Lead is a widespread environmental pollutant with serious adverse effects on human health, but the mechanism underlying its toxicity remains elusive. This study aimed to investigate the role of ...miR-584–5p / Ykt6 axis in the toxic effect of lead on HK-2 cells and the related mechanism. Our data suggested that lead exposure caused significant cytotoxicity, DNA and chromosome damage to HK-2 cells. Mechanistically, lead exposure down-regulated miR-584–5p and up-regulated Ykt6 expression, consequently, autophagosomal number and autophagic flux increased, lysosomal number and activity decreased, exosomal secretion increased. Interestingly, when miR-584–5p level was enhanced with mimic, autophagosomal number and autophagic flux decreased, lysosomal number and activity increased, ultimately, exosomal secretion was down-regulated, which resulted in significant aggravated toxic effects of lead. Further, directly blocking exosomal secretion with inhibitor GW4869 also resulted in exacerbated toxic effects of lead. Herein, we conclude that miR-584–5p / Ykt6 - mediated autophagy - lysosome - exosome pathway may be a critical route affecting the toxic effects of lead on HK-2 cells. We provide a novel insight into the mechanism underlying the toxicity of lead on human cells.
•Lead produced significant toxic effects on HK-2 cells.•Lead activated miR-584–5p / Ykt6 axis in HK-2 cells.•miR-584–5p / Ykt6 regulated autophagy - lysosome - exosome pathway.•Autophagy - lysosome - exosome played a critical role in the toxicity of lead.
The deficiency of effective biomarker for the toxic effects of water pollutants greatly limits the application of biological monitoring. This study aimed to investigate the possibility of circulating ...exosomes of indigenous fish acting as biomarker for the ecotoxicity effect of water environment. The Helong Reservoir in Guangzhou, China, was chosen as the investigating field, of which the water quality belongs to Class V (2013) (GB 3838-2002, China). The clean drinking water source of the upper reaches of the Liuxihe Reservoir was selected as the control. Indigenous fishes including Oreochromis niloticus (Nile tilapia), Labeo rohita (Rohu), Carassius auratus (Crucian carp) were sampled during the period from July 2020 to April 2021. Circulating exosomes of fish samples were isolated by using ultracentrifugation, characterized with transmission electron microscopy (TEM) and quantified by using bicinchoninic acid (BCA) assay. Oxidative stress, DNA and chromosome damage in liver, kidney, brain, gill and blood of fish samples were measured. The results showed that there were significant differences in superoxide dismutase (SOD) activity, glutathione (GSH) and malondialdehyde (MDA) contents, DNA and chromosome damage in fish samples between the Helong Reservoir and the control. Interestingly, there were also significant differences in circulating exosome levels of fish samples between them. Our data suggested that circulating exosome level of indigenous fish may be a novel biomarker for the ecotoxicity effects of water environment.
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•Circulating exosomes of indigenous fish were isolated, characterized and quantified.•Oxidative stress, genetoxic DNA and chromosome damage of fish samples were analyzed.•Circulating exosome levels were consistent with the oxidative stress and genotoxic effects.•Circulating exosome levels may be novel biomarker for ecotoxic effects of water environment.
Bisphenol A (BPA), one of the typical environmental endocrine disruptors (EEDs), can promote the proliferation and migration of cancer cells, but the mechanism of which remains largely unclear. ...Exosome secretion plays an important role in the stress response of cells to environmental stimuli. This study was designed to explore whether exosome secretion was involved in the toxic effect of BPA on the proliferation and migration of MCF-7 cells, and the related mechanism. Our data shows that the IC50 value of MCF-7 exposure to BPA was about 65.82 µM. The exposure of MCF‐7 to 10 µM BPA resulted in a decreased miR-26b expression and the activation of miR-26b/Rab-31 pathway, consequently, the number and activity of lysosomes decreased, the secretion of exosomes increased, cell proliferation and migration were enhanced obviously. Interestingly, miR-26b mimic up-regulated the number and activity of lysosomes via miR-26b/miR-31 pathway, exosome secretion was down-regulated, cell proliferation and migration decreased. Further, when GW4869 was used to directly inhibit the exosome secretion of MCF-7 treated with BPA, their proliferation and migration were down-regulated. Herein, we concluded that the stimulating effect of BPA on the proliferation and migration of MCF-7 cells was associated with the lysosome - related exosome secretion via miR-26b / Rab31 pathway.
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•BPA exposure activated the miR-26b / Rab31 pathway of MCF-7 cells.•BPA exposure reduced the number and activity of lysosomes via miR-26b / Rab31.•BPA exposure promoted exosome secretion via lysosomes-related pathway.•Exosome secretion was associated with the proliferation and migration induced by BPA.
Abstract
Histone modifications are major post-translational mechanisms responsible for regulation of gene transcription involved in cellular senescence. By using immunofluorescence and Western blot, ...we showed that the global acetylated levels of histone H3 and H4 were significantly reduced in both replicative and premature senescence of human embryonic lung fibroblasts. However the whole trimethylated level of histone H4 lysine 20 was higher in senescent cells. The alterations in the mRNA and protein levels of histone acetyltransferases (HATs), histone methyltransferase (HMT), and histone deacetylases (HDACs) indicate that differential expression exists between replicative and premature senescent cells. Meanwhile, the reduced activity of HDACs was accompanied by cellular senescence. By employing the quantitative chromatin immunoprecipitation assay in detecting specific histone modifications in senescence-related genes including p53 and p16, it was demonstrated that the mRNA expression of p53 was associated with increased H4 acetylation in replicative senescence and increased H4 acetylation and trimethylation of histone H3 at lysine 4 (H3K4me3) in premature senescence. Both acetylation and trimethylation of H3 were involved in replicative senescence, while the acetylation of histone H3 and H4 was predominant in premature senescence, contributing to the mRNA expression of p16. In summary, the global hypoacetylation of histone H3 and H4 and the hypertrimethylation of histone H4 lysine 20 account for epigenetic characteristics in senescence, controlled by HATs, HMT, and HDACs differentially between replicative and premature senescence. Taken together, these findings suggest that the specific histone modifications are involved in regulating the expression of genes related to senescence of human embryonic lung fibroblasts.
In this paper, a general template synthesis approach is proposed to prepare composite hollow particles using quaternized polystyrene hollow particles. The crosslinked gel hollow templates are robust ...sufficiently to preserve their spherical contour during template synthesis. The gel shell with positively charged functional groups is infiltrative, and then a diversity of species can be loaded into the gel by electrostatic interaction. The grown materials are homogeneously distributed throughout the whole shell forming composite shells. The generality of the method is proved by extensive growth of the representative materials including metal Au nanoparticles, tungstenic acid and silica. The hollow particles with mesoporous shells are derived by further calcination to remove polymer templates, meanwhile composition of the shell can be transformed for example WC and C from H2WO4/quaternized polystyrene composite.
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•Building the equation of chloride diffusion-convection in unsaturated concrete.•Establishing the concrete model consisting of aggregates, mortar matrix and ITZs.•Revealing the randomness and ...inhomogeneity of chloride concentration distribution.
Based on the transport model of moisture, this paper establishes a prediction model of chloride transport in unsaturated concrete. For the moisture transport model, different water diffusion coefficients are assigned to the drying and wetting processes respectively. Based on considering the interaction between the transport of moisture and chloride ions in concrete and multi-factors influence on chloride diffusion coefficient, the constitutive equation of chloride diffusion-convection in unsaturated concrete is built. Two groups of tests of concrete specimens under drying and wetting cycles with different time ratios of drying-wetting are carried out and verify the rationality of the prediction model. Furthermore, a two-dimensional concrete model based on finite element method is developed to investigate the chloride transport in unsaturated concrete on meso-level. The simulation results show that the random distribution of aggregates could have a significant influence on the chloride transport. Also, the randomness and inhomogeneity of chloride concentration distribution are well reflected in the meso-scale concrete model under the action of drying and wetting cycles.
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•Cellulose nanocrystals-chitosan composite double functionalized with amino group to enhance adsorption.•Diclofenac sodium adsorbed via acid-base interaction between carboxyl and ...amino groups.•The adsorption capacity of CNC-ED@CS-ED is remarkable high.•CNC-ED@CS-ED exhibited good reusability.
Residual diclofenac sodium (DS) in the environment is harmful to human health. A promising method for DS removal is the use of adsorbents functionalized with amino groups that can form an ionic bond with the carboxyl group of DS at a suitable pH. In this work, a novel composite adsorbent composed of cellulose nanocrystals (CNC) and chitosan (CS) has been synthesized and functionalized by ethylenediamine (ED) in both layers. Characterization methods, including scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectrometry, and X-ray photoelectron spectroscopy, were used to confirm the morphology and synthetic mechanism of the double- amino-functionalized adsorbent. Based on the optimization of adsorption conditions and modeling of the adsorption mechanism, the DS adsorption process on CNC-ED@CS-ED involves chemical adsorption, and the maximum adsorption capacity obtained from the Langmuir model is 444.44 mg/g. CNC-ED@CS-ED exhibits good adsorption capacity and high sustainability; thus, it is a promising composite material for the removal of DS from wastewater.
The mechanistic target of rapamycin (RAPA) complex 1 (mTORC1) - transcription factor EB (TFEB) pathway plays a crucial role in response to nutritional status, energy and environmental stress for ...maintaining cellular homeostasis. But there is few reports on its role in the toxic effects of arsenic exposure and the related mechanisms. Here, we show that the exposure of bronchial epithelial cells (BEAS-2B) to sodium arsenite promoted the activation of mTORC1 (p-mTORC1) and the inactivation of TFEB (p-TFEB), the number and activity of lysosomes decreased, the content of reduced glutathione (GSH) and superoxide dismutase (SOD) decreased, the content of malondialdehyde (MDA) increased, the DNA and chromosome damage elevated. Further, when mTORC1 was inhibited with RAPA, p-mTORC1 and p-TFEB down-regulated, GSH and SOD increased, MDA decreased, the DNA and chromosome damage reduced significantly, as compared with the control group. Our data revealed for the first time that mTORC1 - TFEB pathway was involved in sodium arsenite induced lysosomal alteration, oxidative stress and genetic damage in BEAS-2B cells, and it may be a potential intervention target for the toxic effects of arsenic.
•Sodium arsenite exposure promoted the activation of mTORC1 in BEAS-2B cells.•mTORC1 activation stimulated the phosphorylation of TFEB.•Sodium arsenite caused lysosomal alteration, oxidative stress and genetic damage.•mTORC1-TFEB pathway was involved in the toxicity of sodium arsenite.
A novel ethylenediaminetetraacetic acid (EDTA)-functionalized magnetic chitosan oligosaccharide and carboxymethyl cellulose (Fe3O4@CMCCOS-EDTA) nanocomposite adsorbent was successfully fabricated for ...Pb(II) adsorption. The adsorbent was characterized by Fourier transform infrared, and X-ray photoelectron spectroscopy was used to confirm successful EDTA modification and Pb(II) adsorption. Scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometer, and thermogravimetric analysis were used to study the morphology and properties of magnetic particles. EDTA modification considerably improved the capacity of the adsorbent. The batch adsorption experiment results indicated that the pseudo-second-order (PSO) model and the Langmuir isotherm model reliably described the adsorption behavior. The maximum adsorption capacity (qm) for monolayer chemical adsorption was calculated to be 432.34 mg/g at the pH of 5 and temperature of 308 K. Notably, Fe3O4@CMCCOS-EDTA exhibited a high Pb(II) removal rate of ~100% using an initial metal ion solution of 100 mg/L and 200 mg/L.
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•Novel composite based on polyacrylic acid and magnetic chitosan was carried out.•Magnetic composite shows an efficient removal ratio for Pb(II) .•Magnetic composite remove Pb(II) ...efficiently.•Magnetic composite is well tolerated under acidic conditions.
A creative combination of chitosan with polyacrylic acid (PAA) improves the acidity resistance of chitosan and increases its potential in the field of adsorption. In order to facilitate recovery, magnetic nanoparticles were incorporated in CS–PAA to obtain a magnetic-CS–PAA (MCS–PAA) nanocomposite. The physical and chemical characteristics of the composite adsorbent MCS–PAA were determined by SEM, TEM, FTIR, EDX, XRD, and XPS. This environmental-friendly, magnetic, composite adsorbent showed significantly better adsorption performance than those of the individual adsorbents alone. The maximal adsorption capacity was 204.89 mg/g according to the Langmuir isotherm model, when the concentration of Pb(II) was 100 mg/L at the equilibrium time of 70 min. The main adsorption mechanism was the complexation between the carboxyl, amino, and hydroxyl groups in MCS–PAA and Pb(II). Further, introduction of PAA also improved the acid resistance of CS. The new adsorbent MCS–PAA is thus expected to facilitate a wider range of applications for chitosan in the adsorption of Pb(II).
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