Myriocin induces apoptotic lung cancer cell death via activation of DR4 pathway

It has been known that myriocin inhibits melanoma growth. However, the effects and action mechanisms of myriocin on lung cancer cell growth have not been reported. In this study, we examined whether myriocin isolated from Mycelia sterilia inhibits cell growth of lung cancer cells (A549 and NCI-H460) as well as possible signaling pathways involved in cell growth inhibition. Different concentrations of myriocin inhibited the growth of lung cancer cells through the induction of apoptotic cell death. Consistent with cancer cell growth inhibition, myriocin induced the expression of death receptors (DRs) as well as p-JNK and p-p38 in both cell lines. Moreover, the combination of myriocin with DR4 ligand TRAIL, and other well known anti-tumor drugs (docetaxel and cisplatin) synergistically inhibited cancer cell growth, and induced DR4 expression. These results showed that myriocin inhibits lung cancer cells growth through apoptosis via the activation of DR4 pathways, and enhanced anti-cancer effects with well known drugs. Thus, our study indicates that myriocin could be effective for lung cancer cells as an anti-cancer drug and/or a conjunction agent with well known anti-cancers.     

Polychlorinated Biphenyls Disrupt Intestinal Integrity via NADPH Oxidase-Induced Alterations of Tight Junction Protein Expression

Background

Polychlorinated biphenyls (PCBs) are widely distributed environmental toxicants that contribute to numerous disease states. The main route of exposure to PCBs is through the gastrointestinal tract; however, little is known about the effects of PCBs on intestinal epithelial barrier functions.

Objective

The aim of the present study was to address the hypothesis that highly chlorinated PCBs can disrupt gut integrity at the level of tight junction (TJ) proteins.

Methods

Caco-2 human colon adenocarcinoma cells were exposed to one of the following PCB congeners: PCB153, PCB118, PCB104, and PCB126. We then assessed NAD(P)H oxidase (NOX) activity and expression and the barrier function of Caco-2 cells. In addition, the integrity of intestinal barrier function and expression of TJ proteins were evaluated in C57BL/6 mice exposed to individual PCBs by oral gavage.

Results

Exposure of Caco-2 cells to individual PCB congeners resulted in activation of NOX and increased permeability of fluorescein isothiocyanate (FITC)-labeled dextran (4 kDa). Treatment with PCB congeners also disrupted expression of TJ proteins zonula occludens-1 (ZO-1) and occludin in Caco-2 cells. Importantly, inhibition of NOX by apocynin significantly protected against PCB-mediated increase in epithelial permeability and alterations of ZO-1 protein expression. Exposure to PCBs also resulted in alterations of gut permeability via decreased expression of TJ proteins in an intact physiological animal model.

Conclusions

These results suggest that oral exposure to highly chlorinated PCBs disrupts intestinal epithelial integrity and may directly contribute to the systemic effects of these toxicants.     

Use of the Optomap with lid retraction and its sensitivity and specificity#

Background: Optomap uses the ultra‐wide field scanning laser ophthalmoscopy to provide retinal examination. It permits fundus examination without the use of a mydriatic, which is more comfortable for the patients. This paper determines the sensitivity and specificity of the Optomap for detecting retinal signs under non‐mydriatic conditions. Methods: Fifty‐four eyes identified with retinal/choroidal signs and eight normal eyes were recruited from 31 Hong Kong Chinese subjects. Photo‐documentation of fundal changes was obtained with the Optomap under non‐mydriatic conditions before a dilated fundus examination by a clinician using standard procedures. The eyelid was retracted using a cotton bud when necessary. Dilated fundus examinations were performed by another clinician using binocular indirect ophthalmoscopy and slitlamp biomicroscopy with a fundus lens. The Optomap images were evaluated by four other investigators under masked condition. The International Classification of Disease, Ninth Revision (ICD‐9‐CM) was adopted for recording retinal features. Screening results were compared with those obtained using the dilated fundus examination as the gold standard. Results: The cotton bud method for eyelid retraction showed an improvement in the area of retina that could be visualised. The sensitivity and specificity of the Optomap averaged 76.4 and 71.9 per cent, respectively. Some fundal signs were missed by all observers in the Optomap but not with the biomicroscope. These included white‐without‐pressure, lattice degeneration, paramacular drusen and pigmentary changes at central fundus. Conclusion: Optomap serves as a reliable screening tool for fundus examination especially because it covers a much wider area of the peripheral retina than other digital instruments for fundus photography.     

A profile of the online dissemination of national influenza surveillance data

Background  

Influenza surveillance systems provide important and timely information to health service providers on trends in the circulation of influenza virus and other upper respiratory tract infections. Online dissemination of surveillance data is useful for risk communication to health care professionals, the media and the general public. We reviewed national influenza surveillance websites from around the world to describe the main features of surveillance data dissemination.     

Relation of cumulative low-level lead exposure to depressive and phobic anxiety symptom scores in middle-age and elderly women

Background: Different lines of evidence suggest that low-level lead exposure could be a modifiable risk factor for adverse psychological symptoms, but little work has explored this relation.Objective: We assessed whether bone lead—a biomarker of cumulative lead exposure—is associated with depression and anxiety symptoms among middle-age and elderly women.Methods: Participants were 617 Nurses’ Health Study participants with K-shell X-ray fluorescence bone lead measures and who had completed at last one Mental Health Index 5-item scale (MHI-5) and the phobic anxiety scale of the Crown-Crisp Index (CCI) assessment at mean ± SD age of 59 ± 9 years (range, 41–83 years). With exposure expressed as tertiles of bone lead, we analyzed MHI-5 scores as a continuous variable using linear regression and estimated the odds ratio (OR) of a CCI score ≥ 4 using generalized estimating equations.Results: There were no significant associations between lead and either outcome in the full sample, but associations were found among premenopausal women and women who consistently took hormone replacement therapy (HRT) between menopause and bone lead measurement (n = 142). Compared with women in the lowest tertile of tibia lead, those in the highest scored 7.78 points worse [95% confidence interval (CI): –11.73, –3.83] on the MHI-5 (p-trend = 0.0001). The corresponding OR for CCI ≥ 4 was 2.79 (95% CI: 1.02, 7.59; p-trend = 0.05). No consistent associations were found with patella lead.Conclusions: These results provide support for an association of low-level cumulative lead exposure with increased depressive and phobic anxiety symptoms among older women who are premenopausal or who consistently take postmenopausal HRT.     

Cumulative Lead Exposure and Age at Menopause in the Nurses’ Health Study Cohort

Background: Early menopause has been associated with many adverse health outcomes, including increased risk of cardiovascular disease morbidity and mortality. Lead has been found to be adversely associated with female reproductive function, but whether exposures experienced by the general population are associated with altered age at menopause has not been explored.Objective: Our goal was to assess the association between cumulative lead exposure and age at natural menopause.Methods: Self-reported menopausal status and bone lead concentration measured with K-shell X-ray fluorescence—a biomarker of cumulative lead exposure—were obtained from 434 women participants in the Nurses’ Health Study.Results: The mean (± SD) age at natural menopause was 50.8 ± 3.6 years. Higher tibia lead level was associated with younger age at menopause. In adjusted analyses, the average age of menopause for women in the highest tertile of tibia lead was 1.21 years younger (95% CI: –2.08, –0.35) than for women in the lowest tertile (p-trend = 0.006). Although the number of cases was small (n = 23), the odds ratio for early menopause (< 45 years of age) was 5.30 (95% CI: 1.42, 19.78) for women in the highest tertile of tibia lead compared with those in the lowest tertile (p-trend = 0.006). There was no association between patella or blood lead and age at menopause.Conclusions: Our results support an association between low-level cumulative lead exposure and an earlier age at menopause. These data suggest that low-level lead exposure may contribute to menopause-related health outcomes in older women through effects on age at menopause.Citation: Eum KD, Weisskopf MG, Nie LH, Hu H, Korrick SA. 2014. Cumulative lead exposure and age at menopause in the Nurses’ Health Study Cohort. Environ Health Perspect 122:229–234; http://dx.doi.org/10.1289/ehp.1206399     

Tat-DJ-1 inhibits oxidative stress-mediated RINm5F cell death through suppression of NF-κB and MAPK activation

Oxidative stress is highly involved in the development of diabetes mellitus by destruction of pancreatic β-cells. DJ-1 is an antioxidant protein and DJ-1 expression levels are known to be reduced in diabetes mellitus. Thus, we examined the effects of DJ-1 protein against oxidative stress-induced pancreatic β-cell (RINm5F) death using cell permeable wild-type and mutant-type (C106A) Tat-DJ-1 proteins, which both efficiently transduced into RINm5F cells. Intracellular stability of wild-type Tat-DJ-1 persisted two times longer than C106A Tat-DJ-1. Wild-type Tat-DJ-1 protein markedly protected cells from hydrogen peroxide-induced toxicities such as cell death, reactive oxygen species generation, and DNA fragmentation. Further, wild-type Tat-DJ-1 protein significantly inhibited hydrogen peroxide-induced activation of mitogen-activated protein kinases and NF-κB signaling. On the other hand, C106A Tat-DJ-1 protein did not show the same protective effects. These results indicate that wild-type Tat-DJ-1 inhibits oxidative stress-induced cellular toxicity and activation of mitogen-activated protein kinases and NF-κB signals in RINm5F cells. These results suggest that wild-type Tat-DJ-1 protein may be a potential therapeutic agent against diabetes mellitus or toward the prevention of pancreatic β-cell destruction.     

Psychometric properties of the Korean version of the job content questionnaire: data from health care workers

Objectives To test the validity and reliability of selected scales, namely, decision latitude, psychological job demand, social support, job insecurity, and macro-level decision latitude from the Korean version of the job content questionnaire (K-JCQ), as part of a psychosocial epidemiological study among university hospital workers. Methods K-JCQ was developed by translation and back translation complying with the JCQ usage policy, and its psychometric properties were explored among 338 workers (290 females and 48 males) in a university hospital in Korea. Internal consistency was examined using Cronbach’s alpha correlation coefficients. Factorial validity was tested using exploratory factor analysis. Pearson’s correlation coefficients were used for test–retest reliability among a subset of 157 workers who responded to a repeat survey. Criterion-related validity was assessed by investigating the effects of the scales on job satisfaction and self-identity through work in multiple regression models. Results Cronbach’s alpha for all selected scales was higher than 0.6, except for job insecurity (0.53) and macro-level decision authority (0.52), indicating appropriate internal consistency. Correlation coefficients between test and retest scales of decision latitude, psychological job demand, and social support were 0.60, 0.41, and 0.35, respectively. Exploratory factor analysis found three- and four-factor models, i.e., with and without macro-level decision latitude, respectively, closely corresponding to the theoretical constructs. High levels of decision latitude and social support, and low levels of psychological job demand and job insecurity were significantly associated with high level of job satisfaction. Higher self-identity through work was positively related to decision latitude and social support. Conclusions These findings suggest that K-JCQ is valid and reliable for assessing psychosocial job stress among Korean workers. Macro-level decision latitude showed a separate factorial structure and was strongly associated with task-level decision latitude.     

大鼠红细胞流变性变化及抗运动疲劳效应与补服肉碱和糖的作用

目的:观察单独和配合补充肉碱和糖对大鼠红细胞流变性及抗运动疲劳能力的影响。方法:实验于2005-09/11于河北师范大学体育学院运动生理学实验室完成。①选用SD雄性大鼠72只,按随机数字表法分为4组:安静组(n=6)、安静补服组(n=18)、安慰运动组(n=12)和补服运动组(n=36)。安静补服组和补服运动组均给予3种药物形式:左旋肉碱(由沈阳东宇精细化工有限公司生产)、葡萄糖(济南利民制药有限公司生产)、肉碱和葡萄糖。安静补服组和补服运动组每天上午8∶30给予自来水溶解的肉碱和/或糖补剂,安静组和安慰运动组给予相同量的自来水。连续补充7d,补服量:肉碱组、葡萄糖组、肉碱 葡萄糖组分别为650mg/(kg·d),7g/(kg·d),325mg/(kg·d) 3.5g/(kg·d)。②在实验第8天,将安静组取血4mL。安慰运动组和补服运动组进行无负重游泳至力竭,然后取血。采用北京泰诺德新技术研究所生产的BV-100型无摩擦式血液流变仪测全血高切黏度(180s-1)、全血高切还原黏度(180s-1)、全血低切黏度(3s-1)、全血低切还原黏度(3s-1)、刚性指数及聚集指数。③计量资料进行正态分布、方差齐性检验后,再进行方差分析。结果:大鼠72只均进入结果分析。①红细胞流变性指标变化:安静补服组各组虽大部分红细胞流变性指标有改善,但与安静组相比,差异无显著性意义(P>0.05)。安慰运动组运动后5min全血高切黏度和全血高切还原黏度明显高于安静组(P<0.01),运动24h后全血高、低切黏度和红细胞聚集指数明显高于安静组(P<0.01)。一次力竭运动后5min各补服运动组全血低切黏度明显低于安慰运动组(P<0.01)。各组间红细胞刚性指数和红细胞聚集指数差异不明显(P>0.05)。各补服运动组间相比,补服肉碱组的全血低切还原黏度最高(P<0.01)。各补服运动组运动后24h全血低切还原黏度和红细胞聚集指数明显低于安慰运动组(P<0.05～0.01),补服肉碱和肉碱 葡萄糖运动组全血低切还原黏度和全血低切黏度、红细胞聚集指数明显高于补服葡萄糖运动组(P<0.05～0.01)。②抗疲劳作用:补服肉碱、葡萄糖、肉碱 葡萄糖运动组大鼠游泳时间分别为(334.5±27.81),(321.0±51.83),(326.5±39.9)min,均长于安慰运动组[(252.5±42.69)min,P<0.01];各补服运动组间差异不明显(P>0.05)。结论:单独补充或合用肉碱和糖均有利于力竭运动后大鼠红细胞流变性指标的改善,导致其运动能力的提高。