Publications by authors named "Na Mao"

19 Publications

  • Page 1 of 1

Galectin-3/adiponectin as a new biological indicator for assessing the risk of type 2 diabetes: a cross-sectional study in a community population.

Aging (Albany NY) 2021 06 7;13(11):15433-15443. Epub 2021 Jun 7.

Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, People's Republic of China.

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.
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http://dx.doi.org/10.18632/aging.203101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221326PMC
June 2021

Ac-SDKP Attenuates Activation of Lung Macrophages and Bone Osteoclasts in Rats Exposed to Silica by Inhibition of TLR4 and RANKL Signaling Pathways.

J Inflamm Res 2021 27;14:1647-1660. Epub 2021 Apr 27.

Basic Medical College, Hebei Key Laboratory for Chronic Diseases, North China University of Science and Technology, Tangshan, Hebei Province, 063210, People's Republic of China.

Background: Silica-induced inflammatory activation is associated with silicosis and various non-respiratory conditions. The present study was designed to examine the anti-inflammatory effects of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on lung macrophages and bone osteoclasts after silica inhalation in rats.

Methods: Wistar rats and NR8383 and RAW 264.7 cell lines were used in the present study. The receptor activator of nuclear factor kappa-B ligand (RANKL) and toll-like receptor 4 (TLR4) signaling pathways was measured in the lung tissue of rats or NR8383/RAW 264.7 cells exposed to silica. The microarchitecture of the trabecular bone in the tibia and femur was evaluated in silicotic rats. Furthermore, the roles of Ac-SDKP on silicotic rats, silica-treated NR8383/RAW 264.7 cells, and RANKL-induced osteoclast differentiation were studied.

Results: The data indicated that silica inhalation might activate the RANKL and TLR4 signaling pathways in lung macrophages, thus inducing the lung inflammatory and proteolytic phenotype of macrophages and osteoclasts in lung and bone. Ac-SDKP maintained the lung elastin level by inhibiting lung inflammation and macrophage activation via the RANKL and TLR4 signaling pathways. Ac-SDKP also attenuated the reduction in femoral bone mineral density in silicotic rats by inhibiting osteoclast differentiation via the RANKL signaling pathway.

Conclusion: Our findings support the hypothesis that inhalation of crystalline silica induces activation of lung macrophages and bone osteoclasts via the RANKL and TLR4 signaling pathways. Ac-SDKP has the potential to stabilize lung homeostasis and bone metabolism.
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http://dx.doi.org/10.2147/JIR.S306883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088302PMC
April 2021

Heterogeneous Chemistry of Mercuric Chloride on Inorganic Salt Surfaces.

J Phys Chem A 2021 May 29;125(18):3943-3952. Epub 2021 Apr 29.

Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, New Jersey 07102, United States.

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 HgCl, 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 HgCl was quantitatively detected as HgCl·NO. Uptake curves showed a common behavior, where upon exposure of the salt surface to HgCl, the gas-phase concentration of the latter dropped rapidly and then recovered gradually. None of the salts produced a full recovery of HgCl, 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 HgCl, 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 NaSO > NaCl > (NH)SO > NHNO. The uptake on NHNO was nearly fully reversible, with low values of the initial (0.4 × 10) and steady-state (3.3 × 10) uptake coefficients, whereas NaSO was significantly more reactive (3.1 × 10 and 1.7 × 10). Depending on the aerosol loading, the lifetimes of gaseous HgCl on dry urban and marine particles (as pure (NH)SO and NaCl, respectively) were estimated to range from half an hour to about a day.
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http://dx.doi.org/10.1021/acs.jpca.1c02220DOI Listing
May 2021

Matrix stiffness regulates α-TAT1-mediated acetylation of α-tubulin and promotes silica-induced epithelial-mesenchymal transition via DNA damage.

J Cell Sci 2021 01 27;134(2). Epub 2021 Jan 27.

School of Public Health, Medical Research Center, Hebei Key Laboratory for Organ Fibrosis Research, North China University of Science and Technology, Tangshan 063210, China

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.
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http://dx.doi.org/10.1242/jcs.243394DOI Listing
January 2021

Synthesis and Identification of a Novel Peptide, Ac-SDK (Biotin) Proline, That Can Elicit Anti-Fibrosis Effects in Rats Suffering from Silicosis.

Drug Des Devel Ther 2020 19;14:4315-4326. Epub 2020 Oct 19.

Medical Research Center, International Science and Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan, Hebei 063210, People's Republic of China.

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-β1, 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.
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http://dx.doi.org/10.2147/DDDT.S262716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585281PMC
October 2020

N-Acetyl-Seryl-Asparyl-Lysyl-Proline regulates lung renin angiotensin system to inhibit epithelial-mesenchymal transition in silicotic mice.

Toxicol Appl Pharmacol 2020 12 29;408:115255. Epub 2020 Sep 29.

School of Public Health, North China University of Science and Technology, Tangshan 063210, Hebei, China; Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan 063210, Hebei, China. Electronic address:

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 SiO 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.
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http://dx.doi.org/10.1016/j.taap.2020.115255DOI Listing
December 2020

Pulmonary Silicosis Alters MicroRNA Expression in Rat Lung and miR-411-3p Exerts Anti-fibrotic Effects by Inhibiting MRTF-A/SRF Signaling.

Mol Ther Nucleic Acids 2020 Jun 12;20:851-865. Epub 2020 May 12.

School of Public Health, North China University of Science and Technology, Tangshan, 063210 Hebei, China. Electronic address:

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)-β1-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-β1-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.
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http://dx.doi.org/10.1016/j.omtn.2020.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256439PMC
June 2020

Silica Perturbs Primary Cilia and Causes Myofibroblast Differentiation during Silicosis by Reduction of the KIF3A-Repressor GLI3 Complex.

Theranostics 2020 1;10(4):1719-1732. Epub 2020 Jan 1.

Medical Research Center, Hebei Key Laboratory for Organ Fibrosis Research, North China University of Science and Technology, Tangshan, China.

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. : Changes in primary cilia during silicosis and myofibroblast differentiation were detected in silicotic patients, experimental silicotic rats, and a myofibroblast differentiation model induced by SiO. We also explored the mechanisms underlying KIF3A regulation of Glioma-associated oncogene homologs (GLIs) involved in myofibroblast differentiation. : 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 -siRNA blocked activation of SHH signalling, but increased GLI2 as a transcriptional activator of , and reduced the inhibitory effect of GLI3 on . : Our findings indicate that primary cilia are markedly altered during silicosis and the loss of KIF3A may promote myofibroblast differentiation induced by SiO.
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http://dx.doi.org/10.7150/thno.37049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993221PMC
April 2021

Differential expression of lncRNAs during silicosis and the role of LOC103691771 in myofibroblast differentiation induced by TGF-β1.

Biomed Pharmacother 2020 May 3;125:109980. Epub 2020 Feb 3.

School of Public Health, North China University of Science and Technology, Tangshan, 063210 Hebei, China. Electronic address:

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-β1 (TGF-β1).

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-β1. Specific small interfering RNA and an LOC103691771 overexpression plasmid were used to analyze the molecular mechanism in myofibroblast differentiation induced by TGF-β1.

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-β1-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-β1-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-β1, which may serve as a potential therapeutic target for silicosis.
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http://dx.doi.org/10.1016/j.biopha.2020.109980DOI Listing
May 2020

MiR-411-3p alleviates Silica-induced pulmonary fibrosis by regulating Smurf2/TGF-β signaling.

Exp Cell Res 2020 03 28;388(2):111878. Epub 2020 Jan 28.

Basic Medical College, Hebei Medical Collage, Shijiazhuang, Hebei, 050017, China. Electronic address:

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-β1. Enlargement of miR-411-3p could inhibit the cell proliferation and migration in lung fibroblasts with TGF-β1 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-β/Smad signaling. We proposed that increased expression of miR-411-3p abrogates silicosis by blocking activation of TGF-β/Smad signaling through decreasing ubiquitination degradation effect of smurf2 on Smad7.
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http://dx.doi.org/10.1016/j.yexcr.2020.111878DOI Listing
March 2020

Inhibition of miR-155-5p Exerts Anti-Fibrotic Effects in Silicotic Mice by Regulating Meprin α.

Mol Ther Nucleic Acids 2020 Mar 26;19:350-360. Epub 2019 Nov 26.

Medical Research Center, Hebei Key Laboratory for Organ Fibrosis Research, North China University of Science and Technology, Tangshan, Hebei 063210, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.omtn.2019.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939030PMC
March 2020

Enhanced photocatalytic activity of g-CN/MnO composites for hydrogen evolution under visible light.

Dalton Trans 2019 Oct;48(39):14864-14872

Shaanxi Key Laboratory for Advanced Energy Devices, Key Laboratory for Macromolecular Science of Shaanxi Province, School of Materials Science and Engineering, Shaanxi Normal University, Xi'an, Shaanxi 710062, P. R. China.

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.
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http://dx.doi.org/10.1039/c9dt02748cDOI Listing
October 2019

Investigating the Heteronjunction between ZnO/FeO and g-CN for an Enhanced Photocatalytic H production under visible-light irradiation.

Authors:
Na Mao

Sci Rep 2019 Aug 27;9(1):12383. Epub 2019 Aug 27.

Shaanxi Key Laboratory for Advanced Energy Devices, Key Laboratory for Macromolecular Science of Shaanxi Province, School of Materials Science and Engineering, Shaanxi Normal University, Xi'an, Shaanxi, 710062, P.R. China.

A series of ZnO/FeO/g-CN photocatalysts were synthetized by impregnation of g-CN with Zn(NO)·6HO, and Fe(NO)·9HO 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/FeO/g-CN composites was evaluated based on the H evolution from water splitting reaction. The results showed that the ZnO/FeO/g-CN composite can effectively produce more H than pure g-CN when irradiated under visible-light. H production rate over 3-ZnO/FeO/g-CN composite was of 25 μmol·h, which is 4 times higher than that obtained in the presence of pure g-CN, 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-CN and ZnO/FeO, which delayed the recombination of holes-electrons pairs and resulted in a remarkable increase in photocatalytic performance.
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http://dx.doi.org/10.1038/s41598-019-48730-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712215PMC
August 2019

Interaction of N-acetyl-seryl-aspartyl-lysyl-proline with the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas axis attenuates pulmonary fibrosis in silicotic rats.

Exp Physiol 2019 10 13;104(10):1562-1574. Epub 2019 Aug 13.

Basic Medical College, Hebei Medical University, Shijiazhuang, Hebei, China.

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.
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http://dx.doi.org/10.1113/EP087515DOI Listing
October 2019

[CALPUFF Modeling of the Influence of Typical Industrial Emissions on PM in an Urban Area Considering the SOA Transformation Mechanism].

Huan Jing Ke Xue 2019 Apr;40(4):1575-1584

Hong Qing Environmental Technology Co., Ltd., Beijing 100012, China.

120 main industrial installations were screened based on the emissions inventory of 2016 in Cangzhou City, and the air pollution effect of PM, PM, SO, NO, 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 PM, PM, SO, and NO were 3.3%, 5.7%, 5.6%, and 2.9%, respectively. The areas most affected by pollution from primary PM 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 PM was around 27.3%, and rose to 29.0% during heavily polluted periods. The aerosols of alkenes, tolune, xylene, and PAH in PM 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 PM during heavily polluted periods was 3.02 μg·m, accounting for 50% of the requirements in the "Three-year Plan" for Cangzhou City (6.00 μg·m). The top 5 contributors were 1 Petrochemical industry in Cangzhou (0.41 μg·m), 2 Carbon Co. Ltd. (0.29 μg·m), 3 Petrochemical industry in Juhai (0.26 μg·m), 4 Fertilizer Company (0.23 μg·m), 5 Dahua Co. Ltd. (0.19 μg·m). 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.
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http://dx.doi.org/10.13227/j.hjkx.201809076DOI Listing
April 2019

Rho GDP dissociation inhibitor α silencing attenuates silicosis by inhibiting RhoA/Rho kinase signalling.

Exp Cell Res 2019 07 25;380(2):131-140. Epub 2019 Apr 25.

Basic Medical College, Hebei Medical University, Shijiazhuang, China. Electronic address:

Transforming growth factor-β1 (TGF-β1) 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-β1. 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.
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http://dx.doi.org/10.1016/j.yexcr.2019.04.026DOI Listing
July 2019

Proteomic profile of TGF-β1 treated lung fibroblasts identifies novel markers of activated fibroblasts in the silica exposed rat lung.

Exp Cell Res 2019 02 11;375(2):1-9. Epub 2019 Jan 11.

Basic Medical College, North China University of Science and Technology, Tangshan, China; School of public health, North China University of Science and Technology, Tangshan, China; The Hebei key laboratory for organ fibrosis research, North China University of Science and Technology, Tangshan, China. Electronic address:

We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) on control and TGF-β1-exposed rat lung fibroblasts to identify proteins differentially expressed between cell populations. A total of 196 proteins were found to be differentially expressed in response to TGF-β1 treatment. Guided by these results, we next determined whether similar changes in protein expression were detectable in the rat lung after chronic exposure to silica dust. Of the five proteins selected for further analysis, we found that levels of all proteins were markedly increased in the silica-exposed rat lung, including the proteins for the very low density lipoprotein receptor (VLDLR) and the transmembrane (type I) heparin sulfate proteoglycan called syndecan 2 (SDC2). Because VLDLR and SDC2 have not, to our knowledge, been previously linked to the pathobiology of silicosis, we next examined whether knockdown of either gene altered responses to TGF-β1 in MRC-5 lung fibroblasts. Interestingly, we found knockdown of either VLDLR or SDC2 dramatically reduced collagen production to TGF-β1, suggesting that both proteins might play a novel role in myofibroblast biology and pathogenesis of silica-induced pulmonary fibrosis. In summary, our findings suggest that performing LC-MS/MS on TGF-β1 stimulated lung fibroblasts can uncover novel molecular targets of activated myofibroblasts in silica-exposed lung.
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http://dx.doi.org/10.1016/j.yexcr.2019.01.010DOI Listing
February 2019

Silicosis decreases bone mineral density in rats.

Toxicol Appl Pharmacol 2018 06 19;348:117-122. Epub 2018 Apr 19.

Medical Research Center, North China University of Science and Technology, Tangshan, China. Electronic address:

Silicosis is the most common occupational lung disease in China, and is associated with a variety of complications, many of which are poorly understood. For example, recent data indicate that silicosis associates with the development of osteopenia, and in some cases this bone loss is severe, meeting criteria for osteoporosis. Although many factors are likely to contribute to this relationship, including a sedentary lifestyle in patients with advanced silicotic lung disease, we hypothesized that silica might directly reduce bone mineral density. In the present study, six Wistar rats were exposed to silica for 24 weeks in order to induce pulmonary silicosis and examine the relationship to bone mineral density. As expected, all rats exposed to silica developed severe pulmonary fibrosis, as manifested by the formation of innumerable silicotic nodules and the deposition of large amounts of interstitial collagen. Moreover, micro-CT results showed that bone mineral density (BMD) was also significantly reduced in rats exposed to silica when compared control animals and this associated with a modest reduction in serum calcium and 25-hydroxyvitamin D levels. In addition, we found that decreased BMD was also linked to increased osteoclast activity as well as fibrosis-like changes, and to the deposition of silica within bone marrow. In summary, our findings support the hypothesis that silicosis reduces bone mineral density and provide support for ongoing investigations into the mechanisms causing osteopenia in silicosis patients.
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http://dx.doi.org/10.1016/j.taap.2018.04.023DOI Listing
June 2018

Leachate Properties and Cadmium Migration Through Freeze-thaw Treated Soil Columns.

Bull Environ Contam Toxicol 2017 Jan 1;98(1):113-119. Epub 2016 Dec 1.

Key Laboratory of Groundwater Resources and Environment Ministry of Education, College of Environment and Resources, Jilin University, Changchun, 130012, China.

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.
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http://dx.doi.org/10.1007/s00128-016-1982-5DOI Listing
January 2017
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