3-(4-Hydroxy-3-methoxyphenyl) propionic acid contributes to improved hepatic lipid metabolism via GPR41.

3-(4-hydroxy-3-methoxyphenyl) propionic acid (HMPA) is a metabolite produced by the gut microbiota through the conversion of 4-hydroxy-3-methoxycinnamic acid (HMCA), which is a widely distributed hydroxycinnamic acid-derived metabolite found abundantly in plants. Several beneficial effects of HMPA have been suggested, such as antidiabetic properties, anticancer activities, and cognitive function improvement, in animal models and human studies. However, the intricate molecular mechanisms underlying the bioaccessibility and bioavailability profile following HMPA intake and the substantial modulation of metabolic homeostasis by HMPA require further elucidation. In this study, we effectively identified and characterized HMPA-specific GPR41 receptor, with greater affinity than HMCA. The activation of this receptor plays a crucial role in the anti-obesity effects and improvement of hepatic steatosis by stimulating the lipid catabolism pathway. For the improvement of metabolic disorders, our results provide insights into the development of functional foods, including HMPA, and preventive pharmaceuticals targeting GPR41.

Thermal, Mechanical and Tribological Properties of Gamma-Irradiated Plant-Derived Polyamide 1010.

In this study, we investigated the influence of the gamma-irradiation dose and the addition of the cross-linking agent (triallyl isocyanurate (TAIC)) on the thermal, mechanical and tribological properties of plant-derived polyamide 1010 (PA1010). PA1010 and PA1010/TAIC were extruded using a twin screw extruder and injection molded. These specimens were then irradiated with gamma-ray in air with doses of 20 and 50 kGy. After gamma-irradiation, the specimens were heat-treated to remove the free radicals generated in the polymer. The combination of gamma-irradiation and the addition of TAIC significantly changed the crystal structures of PA1010. Glass transition temperature increased with the addition of TAIC and, in particular, with increasing gamma-irradiation dose. Moreover, PA1010/TAIC showed a rubbery plateau originating from cross-links by gamma-irradiation, which was observed in the temperature regions above the melting point in DMA measurements. Mechanical properties such as strength, modulus and hardness, and tribological properties such as frictional coefficient, specific wear rate and limiting pv (pressure p × velocity v) value of PA1010 improved with change in the internal microstructure with the gamma-irradiation and addition of TAIC.

Pharmacokinetic profiles of 3-(4-hydroxy-3-methoxyphenyl) propionic acid and its conjugates in Sprague-Dawley rats.

3-(4-hydroxy-3-methoxyphenyl)propionic acid (HMPA) is one of the end-products from gut microbiota from dietary polyphenols, which might contribute to their health benefits. This study aims to investigate the absorption, metabolism, and tissue accumulation of HMPA in Sprague-Dawley (SD) rats. After HMPA (10 mg/kg body weight) was orally administered, intact and conjugated HMPAs in the bloodstream were detected and reached the maximum concentration in 15 min (HMPA, 2.6 ± 0.4 nmol/mL; sulfated HMPA, 3.6 ± 0.9 nmol/mL; glucuronidated HMPA, 0.55 ± 0.09 nmol/mL). HMPA and its conjugates were also detected in the target organs 6 h postadministration, indicating that HMPA undergoes rapid conversion into conjugates, and they broadly distribute to organs with similar profiles (kidneys > liver > thoracic aorta > heart > soleus muscle > lungs). This study demonstrated that orally administered HMPA (10 mg/kg) in SD rats undergoes rapid metabolism and wide tissue distribution with ≥1.2% absorption ratio.

Influence of Epoxy Resin Treatment on the Mechanical and Tribological Properties of Hemp-Fiber-Reinforced Plant-Derived Polyamide 1010 Biomass Composites.

In this study, we investigated the influence of epoxy resin treatment on the mechanical and tribological properties of hemp fiber (HF)-reinforced plant-derived polyamide 1010 (PA1010) biomass composites. HFs were surface-treated using four types of surface treatment methods: (a) alkaline treatment using sodium chlorite (NaClO2) solution, (b) surface treatment using epoxy resin (EP) solution after NaClO2 alkaline treatment, (c) surface treatment using an ureidosilane coupling agent after NaClO2 alkaline treatment (NaClO2 + A-1160), and (d) surface treatment using epoxy resin solution after the (c) surface treatment (NaClO2 + A-1160 + EP). The HF/PA1010 biomass composites were extruded using a twin-screw extruder and injection-molded. Their mechanical properties, such as tensile, bending, and dynamic mechanical properties, and tribological properties were evaluated by the ring-on-plate-type sliding wear test. The strength, modulus, specific wear rate, and limiting pv value of HF/PA1010 biomass composites improved with surface treatment using epoxy resin (NaClO2 + A-1160 + EP). In particular, the bending modulus of NaClO2 + A-1160 + EP improved by 48% more than that of NaClO2, and the specific wear rate of NaClO2 + A-1160 + EP was one-third that of NaClO2. This may be attributed to the change in the internal microstructure of the composites, such as the interfacial interaction between HF and PA1010 and fiber dispersion. As a result, the mode of friction and wear mechanism of these biomass composites also changed.

3-(4-Hydroxy-3-methoxyphenyl)propionic Acid Produced from 4-Hydroxy-3-methoxycinnamic Acid by Gut Microbiota Improves Host Metabolic Condition in Diet-Induced Obese Mice.

4-Hydroxy-3-methoxycinnamic acid (HMCA), a hydroxycinnamic acid derivative, is abundant in fruits and vegetables, including oranges, carrots, rice bran, and coffee beans. Several beneficial effects of HMCA have been reported, including improvement of metabolic abnormalities in animal models and human studies. However, its mitigating effects on high-fat diet (HFD)-induced obesity, and the mechanism underlying these effects, remain to be elucidated. In this study, we demonstrated that dietary HMCA was efficacious against HFD-induced weight gain and hepatic steatosis, and that it improved insulin sensitivity. These metabolic benefits of HMCA were ascribable to 3-(4-hydroxy-3-methoxyphenyl)propionic acid (HMPA) produced by gut microbiota. Moreover, conversion of HMCA into HMPA was attributable to a wide variety of microbes belonging to the phylum Bacteroidetes. We further showed that HMPA modulated gut microbes associated with host metabolic homeostasis by increasing the abundance of organisms belonging to the phylum Bacteroidetes and reducing the abundance of the phylum Firmicutes. Collectively, these results suggest that HMPA derived from HMCA is metabolically beneficial, and regulates hepatic lipid metabolism, insulin sensitivity, and the gut microbial community. Our results provide insights for the development of functional foods and preventive medicines, based on the microbiota of the intestinal environment, for the prevention of metabolic disorders.

Effect of Silane Coupling Agent on Tribological Properties of Hemp Fiber-Reinforced Plant-Derived Polyamide 1010 Biomass Composites.

We have studied the effects of silane coupling agents used for the surface treatment of fiber on the tribological properties of hemp fiber (HF) reinforced plant-derived polyamide 1010 (PA1010) biomass composites. Hemp fibers were surface-treated by two surface treatment methods: (a) alkali treatment by sodium hydroxide solution and (b) surface treatment by silane coupling agents. Three types of silane coupling agents, namely aminosilane, epoxysilane and ureidosilane were used. These HF/PA1010 biomass composites were extruded using a twin extruder, and injection-molded. The mechanical and tribological properties were evaluated by the ring-on-plate type sliding wear test. It was found that tribological properties of HF/PA1010 biomass composites improved with the surface treatment by the silane coupling agent. This may be attributed to the change in the mode of friction and wear mechanism by the interfacial adhesion between fiber and matrix polymer according to the type of silane coupling agent used. In particular, the ureidosilane coupling agent showed the best improvement effect for the tribological properties of these biomass composites in this study.

Astilbin from Engelhardtia chrysolepis enhances intestinal barrier functions in Caco-2 cell monolayers.

Astilbin, which is one of polyphenolic compounds isolated from the leaves of Engelhardtia chrysolepis HANCE (Chinese name, huang-qui), is available as the effective component in food and cosmetics because of its anti-oxidant and anti-inflammatory effects. The tight junction (TJ) proteins, which protect the body from foreign substances, are related to adhesion between a cell and a cell. Previously, the enhancement of TJ's functions induced by aglycones of flavonoids has been demonstrated, but the effects of the glycosides such as astilbin have not been observed yet. In this study, we investigated the effects of astilbin on the TJ's functions, and human colon carcinoma Caco-2 cell monolayers were used to evaluate the effects of astilbin on transepithelial electrical resistance (TER) value and the mRNA and proteins expressions of TJ-related molecules. Astilbin increased the TER value, mRNA expression levels of claudin-1 and ZO-2, and protein expression levels of occludin and ZO-2 in Caco-2 cells. Astilbin also increased the TER value in Caco-2 cells co-stimulated with TNF-α plus IFN-γ, and moreover upregulated the protein expression of TJ-related molecules in Caco-2 cells co-treated with TNF-α plus IFN-γ. These results suggest that astilbin can enhance the expressions of TJ-related molecules, leading to upregulation of the barrier functions in the intestinal cells.

Lentinan degradation in the Lentinula edodes fruiting body during postharvest preservation is reduced by downregulation of the exo-ß-1,3-glucanase EXG2.

Lentinan from Lentinula edodes fruiting bodies (shiitake mushrooms) is a valuable ß-glucan for medical purposes based on its anticancer activity and immunomodulating activity. However, lentinan content in fruiting bodies decreases after harvesting and storage due to an increase in glucanase activity. In this study, we downregulated the expression of an exo-ß-1,3-glucanase, exg2, in L. edodes using RNA interference. In the wild-type strain, ß-1,3-glucanase activity in fruiting bodies remarkably increased after harvesting, and 41.7% of the lentinan content was lost after 4 days of preservation. The EXG2 downregulated strain showed significantly lower lentinan degrading activity (60-70% of the wild-type strain) in the fruiting bodies 2-4 days after harvesting. The lentinan content of fresh fruiting bodies was similar in the wild-type and EXG2 downregulated strains, but in the downregulated strain, only 25.4% of the lentinan was lost after 4 days, indicating that downregulation of EXG2 enables keeping the lentinan content high longer.

Macrophage activation-mediated hydrogen peroxide generation by the royal sun medicinal mushroom Agaricus brasiliensis (Higher Basidiomycetes).

Agaricus brasiliensis has been demonstrated to have potent antitumor activity. The activity is postulated to act through mediation of the host immune system. We have reported that A. brasiliensis extract (ABE) inhibited compound 48/80 induced a systemic anaphylaxis-like reaction, ear swelling response, and passive cutaneous anaphylaxis-like reaction in mice. There is some recent information available on the mechanism of antiallergic effects resulting from oral administration of ABE. However, information regarding how ABE may activate macrophages through intestinal epithelial cells is still limited. To clarify the mechanism of macrophages activation by ABE, a gut in vitro model constructed of Caco-2 and RAW264.7 cells was applied. Treatment of ABE to the apical compartment resulted in significant increases in tumor necrosis factor (TNF)-α production in the basolateral compartment. Moreover, addition of catalase to the basolateral compartment before ABE treatment suppressed TNF-α production completely, but the addition of superoxide dismutase did not suppress this at all. These data suggest that ABE could potentiate hydrogen peroxide emissions from Caco-2 cells into the basolateral side and activate macrophages, which is important in the immune system.

Intestinal anti-inflammatory activity of lentinan: influence on IL-8 and TNFR1 expression in intestinal epithelial cells.

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. It is unknown whether ß-1,3;1,6-glucan can induce immune suppressive effects. Here, we study intestinal anti-inflammatory activity of Lentinula edodes-derived ß-1,3;1,6-glucan, which is known as lentinan. Dextran sulfate sodium (DSS)-induced colitis mice were used to elucidate effects of lentinan in vivo. In the cellular level assessment, lentinan was added into a co-culture model consisting of intestinal epithelial Caco-2 cells and LPS-stimulated macrophage RAW264.7 cells. Ligated intestinal loop assay was performed for assessing effects of lentinan on intestinal epithelial cells (IECs) in vivo. Oral administration of lentinan (100 µg/mouse) significantly ameliorated DSS-induced colitis in body weight loss, shortening of colon lengths, histological score, and inflammatory cytokine mRNA expression in inflamed tissues. Lentinan reduced interleukin (IL)-8 mRNA expression and nuclear factor (NF)-κB activation in Caco-2 cells without decreasing of tumor necrosis factor (TNF)-α production from RAW264.7 cells. Flow cytometric analysis revealed that surface levels of TNF receptor (TNFR) 1 were decreased by lentinan treatment. A clathrin-mediated endocytosis inhibitor, monodansylcadaverine, canceled lentinan inhibition of IL-8 mRNA expression. Moreover, lentinan inhibited TNFR1 expression in Caco-2 cells in both protein and mRNA level. Lentinan also inhibited TNFR1 mRNA expression in mouse IECs. These results suggest that lentinan exhibits intestinal anti-inflammatory activity through inhibition of IL-8 mRNA expression associated with the inhibition of NF-κB activation which is triggered by TNFR1 endocytosis and lowering of their expression in IECs. Lentinan may be effective for the treatment of gut inflammation including IBD.

Immunomodulating compounds in Basidiomycetes.

Mushrooms are distinguished as important food containing immunomodulating and anticancer agents. These compounds belong mostly to polysaccharides especially ß-d-glucans. Among them, ß-1,3-glucan with side chain ß-1,6-glucose residues have more important roles in immunomodulating and antitumor activities. In this review, we have introduced polysaccharide mainly from Lentinula edodes and Agaricus blazei Murill with immunomodulating and antitumor activities. In addition, the mechanism of activation of immune response and signal cascade are also reviewed.

Intestinal anti-inflammatory activity of luteolin: role of the aglycone in NF-κB inactivation in macrophages co-cultured with intestinal epithelial cells.

The flavonoid luteolin is reported to exert anti-inflammatory properties. In this study, we investigated whether luteolin inhibits gut inflammation, using in vivo and in vitro inflammation models. In a dextran sulfate sodium (DSS)-induced colitis mouse model, luteolin (20 and 50 mg/kg) significantly ameliorated shortening of colon length and histological score. Immunohistochemical analysis showed that luteolin also significantly inhibited infiltration of macrophages and interferon (IFN)-γ-producing CD4⁺ T cells into the colonic mucosa. Treatment with luteolin also improved IFN-γ mRNA expression in the colon. At the cellular level, a co-culture consisting of intestinal epithelial Caco-2 and macrophage RAW264.7 cells, stimulated with lipopolysaccharide, the addition of luteolin (100 µM) suppressed interleukin (IL)-8 mRNA expression in Caco-2 cells without epithelial monolayer disruption. Expression of tumor necrosis factor (TNF)-α protein and proinflammatory cytokines mRNA (TNF-α, IL-6, and IL-1ß) in RAW264.7 cells were also suppressed. HPLC analysis and subsequent cellular assay revealed that aglycone of luteolin was present in the basolateral supernatant of this system at a sufficient concentration to suppress TNF-α production and nuclear factor (NF)-κB activation of RAW264.7 cells. These results suggest that the luteolin aglycones released from the Caco-2 epithelium inhibits NF-κB nuclear translocation in RAW264.7 cells, followed by reduction of TNF-α mRNA expression, which results in downregulation of IL-8 mRNA expression in Caco-2 cells. The mechanism by which aglycone inhibits inflammation is important for understanding the roles of luteolin in diet.

Modulation of platelet aggregation-related eicosanoid production by dietary F-fucoidan from brown alga Laminaria japonica in human subjects.

Laminaria japonica is traditionally eaten in Japan as a beneficial food for thrombosis. The alga contains two specific ingredients, a xanthophyll fucoxanthin (FX) and a polysaccharide, F-fucoidan (FD). The aim of the present study was to investigate whether FX or FD exhibited anti-thrombotic effects. For this purpose, three types of capsules, containing 1 mg FX, 400 mg fucoidan, and both, were prepared from the alga and administered to volunteers for 5 weeks. The dose of FD or FD+FX significantly shortened lysis time (LT) of the thrombus measured by a global thrombosis test in the blood, but FX did not. Examining the mechanism, dietary FD increased H2O2 and the secretion of prostacyclin (PGI2), a potent inhibitor of platelet aggregation, in the blood, although FD was under the detection limit in the blood, determining with its monoclonal antibody. Furthermore, in mouse experiments, dietary FD was totally excreted into the faeces and was not incorporated into the blood. We then employed a co-culture system of a Caco-2 cell monolayer with fresh human blood. The addition of FD to Caco-2 cells stimulated the expression of NADPH oxidase 1 (NOX1) and dual oxidase 2 (DUOX2) mRNA and secreted H2O2 onto the blood side accompanied by a significant increase in serum PGI2 production. These effects were invalidated by the combined addition of FD with its monoclonal antibody. The results suggested that dietary FD stimulated the expression of H2O2-producing enzymes in intestinal epithelial cells and released H2O2 into the blood, which played a signalling role to increase PGI2 production and then shortened LT for thrombi.

Reappraisal of the taxonomy of Streptococcus suis serotypes 20, 22, 26, and 33 based on DNA-DNA homology and sodA and recN phylogenies.

To date, Streptococcus suis was divided into thirty-three serotypes based on its polysaccharide capsular antigens. Although 16S rRNA sequence similarities of serotypes 20, 22, 26, and 33 reference strains to the type strain NCTC 10234(T) were below the threshold value of 98.5% to assign them to S. suis species, no strong evidence support to reclassification. Here, their taxonomic identities were determined by DNA-DNA hybridization assays and by partial sequencing of the sodA and recN genes. Our results confirmed that the serotype 20, 22, 26, and 33 reference strains were distantly related to the type strain NCTC 10234(T) and the whole sequence strain P1/7 of S. suis. Moreover, the reference strains of serotypes 20, 22, and 26 were closely related to each other but distinct from the serotype 33 reference strain. Sequencing analyses of sodA and recN of a total 33 serotype reference strains showed that the serotype 20, 22, and 26 reference strains and the serotype 33 reference strain did not fall with not only other serotypes of S. suis, but also other streptococcal species (63 strains of 56 species for sodA and 87 strains of 55 species for recN). The evidence further substantiates the view that the reference strains of serotypes 20, 22, 26 and 33 should be taxonomically removed from S. suis, although their taxonomic designations and determinative phenotypic characteristics are yet to be addressed.

Anti-allergic effect of lactic acid bacteria isolated from seed mash used for brewing sake is not dependent on the total IgE levels.

Lactic acid bacteria (LAB) in fermented foods have attracted considerable attention recently as treatment options for allergic diseases, the incidence of which has been increasing worldwide. Five strains of LAB isolated from kimoto, the traditional seed mash used for brewing sake, were screened for the ability to suppress IgE-mediated hypersensitivity reaction. Leuconostoc mesenteroides and Lactobacillus sakei, the normal microflora in kimoto, significantly suppressed the reaction, but the contaminant Lactobacillus curvatus did not. Next, we examined the effect of L. sakei LK-117 on atopic dermatitis in the NC/Nga mouse model. LK-117 supplementation significantly reduced the development of atopic dermatitis-like skin lesions in a manner independent of the IgE plasma levels. In the in vitro intestinal model constructed using the human intestinal epithelial cell line Caco-2 and murine macrophage cell line RAW 264.7, treatment with L. sakei LK-117, but not L. curvatus, significantly upregulated TNF-α production from RAW264.7 cells. This result indicated that L. sakei on the apical side affected the macrophages on the basolateral side, and this organism may have the ability to improve allergy symptoms mediated by the intestinal immune system.

Structure-activity relationships of α-, ß(1)-, γ-, and δ-tomatine and tomatidine against human breast (MDA-MB-231), gastric (KATO-III), and prostate (PC3) cancer cells.

Partial acid hydrolysis of the tetrasaccharide (lycotetraose) side chain of the tomato glycoalkaloid α-tomatine resulted in the formation of four products with three, two, one, and zero carbohydrate side chains, which were separated by high-performance liquid chromatography (HPLC) and identified by thin-layer chromatography (TLC) and liquid chromatography ion-trap time-of-flight mass spectrometry (LCMS-IT-TOF). The inhibitory activities in terms of IC(50) values (concentration that inhibits 50% of the cells under the test conditions) of the parent compound and the hydrolysates, isolated by preparative HPLC, against normal human liver and lung cells and human breast, gastric, and prostate cancer cells indicate that (a) the removal of sugars significantly reduced the concentration-dependent cell-inhibiting effects of the test compounds, (b) PC3 prostate cancer cells were about 10 times more susceptible to inhibition by α-tomatine than the breast and gastric cancer cells or the normal cells, (c) the activity of α-tomatine against the prostate cancer cells was 200 times greater than that of the aglycone tomatidine, and (d) the activity increased as the number of sugars on the aglycone increased, but this was only statistically significant at p < 0.05 for the normal lung Hel299 cell line. The effect of the alkaloids on tumor necrosis factor α (TNF-α) was measured in RAW264.7 macrophage cells. There was a statistically significant negative correlation between the dosage of γ- and α-tomatine and the level of TNF-α. α-Tomatine was the most effective compound at reducing TNF-α. The dietary significance of the results and future research needs are discussed.

Pharmacokinetics of fucoxanthinol in human plasma after the oral administration of kombu extract.

Dietary fucoxanthin has been reported to exert several physiological functions, and fucoxanthinol is considered to be the primary active metabolite of fucoxanthin. However, there is no information about the pharmacokinetics of fucoxanthinol in human subjects. In the present study, eighteen human volunteers were orally administered kombu extract containing 31 mg fucoxanthin, and their peripheral blood was collected 5 min before and 0·5, 1, 2, 4, 8 and 24 h after the treatment. Plasma fucoxanthinol concentrations were measured by HPLC, and the pharmacokinetics of fucoxanthinol were as follows: maximum concentration, 44·2 nmol/l; time at maximum concentration, 4 h; terminal half-time, 7·0 h; area under the curve (AUC) for 1-24 h, 578·7 nmol/l × h; AUC(∞), 663·7 nmol/l × h. In addition to fucoxanthinol, we also attempted to detect amarouciaxanthin A, a hepatic metabolite of fucoxanthinol, using HPLC, but it was not present in the volunteers' plasma. On the other hand, a peak that was suspected to represent the cis-isomer of fucoxanthinol was found in the HPLC chromatogram. By comparing the present results with those of a previous study using mice, we found that the bioavailability and metabolism of fucoxanthinol differ between human subjects and mice.

TLR ligands of Lactobacillus sakei LK-117 isolated from seed mash for brewing sake are potent inducers of IL-12.

Many studies have investigated the immunostimulatory effects of bacteria, such as the anti-allergic effects of lactic acid bacteria (LAB) and LAB-fermented milk. Importantly, these anti-allergic effects have been observed for both viable and nonviable bacteria. However, there are no reported immunological effects of LAB isolated from kimoto, the traditional yeast starter culture used for brewing sake, which also involves spontaneous lactate fermentation. In this study, we determined whether the Leuconostoc mesenteroides and Lactobacillus sakei bacterial strains obtained from kimoto affected the production of interleukin-12 (IL-12), an inducer of the T-helper type-1 immune response. By incubating autoclaved bacteria with J774.1 macrophage-like cells, we found that L. sakei LK-117 induced a sustained increase in IL-12p40 production. The IL-12-inducing ability of LK-117 was unaffected by anti-TLR2 neutralization and was entirely inhibited when the LK-117 cells were treated with RNase. When LK-117 cells were treated with M-1, an N-acetylmuramidase, at varying concentrations and for different periods of time, the ability of the bacteria to induce IL-12 decreased quickly. Although an active fraction could be prepared by chromatography from the soluble products of enzymolysis, the fraction's induction ability was <2% of that of intact organisms, and induction ability disappeared completely upon anti-TLR2 neutralization after treating the active fraction with RNase. These results suggest that single-stranded RNA released from cells that were disrupted by autoclaving might act as a TLR ligand and provide a novel mechanism in which heat-killed LAB could be used to regulate immune activity.

Helicobacter suis KB1 derived from pig gastric lymphoid follicles induces the formation of gastric lymphoid follicles in mice through the activation of B cells and CD4 positive cells.

"Helicobacter heilmannii" ("H. heilmannii"), which belongs to the genus Helicobacter, is a group of bacterial species that display a long spiral-shaped morphology. Recent studies have demonstrated that "H. heilmannii" type 1 is actually H. suis, which mainly colonizes the stomachs of various animals and humans. However, the influence of H. suis on gastric diseases remains to be fully elucidated. In this report, we revealed the relationship between natural H. suis infection and follicular gastritis in the pig stomachs. From sequence analysis of the 16S rRNA, urease A, and urease B genes, the presence of H. suis was confirmed in pig gastric lymphoid follicles, and this bacterium was named H. suis KB1. In addition, H. suis KB1 was inoculated into C57BL/6J mice, and the following mouse model of the pathogenesis of follicular gastritis by H. suis infection was established: H. suis KB1 colonizes the mouse stomach, and moreover, induces the development of lymphoid follicles and acquired immune responses characterized by the activation of B cells and CD4 positive cells. These results may lead to better understanding of the relationship between H. suis and gastric diseases, especially follicular gastritis; and furthermore, our findings emphasize the zoonotic aspects of animal-human infection by H. suis.

Oral Treatment with Extract of Agaricus blazei Murill Enhanced Th1 Response through Intestinal Epithelial Cells and Suppressed OVA-Sensitized Allergy in Mice.

To clarify the mechanism of the antiallergic activity of Agaricus blazei Murill extract (ABME), the present paper used an in vivo allergy model and an in vitro intestinal gut model. During OVA sensitization, the serum IgE levels decreased significantly in ABME group. Interleukin (IL)-4 and -5 produced from OVA-restimulated splenocytes was significantly decreased, and anti-CD3ε/CD28 antibody treatment also reduced IL-10, -4, and -5 production and increased IFN-γ production in ABME group. These results suggest that oral administration of ABME improves Th1/Th2 balance. Moreover, a coculture system constructed of Caco-2 cells and splenocytes from OT-II mice or RAW 264.7 cells indicated that the significant increases in IFN-γ production by ABME treatment. Therefore, it was concluded that the antiallergic activity of ABME was due to the activation of macrophages by epithelial cells and the promotion of the differentiation of naïve T cells into Th1 cells in the immune.