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Dietary ω3 fatty acids have important health benefits and exert their potent bioactivity through conversion to lipid mediators. Here, we demonstrate that microbiota play an essential role in the body's use of dietary lipids for the control of inflammatory diseases. We found that amounts of 10-hydroxy-cis-12-cis-15-octadecadienoic acid (αHYA) and 10-oxo-cis-12-cis-15-octadecadienoic acid (αKetoA) increased in the feces and serum of specific-pathogen-free, but not germ-free, mice when they were maintained on a linseed oil diet, which is high in α-linolenic acid. Intake of αKetoA, but not αHYA, exerted anti-inflammatory properties through a peroxisome proliferator-activated receptor (PPAR)γ-dependent pathway and ameliorated hapten-induced contact hypersensitivity by inhibiting the development of inducible skin-associated lymphoid tissue through suppression of chemokine secretion from macrophages and inhibition of NF-κB activation in mice and cynomolgus macaques. Administering αKetoA also improved diabetic glucose intolerance by inhibiting adipose tissue inflammation and fibrosis through decreased macrophage infiltration in adipose tissues and altering macrophage M1/M2 polarization in mice fed a high-fat diet. These results collectively indicate that αKetoA is a novel postbiotic derived from α-linolenic acid, which controls macrophage-associated inflammatory diseases and may have potential for developing therapeutic drugs as well as probiotic food products.

Synthesis of Sm 2 Fe 17 N 3 powder by a reduction-diffusion technique requires a washing process to remove CaO and Ca residues, but it is typically associated with a decrease of coercivity. Synchrotron radiation X-ray diffraction study revealed forming of a SmFe 5 poor hard magnetic phase in a water washing treatment. Cross-sectional electron microscopic analysis of particles revealed an acetic acid washing treatment to dissolve the impurity phases accompanied surface damages on Sm 2 Fe 17 N 3 particles. A new washing process to avoid forming of the factors which decrease coercivity was examined, and Sm 2 Fe 17 N 3 powders having about 20% higher coercivity than that in the previous reports, achieving up to 28.1 kOe, were successfully demonstrated.

ω3 fatty acids show potent bioactivities via conversion into lipid mediators; therefore, metabolism of dietary lipids is a critical determinant in the properties of ω3 fatty acids in the control of allergic inflammatory diseases. However, metabolic progression of ω3 fatty acids in the skin and their roles in the regulation of skin inflammation remains to be clarified. In this study, we found that 12-hydroxyeicosapentaenoic acid (12-HEPE), which is a 12-lipoxygenase metabolite of eicosapentaenoic acid, was the prominent metabolite accumulated in the skin of mice fed ω3 fatty acid-rich linseed oil. Consistently, the gene expression levels of Alox12 and Alox12b, which encode proteins involved in the generation of 12-HEPE, were much higher in the skin than in the other tissues (eg, gut). We also found that the topical application of 12-HEPE inhibited the inflammation associated with contact hypersensitivity by inhibiting neutrophil infiltration into the skin. In human keratinocytes in vitro, 12-HEPE inhibited the expression of two genes encoding neutrophil chemoattractants, CXCL1 and CXCL2, via retinoid X receptor α. Together, the present results demonstrate that the metabolic progression of dietary ω3 fatty acids differs in different organs, and identify 12-HEPE as the dominant ω3 fatty acid metabolite in the skin.

Submicron-sized Sm 2 Fe 17 N 3 powders having high coercivity were prepared by a newly-developed synthesis procedure for submicron-sized Sm 2 Fe 17 powders and nitridation process with a proper post-process for the powders. It was revealed that the washing step, which is performed to remove excess Ca, supplied hydrogen into the Sm 2 Fe 17 N 3 crystal structure, and elongation of the crystal structure along the c-axis by the supplied hydrogen reduced coercivity. This phenomenon was observed clearly in powder with a smaller size and good dispersity. When the powders were subjected to dehydrogenation treatment, they showed high coercivity, as expected from the particle size, and coercivity of 24.7 kOe was achieved with the 0.5 μm powder. The fact that the intrinsic good thermal stability of Sm 2 Fe 17 N 3 is maintained at the submicron-scale was also confirmed. In addition, the obtained powder exhibited a high maximum energy product after disintegration treatment under appropriate conditions. This study demonstrated the high potential of Sm 2 Fe 17 N 3 for surpassing the performance of Nd Fe B magnets under hot environments.

Dietary intake of ω3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid are beneficial for health control because ω3 fatty acids are metabolized to pro-resolution and anti-inflammatory lipid metabolites. We previously identified 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) as a new lipid metabolite endogenously generated from EPA that exhibits potent anti-allergic and anti-inflammatory properties. However, the chemically synthesized 17,18-EpETE is enantiomeric mixture concerning to its epoxy group, i.e., 17(S),18(R)-EpETE and 17(R),18(S)-EpETE, and the stereostructural differences in anti-inflammatory effect of 17,18-EpETE has not been clarified. Because it is necessary to identify which isomer shows physiological function to develop it as a medicine, we evaluated stereospecific effects of 17(S),18(R)-EpETE and 17(R),18(S)-EpETE in amelioration of skin contact hypersensitivity. As a result, we found that anti-inflammatory activity was detected in 17(S),18(R)-EpETE, but not 17(R),18(S)-EpETE. In addition, we found that cytochrome P450 BM-3 derived from Bacillus megaterium stereoselectively converts EPA into 17(S),18(R)-EpETE, which effectively inhibited the development of contact hypersensitivity by inhibiting neutrophil migration in a G protein-coupled receptor 40-dependent manner. These results demonstrated that immune cells (e.g., neutrophils) distinguish biological active lipid metabolites stereoselectively for the control of their activity, which is a new strategy for the development of efficient immunotherapy.

日光に含まれる紫外線A波は、真皮まで到達して水分を分解し、活性酸素を発生する。発生した活性酸素は、真皮の線維芽細胞を構成する脂質や蛋白質、核酸に障害を与え、細胞死をもたらす。その結果、皮膚の構造が乱れ、シワが生じ、日光老化と呼ばれる病態を発症する。温熱負荷が熱ショック蛋白質70(HSP70)を誘導することによって紫外線による細胞障害を軽減するかいなかを、線維芽細胞の過酸化水素負荷モデルに熱ショックを適用して検討した。マウス真皮由来の3T6線維芽細胞に0～10ｍMのH2O2を添加すると、細胞を構成する脂質の酸化、タンパク質の変性、さらにネクローシスとアポトーシスによる細胞死が引き起こされた。一方、3T6に42℃、1時間の熱ショックを負荷すると、細胞保護機能をもつHSP70が発現した。このような熱ショック条件下にH2O2を添加すると、3T6の脂質参加、タンパク質変性、細胞死が抑制された。以上のように熱ショックがH2O2による線維芽細胞障害を減弱したことから、温泉やサウナ、日々の入浴で身体に温熱を負荷することにより、紫外線による日光老化が予防される可能性が示唆された。, Ultraviolet A wave in sunlight reaches dermis and produces reactive oxygen by degradation of water in extracellular fluid. Reactive oxygen species produced in dermis interacts with lipids,proteins and nucleic acids composing dermal fibroblast and causes cell death, which results in a disturbance of the dermal structure, affects the aging of skin, and induces wrinkles.We examined whether skin damage caused by ultraviolet can be reduced through the induction of heat shock protein 70 by hyperthemia using a heat shock model of cultured fibroblasts exposed to hydrogen peroxide (H2O2). H2O2 (0～10mM) induced lipid oxidation, protein denatures and two types of cell death, necrosis and apoptosis,in cultured 3T6 cells derived from mouse dermis. However, when 3T6 were exposed to heat shock at 42℃ for 1 hour prior to the addition of H2O2, the damages of cellular lipid and protein were suppressed and the extent of cell death was reduced by nearly 50％. These results suggest that hyperthermia by hot spring and sauna bathing can prevent dermis from ultraviolet induced aging through the induction of HSP70 by heat shock.

Lowering the SOFC working temperature would also be greatly attractive, but low temperature working SOFCs require high-performance anodes. The cermet SOFC anodes, which are composed of nickel and samarium doped ceria, were prepared by spray pyrolysis (SP), because SP produces spherical particles with small size distributions. SP-derived particles of NiO, SDC, and NiO/SDC composite had a round shape and comprised nanometer-sized primary grains. The cermet anodes were prepared by using SP-derived NiO/SDC composite particles or mixing SP-derived NiO and SDC particles. The anode prepared with the composite particles showed higher SOFC cell performance than that with the mixed ones. The composite particles had high surface areas and a capsule-type form. The outer shell would be composed of SDC and the inner core was NiO. The capsule-type composite particles would depress aggregation of Ni or NiO during reduction from NiO to Ni metals, and this depression would enhance SOFC anode performance.