CYP7A1, NPC1L1, ABCB1, and CD36 Polymorphisms Associated with Coenzyme Q10 Availability Affect the Subjective Quality of Life Score (SF-36) after Long-Term CoQ10 Supplementation in Women.

The single nucleotide polymorphisms (SNPs) rs3808607, rs2072183, rs2032582, and rs1761667 are associated with coenzyme Q10 (CoQ10) bioavailability in women after long-term CoQ10 supplementation. However, the beneficial aspects of the association between these SNPs and CoQ10 supplementation remain unknown. We investigated their relationship using the subjective quality of life score SF-36 by reanalyzing previous data from 92 study participants who were receiving ubiquinol (a reduced form of CoQ10) supplementation for 1 year. Two-way repeated-measures analysis of variance revealed a significant interaction between rs1761667 and the SF-36 scores of role physical (p = 0.016) and mental health (p = 0.017) in women. Subgrouping of participants based on the above four SNPs revealed significant interactions between these SNPs and the SF-36 scores of general health (p = 0.045), role emotional (p = 0.008), and mental health (p = 0.019) and increased serum CoQ10 levels (p = 0.008), suggesting that the benefits of CoQ10 supplementation, especially in terms of psychological parameters, are genotype-dependent in women. However, significant interactions were not observed in men. Therefore, inclusion of SNP subgrouping information in clinical trials of CoQ10 supplementation may provide conclusive evidence supporting other beneficial health effects exerted by the association between these SNPs and CoQ10 on women.

Anti-Obesity Effects of Matoa (Pometia pinnata) Fruit Peel Powder in High-Fat Diet-Fed Rats.

Fruit peels, pericarps, or rinds are rich in phenolic/polyphenolic compounds with antioxidant properties and potentially beneficial effects against obesity and obesity-related non-communicable diseases. This study investigated the anti-obesity effects of matoa (Pometia pinnata) and salak (Salacca zalacca) fruit peel. Neither matoa peel powder (MPP) nor salak peel powder (SPP) affected the body weight, visceral fat weight, or serum glucose or lipid levels of Sprague-Dawley rats when included as 1% (w/w) of a high-fat diet (HFD). However, MPP significantly decreased the hepatic lipid level. MPP at a dose of 3% (w/w) of the HFD decreased body weight, visceral fat, and serum triglyceride levels as well as the hepatic lipid content. The inhibitory effect of MPP on hepatic lipid accumulation was not enhanced when its concentration was increased from 1% to 3% of the HFD. The anti-obesity effect of matoa was partly explained by the inhibitory effect of the matoa peel extract on fatty acid-induced secretion of ApoB-48 protein, a marker of intestinal chylomicrons, in differentiated Caco-2 cell monolayers. We identified hederagenin saponins that are abundant in MPP as potential anti-obesity substances. These results will contribute towards the development of functional foods with anti-obesity effects using the matoa fruit peel.

Integrative taxonomy and molecular phylogeny of three poorly known tintinnine ciliates, with the establishment of a new genus (Protista; Ciliophora; Oligotrichea).

BACKGROUND: The taxonomic classification of the suborder Tintinnina Kofoid & Campbell, 1929, a species-rich group of planktonic ciliated protistans with a characteristic lorica, has long been ambiguous largely due to the lack of cytological and molecular data for most species. Tintinnopsis is the largest, most widespread, and most taxonomically complex genus within this group with about 170 species occurring in nearshore waters. Previous molecular phylogenetic studies have revealed that Tintinnopsis is polyphyletic. RESULTS: Here we document the live morphology, infraciliature, gene sequences, and habitat characteristics of three poorly known tintinnine species, viz. Tintinnopsis karajacensis Brandt, 1896, Tintinnopsis gracilis Kofoid & Campbell, 1929, and Tintinnopsis tocantinensis Kofoid & Campbell, 1929, isolated from the coastal waters of China. Based on a unique cytological feature (i.e., an elongated ciliary tuft with densely arranged kinetids) in the former two species, Antetintinnopsis gen. nov. is erected with Antetintinnopsis hemispiralis (Yin, 1956) comb. nov. (original combination: Tintinnopsis hemispiralis Yin, 1956) designated as the type species. Moreover, A. karajacensis (Brandt, 1896) comb. nov. (original combination: Tintinnopsis karajacensis Brandt, 1896) and A. gracilis (Kofoid & Campbell, 1929) comb. nov. (original combination: Tintinnopsis gracilis Kofoid & Campbell, 1929) are placed in a highly supported clade that branches separately from Tintinnopsis clades in phylogenetic trees based on SSU rDNA and LSU rDNA sequence data, thus supporting the establishment of the new genus. One other species is assigned to Antetintinnopsis gen. nov., namely A. subacuta (Jörgensen, 1899) comb. nov. (original combination Tintinnopsis subacuta Jörgensen, 1899). CONCLUSIONS: The findings of the phylogenetic analyses support the assertion that cytological characters are taxonomically informative for tintinnines. This study also contributes to the broadening of our understanding of the tintinnine biodiversity and evolution.

CYP7A1, NPC1L1, ABCB1, and CD36 Polymorphisms Are Associated with Increased Serum Coenzyme Q10 after Long-Term Supplementation in Women.

Coenzyme Q10 (CoQ10), an essential component for energy production that exhibits antioxidant activity, is considered a health-supporting and antiaging supplement. However, intervention-controlled studies have provided variable results on CoQ10 supplementation benefits, which may be attributed to individual CoQ10 bioavailability differences. This study aimed to investigate the relationship between genetic polymorphisms and CoQ10 serum levels after long-term supplementation. CoQ10 levels at baseline and after one year of supplementation (150 mg) were determined, and eight single nucleotide polymorphisms (SNPs) in cholesterol metabolism and CoQ10 absorption, efflux, and cellular uptake related genes were assessed. Rs2032582 (ABCB1) and rs1761667 (CD36) were significantly associated with a higher increase in CoQ10 levels in women. In addition, in women, rs3808607 (CYP7A1) and rs2072183 (NPC1L1) were significantly associated with a higher increase in CoQ10 per total cholesterol levels. Subgroup analyses showed that these four SNPs were useful for classifying high- or low-responder to CoQ10 bioavailability after long-term supplementation among women, but not in men. On the other hand, in men, no SNP was found to be significantly associated with increased serum CoQ10. These results collectively provide novel evidence on the relationship between genetics and CoQ10 bioavailability after long-term supplementation, which may help understand and assess CoQ10 supplementation effects, at least in women.

Phenotypic Markers Reflecting the Status of Overstressed Tea Plants Subjected to Repeated Shade Cultivation.

Shade cultivation is a traditional Japanese tea cultivation method in which the shoot buds are shaded for several weeks. This technique is increasingly used for green tea production because it produces tea of high quality (as indicated by umami and nutritional content) and commands high prices. However, given that shaded tea plants are grown under low-light stress, concerns exist regarding damage to tea plants caused by repeated shade cultivation. To understand basic physiological responses and accumulative changes in photosynthetic ability and metabolites of tea plants subjected to repeated shading, we performed a pot experiment on immature tea plants grown in a growth chamber subjected to repeated shading treatments. The results demonstrated that shade cultivation caused a decrease in non-structural carbohydrate content and an increase of several degrees in leaf surface temperature, reflecting transpiration through the leaf stomata, as a result of a reduction in photosynthetic ability. An increase of several degrees in canopy temperature and a reduction in photosynthetic ability in the field in the mid-summer season was also observed in overstressed tea plants subjected to repeated shading. Metabolomic analysis identified several candidate biomarkers, such as citrulline and glycine betaine, that were significantly changed in individuals affected by shade cultivation. These physiological changes may be an indicator of the stress status of tea plants grown under repeated shade cultivation.

Antidepressant Effect of Shaded White Leaf Tea Containing High Levels of Caffeine and Amino Acids.

The young leaves of green tea become lighter in color than usual when protected from sunlight by a shading net for about two weeks while growing. These leaves are called "shaded white leaf tea" or SWLT. In the eluate of SWLT, the amount of amino acids (361 mg/L) was significantly higher than that in regular tea (53.5 mg/L). Since theanine and arginine, the first and second most abundant amino acids in SWLT, have significant antistress effects, we examined the antistress effect of SWLT on humans. SWLT or placebo green tea (3 g) was eluted with room-temperature water (500 mL). Participants consumed the tea for one week prior to pharmacy practice and continued for 10 days in the practice period. The state-trait anxiety inventory, an anxiety questionnaire, tended to be scored lower in the SWLT group than the placebo, but other stress markers showed no differences. The effect of the difference in SWLT components examined with mice showed that aspartic acid and asparagine, which are abundant in SWLT, counteracted the antistress effects of theanine and arginine. Large amounts of caffeine also interfered with SWLT's antistress effect. Thus, SWLT, which is high in caffeine and amino acids, suppressed depressant behavior in mice.

Miso Soup Consumption Enhances the Bioavailability of the Reduced Form of Supplemental Coenzyme Q10.

Coenzyme Q10 (CoQ10) is an essential compound that is involved in energy production and is a lipid-soluble antioxidant. Although it has been proposed as an antiaging and a health-supporting supplement, its low bioavailability remains a significant issue. Concurrent food intake enhances the absorption of orally administered CoQ10, but it has not been fully established whether specific food substances affect intestinal CoQ10 absorption. Therefore, to determine whether the bioavailability of supplemental CoQ10 is affected by diet, P30, a granulated and reduced form of CoQ10, was dispersed in four different foods, clear soup, miso soup, milk soup, and raw egg sauce. Those foods which contained CoQ10 were consumed on different occasions at intervals of 6-14 weeks by the same participants. Thirteen participants were recruited in the single-dose and repeated clinical study. When miso soup containing P30 was provided, the serum CoQ10 concentration increased faster than when participants consumed other P30-containing soups or a P30-containing raw egg sauce. The area under the curve for serum CoQ10 during the first 5 h after consumption of the P30-containing miso soup was approximately 1.5 times larger than those after the consumption of other P30-containing meals. These data imply that the absorption of CoQ10 supplements can be enhanced by consuming them with food and in particular with specific food substances, such as miso soup.

Integrated Metabolome and Transcriptome Analyses Reveal Etiolation-Induced Metabolic Changes Leading to High Amino Acid Contents in a Light-Sensitive Japanese Albino Tea Cultivar.

Plant albinism causes the etiolation of leaves because of factors such as deficiency of chloroplasts or chlorophylls. In general, albino tea leaves accumulate higher free amino acid (FAA) contents than do conventional green tea leaves. To explore the metabolic changes of etiolated leaves (EL) in the light-sensitive Japanese albino tea cultivar "Koganemidori," we performed integrated metabolome and transcriptome analyses by comparing EL with green leaves induced by bud-sport mutation (BM) or shading treatments (S-EL). Comparative omics analyses indicated that etiolation-induced molecular responses were independent of the light environment and were largely influenced by the etiolation itself. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and pathway analyses revealed the downregulation of genes involved in chloroplast development and chlorophyll biosynthesis and upregulation of protein degradation-related pathways, such as the ubiquitin-proteasome system and autophagy in EL. Metabolome analysis showed that most quantified FAAs in EL were highly accumulated compared with those in BM and S-EL. Genes involved in the tricarboxylic acid (TCA) cycle, nitrogen assimilation, and the urea cycle, including the drastically downregulated Arginase-1 homolog, which functions in nitrogen excretion for recycling, showed lower expression levels in EL. The high FAA contents in EL might result from the increased FAA pool and nitrogen source contributed by protein degradation, low N consumption, and stagnation of the urea cycle rather than through enhanced amino acid biosynthesis.

Investigation of Natural Radioactivity in a Monazite Processing Plant in Japan.

Monazite is a naturally occurring radioactive material that is processed for use in a variety of domestic applications. At present, there is little information available on potential radiation doses experienced by people working with monazite. The ambient dose rate and activity concentration of natural radionuclides in raw materials, products, and dust in work sites as well as the Rn and Rn concentrations in work sites were measured in a monazite processing plant in Japan. Dose estimations for plant workers were also conducted. The activity concentration of the U series in raw materials and products for the monazite processing plant was found to be higher than the relevant values described in the International Atomic Energy Agency Safety Standards. The ambient dose rates in the raw material yard were higher than those in other work sites. Moreover, the activity concentrations of dust in the milling site were higher than those in other work sites. The Rn concentrations in all work sites were almost the same as those in regular indoor environments in Japan. The Rn concentrations in all work sites were much higher than those in regular indoor environments in Japan. The maximum value of the effective dose for workers was 0.62 mSv y, which is lower than the reference level range (1-20 mSv y) for abnormally high levels of natural background radiation published in the International Commission of Radiological Protection Publication 103.

Inhibitory effect of 13 taxane diterpenoids from Chinese yew (Taxus chinensis var. mairei) on the proliferation of HeLa cervical cancer cells.

The inhibitory effect of 13 taxanes isolated from the Chinese yew (Taxus chinensis var. mairei) on the proliferation of human cervical cancer HeLa cells were examined using an MTT assay. Four compounds having a hydrophobic cinnamate side chain showed antiproliferative activity, which may be due to increased cell permeability.

Overexpression of TMOD1 is associated with enhanced regional lymph node metastasis in human oral cancer.

Tropomodulin1 (TMOD1), which regulates the length and depolymerization of actin filaments by binding to the pointed end of the actin filament, has been reported to be a powerful diagnostic marker for ALK-negative anaplastic large-cell lymphoma; however, little is known about the relevance of TMOD1 in the behavior of oral squamous cell carcinoma (OSCC). We evaluated TMOD1 expression in OSCC-derived cell lines and primary OSCC samples (n=200) using quantitative reverse transcriptase-polymerase chain reaction, immunoblotting and semi-quantitative immunohistochemistry. We also analyzed the clinical correlation between TMOD1 expression status and clinical parameters in patients with OSCC and performed a prospective study using 40 primary OSCC samples. TMOD1 expression was upregulated significantly (p<0.05) in OSCC in vitro and in vivo compared with normal counterparts. TMOD1 expression also was correlated significantly (p=0.0199 and p=0.0064, respectively) with regional lymph node metastasis (RLNM) and 5-year survival rates. This prospective study also showed that high TMOD1 expression was seen in 12 (75%) of 16 cases in RLNM-positive patients and 9 (37.5%) of 24 cases in RLNM-negative patients. The current data provide the first evidence that TMOD1 expression is a critical biomarker for RLNM and prognosis of patients with OSCC.

Microscopic investigation of three species of Diophrys (Ciliophora, Euplotida, Uronychiidae) from Japan, including Diophrys peculiaris nov. spec.

Three species of Diophrys, D. peculiaris nov. spec., D. cf. scutum and D. oligothrix, isolated from the New Nagasaki Fishing Port, Nagasaki, Japan, were investigated using live observation and protargol impregnation. Diophrys peculiaris nov. spec. can be recognized by having two characteristic clusters of rod-like structures and two groups of dikinetids located on anterior dorsal portion of cell. Morphogenetic data show that this part of the life cycle basically proceeds as in congeners, except for the formation of dikinetids under the rod-like structures. In the opisthe, the origin of dikinetids under the rod-like structures is still unknown, but the old dikinetids under the rod-like structures may be retained by the proter. The Japanese population of Diophrys cf. scutum resembles other populations of D. scutum well except for moniliform macronuclear segments. Our populations of D. oligothrix correspond well with other populations in terms of general morphology and ciliary pattern, in particular the continuous dorsal kineties with loosely arranged cilia.

Occupational exposure to natural radiation in zirconium refractory plants in Japan.

The authors measured the ambient dose rate and activity concentration of natural radionuclides in raw materials, products, and aerosols on worksites, as well as the (222)Rn and (220)Rn concentrations in an unshaped refractory, a shaped refractory, and an electrocast refractory plant processing zirconium ore in Japan. Estimations were made of the effective doses to plant workers. The activity concentration of the (238)U series in raw materials and products in the refractory plants was higher than the critical values (10 Bq g(-1) for (40)K and 1 Bq g(-1) for all other radionuclides of natural origin) specified in the International Atomic Energy Agency Safety Guide. The ambient dose rate in the raw material warehouse of the electrocast refractory plant was 0.75 µSv h(-1), which was the highest among all the worksites at all the refractory plants studied. The activity concentrations of aerosols in the product-output site of the unshaped refractory plant was 0.0015 Bq m for U and 0.00078 Bq m(-3) for (232)Th, which were the highest of all the worksites for all refractory plants. The indoor (222)Rn and (220)Rn concentrations in all worksites of all the refractory plants were almost the same levels as those in everyday indoor places in Japan. The maximum value of the effective dose to workers was 430 µSv y(-1), which was lower than the intervention exemption level (1,000 µSv y(-1)) specified in ICRP Publication 82.

Early in situ measurement of radioactive fallout in Fukushima city due to Fukushima Daiichi nuclear accident.

Using a high-purity germanium detector, both indoor and outdoor radionuclides that had deposited 1.5 d after the radioactive fallout events in the city of Fukushima were experimentally measured. Eleven artificial ((131)I, (132)I, (134)Cs, (136)Cs, (137)Cs, (129)Te, (129m)Te, (131m)Te, (132)Te, (140)La and (99m)Tc) and 5 natural radionuclides were identified. Total air kerma rates were mainly due to (132)I, (134)Cs and (136)Cs from 4 to 6 µGy/h at a 7.5-cm height from the ground. Radioactive contamination on the ground was contributed by (132)I and (132)Te, from 330 to 420 Bq/cm(2). In a worst-case scenario, the maximum skin dose rates were estimated to be from 520 to 670 µGy/h. Effective dose rates were evaluated to be 10 to 15 µSv/h and reached 17.9 µSv/h at 4 a.m. on 16 March. In the effective dose rates, (132)I, (134)Cs and (132)Te were the main contributors. Our measurements are useful for estimating dose levels in the public in the city of Fukushima during the days after radioactive fallout contamination.

Extracellular release of annexin II from pancreatic cancer cells and resistance to anticancer drug-induced apoptosis by supplementation of recombinant annexin II.

OBJECTIVES: Extracellular microenvironment plays crucial roles in the development of cancers and chemoresistance. Pancreatic carcinoma is resistant to almost all chemotherapeutic agents. In this study, we identified annexin II in the medium from pancreatic cancer cells as a protein released into the extracellular environment. METHODS: Medium from 5-hour cultures of various cancer cells was collected. Proteins in the medium were detected by molecular mass analysis and immunoblotting. Anticancer drug sensitivity of cells preincubated with or without recombinant annexin II (rANX II) was measured using crystal violet assay and colony survival assay. Apoptosis-related molecules were analyzed by immunoblotting. RESULTS: Recombinant ANX II supplementation in the medium confers resistance to anticancer drugs, including cisplatin, 5-fluorouracil, and gemcitabine, in MiaPaCa-2 and AsPC-1 cells. In MiaPaCa-2 cells, rANX II supplementation resulted in suppression of caspase-3 activation associated with increased Bcl-2/Bax ratios. Suppression of cisplatin-induced cell death by rANX II supplementation was canceled by inhibitors of phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase signal pathways. CONCLUSIONS: The current study is the first report to demonstrate that supplementation of rANX II in the medium increased resistance to anticancer drugs in pancreatic cancer cells. Recombinant ANX II exerts cell death-suppressive function by antagonizing cisplatin-induced apoptosis.

Reduction of thermal fluctuations in a cryogenic laser interferometric gravitational wave detector.

The thermal fluctuation of mirror surfaces is the fundamental limitation for interferometric gravitational wave (GW) detectors. Here, we experimentally demonstrate for the first time a reduction in a mirror's thermal fluctuation in a GW detector with sapphire mirrors from the Cryogenic Laser Interferometer Observatory at 17 and 18 K. The detector sensitivity, which was limited by the mirror's thermal fluctuation at room temperature, was improved in the frequency range of 90 to 240 Hz by cooling the mirrors. The improved sensitivity reached a maximum of 2.2×10(-19) m/√Hz at 165 Hz.

[Radiation measurement and dose assessment].

In order to assess an effective dose, it is necessary to evaluate the external exposure caused by gamma ray or neutron, and the internal exposure caused by ingestion from contaminated food or soil and inhalation from radioactive fallout. It is also necessary to consider the equivalent dose of the skin in case of the existence of a high density surface contamination by beta emitters. An early evaluation on the effective dose should be indispensable by a dose calculation using easy expression and by a suitable radiation measurement for the radiation emergency. The accuracy of the effective dose may not be significant at the first stage, but the true value should be included in the range of the fluctuation. Here, radiation measurement is the most effective means to be able to avoid the misjudgment.

Extracellular recombinant annexin II confers UVC-radiation resistance and increases the Bcl-xL to Bax protein ratios in human UVC-radiation-sensitive cells.

In this study, we found that refractoriness to ultraviolet (UVC) light-induced cell death was increased in UVC-radiation-sensitive cells derived from Cockayne syndrome patients when the cells were precultured in medium supplemented with recombinant annexin II (rANX II). In CS3BES cells, an immortal cell line derived from Cockayne syndrome patients, the rANX II supplementation-induced UVC-radiation resistance was suppressed by treatment with an anti-annexin II antibody and EGTA. The amount of biotinylated annexin II on the cell surface increased in the rANX II-supplemented cells but did not increase in the cells that were cotreated with rANX II and EGTA. The capacity to remove UVC-radiation-damaged DNA, (6-4) photoproducts and cyclobutane pyrimidine dimers, was the same in cells that were precultured with rANX II and in control cells that did not receive rANX II supplementation. The rANX II supplementation-induced UVC-radiation resistance was also observed in nucleotide excision repair-deficient cells and xeroderma pigmentosum group A-downregulated cells. The Bcl-xL to Bax protein ratios, an index of survival activity in cells exposed to lethal stresses, were increased in the cells that had been precultured in rANX II for 24 h prior to UVC irradiation. Treatment with a phosphatidylinositol 3-kinase inhibitor suppressed the increased UVC-radiation resistance and Bcl-xL to Bax ratios in the cells with rANX II supplementation. Furthermore, downregulation of Bcl-xL by siRNA transfection also suppressed the UVC-radiation resistance that was induced by rANX II supplementation. These results suggest that the increase in the Bcl-xL to Bax ratios may be associated with enhanced resistance to UVC-radiation-induced cell death.

The dose response of chromosome aberrations in human lymphocytes induced in vitro by very low-dose γ rays.

This paper considers the dose-effect relationship for unstable chromosome aberration yields in human lymphocytes in very low-dose range. Data are presented for (60)Co γ-ray doses of 0, 10, 20, 40 and 1000 mGy. More than 5,000 metaphases were scored for each data point at the very low doses, and each cell was double-checked using a semi-automated metaphase finding/relocation system. Aberration yields of dicentrics plus centric rings followed an excellent linear dose response down to zero dose; the yields were significantly above the control frequency from 20 mGy.