Tight regulation of a nuclear HAPSTR1-HUWE1 pathway essential for mammalian life.

The recently discovered HAPSTR1 protein broadly oversees cellular stress responses. This function requires HUWE1, a ubiquitin ligase that paradoxically marks HAPSTR1 for degradation, but much about this pathway remains unclear. Here, leveraging multiplexed proteomics, we find that HAPSTR1 enables nuclear localization of HUWE1 with implications for nuclear protein quality control. We show that HAPSTR1 is tightly regulated and identify ubiquitin ligase TRIP12 and deubiquitinase USP7 as upstream regulators titrating HAPSTR1 stability. Finally, we generate conditional Hapstr1 knockout mice, finding that Hapstr1-null mice are perinatal lethal, adult mice depleted of Hapstr1 have reduced fitness, and primary cells explanted from Hapstr1-null animals falter in culture coincident with HUWE1 mislocalization and broadly remodeled signaling. Notably, although HAPSTR1 potently suppresses p53, we find that Hapstr1 is essential for life even in mice lacking p53. Altogether, we identify novel components and functional insights into the conserved HAPSTR1-HUWE1 pathway and demonstrate its requirement for mammalian life.

Thiolated chitosan nanoparticles for stable delivery and smart release of As2O3 for liver cancer through dual actions.

In this work, multifunctional thiolated chitosan derivatives (DCA-CS-PEG-FA-NAC) were synthesized, and arsenic trioxide (ATO) was loaded onto the derivatives through glutathione (GSH)-sensitive AsIII-S bonds, and stable CS-ATO nanodrugs were prepared by simple self-assembly method. By adjusting the thiol substitution degree of CS, the drug loading capacity of the nanodrugs was significantly improved, which could reach 20 ATO per CS molecule (DCA10.7-CS-PEG3.1-FA-NAC20.2-ATO). In vitro release studies obviously showed the low leakage of ATO under physiological conditions while over 95 % ATO was released after 24 h under GSH. In vitro and in vivo investigations demonstrated that the DCA10.7-CS-PEG3.1-FA-NAC20.2-ATO nanodrug could significantly enhance the tumor intracellular accumulation of ATO, reduce the toxic and side effects of ATO on healthy organs, and improve the therapeutic effect of ATO on the HepG2 mice tumor model (tumor inhibition rate was as high as 86.4 %), indicating the potential application of ATO in clinical treatment of liver cancer.

Time- and Dose-Resolved Proteome of PM2.5-Exposure-Induced Lung Injury and Repair in Rats.

In recent years, airborne fine particulate matter (PM2.5) is drawing more public attention due to its various physicochemical features and causing pathological harm, as proven by epidemiological and clinical studies. However, the mechanism of PM2.5-exposure-induced lung injury has not been fully characterized. Here, we established a PM2.5-induced rat injury model for both short-term and long-term exposures at different concentrations. We employed the Fast-seq technique to profile 6316 proteins and the catTFRE approach to profile 387 transcription factors (TFs) in the lung tissue. In short-term exposure, we elucidated gradually upregulated proteins enriched in response to oxidative stress, phagosome, and the extracellular matrix (ECM)-receptor interaction pathway. Long-term exposure mainly showed the immune response pathway to be consisting of increased lymphocytes and cytokines. Intriguingly, we found that immune-related proteins were recoverable during short-term exposure. During the process of PM2.5 exposure, upregulated proteins presented dose-dependence in the lung, including stress response at low dose, minor immune response at middle dose, and severe inflammatory response at high dose. This data set provides a rich resource to facilitate the understanding of PM2.5-induced lung damage and repair mechanism.

Toxicity assessment of electronic cigarettes.

Sale of electronic cigarette (e-cigarette) products has exponentially increased in the past decade, which raise concerns about its safety. This updated review provides the available toxicology profile of e-cigarettes, summarizing evidence from in vitro and in vivo studies. Data regarding which components in e-liquids exhibit potential toxicities are inconsistent. Some studies have reported that nicotine plays a significant role in inducing adverse outcomes and that solvents alone do not induce any adverse effects. However, other studies have suggested that nicotine is not associated with any adverse outcomes, whereas solvents and flavorings are the key components to elicit considerable deleterious effects on cells or animals. In addition, most of the studies that have compared the toxicity of e-cigarettes with tobacco cigarettes have suggested that e-cigarettes are less toxic than tobacco cigarettes. Nevertheless, scientific evidence regarding the toxicity profile of e-cigarette is insufficient owing to the lack of a standardized research approach. In the future, scientific toxicology data derived from standardized testing protocols including nicotine, ingredients analysis, the various e-cigarette devices made from different materials are urgently needed for thorough toxicology assessment. This review aims to update the toxicity profiles, identify knowledge gaps, and outline future directions for e-cigarettes research, which would greatly benefit public health professionals.

[Determination of 11 synthetic musks in imported seafood by solid phase extraction and gas chromatography-mass spectrometry].

A method has been developed for the simultaneous determination of 11 synthetic musks (cashmeran, celestolide, phantolide, musk ambrette, traseolide, galaxolide, musk xylene, tonalide, musk moskene, musk tibetene, and musk ketone) in imported seafood. The method combines solid phase extraction and gas chromatography-mass spectrometry. Samples were extracted by n-hexane and purified using a Florisil column. Internal standards were used to correct for matrix effects. The calibration curves showed good linearity with correlation coefficients greater than 0.99. The limits of detection (S/N>3) ranged from 0.35 to 2.08 µg/kg, and the limits of quantification (S/N>10) were between 1.18 and 5.00 µg/kg. The average recoveries measured at three spiked levels (10, 20, and 30 µg/kg) were in the range 83.1%-117%, with relative standard deviations ranging from 5.1% to 8.5%. Further, the concentrations of 11 synthetic musks in 30 imported seafood in Shanghai were investigated. Galaxolide was detected in 93.3% of samples analysed, in concentration as high as 3.82 µg/kg. Musk ambrette and musk moskene were found in concentrations as high as 15.4 µg/kg and 10.5 µg/kg, respectively. The established method demonstrates high sensitivity and selectivity for the determination and confirmation of 11 synthetic musks in imported seafood.

The protective effects of selenium supplementation on ambient PM2.5-induced cardiovascular injury in rats.

Substantial epidemiological and experimental studies have shown that ambient fine particulate matter (PM2.5) exposure can lead to myocardial damage in human and animal through the mechanism of inflammation and oxidative stress. The purpose of the current study was to investigate whether selenium yeast (SeY) supplementation could prevent cardiovascular injury caused by PM2.5 in rats. Fifty-six Sprague-Dawley rats were randomly divided into seven groups: saline control group; solvent control group, low-, middle-, and high-dose Se pretreatment groups, PM2.5 exposure group, and high-dose Se control group. The rats were pretreated with different concentration of dietary SeY for 28 days, then were exposed to PM2.5 by intratracheal instillation every other day, a total of three times. The levels of inflammatory markers (tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), soluble intercellular adhesion molecule-1 (sICAM-1), and oxidative responses-related indicators total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were measured in blood and myocardium of the left ventricle. The results showed that although PM2.5 caused a decrease of T-AOC, T-AOD, and GSH-Px and increase of MDA and sICM-1, pretreatment with SeY induced a dose-dependent increase in these anti-oxidative indicators and a decrease in oxidative indicators. In addition, the levels of TNF-α and IL-1ß in Se pretreatment groups were significantly lower than that in PM2.5 exposure group. The results indicated that Se supplementation could effectively prevent cardiovascular inflammation and oxidative stress induced by PM2.5. The results also indicated that the nutritional supplementation might be an effective way to protecting people's health from air pollution.

CARD9-mediated ambient PM2.5-induced pulmonary injury is associated with Th17 cell.

Inflammation and oxidative stress are important risk factors in PM2.5-induced injury. The current study attempted to study the role of caspase recruitment domain (CARD) 9 in ambient PM2.5-induced pulmonary injury in mice. The CARD9-/- and C57BL/6 mice were exposed to 3.6, 7.8 and 15.6mg/kgbw of PM2.5 or saline by intratracheal instillation. After the last PM2.5 exposure, the spleen, bronchoalveolar lavage fluid (BALF) and pulmonary tissue were collected and examined. The results showed that PM2.5 exposure induced inflammatory cell infiltration and alveolar septal thickening in the lung. Regulatory T (Treg) cells in spleen of CARD9-/- mice were significantly higher than that in the C57BL/6 mice, whereas the T helper cells 17 (Th17) were lower. The levels of interleukin (IL)-6 and IL-17A in BALF of the CARD9-/- mice were significantly lower than that in the C57BL/6 mice. The mRNA expression of IL-17A, IL-6 and RORγt in the lung of the CARD9-/- mice is significantly lower than that in the C57BL/6 mice, whereas the mRNA levels of Foxp3 in CARD9-/- mice were significantly higher than that in the C57BL/6 mice at the same dose of PM2.5. The protein expression of nuclear factor κB (NF-κB) is higher in the C57BL/6 mice than that in the CARD9-/- mice. This study indicates that ambient PM2.5-induced pulmonary injury is associated with the immune and inflammatory response. CARD9-mediated Th17/Treg differentiation probably played an important role in PM2.5-induced pulmonary damage.

[Intervention effects of selenium yeast on fine particulate matters-induced lung injury in rats].

OBJECTIVE: To evaluate if selenium yeast could inhibit the rat lung injury induced by ambient fine particulate matter( PM_(2. 5) ). METHODS: Fifty-six male SpragueDawley rats were randomly allocated in seven groups( n = 8 each). Saline control group, the rats were exposed to 0. 9% saline by instillation. PM_(2. 5) exposure group, rats were exposed to PM_(2. 5) by intra-tracheal instillation every other day for three times with the accumulated dose of 40 mg/kg. Selenium yeast treatment groups, three groups of rat were exposed to PM_(2. 5) . Then the rats were given low, middle and high dose of selenium yeast, and the doses were 8. 75, 17. 5 and 35 mg/kg, respectively. High dose selenium yeast control group, rats were given high dose of selenium yeast only. Solvent control group, therats were given 1% carboxymethyl cellulose. Saline and PM_(2. 5) were given in the first week. In the second week, selenium yeast and solvent were given by gavage. The rats were sacrificed 24 hours after the last gavage. The bronchoalveolar lavage fluid( BALF)was collected to count the neutrophils numbers and analyze the markers related to inflammation, oxidative stress and cell damage. The lung lobe that was not been lavaged was processed for light microscopic examination. RESULTS: The proportions of neutrophils in BALF and the pathologic scores of lung in PM_(2. 5) - exposed groups were significantly higher than control( P < 0. 05). Selenium yeast treatment caused decrease in tumor necrosis factor-α( TNF-α), interleukin-1ß( IL-1ß), lactate dehydrogenase( LDH), total protein( TP), alkaline phosphatase( AKP) and malondialdehyde( MDA) compared with the only PM_(2. 5) exposure group. Meanwhile, the dose-dependent increase in totalsuperoxide dismutase( T-SOD) and glutathione peroxidase( GSH-Px) activities were observed. There were no significant differences among the groups of saline control group, high dose selenium yeast control group and solvent control group. CONCLUSION: Selenium yeast treatment may protect against acute injury induced by PM_(2. 5) in rat lung.

[Effects of vitamin E and ω-3 fatty acids on protecting ambient PM_(2. 5)-induced cardiovascular injury].

OBJECTIVE: To observe whether vitamin E( Ve) and ω-3 polyunsaturated fatty acids( ω-3 FA) could prevent the fine particulate matter( PM_(2. 5))-induced cardiovascular injury and explore the potential mechanism. METHODS: The SD rats were assigned randomly to 8 groups, those were control group, PM_(2. 5)group, Ve treatment groups( 3, 10, 30 mg/( kg·d)) and ω-3 FA treatment groups( 10, 30 and 90 mg/( kg·d)). The rats were pretreated with different concentration of Ve and ω-3 FA separately for 14 days, then were exposed to ambient PM_(2. 5) by intratracheal instillation( 10 mg/kg BW). All the rats were sacrificed after the last PM_(2. 5) exposure, then the arterial blood, lungs and cardiac tissues were collected. The expressions of tumor necrosis factor-α( TNF-α), interleukin-1ß( IL-1ß), interleukin-6( IL-6) in serum, bronchoalveolar lavage fluid and supernatant of cardiac tissue were detected by ELISA kits. The levels of malondialdehyde( MDA), superoxide dismutase( SOD) and glutathione-peroxidase( GSH-Px) in serum and myocardium were also measured. RESULTS: Compared with the severe injury of rats in PM_(2. 5) exposure group, the rats in Ve or ω-3 FA groups had a slighter injury in lung and cardiac tissue with the increase of Ve and ω-3 FA. Similarly, the levels of IL-1ß, IL-6 in bronchoalveolar lavage fluid had a decreasing trend with the increase of Ve and ω-3 FA compared with the PM_(2. 5) exposure groups. Meanwhile, the expressions of TNF-α in Ve and ω-3 FA high dose groups were significantly reduced when compared with the PM_(2. 5) exposure group( P <0. 05). In addition, the MDA levels in serum were markedly decreased and the activities of SOD were significantly increased compared with the PM_(2. 5)exposure group( P < 0. 05 or P < 0. 01) whereas the SOD activities were elevated only in the ω-3 FA high dose groups( P < 0. 05). Meanwhile, the levels of IL-6 and TNF-α in serum had an obvious decrease compared with the PM_(2. 5) exposure group( P < 0. 01). Similarly, compared with the PM_(2. 5)exposure group, the expressions of MDA were markedly decreased and the activities of SOD and GSH-Px in myocardium were significantly increased( P < 0. 05 or P < 0. 01) in the Ve treatment group. In addition, the activities of GSH-Px was found higher only in the ω-3 FA high treatment group compared with the PM_(2. 5)exposure group( P < 0. 05). Meanwhile, the levels of IL-1ß and TNF-α in cardiac tissue had an obvious decrease trend with the increase of Ve and ω-3 FA. CONCLUSION: PM_(2. 5) exposure may increase inflammatory response and oxidative stress, supplementation with Ve and ω-3 FA could prevent the PM_(2. 5)-induced inflammatory reaction and oxidative stress damage by increasing the activities of SOD and GSH-Px.

Investigation of selenium pretreatment in the attenuation of lung injury in rats induced by fine particulate matters.

Selenium (Se) is vital for health because of its antioxidative and anti-inflammation functions. The aim of this study was to determine if dietary selenium could inhibit the rat lung injury induced by ambient fine particulate matter (PM2.5). Sprague-Dawley rats were randomly allocated in seven groups (n = 8). The rats in PM2.5 exposure group were intratracheally instilled with 40 mg/kg of body weight (b.w.) of PM2.5 suspension. The rats in Se prevention groups were pretreated with 17.5, 35, or 70 µg/kg b.w. of Se for 4 weeks, respectively. Then, the rats were exposed to 40 mg/kg b.w. of PM2.5 in the fifth week. The bronchoalveolar lavage fluid (BALF) was collected to count the neutrophil numbers and to analyze the cytokines (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), soluble intercellular adhesion molecule-1 (sICAM-1)) related to inflammation, the markers related to oxidative stress (total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA)), and the indicators related to cell damage (lactate dehydrogenase (LDH), total protein (TP), alkaline phosphatase (AKP)). The lung lobe that has not undergone bronchoalveolar lavage was processed for light microscopic examination. The results showed that the proportions of neutrophils in the BALF and the pathologic scores of the lung in PM2.5-exposed groups were higher than that in the control group (P < 0.05). Se pretreatment caused a dose-dependent decrease in TNF-α, IL-1ß, sICAM-1, LDH, TP, AKP, and MDA when compared with the PM2.5-only exposure group. Meanwhile, the dose-dependent increase in T-AOC, T-SOD, and GSH-Px activities were observed in rats pretreated with Se. In conclusion, Se pretreatment may protect rat lungs against inflammation and oxidative stress induced by PM2.5, which suggests that Se plays an important role as a kind of potential preventative agent to inhibit the PM2.5-induced lung injury.

VOC characteristics and inhalation health risks in newly renovated residences in Shanghai, China.

BACKGROUND: Exposure to indoor VOCs is expected to link to a variety of negative health outcome. The popularity of decorations and refurbishment in homes in China has given rise to indoor elevated VOC levels, potentially posing health threats to residents. METHODS: In this study, concentrations of 101 VOC compounds and associated health risks were investigated in newly renovated homes in Shanghai. The potential excess inhalation health risks from home exposure of 17 health-related VOCs were estimated by the Inhalation Unit Risk (IUR) and Reference Concentration (RfC) proposed by US EPA. Monte Carlo simulation and sensitivity analysis were used to assess the uncertainty associated with the estimates of health risks. RESULTS: The dominant groups by mass concentration were oxygenated VOCs (o-VOCs), aromatics, alkanes and halogenated VOCs (x-VOCs) .12 VOCs with IARC's confirmed or probable carcinogens ratings were detected with a >60% detection frequency in the total samples. The mean concentrations of BTEX (benzene, toluene, m/p-xylene, o-xylene, ethylbenzene) were 2.32µg/m3, 200.13µg/m3, 39.56µg/m3, 32.59µg/m3 and 26.33µg/m3 respectively, generally higher than those in older homes reported in previous studies except benzene. The mean concentration of methylene chloride (47.43µg/m3) and 1,2-dichloroethane (33.83µg/m3) were noticeably higher than the levels reported in previous studies in Hong Kong, Japan and Canada. Whereas the mean concentration of 1,4-dichlorobenzene (5.53µg/m3) were similar to the results of Canadian national survey but lower than those in Japan. The concentrations of 1,2-dichloroethane, 1,4-dichlorobenzene, and methylene chloride, ethylbenzene presented a mean cancer risk at 7.39×10-6, 1.95×10-6, 1.62×10-6, 1.04×10-6 respectively, above the US EPA proposed acceptable risk level of 1×10-6. Sensitivity analyses indicated that the VOC exposure concentration have a greater impact than the IUR values on the risk assessment. CONCLUSION: This study highlights the characteristics of VOCs in recently renovated homes and has implications for the adverse health effects that result from exposure to chlorinated hydrocarbons in indoor air.

Effect of Vitamin E and Omega-3 Fatty Acids on Protecting Ambient PM2.5-Induced Inflammatory Response and Oxidative Stress in Vascular Endothelial Cells.

Although the mechanisms linking cardiopulmonary diseases to ambient fine particles (PM2.5) are still unclear, inflammation and oxidative stress play important roles in PM2.5-induced injury. It is well known that inflammation and oxidative stress could be restricted by vitamin E (Ve) or omega-3 fatty acids (Ω-3 FA) consumption. This study investigated the effects of Ve and Ω-3 FA on PM2.5-induced inflammation and oxidative stress in vascular endothelial cells. The underlying mechanisms linking PM2.5 to vascular endothelial injury were also explored. Human umbilical vein endothelial cells (HUVECs) were treated with 50 µg/mL PM2.5 in the presence or absence of different concentrations of Ve and Ω-3 FA. The inflammatory cytokines and oxidative stress markers were determined. The results showed that Ve induced a significant decrease in PM2.5-induced inflammation and oxidative stress. Malondialdehyde (MDA) in supernatant and reactive oxygen species (ROS) in cytoplasm decreased by Ve, while the superoxide dismutase (SOD) activity elevated. The inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) also reduced by Ve. Moreover, Ω-3 FA played the same role on decreasing the inflammation and oxidative stress. IL-6 and TNF-α expressions were significantly lower in combined Ve with Ω-3 FA than treatment with Ve or Ω-3 FA alone. The Ve and Ω-3 FA intervention might abolish the PM2.5-induced oxidative stress and inflammation in vascular endothelial cells. There might be an additive effect of these two nutrients in mediating the PM2.5-induced injury in vascular endothelial cells. The results suggested that inflammation and oxidative stress might be parts of the mechanisms linking PM2.5 to vascular endothelial injury.

Hybrid Effect Evaluation of Steel Fiber and Carbon Fiber on the Performance of the Fiber Reinforced Concrete.

Fiber reinforcement is an important method to enhance the performance of concrete. In this study, the compressive test and impact test were conducted, and then the hybrid effect between steel fiber (SF) and carbon fiber (CF) was evaluated by employing the hybrid effect index. Compressive toughness and impact toughness of steel fiber reinforced concrete (SFRC), carbon fiber reinforced concrete (CFRC) and hybrid fiber reinforced concrete (HFRC) were explored at steel fiber volume fraction 0.5%, 1%, 1.5% and carbon fiber 0.1%, 0.2%, 0.3%. Results showed that the addition of steel fiber and carbon fiber can increase the compressive strength. SF, CF and the hybridization between them could increase the compressive toughness significantly. The impact test results showed that as the volume of fiber increased, the impact number of the first visible crack and the ultimate failure also increased. The improvement of toughness mainly lay in improving the crack resistance after the first crack. Based on the test results, the positive hybrid effect of steel fiber and carbon fiber existed in hybrid fiber reinforced concrete. The relationship between the compressive toughness and impact toughness was also explored.

Rat lung response to ozone and fine particulate matter (PM2.5) exposures.

Exposure to different ambient pollutants maybe more toxic to lung than exposure to a single pollutant. In this study, we discussed the inflammation and oxidative stress responses of rat lung caused by ozone and PM2.5 versus that of rats exposed to saline, ozone, or single PM2.5 . Wistar rats inhaled 0.8 ppm ozone or air for 4 h and then placed in air for 3 h following intratracheal instillation with 0, 0.2 (low dose), 0.8 (medium dose), 3.2 (high dose) mg/rat PM2.5 dissolved in sterile saline (0.25 mL/rat), repeated twice per week for 3 weeks, the cumulative doses of PM2.5 in animals were 1.2, 4.8, and 19.2 mg. Rats were sacrificed 24 h after the last (sixth) exposure. The collected bronchoalveolar lavage fluid (BALF) was analyzed for inflammatory cells and cytokines. Lung tissues were processed for light microscopic and transmission electron microscopic (TEM) examinations. Results showed that total cell number in BALF of PM2.5 -exposed groups were higher than control (p < 0.05). PM2.5 instillation caused dose-trend increase in tumor necrosis factor alpha (TNF-α), interleukin-6, lactate dehydrogenase, and total protein of BALF. Exposure to ozone alone only caused TNF-α significant change in above-mentioned indicators of lung injury. On the other hand, ozone could enhance PM2.5-induced inflammatory changes and pathological characters in rat lungs. SOD and GSH-Px activities in lung were reduced in PM2.5-exposed rats with and without prior ozone exposure compared to control. To determine whether the PM2.5 and ozone affect endothelium system, iNOS, eNOS, and ICAM-1 mRNA levels in lung were analyzed by real-time PCR. These data demonstrated that inflammation and oxidative stress were involved in toxicology mechanisms of PM2.5 in rat lung and ozone potentiated these effects induced by PM2.5. These results have implications for understanding the pulmonary effects induced by ozone and PM2.5.

[Effects of airborne fine particulate matters on pulmonary inflammation injury and Th17/Treg balance of sub-chronic exposure mice].

OBJECTIVE: To explore effects of fine particulate matters (PM 2.5) onpulmonary inflammation, and the changes of Th17/Treg balance as well as related cytokines. METHOD: Thirty-two C57BL/6 male mice were randomly divided into 4 groups including 1 saline control group and 3 PM2.5 exposure groups (1.5, 7.5 and 15 mg/kg BW, respectively). Each group received intratracheal instillation twice per week for 3 consecutive months. 24 hours after the last exposure, anaesthetize the mice with chloral hydrate, bronchoalveolar lavage fluid (BALF) was collected for inflammatory cells and cytokines analysis. The Th17- and Treg-related cytokines in BALF was measured by enzyme linked immunosorbent assay (ELISA). The level of the specific transcription factors of Th17 and Treg in lung tissue was determined by real-time PCR. Unlavaged left lung were fixed with 4% paraformaldehyde for histopathological detection. RESULTS: Th17-related cytokine IL-17 increased, but Treg-related cytokine IL-10 decreased significantly in BALF at 7.5 and 15 mg/kg BW PM2.5 exposure groups compared with control group (P < 0.05). Consistently, the relative mRNA expression of ROR-gammat (specific transcription factors of Th17) increased in a dose-response way, the relative mRNA expression of Foxp3 + (specific transcription factors of Treg) decreased in a dose-response way. CONCLUSION: Sub-chronic PM2.5 exposure caused persistent inflammation, immune injury and disordered the Th17/Treg imbalance as well as related cytokines.

Effects of atorvastatin on fine particle-induced inflammatory response, oxidative stress and endothelial function in human umbilical vein endothelial cells.

The study is to explore the toxicity of organic extracts and water-soluble fraction of fine particles on human umbilical vein endothelial cells (HUVECs). The exposure doses were 100, 200 and 400 µg/ml, respectively, for two kinds of fractions. Moreover, atorvastatin was used for intervention study. HUVECs were stimulated by 400 µg/ml organic and water soluble extracts, respectively, immediately followed by treatment with atorvastatin in concentrations of 0.1 µmol/L, 1 µmol/L and 10 µmol/L, respectively. Cell viability, malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), reactive oxygen species (ROS) and the expression of interleukin-6 beta (IL-6), tumor necrosis factor-α (TNF-α), endothelin-1 and P-selectin were determined in cells. The results showed that MDA and ROS increased in HUVECs after exposed to organic extracts and water-soluble fraction, whereas cell viability, NO and SOD decreased. The mRNA expression of IL-6, TNF-α, endothelin-1 (ET-1) and P-selectin increased after exposed to different fractions. Meanwhile, at the same exposure dose, water-soluble fraction caused more significant increase of MDA, IL-6, TNF-α and P-selectin and decrease of cell viability and NO when compared to organic extracts. Compared to no atorvastatin group, the levels of MDA, ROS and the expression of IL-6, TNF-α, ET-1 and P-selectin decreased in HUVECs in adding atorvastatin group, but cell viability, NO and SOD increased, which indicated that atorvastatin attenuated fine particle-induced inflammatory response, oxidative stress and endothelial damage. The results hinted that the inflammatory response, oxidative stress and endothelial dysfunction might be the mechanisms of cardiovascular injury induced by different fractions of ambient fine particles.

Association analyses identify six new psoriasis susceptibility loci in the Chinese population.

We extended our previous genome-wide association study for psoriasis with a multistage replication study including 8,312 individuals with psoriasis (cases) and 12,919 controls from China as well as 3,293 cases and 4,188 controls from Germany and the United States and 254 nuclear families from the United States. We identified six new susceptibility loci associated with psoriasis in the Chinese study containing the candidate genes ERAP1, PTTG1, CSMD1, GJB2, SERPINB8 and ZNF816A (combined P < 5 × 10⁻8) and replicated one locus, 5q33.1 (TNIP1-ANXA6), previously reported (combined P = 3.8 × 10⁻²¹) in the European studies. Two of these loci showed evidence for association in the German study at ZNF816A and GJB2 with P = 3.6 × 10⁻³ and P = 7.9 × 10⁻³, respectively. ERAP1 and ZNF816A were associated with type 1 (early onset) psoriasis in the Chinese Han population (test for heterogeneity P = 6.5 × 10⁻³ and P = 1.5 × 10⁻³, respectively). Comparisons with the results of previous GWAS of psoriasis highlight the heterogeneity of disease susceptibility between the Chinese and European populations. Our study identifies new genetic susceptibility factors and suggests new biological pathways in psoriasis.

[Study of genetic damage of human B lymphocyte cell line induced by 14 nm and 280 nm carbon black particles in vitro].

OBJECTIVE: To assess the genetic damage of human B lymphocyte cell line induced by 14 nm and 280 nm carbon black (CB) particles with micronucleus assay (CBMN), comet assay and hprt gene mutation test in vitro. METHODS: The genetic damage of human B lymphocyte cells exposed to 14 nm and 280 nm CB particles at the doses of 0, 128, 256, 384 and 512 microg/ml for 24 h and 48 h was detected using above three genotoxic assays. Micronucleus (MN) assay, comet assay, hprt gene mutation test were used to detect the genetic damage of human B lymphocyte cells induced by CB. Micronucleus rate (MNR), micronucleated cell rate (MCR), nuclear buds (Buds), nucleoplasmic bridges (NPBs), nuclear division index (NDI) and numbers of apoptotic cells served as indexes of CBMN assay; the percentage of DNA in the tail (% tail DNA) and the olive tail moment (OTM) were used as DNA damage indicators of comet assay; the hprt gene mutation frequency (Mf-hprt) served as the index of hprt gene mutation test. RESULTS: The % tail DNA, OTM in 14 nm CB group at the doses of 384 and 512 microg/ml for 48 h were 8.23% +/- 0.19%, 11.23% +/- 0.42% and 3.72 +/- 0.08, 4.90 +/- 0.18, respectively, which were significantly higher than those in control (5.10% +/- 0.08% and 2.22 +/- 0.03) (P < 0.01). The apoptotic cell rates in 14 nm CB group at the doses of 384 and 512 microg/ml for 48 h were 4.67 +/- 0.33 and 5.33 +/- 0.33, respectively, which were significantly higher than in control (0.00 +/- 0.00) (P < 0.05). The results of Mf-hprt were negative. CONCLUSION: The genetic damage of human B lymphocyte cells exposed to 14 nm CB particles for 48 h could be detected. But the similar effects didn't appear in 280 nm CB group.