Bisphenol A exposure alters release of immune and developmental modulators and expression of estrogen receptors in human fetal lung fibroblasts

Bisphenol A(BPA) has been shown to exert biological effects through estrogen receptor(ER)-dependent and ER-independent mechanisms. Recent studies suggest that prenatal exposure to BPA may increase the risk of childhood asthma. To investigate the underlying mechanisms in the actions of BPA, human fetal lung fibroblasts(h FLFs) were exposed to varying doses of BPA in culture for 24 hr. Effects of BPA on localization and uptake of BPA,cell viability, release of immune and developmental modulators, cellular localization and expression of ERα, ERβ and G-protein coupled estrogen receptor 30(GPR30), and effects of ERs antagonists on BPA-induced changes in endothelin-1(ET-1) release were examined.BPA at 0.01–100 μmol/L caused no changes in cell viability after 24 hr of exposure. h FLFs expresses all three ERs. BPA had no effects on either cellular distribution or protein expression of ERα, however, at 100 μmol/L(or 23 μmol/L intracellular BPA) increased ERβprotein levels in the cytoplasmic fractions and GPR 30 protein levels in the nuclear fractions.These paralleled with increased release of growth differentiation factor-15, decreased phosphorylation of nuclear factor kappa B p65 at serine 536, and decreased release of ET-1,interleukin-6, and interferon gamma-induced protein 10. ERs antagonists had no effects on BPA-induced decrease in ET-1 release. These data suggest that BPA at 100 μmol/L altered the release of immune and developmental modulators in h FLFs, which may negatively influence fetal lung development, maturation, and susceptibility to environmental stressors, although the role of BPA in childhood asthma remains to be confirmed in in vivo studies.     

PM2.5水溶性和有机组分对肺上皮细胞损伤及COPD相关基因和蛋白表达影响

为了检测大气PM_(2.5)对正常肺上皮细胞(BEAS-2B)的损伤作用和慢性阻塞性肺病(COPD)相关基因及蛋白的表达变化,将PM_(2.5)的不同组分对肺上皮细胞进行染毒24 h后,通过MTT、荧光探针、Western Blot、单细胞凝胶电泳、实时荧光定量PCR、ELISA等方法检测细胞损伤、COPD相关基因和蛋白表达的变化情况.结果发现,PM_(2.5)可造成肺上皮细胞活性降低,且呈剂量依赖性,PM_(2.5)的不同组分对细胞造成的损伤也不同,有机相组分在细胞凋亡、紧密连接蛋白表达量、DNA损伤和炎症反应等方面造成的影响都比水相组分严重,而水相组分在氧化应激反应和COPD相关蛋白变化程度方面的作用都高于有机相组分.由此可见,PM_(2.5)可对肺上皮细胞造成多种不同程度、不同水平的损伤作用,其中,氧化应激可能是影响COPD相关基因和蛋白表达的重要因素.     

Radon and lung cancer in Finland: are there signs of radiation hormesis?

Prolonged exposure to any level of radon in indoor air is generally thought to be hazardous to human health and to give rise to lung cancer. On the other hand, low or moderate levels of radon in indoor air may, according to the radiation hormesis hypothesis, be beneficial to human health and even inhibit the growth of cancerous cells. An attempt is made here to test these contrasting views by comparing mortality rates from lung cancer during the 10-year period 1986–1995 with average indoor radon levels in the 435 communes (municipalities) of Finland (excluding Åland). The results show a very low, statistically non-significant correlation between radon and lung cancer mortality (r=–0.0331), which in turn implies that at least in this case neither the possible beneficial hormetic effect of radon nor its cancer-provoking hazardous effect can make itself apparent against the dominant and masking effect of cigarette smoking, the main cause of lung cancer.     

Residential Radon in U.S. Counties V Lung Cancer in Women Who Predominantly Never Smoked

Previous studies have found that mean-residential-radon (Rn) levels for U.S. counties are negatively associated with age-adjusted county rates of lung-cancer mortality (LCM), after adjustments for potentially confounding factors. Those results may be due to (a) confounding unaddressable by any county-level (ecological) study design, or (b) county-level factors such as Rn/smoking or age/radon correlations or exposure misclassifications from the use of disparate data sources. Possibilities (b) were addressed by comparing age-specific LCM rates for white women in 2821 U.S. counties who died in 1950–54 at age 40+ (11% of whom ever smoked), or at age 60+ (% of whom ever smoked), to county Rn levels newly estimated from U.S. Rn, climatic and geological-survey data. Significant negative LCM v Rn trends were found for both age groups, after adjusting for age and subsets of 21 county-level socioeconomic, climatic and other factors. Negative trends were largest for counties with 100 Bq m^–3 Rn (p 0.00087; 420 analyses). Adjusted relative risk (RR_adj) for LCM was significantly elevated (1 < [95% conf. limits on RR_adj] 1.46) in 43 of 210 analyses comparing LCM rates in counties with > 150 Bq m^–3 v 65–100 Bq m^–3 Rn, most involving adjustment for climate- and education-related factors likely to have influenced exposure to indoor air contaminants such as Rn and cigarette smoke. Though inconclusive due to potential ecological-fallacy-related confounding that could not be controlled, results from this ecological study are most consistent with a U-shaped dose-response relationship between 1950–54 LCM risk and U.S. residential radon in white women who predominantly never smoked.     

吸烟烟气对鼠肺细胞膜的损伤和茶多酚的保护作用

本文以香烟气相物质作用鼠肺细胞膜为模型,用脂肪酸自旋标记物5-DOXYL和16DOXYL分别研究膜浅层和深层的动态性质受气相烟的影响,并用紫外可见分光光度法研究气相烟对膜脂的作用。结果发现,在实验的气相烟流量下,香烟气相物质能引发鼠肺细胞膜的脂质过氧化,并且使膜浅层的流动性增大。但对膜深层的动态性质没有明显的改变,如果在鼠肺细胞中预先加入粗晶态或粉态茶多酚。则肺细胞的过氧化和膜的动态性质改变受到抑制,而且这种抑制作用与茶多酚浓度呈量效关系,而茶多酚本身对膜浅层无明显作用,但对膜深层的流动性有一定影响,而且两种茶多酚的作用相似。     

Amniotic fluid analysis in a fetus with laryngeal atresia

Complete laryngeal atresia is a rare congenital malformation that is known to cause hypertrophy of the fetal lung in utero. A fetus with laryngeal atresia was found to have markedly immature amniotic fluid lung maturity studies at term. Inappropriately low amniotic fluid lung maturity studies may be an important clue to the diagnosis of this condition.     

多壁碳纳米管引起白鼠肺部毒性的评价(Comparative Pulmonary Toxic Assessment of Mutil-Wall Carbon Nanotubes in Rats)

以雄性Wistar大白鼠为研究对象,观察了多壁碳纳米管(MWNTs)体内暴露后肺部的病理学变化.采用气管注入方式将直径为40～60nm多壁碳纳米管(40～60MWNTs)和直径小于10nm的多壁碳纳米管(10MWNTs)暴露于大白鼠的体内,同时分别采用纳米二氧化硅(SiO2)和乙炔碳黑(Cb)作为阳性和阴性对照.实验结果表明:实验中采用的纳米颗粒均不同程度地引起了肺部的损伤,同剂量下损伤严重程度顺序为:Cb>10MWNTs>40～60MWNTs>SiO2.多壁碳纳米管对肺部损伤的程度与剂量呈依赖关系,当在低剂量(1mg·kg-1)时,40～60MWNTs仅仅对肺部引起了轻微的炎症损伤,随着剂量的增大,多壁碳纳米管对肺部的损伤越来越严重,出现明显的病理损伤.     

Characterization of enzymes responsible for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) detoxification pathway in lungs of Chinese population: Carbonyl reduction and glucuronidation

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most potent carcinogens found in mainstream and sidestream smoke and considered to be a causative agent for lung cancer in active and passive smokers. Carbonyl reduction followed by glucuronidation is considered to be the main detoxification pathway of NNK. Microsomal 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD 1) and cytosolic carbonyl reductase (CR) are responsible for NNK carbonyl reduction, and UDP-glucuronosyltransferase 1A4 (UGT1A4) and UDP-glucuronosyltransferase 2B7 (UGT2B7) catalyze 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) glucuronidation. To better characterize this pathway, the expression and kinetics of 11β-HSD 1 and CR, as well as the expression of UGT1A4 and UGT2B7, was investigated in lungs of Chinese people. Kinetic studies for 11β-HSD 1 and CR showed that there was large inter-individual variability in the capacity for NNK carbonyl reduction. Compared with cytosol, there was increased catalytic efficiency for NNAL formation in microsomes. The higher activities of both 11β-HSD 1 and CR were observed in lung tissues of males than females. UGT1A4 and UGT2B7 mRNA were detected in lungs from a variety of different patients and wide inter-individual variations were observed. These observations should be useful in improving the risk estimates and prevention of lung cancer for the Chinese population exposed to tobacco smoke.     

Characterization and in vitro biological effects of ambient air PM10 from a rural,an industrial and an urban site in Sulaimani City,Iraq

Abstract

High urban atmospheric pollution is caused by economic and industrial growth, especially in developing countries. The objective of this study was to assess possible relationships between in vitro effects on human alveolar epithelial cells of source-related dust types collected at Sulaimani City (Iraq), and to determine their mineralogical and chemical composition. A passive sampler was used to collect dust particles at a rural, an industrial and an urban sampling site during July and August 2014. The samples were size-fractionated by a low-pressure impactor to obtain respirable dust with aerodynamic diameters of less than 10?µm. The dust was mainly composed of quartz and calcite. Chrysotile fibers (white asbestos) were also found at the urban site. Dust from the industrial and urban sites triggered cytotoxic and genotoxic effects in the cells, whereas only minor effects were observed for the sample from the rural site.     

Impact of environmental and socio-economic stressors leading to unequal distribution of COVID-19 incidences in the state of Louisiana

Louisiana (LA) ranks fifth in the United States in cancer mortality rate. LA's infamous “cancer alley” is a well evidenced region near the southeast part of the Mississippi river surrounding the petrochemical hub of the state. LA has also experienced a high COVID-19 death rate and incidences compared to other states during the recent pandemic. In this study we analyzed publicly available datasets related to health and socio-economic parameters in LA to determine the factors triggering high incidences and deaths caused by COVID-19. Correlation analysis was performed to find the impact of different parameters on the outcome of COVID-19. Our analysis showed higher COVID-19 incidences in the parishes which are in and around the “cancer alley” with a correlation of r = 0.9. Interestingly, results also indicated a strong correlation (r = 0.9) between the death rates caused by asbestos toxicity to COVID-19 caused death rate. Furthermore, we found that office-administration related employment has a positive correlation to COVID-19 incidences in the “cancer alley.” However, we also found both white and black races are equally affected by the COVID-19 pandemic in the “cancer alley” region. In conclusion, our analysis strongly suggests that inhabiting “cancer alley” could significantly enhance the chances of getting affected by SARS-CoV-2 virus compared to other regions in LA.