Changes in cortisol awakening responses (CAR) in menopausal women through short-term marine healing retreat program with specific factors affecting each CAR index.

Recent studies have reported that the cortisol awakening response (CAR) is associated with various health risks. The different indices used to represent the CAR include the average cortisol levels in the morning immediately after waking (AVE); the total area under the curve of cortisol levels with respect to ground (AUCg); and the area under the curve of cortisol levels with respect to increase (AUCi). However, it is unclear which physiological phenomenon each index reflects. This study investigated the factors, such as stress, circadian rhythm, sleep, and obesity, affecting the CAR through a marine retreat-based healing program in which the anticipated stress of the participants could be controlled to some degree. Fifty-one menopausal women in their 50s and 60s were included, who performed beach yoga and Nordic walking for four days at an uncontaminated beach. The baseline CAR indices showed that the AVE and AUCg were significantly higher in the high sleep efficiency group than in the low sleep efficiency group. However, the AUCi decreased substantially with increasing age. The changes in the AVE, AUCg, and AUCi were calculated through the program, and it was found that the AVE and AUCg increased significantly more in the obese group than in the normal and overweight groups. The obese group also showed significantly decreased serum triglyceride and BDNF (brain-derived neurotrophic factor) levels compared to the low BMI group. Thus, it was confirmed that AVE and AUCg reflected physiological phenomena affected by factors such as sleep efficiency and obesity, whereas the AUCi was affected by factors such as age. In addition, the marine retreat program can improve the low levels of CAR associated with obesity and aging.

Effect of the Marine Exercise Retreat Program on Thyroid-Related Hormones in Middle-Aged Euthyroid Women.

This study aimed to investigate the effects of a marine exercise retreat program on thyroid-related hormone levels. A total of 62 middle-aged euthyroid women participated in a 6-day marine exercise retreat program. Using thyroid-stimulating hormone (TSH) and free thyroxine (fT4) hormone levels, the participants were divided into high and low-hormone-level groups. Despite decreased TSH and fT4 levels after the program, the factors influencing changes in each group were different. TSH levels were influenced by changes in the normalized low frequency (nLF) of heart rate variability and carbon monoxide (CO) from all the participants, and changes in body fat percentage, nLF, and nitrogen dioxide (NO2) exposure level in the high TSH group. fT4 levels were influenced by changes in body mass index (BMI), NO2 exposure, and particulate matter diameter of 10 µm or less (PM10) exposure in all participants. Changes in BMI and CO exposure influenced the low fT4 group. Lastly, changes in the exercise stress test affected the high fT4 group. Thus, the marine exercise retreat program affected euthyroid thyroid-related hormone levels, and influencing factors differ depending on the initial value of the hormone.

Reduced branched-chain aminotransferase activity alleviates metabolic vulnerability caused by dim light exposure at night in Drosophila.

The rhythmic pattern of biological processes controlled by light over 24 h is termed the circadian rhythm. Disturbance of circadian rhythm due to exposure to light at night (LAN) disrupts the sleep-wake cycle and can promote cardiovascular disease, diabetes, cancer, and metabolic disorders in humans. We studied how dim LAN affects the circadian rhythm and metabolism using male Drosophila. Wild-type flies exposed to the dim light of 10 lux at night displayed altered 24 h sleep-wake behavior and expression patterns of circadian rhythm genes. In addition, the flies became more vulnerable to metabolic stress, such as starvation. Whole-body metabolite analysis revealed decreased amounts of branched-chain amino acids (BCAAs), such as isoleucine and valine. The dim light exposure also increased the expression of branched-chain amino acid aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKDC) enzyme complexes that regulate the metabolism of BCAAs. Flies with the Bcat heterozygous mutation were not vulnerable to starvation stress, even when exposed to dim LAN, and hemolymph BCAA levels did not decrease in these flies. Furthermore, the vulnerability to starvation stress was also suppressed when the Bcat expression level was reduced in the whole body, neurons, or fat body during adulthood using conditional GAL4 and RNA interference. Finally, the metabolic vulnerability was reversed when BCAAs were fed to wild-type flies exposed to LAN. Thus, short-term dim light exposure at night affects the expression of circadian genes and BCAA metabolism in Drosophila, implying a novel function of BCAAs in suppressing metabolic stress caused by disrupted circadian rhythm.

Plasma Proteomic Signature of Cellular Senescence and Markers of Biological Aging Among Postmenopausal Women.

We aimed to investigate the association of circulatory senescence-associated secretory phenotypes (SASPs) produced by senescent cells with chronological and menopausal age in women aged 45 years or more. The proteomic profiles for 32 SASP factors of plasma samples were measured in 76 healthy postmenopausal women aged 46-82 years from the Korean Genome and Epidemiology Study Cardiovascular Disease Association Study (KoGES-CAVAS). We assessed the association between the SASP factors and aging indicators (chronological age, menopausal age, and years since menopause) using single- and multiprotein models. First, we composed a profile of proteins associated with chronological age, menopausal age, and years since menopause. In a single-protein model, three proteins (growth differentiation factor 15 [GDF15], insulin-like growth factor binding protein-2 [IGFBP-2], and tumor necrosis factor-α [TNF-α]) are positively associated with chronological age. Menopausal age and years since menopause are interrelated with interleukin-8 (IL-8). The direction of association between menopausal age and monocyte chemoattractant protein-1 (MCP-1) was only negative, and IGFBP-2 and TNF-α were significant in all three aging factors. We also constructed parsimonious multiprotein models to confirm the association of the proteomic signature for aging after adjusting for covariates and the combination of proteomic signature of 13 proteins (GDF15, interferon-γ [IFN-γ], IGFBP-2, IGFBP-7, IL-15, IL-1ß, IL-17A, IL-8, MCP-1, tissue inhibitors of metalloproteinase-2 [TIMP-2], TNF-α, vascular endothelial growth factor-A [VEGF-A], and interferon-inducible protein 10 [IP-10]) appear to be associated with chronological age and menopausal state of individuals. Thus, by observing association between the selected SASPs and age-related markers among healthy postmenopausal women, we examine how menopause in women relates to proteomic indicators of aging and highlight the potential use of SASP factors as a marker to reflect the state of biological aging attributed by ovarian senescence.

Females with impaired ovarian function could be vulnerable to environmental pollutants: identification via next-generation sequencing of the vaginal microbiome.

The vaginal microbiome has been widely investigated. However, its relationship with impaired ovarian function has not been evaluated. We conducted a next-generation sequencing (NGS) study of the vaginal microbiome in females with normal and decreased ovarian function and analysed its sensitivity to environmental pollutants. Vaginal swabs were collected from 92 individuals (22 with impaired ovarian function). The 16S rDNA sequences were assembled by FLASH and clustered in OTUs. Diversity analysis was performed using QIIME. The impaired function group showed lower AMH (p < .01) and higher FSH (p = .04). Only two species showed significant differences: Propionibacterium acnes and Prevotella copri. Moreover, more environmental pollutants were related to changes in the vaginal microbiome in the impaired ovarian function group than in the normal group. Vaginal microbiomes in young women with decreased ovarian function tended to be more sensitive to environmental pollutants, especially volatile organic compounds.Impact StatementWhat is already known on this subject? In this study, the possible influence of environmental pollutants, especially volatile organic compounds to ovarian function were identified via next-generation sequencing.What do the results of this study add? This is the first study that shows vaginal microbiomes in young women with decreased ovarian function to be more sensitive to environmental pollutants.What are the implications of these findings for clinical practice and/or further research? The association between impaired ovarian function and environmental pollutants from this study could be helpful when counselling patients with POI.

Association between environmental pollutants and the FSH/AMH ratio as a marker of ovarian reserve.

The ovarian function decreases with age, and various markers, such as follicle stimulating hormone, inhibin B, antral follicle count, and anti-Müllerian hormone, are used for its evaluation. Recently, exposure to various environmental pollutants in daily life has been reported as an important cause of ovarian function decline. Therefore, the present study aimed to confirm the effect of environmental pollutants on the relationship between age and decline in ovarian function. The exposure levels of 16 environmental pollutants were evaluated in women aged 26-40 years, and the AMH levels and FSH/AMH ratios were used as markers for the decline of ovarian function. The participants were divided into two groups: low-level or high-level for each environmental pollutant if their exposure level was below or above the median respectively. The slope of the decrease or increase in the AMH level and FSH/AMH ratio of each group with age was evaluated. The FSH/AMH ratio better presented the difference in the rate of change with age in each group than did AMH alone. In particular, the rate of change in the FSH/AMH ratio increased 5.2 and 3.7 times (p<0.05) in the group exposed to high levels of the volatile organic compound metabolite, trans, trans-muconic acid and the polycyclic aromatic hydrocarbons metabolite, 2-hydroxynaphthalene, respectively, than in the low-level exposure groups for those metabolites. This study confirmed that environmental pollutants influenced the rate of change in the FSH/AMH ratio with age. Further studies on larger populations are necessary in the future.

Assessment of an Emergency Medicine System for Radiation Accidents in Korea: A State Survey of the Workers Involved the Medical Response to Radiation Accidents.

Radiation emergency medicine systems are operated around the world to provide special care for the injured that require immediate medical attention in accidents. The objective of this survey was to evaluate people's perception of those who design the emergency medical plan for radiation accidents and those who supervise it in Korea. A questionnaire survey was conducted on the people involved in a regulatory system for medical response in a radiation emergency. Of 150 survey recipients, 133 (88.7%) completed the survey, including 92 workers and 41 inspectors. The respondents expressed the view that the national emergency medical plan is prepared above the average level using a Likert-style scale of 1 to 5 (mean = 3.55, SD = 0.74). Interestingly, using the Mann-Whitney U test, it could be shown that inspectors evaluated the emergency medical system for radiation accidents more strictly in all of the questions than the licensee workers, especially on radiation medical emergency preparedness (p = 0.004) and the governmental regulatory policy for radiation safety (p = 0.007). For a more efficient system of radiation emergency medicine, licensee workers prioritized the workforce, whereas inspectors favored laws and regulations for safety. The survey results show different perspectives between inspectors and licensee workers, which stem from the actual properties of each occupational role in the regulatory system for radiation medical emergency. These data could be utilized for communication and interaction with relevant people to improve the medical response preparedness against radiation accidents.

Effects of Asian dust-derived particulate matter on ST-elevation myocardial infarction: retrospective, time series study.

BACKGROUND: Dust storms affect human health by impairing visibility and promoting interactions with microscopic organisms, such as bacteria and fungi. Although ST-elevation MI (STEMI) and non-ST-elevation MI (NSTEMI) differ mechanistically, few studies have investigated the incidence of cardiovascular diseases according to infarction type; these studies have yielded inconsistent findings. This study aimed to examine whether PM size (< 2.5 µm (PM2.5) and < 10 µm (PM10)) modifies the effect of Asian dust on acute myocardial infarction (AMI), with separate analyses for STEMI and NSTEMI. METHODS: MI-related data from 9934 emergency visits were collected from the Korea AMI Registry from 2005 to 2017. Asian dust events were defined as days with visibility of ≤10 km. Generalized linear models were used to analyze data with natural cubic splines. To examine potential modifiers, analyses were stratified by age, smoking status, and body mass index (BMI). RESULTS: No significant associations were observed between Asian dust and AMI. By adjusting for different lag structures, a significant effect was exclusively observed in STEMI. For moving average lags, the largest value at lag 5 (relative risk [RR] 1.083; 95% confidence interval [CI], 1.007-1.166) for single and lags 0-7 (RR 1.067; 95% CI: 1.002-1.136) was observed for PM2.5; for PM10, the largest significant effect was observed at lag 4 (RR 1.075; 95% CI: 1.010-1.144) for single and lags 0-7 (RR 1.067; 95% CI: 1.002-1.136). RRs were significantly higher in < 65-year-olds than in ≥65-year-olds. Additionally, RRs between the BMI < 25 and BMI ≥ 25 groups were not different; statistically significant effects were observed for concentration at lags 0-5 (RR: 1.073; 95% CI: 1.002-1.150) and lags 0-6 (RR: 1.071; 95% CI: 1.001-1.146) in the BMI < 25 group. A negative exposure-response association was observed between daily average visibility-adjusted PM and STEMI and daily average visibility-adjusted PM in < 65-year-olds. CONCLUSIONS: Reducing PM2.5 and PM10 emissions, particularly during the days of Asian dust, may be crucial and reduce STEMI and AMI incidence among < 65-year-olds. These results indicate that the Asian dust alarm system needs revision to protect vulnerable populations.

Association of an APBA3 Missense Variant with Risk of Premature Ovarian Failure in the Korean Female Population.

Premature ovarian failure (POF) is a complex disease of which the etiology is influenced by numerous genetic variations. Several POF candidate genes have been reported. However, no causal genes with high odds ratio (OR) have yet been discovered. This study included 564 females of Korean ethnicity, comprising 60 patients with POF and 182 controls in the discovery set and 105 patients with POF and 217 controls in the replication set. We conducted genome-wide association analysis to search for novel candidate genes predicted to influence POF development using Axiom Precision Medicine Research Arrays and additive model logistic regression analysis. One statistically significant single nucleotide polymorphism (SNP), rs55941146, which encodes a missense alteration (Val > Gly) in the APBA3 gene, was identified with OR values for association with POF of 13.33 and 4.628 in the discovery and replication sets, respectively. No rs55941146 minor allele homozygotes were present in either cases or controls. The APBA3 protein binds FIH-1 that inhibits hypoxia inducible factor-1α (HIF-1α). HIF-1α contributes to granulosa cell proliferation, which is crucial for ovarian follicle growth, by regulating cell proliferation factors and follicle stimulating hormone-mediated autophagy. Our data demonstrate that APBA3 is a candidate novel causal gene for POF.

Bibliometric analysis of studies about acute myeloid leukemia conducted globally from 1999 to 2018.

A bibliometric study is performed to analyze publication patterns in a specific research area and to establish a landscape model that can be used to quantitatively weigh publications. This study aimed to investigate AML research networks and to conduct a trend-related keyword analysis. We analyzed 48,202 studies about AML published from 1999 to 2019 in the Web of Science Core Collection. The network analysis was conducted using the R&R studio software. The journal Blood had the highest number of published articles with an h-index of 410. The USA had the highest number of total publications (18,719, 38.3%) and research funded by the government, institutions, and pharmaceutical companies (5,436, 10.8%). The institute with the largest number of publications was the MD Anderson Cancer Center. Kantarjian H, Garcia-Manero G, and Ravandi F were the leading authors of publications about AML. Keyword analysis revealed that FLT 3, micro-RNA, and NK cell topics were the hotspots in the cell and gene area in all publications. The overall AML research landscape is popular in the field of translational research as it can identify molecular, cell, and gene studies conducted by different funding agencies, countries, institutions, and author networks. With active funding and support from the Chinese government, the productivity of scientific research is increasing not only in the AML field but also in the medical/health-related science field.

The Association between Bisphenol A Exposure and Obesity in Children-A Systematic Review with Meta-Analysis.

Bisphenol A (BPA) is an environmental chemical that has adverse effects on health, probably causing childhood obesity. However, this association remains controversial, and it is difficult to find evidence for direct causality between environmental exposure and disease using epidemiological studies. In this study, we sought to elucidate the possible causality between BPA exposure and childhood obesity by conducting two meta-analyses showing bidirectional associations, including exposure effect by obesity and obesity risk by exposure. Articles published up to September 2017 were searched in PubMed, Embase, and Cochrane Library. We evaluated observational studies that included measurements of urinary BPA concentration and BMI or body weight. Of 436 articles, a total of 13 studies were included in the meta-analysis. Two meta-analyses were performed to investigate the association between BPA exposure and childhood obesity. The results showed that the relatively high-exposed group had a significantly higher risk of childhood obesity than the relatively low-exposed group (odds ratio = 1.566, 95% confidence interval [CI]: 1.097 to 2.234, p = 0.014). However, the obese group showed no significant difference in the BPA concentration when compared to the normal group (standardized mean difference = 0.166, 95% CI: -0.121 to 0.453, p = 0.257). This study suggested possible causality between BPA exposure and childhood obesity using data from epidemiological studies and showed that BPA exposure itself increased the risk of obesity in children.

Identification of serum biomarkers for premature ovarian failure.

Premature ovarian failure (POF) is defined when a female achieves menopause before the age of 40. Although many conditions are known to be causative for POF, the most common one is idiopathic. This study was undertaken to investigate the pathogenesis of POF using proteomic tools. Two-dimensional electrophoresis (2-DE) analysis was performed to screen for proteins differentially expressed in patients with POF. Using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS), we identified 11 significant proteins differentially expressed in the serum of POF patients: 5 proteins with expression increased more than two folds, 5 proteins with expression decreased more than two folds, and 1 protein expressed specifically in the serum of patients with POF. The results of the 2-DE analysis were further validated by Western blotting and ELISA analyses, which 5 reproductive system-related proteins (Ceruloplasmin, Complement C3, Fibrinogen α, Fibrinogen ß, and SHBG) were selected. The different expression levels for these proteins were confirmed and demonstrated the possibility of using them as biomarkers to screen POF. These pre-clinical data provide plausible translational implications for targeting the pathogenesis of POF for each protein.

Increase in anthropogenic mercury in marginal sea sediments of the Northwest Pacific Ocean.

Over the past century, the addition of anthropogenic mercury (HgANTH) to vast areas of North Pacific marginal seas adjacent to the northeast Asian continent has tripled. Analysis of sediment cores showed that the rate of HgANTH addition (HgANTH flux) was greatest in the East China and Yellow Seas (9.1 µg m-2 yr-1) in the vicinity of China (the source continent), but was small in the Bering and western Arctic Ocean (Chukchi Sea) (0.9 µg m-2 yr-1; the regions furthest from China). Our results show that HgANTH has reached open ocean sedimentary environments over extended areas of the northwestern Pacific Ocean, via the formation of organic-mercury complexes and deposition. The implication of these findings is that the addition of HgANTH (via atmospheric deposition and riverine input) to the ocean environment is responsible for elevated Hg flux into sedimentary environments in the northwest Pacific Ocean.

Bright light exposure before bedtime impairs response inhibition the following morning: a non-randomized crossover study.

INTRODUCTION: Bright light exposure in the late evening can affect cognitive function the following morning either by changing the biological clock and/or disturbing sleep, but the evidence for this effect is scarce, and the underlying mechanism remains unknown. In this study, we first aimed to evaluate the effect of bright light exposure before bedtime on frontal lobe activity the following morning using near-infrared spectroscopy (NIRS) during a Go/NoGo task. Second, we aimed to evaluate the effects of bright light exposure before bedtime on polysomnographic measures and on a frontal lobe function test the following morning. METHODS: Twenty healthy, young males (mean age, 25.5 years) were recruited between September 2013 and August 2014. They were first exposed to control light (150 lux) before bedtime (from 20:00 h to 24:00 h) for 2 days and then to bright light (1,000 lux) before bedtime for an additional 5 days. We performed polysomnography (PSG) on the final night of each light exposure period (on nights 2 and night 7) and performed NIRS, which measures the concentrations of oxygenated and deoxygenated hemoglobin (OxyHb and DeoxyHb, respectively), coupled with a Go/NoGo task the following morning (between 09:30 h and 11:30 h). The participants also completed frontal lobe function tests the following morning. RESULTS: NIRS showed decreased hemodynamic activity (lower OxyHb and a tendency toward higher DeoxyHb concentration) in the right frontal lobe during the NoGo block after 1000-lux light exposure compared with that during the NoGo block after 150-lux light exposure. The commission error rate (ER) during the Go/NoGo task was higher after 1000-lux light exposure than that during the Go/NoGo task after 150-lux light exposure (1.24 ± 1.09 vs. 0.6 ± 0.69, P = 0.002), suggesting a reduced inhibitory response. CONCLUSION: This study shows that exposure to bright light before bedtime for 5 days impairs right frontal lobe activation and response inhibition the following morning.

Impact of Exposure to Dim Light at Night on Sleep in Female and Comparison with Male Subjects.

OBJECTIVE: Light pollution has become a social and health issue. We performed an experimental study to investigate impact of dim light at night (dLAN) on sleep in female subjects, with measurement of salivary melatonin. METHODS: The 25 female subjects (Group A: 12; Group B: 13 subjects) underwent a nocturnal polysomnography (NPSG) session with no light (Night 1) followed by an NPSG session randomly assigned to two conditions (Group A: 5; Group B: 10 lux) during a whole night of sleep (Night 2). Salivary melatonin was measured before and after sleep on each night. For further investigation, the female and male subjects of our previous study were collected (48 subjects), and differences according to gender were compared. RESULTS: dLAN during sleep was significantly associated with decreased total sleep time (TST; F=4.818, p=0.039), sleep efficiency (SE; F=5.072, p=0.034), and Stage R latency (F=4.664, p=0.041) for female subjects, and decreased TST (F=14.971, p<0.001) and SE (F=7.687, p=0.008), and increased wake time after sleep onset (F=6.322, p=0.015) and Stage R (F=5.031, p=0.03), with a night-group interaction (F=4.579, p=0.038) for total sample. However, no significant melatonin changes. There was no significant gender difference of the impact of dLAN on sleep, showing the negative changes in the amount and quality of sleep and the increase in REM sleep in the both gender group under 10 lux condition. CONCLUSION: We found a negative impact of exposure to dLAN on sleep in female as well as in merged subjects. REM sleep showed a pronounced increase under 10 lux than under 5 lux in merged subjects, suggesting the possibility of subtle influences of dLAN on REM sleep.

Short-term exposure to dim light at night disrupts rhythmic behaviors and causes neurodegeneration in fly models of tauopathy and Alzheimer's disease.

The accumulation and aggregation of phosphorylated tau proteins in the brain are the hallmarks for the onset of Alzheimer's disease (AD). In addition, disruptions in circadian rhythms (CRs) with altered sleep-wake cycles, dysregulation of locomotion, and increased memory defects have been reported in patients with AD. Drosophila flies that have an overexpression of human tau protein in neurons exhibit most of the symptoms of human patients with AD, including locomotion defects and neurodegeneration. Using the fly model for tauopathy/AD, we investigated the effects of an exposure to dim light at night on AD symptoms. We used a light intensity of 10 lux, which is considered the lower limit of light pollution in many countries. After the tauopathy flies were exposed to the dim light at night for 3 days, the flies showed disrupted CRs, altered sleep-wake cycles due to increased pTau proteins and neurodegeneration, in the brains of the AD flies. The results indicate that the nighttime exposure of tauopathy/AD model Drosophila flies to dim light disrupted CR and sleep-wake behavior and promoted neurodegeneration.

The effect of dim light at night on cerebral hemodynamic oscillations during sleep: A near-infrared spectroscopy study.

Recent studies have reported that dim light at night (dLAN) is associated with risks of cardiovascular complications, such as hypertension and carotid atherosclerosis; however, little is known about the underlying mechanism. Here, we evaluated the effect of dLAN on the cerebrovascular system by analyzing cerebral hemodynamic oscillations using near-infrared spectroscopy (NIRS). Fourteen healthy male subjects underwent polysomnography coupled with cerebral NIRS. The data collected during sleep with dim light (10 lux) were compared with those collected during sleep under the control dark conditions for the sleep structure, cerebral hemodynamic oscillations, heart rate variability (HRV), and their electroencephalographic (EEG) power spectrum. Power spectral analysis was applied to oxy-hemoglobin concentrations calculated from the NIRS signal. Spectral densities over endothelial very-low-frequency oscillations (VLFOs) (0.003-0.02 Hz), neurogenic VLFOs (0.02-0.04 Hz), myogenic low-frequency oscillations (LFOs) (0.04-0.15 Hz), and total LFOs (0.003-0.15 Hz) were obtained for each sleep stage. The polysomnographic data revealed an increase in the N2 stage under the dLAN conditions. The spectral analysis of cerebral hemodynamics showed that the total LFOs increased significantly during slow-wave sleep (SWS) and decreased during rapid eye movement (REM) sleep. Specifically, endothelial (median of normalized value, 0.46 vs. 0.72, p = 0.019) and neurogenic (median, 0.58 vs. 0.84, p = 0.019) VLFOs were enhanced during SWS, whereas endothelial VLFOs (median, 1.93 vs. 1.47, p = 0.030) were attenuated during REM sleep. HRV analysis exhibited altered spectral densities during SWS induced by dLAN, including an increase in very-low-frequency and decreases in low-frequency and high-frequency ranges. In the EEG power spectral analysis, no significant difference was detected between the control and dLAN conditions. In conclusion, dLAN can disturb cerebral hemodynamics via the endothelial and autonomic systems without cortical involvement, predominantly during SWS, which might represent an underlying mechanism of the increased cerebrovascular risk associated with light exposure during sleep.

Widespread Anthropogenic Nitrogen in Northwestern Pacific Ocean Sediment.

Sediment samples from the East China and Yellow seas collected adjacent to continental China were found to have lower δ15N values (expressed as δ15N = [15N:14Nsample/15N:14Nair - 1] × 1000‰; the sediment 15N:14N ratio relative to the air nitrogen 15N:14N ratio). In contrast, the Arctic sediments from the Chukchi Sea, the sampling region furthest from China, showed higher δ15N values (2-3‰ higher than those representing the East China and the Yellow sea sediments). Across the sites sampled, the levels of sediment δ15N increased with increasing distance from China, which is broadly consistent with the decreasing influence of anthropogenic nitrogen (NANTH) resulting from fossil fuel combustion and fertilizer use. We concluded that, of several processes, the input of NANTH appears to be emerging as a new driver of change in the sediment δ15N value in marginal seas adjacent to China. The present results indicate that the effect of NANTH has extended beyond the ocean water column into the deep sedimentary environment, presumably via biological assimilation of NANTH followed by deposition. Further, the findings indicate that NANTH is taking over from the conventional paradigm of nitrate flux from nitrate-rich deep water as the primary driver of biological export production in this region of the Pacific Ocean.

Epidermal growth factor receptor (EGFR)-MAPK-nuclear factor(NF)-κB-IL8: A possible mechanism of particulate matter(PM) 2.5-induced lung toxicity.

Airway inflammation plays a central role in the pathophysiology of diverse pulmonary diseases. In this study, we investigated whether exposure to particulate matter (PM) 2.5, a PM with an aerodynamic diameter of less than 2.5 µm, enhances inflammation-related toxicity in the human respiratory system through activation of the epidermal growth factor receptor (EGFR) signaling pathway. Through cytokine antibody array analysis of two extracts of PM2.5 [water (W-PM2.5 ) and organic (O-PM2.5 ) soluble extracts] exposed to A549 (human alveolar epithelial cell), we identified eight cytokines changed their expression with W-PM2.5 and three cytokines with O-PM2.5 . Among them, epidermal growth factor (EGF) was commonly up-regulated by W-PM2.5 and O-PM2.5 . Then, in both groups, we can identify the increase in EGF receptor protein levels. Likewise, increases in the phosphorylation of ERK1/2 MAP kinase and acetylation of nuclear factor(NF)-κB were detected. We also detected an increase in IL-8 that was related to inflammatory response. And using the erlotinib as an inhibitor of EGFR, we identified the erlotinib impaired the phosphorylation of EGFR, ERK1/2, acetylation of NF-κB proteins and decreased IL-8. Furthermore, at in vivo model, we were able to identify similar patterns. These results suggest that PM2.5 may contribute to an abnormality in the human respiratory system through EGFR, MAP kinase, NF-κB, and IL-8 induced toxicity signaling. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1628-1636, 2017.

Integrative analysis of mRNA and microRNA expression of a human alveolar epithelial cell(A549) exposed to water and organic-soluble extract from particulate matter (PM)2.5.

MicroRNA (miRNA) is now attracting attention as a powerful negative regulator of messenger RNA(mRNA) levels, and is implicated in the modulation of important mRNA networks involved in toxicity. In this study, we assessed the effects of particulate matter 2.5 (PM2.5 ), one of the most significant air pollutants, on miRNA and target gene expression. We exposed human alveolar epithelial cell (A549) to two types of PM2.5 [water (W-PM2.5 ) and organic (O-PM2.5 ) soluble extracts] and performed miRNA microarray analysis. A total of 37 miRNAs and 62 miRNAs were altered 1.3-fold in W-PM2.5 and O-PM2.5 , respectively. Integrated analyses of miRNA and mRNA expression profiles identified negative correlations between miRNA and mRNA in both W-PM2.5 and O-PM2.5 exposure groups. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses showed that the 35 W-PM2.5 target genes are involved in responses to nutrients, positive regulation of biosynthetic processes, positive regulation of nucleobase, nucleoside, and nucleotide, and nucleic acid metabolic processes; while the 69 O-PM2.5 target genes are involved in DNA replication, cell cycle processes, the M phase, and the cell cycle check point. We suggest that these target genes may play important roles in PM2.5 -induced respiratory toxicity by miRNA regulation. These results demonstrate an integrated miRNA-mRNA approach for identifying molecular events induced by environmental pollutants in an in vitro human model. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 302-310, 2017.