Lactobacillus-derived extracellular vesicles counteract Aß42-induced abnormal transcriptional changes through the upregulation of MeCP2 and Sirt1 and improve Aß pathology in Tg-APP/PS1 mice.

Mounting evidence suggests that probiotics are beneficial for treating Alzheimer's disease (AD). However, the mechanisms by which specific probiotics modify AD pathophysiology are not clearly understood. In this study, we investigated whether Lactobacillus paracasei-derived extracellular vesicles (Lpc-EV) can directly act on neuronal cells to modify amyloid-beta (Aß)-induced transcriptional changes and Aß pathology in the brains of Tg-APP/PS1 mice. Lpc-EV treatment in HT22 neuronal cells counteracts Aß-induced downregulation of Brain-derived neurotrophic factor (Bdnf), Neurotrophin 3 (Nt3), Nt4/5, and TrkB receptor, and reverses Aß-induced altered expression of diverse nuclear factors, including the downregulation of Methyl-CpG binding protein 2 (Mecp2) and Sirtuin 1 (Sirt1). Systematic siRNA-mediated knockdown experiments indicate that the upregulation of Bdnf, Nt3, Nt4/5, and TrkB by Lpc-EV is mediated via multiple epigenetic factors whose activation converges on Mecp2 and Sirt1. In addition, Lpc-EV reverses Aß-induced downregulation of the Aß-degrading proteases Matrix metalloproteinase 2 (Mmp-2), Mmp-9, and Neprilysin (Nep), whose upregulation is also controlled by MeCP2 and Sirt1. Lpc-EV treatment restores the downregulated expression of Bdnf, Nt4/5, TrkB, Mmp-2, Mmp-9, and Nep; induces the upregulation of MeCP2 and Sirt1 in the hippocampus; alleviates Aß accumulation and neuroinflammatory responses in the brain; and mitigates cognitive decline in Tg-APP/PS1 mice. These results suggest that Lpc-EV cargo contains a neuroactive component that upregulates the expression of neurotrophic factors and Aß-degrading proteases (Mmp-2, Mmp-9, and Nep) through the upregulation of MeCP2 and Sirt1, and ameliorates Aß pathology and cognitive deficits in Tg-APP/PS1 mice.

Predictive model of Staphylococcus aureus growth on egg products.

Egg products are widely consumed in Korea and continue to be associated with risks of Staphylococcus aureus-induced food poisoning. This prompted the development of predictive mathematical models to understand growth kinetics of S. aureus in egg products in order to improve the production of domestic food items. Egg products were inoculated with S. aureus and observe S. aureus growth. The growth kinetics of S. aureus was used to calculate lag-phase duration (LPD) and maximum specific growth rate (µmax) using Baranyi model as the primary growth model. The secondary models provided predicted values for the temperature changes and were created using the polynomial equation for LPD and a square root model for µmax. In addition, root mean square errors (RMSE) were analyzed to evaluate the suitability of the mathematical models. The developed models demonstrated 0.16-0.27 RMSE, suggesting that models properly represented the actual growth of S. aureus in egg products.

Simultaneous analysis and exposure assessment of migrated bisphenol analogues, phenol, and p-tert-butylphenol from food contact materials.

A simple, rapid, and novel liquid chromatography tandem-mass spectrometry (LC-MS/MS) method was developed and validated to determine levels of eight bisphenol analogues (A, S, F, B, P, AF, AP, and Z), phenol, and p-tert-butylphenol migrated from food contact material (FCM) into food simulants. Method validation showed acceptable values in terms of linearity, precision, and accuracy. The limits of detection and quantification were 0.53-29.6 and 1.77-29.6 µg L-1, respectively. Water, 4% acetic acid, 50% ethanol, and n-heptane were employed as food simulants for the migration tests, and the proposed method was applied to 234 articles of 11 FCMs including polycarbonate, polyethersulfone, polypropylene, and polyethyleneterephthalate, obtained from domestic markets and manufacturers in Korea. Only phenol was found in the FCMs poly(cyclophexane-1,4-dimethylene terephthalate), polylactide, and thermoplastic polyurethane. Eight bisphenol analogues and p-tert-butyl phenol were not found in any samples. Using the obtained migration results, the estimated daily intake (EDI) of phenol was calculated. Exposure assessments were carried out to compare the EDI with the tolerable daily intake (TDI), showing a low percentage (0.18%) of the TDI reported. This is the first study to examine eight bisphenol analogues and two phenols simultaneously in FCMs using the LC-MS/MS.

Association between beverage intake and obesity in children: The Korea National Health and Nutrition Examination Survey (KNHANES) 2013-2015.

BACKGROUND/OBJECTIVES: Numerous researches have studied the association between sugar intake and obesity of children in many countries. This study was undertaken to investigate the association between beverage intake and obesity of children by reviewing a database for total sugar contents established in all foods and presented in a nutrition survey by the Korea National Health and Nutrition Examination Survey (KNHANES). SUBJECTS/METHODS: Data of 1,520 children aged 6-11 years in the 6th KNHANES (2013-2015) were analyzed for this study. A database for total sugar intake comprises the total sugar contents of all foods included in the results of a nutrition survey using the 24-hour recall method of 6th KNHANES. Beverages were categorized into carbonated beverages, fruit & vegetable drinks, other drinks, tea, and coffee. RESULTS: The average daily beverage intake of all children was 131.75 g/day, and the average daily total sugar intake in beverages was 13.76 g/day. Carbonated beverages had the highest intake rate (58.85 g/day) and also ranked highest for sugar intake (6.36 g/day). After adjusting for confounding variables, the odds ratio for obesity in children with beverage intake of ≥ 200 mL/day significantly increased by 1.83 times (95% CI, 1.11-3.00) as compared to children with beverage intake of < 200 mL/day. Also, a significant increase was observed in the odds ratio for obesity in total children (2.41 times; 95% CI, 1.35-4.33) and boys (3.15 times; 95% CI, 1.53-6.49) with carbonated beverage intake of ≥ 200 mL/day when compared with children who consumed < 200 mL/day. CONCLUSION: A positive association is observed between beverage intake and obesity in Korean children. In particular, an intake of carbonated beverages has a positive correlation with childhood obesity in boys. This study can therefore be used as scientific evidence for reducing sugar, and for the continuous management and research on beverages.

Veterinary drug, 17ß-trenbolone promotes the proliferation of human prostate cancer cell line through the Akt/AR signaling pathway.

Trenbolone acetate (TBA) is a synthetic anabolic steroidal growth factor that is used for rapid muscle development in cattle. The absorbed TBA is hydrolyzed to the active form, 17ß-trenbolone (17 TB; 17ß-hydroxy-estra-4,9,11-trien-3-one) in meat and milk products, which can cause adverse health effects in humans. Similar to 5α-dihydrotestosterone (DHT), 17 TB was reported to exhibit endocrine disrupting effects on animals and humans due to its androgenic effect via binding to the androgen receptor. The purpose of this study is to investigate the molecular mechanism of cell proliferation in prostate cancer (PCa) cells treated with 17 TB. We found that 17 TB induces AR-dependent cell proliferation in the human prostate cancer cell line, 22Rv1 in a concentration dependent manner. Treatment with 17 TB increased the expression of cell cycle regulatory proteins, cyclin D2/CDK-4 and cyclin E/CDK-2, whereas the expression of p27 was down-regulated. Furthermore, phosphorylation of Rb and activation of E2F were also induced, which suggests the activation of cyclin D2/CDK-4 and cyclin E/CDK-2 in the cells. When 22Rv1 cells were exposed to 30 pM of 17 TB, which is the effective concentration (EC50) value required to observe proliferative effects on 22Rv1 cells, the expression levels of the phosphorylated forms of Akt and GSK3ß were increased. This study demonstrates that 17 TB induces AR-dependent proliferation through the modulation of cell cycle-related proteins in the Akt signaling pathway. The present study provides an effective methodology for identifying cell proliferation signaling of veterinary drugs that exert AR agonistic effects.

Assessment of androgen receptor agonistic/antagonistic effects on 25 chemicals in household applicants by OECD in vitro stably transfected transcriptional activation assays.

The aim of this study is to assess the androgen receptor (AR) agonistic/antagonistic effects on various chemicals, which are used in household products including cleaning agents and wetted tissues by in vitro OECD test guideline No. 458 (using AR-EcoScreen™ cell line) and the me-too test method (using 22Rv1cell line), which was adopted as OECD project No. 4.99. All chemicals were not determined as AR agonists. However α-dodecyl-ω-hydroxypoly (oxyethylene) and 3-iodo-2-propynyl butylcarbamate have shown a weak AR antagonistic effects with IC50 values of 2.18 ±â€¯0.12 and 4.26 ±â€¯0.17 µg/ml via binding affinity to AR in only 22Rv1/mouse mammary tumor virus using AR transcriptional activation assay, because of their different cytotoxicity on each applied cell line. This report firstly provides information about agonistic/antagonistic effects against human AR of various chemicals including surfactants and biocides by OECD in vitro stably transfected transcriptional activation assays. However, further in vivo and human model studies are needed to confirm their adverse effects.

Safety assessment of 16 sweeteners for the Korean population using dietary intake monitoring and poundage method.

A sweetener is a food additive that imparts a sweet taste to food products. Sweeteners have been increasingly used in Korea since the approval of sodium saccharin and d-sorbitol in 1962. Unlike food contaminants, humans are exposed to food additives only through the consumption of processed food products. For exposure assessments of sweeteners, the dietary intakes of food products containing acesulfame-K, aspartame, saccharin-Na, and sucralose were determined, and the resulting calculated estimated daily intake (EDI) values were compared directly with each additive's ADI. The poundage method was used to calculate the daily intake per capita for 12 additional sweeteners, such as lactitol, for which appropriate analytical methods for food products do not exist. The risk, as evaluated by comparing the EDI with the ADI, was determined to be 2.9% for acesulfame-K, 0.8% for aspartame, 3.6% for saccharin-Na, 4.3% for steviol glycosides, and 2.1% for sucralose. No hazardous effect was predicted for the other 11 sweeteners, including lactitol.

Event-specific qualitative and quantitative detection of five genetically modified rice events using a single standard reference molecule.

One novel standard reference plasmid, namely pUC-RICE5, was constructed as a positive control and calibrator for event-specific qualitative and quantitative detection of genetically modified (GM) rice (Bt63, Kemingdao1, Kefeng6, Kefeng8, and LLRice62). pUC-RICE5 contained fragments of a rice-specific endogenous reference gene (sucrose phosphate synthase) as well as the five GM rice events. An existing qualitative PCR assay approach was modified using pUC-RICE5 to create a quantitative method with limits of detection correlating to approximately 1-10 copies of rice haploid genomes. In this quantitative PCR assay, the square regression coefficients ranged from 0.993 to 1.000. The standard deviation and relative standard deviation values for repeatability ranged from 0.02 to 0.22 and 0.10% to 0.67%, respectively. The Ministry of Food and Drug Safety (Korea) validated the method and the results suggest it could be used routinely to identify five GM rice events.

In vitro OECD test methods applied to screen the estrogenic effect of chemicals, used in Korea.

In this study, 27 chemicals found in household products, which became an issue in Korea were screened for the agonistoc and antagonistic effects against human estrogen receptor using official Organization for Economic Cooperation and Development (OECD) in vitro assays, STTA assay using ERα-HeLa-9903 cell line and BG1Luc ER TA assay. In the case of human ER agonist screening by two assays, all tested chemicals did not show agonist effect against ER. In ER antagonist test by BG1Luc ER TA assay, five surfactants α-dodecyl-ω-hydroxypoly(oxyethylene), alcohols C16-18 ethoxylated, nonylphenol, ethoxylated, 3,6,9,12,15,18,21-heptaoxatritriacontan-1-ol, and α-dodecyl-ω-hydroxypoly(oxy-1,2-ethanediyl)) were found to exhibit weak antagonistic activities. The agonist/antagonist effects against human estrogen receptor of various chemicals, used in Korea by OECD test guideline are reported in this study. These results indicated that two OECD in vitro assays will can be applied in Korea by screening of agonistic/antagonistic effects against human ER of various chemicals.

Urinary benzophenone concentrations and their association with demographic factors in a South Korean population.

Benzophenone (BP) and its derivatives are widely used in various cosmetics, personal care products, and food packaging ink. The use of BP has raised concerns about the potential health risks associated with its endocrine-disrupting effects. This study evaluated urinary concentrations of BP derivatives in a national sample of the South Koreans population aged 6-89 years. From July to September in each 2010 and 2011, 1576 urine samples were collected. Urinary concentrations of benzophenone-1 (BP-1), benzophenone-2 (BP-2), benzophenone-3 (BP-3), benzophenone-4 (BP-4), benzophenone-8 (BP-8), and 4-hydroxybenzophenone (4-OH-BP) were analyzed using liquid chromatography-mass spectrometry. The detection rate for BP-1 and 4-OH-BP were 56% [limit of detection (LOD) 0.59ng/mL] and 88% (LOD 0.04ng/mL), respectively, whereas those for BP-2, BP-3, BP-4, and BP-8 were all below 25%. The geometric means of urinary BP-1 and 4-OH-BP concentrations were 1.24ng/mL and 0.45ng/mL, respectively. Multiple linear regression analysis indicated that concentrations of BP-1 in and of 4-OH-BP in adults were associated with sex and age. The BP-1 and 4-OH-BP concentration of children and adolescents was associated with sex, age, income, and current area of residence. The correlation was observed between urinary concentrations of BP derivatives, which is an important indication of exposure biomarkers and the metabolic pathways from BP-3. This is the first national study to evaluate the presence of BP derivatives in urine samples from the South Korean population, stratified by demographic factors.

Urinary concentrations of parabens and their association with demographic factors: A population-based cross-sectional study.

Parabens are broad-spectrum antimicrobial agents used in a range of consumer products, including personal care products, cosmetics, and food. Recently, the widespread use of parabens has raised concerns about the potential health risks associated with their endocrine-disrupting effect. In the present study, 2541 urine samples were collected and analyzed by liquid chromatography-mass spectrometry for the determination of the concentrations of methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP) and butyl paraben (BuP). The detection rate and geometric mean concentrations of parabens in the general population followed the order MeP (97.7%; 116ng/mL)>EtP (97.2%; 24.7ng/mL)>PrP (96.7%; 11.0ng/mL)>BuP (83.5%; 1.13ng/mL). The composition profiles showed that MeP and EtP accounted for >90% of the urinary paraben concentration. We performed statistical analysis in order to evaluate differences between demographic variables and urinary concentrations. Our results showed that adjusted proportional change of MeP, PrP, and BuP in adults were 2.67-6.13 times higher in females than in males. The urinary concentrations of PrP in adults increased significantly with age. The adjusted proportional changes of MeP and PrP in adults were associated with increased body mass index (BMI). The adjusted proportional changes of BuP and PrP in children and adolescents were 1.44 and 1.69 times higher in females than in males. However, there was no clear association between paraben concentrations and demographic variables in the children and adolescents groups. The estimated daily intake (EDIurine) of MeP and EtP in adults were 301µg/kg bw/day, which is lower than the acceptable daily intake (ADI; 10mg/kg bw/day). In summary, our results revealed that the general population in Korea was exposed to parabens during 2009-2010, and most Koreans are exposed to parabens. The urinary levels of parabens varied by age group with demographic factors in the Korean population. The results of study may be used to establish a nationally representative baseline of exposure to parabens in risk assessment.

Corrigendum to "Exposure to Dichlorodiphenyltrichloroethane and the Risk of Breast Cancer: A Systematic Review and Meta-analysis [Volume 5, Issue 2, April 2014, Pages 77-84]".

[This corrects the article DOI: 10.1016/j.phrp.2014.02.001.].

A simplified and accurate detection of the genetically modified wheat MON71800 with one calibrator plasmid.

With the increasing number of genetically modified (GM) events, unauthorized GMO releases into the food market have increased dramatically, and many countries have developed detection tools for them. This study described the qualitative and quantitative detection methods of unauthorized the GM wheat MON71800 with a reference plasmid (pGEM-M71800). The wheat acetyl-CoA carboxylase (acc) gene was used as the endogenous gene. The plasmid pGEM-M71800, which contains both the acc gene and the event-specific target MON71800, was constructed as a positive control for the qualitative and quantitative analyses. The limit of detection in the qualitative PCR assay was approximately 10 copies. In the quantitative PCR assay, the standard deviation and relative standard deviation repeatability values ranged from 0.06 to 0.25 and from 0.23% to 1.12%, respectively. This study supplies a powerful and very simple but accurate detection strategy for unauthorized GM wheat MON71800 that utilizes a single calibrator plasmid.

Total mercury concentrations in the general Korean population, 2008-2011.

The purpose of this study was to evaluate the blood mercury levels of the general Korean population. The data from subjects of all ages were pooled from recent national surveys. In the combined surveys, the geometric means (GMs) of the blood mercury concentrations in subjects aged 0-7, 8-18, and 19years and above were 2.05 (2010-2011), 2.12 (2010-2011), and 3.74µg/L (2008-2011), respectively. There was an increasing trend in blood mercury levels with age until 59years and then a slight decline in the group above 60years. The time trend for exposure to mercury in Korea also showed a marked decline. In comparing estimated methylmercury exposure to the Korean health-based guidance value (tolerable weekly intake [TWI]: 2.0µg/kgbw/week), the GMs of methylmercury exposure for subjects aged 0-7, 8-18, and 19years and above were 0.30, 0.31, and 0.43µg/kgbw/week, respectively, while methylmercury exposure did not exceed the TWI (15.0%, 15.5%, and 21.5% compared to the TWI, respectively). The 95th percentiles of estimated methylmercury exposure ranged from 0.71 to 1.61µg/kgbw/week, which was not above the TWI (range, 35.5-80.5%).

Bisphenol A exerts estrogenic effects by modulating CDK1/2 and p38 MAP kinase activity.

Bisphenol A (BPA) is considered to be an endocrine disruptor, but the mechanisms by which it disrupts endocrine functions are poorly understood. Here, we have shown that BPA binds both estrogen receptor (ER)-α and ER-beta (ER-ß) using a fluorescence polarization competitive binding assay. In addition, we found that BPA induced cell proliferation by modulating cell cycle-related genes in the MCF-7 human mammary cancer cell line. Moreover, using a BG1 luciferase ER transactivation assay, we found that BPA has estrogenic activity. Modulating the MAPK pathway by using an ERK inhibitor (PD98059) or a JNK inhibitor (SP600125) had no effect on the ability of BPA to induce estrogenic activity. However, the antiestrogen, ICI 182,780, and the p38 inhibitor, PD 169316 successfully blocked BPA-induced estrogenic activity. Our findings suggest that BPA mimics ER-dependent estrogenic activity by targeting proteins that regulate the cell cycle and p38 MAPK.

Exposure to Dichlorodiphenyltrichloroethane and the Risk of Breast Cancer: A Systematic Review and Meta-analysis.

OBJECTIVES: This study extended and updated a meta-analysis of the association between exposure to dichlorodiphenyltrichloroethane (DDT) and the risk of breast cancer. METHODS: We reviewed the published literature on exposure to DDE and breast cancer risk to update a meta-analysis from 2004. The total of 35 studies included 16 hospital-based case-control studies, 11 population-based case-control studies, and 10 nested case-control studies identified through keyword searches in the PubMed and EMBASE databases. RESULTS: The summary odds ratio (OR) for the identified studies was 1.03 (95% confidence interval 0.95-1.12) and the overall heterogeneity in the OR was observed (I (2) = 40.9; p = 0.006). Subgroup meta-analyses indicated no significant association between exposure to DDE and breast cancer risk by the type of design, study years, biological specimen, and geographical region of the study, except from population-based case-control studies with estimated DDE levels in serum published in 1990s. CONCLUSION: Existing studies do not support the view that DDE increases the risk of breast cancer in humans. However, further studies incorporating more detailed information on DDT exposure and other potential risk factors for breast cancer are needed.

Association between Urinary Bisphenol A and Waist Circumference in Korean Adults.

Bisphenol A (BPA) is widely used in the production of polycarbonate plastics, epoxy resins, and food and beverage containers. In the present study, we aimed to investigate the relationship between urinary concentrations of BPA and waist circumference in Korean adults. A total of 1,030 Korean adults (mean age, 44.3 ± 14.6 years) were enrolled in the study on the integrated exposure to hazardous materials for safety control, conducted by the Ministry of Food and Drug Safety from 2010 to 2012. Abdominal obesity was defined as having a waist circumference of at least 90 cm and 85 cm for men and women, respectively. The participants were divided into 4 groups according to the urinary BPA concentration quartile. Waist circumference was significantly higher among subjects with a urinary BPA concentration in the highest quartile relative to those in the lowest quartile (p = 0.0071). Linear regression analysis revealed a significant positive association between urinary BPA concentrations and body mass index, body fat, after adjusting for potential confounders. Moreover, subjects with urinary BPA concentrations in the fourth quartile were more likely to be obese compared to those with urinary BPA concentrations in the first quartile (odds ratio, 1.938; 95% CI: 1.314~2.857; p for trend = 0.0106). These findings provide evidence for a positive association between urinary BPA concentration and waist circumference in Korean adults.

Effect of di(n-butyl) phthalate on testicular oxidative damage and antioxidant enzymes in hyperthyroid rats.

This study compared the effects of di(n-butyl) phthalate (DBP) on the oxidative damage and antioxidant enzymes activity in testes of hyperthyroid rats. Hyperthyroidism was induced in pubertal male rats by intraperitoneal injection of triiodothyronine (T3, 10 microg/kg body weight) for 30 days. An oral dose of DBP (750 mg/kg) was administered simultaneously to normal or hyperthyroid (T3) rats over a 30-day period. No changes in body weight were observed in the hyperthyroid groups (T3, T3 + DBP) compared with controls. There were significantly higher serum T3 levels observed in the hyperthyroid rats than in the control, but the serum thyroid stimulating hormone levels were markedly lower in the hyperthyroid rats. DBP significantly decreased the weight of the testes in the normal (DBP) and hyperthyroid (T3 + DBP) groups. The serum testosterone concentrations were significantly lower in only DBP group. DBP significantly increased the 8-hydroxy-2-deoxyguanosine (8-OHdG) level in the testes, whereas the DBP-induced 8-OHdG levels were slightly higher in T3 + DBP group. Superoxide dismutase and glutathione peroxidase activities were significantly higher in the testes of the DBP or T3 + DBP groups. Catalase (CAT) activity was significantly higher in the DBP treatment group, but the T3 + DBP group showed slightly lower DBP-induced CAT activity. The testicular expression of thyroid hormone receptor alpha-1 (TRalpha-1) was significantly higher in the DBP groups, and androgen receptor (AR) expression was not detected in the DBP treatment group. In addition, DBP significantly increased the peroxisome proliferator-activated receptor-r (PPAR-r) levels in the testis. These results suggest that hyperthyroidism can cause a change in the expression level of PPAR-r in testes, and may increase the levels of oxidative damage induced by the metabolic activation of DBP.

Gestational exposure to nonylphenol causes precocious mammary gland development in female rat offspring.

This study examined whether or not exposure to 4-nonylphenol (NP) during late gestation affects reproductive and mammary development in the offspring of female rats. Time pregnant Long Evans rats were gavaged with NP (10 or 100 mg/kg), atrazine (ATR, 100 mg/kg), or corn oil on gestation days 15-19. The uterus weights of the NP (100 mg/kg/d)-exposed pups were higher than those of the controls but the weights of the other organs were unchanged. Delayed mammary gland (MG) development was detected in the ATR pups on PND 4 and persisted through to PND 66. The high dose NP pups had advanced lobular development of their MG on PND 22, while the glands from the low dose NP pups were no different morphologically from the controls. Immunohistochemical comparisons of the mammary sections from PND 41 demonstrated low levels of estrogen receptor (ER) staining in the control gland stroma and epithelium but higher levels in the tissue of the pups exposed to NP and ATR. ATR also elevated ER in the stroma surrounding the epithelial layer of the terminal end buds. The level of progesterone receptor (PR) staining was markedly lower in the epithelium of the 100 mg/kg NP glands vs. the control glands. However, PR was present at high levels in the epithelium of the 10 mg/kg NP glands and was even more prominent in the ATR-exposed ductal epithelium and fat cell nuclei. The level of prolactin staining was only elevated in glands containing lobule areas (NP-exposed) compared with the control levels. These results suggest that NP and ATR have opposite effects on the development of MG after gestational exposure. Exposure to them during the critical period of epithelial outgrowth altered the receptor levels of mammary progesterone and prolactin and might contribute to the differences in the mammary morphology at PND 41.