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1.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576239

RESUMO

Glycolytic reprogramming is an important metabolic feature in the development of pulmonary fibrosis. However, the specific mechanism of glycolysis in silicosis is still not clear. In this study, silicotic models and silica-induced macrophage were used to elucidate the mechanism of glycolysis induced by silica. Expression levels of the key enzymes in glycolysis and macrophage activation indicators were analyzed by Western blot, qRT-PCR, IHC, and IF analyses, and by using a lactate assay kit. We found that silica promotes the expression of the key glycolysis enzymes HK2, PKM2, LDHA, and macrophage activation factors iNOS, TNF-α, Arg-1, IL-10, and MCP1 in silicotic rats and silica-induced NR8383 macrophages. The enhancement of glycolysis and macrophage activation induced by silica was reduced by Ac-SDKP or siRNA-Ldha treatment. This study suggests that Ac-SDKP treatment can inhibit glycolytic reprogramming in silica-induced lung macrophages and silicosis.

2.
J Cell Sci ; 134(2)2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34432034

RESUMO

Silicosis is characterized by silica exposure-induced lung interstitial fibrosis and formation of silicotic nodules, resulting in lung stiffening. The acetylation of microtubules mediated by α-tubulin N-acetyltransferase 1 (α-TAT1) is a posttranslational modification that promotes microtubule stability in response to mechanical stimulation. α-TAT1 and downstream acetylated α-tubulin (Ac-α-Tub) are decreased in silicosis, promoting the epithelial-mesenchymal transition (EMT); however, the underlying mechanisms are unknown. We found that silica, matrix stiffening or their combination triggered Ac-α-Tub downregulation in alveolar epithelial cells, followed by DNA damage and replication stress. α-TAT1 elevated Ac-α-Tub to limit replication stress and the EMT via trafficking of p53-binding protein 1 (53BP1, also known as TP53BP1). The results provide evidence that α-TAT1 and Ac-α-Tub inhibit the EMT and silicosis fibrosis by preventing 53BP1 mislocalization and relieving DNA damage. This study provides insight into how the cell cycle is regulated during the EMT and why the decrease in α-TAT1 and Ac-α-Tub promotes silicosis fibrosis. This article has an associated First Person interview with the first authors of the paper.


Assuntos
Transição Epitelial-Mesenquimal , Tubulina (Proteína) , Acetilação , Dano ao DNA , Transição Epitelial-Mesenquimal/genética , Humanos , Processamento de Proteína Pós-Traducional , Dióxido de Silício/toxicidade , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo
3.
Oxid Med Cell Longev ; 2021: 4158495, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34426759

RESUMO

Cellular senescence has been considered an important driver of many chronic lung diseases. However, the specific mechanism of cellular senescence in silicosis is still unknown. In the present study, silicotic rats and osteoclast stimulatory transmembrane protein (Ocstamp) overexpression of MLE-12 cells were used to explore the mechanism of OC-STAMP in cellular senescence in alveolar epithelial cell type II (AEC2). We found an increasing level of OC-STAMP in AEC2 of silicotic rats. Overexpression of Ocstamp in MLE-12 cells promoted epithelial-mesenchymal transition (EMT), endoplasmic reticulum (ER) stress, and cellular senescence. Myosin heavy chain 9 (MYH9) was a potential interacting protein of OC-STAMP. Knockdown of Ocstamp or Myh9 inhibited cellular senescence in MLE-12 cells transfected with pcmv6-Ocstamp. Treatment with 4-phenylbutyrate (4-PBA) to inhibit ER stress also attenuated cellular senescence in vitro or in vivo. In conclusion, OC-STAMP promotes cellular senescence in AEC2 in silicosis.

4.
Aging (Albany NY) ; 13(11): 15433-15443, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34096884

RESUMO

OBJECTIVE: This study aimed to explore the association between the risk of newly diagnosed type 2 diabetes and galectin-3 and adiponectin and to investigate whether their joint action shows a favorable diabetes assessment performance. METHODS: We conducted a community-based study in 135 newly diagnosed patients with type 2 diabetes and 270 age- and sex-matched nondiabetic patients. Odds ratios and 95% confidence intervals were determined using logistic regression analysis. Receiver operating characteristic curve, decision curve analysis and calibration plot were used to explore their efficacy and clinical utility for models. RESULTS: High quartiles of galectin-3/adiponectin (quartile 4 vs 1: OR 2.43 [95% CIs: 1.21-5.00]) showed the strongest correlation with an increased risk of type 2 diabetes in the total population, which was consistent in the older population (age≥50 years old) in adjustment models. The combination + lipids + galectin-3/adiponectin model (AUC = 0.72 [95% CIs: 0.66-0.77]) displayed better diabetes assessment performance than the other two models. CONCLUSIONS: High galectin-3 and low adiponectin levels were associated with the high risk of diabetes, and their joint action was a superior promising factor for evaluating diabetes risk. The diabetes discriminative strength of galectin-3/adiponectin was better in the older population than the younger.


Assuntos
Adiponectina/metabolismo , Diabetes Mellitus Tipo 2/sangue , Galectina 3/sangue , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Razão de Chances , Curva ROC , Fatores de Risco
5.
J Phys Chem A ; 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33914544

RESUMO

Gaseous oxidized mercury (GOM) is a major chemical form responsible for deposition of atmospheric mercury, but its interaction with environmental surfaces is not well understood. To address this knowledge gap, we investigated the uptake of gaseous HgCl2, used as a GOM surrogate, by several inorganic salts representative of marine and urban aerosols. The process was studied in a fast flow reactor coupled to an ion drift-chemical ionization mass spectrometer, where gaseous HgCl2 was quantitatively detected as HgCl2·NO3-. Uptake curves showed a common behavior, where upon exposure of the salt surface to HgCl2, the gas-phase concentration of the latter dropped rapidly and then recovered gradually. None of the salts produced a full recovery of HgCl2, indicating the presence of an irreversible chemical reaction in addition to reversible adsorption, and all salts showed reactive behavior consistent with the presence of surface sites of a high and a low reactivity. On the basis of the decrease in the uptake coefficient with increasing concentration of gaseous HgCl2, we conclude that the interaction follows the Langmuir-Hinshelwood mechanism. The reactivity of a deactivated salt surface after uptake could be partially restored by cycling through an elevated relative humidity at atmospheric pressure. The overall surface reactivity decreased in the series Na2SO4 > NaCl > (NH4)2SO4 > NH4NO3. The uptake on NH4NO3 was nearly fully reversible, with low values of the initial (0.4 × 10-2) and steady-state (3.3 × 10-4) uptake coefficients, whereas Na2SO4 was significantly more reactive (3.1 × 10-2 and 1.7 × 10-3). Depending on the aerosol loading, the lifetimes of gaseous HgCl2 on dry urban and marine particles (as pure (NH4)2SO4 and NaCl, respectively) were estimated to range from half an hour to about a day.

6.
J Cell Sci ; 134(2)2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33310909

RESUMO

Silicosis is characterized by silica exposure-induced lung interstitial fibrosis and formation of silicotic nodules, resulting in lung stiffening. The acetylation of microtubules mediated by α-tubulin N-acetyltransferase 1 (α-TAT1) is a posttranslational modification that promotes microtubule stability in response to mechanical stimulation. α-TAT1 and downstream acetylated α-tubulin (Ac-α-Tub) are decreased in silicosis, promoting the epithelial-mesenchymal transition (EMT); however, the underlying mechanisms are unknown. We found that silica, matrix stiffening or their combination triggered Ac-α-Tub downregulation in alveolar epithelial cells, followed by DNA damage and replication stress. α-TAT1 elevated Ac-α-Tub to limit replication stress and the EMT via trafficking of p53-binding protein 1 (53BP1, also known as TP53BP1). The results provide evidence that α-TAT1 and Ac-α-Tub inhibit the EMT and silicosis fibrosis by preventing 53BP1 mislocalization and relieving DNA damage. This study provides insight into how the cell cycle is regulated during the EMT and why the decrease in α-TAT1 and Ac-α-Tub promotes silicosis fibrosis.This article has an associated First Person interview with the first authors of the paper.


Assuntos
Transição Epitelial-Mesenquimal , Tubulina (Proteína) , Acetilação , Dano ao DNA , Transição Epitelial-Mesenquimal/genética , Processamento de Proteína Pós-Traducional , Dióxido de Silício/toxicidade , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo
7.
Toxicol Appl Pharmacol ; 408: 115255, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33007385

RESUMO

Silicosis is a major public health concern with various contributing factors. The renin-angiotensin system (RAS)is a critical regulator in the pathogenesis of this disease. We focused on two key RAS enzymes, angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2), to elucidate the activation of the ACE-angiotensin II (Ang II)-angiotensin II receptor 1 (AT1) axis and the inhibition of the ACE2-angiotensin-(1-7) [Ang-(1-7)]-Mas receptor axis in C57BL/6mice following SiO2 treatment. Silica exposure caused nodule formation, pulmonary interstitial fibrosis, epithelial-mesenchymal transition (EMT), abnormal deposition of extracellular matrix, and impaired lung function in mice. These effects were attenuated by the inhibition of ACE (captopril), blockade of the AT1(losartan), or systemic knockdown of the Ace gene. These effects were exacerbated by the inhibition of ACE2 (MLN-4760), blockade of the Mas (A779), or knockdown of the Ace2 gene. N-Acetyl-Seryl-Asparyl-Lysyl-Proline (Ac-SDKP), an anti-fibrotic peptide, ameliorated the silica-exposure-induced pathological changes by targeting the RAS system by activating the protective ACE2-Ang-(1-7)-Mas axis and inhibiting the deleterious ACE-Ang II-AT1 axis, thereby exerting a protective effect. This was confirmed in mouse lung type II epithelial cells (MLE-12) pretreated with Ang II and/or gene silencing separately targeting Ace and Ace2.The effects of Ac-SDKP were similar to those produced by Ace gene silencing and were partly attenuated by Ace2 deficiency. These findings suggested that RAS plays critical roles in the pathomechanism of silicosis fibrosis and that Ac-SDKP regulates lung RAS to inhibit EMT in silicotic mice and MLE-12 cells.


Assuntos
Transição Epitelial-Mesenquimal , Pulmão/metabolismo , Oligopeptídeos , Sistema Renina-Angiotensina , Silicose/metabolismo , Angiotensina I/antagonistas & inibidores , Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Enzima de Conversão de Angiotensina 2/genética , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Captopril/farmacologia , Linhagem Celular , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibrose , Losartan/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/antagonistas & inibidores , Peptidil Dipeptidase A , Sistema Renina-Angiotensina/efeitos dos fármacos , Silicose/patologia , Silicose/fisiopatologia
8.
Drug Des Devel Ther ; 14: 4315-4326, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116418

RESUMO

Background: N-Acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a short peptide with an anti-silicosis effect. However, the short biological half-life and low plasma concentration of Ac-SDKP hamper discovery of specific targets in organisms and reduce the anti-silicosis effect. A novel peptide, Ac-SDK (biotin) proline, termed "Ac-B", with anti-fibrotic properties was synthesized. Methods: Ac-B was detected quantitatively by high-performance liquid chromatography. Phagocytosis of Ac-B by the alveolar epithelial cell line A549 was investigated by confocal laser scanning microscopy and flow cytometry. To further elucidate the cellular-uptake mechanism of Ac-B, chemical inhibitors of specific uptake pathways were used. After stimulation with transforming growth factor-ß1, the effects of Ac-B on expression of the myofibroblast marker vimentin and accumulation of collagen type I in A549 cells were analyzed by Western blotting. Sirius Red staining and immunohistochemical analyses of the effect of Ac-B on expression of α-smooth muscle actin (SMA) in a rat model of silicosis were undertaken. Results: Ac-B had good traceability during the uptake, entry, and distribution in cells. Ac-B treatment prevented an increase in α-SMA expression in vivo and in vitro and was superior to that of Ac-SDKP. Caveolae-mediated uptake of Ac-B by A549 cells led to achieving anti-epithelial-mesenchymal transformation (EMT) effects. Conclusion: Ac-B had an anti-fibrotic effect and could be a promising agent for the fibrosis observed in silicosis in the future.

9.
Mol Ther Nucleic Acids ; 20: 851-865, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32464548

RESUMO

To identify potential therapeutic targets for pulmonary fibrosis induced by silica, we studied the effects of this disease on the expression of microRNAs (miRNAs) in the lung. Rattus norvegicus pulmonary silicosis models were used in conjunction with high-throughput screening of lung specimens to compare the expression of miRNAs in control and pulmonary silicosis tissues. A total of 70 miRNAs were found to be differentially expressed between control and pulmonary silicosis tissues. This included 41 miRNAs that were upregulated and 29 that were downregulated relative to controls. Among them, miR-292-5p, miR-155-3p, miR-1193-3p, miR-411-3p, miR-370-3p, and miR-409a-5p were found to be similarly altered in rat lung and transforming growth factor (TGF)-ß1-induced cultured fibroblasts. Using miRNA mimics and inhibitors, we found that miR-1193-3p, miR-411-3p, and miR-370-3p exhibited potent anti-fibrotic effects, while miR-292-5p demonstrated pro-fibrotic effects in TGF-ß1-stimulated lung fibroblasts. Moreover, we also found that miR-411-3p effectively reduced pulmonary silicosis in the mouse lung by regulating Mrtfa expression, as demonstrated using biochemical and histological assays. In conclusion, our findings indicate that miRNA expression is perturbed in pulmonary silicosis and suggest that therapeutic interventions targeting specific miRNAs might be effective in the treatment of this occupational disease.

10.
Biomed Pharmacother ; 125: 109980, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32028236

RESUMO

OBJECTIVE: The role and molecular mechanism of long non-coding RNA (lncRNA)-related pathways in silicosis have not been elucidated clearly. The aims of this study were to evaluate the expression of lncRNAs during silica-induced pulmonary fibrosis and verify the function and molecular mechanism of LOC103691771 in myofibroblast differentiation induced by transforming growth factor-ß1 (TGF-ß1). METHODS: RNA-sequencing was performed to assess differential expression of lncRNAs in control and silicotic rat lungs. Differential expression of lncRNAs was analyzed by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes to identify their biological roles. LOC103691771, LOC102549714, LOC102550137, LOC103693125, and LOC103692016 were selected to verify their expression by real-time PCR of silicotic rat lung tissue and lung fibroblasts stimulated by TGF-ß1. Specific small interfering RNA and an LOC103691771 overexpression plasmid were used to analyze the molecular mechanism in myofibroblast differentiation induced by TGF-ß1. RESULT: A total of 306 lncRNAs were expressed differentially in silicotic rat lungs, including 224 upregulated and 82 downregulated lncRNAs. The expression of LOC103691771, LOC102549714 and LOC102550137 was upregulated, while the expression of LOC103693125 and LOC103692016 was downregulated in silicotic rat lungs and TGF-ß1-induced fibroblast, which was consistent with the results of RNA-sequencing. Furthermore, LOC103691771 gene silencing attenuated myofibroblast differentiation, whereas LOC103691771 overexpression promoted myofibroblast differentiation via regulation of the TGF-ß1-Smad2/3 signaling pathway. CONCLUSION: Our findings revealed that differential expression of lncRNAs was related to the development of silicosis, and LOC103691771 played a major role in myofibroblast differentiation induced by TGF-ß1, which may serve as a potential therapeutic target for silicosis.


Assuntos
Diferenciação Celular/genética , Regulação da Expressão Gênica , Miofibroblastos/citologia , Miofibroblastos/metabolismo , RNA Longo não Codificante/genética , Silicose/genética , Silicose/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Biologia Computacional/métodos , Modelos Animais de Doenças , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Ratos , Transdução de Sinais/efeitos dos fármacos , Silicose/patologia , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
11.
Exp Cell Res ; 388(2): 111878, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32004504

RESUMO

Occupational exposure to silica dust particles was the major cause of pulmonary fibrosis, and many miRNAs have been demonstrated to regulate target mRNAs in silicosis. In the present study, we found that a decreasing level of miR-411-3p in silicosis rats and lung fibroblasts induced by TGF-ß1. Enlargement of miR-411-3p could inhibit the cell proliferation and migration in lung fibroblasts with TGF-ß1 treatment and attenuate lung fibrosis in silicotic mice. In addition, a mechanistic study showed that miR-411-3p exert its inhibitory effect on Smad ubiquitination regulatory factor 2 (Smurf2) expression and decrease ubiquitination degradation of Smad7 regulated by smurf2, result in blocking of TGF-ß/Smad signaling. We proposed that increased expression of miR-411-3p abrogates silicosis by blocking activation of TGF-ß/Smad signaling through decreasing ubiquitination degradation effect of smurf2 on Smad7.


Assuntos
Regulação da Expressão Gênica , MicroRNAs/genética , Fibrose Pulmonar/prevenção & controle , Dióxido de Silício/toxicidade , Silicose/prevenção & controle , Fator de Crescimento Transformador beta/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Masculino , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Ratos , Ratos Wistar , Silicose/genética , Silicose/patologia , Fator de Crescimento Transformador beta/genética , Ubiquitina-Proteína Ligases/genética
12.
Theranostics ; 10(4): 1719-1732, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32042332

RESUMO

The purpose of this study was to determine the effects of Kinesin family member 3A (KIF3A) on primary cilia and myofibroblast differentiation during silicosis by regulating Sonic hedgehog (SHH) signalling. Methods: Changes in primary cilia during silicosis and myofibroblast differentiation were detected in silicotic patients, experimental silicotic rats, and a myofibroblast differentiation model induced by SiO2. We also explored the mechanisms underlying KIF3A regulation of Glioma-associated oncogene homologs (GLIs) involved in myofibroblast differentiation. Results: Primary cilia (marked by ARL13B and Ac-α-Tub) and ciliary-related proteins (IFT 88 and KIF3A) were increased initially and then decreased as silicosis progressed. Loss and shedding of primary cilia were also found during silicosis. Treatment of MRC-5 fibroblasts with silica and then transfection of KIF3A-siRNA blocked activation of SHH signalling, but increased GLI2FL as a transcriptional activator of SRF, and reduced the inhibitory effect of GLI3R on ACTA2. Conclusion: Our findings indicate that primary cilia are markedly altered during silicosis and the loss of KIF3A may promote myofibroblast differentiation induced by SiO2.


Assuntos
Cílios/metabolismo , Cinesina/farmacologia , Dióxido de Silício/farmacologia , Silicose/patologia , Proteína Gli3 com Dedos de Zinco/farmacologia , Actinas , Animais , Diferenciação Celular/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/metabolismo , Proteínas Hedgehog/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , Humanos , Cinesina/metabolismo , Masculino , Miofibroblastos/citologia , Miofibroblastos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Dióxido de Silício/efeitos adversos , Silicose/metabolismo , Fatores de Transcrição/metabolismo , Proteína Gli3 com Dedos de Zinco/metabolismo
13.
Mol Ther Nucleic Acids ; 19: 350-360, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-31877411

RESUMO

Silicosis is a fatal profession-related disease linked to long-term inhalation of silica. The present study aimed to determine whether meprin α, a master regulator of anti-fibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), is diminished by miR-155-5p in silicotic and control lung macrophages and fibroblasts upon activation. NR8383 macrophages, primary lung fibroblasts, and mouse embryonic fibroblasts were used to evaluate the expression and function of meprin α and miR-155-5p. In vitro meprin α manipulation was performed by recombinant mouse meprin α protein, actinonin (its inhibitor), and small interfering RNA knockdown. Macrophage and fibroblast activation was assessed by western blotting, real-time PCR, matrix deposition, and immunohistochemical staining. The roles of meprin α and miR-155-5p were also investigated in mice exposed to silica. We found that the meprin α level was stably repressed in silicotic rats. In vitro, silica decreased meprin α, and exogenous meprin α reduced activation of macrophages and fibroblasts induced by profibrotic factors. miR-155-5p negatively regulated Mep1a by binding to the 3' untranslated region. Treatment with anti-miR-155-5p elevated meprin α, ameliorated macrophage and fibroblast activation, and attenuated lung fibrosis in mice induced by silica. The sustained repression of meprin α and beneficial effects of its rescue by inhibition of miR-155-5p during silicosis indicate that miR-155-5p/meprin α are two of the major regulators of silicosis.

14.
J Cell Sci ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34005428

RESUMO

Silicosis is characterized by silica exposure-induced lung interstitial fibrosis and formation of silicotic nodules, resulting in lung stiffening. The acetylation of microtubules mediated by α-tubulin N-acetyltransferase 1 (α-TAT1) is a posttranslational modification that promotes microtubule stability in response to mechanical stimulation. α-TAT1 and downstream-acetylated α-tubulin (Ac-α-Tub) are decreased in silicosis, promoting the epithelial-mesenchymal transition (EMT); however, the underlying mechanisms are unknown. We found that silica, matrix stiffening, or their combination triggered Ac-α-Tub downregulation in alveolar epithelial cells, followed by DNA damage and replication stress. α-TAT1 elevated Ac-α-Tub to limit replication stress and the EMT via trafficking of p53-binding protein 1 (53BP1). The results provide evidence that α-TAT1/Ac-α-Tub inhibits the EMT and silicosis fibrosis by preventing 53BP1 mislocalization and relieving DNA damage. This study provides insight into how the cell cycle is regulated during the EMT, and why the decrease in α-TAT1/Ac-α-Tub promotes silicosis fibrosis.

15.
Dalton Trans ; 48(39): 14864-14872, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31555781

RESUMO

In this work, a range of g-C3N4/MnO composites were constructed using g-C3N4 nanosheets modified with MnO, and the photocatalytic performance for hydrogen evolution was evaluated by using these as-prepared g-C3N4/MnO composites as photocatalysts. It was found that the photocatalytic activity of the g-C3N4/MnO composites for hydrogen evolution is significantly enhanced compared with that of pristine g-C3N4 since the formation of heterojunctions between the MnO nanoparticles and g-C3N4 nanosheets through coordination covalent bonds promotes the charge carrier transfer and separation abilities of the composites. The loading mass of MnO also has a large influence on the photocatalytic activity of the g-C3N4/MnO composites. Particularly, the g-C3N4/MnO-5 composite with 5 wt% MnO shows superior photocatalytic activity with a hydrogen evolution rate of 559 µmol h-1 g-1 under visible light, which is about 9 times that of the bulky g-C3N4. These findings demonstrate that the combination of metal oxides and g-C3N4 to construct composite photocatalysts is an effective method to improve the photocatalytic performance.

16.
Sci Rep ; 9(1): 12383, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455882

RESUMO

A series of ZnO/Fe2O3/g-C3N4 photocatalysts were synthetized by impregnation of g-C3N4 with Zn(NO3)2·6H2O, and Fe(NO3)2·9H2O followed by calcination. The morphology, chemical composition, and structure of the resulted materials were carefully analyzed by various characterization techniques. The photocatalytic performance of ZnO/Fe2O3/g-C3N4 composites was evaluated based on the H2 evolution from water splitting reaction. The results showed that the ZnO/Fe2O3/g-C3N4 composite can effectively produce more H2 than pure g-C3N4 when irradiated under visible-light. H2 production rate over 3-ZnO/Fe2O3/g-C3N4 composite was of 25 µmol·h-1, which is 4 times higher than that obtained in the presence of pure g-C3N4, clearly showing a significant improvement of the photocatalytic activity of the prepared nanocomposite. This result was attributed to the formation of a heterojunction between g-C3N4 and ZnO/Fe2O3, which delayed the recombination of holes-electrons pairs and resulted in a remarkable increase in photocatalytic performance.

17.
Exp Physiol ; 104(10): 1562-1574, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31290182

RESUMO

NEW FINDINGS: What is the central question of this study? What are the effects of the antifibrotic peptide acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on the angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas axis during the occurrence and progression of silicosis? What is the main finding and its importance? Ac-SDKP inhibited lung fibrosis in rats exposed to silica by activation of the ACE2-angiotensin-(1-7)-Mas axis. Angiotensin-(1-7) potentially promotes Ac-SDKP by increasing the level of meprin α, the major synthetase of Ac-SDKP. Thus, the interaction Ac-SDKP and angiotesin-(1-7) in silicosis could provide a new therapeutic strategy. ABSTRACT: The central role of angiotensin-converting enzyme (ACE) in the occurrence and progression of silicosis has been established. The antifibrotic peptide acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) can be degraded by ACE. The ACE2-angiotensin-(1-7)-Mas axis is protective and acts to counterbalance the detrimental effects of ACE-angiotensin II (Ang II)-Ang II type 1 receptor and exerts antifibrotic effects. Here, we demonstrate an interaction between Ac-SDKP and Ang-(1-7) in the inhibition of collagen deposition and myofibroblast differentiation in rats exposed to silica. Treatment with Ac-SDKP increased the level of ACE2-Ang-(1-7)-Mas in rats or in cultured fibroblasts and decreased the levels of collagen type I and α-smooth muscle actin. Furthermore, exogenous Ang-(1-7) had similar antifibrotic effects and increased the level of meprin α, a major Ac-SDKP synthetase, both in vivo and in vitro. Compared with non-silicotic patients exposed to silica, the level of serum ACE was increased in patients with silicosis phase III; the levels of Ang II and Ang-(1-7) were high in patients with silicosis phase II; and the level of Ac-SDKP was high in the silicosis phase III group. These data imply that Ac-SDKP and Ang-(1-7) have an interactive effect as regulatory peptides of the renin-angiotensin system and exert antifibrotic effects.


Assuntos
Angiotensina I/sangue , Oligopeptídeos/uso terapêutico , Fragmentos de Peptídeos/sangue , Proteínas Proto-Oncogênicas/efeitos dos fármacos , Receptores Acoplados a Proteínas G/efeitos dos fármacos , Silicose/tratamento farmacológico , Actinas/metabolismo , Angiotensina II/sangue , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Colágeno/metabolismo , Colágeno Tipo I/análise , Colágeno Tipo I/metabolismo , Fibroblastos/efeitos dos fármacos , Humanos , Masculino , Peptidil Dipeptidase A/sangue , Fibrose Pulmonar/patologia , Fibrose Pulmonar/prevenção & controle , Ratos , Ratos Wistar , Sistema Renina-Angiotensina/efeitos dos fármacos , Silicose/patologia
18.
Huan Jing Ke Xue ; 40(4): 1575-1584, 2019 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087897

RESUMO

120 main industrial installations were screened based on the emissions inventory of 2016 in Cangzhou City, and the air pollution effect of PM2.5, PM10, SO2, NO2, sulfates, nitrates, and secondary organic aerosol (SOA) was simulated for 2017 autumn-winter season for different levels of pollution using the CALPUFF model after code recompilation. The results showed that the ratios of the modelled and measured concentrations of PM2.5, PM10, SO2, and NO2 were 3.3%, 5.7%, 5.6%, and 2.9%, respectively. The areas most affected by pollution from primary PM10 were the southwest and southeast part of Cangzhou, while sulfate, nitrate, and SOA pollution mainly affected the southeast part. The proportion of SOA in the PM2.5 was around 27.3%, and rose to 29.0% during heavily polluted periods. The aerosols of alkenes, tolune, xylene, and PAH in PM2.5 accouted for 12.1%, 6.0%, 7.0%, and 2.2% of the total aerosols respectively. The result of the simulation of individual enterprises showed that their total contribution to PM2.5 during heavily polluted periods was 3.02 µg·m-3, accounting for 50% of the requirements in the "Three-year Plan" for Cangzhou City (6.00 µg·m-3). The top 5 contributors were 1 Petrochemical industry in Cangzhou (0.41 µg·m-3), 2 Carbon Co. Ltd. (0.29 µg·m-3), 3 Petrochemical industry in Juhai (0.26 µg·m-3), 4 Fertilizer Company (0.23 µg·m-3), 5 Dahua Co. Ltd. (0.19 µg·m-3). These industrial installations were mainly located in Xinhua District, Cangxian, and Bohai New District. This research can provide a scientific ground for production restrictions and limitations and emissions reduction of each industry during heavily polluted periods.

19.
Exp Cell Res ; 380(2): 131-140, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31029634

RESUMO

Transforming growth factor-ß1 (TGF-ß1) alters the fibroblast phenotype by promoting transdifferentiation into myofibroblasts, which exhibit the ability to promote collagen synthesis and extracellular matrix (ECM) deposition, thereby playing a significant role in the pathology of silicosis. In this study, we investigated the regulatory mechanisms involved in myofibroblast transdifferentiation. Two-dimensional gel electrophoresis showed that Rho GDP-dissociation inhibitor α (RhoGDIα) was upregulated following myofibroblast transdifferentiation stimulated by TGF-ß1. We hypothesised that RhoGDIα may induce myofibroblast transdifferentiation and thus result in silicosis. Accordingly, the biological significance of RhoGDIα in cell proliferation and apoptosis was investigated by deletion of RhoGDIα in MRC-5 cells. In addition, a mechanistic study showed that fasudil, an inhibitor of the RhoA/Rho kinase (ROCK) signalling pathway, reduced the levels of RhoGDIα, RhoA, and phospho-myosin phosphatase (phospho-MYPT) in MRC-5 cells and silicosis model rats. Knockdown of RhoGDIα inhibited myofibroblast transdifferentiation and collagen deposition through RhoGDIα/RhoA/ROCK signalling in silicosis model mice. Overall, downregulation of RhoGDIα may significantly promote cell apoptosis and inhibit cell growth, resulting in reversal of myofibroblast transdifferentiation by RhoA/ROCK in vitro and in vivo. These data will facilitate further exploration of the potential use of RhoGDIα as a target for silicosis therapy.


Assuntos
Silicose/tratamento farmacológico , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho/metabolismo , Quinases Associadas a rho/antagonistas & inibidores , Proteína rhoA de Ligação ao GTP/antagonistas & inibidores , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Silicose/metabolismo , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
20.
Bull Environ Contam Toxicol ; 98(1): 113-119, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27909755

RESUMO

Soil column leaching experiments were conducted to study the effects of multiple freeze-thaw cycles on the vertical migration of cadmium (Cd). Three Cd-spiked leaching solutions of different properties were derived from snowmelt, sludge, and straw, designated as B, W and J, respectively. The leaching solutions varied in dissolved organic matter (DOM) concentrations in the order of J > W > B. Changes in leachate properties and Cd concentration were observed. The results showed that pH values of all the leachate solutions through freeze-thaw treated soil columns were higher than those of leachates through unfrozen soils. However, electrical conductivity (EC) values decreased compared with leachates in unfrozen treated soil columns. Although the concentrations of DOM in leachate solutions had no evident differences between the freeze-thaw and unfrozen treated soil columns, the concentrations of DOM in the leachate solutions B, W and J were different. Freeze-thaw cycles resulted in increased concentrations of Cd in the leachate solutions in the order J > W > B, and promoted a deeper migration of Cd in the soil columns. Thus, it was shown that freeze-thaw cycles may increase the risk of groundwater pollution by Cd.


Assuntos
Cádmio/análise , Congelamento , Água Subterrânea/química , Poluentes do Solo/análise , Solo/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química
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