occurring phytomedicines quercetin (Qu) has emerged in antagonizing fibrotic disorders involving oxidative stress and inflammation, but unfortunately the hydrophilicity deficiency. Herein, chitosan-assisted encapsulation of Qu in nanoparticles (Qu/CS-NPs) was first fabricated for silicosis-associated fibrosis treatment by pulmonary delivery. Qu/CS-NPs with spherical diameters of ~160 nm, demonstrated a high Qu encapsulated capability, excellent hydrophilic stability, fantastic oxidation radical scavenging action, and outstanding controlled as well as slow release Qu action. A silicosis rat model induced by intratracheal instillation silica was established to estimate the anti-fibrosis effect of Qu/CS-NPs. After intratracheal administration, CS-NPs markedly enhanced Qu anti-fibrotic therapy efficacy, accompanying the evident changes in reducing ROS and MDA production to mitigate oxidative stress, inhibiting IL-1ß and TNF-α release, improving lung histological architecture, down-regulating α-SAM levels and suppressing ECM deposition, and thereby ameliorating silica-induced pulmonary fibrosis. Results manifested that the augmented antioxidant and anti-inflammatory activities of Qu by CS-NPs delivery was a result of achieving this remarkable improvement in curative effects. Combined with negligible systemic toxicity, nano-decorated Qu may provide a feasible therapeutic option for silicosis therapy.

Serum Concentration of Prostaglandin E2 as a Diagnostic Biomarker in Patients With Silicosis: A Case-Control Study.

OBJECTIVE: Silicosis is a prevalent incurable pneumoconiosis caused by inhalation of silica dust. Study aimed to investigate inflammatory, hematological, and biochemical parameters as additional biomarkers for diagnosing or monitoring silicosis. METHODS: Research enrolled 14 workers with silicosis and 7 healthy controls (without exposure and silicosis). The serum level of prostaglandin E2, C-reactive protein, fibrinogen, biochemical, and hematological parameters were measured. The receiver operating characteristic curve was used to determine diagnostic sensitivity of each biomarker. RESULTS: Patients with silicosis have a significantly higher level of prostaglandin E2, erythrocyte, hemoglobin, and hematocrit than patients without silicosis. Prostaglandin E2, hemoglobin, and the erythrocyte count are significant in separating the silicosis cases from healthy controls. CONCLUSIONS: Prostaglandin E2 might be an adjuvant peripheral diagnostic biomarker for silicosis, while hematological parameters (erythrocytes, hemoglobin, and hematocrit) might be prognostic biomarkers.

Effects of Green Tea Polyphenol Epigallocatechin-3-Gallate on Markers of Inflammation and Fibrosis in a Rat Model of Pulmonary Silicosis.

Inhalation of silica particles causes inflammatory changes leading to fibrotizing silicosis. Considering a lack of effective therapy, and a growing information on the wide actions of green tea polyphenols, particularly epigallocatechin-3-gallate (EGCG), the aim of this study was to evaluate the early effects of EGCG on markers of inflammation and lung fibrosis in silicotic rats. The silicosis model was induced by a single transoral intratracheal instillation of silica (50 mg/mL/animal), while controls received an equivalent volume of saline. The treatment with intraperitoneal EGCG (20 mg/kg, or saline in controls) was initiated the next day after silica instillation and was given twice a week. Animals were euthanized 14 or 28 days after the treatment onset, and the total and differential counts of leukocytes in the blood and bronchoalveolar lavage fluid (BALF), wet/dry lung weight ratio, and markers of inflammation, oxidative stress, and fibrosis in the lung were determined. The presence of collagen and smooth muscle mass in the walls of bronchioles and lung vessels was investigated immunohistochemically. Early treatment with EGCG showed some potential to alleviate inflammation, and a trend to decrease oxidative stress-induced changes, including apoptosis, and a prevention of fibrotic changes in the bronchioles and pulmonary vessels. However, further investigations should be undertaken to elucidate the effects of EGCG in the lung silicosis model in more detail. In addition, because of insufficient data from EGCG delivery in silicosis, the positive and eventual adverse effects of this herbal compound should be carefully studied before any preventive use or therapy with EGCG may be recommended.

Lipid dysregulation associated with progression of silica-induced pulmonary fibrosis.

Silicosis is an irreversible, progressive, fibrotic lung disease caused by long-term exposure to dust-containing silica particles at the workplace. Despite the precautions enforced, the rising incidence of silicosis continues to occur globally, particularly in developing countries. A better understanding of the disease progression and potential metabolic reprogramming of silicosis is warranted. The low- or high-dose silica-induced pulmonary fibrosis in mice was constructed to mimic chronic or accelerated silicosis. Silica-induced mice lung fibrosis was analyzed by histology, lung function, and computed tomography scans. Non-targeted metabolomics of the lung tissues was conducted by ultra-high-performance liquid chromatography-mass spectrometry to show the temporal metabolic trajectory. The low-dose silica-induced silicosis characterized inflammation for up to 42 days, with the onset of cellular silicon nodules. Conversely, the high-dose silica-induced silicosis characterized inflammation for up to 14 days, after which the disease developed rapidly, with a large volume of collagen deposition, presenting progressive massive fibrosis. Both low- and high silica-induced fibrosis had aberrant lipid metabolism. Combined with the RNA-Seq data, this multiomics study demonstrated alterations in the enzymes involved in sphingolipid metabolism. Time-dependent metabolic reprogramming revealing abnormal glycerophospholipid metabolism was intimately associated with the process of inflammation, whereas sphingolipid metabolism was crucial during lung fibrosis. These findings suggest that lipid dysregulation, especially sphingolipid metabolism, was involved in the process of silicosis.

Yangqing Chenfei formula attenuates silica-induced pulmonary fibrosis by suppressing activation of fibroblast via regulating PI3K/AKT, JAK/STAT, and Wnt signaling pathway.

BACKGROUND: Yangqing Chenfei formula (YCF) has been demonstrated its clinical efficiency on silicosis patients. However, the effect of YCF against silicotic fibrosis and its mechanism remain unclear. PURPOSE: This study is aimed to investigate active compounds and molecular mechanism of YCF in treating silicosis. METHOD: YCF was orally administrated to silicosis rats induced by crystalline silica. The effective fraction of YCF and the compounds was isolated and identified by using macroporous resin and HPLC-MS, respectively. The targets and potential molecular mechanism of YCF against silicotic fibrosis were investigated through pharmacological network and RNA-sequencing analysis and in vitro-experimental validation. RESULTS: YCF could remarkably improve the lung function and pathological changes of silicotic rats, reduce the aggregation of fibrocytes and deposition of ECM, such as collagen I, III, FN, and α-SMA, and suppress the TGF-ß/Smad3 signaling. Furthermore, YCF6, the effective fraction derived from YCF, could significantly inhibit fibroblast activation induced by TGF-ß. Then, 135 compounds were identified from YCF6 by using HPLC-MS, and Network pharmacology analysis predicted total 941 targets for these compounds. Moreover, 409 differentially expressed genes of fibroblast activation induced by TGF-ß were identified. Then, integrated analysis of the 941 targets with 409 differentially expressed genes showed that YCF6 contains multiple compounds, such as tangeretin, L-Malic acid, 2-Monolinolein etc., which inhibits fibroblast activation probably by targeting different proteins, such as PIK3CA, AKT1, JAK2, STAT3, GSK3ß, leading to regulate the signal network, such as PI3K/AKT signaling pathway, JAK/STAT signaling pathway, and Wnt signaling pathway. Finally, in vitro experiment indicated that tangeretin, the active compound contained in YCF6, could significantly inhibit TGF-ß induced fibroblast activation. Moreover, YCF6 and tangeretin could markedly inhibit the activation of PI3K/AKT, JAK/STAT, and Wnt pathway. CONCLUSION: YCF contained multiple compounds and targeted various proteins that regulated the fibroblast activation, which might be the molecular mechanisms of it in treating silicosis.

La epidemia de silicosis en la Andalucía del siglo XX / The silicosis epidemic in Andalusia in the 20th century

La silicosis por compactos de cuarzo es una presentación nueva de una enfermedad antigua por un producto nuevo. Se conocía pocos casos, porque el CEPROSS solo reconoce casos con baja y dos en la misma empresa. Y se atienden por Mutualidad. Lo novedoso es el cambio de perspectiva, de laboral a epidemiológico. Y se investiga como un problema de salud pública, en el que un solo caso, con o sin baja, lleva a su investigación. Y se llevan los casos por el Servicio Andaluz de Salud. (AU)

Nonmalignant respiratory disease mortality in male Colorado Plateau uranium miners, 1960-2016.

BACKGROUND: To evaluate trends of nonmalignant respiratory disease (NMRD) mortality among US underground uranium miners on the Colorado Plateau, and to estimate the exposure-response association between cumulative radon progeny exposure and NMRD subtype mortality. METHODS: Standardized mortality ratios (SMRs) and excess relative rates per 100 working level months (excess relative rate [ERR]/100 WLM) were estimated in a cohort of 4021 male underground uranium miners who were followed from 1960 through 2016. RESULTS: We observed elevated SMRs for all NMRD subtypes. Silicosis had the largest SMR (n = 52, SMR = 41.4; 95% confidence interval [CI]: 30.9, 54.3), followed by other pneumoconiosis (n = 49, SMR = 39.6; 95% CI: 29.6, 52.3) and idiopathic pulmonary fibrosis (IPF) (n = 64, SMR = 4.77; 95% CI 3.67, 6.09). SMRs for silicosis increased with duration of employment; SMRs for IPF increased with duration of employment and calendar period. There was a positive association between cumulative radon exposure and silicosis with evidence of modification by smoking (ERR/100 WLM≥10 pack-years = 0.78; 95% CI: 0.05, 24.6 and ERR/100 WLM<10 pack-years = 0.01; 95% CI: -0.03, 0.52), as well as a small positive association between radon and IPF (ERR/100 WLM = 0.06, 95% CI: 0.00, 0.24); these associations were driven by workers with prior employment in hard rock mining. CONCLUSIONS: Uranium mining workers had excess NMRD mortality compared with the general population; this excess persisted throughout follow-up. Exposure-response analyses indicated a positive association between radon exposure and IPF and silicosis, but these analyses have limitations due to outcome misclassification and missing information on occupational co-exposures such as silica dust.

[Analysis of incidence characteristics and trend of pneumoconiosis in Ningbo City from 1967 to 2019].

Objective: To understand the incidence of pneumoconiosis in Ningbo city from 1967 to 2019, and to analyze the distribution characteristics and change trend of pneumoconiosis. Methods: In February 2021, the data of pneumoconiosis patients in Ningbo city from 1967 to 2019 were sorted out. The data from 1967 to 1987 were from historical case files of Zhejiang Center for Disease Control and Prevention, the data from 1988 to 2005 were from the historical case files of Ningbo Center for Disease Control and Prevention, and the data from 2006 to 2019 were from the pneumoconiosis report card in China Disease Prevention and Control Information System; Followed up and supplement relevant information, including basic information, basic information of employers and information related to pneumoconiosis diagnosis, and comprehensively analyze the composition and development trend, population characteristics and industry characteristics of pneumoconiosis. Results: From 1967 to 2019, a total of 1715 cases of pneumoconiosis were reported in Ningbo City, including 1254 cases of stageⅠpneumoconiosis, 258 cases of stageⅡpneumoconiosis, 172 cases of stage Ⅲpneumoconiosis. 1202 cases of silicosis (70.09%) , 296 cases of asbestosis (17.26%) , 40 cases of welder's pneumoconiosis (2.33%) , 32 cases of graphite pneumoconiosis (1.87%) were reported. There were 1296 male cases (75.57%) and 419 female cases (24.43%) were reported. Silicosis (91.15%, 1102/1209) and welder's pneumoconiosis (100.00%, 40/40) were the most common pneumoconiosis in males, while asbestosis (90.24%, 268/297) and graphite pneumoconiosis (87.50%, 28/32) were the most common pneumoconiosis in females. The average age was (49.71±10.90) years old and the average length of service was (10.98±6.96) years. The top three reported pneumoconiosis cases were construction industry (336 cases, 19.59%) , ferrous metal smelting and rolling industry (317 cases, 18.48%) and non-metallic mineral products industry (315 cases, 18.37%) . The top three reported pneumoconiosis cases were 414 cases (24.14%) in Ninghai County, 294 cases (17.14%) in Yuyao City and 272 cases (15.86%) in Yinzhou District. Conclusion: With the development of industries in Ningbo City, government departments should strengthen supervision and management of enterprises involving silica dust and welding fume to curb the high incidence of pneumoconiosis.

Protective effects of intranasal curcumin on silica-induced lung damage.

OBJECTIVE: Being anti-inflammatory and an antioxidant in nature, curcumin has been studied for its anti-asthmatic effects, but its impact on silicosis has not been investigated before. It is a form of occupational lung illness caused by inhaling crystalline silica. It is particularly common among those who work in construction-related sectors. Therefore, present study has been undertaken to investigate impact of intranasal curcumin on silica induced lung damage in mice model of silicosis. MATERIALS AND METHODS: Mice model of silicosis was developed by intranasal silica instillation (2.5 mg/mice) for different durations mainly 7, 14 and 21 days, where the longest duration of silica exposure (21 days) mimics chronic occupational exposure of silica dust leading to silicosis. Curcumin (5 mg/kg,i.n) and /or dexamethasone, a known corticosteroid (10 mg/kg,i.p) was administered an hour prior to silica administration. RESULTS: Present study revealed silica induced lung damage in the mice model of silicosis characterized by airway inflammation, collagen deposition and enhanced expression of fibrosis markers (MMP-9, α-SMA, Hydroxyproline), which were significantly reduced in curcumin treatment groups. Inhibitory effects of curcumin were compared with standard drug, dexamethasone, a corticosteroid and was found better in protecting structural alterations in the lung. Damaged and abnormal mitochondria (enlarged and irregular shapes) were observed in silicosis group which were reduced in curcumin and dexamethasone treatment groups as revealed in transmission electron microscopic studies. CONCLUSIONS: Present study shows protective effects of intranasal curcumin on silica-induced airway inflammation and structural changes thereby lung damage. Hence, it can be considered as an alternative and complementary medication for silicosis.

[Interventional effect of asiaticosdide on rats exposed to silica dust].

Objective: To investigate the effect of asiaticoside for fibrosis in lung tissues of rats exposed to silica and to explore its possible mechanism. Methods: 144 SD male rats were randomly divided into control group, model group, positive drug control group, asiaticoside high-dose group, medium-dose group and low-dose group, each group included 24 rats. Rats in the control group were perfused with 1.0 ml of normal saline, and the other groups were given 1.0 ml 50 mg/ml SiO(2) suspension. Gavage of herbal was given from the next day after model establishment, once a day. Rats in the positive drug control group were administration with 30 mg/kg tetrandrine and rats in the low-dose group, medium-dose group and high-dose group were given 20 mg/kg, 40 mg/kg and 60 mg/kg asiaticoside for fibrosis respectively. Rats in the control group and the model group were given 0.9% normal saline. The rats were sacrificed in on the 14th, 28th and 56th day after intragastric administration and collect the lung tissues to detect the content of hydroxyproline, TGF-ß(1) and IL-18, observe the pathological changes of the lung tissues by HE and Masson staining and determine the expressions of Col-I, a-SMA, TGF-ß in lung tissues by Western Blot. Results: On the 14th day, 28th day and 56th day after model establishment, the lung tissues of rats in the model group showed obvious inflammatory response and accumulation of collagen fibers, and the degree of inflammation and fibrosis increased with time. The intervention of asiaticoside could effectively inhibit the pathological changes of lung tissues. The contents of hydroxyproline, IL-18 and TGF-ß1 in lung tissues of model group were higher than those in the control group (P<0.05) , while the level of hydroxyproline, IL-18 and TGF-ß1 in asiaticoside groups were significantly decreased, and the difference was statistically signicant (P<0.05) . Compared with the control group, the expression levels of Col-I, TGF-ß1and α-SMA in lung tissue of model group were increased (P<0.05) , while the expression level of Col-I, TGF-ß1 and α-SMA were decreased after the intervention of asiaticoside, and the difference was statistically signicant (P<0.05) . Conclusion: Asiaticoside can inhibit the increase of Col-I, TGF-ß1 and α-SMA content in the SiO(2)-induced lung tissues of rats, reduce the release of TGF-ß1 and IL-18 inflammatory factors in lung tissue, and then inhibit the synthesis and deposition of extracellular matrix in rat lung tissue, and improve silicosis fibrosis.

Isoandrographolide inhibits NLRP3 inflammasome activation and attenuates silicosis in mice.

Silicosis is an irreversible occupational disease caused by silica particle exposure. Abundant evidences suggest that NLRP3-mediated inflammation acts an essential role in fibrogenesis and the pathogenesis of silicosis. In the current work, we firstly reported that (8R-12S)-isoandrographolide (ISA), a diterpenoid lactone ingredient of Chinese traditional medicinal plant Andrographis paniculata (Burm.f.) Nees, could reduce pulmonary inflammation and fibrosis by inhibiting NLRP3, and thereby ameliorate silicosis. ISA administration significantly alleviated lung injury, and attenuated inflammatory response, EMT, as well as collagen deposition in the lung of silica-induced mice. Further studies verified that ISA inhibited the expressions of NLRP3 inflammasome-related proteins NLRP3, ASC and caspase-1 in vivo and in vitro, leading to the attenuation of inflammation and EMT. Additionally, the molecular docking assay indicated that ISA possibly interacted with the residues of LYS26 and GLU47 of NLRP3, implying that ISA might directly bond to protein NLRP3. Of note, ISA revealed a lower cytotoxicity but more potent therapeutic effect than andrographolide (AD), the major active extract of A. paniculata, which has been traditionally used to treat inflammation-related diseases. Taken together, our study clarified a novel role of ISA in attenuating inflammation and fibrosis in silicosis, and indicated a bright future of ISA as a lead compound for developing therapeutic drug for silicosis.

Physical and chemical properties of dust in the Pre-Aral region of Uzbekistan.

The aim of this work is study of physical and chemical properties of dust of the Pre-Aral region of Uzbekistan such as Karakalpakstan and Khorezm that are located near the three deserts such as the Aralkum, Karakum, and Kyzylkum. The dust particles fell on glass have been collected in Karakalpakstan and Khorezm and studied systematically by employing wide range of methods. Particle volume vs size distribution has been measured with maximum around 600 nm and ~ 10 µm. The major and minor constituent materials present in the dust have been studied systematically by X-ray fluorescence spectroscopy, energy dispersive X-ray diffraction, and inductively coupled plasma optical emission spectroscopy. Main characteristic absorption bands corresponding to Si-O, Si-O-Si bonding in quartz and Fe-O bonds in hematite Fe2O3 have been identified by infrared and Raman spectroscopy. Quartz, hematite, lime, corundum, magnesia, and several other trace minerals have been identified in the dust particles. X-ray diffraction peaks corresponding to quartz, hematite, and corundum are sharp and are found to be more crystalline with some level of disorder. Analysis of the particle size and crystallinity on human being has been performed: disordered or crystalline quartz can create the lung disease; the particles in the size of 0.5-0.7 µm may produce diseases such as chronic silicosis, silicosis, and silica tuberculosis whereas hematite might create lung disease. Dust particles worsen optical transmittance of glass of the panels.

Exploration study on serum metabolic profiles of Chinese male patients with artificial stone silicosis, silicosis, and coal worker's pneumoconiosis.

Long-term exposure to inhaled silica dust induces pneumoconiosis, which remains a heavy burden in developing countries. Modern industry provides new resources of occupational SiO2 leading to artificial stone silicosis especially in developed countries. This study aimed to characterize the serum metabolic profile of pneumoconiosis and artificial stone silicosis patients. Our case-control study recruited 46 pairs of pneumoconiosis patients and dust-exposed workers. Nontargeted metabolomics and lipidomics by ultra-high-performance liquid chromatography-tandem mass spectrometry platform were conducted to characterize serum metabolic profile in propensity score-matched (PSM) pilot study. 54 differential metabolites were screened, 24 of which showed good screening efficiency through receiver operating characteristics (ROC) in pilot study and validation study (both AUC > 0.75). 4 of the 24 metabolites can predict pneumoconiosis stages, which are 1,2-dioctanoylthiophosphatidylcholine, phosphatidylcholine(O-18:1/20:1), indole-3-acetamide and l-homoarginine. Kynurenine, N-tetradecanoylsphingosine 1-phosphate, 5-methoxytryptophol and phosphatidylethanolamine(22:6/18:1) displayed the potential as specific biomarkers for artificial stone silicosis. Taken together, our results confirmed that tryptophan metabolism is closely related to pneumoconiosis and may be related to disease progression. Hopefully, our results could supplement the biomarkers of pneumoconiosis and provide evidence for the discovery of artificial stone silicosis-specific biomarkers.

Nicotinamide Mononucleotide Ameliorates Silica-Induced Lung Injury through the Nrf2-Regulated Glutathione Metabolism Pathway in Mice.

Nicotinamide mononucleotide (NMN) is a natural antioxidant approved as a nutritional supplement and food ingredient, but its protective role in silicosis characterized by oxidative damage remains unknown. In this study, we generated a silicosis model by intratracheal instillation of silica, and then performed histopathological, biochemical, and transcriptomic analysis to evaluate the role of NMN in silicosis. We found that NMN mitigated lung damage at 7 and 28 days, manifested as a decreasing coefficient of lung weight and histological changes, and alleviated oxidative damage by reducing levels of reactive oxygen species and increasing glutathione. Meanwhile, NMN treatment also reduced the recruitment of inflammatory cells and inflammatory infiltration in lung tissue. Transcriptomic analysis showed that NMN treatment mainly regulated immune response and glutathione metabolism pathways. Additionally, NMN upregulated the expression of antioxidant genes Gstm1, Gstm2, and Mgst1 by promoting the expression and nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf2). Gene interaction analysis showed that Nrf2 interacted with Gstm1 and Mgst1 through Gtsm2. Promisingly, oxidative damage mediated by these genes occurred mainly in fibroblasts. In summary, NMN alleviates silica-induced oxidative stress and lung injury by regulating the endogenous glutathione metabolism pathways. This study reveals that NMN supplementation might be a promising strategy for mitigating oxidative stress and inflammation in silicosis.