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 5

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
Takaaki Tomofuji Daisuke Ekuni Koichiro Irie Tetsuji Azuma Naofumi Tamaki Takayuki Maruyama Tatsuo Yamamoto Tatsuo Watanabe Manabu Morita
出版者
バイオメディカルリサーチプレス
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.32, no.5, pp.343-349, 2011 (Released:2011-10-28)
参考文献数
31
被引用文献数
4 22

Gingival response to periodontal inflammation generates excessive lipid peroxide and such a condition may augment systemic health through increased circulating lipid peroxide. The purpose of the present study was to investigate whether the generation of lipid peroxide in periodontal inflammation could induce tissue injury in the liver, heart, kidney and brain using a rat model. Twelve Wistar rats (8 week-old male) were divided into 2 groups: the periodontal inflammation group, receiving topical application of lipopolysaccharide and proteases to the gingival sulcus for 4 weeks, and the control group using instead pyrogen-free water. After blood samples were collected, specimens from the brain, heart, liver and kidney were resected to determine the concentration of 8-hydroxydeoxyguanosine (an indicator of oxidative DNA damage). Gingival and serum levels for hexanoyl-lysine were measured to evaluate lipid peroxide. Administration of lipopolysaccharide and proteases induced periodontal inflammation, with increasing gingival and serum levels of hexanoyl- lysine. The level of 8-hydroxydeoxyguanosine increased 2.27, 2.01, 1.49 and 1.40 times in mitochondrial DNA from the liver, heart, kidney and brain of rats with periodontal inflammation, respectively. The results reveal that excessive production of lipid peroxide following periodontal inflammation is involved in oxidative DNA damage of the brain, heart, liver and kidney.
著者
Hirotoshi UTSUNOMIYA Tadashi YAMAKAWA Junzo KAMEI Kazuaki KADONOSONO Shun-Ichi TANAKA
出版者
バイオメディカルリサーチプレス
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.26, no.5, pp.193-200, 2005 (Released:2005-12-05)
参考文献数
30
被引用文献数
11 19

Dried plums, considered a healthy food in the West and used as medicine in India, contain phenolic compounds with protective actions against age-related diseases. Effects of oral plum ekisu (concentrated juice) on lipid and glucose tolerance were assessed in insulin-resistant obese Wistar fatty rats. Plum ingestion decreased blood glucose (P < 0.05) and plasma triglyceride concentrations (P < 0.01) compared with controls. Plum treatment for 2 weeks reduced areas under the curve (AUCs) for glucose and insulin during a glucose tolerance test. In db/db mice, plum decreased these AUCs, and also blood glucose during an insulin tolerance test. Plum treatment significantly increased plasma adiponectin concentrations and PPARγ mRNA expression in adipose tissue from Wistar fatty rats. Plum thus may increase insulin sensitivity in these rats via adiponectin-related mechanisms.
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
Isao Nadaoka Masaaki Yasue Yasushi Kitagawa Yoshihiko Koga
出版者
バイオメディカルリサーチプレス
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.33, no.3, pp.145-152, 2012 (Released:2012-07-05)
参考文献数
60
被引用文献数
3 7 4

Dried rhizomes of Cimicifuga racemosa (CR), which are known as black cohosh, have been widely used as herbal dietary supplements to treat menopausal symptoms. The present study examined the effect of CR extracts on human psychological and physiological responses to acute stress induced by mental arithmetic tests, by measuring the subjective stress intensity, the brain-wave patterns according to electroencephalography, and the concentrations of salivary chromogranin-A and cortisol. The experiments were performed double-blind and their order was counterbalanced. Treatment with CR significantly attenuated the elevated subjective perception of stress and the increased salivary chromogranin-A levels compared with placebo treatment. CR extract also rapidly recovered the decrease in alpha waveband induced by performing the mental arithmetic task. We therefore propose that CR extracts might be suitable for the prevention and treatment of stressrelated disorders.
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
Mayumi Watanabe Osamu Takano Chikako Tomiyama Hiroaki Matsumoto Takahiro Kobayashi Nobuatsu Urahigashi Nobuatsu Urahigashi Toru Abo
出版者
バイオメディカルリサーチプレス
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.33, no.4, pp.243-248, 2012 (Released:2012-09-04)
参考文献数
24
被引用文献数
4 5

Skin rubdown using a dry towel (SRDT) to scrub the whole body is a traditional therapy for health promotion. To investigate its mechanism, 24 healthy male volunteers were studied. Body temperature, pulse rate, red blood cells (RBCs), serum levels of catecholamines and cortisol, blood gases (PO2, sO2, PCO2 and pH), lactate and glucose, and the ratio and number of white blood cells (WBCs) were assessed before and after SRDT. After SRDT, pulse rate and body temperature were increased. PO2, sO2 and pH were also increased and there was no Rouleaux formation by RBCs. Lactate level tended to increase, whereas that of glucose did not. Adrenaline and noradrenaline levels increased, indicating sympathetic nerve (SN) dominance with increase in granulocytes. WBC number and ratio were divided into two groups according to granulocyte ratio (≤ or < 60%) before SRDT: a normal group and a SN group. Only in the SN group did the granulocyte ratio decrease and the lymphocyte ratio and number increase after SRDT. It is suggested that SRDT is a mild aerobic, systemic exercise that might affect the immune system via the autonomic nervous system.
著者
Ken YAMAGUCHI Kenichi URAKAMI Takeshi NAGASHIMA Yuji SHIMODA Shumpei OHNAMI Sumiko OHNAMI Keiichi OHSHIMA Tohru MOCHIZUKI Keiichi HATAKEYAMA Masakuni SERIZAWA Yasuto AKIYAMA Kouji MARUYAMA Hirohisa KATAGIRI Yuji ISHIDA Kaoru TAKAHASHI Seiichiro NISHIMURA Masanori TERASHIMA Taiichi KAWAMURA Yusuke KINUGASA Yushi YAMAKAWA Tetsuro ONITSUKA Yasuhisa OHDE Takashi SUGINO Ichiro ITO Hiroyuki MATSUBAYASHI Yasue HORIUCHI Maki MIZUGUCHI Mutsumi YAMAZAKI Kengo INOUE Kimiko WAKAMATSU Misato SUGIYAMA Katsuhiko UESAKA Masatoshi KUSUHARA
出版者
バイオメディカルリサーチプレス
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.37, no.4, pp.259-264, 2016-08-01 (Released:2016-08-20)
参考文献数
25
被引用文献数
2

Using whole exome sequencing data obtained from 1,685 Japanese cancer patients, we examined genetic variations of germline TP53 and found 10 types of non-synonymous single nucleotide variants. In the present study, we focused on 6 patients with germline D49H mutation located in the transactivation domain 2 of p53 protein, since the mutation seemed to be prevalent in cancer patients and to be pathogenic. According to the initial survey for family history of the proband with the germline TP53 D49H mutation, one osteosarcoma patient and his pedigree fulfill the criteria for Li-Fraumeni-like syndrome and the 2009 Chompret criteria for germline TP53 mutation screening. Since this patient possesses double germline mutations of TP53 D49H and A159D, further studies are required to evaluate contribution of the D49H mutation in this morbidity. The remaining 5 patients had family histories of cancer, but none fulfills the criteria either for the Li-Fraumeni/Li-Fraumeni-like syndromes or the 2009 Chompret criteria for germline TP53 mutation screening. It is possible to postulate that the germline TP53 D49H mutation is likely to be low-penetrant in some pedigrees. The present study also indicates that the survey for the germline TP53 mutation plays an important role in clinical practice as it will prevent mistaking cancer patients with unusual heredities for sporadic cases.
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
Fuminori Kawabata Tomoko Tsuji
出版者
バイオメディカルリサーチプレス
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.32, no.6, pp.387-393, 2011 (Released:2011-12-25)
参考文献数
14
被引用文献数
3 8

The aim of this study was to determine the effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans by a double- blind, randomized, parallel-group, and placebo-controlled trial. In the Active group, eleven subjects ingested a supplement containing omega-3 fatty acid-rich fish oil (docosahexaenoic acid 783 mg/day, eicosapentaenoic acid 162 mg/day), bilberry extract (anthocyanidin 59 mg/day), and lutein (17.5 mg/day) in soft gel capsule form, every day for 4 weeks. In the Placebo group, nine subjects ingested placebo capsules. Before and after supplementation, subjects completed a questionnaire to determine their asthenopia symptoms and were also assessed for mental fatigue symptom by the visual analog scale (VAS) test. Asthenopia symptoms such as “stiff shoulder, low back pain”, “frustration”, “dry-eye”, and “stuffy head” were improved in the Active group. Furthermore, a score of mental fatigue was improved after 4 weeks of supplementation, and no side effects were observed after the 4-week supplementation and a 2-week washout period in the Active group. These results suggest that dietary supplementation with the combination of omega-3 fatty acid-rich fish oil, bilberry extract, and lutein may safely improve subjective symptoms of asthenopia and mental fatigue in humans.
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
Shimi Rani ROY Jun WANG Md. Rubel RANA Mikiko NAKASHIMA Toshinobu TOKUMOTO
出版者
バイオメディカルリサーチプレス
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.38, no.1, pp.79-87, 2017-02-01 (Released:2017-02-24)
参考文献数
25
被引用文献数
1

Oocyte maturation in medaka is induced by the maturation-inducing hormone (MIH) via its membrane receptor. The most likely candidates for the membrane receptor are membrane progestin receptors (mPRs). In order to characterize the mPRα subtype of medaka, a human cell line expressing the mPRα gene of medaka was established and its steroid binding property was assessed. The α subtype exhibited high binding affinity for 17,20β-DHP, the MIH in medaka. Treatment with a morpholino antisense oligonucleotide to mPRα blocked oocyte maturation in vivo. These results suggest that the medaka mPRα protein acts as an intermediary during MIH-induced oocyte maturation in medaka in a manner similar to that described previously for fish species.
著者
Tomomi SATOH-NAKAMURA Nozomu KUROSE Takafumi KAWANAMI Takuji NAKAMURA Haruka IWAO-KAWANAMI Akio NAKAJIMA Miyuki MIKI Tomoyuki SAKAI Yoshimasa FUJITA Masao TANAKA Toshihiro FUKUSHIMA Yasufumi MASAKI
出版者
バイオメディカルリサーチプレス
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.36, no.2, pp.143-153, 2015-04-01 (Released:2015-04-16)
参考文献数
43
被引用文献数
3 6 1

Proliferated IgG4+ plasma cells are polyclonal, suggesting that the pathogenesis of IgG4-related disease (IgG4-RD) involves upstream events related to the regulation of IgG4 expansion. We hypothesized that lymphoid follicle formation may play an important role in the pathogenesis of IgG4-RD. Using various antibodies, especially against monocyte, macrophage, and follicular dendritic cell markers, we immunohistochemically assessed the distribution of immune cells in lymphoid follicles. Pathological findings of tissue samples from patients with IgG4-RD (n = 22), reactive hyperplasia (n = 3), multicentric Castleman’s disease (n = 3), and Sjögren’s syndrome (n = 13) were analyzed. CD14-positive lymphoid follicles were observed only in patients with IgG4-RD, and CD14-positive cells were identified as follicular dendritic cells by multicolor immunohistochemistry. There were few differences in the distributions of other cell types between the IgG4-RD and control groups. The presence of CD14+ follicular dendritic cells in lymphoid follicles may play a pathophysiological role in IgG4-RD.
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
Eri Matsubara Kuniyoshi Shimizu Mio Fukagawa Yuka Ishizi Chikako Kakoi Tomoko Hatayama Jun Nagano Tsuyoshi Okamoto Koichiro Ohnuki Ryuichiro Kondo
出版者
バイオメディカルリサーチプレス
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.33, no.5, pp.299-308, 2012 (Released:2012-11-01)
参考文献数
34
被引用文献数
1 2

The perennial grass Vetiveria zizanioides (vetiver) is mainly cultivated for its fragrant essential oil. Although the components of the oil and their biological activities have been studied extensively, the effect of the volatiles emitted from the roots of V. zizanioides on humans has so far remained unexplored. We investigated the effects of volatile compounds emitted from the cut roots of V. zizanioides (1.0 g, low-dose conditions; 30 g, high-dose conditions) on individuals during a visual display terminal task. Participants who breathed the volatile compounds emitted under low-dose conditions showed faster reaction times and stimulation of sympathetic nerve activity as measured by electrocardiography. These effects were not observed under high-dose conditions. The total amounnt of volatiles emitted during the experiment was 0.25 μg under low-dose conditions and 1.35 &me;g under high-dose conditions. These findings indicate that volatile compounds emitted from the roots of V. zizanioides under low-dose conditions may have helped subjects to maintain performance in visual discrimination tasks while maintaining high sympathetic nerve system activity.
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
Yoshinao HOSAKA Sachiko OZOE Rikio KIRISAWA Hiromi UEDA Kazushige TAKEHANA Mamoru YAMAGUCHI
出版者
バイオメディカルリサーチプレス
雑誌
Biomedical Research (ISSN:03886107)
巻号頁・発行日
vol.27, no.5, pp.233-241, 2006 (Released:2006-11-13)
参考文献数
46
被引用文献数
11 17

The aim of this study was to clarify whether matrix metalloproteinases (MMP-2 and -9: gelatinases) and pro-inflammatory cytokines [tumor necrosis factor (TNF) α and interleukin (IL)-1β] are induced by heat in tendon tissue in vitro and to test the hypothesis that heat exposure causes tendinocytes to synthesize pro-inflammatory cytokines and that synthesis of these cytokines, in turn, leads to up-regulation of synthesis of gelatinases. Isolated tendinocytes from equine superficial digital flexor tendons were cultured and all experiments were performed on cells passaged 3 or 4 times. In the cells exposed to heat (37 to 45°C, 0 to 60 min), the survival rate decreased sharply in a temperature- and time-dependent manner, especially at 42 and 45°C. Cells exposed at 40°C, however, showed little change in survival rate and morphology. Gelatin zymograms revealed that proMMP-2 and -9 were the only two MMPs remaining in the supernatant of the cultured tendinocytes, including that of untreated cells. Addition of TNFα and IL-1β to the culture medium of tendinocytes accelerated proMMP-9 synthesis considerably. Heating the tendinocytes (40°C) led to a three-fold increase in proMMP-9 synthesis in a short time. Only TNFα was detected in tendinocytes after heat exposure for 30 and 60 min. In contrast, IL-1β was under the detectable level in ELISA. Cooling of heat-exposed cells from 40°C to 37°C considerably down-regulated cellular proMMP-9 synthesis. Furthermore, proMMP-9 level was greatly reduced in cells treated at lower temperatures, 20°C and 5°C. These findings support our hypothesis that hyperthermia in the horse tendon induces tendinocytes to synthesize pro-inflammatory cytokines and that the synthesis of these cytokines results in the up-regulation of gelatinases.