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Background: Clarifying the physicochemical properties of nanomaterials is crucial for hazard assessment and the safe application of these substances. With this in mind, we analyzed the relationship between particle size and the in vitro effect of amorphous nanosilica (nSP). Specifically, we evaluated the relationship between particle size of nSP and the in vitro biological effects using human keratinocyte cells (HaCaT). Results: Our results indicate that exposure to nSP of 70 nm diameter (nSP70) induced an elevated level of reactive oxygen species (ROS), leading to DNA damage. A markedly reduced response was observed using submicron-sized silica particles of 300 and 1000 nm diameter. In addition, cytochalasin D-treatment reduced nSP70-mediated ROS generation and DNA damage, suggesting that endocytosis is involved in nSP70-mediated cellular effects. Conclusions: Thus, particle size affects amorphous silica-induced ROS generation and DNA damage of HaCaT cells. We believe clarification of the endocytosis pathway of nSP will provide useful information for hazard assessment as well as the design of safer forms of nSPs. [ABSTRACT FROM AUTHOR]

The senescence-accelerated prone mouse strain 8 (SAMP8) exhibits a remarkable age-accelerated deterioration in learning and memory. In this study, we identified carbonyl modification, a marker of protein oxidation, in liver and brain of SAMP8 from peptide mass fingerprints using MALDI-TOF mass spectrometry in combination with LC-MS/MS analysis. Carbonyl modification of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) in liver at 3 month and hippocampal cholinergic neurostimulating peptide precursor protein (HCNP-pp) in brain at 9 month were higher in SAMP8 compared with control SAMR1. We demonstrated carbonyl modification of purified Cu,Zn-SOD increased by the reaction with H2O2. Therefore, progressive accumulation of oxidative damage to Cu,Zn-SOD, may cause dysfunction of defense systems against oxidative stress in SAMP8 with a higher oxidative states, leading to acceleration of aging. Furthermore, carbonyl modification of HCNP-pp may be involved in pathophysiological alterations associated with deterioration in the learning and memory in the brain seen in SAMP8. [ABSTRACT FROM AUTHOR]

Radionuclide contamination in foods has been a public concern in Japan after the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. To estimate time and regional trends of daily intake and annual committed effective dose of strontium-90 ( 90 Sr) after the accident, we analysed Market basket samples using a low background 2π gas-flow counter. Samples were collected from six regions, once a year from 2013 to 2018. There appeared to be little variation in estimated daily intake and annual committed effective dose of 90 Sr across the time periods and regions. The estimated maximum annual committed effective dose of 90 Sr was 0.00076 mSv/year, a value sufficiently lower than the intervention exemption level, 1 mSv/year, in foods in Japan. There was no noticeable difference between the range of estimated daily intake of 90 Sr in this study compared with daily intake measured before the FDNPP accident. These results suggested that no obvious increase in dietary intake of 90 Sr was observed after the FDNPP accident, and that the effects on commercial foods from 90 Sr due to the FDNPP accident were negligible.

To ensure food safety during emergency events such as nuclear disasters, we developed a practical rapid determination method for strontium-90 (Sr-90) in foods. Purification of Sr from foods was simplified using a commercial Sr-extraction column. We also reduced the waiting time to achieve radiative equilibrium between Sr-90 and Y-90. Finally, we developed a rapid determination method for Sr-90 that can be completed in about a week. Using the new method, stable Sr recoveries exceeded 85%. The trueness of the method ranged from 109 to 115% and the detection limit of Sr-90 was estimated to be 0.07 Bq/kg fresh weight according to a performance evaluation using standard materials. Sr-90 radioactivity concentrations in food samples determined by the new method were highly correlated and nearly equal to concentrations determined by the conventional method. The present study suggests that the new method offers highly sensitive and rapid detection of Sr-90 which are necessary attributes for food tests during emergency events.

Between fiscal years 2014 and 2016, we surveyed the concentration of radioactive cesium in commercial foods produced in areas where there is a risk of radiation contamination due to the Fukushima Daiichi nuclear disaster. The number of samples with a concentration of radioactive cesium that exceeded the regulatory limit （100 Bq/kg for general foods） was 9 out of 1,516 （0.6％） in fiscal 2014, 12 out of 900 （1.3％） in fiscal 2015, and 10 out of 654 （1.5％） in fiscal 2016. Even though some samples were expected to be contaminated with radioactive cesium, because wild mushrooms and edible wild plants were intentionally included in this survey, the percentage of samples that exceeded the regulatory limit was only around 1％. The surveillance results confirmed that the pre-shipment food monitoring conducted by local governments was properly and efficiently performed, although continuous monitoring of the concentration of radioactive cesium in cultivated and wild mushrooms, edible wild plants, and wild animal meats is still required.

As a result of the Fukushima Daiichi nuclear power plant (NPP) accident, various radionuclides were released into the environment. In this study, we surveyed strontium-90 ((90)Sr) concentrations in several foodstuffs. Strontium-90 is thought to be the third most important residual radionuclide in food collected after the Fukushima Daiichi, NPP accident after following cesium-137 ((137)Cs) and cesium-134 ((134)Cs). Results of (90)Sr analyses indicated that (90)Sr was detect in 25 of the 40 radioactive cesium (r-Cs) positive samples collected in areas around the Fukushima Daiichi NPP, ranging in distance from 50 to 250 km. R-Cs positive samples were defined as containing both (134)Cs and (137)Cs which are considered to be indicators of the after-effects of the Fukushima Daiichi NPP accident. We also detected (90)Sr in 8 of 13 r-Cs negative samples, in which (134)Cs was not detected. Strontium-90 concentrations in the r-Cs positive samples did not significantly exceed the (90)Sr concentrations in r-Cs negative samples or the (90)Sr concentration ranges in comparable food groups found in previous surveys before the Fukushima Daiichi NPP accident. Thus, (90)Sr concentrations in r-Cs positive samples were indistinguishable from the background (90)Sr concentrations arising from global fallout prior to the Fukushima accident, suggesting that no marked increase of (90)Sr concentrations has occurred in r-Cs positive samples as a result of the Fukushima Daiichi NPP accident.

We surveyed the concentration of radioactive cesium in foods purchased at markets in areas where possible contamination has been a concern after the Fukushima accident. In fiscal years 2012 and 2013, we surveyed 1,735 and 1,674 foods, respectively, using a NaI (Tl) scintillation spectrometer for the screening test and a γ-ray spectrometer with a germanium semiconductor detector for the final test. Only 3 and 4 samples (0.2% of our total samples) exceeded the regulatory limit (100 Bq/kg) for radioactive cesium in fiscal years 2012 and 2013, respectively. Our surveillance indicates that the pre-shipment monitoring of foods by local governments has been working effectively.

Radioactive contamination in foods is a matter of great concern after the Tokyo Electric Power Company's Fukushima Daiichi nuclear power plant disaster caused by the Great East Japan Earthquake. In order to estimate human intake and annual committed effective dose of radioactive materials, market basket and duplicate diet samples from various areas in Japan were analyzed for cesium-134 ((134)Cs), -137 ((137)Cs), and natural radionuclide potassium-40 ((40)K) by γ-ray spectroscopy. Dietary intake of radioactive cesium around Fukushima area was somewhat higher than in other areas. However, maximum committed effective doses obtained by the market basket and duplicate diet samples were 0.0094 and 0.027 mSv/year, respectively, which are much lower than the maximum permissible dose (1 mSv/year) in foods in Japan.

In Japan, seafood may be eaten raw or after having been cooked in diverse ways. Therefore, it is important to understand the effect of cooking on the extent of contamination with radioactive materials in order to avoid internal exposure to radioactive materials via seafood. In this study, we investigated the changes in radioactive cesium content in pond smelt cooked in four different ways: grilled, stewed (kanroni), fried and soaked (nanbanzuke). The radioactive cesium content in grilled, kanroni and fried pond smelt was almost unchanged compared with the uncooked state. In contrast, radioactive cesium content in nanbanzuke pond smelt was decreased by about 30%. Our result suggests that soaking cooked pond smelt in seasoning is an effective method of reducing the burden radioactive cesium.

The Tokyo Electric Power Company's Fukushima Daiichi nuclear power plant disaster after the Great East Japan Earthquake has caused radioactive contamination in food. Using the market basket method, total diet samples in Tokyo, Miyagi prefecture and Fukushima prefecture were analyzed for cesium-134 and -137 (radioactive cesium) and naturally occurring potassium-40 (radioactive potassium) in order to estimate the committed effective doses of these radioactive materials from food. Doses were calculated on the assumption that "not detected" corresponded to zero or to half the limit of detection (values in brackets). The estimated doses of radioactive cesium in Tokyo, Miyagi and Fukushima were 0.0021 (0.0024), 0.017 (0.018) and 0.019 (0.019) mSv/year, respectively. Although the doses in Miyagi and Fukushima were more than 8 times the dose in Tokyo, they were significantly lower than the maximum permissible dose (1 mSv/year) determined by the Ministry of Health, Labour and Welfare, Japan. The estimated doses of naturally occurring radioactive potassium in these areas were in the range of 0.17-0.20 (0.18-0.20) mSv/year, and there were no significant differences between the areas.

It is important to obtain information about ways of removing radioactive cesium from foods in order to reduce internal radiation exposure from food and to ensure the safety and security of food. In this study, we investigated the change of radioactive cesium content in beef due to soaking in seasoning. Our results revealed that soaking beef in liquid seasoning (salt concentration: 8-10%) for 24 h or in miso seasoning (salt concentration: about 9%) for 7 days decreased the radioactive cesium content by about 20% and 55%, respectively, compared with that present in beef before soaking. Furthermore, soaking beef in 10% salt solution for 7 days while changing the salt solution every day or every three days decreased the radioactive cesium content by about 75%, compared with that present in beef before soaking. Because the seasoning is usually discarded after soaking, the procedure of soaking beef in seasoning is a useful method of reducing the burden of radioactive cesium.

We surveyed foods on the market from areas that had been exposed to radioactive materials contamination following the Fukushima accident. We used a NaI (Tl) scintillation spectrometer for the screening tests and a germanium semiconductor detector for the final tests. Test results from 1,427 samples showed that 6 samples (0.4%) exceeded the regulatory limit of 500 Bq/kg. Considering the detection rate of radioactive cesium in each food category, we suggest that it is necessary to continue monitoring fruits such as chestnuts and ginkgo nuts, mushrooms (especially raw wood-shiitake), mountain vegetables, and sea fish.

After the Fukushima No. 1 Nuclear Power Plant accident, high levels of radioactive cesium were detected in beef. Many prefectural governments decided to conduct blanket tests on meat from local beef cattle to prevent distribution of beef contaminated with radioactive cesium exceeding the provisional regulation value. In some cases, different concentrations of radioactive cesium were found in different cuts of beef from the same cows. These results raised questions about the reliability of the test results. Here, we investigated the reason for the differences in radioactive cesium concentration in different cuts of beef from the same cows. The concentrations of radioactive cesium in five different parts cuts of beef from three cows were negatively correlated with fat content, suggesting that the difference in radioactive cesium concentration is due to differences in fat content in the meat. In addition, our results showed that the concentration of radioactive cesium in muscle was more than 7-fold higher than that in fat in the same cow. These results suggested that it is necessary to use muscle for testing of radioactive cesium in cows.

We investigated the change of radioactive cesium content in food due to cooking in order to estimate the internal radiation exposure due to from radioactive materials in food. Our results revealed that soaking dry shiitake in water decreased the radioactive cesium content by about 50%, compared with that present in uncooked shiitake. Radioactive cesium in beef was decreased by about 10%, 12%, 60-65% and 80% by grilling, frying, boiling and stewing, respectively, compared to uncooked beef. For cooked beef, the decrease in the ratio of radioactive cesium was significantly different among the types of cooking. The decrease ratio of radioactive cesium in boiled and stewed beef was 8 times higher than that in grilled and fried beef.

Tumor necrosis factor-alpha (TNF) induces inflammatory response predominantly through the TNF receptor-1 (TNFR1). Thus, blocking the binding of TNF to TNFR1 is an important strategy for the treatment of many inflammatory diseases, such as hepatitis and rheumatoid arthritis. In this study, we identified a TNFR1-selective antagonistic mutant TNF from a phage library displaying structural human TNF variants in which each one of the six amino acid residues at the receptor-binding site (amino acids at positions 84-89) was replaced with other amino acids. Consequently, a TNFR1-selective antagonistic mutant TNF (R1antTNF), containing mutations A84S, V85T, S86T, Y87H, Q88N, and T89Q, was isolated from the library. The R1antTNF did not activate TNFR1-mediated responses, although its affinity for the TNFR1 was almost similar to that of the human wild-type TNF (wtTNF). Additionally, the R1antTNF neutralized the TNFR1-mediated bioactivity of wtTNF without influencing its TNFR2-mediated bioactivity and inhibited hepatic injury in an experimental hepatitis model. To understand the mechanism underlying the antagonistic activity of R1antTNF, we analyzed this mutant using the surface plasmon resonance spectroscopy and x-ray crystallography. Kinetic association/dissociation parameters of the R1antTNF were higher than those of the wtTNF, indicating very fast bond dissociation. Furthermore, x-ray crystallographic analysis of R1antTNF suggested that the mutation Y87H changed the binding mode from the hydrophobic to the electrostatic interaction, which may be one of the reasons why R1antTNF behaved as an antagonist. Our studies demonstrate the feasibility of generating TNF receptor subtype-specific antagonist by extensive substitution of amino acids of the wild-type ligand protein.