Mesoporous carbon nanomaterials induced pulmonary surfactant inhibition, cytotoxicity, inflammation and lung fibrosis

Environmental exposure and health risk upon engineered nanomaterials are increasingly concerned. The family of mesoporous carbon nanomaterials(MCNs) is a rising star in nanotechnology for multidisciplinary research with versatile applications in electronics,energy and gas storage, and biomedicine. Meanwhile, there is mounting concern on their environmental health risks due to the growing production and usage of MCNs. The lung is the primary site for particle invasion under environmental exposure to nanomaterials. Here, we studied the comprehensive toxicological profile of MCNs in the lung under the scenario of moderate environmental exposure. It was found that at a low concentration of 10 μg/mL MCNs induced biophysical inhibition of natural pulmonary surfactant. Moreover, MCNs at similar concentrations reduced viability of J774 A.1 macrophages and lung epithelial A549 cells.Incubating with nature pulmonary surfactant effectively reduced the cytotoxicity of MCNs.Regarding the pro-inflammatory responses, MCNs activated macrophages in vitro, and stimulated lung inflammation in mice after inhalation exposure, associated with lung fibrosis.Moreover, we found that the size of MCNs played a significant role in regulating cytotoxicity and pro-inflammatory potential of this nanomaterial. In general, larger MCNs induced more pronounced cytotoxic and pro-inflammatory effects than their smaller counterparts. Our results provided valuable information on the toxicological profile and environmental health risks of MCNs, and suggested that fine-tuning the size of MCNs could be a practical precautionary design strategy to increase safety and biocompatibility of this nanomaterial.     

燃烧法处理酚醛废水的试验

论述了燃烧法处理高浓度含苯酚,甲醛废水的原理及技术方法。该法一次性投资代,占地少,操作简单,运作费用低。去除效果明显,同时为回收废水中酚醛的技术留有余地,具有良好的推广应用前景．     

Neutralization of interleukin-11 attenuates silica particles-induced pulmonary inflammation and fibrosis in vivo

Environmental exposure to crystalline silica particles can lead to silicosis, which is one of the most serious pulmonary interstitial fibrosis around the world. Unfortunately, the exact mechanism on silicosis is unclear, and the effective treatments are lacking to date. In this study, we aim to explore the molecular mechanism by which interleukin-11 (IL-11) affects silica particles-induced lung inflammation and fibrosis. We observed that IL-11 expressions in mouse lungs were significantly increased after silica exposure, and maintained at high levels across both inflammation and fibrosis phase. Immunofluorescent dual staining further revealed that the overexpression of IL-11 mainly located in mouse lung epithelial cells and fibroblasts. Using neutralizing anti-IL-11 antibody could effectively alleviate the overexpression of pro-inflammatory cytokines (i.e., interleukin-6 and tumor necrosis factor-α) and fibrotic proteins (i.e., collagen type I and matrix metalloproteinase-2) induced by silica particles. Most importantly, the expressions of IL-11 receptor subunit α (IL-11Rα), Glycoprotein 130 (GP130), and phosphorylated extracellular signal-regulated kinase (p-ERK) were significantly increased in response to silica, whereas blocking of IL-11 markedly reduced their levels. All findings suggested that the overexpression of IL-11 was involved in the pathological of silicosis, while neutralizing IL-11 antibody could effectively alleviate the silica-induced lung inflammation and fibrosis by inhibiting the IL-11Rα/GP130/ERK signaling pathway. IL-11 might be a promising therapeutic target for lung inflammation and fibrosis caused by silica particles exposure.     

Zn2+ loading as a critical contributor to the circ_0008553-mediated oxidative stress and inflammation in response to PM2.5 exposures

Inflammation is a major adverse outcome induced by inhaled particulate matter with a diameter of ≤ 2.5 µm (PM_2.5), and a critical trigger of most PM_2.5 exposure-associated diseases. However, the key molecular events regulating the PM_2.5-induced airway inflammation are yet to be elucidated. Considering the critical role of circular RNAs (circRNAs) in regulating inflammation, we predicted 11 circRNAs that may be involved in the PM_2.5-induced airway inflammation using three previously reported miRNAs through the starBase website. A novel circRNA circ_0008553 was identified to be responsible for the PM_2.5-activated inflammatory response in human bronchial epithelial cells (16HBE) via inducing oxidative stress. Using a combinatorial model PM_2.5 library, we found that the synergistic effect of the insoluble core and loaded Zn²⁺ ions at environmentally relevant concentrations was the major contributor to the upregulation of circ_0008553 and subsequent induction of oxidative stress and inflammation in response to PM_2.5 exposures. Our findings provided new insight into the intervention of PM_2.5-induced adverse outcomes.     

Static magnetic field action on some markers of inflammation in animal model system—in vivo

Experimentally induced acute inflammation in rats is a good model system which includes the complexity and dynamics of the processes; moreover there are many defined markers for following and estimating changes in an observed system. In this paper, we discuss an in vivo model of acute inflammation induced by carrageenan. Carrageenan-induced paw edema is a model of non-infectious acute inflammatory reaction to assess the contribution of mediators involved in vascular changes associated with acute inflammation and potential treatments. A complex approach into the investigation of possible effects of static magnetic fields (SMF) action on experimentally induced acute inflammation in rats (by measurements of the levels of specific stress markers) is very important in understanding the possible inflammatory mitigation effects, pain relief, and oxidative stress state of an organism. This approach could help for better understanding of the possible mechanisms of interaction of dynamic processes such as inflammation healing and pain relief with external SMF (25 mT at 10, 20 and 30 min exposure time). Results indicate that SMF with B = 25 mT for 30 min diminished the inflammatory process and decreased the levels of inflammatory markers (fibrinogen) and stress markers (ACTH, Cor) into the blood plasma in rats as when compared with sham exposed animals. The exact mechanism by which SMF contributes to the acceleration of inflammatory healing and decrease of inflammation markers in blood plasma in rats still remains unclear. We assume that two possible mechanisms exist. One is the direct interaction of SMF with free active oxygen forms (free radicals) affected by their membrane processes and related with the physiological functions. Another possible mechanism might be related to dynamic regulation of inflammation healing process.     

Toxicity of silver nanoparticles to rainbow trout: A toxicogenomic approach

Silver (Ag) nanoparticles are used as antimicrobial adjuvant in various products such as clothes and medical devices where the release of nano-Ag could contaminate the environment and harm wildlife. The purpose of this study was to examine the sublethal effects of nano-Ag and dissolved Ag on Oncorhynchus mykiss rainbow trout. Hepatic Ag contents and changes in gene expression were monitored to provide insights on bioavailability and mode of action of both forms of silver. Fish were exposed to increasing concentrations (0.06, 0.6 and 6 μg L⁻¹) of nano-Ag (20 nm) and silver nitrate (AgNO₃) for 96 h at 15 °C. A gene expression analysis was performed in the liver using a DNA microarray of 207 stress-related genes followed by a quantitative polymerase chain reaction on a selection of genes for validation. The biochemical markers consisted of the determination of labile zinc, metallothioneins, DNA strand breaks, lipid peroxidation (LPO) and vitellogenin-like proteins. The analysis of total Ag in the aquarium water revealed that nano-Ag was mostly aggregated, with 1% of the total Ag being dissolved. Nevertheless, hepatic Ag content was significantly increased in exposed fish. Indeed, dissolved Ag was significantly more bioavailable than nano-Ag only at the highest concentration with 38 ± 10 and 11 ± 3 ng Ag mg⁻¹ proteins for dissolved and nano-Ag respectively. Exposure to both forms of Ag led to significant changes in gene expression for 13% of tested gene targets. About 12% of genes responded specifically to nano-Ag, while 10% of total gene targets responded specifically to dissolved Ag. The levels of vitellogenin-like proteins and DNA strand breaks were significantly reduced by both forms of Ag, but DNA break levels were lower with nano-Ag and could not be explained by the presence of ionic Ag. Labile zinc and the oxidized fraction of metallothioneins were increased by both forms of Ag, but LPO was significantly induced by nano-Ag only. A discriminant function analysis revealed that the responses obtained by biochemical markers and a selection of ten target genes were able to discriminate completely (100%) the effects of both forms of Ag. Exposure to nano-Ag involved genes in inflammation and dissolved Ag involved oxidative stress and protein stability. Hence, the toxicity of Ag will differ depending on the presence of Ag nanoparticles and aggregates.     

Human bronchial epithelial cell injuries induced by fine particulate matter from sandstorm and non-sandstorm periods: Association with particle constituents

Epidemiological studies have demonstrated the exacerbation of respiratory diseases following sandstorm-derived particulate matter(PM) exposure.The presence of anthropogenic and biological agents on the sandstorm PM and the escalation of PM 2.5 μm(PM2.5)pollution in China have led to serious concerns regarding the health effects of PM2.5during Asian sandstorms.We investigated how changes in PM2.5composition,as the weather transitioned towards a sandstorm,affected human airway epithelial cells.Six PM2.5samples covering two sandstorm events and their respective background and transition periods were collected in Baotou,an industrial city near the Gobi Desert in China.PM samples from all three periods had mild cytotoxicity in human bronchial epithelial cell line BEAS-2B,which was positively correlated with the contents of polycyclic aromatic hydrocarbons and several metals.All PM samples potently increased the release of interleukin-6(IL-6) and interleukin-8(IL-8).Endotoxin in all samples contributed significantly to the IL-6 response,with only a minor effect on IL-8.Cr was positively correlated with both IL-6 and IL-8 release,while Si was only associated with the increase of IL-6.Our study suggests that local agricultural and industrial surroundings in addition to the sandstorm play important roles in the respiratory effects of sandstorm-derived PM.     

A human embryonic stem cell-based in vitro model revealed that ultrafine carbon particles may cause skin inflammation and psoriasis

Air pollution has been linked to many health issues,including skin conditions,especially in children.Among all the atmospheric pollutants,ultrafine particles have been deemed very dangerous since they can readily penetrate the lungs and skin,and be absorbed into the bloodstream.Here,we employed a human embryonic stem cell(h ESC)-based differentiation system towards keratinocytes,to test the effects of ultrafine carbon particles,which mimic ambient ultrafine particles,at environment related concentrations.We found that10 ng/mL to 10 μg/mL ultrafine carbon particles down-regulated the expression of the pluripotency marker SOX2 in h ESCs.Moreover,1 μg/mL to 10 μg/mL carbon particle treatments disrupted the keratinocyte differentiation,and up-regulated inflammationand psoriasis-related genes,such as IL-1β,IL-6,CXCL1,CXCL2,CXCL3,CCL20,CXCL8,and S100 A7 and S100 A9,respectively.Overall,our results provide a new insight into the potential developmental toxicity of atmospheric ultrafine particles.     

Characterization of the pattern of the nongenomic signaling pathway through which TCDD-induces early inflammatory responses in U937 human macrophages

2,3,7,8-Tetrachlorodibenzo(p)dioxin (TCDD) has been known to induce inflammatory signaling in a number of cell types and tissues. We found that in U937 macrophages TCDD causes rapid activation of cytosolic phospholipase A2 (cPLA2) within 30 min as judged by the increase in the serine 505 phosphorylated form of cPLA2 protein and the increased cellular release of free arachidonic acid. This initial action of TCDD is accompanied with the up-regulation of an important inflammation marker, COX-2 mRNA expression within 1 h, and by 3 h, several other markers become up-regulated. These effects appear to be dependent on the initial increase in the intracellular concentration of Ca²⁺, and activation of cPLA2 and COX-2. A comparative study among three different human cell lines showed that activation of COX-2 within 1 h of action of TCDD is a common feature exhibited by all cell lines. On the other hand, the U937 macrophage line appears to be unique among them with respect to its ability to activate TNF-α and IL-8 mRNA expressions, and not requiring Src kinase in propagating the initial signaling of cPLA2. Based on the rapidity of activation of cPLA2 and COX-2, which occurs within 1 h of cell exposure to TCDD, when no change in mRNA expression of CYP1A1 has been observed, it is apparent that this unique action of TCDD is carried out through a distinct “nongenomic” pathway which, is clearly discernable from the classical, “genomic” action pathway of the AhR by not requiring the participation of ARNT.