著者
Saori TAKAHASHI Taku YOSHIYA Kumiko YOSHIZAWA-KUMAGAYE Toshihiro SUGIYAMA
出版者
Biomedical Research Press
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.36, no.3, pp.219-224, 2015-06-01 (Released:2015-06-24)
参考文献数
23
被引用文献数
2 6

Angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase which is highly homologous to angiotensin-converting enzyme (ACE). ACE2 produces vasodilator peptides angiotensin 1-7 from angiotensin II. In the present study, we synthesized various internally quenched fluorogenic (IQF) substrates (fluorophore-Xaa-Pro-quencher) based on the cleavage site of angiotensin II introducing N-terminal fluorophore N-methylanthranilic acid (Nma) and C-terminal quencher Nε-2,4- dinitrophenyl-lysine [Lys(Dnp)]. The synthesized mixed substrates “Nma-Xaa-Pro-Lys(Dnp)” were hydrolyzed by recombinant human (rh) ACE2. The amount of each product was determined by liquid chromatography mass spectrometry (LC-MS) with fluorescence detection and it was found that Nma-His-Pro-Lys(Dnp) is the most suitable substrate for rhACE2. The Km, kcat, and kcat/Km values of Nma-His-Pro-Lys(Dnp) on rhACE2 were determined to be 23.3 μM, 167 s−1, and 7.17 μM−1 s−1, respectively. Using the rhACE2 and the newly developed IQF substrate, we found rhACE2 inhibitory activity in soybean and isolated the active compound soybean ACE2 inhibitor (ACE2iSB). The physicochemical data on the isolated ACE2iSB were identical to those of nicotianamine. ACE2iSB strongly inhibited rhACE2 activity with an IC50 value of 84 nM. This is the first demonstration of an ACE2 inhibitor from foodstuffs.
著者
Miro SMRIGA Toshihiko ANDO Masahisa AKUTSU Yasushi FURUKAWA Kiyoshi MIWA Yasushi MORINAGA
出版者
Biomedical Research Press
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.28, no.2, pp.85-90, 2007 (Released:2007-05-16)
参考文献数
43
被引用文献数
18 26 26

Dietary supplementation with an essential amino acid L-lysine has been shown to reduce chronic anxiety in humans with low dietary intake of L-lysine. A combination of L-lysine and L-arginine has been documented to normalize hormonal stress responses in humans with high trait anxiety. The present study was carried out in one hundred eight healthy Japanese adults. The aim of study was to find out whether a week-long oral treatment with L-lysine (2.64 g per day) and L-arginine (2.64 g per day) reduces trait and stress-induced state anxiety and basal levels of stress hormones. We confirmed that, without regard to gender, the amino acid treatment significantly reduced both trait anxiety and state anxiety induced by cognitive stress battery. In addition, we found that the treatment with L-lysine and L-arginine decreased the basal levels of salivary cortisol and chromogranin-A (a salivary marker of the sympatho-adrenal system) in male subjects. These results of this double-blind, placebo controlled and randomized study confirm the previous findings in humans and animals and point to a combination of L-lysine and L-arginine as a potentially useful dietary intervention in otherwise healthy humans with high subjective levels of mental stress and anxiety.
著者
Chikako TOMIYAMA-MIYAJI Mayumi WATANABE Takahiko OHISHI Yasuhiro KANDA Eisuke KAINUMA Hanaa Y. BAKIR JiWei SHEN HongWei REN Masashi INOUE Keiho TAJIMA XueFeng BAI Toru ABO
出版者
Biomedical Research Press
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.28, no.3, pp.119-125, 2007 (Released:2007-07-12)
参考文献数
23
被引用文献数
11 11

Since high levels of hyperthermia induce immunosuppression to a certain extent (i.e., granulocytosis and lymphocytopenia) in patients, we applied mild hyperthermia in volunteers using equipment enabling well-controlled hyperthermia. Restricted control of rectal temperature at 39.4 (± 0.2)°C for 30 min was conducted and various parameters of the body were examined. The most prominent change observed during exposure to hyperthermia was elevated levels of pH and PO2 in the blood, even in the venous blood. A transient elevation of ACTH, cortisol and growth hormone in the blood was also seen during this time. In parallel with this phenomenon, the number of total lymphocytes and those of its subsets (especially CD57+ or CD56+ NK cells and NKT cells) increased. More interestingly, the proportion of HLA-DR (MHC class II antigens) increased in NK and NKT cells, and their intensity on the surface of CD20+ B cells increased. These results suggest that mild hyperthermia is important for modulation of the functions of the circulatory, endocrine and immune systems.
著者
Masahiro TODA Kanehisa MORIMOTO Shingo NAGASAWA Kazuyuki KITAMURA
出版者
Biomedical Research Press
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.27, no.1, pp.11-14, 2006 (Released:2006-03-15)
参考文献数
19
被引用文献数
37 38

We assessed the stress relief effect of spa bathing by measuring sensitive salivary stress markers, cortisol and chromogranin A (CgA). From 12 healthy males, saliva samples were collected immediately before and after spa bathing, and 30 min after that. Salivary cortisol and CgA levels were determined by ELISA. Salivary cortisol levels decreased after spa bathing. This tendency was more pronounced in individuals with higher levels of stress. The high-stress group showed lower salivary CgA levels after spa bathing, while the low-stress group higher salivary CgA levels in the same condition. These findings suggest that the spa bathing has a moderate affect on the stress relief.
著者
Satoshi Haramizu Fuminori Kawabata Koichiro Ohnuki Naohiko Inoue Tatsuo Watanabe Susumu Yazawa Tohru Fushiki
出版者
Biomedical Research Press
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.32, no.4, pp.279-284, 2011 (Released:2011-08-30)
参考文献数
22
被引用文献数
6 9 5

Enhancement of energy expenditure and reducing energy intake are crucial for weight control. Capsiate, a non-pungent capsaicin analog, is known to suppress body fat accumulation and reduce body weight by enhancing of energy expenditure in both mice and humans. However, it is poorly understood whether suppressing body fat accumulation by capsiate administration is equal to exercise or not. The aim of this study is to compare the effects of repeated administration of capsiate and exercise and to investigate the weight rebound after repeated capsiate administration and/or exercise. In the present study, we report that 2 weeks treatment of capsiate and exercise increased energy metabolism and suppressed body fat accumulation during 4 more weeks of ad libitum feeding. The body weight in capsiate and exercise groups was significantly lower than that of control group. The oxygen consumption was significanlty increased in capsiate and exercise groups than in the vehicle administered mice. In addition, the abdominal adipose tissue weight in capsiate and exercise groups was significantly lower than that of control group. These results indicate that suppressing body fat accumulation by capsiate intake is beneficial for maintaining an ideal body weight as exercise.
著者
Mayumi Nagano Kuniyoshi Shimizu Ryuichiro Kondo Chickako Hayashi Daigo Sato Katsuyuki Kitagawa Koichiro Ohnuki
出版者
Biomedical Research Press
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.31, no.4, pp.231-237, 2010 (Released:2010-09-08)
参考文献数
27
被引用文献数
21 30 24

Hericium erinaceus, a well known edible mashroom, has numerous biological activities. Especially hericenones and erinacines isolated from its fruiting body stimulate nerve growth factor (NGF) synthesis, which expects H. erinaceus to have some effects on brain functions and autonomic nervous system. Herein, we investigated the clinical effects of H. erinaceus on menopause, depression, sleep quality and indefinite complaints, using the Kupperman Menopausal Index (KMI), the Center for Epidemiologic Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQI), and the Indefinite Complaints Index (ICI). Thirty females were randomly assigned to either the H. erinaceus (HE) group or the placebo group and took HE cookies or placebo cookies for 4 weeks. Each of the CES-D and the ICI score after the HE intake was significantly lower than that before. In two terms of the ICI, “insentive” and “palpitatio”, each of the mean score of the HE group was significantly lower than the placebo group. “Concentration”, “irritating” and “anxious” tended to be lower than the placebo group. Our results show that HE intake has the possibility to reduce depression and anxiety and these results suggest a different mechanism from NGF-enhancing action of H. erinaceus.
著者
Atsushi TOYODA Takahiro KAWASE Takamitsu TSUKAHARA
出版者
Biomedical Research Press
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.41, no.2, pp.101-111, 2020-04-01 (Released:2020-04-19)
参考文献数
41

The intestinal ecosystem is involved in the pathogenesis of mood disorders such as depression. Intestinal microbes can affect the central nervous system through the gut–brain axis, which raises the possibility of using probiotics for preventing depression. In this study, we examined the effect of heat-inactivated Lactobacillus gasseri CP2305 (CP2305) in a subchronic and mild social defeat stress (sCSDS) mouse model. sCSDS suppressed food intake. However, dietary CP2305 intake rescued it, suggesting that CP2305 improved the decreased appetite in sCSDS mice. sCSDS did not alter the gene expression of brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 in the hippocampus. However, dietary CP2305 provided following sCSDS increased the gene expression of these neurotrophins in the hippocampus. These findings suggest that CP2305 supplementation would aid in preventing psychosocial stress–induced disorders.
著者
Yuusuke SAITSU Akemi NISHIDE Kenji KIKUSHIMA Kuniyoshi SHIMIZU Koichiro OHNUKI
出版者
Biomedical Research Press
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.40, no.4, pp.125-131, 2019-08-01 (Released:2019-08-14)
参考文献数
42

Hericium erinaceus has been recognized as medical mushroom since ancient time, but its scientific evidence for human health has been still uncertain. In this study, we tested a randomized, double-blind, placebo-controlled parallel-group comparative study to evaluate the improvement of the cognitive functions by taking supplements containing fruiting body of H. erinaceus for 12 weeks. We performed three kinds of tests: Mini Mental State Examination (MMSE), Benton visual retention test, and Standard verbal paired-associate learning test (S-PA). MMSE alone showed that oral intake of H. erinaceus significantly improved cognitive functions and prevented from the deterioration. We speculate that various chemical compounds, including hericenones, in the mushroom have multiple effects to the brain neural networks and improve cognitive functions. Oral intake of H.erinaceus is safe and convenient method for dementia prevention so far.
著者
Takashi HAYASHI Satoru TSUJII Tadao IBURI Tamiko TAMANAHA Keiko YAMAGAMI Rieko ISHIBASHI Miyo HORI Shigeko SAKAMOTO Hitoshi ISHII Kazuo MURAKAMI
出版者
Biomedical Research Press
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.28, no.6, pp.281-285, 2007 (Released:2008-01-18)
参考文献数
26
被引用文献数
20 22

To elucidate the sustainable effects of laughter on gene expression, we recruited type 2 diabetic patients who were in-patient for receiving self-management education and examined time-dependent regulation for gene expression by laughter. Two-day experiment was performed. On one day, the patients watched comic video and laughed together with hospital staffs. On the other day, they participated in an inpatient diabetes educational program. Blood samples were collected before and 1.5, 4 h after watching comic video or spending lecture time, and changes in gene expression were comprehensively analyzed by microarray technique. Of the 41,000 genes analyzed, the laughter relatively up-regulated 39 genes, among which, 27 genes were relatively increased in the expression for all the observation period after watching comic video. By functional classification of these genes, 14 genes were found to be related to natural killer cell activity. No genes were included that are directly involved in blood glucose regulation, though successive suppression of postprandial blood glucose levels was observed. These results suggest that the laughter influences the expression of many genes classified into immune responses, and may contribute to amelioration of postprandial blood glucose elevation through a modulation of NK cell activity caused by up-regulation of relating genes.
著者
Won Jae HUH Joseph TE ROLAND Masato ASAI Izumi KAJI
出版者
Biomedical Research Press
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.41, no.2, pp.113-118, 2020-04-01 (Released:2020-04-19)
参考文献数
19

Clinical interest into the function of tuft cells in human intestine has increased in recent years. However, no quantitative study has examined intestinal tuft cells in pathological specimens from patients. This study quantified tuft cell density by using a recently identified marker, specific for tyrosine phosphorylation (pY1798) of girdin (also known as CCDC88A or GIV) in the duodenum of pediatric patients. Deidentified sections with pathological diagnosis of acute duodenitis, ulcer, or celiac disease, and age-matched normal control were analyzed under double-blind conditions. Immunostaining for pY1798-girdin demonstrated the distinct shape of tuft cells with and filopodia-like basolateral membrane structure and a small apical area, which densely expressed gamma-actin. As compared to normal tissues, the specimens diagnosed as celiac disease and duodenal ulcer had significantly fewer tuft cell numbers. In contrast, acute duodenitis showed varied population of tuft cells. The mucosa with severe inflammation showed lower tuft cell numbers than the specimens with none to mild inflammation. These results suggest that loss of tuft cells may be involved in prolonged inflammation in the duodenal mucosa and disrupted mucosal integrity. pY1798-girdin and gamma-actin are useful markers for investigating the distribution and morphologies of human intestinal tuft cells under healthy and pathological conditions.
著者
Hiroki YOKOYAMA Shinichi OKADA Yuko YAMADA Koichi KITAMOTO Sumire INAGA Hironobu NAKANE Toshiyuki KAIDOH Kazuho HONDA Susumu KANZAKI Noriyuki NAMBA
出版者
Biomedical Research Press
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.41, no.2, pp.81-90, 2020-04-01 (Released:2020-04-19)
参考文献数
21

Antibody-mediated rejection (ABMR) is an important cause of both short- and long-term injury to renal allografts. Transplant glomerulopathy (TG) is strongly associated with ABMR and reduced graft survival. Ultrastructural changes in early-stage ABMR include TG as a duplication of the glomerular basement membrane (GBM), which can be observed only by transmission electron microscopy (TEM). Low-vacuum scanning electron microscopy (LVSEM) is a new technique that allows comparatively inexpensive, rapid, and convenient observations with high magnification. We analyzed human renal transplants using LVSEM and evaluated the ultrastructural changes representing TG in ABMR. GBM duplication was more clearly visible in the LVSEM images than in the light microscopy (LM) images. In the ABMR group, the cg score of the Banff classification was higher in 54% (7/13) of specimens for LVSEM images than for LM images. And 4 specimens exhibited duplication of the GBM analyzed by LVSEM, but not by LM. In addition, three-dimensional ultrastructural changes, such as coarse meshwork structures of GBM, were observed in ABMR specimens. The ABMR group also exhibited ultrastructural changes in the peritubular capillary basement membranes. In conclusion, analyses of renal transplant tissues using LVSEM allows the identification of GBM duplication and ultrastructural changes of basement membranes at the electron microscopic level, and is useful for early-stage diagnosis of ABMR.
著者
Hikaru TAKESHITA Eri WATANABE Yoshihiko NOROSE Yasuhiko ITO Hidemi TAKAHASHI
出版者
Biomedical Research Press
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.40, no.2, pp.87-95, 2019-04-01 (Released:2019-04-13)
参考文献数
22

Helicobacter pylori (H. pylori) urease is a key protein for persistent infection of the bacteria in the stomach. Although H. pylori generally induce anti-H. pylori-specific antibodies (Abs), these Abs do not usually work for eradication or prevention of the H. pylori infection. In our previous study, we identified a linear epitope composed of 19-mer peptides termed UB-33, CHHLDKSIKEDVQFADSRI, within the large subunit of H. pylori urease. Anti-UB-33-specific Abs neutralized the enzymatic activity of H. pylori urease in vitro. In the present study, we evaluated the effect of immunization of BALB/c mice with H. pylori UB-33 peptide. After confirming the production of anti-UB-33-specific Abs, mice were challenged orally with H. pylori Sydney Strain-1 (SS-1). Mice producing anti-UB-33-specific Abs were not infected with SS-1, and the amount of SS-1 isolate in their stomach was significantly reduced. Also, the urease-negative mutant of H. pylori, HPP1801, did not colonize in the stomach, indicating that H. pylori urease was a critical element for infection of H. pylori in the gastric mucosa. Moreover, mice producing UB-33-specific Abs apparently suppressed H. pylori infection in the stomach where anti-UB-33 Abs were secreted in the gastric juice, indicating that H. pylori colonization was inhibited in the presence of anti-UB-33 Abs. In addition, the neutralization activity of sera from mice immunized with purified urease was less potent than that in the sera from mice immunized with UB-33. Furthermore, the recognition of epitope UB-33 was mediated through Toll-like receptor 2 (TLR2) on the B-1 cells using TLR2-knockout BALB/c mice in vivo. These results indicate that liner peptide UB-33 should be used for immunization to induce neutralizing Abs instead of purified H. pylori urease to prevent H. pylori infection and their colonization in the stomach.
著者
Kakeru ITO Miho YASUDA Yuki MAEDA Jean-Michel FUSTIN Yoshiaki YAMAGUCHI Yuka KONO Hiromitsu NEGORO Akihiro KANEMATSU Osamu OGAWA Masao DOI Hitoshi OKAMURA
出版者
Biomedical Research Press
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.39, no.2, pp.57-63, 2018-04-01 (Released:2018-04-18)
参考文献数
29

Micturition behavior follows regular day/night fluctuations, and unwanted increase in micturition could occur during night in jet lag condition. To clarify the effect of jet lag on micturition behavior, we simultaneously detected circadian micturition patterns and locomotor activity rhythms of mice under experimental jet lag conditions, by applying the improved automated Voided Stain on Paper (aVSOP) method. When wild-type (WT) mice were phase-advanced for 8 hours, day-night variation of micturition was disrupted suddenly, and this irregular daily micturition continued until 8 days, although their activity rhythms entrained gradually day by day until 8 days. We also examined how jet lag induced changes of micturition in Per-null mice lacking Per1, Per2 and Per3 genes, whose endogenous clock is completely disrupted. We found both micturition and locomotor activity of Per-null mice promptly entrained to the new LD cycle. These findings suggest that the irregular micturition during jet lag is caused along with the gradual shift of the endogenous clock, and paradoxically, jet lag-associated abnormality was absent when endogenous circadian oscillations were genetically disrupted.
著者
Masahiro TODA Shinsuke KUSAKABE Shingo NAGASAWA Kazuyuki KITAMURA Kanehisa MORIMOTO
出版者
Biomedical Research Press
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.28, no.2, pp.115-118, 2007 (Released:2007-05-16)
参考文献数
19
被引用文献数
17 27

We investigated the effect of laughter on salivary endocrinological stress marker chromogranin A (CgA). In saliva samples collected from 11 healthy males before and after watching a comic film or a non-humorous control film, salivary CgA levels were determined by enzyme-linked immunosorbent assay (ELISA). Samples taken after watching the comic film showed increased levels of CgA. This tendency was more pronounced in individuals with lower initial levels of stress. The control samples showed no significant change in CgA levels. Stress score, subjectively evaluated using a visual analog scale, decreased significantly after watching the comic film. These findings suggest that, in addition to a stress relief effect, laughter can bring about feeling uplifted or fulfilled.
著者
Yasuyuki Kudo Satoko Morohashi Kaori Takasugi Shinji Tsutsumi Hiroshi Ogasawara Norihiro Hanabata Tetsuro Yoshimura Fuyuki Sato Shinsaku Fukuda Hiroshi Kijima
出版者
Biomedical Research Press
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.32, no.2, pp.127-134, 2011 (Released:2011-05-03)
参考文献数
23
被引用文献数
2 3

Recent advances in endoscopic submucosal dissection (ESD) techniques contribute to endoscopic treatment of early gastric cancer (EGC). Recognition of chronic atrophic gastritis as the background is important for high-quality detection and diagnosis of EGC. But, relationships between EGC and atrophy of the background gastric mucosa caused by Helicobacter pylori are not well understood. The present study demonstrated histopathological phenotypes of EGC, as well as chronic atrophic gastritis as background mucosa of EGC. We evaluated mucosal heights, number of glands, and degree of intestinal metaplasia (IM) of the background gastric mucosa, using 81 cases of EGC resected by ESD. Gastric phenotype cancer cases showed IM of the background gastric mucosa less frequently, compared with intestinal phenotype cancer cases (score of IM, 1.15 vs. 1.65, P = 0.012). The average mucosal heights around EGC were lower in moderately to poorly differentiated adenocarcinoma cases than well differentiated adenocarcinoma cases (442.6 μm vs. 500.2 μm, P = 0.011). The mucosal atrophy indicated by average heights of background mucosa was low in the gastric phenotype cancer cases, compared with the intestinal phenotype cancercases (452.8 μm vs. 505.6 μm, P = 0.018). In the fundic gland area, the mucosal heights were low in the gastric phenotype cancer cases, compared with the intestinal phenotype cancer cases (413.2 μm vs. 495.5 μm, P = 0.015). Our results using EGC specimens indicated that gastric phenotype cancer and moderately to poorly differentiated adenocarcinoma had atrophic background mucosa with lower mucosal heights and less IM. The atrophic gastric mucosa with less IM is thought to play an important role in gastric carcinogenesis, especially tumoriogenesis of gastricphenotype cancer.