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1.
Heliyon ; 10(19): e37940, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39381106

RESUMEN

Coal worker's pneumoconiosis (CWP), a pulmonary condition resulting from prolonged exposure to coal mining environments, not only leads to a high prevalence of morbidity and mortality among miners but also incurs substantial economic burdens and diminishes the labor force within society. In light of evolving trends in the global coal industry, the ramifications of CWP are anticipated to manifest in new patterns and variations. This study seeks to comprehensively assess the present landscape, trend dynamics, and future projections of the global CWP burden from 1990 to 2019. The objective is to provide a scientific framework for nations to develop and enhance pertinent policies and preventative strategies, thereby promoting the health and occupational safety of coal miners.

2.
Front Biosci (Landmark Ed) ; 29(8): 291, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39206899

RESUMEN

Neurodegenerative disorders are typified by the progressive degeneration and subsequent apoptosis of neuronal cells. They encompass a spectrum of conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), epilepsy, brian ischemia, brian injury, and neurodegeneration with brain iron accumulation (NBIA). Despite the considerable heterogeneity in their clinical presentation, pathophysiological underpinning and disease trajectory, a universal feature of these disorders is the functional deterioration of the nervous system concomitant with neuronal apoptosis. Ferroptosis is an iron (Fe)-dependent form of programmed cell death that has been implicated in the pathogenesis of these conditions. It is intricately associated with intracellular Fe metabolism and lipid homeostasis. The accumulation of Fe is observed in a variety of neurodegenerative diseases and has been linked to their etiology and progression, although its precise role in these pathologies has yet to be elucidated. This review aims to elucidate the characteristics and regulatory mechanisms of ferroptosis, its association with neurodegenerative diseases, and recent advances in ferroptosis-targeted therapeutic strategies. Ferroptosis may therefore be a critical area for future research into neurodegenerative diseases.


Asunto(s)
Ferroptosis , Hierro , Enfermedades Neurodegenerativas , Ferroptosis/fisiología , Humanos , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/fisiopatología , Hierro/metabolismo , Animales , Neuronas/metabolismo , Neuronas/patología
3.
Front Immunol ; 15: 1444958, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39211045

RESUMEN

As a small molecule, hydrogen is colorless, odorless and lightest. Many studies conducted that hydrogen can protect almost every organ, including the brain, heart muscle, liver, small intestine, and lungs. To verify whether high concentrations of hydrogen (HCH) has anti-inflammatory and antioxidant activities on respiratory system, we product a systematic review and meta-analysis. We investigated MEDLINE-PubMed, Cochrane Library, ScienceDirect, Wiley and SpringerLink database and selected in vivo studies related to the anti-inflammatory or antioxidant effects of HCH in the lung diseases which were published until September 2023. We firstly identified 437 studies and only 12 met the inclusion criteria. They all conducted in rodents. The results showed that HCH had a positive effect on the reduction of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-4, IL-8, malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS); but there is no effect on IL-6, we speculated that may contribute to the test results for different body fluids and at different points in time. This meta-analysis discovered the protective effects on inflammation and oxidative stress, but whether there exists more effects on reduction of inflammatory and oxidant mediators needs to be further elucidated.


Asunto(s)
Antiinflamatorios , Antioxidantes , Hidrógeno , Enfermedades Pulmonares , Estrés Oxidativo , Animales , Humanos , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Citocinas/metabolismo , Hidrógeno/análisis , Mediadores de Inflamación/metabolismo , Enfermedades Pulmonares/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
4.
Int Immunopharmacol ; 138: 112563, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-38943976

RESUMEN

Silicosis is a progressive disease characterized by interstitial fibrosis resulting from inhalation of silica particles, and currently lacks specific treatment. Hydrogen (H2) has demonstrated antioxidative, anti-inflammatory, and anti-fibrotic properties, yet its efficacy in treating silicosis remains unexplored. In this study, rats exposed to silica were administered interventions of H2 combined with tetrandrine, and euthanized at 14, 28, and 56 days post-intervention. Lung tissues and serum samples were collected for analysis. Histological examination, MDA assay, enzyme-linked immunosorbent assay, hydroxyproline assay, and Western blotting were employed to assess the impact of H2 combined with tetrandrine on pulmonary fibrosis. The results revealed that this combination significantly alleviated inflammation in silicosis-afflicted rats, effectively suppressed levels of MDA, TNF-α, and IL-1ß expression, and inhibited epithelial-mesenchymal transition (EMT), thereby ameliorating pulmonary fibrosis. Notably, protein expression level of E-cadherin was increased,however protein expression levels of vimentin and α-SMA were reduced, and TGF-ß were reduced, alongside a significant decrease in hydroxyproline content. Furthermore, H2 combined with tetrandrine downregulated protein expression of NF-κB p65, NF-κB p-p65, Caspase-1, ASC, and NLRP3. These findings substantiate the hypothesis that H2 combined with tetrandrine mitigates inflammation associated with silicosis and suppresses the EMT process to ameliorate fibrosis via the NF-κB/NLRP3 signaling pathway. However, the pressure of airway opening was not assessed in this study and dynamic readings of lung physiological function were not obtained, which is a major limitation of this study.


Asunto(s)
Bencilisoquinolinas , Transición Epitelial-Mesenquimal , Hidrógeno , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Fibrosis Pulmonar , Transducción de Señal , Dióxido de Silicio , Silicosis , Animales , Bencilisoquinolinas/farmacología , Bencilisoquinolinas/uso terapéutico , Bencilisoquinolinas/administración & dosificación , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Transducción de Señal/efectos de los fármacos , FN-kappa B/metabolismo , Masculino , Silicosis/tratamiento farmacológico , Silicosis/metabolismo , Ratas , Hidrógeno/uso terapéutico , Hidrógeno/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Humanos
5.
iScience ; 27(6): 109948, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38799583

RESUMEN

This study aims to establish a scientific foundation for early detection and diagnosis of silicosis by conducting meta-analysis on the role of single biomarkers in independent diagnosis. The combined sensitivity (Sen), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic score, and diagnostic odds ratio (DOR) were 0.84 (95% confidence interval (CI): 0.77-0.90), 0.83 (95% CI: 0.78-0.88), 5.08 (95% CI: 3.92-6.59), 0.19 (95% CI: 0.13-0.27), 3.31 (95% CI: 2.88-3.74) and 27.29 (95% CI: 17.77-41.91), respectively. The area under the curve (AUC) was 0.90 (95% CI: 0.88-0.93). The Fagan plot shows a positive posterior probability of 82% and a negative posterior probability of 15%. This study establishes an academic basis for the swift identification, mitigation, and control of silicosis through scientific approaches. The assessed biomarkers offer precision and dependability in silicosis diagnosis, opening novel paths for early detection and intervention, thereby mitigating the disease burden associated with silicosis.

6.
BMC Pulm Med ; 24(1): 224, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720270

RESUMEN

BACKGROUND: Simvastatin (Sim), a hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in prevention and treatment of cardiovascular diseases. Studies have suggested that Sim exerts anti-fibrotic effects by interfering fibroblast proliferation and collagen synthesis. This study was to determine whether Sim could alleviate silica-induced pulmonary fibrosis and explore the underlying mechanisms. METHODS: The rat model of silicosis was established by the tracheal perfusion method and treated with Sim (5 or 10 mg/kg), AICAR (an AMPK agonist), and apocynin (a NOX inhibitor) for 28 days. Lung tissues were collected for further analyses including pathological histology, inflammatory response, oxidative stress, epithelial mesenchymal transformation (EMT), and the AMPK-NOX pathway. RESULTS: Sim significantly reduced silica-induced pulmonary inflammation and fibrosis at 28 days after administration. Sim could reduce the levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α and transforming growth factor-ß1 in lung tissues. The expressions of hydroxyproline, α-SMA and vimentin were down-regulated, while E-cad was increased in Sim-treated rats. In addition, NOX4, p22pox, p40phox, p-p47phox/p47phox expressions and ROS levels were all increased, whereas p-AMPK/AMPK was decreased in silica-induced rats. Sim or AICAR treatment could notably reverse the decrease of AMPK activity and increase of NOX activity induced by silica. Apocynin treatment exhibited similar protective effects to Sim, including down-regulating of oxidative stress and inhibition of the EMT process and inflammatory reactions. CONCLUSIONS: Sim attenuates silica-induced pulmonary inflammation and fibrosis by downregulating EMT and oxidative stress through the AMPK-NOX pathway.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Fibrosis Pulmonar , Dióxido de Silicio , Simvastatina , Animales , Masculino , Ratas , Acetofenonas/farmacología , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , NADPH Oxidasa 4/metabolismo , NADPH Oxidasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Neumonía/inducido químicamente , Neumonía/prevención & control , Neumonía/tratamiento farmacológico , Neumonía/metabolismo , Neumonía/patología , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Ribonucleótidos/farmacología , Transducción de Señal/efectos de los fármacos , Silicosis/tratamiento farmacológico , Silicosis/patología , Silicosis/metabolismo , Simvastatina/farmacología , Factor de Crecimiento Transformador beta1/metabolismo
7.
Environ Int ; 186: 108631, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38588609

RESUMEN

Methylmercury (MeHg) is a global environmental pollutant with neurotoxicity, which can easily crosses the blood-brain barrier and cause irreversible damage to the human central nervous system (CNS). CNS inflammation and autophagy are known to be involved in the pathology of neurodegenerative diseases. Meanwhile, MeHg has the potential to induce microglia-mediated neuroinflammation as well as autophagy. This study aims to further explore the exact molecular mechanism of MeHg neurotoxicity. We conducted in vitro studies using BV2 microglial cell from the central nervous system of mice. The role of inflammation and autophagy in the damage of BV2 cells induced by MeHg was determined by detecting cell viability, cell morphology and structure, reactive oxygen species (ROS), antioxidant function, inflammatory factors, autophagosomes, inflammation and autophagy-related proteins. We further investigated the relationship between the inflammatory response and autophagy induced by MeHg by inhibiting them separately. The results indicated that MeHg could invade cells, change cell structure, activate NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and autophagosome, release a large amount of inflammatory factors and trigger the inflammatory response and autophagy. It was also found that MeHg could disrupt the antioxidant function of cells. In addition, the inhibition of NLRP3 inflammasome alleviated both cellular inflammation and autophagy, while inhibition of autophagy increased cellular inflammation. Our current research suggests that MeHg might induce BV2 cytotoxicity through inflammatory response and autophagy, which may be mediated by the NLRP3 inflammasome activated by oxidative stress.


Asunto(s)
Autofagia , Inflamasomas , Inflamación , Compuestos de Metilmercurio , Microglía , Proteína con Dominio Pirina 3 de la Familia NLR , Compuestos de Metilmercurio/toxicidad , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Autofagia/efectos de los fármacos , Ratones , Inflamasomas/metabolismo , Animales , Inflamación/inducido químicamente , Especies Reactivas de Oxígeno/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos
8.
Environ Res ; 250: 118506, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38387496

RESUMEN

Polystyrene nanoplastics (PS-NPs), a group of ubiquitous pollutants, may injure the central nervous system through the blood‒brain barrier (BBB). However, whether exposure to PS-NPs contributes to BBB disruption and the underlying mechanisms are still unclear. In vivo, we found that PS-NPs (25 mg/kg BW) could significantly increase BBB permeability in mice and downregulate the distribution of the tight junction-associated protein zona occludens 1 (ZO-1) in brain microvascular endothelial cells (BMECs). Using an in vitro BBB model, exposure to PS-NPs significantly reduced the transendothelial electrical resistance and altered ZO-1 expression and distribution in a dose-dependent manner. RNA-seq analysis and functional investigations were used to investigate the molecular pathways involved in the response to PS-NPs. The results revealed that the ferroptosis and glutathione metabolism signaling pathways were related to the disruption of the BBB model caused by the PS-NPs. PS-NPs treatment promoted ferroptosis in bEnd.3 cells by inducing disordered glutathione metabolism in addition to Fe2+ and lipid peroxide accumulation, while suppressing ferroptosis with ferrostatin-1 (Fer-1) suppressed ferroptosis-related changes in bEnd.3 cells subjected to PS-NPs. Importantly, Fer-1 alleviated the decrease in ZO-1 expression in bEnd.3 cells and the exacerbation of BBB damage induced by PS-NPs. Collectively, our findings suggest that inhibiting ferroptosis in BMECs may serve as a potential therapeutic target against BBB disruption induced by PS-NPs exposure.


Asunto(s)
Barrera Hematoencefálica , Células Endoteliales , Ferroptosis , Poliestirenos , Animales , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Ferroptosis/efectos de los fármacos , Poliestirenos/toxicidad , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Ratones , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/irrigación sanguínea , Nanopartículas/toxicidad , Masculino
9.
Ecotoxicol Environ Saf ; 270: 115889, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38150751

RESUMEN

Silica nanoparticles (SiNPs) have been widely used in electronics, chemistry, and biomedicine. Human exposure to SiNPs and possible health effects have attracted much attention. The potential cardiovascular toxicity of SiNPs and their related mechanisms are still unclear. Therefore, in this study, we investigated the toxic effects of SiNPs on human umbilical vein endothelial cells (HUVECs). We found that SiNPs could induce HUVECs ferroptosis. The results showed that the level of intracellular divalent iron and lipid peroxidation increased, and mitochondrial cristae decreased. In addition, the pretreatment of the iron chelator deferoxamine mesylate (DFO) could alleviate the ferroptosis of cells. Interestingly, pretreatment of 3-methyladenine (3-MA), an autophagy/PI3K inhibitor could partially inhibit autophagy and reduce ferroptosis, which indicated that autophagy played an important role in cell ferroptosis. Additionally, after knocking down nuclear receptor coactivator 4 (NCOA4), Ferritin Heavy Chain 1 (FTH1) expression was up-regulated, and the levels of divalent iron and lipid peroxidation decreased, which suggested that NCOA4 mediated the ferroptosis of HUVECs induced by SiNPs. In conclusion, this study shows that SiNPs can induce cardiovascular toxicity in which there is ferroptosis. NCOA4-mediated ferritinophagy and resultant ferroptosis by SiNPs may play an important role. This study provides a new theoretical strategy for the treatment and prevention of cardiovascular diseases in the future.


Asunto(s)
Ferroptosis , Nanopartículas , Humanos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Dióxido de Silicio/toxicidad , Fosfatidilinositol 3-Quinasas/metabolismo , Hierro/metabolismo , Factores de Transcripción/metabolismo , Nanopartículas/toxicidad , Autofagia , Coactivadores de Receptor Nuclear/genética , Coactivadores de Receptor Nuclear/metabolismo
10.
Int J Mol Med ; 52(1)2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37264973

RESUMEN

Nanoplastics (NPs) are a newly discovered type of environmental pollutant. The potential for neurotoxicity caused by NPs and their mechanisms are unclear. The present study aimed to determine the molecular mechanism underlying neurotoxicity induced by NPs. Microglia (BV2) cells were used for in vitro studies, and it was found that NPs invaded cells, activated inflammasomes, induced the release of significant quantities of inflammatory factors by detection of inflammatory response­associated proteins through Western blot and ELISA. By detection of FITC, SOD, GSH, cellular iron level, and ferroptosis­related proteins, it was found that NPs compromised the anti­oxidative mechanisms of cells, increased intracellular lipid peroxidation and Fe2+ concentration and triggered inflammatory reactions and ferroptosis. Pretreatment with reactive oxygen species (ROS) inhibitor N­acetylcysteine (NAC) alleviated induction of inflammatory reactions and ferroptosis of cells. In addition, inhibiting expression of c­Jun N­terminal kinase (JNK) increased expression of heme oxygenase (HO­1), resulting in decreased ferroptosis, indicating that the JNK/HO­1 signaling pathway was involved in NP­induced effects on ferroptosis in BV2 cells. In conclusion, NPs could induce inflammatory responses and ferroptosis in BV2 cells. JNK/HO­1 mediated ferroptosis may serve an important role in the toxicity of microglia induced by NPs. This study provided novel evidence for the toxic effects of NPs and highlighted a theoretical mechanistic basis for safe prevention and treatment of plastic pollution­induced neurotoxicity.


Asunto(s)
Ferroptosis , Humanos , Microplásticos/metabolismo , Microplásticos/farmacología , Microglía/metabolismo , Sistema de Señalización de MAP Quinasas , Especies Reactivas de Oxígeno/metabolismo , Inflamación/metabolismo , Ferritinas/metabolismo , Ferritinas/farmacología , Oxidorreductasas/metabolismo , Oxidorreductasas/farmacología
11.
Iran J Public Health ; 52(1): 1-9, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36824257

RESUMEN

Background: Cell transplantation is a promising therapeutic strategy for pulmonary fibrosis. In order to clarify the alveolar type II epithelial cell potential utility in the treatment of lung disease, we conducted a meta-analysis, to evaluate alveolar type II epithelial cells in animal models of lung injury and pulmonary fibrosis. Methods: This review followed the recommendations from the PRISMA statements, Comprehensive retrieval method was used to search Embase, PubMed, Cochrane, Chinese Knowledge Infrastructure, VIP and Wanfang databases. A total of 7 studies and 286 model rats were included. Two researchers independently screened the identified studies, based on inclusion and exclusion criteria. All analyses were conducted using Review Manager V.5.3 software. The combined standard mean difference (SMD) and 95% confidence interval (CI) of data from the included studies were calculated using fixed or random-effects models. Results: The analysis of three outcome indexes showed that the heterogeneity of the oxygen saturation group was high (I2=85%), the lung weight group (I2=64%) was close to moderate heterogeneity, and the lung hydroxyproline content group (I2=0) was not heterogeneous. Conclusion: Meta-analysis showed that transplantation of alveolar type II epithelial cells has beneficial effects, and no obvious adverse reactions. Alveolar type II epithelial cell transplantation can significantly reduce the intervention group and lung hydroxyproline content weight, improve the blood oxygen saturation, lung histo-pathology showed significant improvement in pulmonary fibrosis.

12.
Int J Nanomedicine ; 17: 5247-5264, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36388872

RESUMEN

Introduction: Silica nanoparticles (SiNPs) have been widely used in food, cosmetics, medicine and other fields; however, there have been growing concerns regarding their potential adverse effects on health. A large number of studies have confirmed that SiNPs with small particle diameters can pass through the blood brain barrier, causing irreversible damage to the nervous system. This study aims to further explore the molecular mechanism of neurotoxicity of SiNPs and provide a toxicological basis for the medical application of SiNPs. Methods: We conducted an in vitro study using neuroimmune cells (mouse microglial cells, BV2) of the central nervous system to study inflammation and ferroptosis after exposure to SiNPs. We detected cell viability, morphology and ultrastructure, antioxidant function, inflammation, and ferroptosis-related proteins to explore the role of pyroptosis and ferroptosis in the damage of BV2 cells induced by SiNPs. We further explored the relationship between the inflammatory response and ferroptosis induced by SiNPs by silencing the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) gene and inhibiting ferroptosis. Results: The results showed that SiNPs could invade the cytoplasm, change the ultrastructure, activate NLRP3 inflammasomes, release a large number of inflammatory factors, and trigger inflammatory reaction. We also found that SiNPs could disrupt cellular antioxidant function, increase intracellular ferrous ion level and induce ferroptosis. In addition, both inflammation and ferroptosis are alleviated in NLRP3 gene-silenced cells. Conclusion: SiNPs could induce BV2 cytotoxicity through inflammatory response and ferroptosis, which may be mediated by the activation of the NLRP3 inflammasomes.


Asunto(s)
Nanopartículas , Dióxido de Silicio , Animales , Ratones , Dióxido de Silicio/toxicidad , Dióxido de Silicio/química , Inflamasomas/metabolismo , Microglía/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Antioxidantes/metabolismo , Nanopartículas/toxicidad , Nanopartículas/química , Inflamación/inducido químicamente , Inflamación/metabolismo
13.
Environ Toxicol ; 37(8): 1891-1901, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35396826

RESUMEN

Methylmercury (MeHg) is an environmental neurotoxic substance, which can easily cross the blood-brain barrier, causing irreversible damage to the human central nervous system. Reactive oxygen species (ROS) are involved in various ways of intracellular physiological or pathological processes including neuronal apoptosis. This study attempted to explore the role of ROS-mediated poly ADP-ribose polymerase (PARP)/apoptosis-inducing factor (AIF) apoptosis signaling pathway in the process of MeHg-induced cell death of human neuroblastoma cells (SH-SY5Y). Here, we found that SH-SY5Y cells underwent apoptosis in response to MeHg, which was accompanied by the increased levels of ROS and calcium ion, and the activation of caspase cascades and PARP. Inhibiting the production of ROS can reduce the apoptosis rate to a certain extent. PARP/AIF apoptotic pathway is independent of caspase dependent signaling pathway and regulates it. In conclusion, these results suggest that ROS mediated activation of caspase pathway and PARP/AIF signaling pathway are involved in MeHg induced apoptosis, and these two pathways interact with each other.


Asunto(s)
Compuestos de Metilmercurio , Neuroblastoma , Adenosina Difosfato Ribosa/farmacología , Apoptosis , Factor Inductor de la Apoptosis/metabolismo , Factor Inductor de la Apoptosis/farmacología , Caspasas/metabolismo , Humanos , Compuestos de Metilmercurio/toxicidad , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Poli(ADP-Ribosa) Polimerasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo
14.
BMC Pulm Med ; 22(1): 13, 2022 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-34991559

RESUMEN

BACKGROUND: Silicosis is a systemic disease characterized by persistent inflammation and incurable pulmonary fibrosis. Although great effort has been made to understand the pathogenesis of the disease, molecular mechanism underlying silicosis is not fully elucidated. This study was aimed to explore proteomic and transcriptomic changes in rat model of silicosis. METHODS: Twenty male Wistar rats were randomly divided into two groups with 10 rats in each group. Rats in the model group were intratracheally instilled with 50 mg/mL silicon dioxide (1 mL per rat) and rats in the control group were treated with 1.0 mL saline (1 mL per rat). Twenty-eight days later, transcriptomic analysis by microarray and tandem mass tags (TMT)-based proteomic analysis were performed to reveal the expression of mRNAs and proteins in lung tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to analyze the altered genes and proteins. The integrated analysis was performed between transcriptome and proteome. The data were further verified by RT-qPCR and parallel reaction monitoring (PRM). RESULTS: In total, 1769 differentially expressed genes (DEGs) and 650 differentially expressed proteins (DEPs) were identified between the silicosis model and control groups. The integrated analysis showed 250 DEPs were correlated to the corresponding DEGs (cor-DEPs-DEGs), which were mainly enriched in phagosome, leukocyte transendothelial migration, complement and coagulation cascades and cellular adhesion molecule (CAM). These pathways are interrelated and converged at common points to produce an effect. GM2a, CHI3L1, LCN2 and GNAI1 are involved in the extracellular matrix (ECM) and inflammation contributing to fibrosis. CONCLUSION: Our comprehensive transcriptome and proteome data provide new insights into the mechanisms of silicosis and helpful information for more targeted prevention and treatment of silicosis.


Asunto(s)
Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/genética , Dióxido de Silicio/efectos adversos , Silicosis/genética , Animales , China , Expresión Génica , Masculino , Proteómica , Fibrosis Pulmonar/patología , ARN Mensajero , Ratas , Ratas Wistar , Silicosis/patología , Transcriptoma
15.
Environ Toxicol ; 37(3): 385-400, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34766707

RESUMEN

The mechanism of the sterile inflammatory response in the respiratory tract induced by exposure to sterile particles has not been fully elucidated. The aim of our study is to explore the earlier events in initiating inflammatory response at molecular and cellular level in primary cultured human airway epithelial cells (AEC) exposed to silica particles in order to provide information for earlier diagnosis and prevention of silica particle-induced toxicity as well as possible information on the genesis of silicosis. We isolated primary AEC from three healthy adults and treated them with silica particles at different concentrations for 48 h. We found evidence for silica-induced inflammasome activation by the co-localization of Caspase-1 and NLRP3, as well as increased levels of IL-1ß and IL-18. Lactate dehydrogenase and NucGreen analysis proved the occurrence of pyroptosis. High throughput mRNA sequencing showed that the inflammatory response and NF-κB signaling pathways were significantly enriched in gene ontology and Kyoto encyclopedia of genes and genomes analysis, and pyroptosis-related genes were up-regulated. The miR-455-3p and five lncRNAs (LOC105375913, NEAT1, LOC105375181, LOC100506098, and LOC105369370) were verified as key factors related to the mechanism by ceRNA network analysis. LOC105375913 was first discovered to be associated with inflammation in AEC. These data suggest that microcrystalline silica can induce significant inflammation and pyroptosis in human primary AEC through NLRP3 inflammasome pathway and NF-κB signaling pathway at both the gene and protein levels, and the possible mechanism could be miR-455-3p mediated ceRNA hypothesis. Our data provide a method for the studies of the respiratory toxicity of fine particulate matter and the pathogenesis of early silicosis. The miR-455-3p and five lncRNAs related ceRNA network might be the toxicity mechanism of microcrystalline silica particles to AEC.


Asunto(s)
MicroARNs , Piroptosis , Células Epiteliales , Humanos , Inflamasomas/genética , MicroARNs/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Sistema Respiratorio , Dióxido de Silicio/toxicidad
16.
Chemosphere ; 291(Pt 2): 132944, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34793849

RESUMEN

Microplastics (MPs) are new environmental pollutants and have received widespread attention in recent years, but the toxicity of the MPs remains to be fully elucidated. To explore the effect of MPs on hepatotoxicity in mice and unravel the mechanism of pyroptosis and ferroptosis in the process of liver injury, we treated mice with 5.0 µm polypropylene microplastics (MPs) at 0.1, 0.5 and 1 mg/mL for 4 weeks. Results revealed that MPs could damage liver structure and function with broken and reduced mitochondrial cristae, as well as increased levels of aspartate minotransferase (AST), alanine aminotransferase (ALT), AST/ALT, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Treatment with MPs resulted in pyroptosis as evidenced by increasing expressions of interleukin IL-1ß, IL-18. Additionally, MPs were shown to induce the NOD-like receptor protein 3 (NLRP3) inflammasomes and apoptosis associated speck-like protein (ASC) containing a caspase recruitment domain activation in liver tissue, enabling activation of Caspase-1-dependent signaling pathway induced by inflammatory stimuli resulting from oxidative stress. In addition, the increase of malondialdehyde (MDA) and decrease of glutathione (GSH) and superoxide dismutase (SOD) in the liver indicated that MPs could induce oxidative damage. Moreover, MPs induced lipid peroxidation in the liver of mice could activate the expression of ferroptosis related proteins, including iron metabolism, such as transferrin receptor (TFRC) was active but ferritin heavy chain 1 (FTH1) was inhibited; amino acid metabolism, such as XCT system and glutathione peroxidase 4 (GPX4) were inhibited; lipid metabolism, such as acyl-CoA synthetase long-chain family member 4 (ACSL4) was inhibited. Collectively, these findings evidenced that pyroptosis and ferroptosis occurred in MPs-induced liver injury accompanied by intense oxidative stress and inflammation.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Ferroptosis , Animales , Ratones , Microplásticos , Estrés Oxidativo , Plásticos , Poliestirenos , Piroptosis
17.
Toxicol Mech Methods ; 31(9): 655-666, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34225584

RESUMEN

Pulmonary fibrosis induced by silica dust is an irreversible, chronic, and fibroproliferative lung disease with no effective treatment at present. BMSCs-derived exosomes (BMSCs-Exo) possess similar functions to their parent cells. In this study, we investigated the therapeutic potential and underlying molecular mechanism for BMSCs-Exo in the treatment of silica-induced pulmonary fibrosis. The rat model of experimental silicosis pulmonary fibrosis was induced with 1.0 mL of one-off infusing silica suspension using the non-exposed intratracheal instillation (50 mg/mL/rat). In vivo transplantation of BMSCs-Exo effectively alleviated silica-induced pulmonary fibrosis, including a reduction in collagen accumulation, inhibition of TGF-ß1, and decreased HYP content. Treatment of BMSCs-Exo increased the expression of epithelial marker proteins including E-cadherin (E-cad) and cytokeratin19 (CK19) and reduced the expression of fibrosis marker proteins including α-Smooth muscle actin (α-SMA) after exposure to silica suspension. Furthermore, we found that BMSCs-Exo inhibited the expression of Wnt/ß-catenin pathway components (P-GSK3ß, ß-catenin, Cyclin D1) in pulmonary fibrosis tissue. BMSCs-Exo is involved in the alleviation of silica-induced pulmonary fibrosis by reducing the level of profibrotic factor TGF-ß1 and inhibiting the progression of epithelial-mesenchymal transition (EMT). Additionally, attenuation of the Wnt/ß-catenin signaling pathway closely related to EMT may be one of the mechanisms involved in anti-fibrotic effects of exosomes.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , Fibrosis Pulmonar , Animales , Transición Epitelial-Mesenquimal , Exosomas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/prevención & control , Ratas , Dióxido de Silicio/toxicidad , Factor de Crecimiento Transformador beta1 , Vía de Señalización Wnt , beta Catenina/metabolismo
18.
Environ Toxicol ; 36(7): 1389-1401, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33764603

RESUMEN

Silica nanoparticles (SiNPs) as one of the most productive nano-powder, has been extensively applied in various fields. There has been increasing concern about the adverse effects of SiNPs on the health of ecological organisms and human. The potential cardiovascular toxicity of SiNPs and involved mechanisms remain elusive. Hence, in this study, we investigated the cardiovascular toxicity of SiNPs (60 nm) and explored the underlying mechanisms using H9c2 cardiomyocytes. Results showed that SiNPs induced oxidative stress and activated the Nrf2/HO-1 antioxidant pathway. Autophagy was also activated by SiNPs. Interestingly, N-acetyl-L-cysteine (NAC)attenuated autophagy after inhibiting reactive oxygen species (ROS). Meanwhile, down-regulation of Nrf2 enhanced autophagy. In summary, these data indicated that SiNPs induce autophagy in H9c2 cardiomyocytes through oxidative stress, and the Nrf2/HO-1 pathway has a negative regulatory effect on autophagy. This study provides new evidence for the cardiovascular toxicity of SiNPs and provides a reference for the safe use of nanomaterials in the future.


Asunto(s)
Nanopartículas , Dióxido de Silicio , Autofagia , Humanos , Factor 2 Relacionado con NF-E2/genética , Nanopartículas/toxicidad , Estrés Oxidativo , Especies Reactivas de Oxígeno , Transducción de Señal , Dióxido de Silicio/toxicidad
19.
Environ Toxicol ; 36(7): 1412-1421, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33749115

RESUMEN

Environmental exposure to lead (Pb) can damage to the central nervous system (CNS) in humans. High-fat diet (HFD) also has been suggested to impair neurocognitive function. Blood-brain barrier (BBB) is a rigorous permeability barrier for maintaining homeostasis of CNS. The damage of BBB caused by tight junctions (TJs) disruption is central to the etiology of various CNS disorders. This study aimed to investigate whether HFD could exacerbate Pb exposure induced the destruction of BBB integrity by TJs disruption. To this end, we measured cell viability assay, trans-endothelial electrical resistance assay, horseradish peroxidase flux measurement, Western blot analysis, and immunofluorescence experiments. The results showed that palmitic acid (PA), the most common saturated fatty acid found in the human body, can increase the permeability of the BBB in vitro which formed in bEnd.3 cells induced by Pb exposure, and decrease the expression of TJs, such as zonula occludins-1 (ZO-1) and occludin. Besides, we found that PA could promote the up-regulation of matrix metalloproteinase (MMP)-9 expression and activate the c-Jun N-terminal kinase (JNK) pathway induced by Pb. MMP-9 inhibitor or JNK inhibitor could increase BBB integrity and up-regulate the expressions of ZO-1 and occludin after treatment, respectively. Moreover, the JNK inhibitor could down-regulate the expression of MMP-9. In conclusion, these results suggested that HFD exacerbates Pb-induced BBB disruption by disrupting TJs integrity. This may be because PA promotes the activation of JNK pathway and then up-regulated the expression of MMP-9 after Pb-exposure. It is suggested that people with HFD exposed to environmental Pb may cause more serious damage to the CNS.


Asunto(s)
Barrera Hematoencefálica , Uniones Estrechas , Barrera Hematoencefálica/metabolismo , Dieta Alta en Grasa/efectos adversos , Humanos , Plomo/toxicidad , Ocludina/metabolismo , Uniones Estrechas/metabolismo
20.
Artículo en Inglés | MEDLINE | ID: mdl-32602269

RESUMEN

As a consequence of recent progression in biomedicine and nanotechnology, nanomedicine has emerged rapidly as a new discipline with extensive application of nanomaterials in biology, medicine, and pharmacology. Among the various nanomaterials, silica nanoparticles (SNPs) are particularly promising in nanomedicine applications due to their large specific surface area, adjustable pore size, facile surface modification, and excellent biocompatibility. This paper reviews the synthesis of SNPs and their recent usage in drug delivery, biomedical imaging, photodynamic and photothermal therapy, and other applications. In addition, the possible adverse effects of SNPs in nanomedicine applications are reviewed from reported in vitro and in vivo studies. Finally, the potential opportunities and challenges for the future use of SNPs are discussed. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.


Asunto(s)
Nanopartículas , Preparaciones Farmacéuticas , Sistemas de Liberación de Medicamentos , Nanomedicina , Nanotecnología , Dióxido de Silicio
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