Zhenhua Yang

Effect of ambient PM(2.5) on lung mitochondrial damage and fusion/fission gene expression in rats.

Exposure to ambient fine particulate matter (PM2.5) increases the risk of respiratory disease. Although previous mitochondrial research has provided new information about PM toxicity in the lung, the exact mechanism of PM2.5-mediated structural and functional damage of lung mitochondria remains unclear. In this study, changes in lung mitochondrial morphology, expression of mitochondrial fission/fusion markers, lipid peroxidation, and transport ATPase activity in SD rats exposed to ambient PM2.5 at different dosages were investigated. Also, the release of reactive oxygen species (ROS) via the respiratory burst in rat alveolar macrophages (AMs) exposed to PM2.5 was examined by luminol-dependent chemiluminescence (CL). The results showed that (1) PM2.5 deposited in the lung and induced pathological damage, particularly causing abnormal alterations of mitochondrial structure, including mitochondrial swelling and cristae disorder or even fragmentation in the presence of higher doses of PM2.5; (2) PM2.5 significantly affected the expression of specific mitochondrial fission/fusion markers (OPA1, Mfn1, Mfn2, Fis1, and Drp1) in rat lung; (3) PM2.5 inhibited Mn superoxide dismutase (MnSOD), Na(+)K(+)-ATPase, and Ca(2+)-ATPase activities and elevated malondialdehyde (MDA) content in rat lung mitochondria; and (4) PM2.5 induced rat AMs to produce ROS, which was inhibited by about 84.1% by diphenyleneiodonium chloride (DPI), an important ROS generation inhibitor. It is suggested that the pathological injury observed in rat lung exposed to PM2.5 is associated with mitochondrial fusion-fission dysfunction, ROS generation, mitochondrial lipid peroxidation, and cellular homeostasis imbalance. Damage to lung mitochondria may be one of the important mechanisms by which PM2.5 induces lung injury, contributing to respiratory diseases.

High-quality water-soluble luminescent carbon dots for multicolor patterning, sensors, and bioimaging

An ingenious method for large-scale fabrication of water-soluble photoluminescent carbon dots (CDs) by a one-step microwave pyrolysis of oxalic acid (OA) and urea is developed. The structure and optical properties of the CDs are characterized by transmission electron microscopy, high-resolution transmission electron microscopy, X-ray diffraction patterns, elemental analysis, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, UV-vis absorption, and photoluminescence spectroscopy. The mechanism for the formation of the CDs is also discussed. In contrast to other CD-based nanomaterials, the as-prepared CDs exhibit high fluorescent quantum yield and excellent stability in both organic and inorganic phases. After simple post-treatment, the CDs are applied as fluorescent powder, showing their promising potential for further wide usage. In addition, the CDs can be utilized as a modification-free biosensor reagent capable of detecting Fe3+ and Ag+ in complex environments. The linear ranges for Fe3+ and Ag+ were 1.0–130 and 0.50–200 μM with the corresponding detection limits of 4.8 and 2.4 nM, respectively. More significantly, the CDs are superior fluorescent bioimaging agents in plants and cells based on their excellent water-solubility and ultra-low toxicity. Finally, the as-synthesized CDs are successfully applied for detecting Fe3+ and Ag+ in biosystems.

Investigation of fine chalk dust particles’ chemical compositions and toxicities on alveolar macrophages in vitro

The aim of the study is to investigate chemical compositions of fine chalk dust particles (chalk PM2.5) and examine their adverse effects on alveolar macrophages (AMs) in vitro. Morphologies and element concentrations of individual chalk particles were analyzed by using the quantitative energy-dispersive electron probe X-ray microanalysis (ED-EPMA). The oxidative response of AMs and the potential to generate nitric oxide (NO) by luminol-dependent chemiluminescence (CL) and nitrate reductase method were assessed 4h following the treatment of AMs with differing dosages of fine chalk particles, respectively. Oxidative stress and cytotoxicity elicited by chalk PM2.5 were also examined. The results showed that fine chalk particles were mainly composed of gypsum, calcite, dolomite and a little amount of organic adhesives. Exposure to chalk PM2.5 at 100 μg mL(-1) or 300 μg mL(-1) significantly increased intracellular catalase, malondialdehyde, and NO levels and decreased superoxide dismutase level in AMs, leading to leakage of lactate dehydrogenase (LDH) and reduction of the cell viability. Furthermore, luminol-dependent CL from respiratory burst in AMs was enhanced. It was suggested that chalk PM2.5 could make oxidative damages on AMs and result in cytotoxicity, being likely attributed to excessive reactive oxygen species or reactive nitrogen species induced by mixture of fine gypsum and calcite/dolomite particles.

Effect of sulfur dioxide inhalation on the expression of KATP and L-Ca2+ channels in rat hearts

Epidemiological studies have revealed an association between sulfur dioxide (SO2) exposure and cardiovascular diseases. This study is designed to investigate the SO2 effect on the expression of ATP-sensitive K(+) (KATP) channel and L-type calcium (L-Ca(2+)) channel in rat hearts. The results show that the mRNA and protein levels of the KATP channel subunits Kir6.2 and SUR2A of rat hearts in SO2 groups were higher than those in control group. SO2 at 14mg/m(3) significantly decreased the expression of the L-Ca(2+) channel subunits Cav1.2 and Cav1.3. This suggests that SO2 can activate the KATP channels by up-regulating the expression of Kir6.2 and SUR2A, while it inhibits the L-Ca(2+) channels by down-regulating the expression of Cav1.2 and Cav1.3 in rat hearts. The molecular mechanism of SO2-induced negative inotropic effect might be linked to the expression changes of these subunits, which may contribute to the pathogenesis of SO2-associated cardiovascular diseases.

Effects of gaseous sulfur dioxide and its derivatives on the expression of KATP, BKCa and L-Ca2+ channels in rat aortas in vitro

Epidemiological investigations have revealed that sulfur dioxide (SO2) exposure is linked to cardiovascular diseases. Our previous study indicated that the vasorelaxant effect of SO2 might be partly related to ATP-sensitive K(+) (KATP), big-conductance Ca(2+)-activated K(+) (BKCa) and L-type calcium (L-Ca(2+)) channels. The present study was designed to further investigate the effects of gaseous SO2 and its derivatives on the gene and protein expression of these channels in the rat aortas in vitro. The results showed that the mRNA and protein levels of the KATP channel subunits Kir6.1, Kir6.2 and SUR2B of the rat aortas in SO2 and its derivatives groups were higher than those in control group. Similarly, the expression of the BKCa channel subunits α and β1 was increased by SO2 and its derivatives. However, SO2 and its derivatives at 1500μM significantly decreased the expression of the L-Ca(2+) channel subunits Cav1.2 and Cav1.3. Histological examination of the rat aorta tissues showed moderate injury of tunica media induced by SO2 and its derivatives at 1500μM. These results suggest that SO2 and its derivatives can activate the KATP and BKCa channels by increasing the expression of Kir6.1, Kir6.2, SUR2B and α, β1, respectively, while also inhibiting the L-Ca(2+) channels by decreasing the expression of Cav1.2 and Cav1.3 of the rat aortas. The molecular mechanism of the vasorelaxant effect of SO2 and its derivatives might be related to the expression changes of KATP, BKCa and L-Ca(2+) channel subunits, which may play a role in the pathogenesis of SO2-associated cardiovascular diseases.

The molecular mechanism of the effect of sulfur dioxide inhalation on the potassium and calcium ion channels in rat aortas.

This study investigated the molecular mechanism of the effect of sulfur dioxide (SO2) on the expression of adenosine triphosphate (ATP)-sensitive potassium ion (K+; KATP) channel, big-conductance calcium ion (Ca2+)-activated K+ (BKCa) channel, and L-type (L-Ca2+) channel subunits in rat aortas with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. The results showed that the messenger RNA and protein levels of the KATP channel subunits Kir6.1, Kir6.2, and sulfonylurea receptor 2B (SUR2B) of rat aortas were significantly increased by SO2 at 14 mg/m3, whereas the levels of SUR2A were not changed. SO2 at all the treated concentrations markedly raised the expression of the BKCa channel subunits α and β1. SO2 at 14 mg/m3 significantly decreased the expression of the L-Ca2+ channel Cav1.2 and Cav1.3. The histological examination of rat aorta tissues showed moderate injury of tunica media in the presence of SO2 at 14 mg/m3. These suggest that SO2 can activate the KATP and BKCa channels by upregulating the expression of Kir6.1, Kir6.2, SUR2B, BKCa α, and BKCa β1, while inhibit the L-Ca2+ channels by downregulating the expression of Cav1.2 and Cav1.3 in rat aortas. The molecular mechanism of SO2-induced vasorelaxant effect might be linked to the changes in expression of these channel subunits, which plays an important role in the pathogenesis of SO2-associated cardiovascular diseases.

Effects of sodium metabisulfite on the expression of BKCa, KATP, and L-Ca2+ channels in rat aortas in vivo and in vitro

Sodium metabisulfite (SMB) is most commonly used as the preservative in many food preparations and drugs. So far, few studies about its negative effects were reported. The purpose of this study was to investigate the effect of SMB on the expression of big-conductance Ca(2+)-activated K(+) (BKCa), ATP-sensitive K(+) (KATP), and L-type calcium (L-Ca(2+)) channels in rat aorta in vivo and in vitro. The results showed that the mRNA and protein levels of the BKCa channel subunits α and β1 of aorta in rats were increased by SMB in vivo and in vitro. Similarly, the expression of the KATP channel subunits Kir6.1, Kir6.2, and SUR2B were increased by SMB. However, SMB at the highest concentration significantly decreased the expression of the L-Ca(2+) channel subunits Cav1.2 and Cav1.3. These results suggest that SMB can activate BKCa and KATP channels by increasing the expression of α, β1, and Kir6.1, Kir6.2, SUR2B respectively, while also inhibit L-Ca(2+) channels by decreasing the expression of Cav1.2 and Cav1.3 of aorta in rats. The molecular mechanism of SMB-induced vasorelaxant effect might be related to the expression changes of BKCa, KATP, and L-Ca(2+) channels subunits. Further work is needed to determine the relative contribution of each channel in SMB-mediated vasorelaxant effect.

Fine chalk dust induces inflammatory response via p38 and ERK MAPK pathway in rat lung

Chalk teaching is widely used in the world due to low cost, especially in some developing countries. During teaching with chalks, a large amount of fine chalk dust is produced. Although exposure to chalk dust is associated with respiratory diseases, the mechanism underlying the correlation between chalk dust exposure and adverse effects has not fully been elucidated. In this study, inflammation and its signal pathway in rat lungs exposed to fine chalk dust were examined through histopathology analyses; pro-inflammatory gene transcription; and protein levels measured by HE staining, RT-PCR, and western blot analysis. The results demonstrated that fine chalk dust increased neutrophils and up-regulated inflammatory gene mRNA levels (TNF-α, IL-6, TGF-β1, iNOS, and ICAM-1), and oxidative stress marker (HO-1) level, leading to the increase of inflammatory cell infiltration and inflammatory injury on the lungs. These inflammation responses were mediated, at least in part, via p38 and extracellular regulated proteinase (ERK) mitogen-activated protein kinase (MAPK) signaling mechanisms. In contrast, N-acetyl-L-cysteine (NAC) supplement significantly ameliorated these changes in inflammatory responses. Our results support the hypothesis that fine chalk dust can damage rat lungs and the NAC supplement may attenuate fine chalk dust-associated lung inflammation.

The role of pro-/anti-inflammation imbalance in Aβ42 accumulation of rat brain co-exposed to fine particle matter and sulfur dioxide

Abstract Taiyuan is a center of coal-based electricity production and many chemicals industries, where mixtures of sulfur dioxide (SO2) and particulate matter may be more prominent. The focus of the present study was to determine if there is a link between adverse effects in the brain and the combined-exposure to SO2 and fine particulate matter (PM2.5). Rats were exposed alternately to PM2.5 with different dosages (1.5, 6.0 and 24.0 mg/kg body weight) and SO2 at the level of 5.6 mg/m3. The results showed that the combined exposure to PM2.5 and SO2 enhanced the mRNA expression and protein level of TNF-α and IL-6 in rat cortex and hippocampus relative to the control, SO2 and PM2.5 alone. Instead, TGF-β1 mRNA and protein level were down-regulated in the brain. Additionally, PM2.5 at medium and/or high dose caused marked increase in Aβ42 level and PM2.5 + SO2 induced further increase of Aβ42 level in the cortex and hippocampus. It suggests that SO2 and PM2.5 can synergistically exert inflammation responses and induce Aβ42 accumulation in the brain. Also, it is notable that the Aβ42 accumulation of rat cortex and hippocampus were closely associated with pro-/anti-inflammatory cytokines ratio. These results clearly demonstrated that the combined exposure to PM2.5 and SO2 can induce the imbalance of pro-/anti-inflammatory cytokine, resulting in Aβ42 accumulation of rat brain cortex and hippocampus.

The vasorelaxant mechanisms of methanol on isolated rat aortic rings: Involvement of ion channels and signal transduction pathways.

It is reported that methanol is generally used as an industrial solvent, antifreeze, windshield washer fluid, cooking fuel and perfume. Methanol ingestion can lead to severe metabolic disturbances, blindness, or even death. So far, few studies about its negative effects on cardiovascular system have been reported. The purpose of this study was to determine the vasoactive effect of methanol and roles of ion channels and signal transduction pathways on isolated rat aorta. The results suggested that the mechanism of methanol-induced vasorelaxation at low concentrations (<500 mM) was mediated by ATP-sensitive K+ (KATP) and L-type Ca2+ channels, but the mechanism at high concentrations (>600 mM) was related to KATP, voltage-dependent K+, big-conductance Ca2+-activated K+, L-type Ca2+ channels as well as prostacyclin, protein kinase C, β-adrenoceptors pathways. In addition, methanol induced a dose-dependent inhibition of vasoconstrictions caused by calcium chloride, potassium chloride, or norepinephrine. Further work is needed to investigate the relative contribution of each channel and pathway in methanol-induced vasoactive effect.