Multilevel Screening Strategy to Identify the Hydrophobic Organic Components of Ambient PM2.5 Associated with Hepatocellular Steatosis.

Hepatic steatosis is the first step in a series of events that drives hepatic disease and has been considerably associated with exposure to fine particulate matter (PM2.5). Although the chemical constituents of particles matter in the negative health effects, the specific components of PM2.5 that trigger hepatic steatosis remain unclear. New strategies prioritizing the identification of the key components with the highest potential to cause adverse effects among the numerous components of PM2.5 are needed. Herein, we established a high-resolution mass spectrometry (MS) data set comprising the hydrophobic organic components corresponding to 67 PM2.5 samples in total from Taiyuan and Guangzhou, two representative cities in North and South China, respectively. The lipid accumulation bioeffect profiles of the above samples were also obtained. Considerable hepatocyte lipid accumulation was observed in most PM2.5 extracts. Subsequently, 40 of 695 components were initially screened through machine learning-assisted data filtering based on an integrated bioassay with MS data. Next, nine compounds were further selected as candidates contributing to hepatocellular steatosis based on absorption, distribution, metabolism, and excretion evaluation and molecular dockingin silico. Finally, seven components were confirmed in vitro. This study provided a multilevel screening strategy for key active components in PM2.5 and provided insight into the hydrophobic PM2.5 components that induce hepatocellular steatosis.

Circadian rhythm disturbances involved in ozone-induced glucose metabolism disorder in mouse liver.

Ozone (O3) is a key environmental factor for developing diabetes. Nevertheless, the underlying mechanisms remain unclear. This study aimed to investigate alterations of glycometabolism in mice after O3 exposure and the role of circadian rhythms in this process. C57BL/6 male mice were randomly assigned to O3 (0.5 ppm) or filtered air for four weeks (4 h/day). Then, hepatic tissues of mice were collected at 4 h intervals within 24 h after O3 exposure to test. The results showed that hepatic circadian rhythm genes oscillated abnormally, mainly at zeitgeber time (ZT)8 and ZT20 after O3 exposure. Furthermore, detection of glycometabolism (metabolites, enzymes, and genes) revealed that O3 caused change in the daily oscillations of glycometabolism. The serum glucose content decreased at ZT4 and ZT20, while hepatic glucose enhanced at ZT16 and ZT24(0). Both G6pc and Pck1, which are associated with hepatic gluconeogenesis, significantly increased at ZT20. O3 exposure disrupted glycometabolism by increasing gluconeogenesis and decreasing glycolysis in mice liver. Finally, correlation analysis showed that the association between Bmal1 and O3-induced disruption of glycometabolism was the strongest. The findings emphasized the interaction between adverse outcomes of circadian rhythms and glycometabolism following O3 exposure.

The Flow Stress Behavior and Physical-Based Constitutive Model for As-Quenched Al-Zn-Mg-Cu Alloy.

Although heat-treatable Al-Zn-Mg-Cu alloys are widely used in aerospace industries, distortion and cracks exist due to the residual stress during quenching. Understanding the flow stress behavior and numerically modeling the process is the key to predicting the residual stress. This paper investigated the flow stress behavior of the as-quenched 7050 alloy at strain rates from 0.1 s-1 to 1 s-1, temperatures between 423 K and 723 K, and cooling rates from 0.1 K/s to 10 K/s. The experimental results showed that the strain rate, cooling rate, and temperature have effects on the flow stress value, except for the cooling rates at a temperature of 423 K or 723 K. The kinetics model was used to obtain the precipitate features, i.e., precipitate size and volume fraction. Then, a physical constitutive model based on the evolution of immobile dislocation, solutes, and precipitates was developed. The predicted flow stresses showed good agreement with the experimental data. The findings of this work expand the knowledge on the as-quenched flow behavior of Al-Zn-Mg-Cu alloys, improving the prediction accuracy of residual stress by FEM.

Effects of differential regional PM2.5 induced hepatic steatosis and underlying mechanism.

Emerging evidence suggests that exposure to PM2.5 is associated with a high risk of nonalcoholic fatty liver disease (NAFLD). NAFLD is typically characterised by hepatic steatosis. However, the underlying mechanisms and critical components of PM2.5-induced hepatic steatosis remain to be elucidated. In this study, ten-month-old C57BL/6 female mice were exposed to PM2.5 from four cities in China (Taiyuan, Beijing, Hangzhou, and Guangzhou) via oropharyngeal aspiration every other day for four weeks. After the exposure period, hepatic lipid accumulation was evaluated by biochemical and histopathological analyses. The expression levels of genes related to lipid metabolism and metabolomic profiles were assessed in the mouse liver. The association between biomarkers of hepatic steatosis (hepatic Oil Red O staining area and serum and liver triglyceride contents) and typical components of PM2.5 was identified using Pearson correlation analysis. Oil Red O staining and biochemical results indicated that PM2.5 from four cities significantly induced hepatic lipid accumulation. The most severe hepatic steatosis was observed after Guangzhou PM2.5 exposure. Moreover, Guangzhou PM2.5-induced the most significant changes in gene expression associated with lipid metabolism, including increased hepatic fatty acid uptake and lipid droplet formation and decreased fatty acid synthesis and lipoprotein secretion. Contemporaneously, exposure to Guangzhou PM2.5 significantly perturbed hepatic lipid metabolism. According to metabolomic analysis, disturbed hepatic lipid metabolism was primarily concentrated in linoleic acid, α-linoleic acid, and arachidonic acid metabolism. Finally, correlation analysis revealed that copper (Cu) and other inorganic components, as well as the majority of polycyclic aromatic hydrocarbons (PAHs), were related to changes in biomarkers of hepatic steatosis. These findings showed that PM2.5 exposure caused hepatic steatosis in aged mice, which could be related to the critical chemical components of PM2.5. This study provides critical information regarding the components of PM2.5, which cause hepatic steatosis.

Overview of PM2.5 and health outcomes: Focusing on components, sources, and pollutant mixture co-exposure.

PM2.5 varies in source and composition over time and space as a complicated mixture. Consequently, the health effects caused by PM2.5 varies significantly over time and generally exhibit significant regional variations. According to numerous studies, a notable relationship exists between PM2.5 and the occurrence of many diseases, such as respiratory, cardiovascular, and nervous system diseases, as well as cancer. Therefore, a comprehensive understanding of the effect of PM2.5 on human health is critical. The toxic effects of various PM2.5 components, as well as the overall toxicity of PM2.5 are discussed in this review to provide a foundation for precise PM2.5 emission control. Furthermore, this review summarizes the synergistic effect of PM2.5 and other pollutants, which can be used to draft effective policies.

Biochemical evidence of PM2.5 critical components for inducing myocardial fibrosis in vivo and in vitro.

PM2.5 constituents are tightly linked to the initiation of many cardiovascular diseases (CVDs). Little is known, however, about the events which critical components of PM2.5 can induce the initiating events in CVDs. C57BL/6 female mice were exposed to PM2.5 (3 mg/kg b.w.) from four different cities (Taiyuan, Beijing, Hangzhou, and Guangzhou) by oropharyngeal aspiration every other day. PM2.5 from Taiyuan increased the diastolic function of the hearts and induced myocardial fibrosis with increased areas of interstitial fibrosis through the NOX4/TGF-ß1/Smad 3/Col1a1 pathways. Pb, Cr, Mn, Zn, and most of the polycyclic aromatic hydrocarbons (PAHs) were positively associated with the related indicators of cardiac diastolic function and myocardial fibrosis by using Pearson correlation (R2 = 0.9085-0.9897). To determine the critical components in PM2.5 that can induce the occurrence of myocardial fibrosis, BEAS-2b cells were treated with one or more of five candidate components with/without Guangzhou PM2.5, and then the conditioned medium of BEAS-2b was used to culture AC16 cells. The results showed that Zn + Pb + Mn + BaP with PM2.5 from Guangzhou exposure significantly increased reactive oxygen species production of BEAS-2b cells and induced a dramatic increase of myocardial fiber-related gene expression (Col1a1 and TGF-ß) in AC16 cells. It indicated that the different mass concentrations of Zn, Pb, Mn, and ΣPAHs in PM2.5 might be the critical factors that modulated myocardial fibrosis induction by targeted. Our study provided a novel avenue for further elucidation of molecular mechanisms of PM2.5 components-induced myocardial fibrosis.

Suppression of NADPH oxidase 4 inhibits PM2.5-induced cardiac fibrosis through ROS-P38 MAPK pathway.

Fine particulate matter (PM2.5) has been consistently linked to cardiovascular diseases, and cardiac fibrosis plays a crucial role in the occurrence and development of heart diseases. It is reported that NOX4-dependent redox signaling are responsible for TGFß-mediated profibrotic responses. The current study was designed to explore the possible mechanisms of cardiac fibrosis by PM2.5 both in vitro and in vivo. Female C57BL/6 mice received PM2.5 (3 mg/kg b.w.) exposure with/without NOX4 inhibitor (apocynin, 25 mg/kg b.w.) or ROS scavenger (NALC, 50 mg/kg b.w.), every other day, for 4 weeks. H9C2 cells were incubated with PM2.5 (3 µg/mL) with/without 5 mM NALC, TGFß inhibitor (SB431542, 10 µM), or siRNA-NOX4 for 24 h. The results demonstrated that PM2.5 induced evident collagen deposition and elevated expression of fibrosis biomarkers (Col1a1 & Col3a1). Significant systemic inflammatory response and cardiac oxidative stress were triggered by PM2.5. PM2.5 increased the protein expression of TGFß1, NOX4, and P38 MAPK. Notably, the increased effects of PM2.5 could be suppressed by SB431542, siRNA-NOX4 in vitro or apocynin in vivo, and NALC. The reverse verification experiments further supported the involvement of the TGFß/NOX4/ROS/P38 MAPK signaling pathway in the myocardial fibrosis induced by PM2.5. In summary, the current study provided evidence that PM2.5 challenge led to cardiac fibrosis through oxidative stress, systemic inflammation, and subsequent TGFß/NOX4/ROS/P38 MAPK pathway and may offer new therapeutic targets in cardiac fibrosis.

Activation of δ-opioid Receptors in Anterior Cingulate Cortex Alleviates Affective Pain in Rats.

The negative emotions caused by persistent pain, called affective pain, are known to seriously affect human physical and mental health. The anterior cingulate cortex (ACC), especially the rostral ACC (rACC) plays a key role in the development of this affective pain. N-methyl-d-aspartate (NMDA) receptors, which are widely distributed in the ACC, are involved in the regulation of emotional behavior. It is well known that activation of opioid receptors can relieve pain, but whether it can alleviate affective pain is not clear. In the present study, conditioned place avoidance (CPA) responses induced by complete Freund's adjuvant (CFA) were used to represent the affective pain of place aversion. The behavioral measurements were synchronously combined with multichannel electrophysiological recordings of the discharge frequency of rACC pyramidal neurons to explore whether affective pain could be alleviated by the synthetic opioid [D-Ala2, D-Leu5]-Enkefalin (DADLE), an agonist of δ-opioid receptors. To further investigate this treatment as a mechanism for the relief of affective pain in CFA-treated animals, we used whole-cell patch recordings in slice preparations of the rACC region to determine the dose-dependent effects of DADLE on NMDA receptor-mediated currents. Then, western blot was used to determine levels of phosphorylated NMDA receptor subunits GluN1, GluN2 and GluN3 as affected by the δ-opioid receptor activation. The results showed that activation of δ-opioid receptors down-regulates the phosphorylation of NMDA receptor subunits, thereby inhibiting NMDA currents, decreasing the discharge frequency of rACC pyramidal neurons, and reversing the CPA response. Thus, δ-opioid receptor activation in the rACC region can alleviate affective pain.

Association of exposure to ambient air pollution with ovarian reserve among women in Shanxi province of north China.

Air pollution has been an important risk factor for female reproductive health. However, epidemiological evidence of ambient air pollution on the predictor for ovarian reserve (antral follicle count, AFC) is deficient. We aim to comprehensively evaluate the association of long-term exposure to ambient air pollution with AFC among women of reproductive age in Shanxi of north China. 600 women with spontaneous menstrual cycle, not using controlled ovarian stimulation, were enrolled in the retrospective study. Two distinct periods of antral follicle development were designed as exposure windows. Generalized linear model was employed to estimate the change of AFC associated with exposure of atmospheric pollutants (SO2, NO2, PM10, PM2.5, CO and O3). Stratification analysis based on age (<30, ≥30 years), university degree (yes, no), years of exposure (2013-2016, 2017-2019) and duration of infertility (<2, 2-5, >5 years) along with two pollutants model were employed to further illustrate the association. We found every 10 µg/m3 increase in SO2 concentration level during the entire development stage of antral follicle was associated with a -0.01 change in AFC (95% confidence interval: -0.016, -0.002) adjusting for the confounders including age, BMI, parity and infertility diagnosis factors. The significant association of increased SO2 level with decreased AFC was particularly observed during the early transition from primary follicle to preantral follicle stage by 10 µg/m3 increase in SO2 exposure level with a -0.01 change (95% CI: -0.015, -0.002) in AFC. The negative association was pronounced among women aged ≥30 years old, and also significant in two pollutants model after adjusting the confounders. No significant associations between other air pollutants and AFC were observed. Our finding suggests that long-term exposure to air pollutant SO2 is associated with lower AFC, raising our concern that atmospheric SO2 exposure may have potential adverse impact on women ovarian reserve.

Comparative studies on regional variations in PM2.5 in the induction of myocardial hypertrophy in mice.

Exposure to fine particulate matter (PM2.5) has been indicated to be related to an increased risk of cardiovascular diseases (CVDs) in sensitive people. However, the underlying mechanisms of PM2.5-induced CVDs are poorly understood. In the present study, PM2.5 samples were collected during winter from four cities (Taiyuan, Beijing, Hangzhou, and Guangzhou) in China. Ten-month-old C57BL/6 female mice were exposed to PM2.5 suspension at a dosage of 3 mg·kg-1 (b. w.) every other day for 4 weeks by oropharyngeal aspiration. PM2.5 from Taiyuan increased the blood pressure and the thicknesses of the left ventricular anterior and posterior walls, decreased the ratio of nucleus to cytoplasm in cardiomyocytes and reduced the systolic function of the heart in mice. Further investigation revealed that PM2.5 from Taiyuan induced lung inflammatory cytokines with up-regulated expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The mRNA expression levels of myocardial hypertrophy markers atrial natriuretic peptide and the ß isoform of myosin heavy chain (ANP and ß-MHC), matrix metalloproteinase 2 (MMP2), MMP9, and inflammatory cytokines TNF-α and IL-6 in the myocardium were significantly increased after exposure to PM2.5 of Taiyuan. Furthermore, PM2.5 from Taiyuan activated the IL-6/JAK2/STAT3/ß-MHC signaling pathway in the myocardium. The correlation between the PM2.5 components and myocardial hypertrophy markers suggested that Zinc (Zn) and acenaphthene (AC) are related to the changes in ANP and ß-MHC at the transcriptional level, respectively. The above results indicated that PM2.5 exposure induced myocardial hypertrophy in older mice, which might be related to the critical contributions of Zn and AC in PM2.5. The present study provides new insights into the mechanism of myocardial hypertrophy after PM2.5 exposure.

Complex to simple: In vitro exposure of particulate matter simulated at the air-liquid interface discloses the health impacts of major air pollutants.

Particulate matter (PM) exposure poses many adverse effects on human health. However, it is challenging to clearly differentiate between the contributions of individual pollutants on toxicity from complex mixtures of ambient air pollutants. The aim of this study is to generate aerosols constituted by silica nanoparticles (NPs) and bisulfate to serve as simulators of particle-associated high-sulfur air pollution. Then, the health impacts of sulfur dioxide were evaluated at the cellular level using an air-liquid interface (ALI) exposure chamber. BEAS-2B cells were exposed to either nano-silica or bisulfite aerosol individually or bisulfate-coated silica (SiO2-NH2@HSO3) for 3 h using the ALI. The cellular toxicities were carefully compared based on the exposure dosages. The ALI exposure of SiO2 NPs alone did not produce any apparent cytotoxicity in cells, but the aerosol exposure of SiO2-NH2@HSO3 significantly decreased the cell viability and enhanced the production of cellular reactive oxygen species in a dose-dependent manner. Consequently, the excessive oxidative stress resulted in mitochondrial damage as well as cellular apoptosis. ALI exposure can possibly reflect the realistic physiological exposure condition of the human respiratory system. As a derivative of the sulfur dioxide component of air pollution, sulfate exacerbates the toxic effects of inhalable PMs. This result may be due to the large surface area of the nanoparticles, with the possibility of carrying more sulfite to the target cells during aerosol exposure. The sulfate levels offer a meaningful complement to the present PM2.5 index of air pollution for achieving better human health protection.

Sulfur dioxide induces apoptosis via reactive oxygen species generation in rat cardiomyocytes.

Epidemiological evidence suggests that the incidence and mortality of cardiovascular diseases are closely related to sulfur dioxide (SO2). In the present study, H9C2 cells were incubated with 100 µM NaHSO3 with or without pretreatment of an antioxidant, N-acetyl-L-cysteine (NAC). The changes of apoptosis rate, mitochondrial membrane potential (MMP), ATP content, caspase-3 activity, and reactive oxygen species (ROS) were detected. Rats were inhaled 7 mg/m3 SO2 and/or intraperitoneal injected with 50 mg/kg (bw) of NAC for 30 days. RT-PCR and Western blot were used to detect the mRNA and protein levels of apoptosis-related genes. We found that the apoptosis of H9C2 cells was induced by NaHSO3, which decreased the content of MMP and ATP, and induced the expression of caspase-3. NAC can inhibit the apoptosis induced by NaHSO3 treatment. SO2 and NaHSO3 decreased the expression of Bcl-2 and the ratio of Bcl-2/Bax, increased the expression of Bax and P53 accumulation and phosphorylation, and activated caspase-9 and caspase-3. Whereas NAC can reduce the changes of apoptosis-related proteins in rat heart. Our results suggest that SO2 induces ROS-mediated P53 and caspase-dependent mitochondrial signaling pathways in H9C2 cells and rat hearts. Antioxidant therapy can reduce the adverse reactions of SO2 and lead to a decline in the cardiovascular disease induced by SO2.

The Martensitic Transformation and Mechanical Properties of Ti6Al4V Prepared via Selective Laser Melting.

This article investigated the microstructure of Ti6Al4V that was fabricated via selective laser melting; specifically, the mechanism of martensitic transformation and relationship among parent ß phase, martensite (α') and newly generated ß phase that formed in the present experiments were elucidated. The primary X-ray diffraction (XRD), transmission electron microscopy (TEM) and tensile test were combined to discuss the relationship between α', ß phase and mechanical properties. The average width of each coarse ß columnar grain is 80⁻160 µm, which is in agreement with the width of a laser scanning track. The result revealed a further relationship between ß columnar grain and laser scanning track. Additionally, the high dislocation density, stacking faults and the typical ( 10 1 ¯ 1 ) twinning were identified in the as-built sample. The twinning was filled with many dislocation lines that exhibited apparent slip systems of climbing and cross-slip. Moreover, the α + ß phase with fine dislocation lines and residual twinning were observed in the stress relieving sample. Furthermore, both as-built and stress-relieved samples had a better homogeneous density and finer grains in the center area than in the edge area, displaying good mechanical properties by Feature-Scan. The α' phase resulted in the improvement of tensile strength and hardness and decrease of plasticity, while the newly generated ß phase resulted in a decrease of strength and enhancement of plasticity. The poor plasticity was ascribed to the different print mode, remained support structures and large thermal stresses.

Synergistic effects of sulfur dioxide and polycyclic aromatic hydrocarbons on pulmonary pro-fibrosis via mir-30c-1-3p/ transforming growth factor ß type II receptor axis.

SO2 and PAHs are well-known pollutants of coal burning and significant contributors to haze episodes. The purpose of the study is to determine whether the combined effects of SO2 and BaP are synergetic and to investigate the pro-fibrotic influences and possible mechanism from the aspect of microRNAs. In the present study cellular metabolic activity of BEAS-2B was assessed using MTT probe. C57BL/6 mice were exposed to BaP (40 mg/kg b.w.) for 5 days or SO2 (7 mg/m3) inhalation for 4 weeks alone or together. Lung tissues were processed for histology to assess pulmonary fibrosis. The protein level of pulmonary pro-fibrotic genes (Col1a1, Col3a1, alpha-SMA, fibronectin) and TGFßR2 were analyzed by Western blot and immunofluorescence in vivo and in vitro. Furthermore, we clarified that the microRNA expression of mir-30c-1-3p by real-time RT-PCR. The luciferase reporter assay was used to determine the binding sites of mir-30c-1-3p in the 3'-UTR of TGFßR2. It was confirmed that SO2 and BaP acted together to produce synergistic effects in cellular metabolic activity. Coexisting of SO2 and BaP increased the protein expression of pro-fibrotic genes and TGFßR2 and decreased mir-30c-1-3p in vivo and in vitro. Dual-luciferase reporter gene assays showed that TGFßR2 was a validated target of mir-30c-1-3p. All above results demonstrated that mir-30c-1-3p was involved in the synergistic pro-fibrotic effects of SO2 and BaP in lung via targeting TGFßR2. This work implies the potential risk of pulmonary fibrosis from the co-existence of SO2 and PAHs and provides new insights into the molecular markers for relevant diseases.

Ambient fine particulate matter exposure induces reversible cardiac dysfunction and fibrosis in juvenile and older female mice.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in the advanced world, and age is an important determinant of cardiac function. The purpose of the study is to determine whether the PM2.5-induced cardiac dysfunction is age-dependent and whether the adverse effects can be restored after PM2.5 exposure withdrawal. METHODS: Female C57BL/6 mice at different ages (4-week-old, 4-month-old, and 10-month-old) received oropharyngeal aspiration of 3 mg/kg b.w. PM2.5 every other day for 4 weeks. Then, 10-month-old and 4-week-old mice were exposed to PM2.5 for 4 weeks and withdrawal PM2.5 1 or 2 weeks. Heart rate and systolic blood pressure were measured using a tail-cuff system. Cardiac function was assessed by echocardiography. Left ventricles were processed for histology to assess myocardial fibrosis. ROS generation was detected by photocatalysis using 2',7'-dichlorodihydrofluorescein diacetate (DCFHDA). The expression of cardiac fibrosis markers (Col1a1, Col3a1) and possible signaling molecules, including NADPH oxidase 4 (NOX-4), transforming growth factor ß1 (TGFß1), and Smad3, were detected by qPCR and/ or Western blot. RESULTS: PM2.5 exposure induced cardiac diastolic dysfunction of mice, elevated the heart rate and blood pressure, developed cardiac systolic dysfunction of 10-month-old mice, and caused fibrosis in both 4-week-old and 10-month-old mice. PM2.5 exposure increased the expression of Col1a1, Col3a1, NOX-4, and TGFß1, activated Smad3, and generated more reactive oxygen species in the myocardium of 4-week-old and 10-month-old mice. The withdrawal from PM2.5 exposure restored blood pressure, heart rate, cardiac function, expression of collagens, and malonaldehyde (MDA) levels in hearts of both 10-month-old and 4-week-old mice. CONCLUSION: Juvenile and older mice are more sensitive to PM2.5 than adults and suffer from cardiac dysfunction. PM2.5 exposure reversibly elevated heart rate and blood pressure, induced cardiac systolic dysfunction of older mice, and reversibly induced fibrosis in juvenile and older mice. The mechanism by which PM2.5 exposure resulted in cardiac lesions might involve oxidative stress, NADPH oxidase, TGFß1, and Smad-dependent pathways.

Cadmium exposure on tissue-specific cadmium accumulation and alteration of hemoglobin expression in the 4th-instar larvae of Propsilocerus akamusi (Tokunaga) under laboratory conditions.

The expression of hemoglobin (Hb) genes has considerable potential as a biomarker for environmental monitoring in Chironomus. However, no sequence information is available regarding Hb genes in Propsilocerus akamusi (Tokunaga), thus the change in Hb mRNA gene expression caused by environmental pollutants remains unknown. In this study, we cloned two Hb gene fragments (PaHbV and PaHbVII) from P. akamusi, analyzed the expression patterns of the PaHbV and PaHbVII transcripts in different tissues using Real-Time quantitative PCR (RT-qPCR), and also measured the Cd levels in different tissues exposed to a sublethal concentration. The results showed significantly increased Cd concentrations and tissue-specific Cd distribution patterns in all of the tissues tested, including the hemolymph, during all time courses. A model describing the roles of specific tissues in Cd uptake and accumulation dynamics was also determined. The Malpighian tubules, gut, and epidermis were the primary sites of Cd accumulation, whereas the hemolymph was the temporary target organ of Cd accumulation, with the Cd being transferred to other internal tissues via the hemolymph. The relative mRNA expression profiles of PaHbV and PaHbVII indicated that their expression levels differed across the different tissues, indicating a tissue-specific response. Our results suggested a reverse effect between Hb expression and Cd accumulation during long-term Cd exposure in comparison with previous studies. The expressions of Hb genes in P. akamusi could be developed as biomarkers for assessing the general health conditions of freshwater ecosystems.

Sulfur dioxide inhibits expression of mitochondrial oxidative phosphorylation genes encoded by both nuclear DNA and mitochondrial DNA in rat lungs.

Epidemiological studies show that sulfur dioxide (SO2), a major air pollutant, is associated with the morbidity and mortality of respiratory tract diseases. The aim of the present study was to determine the effects of SO2 on mitochondria and the corresponding molecular characterization in the lung. Male Wistar rats were exposed to 0, 3.5, 7, and 14 mg/m3 SO2 (4 h/day, 30 days). Mitochondrial dysfunction including decreases of cytochrome c oxidase (COX) activity and mitochondrial membrane potential (MMP) was observed in the lungs of rats after SO2 inhalation. We showed that total mitochondrial DNA (mtDNA) content was significantly decreased in the lungs from rats exposed to SO2. Furthermore, SO2 repressed the expression of complex IV and V subunits encoded by both nuclear DNA (nDNA) and mtDNA. Moreover, such changes were accompanied by depressions of three regulatory factors: peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). The findings suggest that SO2 exposure induced mitochondrial dysfunction in rat lungs. Both nDNA and mtDNA are involved in SO2-induced depression of mitochondrial biogenesis in the lungs. There might be a tissue-specific response of mitochondrial biosynthesis to SO2 inhalation. Such impairment may lead to cellular dysfunction and eventually lung diseases.

Sulfur Dioxide Contributes to the Cardiac and Mitochondrial Dysfunction in Rats.

Epidemiological studies have demonstrated an association between sulfur dioxide (SO2) and an increase of morbidity and mortality of cardiovascular diseases, such as ischemic heart disease, heart failure, and arrhythmia. Mitochondrion is the most sensitive organelle in myocardium of animals exposed to SO2 Here we study the molecular characterization of mitochondrial dysfunction in cardiac muscles of rat after SO2 exposure. We found that the cytochrome c oxidase (COX) activity, mitochondrial membrane potential (ΔΨm), ATP contents, mitochondrial DNA (mtDNA) contents, and mRNA expression of complexes IV and V subunits encoded by mtDNA were decreased after NaHSO3 treatment in vitro or SO2 inhalation in vivo The mitochondrial dysfunctions were accompanied by depressions of co-activator of peroxisome proliferator activated receptor gamma (PGC-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A (TFAM) mRNA and protein. We observed swollen mitochondria and lower amounts of cristae in hearts of rats after 3.5 mg/m(3) SO2 inhalation for 30 days. Interestingly, NaHSO3 induced mitochondrial dysfunctions marked by ΔΨm and ATP reduction could be inhibited by an antioxidant N-acetyl-L-cysteine (NALC), accompanied by the restoration of transcriptional factors expressions. The cardiac mitochondrial dysfunctions could also be alleviated by overexpression of TFAM. SO2 induced abnormal left ventricular function was restored by NALC in vivo Our findings demonstrate that SO2 induces cardiac and mitochondrial dysfunction. And inhibition of reactive oxygen species and enhancing the transcriptional network controlling mitochondrial biogenesis can mitigate the SO2-induced mitochondrial dysfunction.

Sulfur dioxide and benzo(a)pyrene trigger apoptotic and anti-apoptotic signals at different post-exposure times in mouse liver.

There is considerable concern that exposure to PAHs in combination with other air pollutants may lead to cancer or apoptosis in different cells. This study investigated the interaction effects between SO2 and BaP in mouse liver after long-term exposure. Mice were exposed to BaP for 5days or SO2 inhalation for 4weeks alone or together. The mitochondrial membrane potential (MMP) was assessed using the lipophilic cationic probe JC-1. The mRNA and protein level of several mitochondrial respiratory complex subunits and apoptosis-related genes were analyzed by real-time RT-PCR and/or western blot, respectively. We observed the pathology change of the mouse liver after 4-week treatments. It was revealed that MMP was reduced after co-exposure of SO2 and BaP after a 4-week treatment (1day post-exposure, p.e. 1d), with the suppression of the mRNA expression of complexes IV and V subunits, CO1, CO4, and ATP6. Co-exposure of SO2 and BaP appeared to be able to cause apoptotic signals, as judged by the suppression of bcl-2 and the bcl-2/bax ratio and the elevation of bax, caspase 3 activation, p53 accumulation and phosphorylation 1d post-exposure to SO2 and BaP, while the anti-apoptotic signal was detected by the elevation of bcl-2 and the bcl-2/bax ratio as well as the suppression of bax and p53 expression after a 13-week post-exposure (p.e. 13w) of SO2 and BaP. These results indicate that co-exposure to SO2 and BaP appears to lead to apoptotic as well as anti-apoptotic signals at different post-exposure times.