165 results on '"Noriyuki Miyoshi"'
Search Results
2. Non-target GC–MS analyses of fecal VOCs in NASH-hepatocellular carcinoma model STAM mice
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Mai Kato, Momoka Yamaguchi, Akira Ooka, Ryota Takahashi, Takuji Suzuki, Keita Onoda, Yuko Yoshikawa, Yuta Tsunematsu, Michio Sato, Yasukiyo Yoshioka, Miki Igarashi, Sumio Hayakawa, Kumiko Shoji, Yutaka Shoji, Tomohisa Ishikawa, Kenji Watanabe, and Noriyuki Miyoshi
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Medicine ,Science - Abstract
Abstract The increased incidence of obesity in the global population has increased the risk of several chronic inflammation-related diseases, including non-alcoholic steatohepatitis (NASH)-hepatocellular carcinoma (HCC). The progression from NASH to HCC involves a virus-independent liver carcinogenic mechanism; however, we currently lack effective treatment and prevention strategies. Several reports have suggested that fecal volatile organic compounds (VOCs) are strongly associated with NASH-HCC; therefore, we explored the biomarkers involved in its pathogenesis and progression. Fecal samples collected from control and NASH-HCC model STAM mice were subjected to headspace autosampler gas chromatography-electron ionization-mass spectrometry. Non-target profiling analysis identified diacetyl (2,3-butandione) as a fecal VOC that characterizes STAM mice. Although fecal diacetyl levels were correlated with the HCC in STAM mice, diacetyl is known as a cytotoxic/tissue-damaging compound rather than genotoxic or mutagenic; therefore, we examined the effect of bioactivity associated with NASH progression. We observed that diacetyl induced several pro-inflammatory molecules, including tumor necrosis factor-α, cyclooxygenase-2, monocyte chemoattractant protein-1, and transforming growth factor-β, in mouse macrophage RAW264.7 and Kupffer KPU5 cells. Additionally, we observed that diacetyl induced α-smooth muscle actin, one of the hallmarks of fibrosis, in an ex vivo cultured hepatic section, but not in in vitro hepatic stellate TWNT-1 cells. These results suggest that diacetyl would be a potential biomarker of fecal VOC in STAM mice, and its ability to trigger the macrophage-derived inflammation and fibrosis may partly contribute to NASH-HCC carcinogenesis.
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- 2023
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3. Screening method toward ClbP-specific inhibitors
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Tao Zhou, Takayuki Ando, Akihiro Kudo, Michio Sato, Noriyuki Miyoshi, Michihiro Mutoh, Hideki Ishikawa, Keiji Wakabayashi, and Kenji Watanabe
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Colibactin ,ClbP ,Inhibitor ,Screening ,Fluorescent ,Probe ,Ecology ,QH540-549.5 ,Genetics ,QH426-470 - Abstract
Abstract Background Colibactin is a genotoxin produced by Escherichia coli and other Enterobacteriaceae that is believed to increase the risk of colorectal cancer (CRC) of their symbiosis hosts, including human. A peptidase ClbP is the key enzyme for activation of colibactin. Inhibition of ClbP is considered to impede maturation of precolibactin into genotoxic colibactin. Therefore, ClbP-specific inhibitors could potentially prevent the onset of CRC, one of the leading causes of cancer-related deaths in the world. This study intends to establish an efficient screening system for identifying inhibitors that are specific to ClbP. Methods Two types of assays were applied in the screening procedure: a probe assay and an LC–MS assay. For the probe assay, we employed the synthesized probe which we described in our previous report. This probe can be hydrolyzed efficiently by ClbP to release a fluorophore. Hence it was applied here for detection of inhibition of ClbP. For the LC–MS assay, formation of the byproduct of precolibactin maturation process, N-myristoyl-D-asparagine, was quantified using a liquid chromatography–mass spectrometry (LC–MS) technique. The probe assay can be performed much faster, while the LC–MS assay is more accurate. Therefore, our method employed the two assays in sequence to screen a large number of compounds for inhibition of ClbP. Results A library of 67,965 standard compounds was evaluated by the screening method established in the current study, and one compound was found to show a moderate inhibitory activity against ClbP. Conclusion A simple screening method for ClbP-specific inhibitors was established. It was proven to be reliable and is believed to be useful in developing potential prophylactic agents for CRC.
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- 2023
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4. Mother-to-infant transmission of the carcinogenic colibactin-producing bacteria
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Yuta Tsunematsu, Koji Hosomi, Jun Kunisawa, Michio Sato, Noriko Shibuya, Emiko Saito, Haruka Murakami, Yuko Yoshikawa, Yuji Iwashita, Noriyuki Miyoshi, Michihiro Mutoh, Hideki Ishikawa, Haruhiko Sugimura, Motohiko Miyachi, Keiji Wakabayashi, and Kenji Watanabe
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Colibactin ,Natural product ,Escherichia coli ,Perinatal transmission ,Colorectal cancer ,Microbiology ,QR1-502 - Abstract
Abstract Background The Escherichia coli strain that is known to produce the genotoxic secondary metabolite colibactin is linked to colorectal oncogenesis. Therefore, understanding the properties of such colibactin-positive E. coli and the molecular mechanism of oncogenesis by colibactin may provide us with opportunities for early diagnosis or prevention of colorectal oncogenesis. While there have been major advances in the characterization of colibactin-positive E. coli and the toxin it produces, the infection route of the clb + strain remains poorly characterized. Results We examined infants and their treatments during and post-birth periods to examine potential transmission of colibactin-positive E. coli to infants. Here, analysis of fecal samples of infants over the first month of birth for the presence of a colibactin biosynthetic gene revealed that the bacterium may be transmitted from mother to infant through intimate contacts, such as natural childbirth and breastfeeding, but not through food intake. Conclusions Our finding suggests that transmission of colibactin-positive E. coli appears to be occurring at the very early stage of life of the newborn and hints at the possibility of developing early preventive measures against colorectal cancer.
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- 2021
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5. Anti-Inflammatory Effects of Dietary Polyphenols through Inhibitory Activity against Metalloproteinases
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Takuji Suzuki, Tomokazu Ohishi, Hiroki Tanabe, Noriyuki Miyoshi, and Yoriyuki Nakamura
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inflammatory diseases ,matrix metalloproteinases ,dietary polyphenols ,chlorogenic acid ,curcumin ,EGCG ,Organic chemistry ,QD241-441 - Abstract
Matrix metalloproteinases (MMPs) are zinc-dependent metalloproteinases that play important roles in a variety of diseases, including cancer, cardiovascular disease, diabetes, obesity, and brain diseases. Dietary polyphenols are thought to have a variety of beneficial effects on these diseases characterized by inflammation. Clinical studies have demonstrated that MMPs are in most cases upregulated in various inflammatory diseases, including osteoarthritis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimer’s disease. Studies using patient-derived human samples, animal studies, and cellular experiments have suggested that polyphenols may be beneficial against inflammatory diseases by suppressing MMP gene expression and enzyme activity. One important mechanism by which polyphenols exert their activity is the downregulation of reactive oxygen species that promote MMP expression. Another important mechanism is the direct binding of polyphenols to MMPs and their inhibition of enzyme activity. Molecular docking analyses have provided a structural basis for the interaction between polyphenols and MMPs and will help to explore new polyphenol-based drugs with anti-inflammatory properties.
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- 2023
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6. Chemoenzymatic synthesis of 3-ethyl-2,5-dimethylpyrazine by L-threonine 3-dehydrogenase and 2-amino-3-ketobutyrate CoA ligase/L-threonine aldolase
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Tomoharu Motoyama, Shogo Nakano, Fumihito Hasebe, Ryo Miyata, Shigenori Kumazawa, Noriyuki Miyoshi, and Sohei Ito
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Chemistry ,QD1-999 - Abstract
Threonine is a biosynthetic precursor to dimethylpyrazine derivatives, but the pathway by which this occurs is not fully established. Here l-throenine-3-dehydrogenase and 2-amino-3-ketobutyrate CoA ligase together are shown to convert l-threonine to dimethylpyrazine derivatives as a byproduct of glycine metabolism.
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- 2021
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7. Stool pattern is associated with not only the prevalence of tumorigenic bacteria isolated from fecal matter but also plasma and fecal fatty acids in healthy Japanese adults
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Daiki Watanabe, Haruka Murakami, Harumi Ohno, Kumpei Tanisawa, Kana Konishi, Kikue Todoroki-Mori, Yuta Tsunematsu, Michio Sato, Yuji Ogata, Noriyuki Miyoshi, Naoto Kubota, Jun Kunisawa, Keiji Wakabayashi, Tetsuya Kubota, Kenji Watanabe, and Motohiko Miyachi
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Tumorigenic bacteria ,Stool pattern ,Fatty acid ,Cross-sectional study ,Microbiology ,QR1-502 - Abstract
Abstract Background Colibactin-producing Escherichia coli containing polyketide synthase (pks + E. coli) has been shown to be involved in colorectal cancer (CRC) development through gut microbiota analysis in animal models. Stool status has been associated with potentially adverse gut microbiome profiles from fecal analysis in adults. We examined the association between stool patterns and the prevalence of pks + E. coli isolated from microbiota in fecal samples of 224 healthy Japanese individuals. Results Stool patterns were determined through factorial analysis using a previously validated questionnaire that included stool frequency, volume, color, shape, and odor. Factor scores were classified into tertiles. The prevalence of pks + E. coli was determined by using specific primers for pks + E. coli in fecal samples. Plasma and fecal fatty acids were measured via gas chromatography-mass spectrometry. The prevalence of pks + E. coli was 26.8%. Three stool patterns identified by factorial analysis accounted for 70.1% of all patterns seen (factor 1: lower frequency, darker color, and harder shape; factor 2: higher volume and softer shape; and factor 3: darker color and stronger odor). Multivariable-adjusted odds ratios (95% confidence intervals) of the prevalence of pks + E. coli for the highest versus the lowest third of the factor 1 score was 3.16 (1.38 to 7.24; P for trend = 0.006). This stool pattern exhibited a significant positive correlation with fecal isobutyrate, isovalerate, valerate, and hexanoate but showed a significant negative correlation with plasma eicosenoic acid and α-linoleic acid, as well as fecal propionate and succinate. No other stool patterns were significant. Conclusions These results suggest that stool patterns may be useful in the evaluation of the presence of tumorigenic bacteria and fecal fatty acids through self-monitoring of stool status without the requirement for specialist technology or skill. Furthermore, it may provide valuable insight about effective strategies for the early discovery of CRC.
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- 2021
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8. Enokitake Mushroom and Its Active Component, Adenosine, Which Restores Testosterone Production in Impaired and Fatigued Mouse Models
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Kazuaki Iguchi, Koji Nagashima, Jun Mochizuki, Hiroyuki Yamamoto, Keiko Unno, and Noriyuki Miyoshi
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testosterone ,adenosine ,enokitake ,mushroom ,vegetable ,Cordyceps ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Several studies have reported the effects of the consumption of various mushroom species on the testes in animal experimental models. Mushrooms, including enokitake mushrooms (Flammulina velutipes), and vegetables contain adenosine may affect testosterone production. Here, we aimed to elucidate the effects of enokitake and its active component, adenosine, on testosterone production in primary cultures of testicular cells in vivo using mice models and in vitro. The administration of enokitake ethanolic extract increased testosterone production in the cisplatin-impaired mouse model. The direct effect of mushroom extracts on testicular cells was examined and liquid chromatography–mass spectrometry analysis confirmed that the mushroom- and vegetable-induced increase in testosterone production mainly involved adenosine. Additionally, the administration of enokitake extract or adenosine to wet floor fatigue model mice promoted testicular testosterone production and enhanced Leydig cell function through insulin-like peptide three level upregulation. Structurally related compounds, including cordycepin, showed lower bioactivity than adenosine. This study showed that the ingestion of adenosine-containing mushrooms and vegetables may effectively increase testicular testosterone production. We conclude that mushrooms with a relatively high adenosine content, such as enokitake, may be useful against aging and fatigue.
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- 2023
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9. Genotyping of a gene cluster for production of colibactin and in vitro genotoxicity analysis of Escherichia coli strains obtained from the Japan Collection of Microorganisms
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Masanobu Kawanishi, Chiaki Shimohara, Yoshimitsu Oda, Yuuta Hisatomi, Yuta Tsunematsu, Michio Sato, Yuichiro Hirayama, Noriyuki Miyoshi, Yuji Iwashita, Yuko Yoshikawa, Haruhiko Sugimura, Michihiro Mutoh, Hideki Ishikawa, Keiji Wakabayashi, Takashi Yagi, and Kenji Watanabe
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Colibactin ,Genotyping ,Genotoxicity ,Ecology ,QH540-549.5 ,Genetics ,QH426-470 - Abstract
Abstract Introduction Colibactin is a small genotoxic molecule produced by enteric bacteria, including certain Escherichia coli (E. coli) strains harbored in the human large intestine. This polyketide-peptide genotoxin is considered to contribute to the development of colorectal cancer. The colibactin-producing (clb +) microorganisms possess a 54-kilobase genomic island (clb gene cluster). In the present study, to assess the distribution of the clb gene cluster, genotyping analysis was carried out among E. coli strains randomly chosen from the Japan Collection of Microorganisms, RIKEN BRC, Japan. Findings The analysis revealed that two of six strains possessed a clb gene cluster. These clb + strains JCM5263 and JCM5491 induced genotoxicity in in vitro micronucleus (MN) tests using rodent CHO AA8 cells. Since the induction level of MN by JCM5263 was high, a bacterial umu test was carried out with a cell extract of the strain, revealing that the extract had SOS-inducing potency in the umu tester bacterium. Conclusion These results support the observations that the clb gene cluster is widely distributed in nature and clb + E. coli having genotoxic potencies is not rare among microorganisms.
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- 2020
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10. Establishment of Novel Genotoxicity Assay System Using Murine Normal Epithelial Tissue-Derived Organoids
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Masami Komiya, Rikako Ishigamori, Mie Naruse, Masako Ochiai, Noriyuki Miyoshi, Toshio Imai, and Yukari Totsuka
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murine organoids ,gpt delta mice ,PhIP ,acrylamide ,base substitution ,Genetics ,QH426-470 - Abstract
Short-/middle-term and simple prediction studies for carcinogenesis are needed for the safety assessment of chemical substances. To establish a novel genotoxicity assay with an in vivo mimicking system, we prepared murine colonic/pulmonary organoids from gpt delta mice according to the general procedure using collagenase/dispase and cultured them in a 3D environment. When the organoids were exposed to foodborne carcinogens—2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) and acrylamide (AA)—in the presence of metabolic activation systems, mutation frequencies (MFs) occurring in the gpt gene dose-dependently increased. Moreover, the mutation spectrum analysis indicated predominant G:C to T:A transversion with PhIP, and A:T to C:G and A:T to T:A transversion with AA. These data correspond to those of a previous study describing in vivo mutagenicity in gpt delta mice. However, organoids derived from the liver, a non-target tissue of PhIP-carcinogenesis, also demonstrated genotoxicity with a potency comparable to colonic organoids. Organoids and PhIP were directly incubated in the presence of metabolic activation systems; therefore, there was a lack of organ specificity, as observed in vivo. Additionally, PhIP-DNA adduct levels were comparable in hepatic and colonic organoids after PhIP exposure. Taken together, the organoids prepared in the present study may be helpful to predict chemical carcinogenesis.
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- 2021
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11. Health Effects of Soy Isoflavones and Green Tea Catechins on Cancer and Cardiovascular Diseases Based on Urinary Biomarker Levels
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Tomokazu Ohishi, Noriyuki Miyoshi, Mari Mori, Miki Sagara, and Yukio Yamori
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soy isoflavones ,genistein ,green tea catechins ,EGCG ,urinary biomarkers ,cancer ,Organic chemistry ,QD241-441 - Abstract
Plant polyphenols have various health effects. Genistein, which is abundant in soybeans, and epigallocatechin-3-gallate, which is abundant in green tea, are major flavonoids, a subclass group of polyphenols. Several epidemiological studies have shown that these flavonoids have beneficial effects against cancer and cardiovascular diseases. However, other studies did not show such effects. Several confounding factors, including recall bias, are related to these inconsistent findings, and the determination of metabolites in the urine may be useful in reducing the number of confounding factors. Equipment, which can be used by research participants to collect samples from a portion of voided urine within 24 h without the help of medical workers, has been developed for epidemiological investigations. Previous studies, in which flavonoid metabolites in these urine samples were measured, revealed that soy intake was correlated with a reduced risk of certain types of cancer and cardiovascular diseases worldwide. Although soybeans and green tea consumption may have protective effects against cancer and cardiovascular diseases, further clinical studies that consider different confounding factors are required to provide evidence for the actual impact of dietary flavonoids on human diseases, including cancer and cardiovascular diseases. One possible mechanism involved is discussed in relation to the downregulation of reactive oxygen species and the upregulation of 5′-adenosine monophosphate-activated protein kinase elicited by these flavonoids.
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- 2022
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12. Contribution of Non-Coding RNAs to Anticancer Effects of Dietary Polyphenols: Chlorogenic Acid, Curcumin, Epigallocatechin-3-Gallate, Genistein, Quercetin and Resveratrol
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Sumio Hayakawa, Tomokazu Ohishi, Yumiko Oishi, Mamoru Isemura, and Noriyuki Miyoshi
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dietary polyphenols ,anticancer ,ROS ,noncoding RNAs ,microRNA ,long noncoding RNA ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Growing evidence has been accumulated to show the anticancer effects of daily consumption of polyphenols. These dietary polyphenols include chlorogenic acid, curcumin, epigallocatechin-3-O-gallate, genistein, quercetin, and resveratrol. These polyphenols have similar chemical and biological properties in that they can act as antioxidants and exert the anticancer effects via cell signaling pathways involving their reactive oxygen species (ROS)-scavenging activity. These polyphenols may also act as pro-oxidants under certain conditions, especially at high concentrations. Epigenetic modifications, including dysregulation of noncoding RNAs (ncRNAs) such as microRNAs, long noncoding RNAs, and circular RNAs are now known to be involved in the anticancer effects of polyphenols. These polyphenols can modulate the expression/activity of the component molecules in ROS-scavenger-triggered anticancer pathways (RSTAPs) by increasing the expression of tumor-suppressive ncRNAs and decreasing the expression of oncogenic ncRNAs in general. Multiple ncRNAs are similarly modulated by multiple polyphenols. Many of the targets of ncRNAs affected by these polyphenols are components of RSTAPs. Therefore, ncRNA modulation may enhance the anticancer effects of polyphenols via RSTAPs in an additive or synergistic manner, although other mechanisms may be operating as well.
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- 2022
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13. Anti-Cancer Effects of Dietary Polyphenols via ROS-Mediated Pathway with Their Modulation of MicroRNAs
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Yasukiyo Yoshioka, Tomokazu Ohishi, Yoriyuki Nakamura, Ryuuta Fukutomi, and Noriyuki Miyoshi
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dietary polyphenols ,microRNA ,cancer ,reactive oxygen species ,anticancer pathway ,Organic chemistry ,QD241-441 - Abstract
Consumption of coffee, tea, wine, curry, and soybeans has been linked to a lower risk of cancer in epidemiological studies. Several cell-based and animal studies have shown that dietary polyphenols like chlorogenic acid, curcumin, epigallocatechin-3-O-gallate, genistein, quercetin and resveratrol play a major role in these anticancer effects. Several mechanisms have been proposed to explain the anticancer effects of polyphenols. Depending on the cellular microenvironment, these polyphenols can exert double-faced actions as either an antioxidant or a prooxidant, and one of the representative anticancer mechanisms is a reactive oxygen species (ROS)-mediated mechanism. These polyphenols can also influence microRNA (miR) expression. In general, they can modulate the expression/activity of the constituent molecules in ROS-mediated anticancer pathways by increasing the expression of tumor-suppressive miRs and decreasing the expression of oncogenic miRs. Thus, miR modulation may enhance the anticancer effects of polyphenols through the ROS-mediated pathways in an additive or synergistic manner. More precise human clinical studies on the effects of dietary polyphenols on miR expression will provide convincing evidence of the preventive roles of dietary polyphenols in cancer and other diseases.
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- 2022
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14. Metastasis of Breast Cancer Promoted by Circadian Rhythm Disruption due to Light/Dark Shift and its Prevention by Dietary Quercetin in Mice
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Minoru Numata, Akane Hirano, Yukika Yamamoto, Michiko Yasuda, Nobuhiko Miura, Kazutoshi Sayama, Masa-Aki Shibata, Tomohiro Asai, Naoto Oku, Noriyuki Miyoshi, and Kayoko Shimoi
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light/dark shift ,circadian rhythm ,breast cancer ,lymph node metastasis ,quercetin ,Biology (General) ,QH301-705.5 - Abstract
Epidemiological studies have indicated that a disturbed circadian rhythm resulting from night-shift work is a potential risk factor for breast cancer. However, the mechanism of increased risk of breast cancer by night-shift work remains unclear, and there have been few in vivo studies conducted to definitively associate the two factors. In this study, BJMC3879Luc2 mouse breast cancer cells were transplanted into BALB/c mice. Mice were maintained under lighting conditions that modeled the two-shift system and were investigated for the effect of light/dark cycle disruption on tumor growth and lymph node metastasis. Circadian dysfunction, which was confirmed by measuring circadian locomotor activities using a nano tag device in our light/dark shift model, did not affect tumor growth. However, a significant increase in the number of lymph nodes with distant metastasis was observed. Neutrophil-to-lymphocyte ratio, which is an adverse prognostic factor of breast cancer and also indicator of inflammation, also increased. It has been demonstrated that a chronic inflammatory response is associated with cancer malignancy and poor prognosis in various cancers. These results suggest that night-shift work may also affect distant metastasis and prognosis. In addition, we investigated whether dietary quercetin has anti-metastatic activity against light/dark shift-induced metastasis. A diet containing 0.3 % quercetin significantly inhibited distant lymph node metastasis, particularly metastasis to the iliac and kidney lymph nodes. Our results contribute to our understandings of the effects of the external light environment on breast cancer metastasis and provide a glimpse into potential protective effects of dietary quercetin on light/dark disturbance-induced metastasis.
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- 2021
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15. Fasting increases 18:2-containing phosphatidylcholines to complement the decrease in 22:6-containing phosphatidylcholines in mouse skeletal muscle.
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Nanami Senoo, Takumi Akahori, Hiyori Ichida, Noriyuki Miyoshi, Akihito Morita, Takao Shimizu, Hideo Shindou, and Shinji Miura
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Medicine ,Science - Abstract
Fasting stimulates catabolic reactions in skeletal muscle to survive nutrient deprivation. Cellular phospholipids have large structural diversity due to various polar-heads and acyl-chains that affect many cellular functions. Skeletal muscle phospholipid profiles have been suggested to be associated with muscle adaptations to nutritional and environmental status. However, the effect of fasting on skeletal muscle phospholipid profiles remains unknown. Here, we analyzed phospholipids using liquid chromatography mass spectrometry. We determined that fasting resulted in a decrease in 22:6-containing phosphatidylcholines (PCs) (22:6-PCs) and an increase in 18:2-containing PCs (18:2-PCs). The fasting-induced increase in 18:2-PCs was sufficient to complement 22:6-PCs loss, resulting in the maintenance of the total amount of polyunsaturated fatty acid (PUFA)-containing PCs. Similar phospholipid alterations occurred in insulin-deficient mice, which indicate that these observed phospholipid perturbations were characteristic of catabolic skeletal muscle. In lysophosphatidic acid acyltransferase 3-knockout muscles that mostly lack 22:6-PCs, other PUFA-containing PCs, mainly 18:2-PCs, accumulated. This suggests a compensatory mechanism for skeletal muscles to maintain PUFA-containing PCs.
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- 2021
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16. Tomato saponin supplementation ameliorates the development of experimental arthritis by regulating inflammatory responses
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Yuko Yoshikawa, Yuki Katayanagi, Manatsu Kamiya, Yuri Yamamoto, Ryuta Fukutomi, Shinjiro Imai, Noriyuki Miyoshi, and Norio Ohashi
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Collagen-induced arthritis ,Esculeogenin A ,Inflammatory cytokines ,Tomato saponin ,Nutrition. Foods and food supply ,TX341-641 - Abstract
We evaluated the effect of tomato saponin, containing esculeoside A, a major saponin found in Japanese pink-colored tomato, on collagen-induced arthritis DBA/1J mice. Arthritis scores in collagen-injected mice were markedly lower by tomato saponin supplementation than that of the control throughout the 15-days observation period. Notably, there was a significant negative correlation between the arthritis scores and serum concentrations of esculeogenin A, an aglycon of esculeoside A (R2 = 0.84, p
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- 2018
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17. PGC-1α-mediated changes in phospholipid profiles of exercise-trained skeletal muscle
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Nanami Senoo, Noriyuki Miyoshi, Naoko Goto-Inoue, Kimiko Minami, Ryoji Yoshimura, Akihito Morita, Naoki Sawada, Junichiro Matsuda, Yoshihiro Ogawa, Mitsutoshi Setou, Yasutomi Kamei, and Shinji Miura
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biochemical assays ,fatty acid ,lipidomics ,mass spectrometry ,molecular imaging ,nuclear receptors ,Biochemistry ,QD415-436 - Abstract
Exercise training influences phospholipid fatty acid composition in skeletal muscle and these changes are associated with physiological phenotypes; however, the molecular mechanism of this influence on compositional changes is poorly understood. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a nuclear receptor coactivator, promotes mitochondrial biogenesis, the fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle. Because exercise training induces these adaptations, together with increased PGC-1α, PGC-1α may contribute to the exercise-mediated change in phospholipid fatty acid composition. To determine the role of PGC-1α, we performed lipidomic analyses of skeletal muscle from genetically modified mice that overexpress PGC-1α in skeletal muscle or that carry KO alleles of PGC-1α. We found that PGC-1α affected lipid profiles in skeletal muscle and increased several phospholipid species in glycolytic muscle, namely phosphatidylcholine (PC) (18:0/22:6) and phosphatidylethanolamine (PE) (18:0/22:6). We also found that exercise training increased PC (18:0/22:6) and PE (18:0/22:6) in glycolytic muscle and that PGC-1α was required for these alterations. Because phospholipid fatty acid composition influences cell permeability and receptor stability at the cell membrane, these phospholipids may contribute to exercise training-mediated functional changes in the skeletal muscle.
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- 2015
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18. Anti-Cancer Effects of Green Tea Epigallocatchin-3-Gallate and Coffee Chlorogenic Acid
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Sumio Hayakawa, Tomokazu Ohishi, Noriyuki Miyoshi, Yumiko Oishi, Yoriyuki Nakamura, and Mamoru Isemura
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cancer ,tea ,coffee ,EGCG ,chlorogenic acid ,ROS ,Organic chemistry ,QD241-441 - Abstract
Tea and coffee are consumed worldwide and epidemiological and clinical studies have shown their health beneficial effects, including anti-cancer effects. Epigallocatechin gallate (EGCG) and chlorogenic acid (CGA) are the major components of green tea polyphenols and coffee polyphenols, respectively, and believed to be responsible for most of these effects. Although a large number of cell-based and animal experiments have provided convincing evidence to support the anti-cancer effects of green tea, coffee, EGCG, and CGA, human studies are still controversial and some studies have suggested even an increased risk for certain types of cancers such as esophageal and gynecological cancers with green tea consumption and bladder and lung cancers with coffee consumption. The reason for these inconsistent results may have been arisen from various confounding factors. Cell-based and animal studies have proposed several mechanisms whereby EGCG and CGA exert their anti-cancer effects. These components appear to share the common mechanisms, among which one related to reactive oxygen species is perhaps the most attractive. Meanwhile, EGCG and CGA have also different target molecules which might explain the site-specific differences of anti-cancer effects found in human studies. Further studies will be necessary to clarify what is the mechanism to cause such differences between green tea and coffee.
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- 2020
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19. Applications of a Standardized Green Tea Catechin Preparation for Viral Warts and Human Papilloma Virus-Related and Unrelated Cancers
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Noriyuki Miyoshi, Hiroki Tanabe, Takuji Suzuki, Koichi Saeki, and Yukihiko Hara
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green tea catechins ,epigallocatechin gallate ,human papillomavirus ,gene expression ,Organic chemistry ,QD241-441 - Abstract
Most cell-based and animal experiments have shown that green tea catechins (GTC) exhibit various health benefits. In human experimental and epidemiological studies, there are conflicting results, and more precise investigations are required. One of the most effective ways to prove beneficial health effects in humans might be clinical intervention studies. Polyphenon®E was developed as a standardized GTC preparation, which was approved by Food and Drug Administration of US in 2006 as a medication to treat genital warts (Veregen® or sinecatechins). Positive efficacy of Polyphenon®E/sinecatechins/Veregen® (PSV) on anogenital warts has been demonstrated in several epidemiological studies and there have been several case reports to show the clinical effectiveness of PSV. In addition, several studies have provided evidence to suggest that PSV is effective in other human papillomavirus (HPV)-related diseases, although some studies failed to show such effects. Since (−)-epigallocatechin gallate (EGCG) is the major component of PSV, the mechanism of the action of PSV might be deduced from that of EGCG. The microarray analysis of the biopsy samples from the patients suggested that apoptosis induction and the downregulation of inflammation are involved in the mechanism of the action of PSV in the clearance of anogenital warts. Cell-based and animal experiments using PSV also demonstrated effects similar to those elicited by EGCG, explaining how PSV works to induce apoptosis and exert anti-inflammatory actions in HPV-related diseases. Future studies would clarify what kinds of diseases respond effectively to PSV, showing health benefits of GTC and EGCG in humans.
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- 2020
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20. Phenethyl isothiocyanate activates leptin signaling and decreases food intake.
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Miho Yagi, Yukiko Nakatsuji, Ayumi Maeda, Hiroki Ota, Ryosuke Kamikubo, Noriyuki Miyoshi, Yoshimasa Nakamura, and Mitsugu Akagawa
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Medicine ,Science - Abstract
Obesity, a principal risk factor for the development of diabetes mellitus, heart disease, and hypertension, is a growing and serious health problem all over the world. Leptin is a weight-reducing hormone produced by adipose tissue, which decreases food intake via hypothalamic leptin receptors (Ob-Rb) and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Protein tyrosine phosphatase 1B (PTP1B) negatively regulates leptin signaling by dephosphorylating JAK2, and the increased activity of PTP1B is implicated in the pathogenesis of obesity. Hence, inhibition of PTP1B may help prevent and reduce obesity. In this study, we revealed that phenethyl isothiocyanate (PEITC), a naturally occurring isothiocyanate in certain cruciferous vegetables, potently inhibits recombinant PTP1B by binding to the reactive cysteinyl thiol. Moreover, we found that PEITC causes the ligand-independent phosphorylation of Ob-Rb, JAK2, and STAT3 by inhibiting cellular PTP1B in differentiated human SH-SY5Y neuronal cells. PEITC treatment also induced nuclear accumulation of phosphorylated STAT3, resulting in enhanced anorexigenic POMC expression and suppressed orexigenic NPY/AGRP expression. We demonstrated that oral administration of PEITC to mice significantly reduces food intake, and stimulates hypothalamic leptin signaling. Our results suggest that PEITC might help prevent and improve obesity.
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- 2018
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21. Formation of cholesterol ozonolysis products in vitro and in vivo through a myeloperoxidase-dependent pathway
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Susumu Tomono, Noriyuki Miyoshi, Hidemi Shiokawa, Tomoe Iwabuchi, Yasuaki Aratani, Tatsuya Higashi, Haruo Nukaya, and Hiroshi Ohshima
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secosterol ,neutrophils ,myeloperoxidase ,inflammation ,Biochemistry ,QD415-436 - Abstract
3β-Hydroxy-5-oxo-5,6-secocholestan-6-al (secosterol-A) and its aldolization product 3β-hydroxy-5β-hydroxy-B-norcholestane-6β-carboxaldehyde (secosterol-B) were recently detected in human atherosclerotic tissues and brain specimens, and they may play pivotal roles in the pathogenesis of atherosclerosis and neurodegenerative diseases. However, as their origin remains unidentified, we examined the formation mechanism, the stability, and the fate of secosterols in vitro and in vivo. About 40% of secosterol-A remained unchanged after 3 h incubation in the FBS-free medium, whereas 20% and 40% were converted to its aldehyde-oxidation product, 3β-hydroxy-5-oxo-secocholestan-6-oic acid, and secosterol-B, respectively. In the presence of FBS, almost all secosterol-A was converted immediately to these compounds. Secosterol-B in the medium, with and without FBS, was relatively stable, but ∼30% was converted to its aldehyde-oxidation product, 3β-hydroxy-5β-hydroxy-B-norcholestane-6-oic acid (secoB-COOH). When neutrophil-like differentiated human leukemia HL-60 (nHL-60) cells activated with PMA were cultured in the FBS-free medium containing cholesterol, significantly increased levels of secosterol-A and its aldehyde-oxidation product, but not secosterol-B, were formed. This secosterol-A formation was decreased in the culture of PMA-activated nHL-60 cells containing several reactive oxygen species (ROS) inhibitors and scavengers or in the culture of PMA-activated neutrophils isolated from myeloperoxidase (MPO)-deficient mice. Our results demonstrate that secoterol-A is formed by an ozone-like oxidant generated with PMA-activated neutrophils through the MPO-dependent mechanism.
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- 2011
- Full Text
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22. Beneficial Effects of Green Tea Catechins on Neurodegenerative Diseases
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Monira Pervin, Keiko Unno, Tomokazu Ohishi, Hiroki Tanabe, Noriyuki Miyoshi, and Yoriyuki Nakamura
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green tea ,catechin ,EGCG ,brain ,cognitive function ,Alzheimer’s disease ,Parkinson’s disease ,neuroprotection ,epidemiology ,inflammation ,Organic chemistry ,QD241-441 - Abstract
Tea is one of the most consumed beverages in the world. Green tea, black tea, and oolong tea are made from the same plant Camellia sinensis (L.) O. Kuntze. Among them, green tea has been the most extensively studied for beneficial effects on diseases including cancer, obesity, diabetes, and inflammatory and neurodegenerative diseases. Several human observational and intervention studies have found beneficial effects of tea consumption on neurodegenerative impairment, such as cognitive dysfunction and memory loss. These studies supported the basis of tea’s preventive effects of Parkinson’s disease, but few studies have revealed such effects on Alzheimer’s disease. In contrast, several human studies have not reported these favorable effects with regard to tea. This discrepancy may be due to incomplete adjustment of confounding factors, including the method of quantifying consumption, beverage temperature, cigarette smoking, alcohol consumption, and differences in genetic and environmental factors, such as race, sex, age, and lifestyle. Thus, more rigorous human studies are required to understand the neuroprotective effect of tea. A number of laboratory experiments demonstrated the benefits of green tea and green tea catechins (GTCs), such as epigallocatechin gallate (EGCG), and proposed action mechanisms. The targets of GTCs include the abnormal accumulation of fibrous proteins, such as Aβ and α-synuclein, inflammation, elevated expression of pro-apoptotic proteins, and oxidative stress, which are associated with neuronal cell dysfunction and death in the cerebral cortex. Computational molecular docking analysis revealed how EGCG can prevent the accumulation of fibrous proteins. These findings suggest that GTCs have the potential to be used in the prevention and treatment of neurodegenerative diseases and could be useful for the development of new drugs.
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- 2018
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23. Biosynthetic Gene Expression and Tissue Distribution of Diosgenin in Dioscorea japonica
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Keita Onoda, Mai Kato, Yuta Tsunematsu, Fumihiro Eto, Michio Sato, Yasukiyo Yoshioka, Takuya Yoshida, Kentaro Tamura, Ikuko Yao, Hideo Dohra, Kenji Watanabe, and Noriyuki Miyoshi
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General Chemistry ,General Agricultural and Biological Sciences - Published
- 2023
24. Cytotoxic Homo- and Hetero-Dimers of o-toluidine, o-anisidine, and Aniline Formed by In Vitro Metabolism
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Takuma Kobayashi, Shinji Kishimoto, Shogo Watanabe, Yasukiyo Yoshioka, Takeshi Toyoda, Kumiko Ogawa, Kenji Watanabe, Yukari Totsuka, Keiji Wakabayashi, and Noriyuki Miyoshi
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General Medicine ,Toxicology - Published
- 2022
25. Data from Chemoprevention of Azoxymethane/Dextran Sodium Sulfate–Induced Mouse Colon Carcinogenesis by Freeze-Dried Yam Sanyaku and Its Constituent Diosgenin
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Hiroshi Ohshima, Takuji Tanaka, Keiji Wakabayashi, Yumiko Yasui, Ryota Mabuchi, Tomoki Nagasawa, and Noriyuki Miyoshi
- Abstract
The effects of sanyaku, a traditional Chinese medicine [freeze-dried powder of the yam tuber (Dioscorea)], and its major steroidal saponin constituent, diosgenin, on colon carcinogenesis were investigated. Male ICR mice were subjected to a single intraperitoneal injection of azoxymethane (AOM; 10 mg/kg body weight) followed by administration of 1.5% dextran sodium sulfate (DSS) in drinking water for 7 days to establish carcinogenesis. Commercial diosgenin or sanyaku, which contained diosgenin at 63.8 ± 1.2 mg/kg dry weight, was given in the diet at 20, 100, or 500 mg/kg for 17 weeks. Groups of mice that received diosgenin or sanyaku at all doses yielded significantly less number of colon tumors compared with the AOM/DSS-treated mice. Occurrence of colonic mucosal ulcer and dysplastic crypt induced by AOM/DSS treatment was also significantly decreased by the administration of diosgenin and sanyaku, which was in accordance with the significant reduction of AOM/DSS-mediated increases in expression of inflammatory cytokines such as IL-1β by diosgenin and sanyaku. Furthermore, elevated levels of serum triglyceride in the AOM/DSS-treated mice tended to be reduced in mice given diosgenin and sanyaku. Microarray and real-time reverse transcriptase PCR analyses revealed that diosgenin administration increased 12-fold the expression of lipoprotein lipase, which may contribute to reduced serum triglyceride levels. Other genes altered by diosgenin included those associated with antioxidative stress responses and apoptosis, such as heme oxygenase-1, superoxide dismutase-3, and caspase-6. Our results imply that the Chinese medicine sanyaku and the tubers of various yams containing diosgenin as food could be ingested to prevent colon carcinogenesis in humans. Cancer Prev Res; 4(6); 924–34. ©2011 AACR.
- Published
- 2023
26. Supplementary Figure and Table from Chemoprevention of Azoxymethane/Dextran Sodium Sulfate–Induced Mouse Colon Carcinogenesis by Freeze-Dried Yam Sanyaku and Its Constituent Diosgenin
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Hiroshi Ohshima, Takuji Tanaka, Keiji Wakabayashi, Yumiko Yasui, Ryota Mabuchi, Tomoki Nagasawa, and Noriyuki Miyoshi
- Abstract
Supplementary Figure and Table from Chemoprevention of Azoxymethane/Dextran Sodium Sulfate–Induced Mouse Colon Carcinogenesis by Freeze-Dried Yam Sanyaku and Its Constituent Diosgenin
- Published
- 2023
27. Supplementary Data from A Link between Benzyl Isothiocyanate-Induced Cell Cycle Arrest and Apoptosis: Involvement of Mitogen-Activated Protein Kinases in the Bcl-2 Phosphorylation
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Yoshimasa Nakamura, Toshihiko Osawa, Koji Uchida, and Noriyuki Miyoshi
- Abstract
Supplementary Data from A Link between Benzyl Isothiocyanate-Induced Cell Cycle Arrest and Apoptosis: Involvement of Mitogen-Activated Protein Kinases in the Bcl-2 Phosphorylation
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- 2023
28. Data from A Link between Benzyl Isothiocyanate-Induced Cell Cycle Arrest and Apoptosis: Involvement of Mitogen-Activated Protein Kinases in the Bcl-2 Phosphorylation
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Yoshimasa Nakamura, Toshihiko Osawa, Koji Uchida, and Noriyuki Miyoshi
- Abstract
In the present study, we clarified the molecular mechanism underlying the relationship between benzyl isothiocyanate (BITC)-induced cell cycle arrest and apoptosis and the involvement of mitogen-activated protein kinases (MAPKs). The exposure of Jurkat human T-cell leukemia cells to BITC resulted in the inhibition of the G2-M progression that coincided with the apoptosis induction. The experiment using the phase-specific synchronized cells demonstrated that the G2-M phase-arrested cells are more sensitive to undergoing apoptotic stimulation by BITC than the cells in other phases. We also confirmed that BITC activated c-Jun N-terminal kinase (JNK) and p38 MAPK, but not extracellular signal-regulated kinase, at the concentration required for apoptosis induction. An experiment using a JNK-specific inhibitor SP600125 or a p38 MAPK inhibitor SB202190 indicated that BITC-induced apoptosis might be regulated by the activation of these two kinases. Conversely, BITC is likely to confine the Jurkat cells in the G2-M phase mainly through the p38 MAPK pathway because only the p38 MAPK inhibitor significantly attenuated the accumulation of inactive phosphorylated Cdc2 protein and the G2-M-arrested cell numbers. We reported here for the first time that the antiapoptotic Bcl-2 protein was phosphorylated by the BITC treatment without significant alteration of the Bcl-2 total protein amount. This was abrogated by a JNK specific inhibitor SP600125 at the concentration required for specific inhibition of the c-Jun phosphorylation. Moreover, the spontaneous phosphorylation of antiapoptotic Bcl-2 in the G2-M synchronized cells was enhanced synergistically by the BITC treatment. Involvement of the MAPK activation in the Bcl-2 phosphorylation and apoptosis induction also was observed in HL-60 and HeLa cells. Thus, we identified the phosphorylated Bcl-2 as a key molecule linking the p38 MAPK-dependent cell cycle arrest with the JNK activation by BITC.
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- 2023
29. Involvement of microRNA modifications in anticancer effects of major polyphenols from green tea, coffee, wine, and curry
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Tomokazu Ohishi, Sumio Hayakawa, and Noriyuki Miyoshi
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General Medicine ,Industrial and Manufacturing Engineering ,Food Science - Abstract
Epidemiological studies have shown that consumption of green tea, coffee, wine, and curry may contribute to a reduced risk of various cancers. However, there are some cancer site-specific differences in their effects; for example, the consumption of tea or wine may reduce bladder cancer risk, whereas coffee consumption may increase the risk. Animal and cell-based experiments have been used to elucidate the anticancer mechanisms of these compounds, with reactive oxygen species (ROS)-based mechanisms emerging as likely candidates. Chlorogenic acid (CGA), curcumin (CUR), epigallocatechin gallate (EGCG), and resveratrol (RSV) can act as antioxidants that activate AMP-activated protein kinase (AMPK) to downregulate ROS, and as prooxidants to generate ROS, leading to the downregulation of NF-κB. Polyphenols can modulate miRNA (miR) expression, with these dietary polyphenols shown to downregulate tumor-promoting miR-21. CUR, EGCG, and RSV can upregulate tumor-suppressing miR-16, 34a, 145, and 200c, but downregulate tumor-promoting miR-25a. CGA, EGCG, and RSV downregulate tumor-suppressing miR-20a, 93, and 106b. The effects of miRs may combine with ROS-mediated pathways, enhancing the anticancer effects of these polyphenols. More precise analysis is needed to determine how the different modulations of miRs by polyphenols relate to the cancer site-specific differences found in epidemiological studies related to the consumption of foods containing these polyphenols.
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- 2022
30. Induction of DNA Damage in Mouse Colorectum by Administration of Colibactin-producing Escherichia coli, Isolated from a Patient With Colorectal Cancer
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TAKUMI NARITA, YUTA TSUNEMATSU, NORIYUKI MIYOSHI, MASAMI KOMIYA, TAKAHIRO HAMOYA, GEN FUJII, YUKO YOSHIKAWA, MICHIO SATO, MASANOBU KAWANISHI, HARUHIKO SUGIMURA, YUJI IWASHITA, YUKARI TOTSUKA, MASARU TERASAKI, KENJI WATANABE, KEIJI WAKABAYASHI, and MICHIHIRO MUTOH
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Pharmacology ,Cancer Research ,General Biochemistry, Genetics and Molecular Biology - Published
- 2022
31. Toxicological effects of two metabolites derived from o-toluidine and o-anisidine after 28-day oral administration to rats
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Takeshi Toyoda, Takuma Kobayashi, Noriyuki Miyoshi, Kohei Matsushita, Hirotoshi Akane, Tomomi Morikawa, and Kumiko Ogawa
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Toxicology - Published
- 2022
32. LPGAT1/LPLAT7 regulates acyl chain profiles at the sn-1 position of phospholipids in murine skeletal muscles
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Tomoki Sato, Shuhei Umebayashi, Nanami Senoo, Takumi Akahori, Hiyori Ichida, Noriyuki Miyoshi, Takuya Yoshida, Yuki Sugiura, Naoko Goto-Inoue, Hiroki Kawana, Hideo Shindou, Takashi Baba, Yuki Maemoto, Yasutomi Kamei, Takao Shimizu, Junken Aoki, and Shinji Miura
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Cell Biology ,Molecular Biology ,Biochemistry - Published
- 2023
33. Isolation of New Colibactin Metabolites from Wild-Type Escherichia coli and In Situ Trapping of a Mature Colibactin Derivative
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Yuji Iwashita, Nahoko Uchiyama, Noriyuki Miyoshi, Seiji Tanaka, Michio Sato, Hideki Ishikawa, Haruhiko Sugimura, Tao Zhou, Yuichiro Hirayama, Kenji Watanabe, Nanami Suzuki, Yukihiro Goda, Yuta Tsunematsu, Michihiro Mutoh, Yuko Yoshikawa, and Keiji Wakabayashi
- Subjects
In situ ,chemistry.chemical_classification ,Chemistry ,Wild type ,Peptide ,General Chemistry ,Secondary metabolite ,010402 general chemistry ,medicine.disease_cause ,01 natural sciences ,Biochemistry ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Colibactin ,medicine ,Escherichia coli ,Derivative (chemistry) ,DNA ,medicine.drug - Abstract
Colibactin is a polyketide-nonribosomal peptide hybrid secondary metabolite that can form interstrand cross-links in double-stranded DNA. Colibactin-producing Escherichia coli has also been linked to colorectal oncogenesis. Thus, there is a strong interest in understanding the role colibactin may play in oncogenesis. Here, using the high-colibactin-producing wild-type E. coli strain we isolated from a clinical sample with the activity-based fluorescent probe we developed earlier, we were able to identify colibactin 770, which was recently identified and proposed as the complete form of colibactin, along with colibactin 788, 406, 416, 420, and 430 derived from colibactin 770 through structural rearrangements and solvolysis. Furthermore, we were able to trap the degrading mature colibactin species by converting the diketone moiety into quinoxaline in situ in the crude culture extract to form colibactin 860 at milligram scale. This allowed us to determine the stereochemically complex structure of the rearranged form of an intact colibactin, colibactin 788, in detail. Furthermore, our study suggested that we were capturing only a few percent of the actual colibactin produced by the microbe, providing a crude quantitative insight into the inherent instability of this compound. Through the structural assignment of colibactins and their degradative products by the combination of LC-HRMS and NMR spectroscopies, we were able to elucidate further the fate of inherently unstable colibactin, which could help acquire a more complete picture of colibactin metabolism and identify key DNA adducts and biomarkers for diagnosing colorectal cancer.
- Published
- 2021
34. o-Anisidine Dimer, 2-Methoxy-N4-(2-methoxyphenyl) Benzene-1,4-diamine, in Rat Urine Associated with Urinary bladder Carcinogenesis
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Shuichi Masuda, Masako Ochiai, Kumiko Ogawa, Michio Sato, Yuko Shimamura, Yukari Totsuka, Takuma Kobayashi, Shinji Kishimoto, Kenji Watanabe, Yuta Tsunematsu, Yuya Tajima, Noriyuki Miyoshi, Keiji Wakabayashi, Kohei Matsushita, Takeshi Toyoda, Takanori Yamada, and Takeji Takamura-Enya
- Subjects
0303 health sciences ,Urinary bladder ,DNA damage ,Metabolite ,Urinary system ,o-Anisidine ,General Medicine ,010501 environmental sciences ,Toxicology ,medicine.disease_cause ,01 natural sciences ,Molecular biology ,03 medical and health sciences ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,In vivo ,medicine ,bacteria ,Carcinogen ,Genotoxicity ,030304 developmental biology ,0105 earth and related environmental sciences - Abstract
Monocyclic aromatic amines, o-toluidine (o-Tol) and its structural analog o-anisidine (o-Ans), are IARC Group 1 and Group 2A urinary bladder carcinogens, respectively, and are involved in metabolic activation and DNA damage. Our recent study revealed that 2-methyl-N4-(2-methylphenyl) benzene-1,4-diamine (MMBD), a p-semidine-type homodimer of o-Tol, was detected and identified in an in vitro reaction of o-Tol with S9 mix and in vivo urinary samples of o-Tol-exposed rats. Potent mutagenic, genotoxic, and cytotoxic activities were reported with MMBD, suggesting its involvement in urinary bladder carcinogenesis. However, it remains unknown whether o-Ans is converted to active metabolites to induce DNA damage in a similar manner as o-Tol. In this study, we report that a novel o-Ans metabolite, 2-methoxy-N4-(2-methoxyphenyl) benzene-1,4-diamine (MxMxBD), a dimer by head-to-tail binding (p-semidine form), was for the first time identified in o-Ans-exposed rat urine. MxMxBD induced a stronger mutagenicity in N-acetyltransferase overexpressed Salmonella typhimurium strains and potent genotoxicity and cytotoxicity in human bladder carcinoma T24 cells compared with o-Ans. These results suggest that MxMxBD may to some extent contribute toward urinary bladder carcinogenesis. In addition to homodimerization, such as MxMxBD, heterodimerizations were observed when o-Ans was coincubated with o-Tol or aniline (Ani) in in vitro reactions with S9 mix. This study highlights the important consideration of homodimerizations and heterodimerizations of monocyclic aromatic amines, including o-Ans, o-Tol, and Ani, in the evaluation of the combined exposure risk of bladder carcinogenesis.
- Published
- 2021
35. Characterization of Colibactin-Producing Escherichia coli Isolated from Japanese Patients with Colorectal Cancer
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Fumi Higashiguchi, Hideki Ishikawa, Yuji Iwashita, Haruhiko Sugimura, Yuichiro Hirayama, Kenji Watanabe, Noriyuki Miyoshi, Nobuo Matsuzaki, Michihiro Mutoh, Yuta Tsunematsu, Keiji Wakabayashi, Yuko Yoshikawa, and Michio Sato
- Subjects
0301 basic medicine ,Microbiology (medical) ,biology ,Colorectal cancer ,030106 microbiology ,General Medicine ,medicine.disease_cause ,medicine.disease ,biology.organism_classification ,Molecular biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Infectious Diseases ,Biosynthesis ,chemistry ,Colibactin ,medicine ,Selective advantage ,Colorectal adenocarcinoma ,030212 general & internal medicine ,Carcinogenesis ,Escherichia coli ,Bacteria - Abstract
We investigated the relationship between colibactin-producing (clb+) Escherichia coli and colorectal adenocarcinoma. In total, 729 E. coli colonies were isolated from tumor and surrounding non-tumor regions in resected specimens from 34 Japanese patients; 450 colonies were from the tumor regions and 279 from the non-tumor regions. clb+ bacteria were found in tumor regions of 11 patients (11/34, 32.4%) and they were also detected in the non-tumor regions of 7 out of these 11 patients (7/34, 20.6%). The prevalence of clb+ isolates was 72.7% (327/450) and 44.1% (123/279) in tumor and non-tumor regions, respectively. All the recovered clb+ isolates belonged to the phylogenetic group B2 and were the most predominant type in tumor regions. Hemolytic (α-hemolysin-positive, hlyA+) and non-hemolytic (α-hemolysin-negative, hlyA-) clb+ isolates were obtained from patient #19; however, the prevalence of hlyA+ clb+ isolates was significantly higher in tumor regions (35/43, 81.4%) than in non-tumor regions (3/19, 15.8%). Moreover, a significantly higher production of N-myristoyl-D-asparagine, a by-product of colibactin biosynthesis, was observed in hlyA+ clb+ isolates than in hlyA- clb+ isolates. Our results suggest that hlyA+ clb+ E. coli may have a selective advantage in colorectal colonization and, consequently, might play a role in carcinogenesis. The presence of hlyA+ clb+ bacteria in healthy individuals is a potential risk marker of colorectal cancer.
- Published
- 2020
36. Glycerophospholipid profile alterations are associated with murine muscle‐wasting phenotype
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Eri Kobayashi, Nanami Senoo, Akihito Morita, Shin'ichi Takeda, Shinji Miura, Jun Tanihata, and Noriyuki Miyoshi
- Subjects
Male ,musculoskeletal diseases ,0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,Physiology ,Duchenne muscular dystrophy ,Phospholipid ,Glycerophospholipids ,030105 genetics & heredity ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Tandem Mass Spectrometry ,Physiology (medical) ,medicine ,Animals ,Muscular dystrophy ,Muscle, Skeletal ,chemistry.chemical_classification ,Phosphatidylethanolamine ,biology ,Chemistry ,Fatty acid ,Skeletal muscle ,musculoskeletal system ,medicine.disease ,Cell biology ,Muscular Dystrophy, Duchenne ,Disease Models, Animal ,Muscular Atrophy ,Phenotype ,medicine.anatomical_structure ,Glycerophospholipid ,Mice, Inbred mdx ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Neurology (clinical) ,Dystrophin ,030217 neurology & neurosurgery ,Chromatography, Liquid - Abstract
Introduction Phospholipids are essential components of cellular membranes and are closely associated with cellular functions, but relationships involving skeletal muscle phospholipid profiles and their physiological phenotypes have remained unclear. Methods We carried out comprehensive phospholipid analyses using liquid chromatography-tandem mass spectrometry to determine the phospholipid profiles of skeletal muscles derived from muscle-wasting mouse models, including denervated and Duchenne muscular dystrophy mouse models (mdx) as well as rescued mdx mice expressing truncated dystrophin. Results Consistent phosphatidylcholine and phosphatidylethanolamine alterations in skeletal muscles isolated from denervated and mdx mice were observed. Notably, the levels of these phospholipids binding polyunsaturated fatty acids were reduced in denervated and mdx muscles. Moreover, rescuing the mdx pathology by expressing truncated dystrophin led to the restoration of phospholipid profiles. Discussion Our findings support the hypothesis that phospholipid profiles of the skeletal muscle may be associated with skeletal muscle function.
- Published
- 2020
37. β-Aminoisobutyric Acid Suppresses Atherosclerosis in Apolipoprotein E-Knockout Mice
- Author
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Noriyuki Miyoshi, Yuki Shimba, Masahiko Ikeda, Shinji Miura, Akihito Morita, and Keigo Katayama
- Subjects
0301 basic medicine ,Apolipoprotein E ,medicine.medical_specialty ,Aminoisobutyric Acids ,Apolipoprotein B ,Mice, Knockout, ApoE ,Galectin 3 ,Vascular Cell Adhesion Molecule-1 ,Pharmaceutical Science ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Myokine ,medicine ,Animals ,Receptor ,Chemokine CCL2 ,Pharmacology ,biology ,Chemistry ,Monocyte ,Skeletal muscle ,General Medicine ,Atherosclerosis ,Lipids ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Aortic Valve ,030220 oncology & carcinogenesis ,Knockout mouse ,biology.protein ,Tumor necrosis factor alpha - Abstract
Endurance exercise training has been shown to induce peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression in skeletal muscle. We recently reported that skeletal muscle-specific PGC-1α overexpression suppressed atherosclerosis in apolipoprotein E-knockout (ApoE-/-) mice. β-Aminoisobutyric acid (BAIBA) is a PGC-1α-dependent myokine secreted from myocytes that affects multiple organs. We have also reported that BAIBA suppresses tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) gene expression in endothelial cells. In the present study, we hypothesized that BAIBA suppresses atherosclerosis progression, and tested that hypothesis with ApoE-/- mice. The mice were administered water containing BAIBA for 14 weeks, and were then sacrificed at 20 weeks of age. Atherosclerotic plaque area, plasma BAIBA concentration, and plasma lipoprotein profiles were assessed. Immunohistochemical analyses of the plaque were performed to assess VCAM-1 and MCP-1 protein expression levels and macrophage infiltration. The results showed that BAIBA administration decreased atherosclerosis plaque area by 30%, concomitant with the elevation of plasma BAIBA levels. On the other hand, plasma lipoprotein profiles were not changed by the administration. Immunohistochemical analyses indicated reductions in VCAM-1, MCP-1, and Mac-2 protein expression levels in the plaque. These results suggest that BAIBA administration suppresses atherosclerosis progression without changing plasma lipoprotein profiles. We propose that the mechanisms of this suppression are reductions in both VCAM-1 and MCP-1 expression as well as macrophage infiltration into the plaque.
- Published
- 2020
38. Novel o-Toluidine Metabolite in Rat Urine Associated with Urinary Bladder Carcinogenesis
- Author
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Keiji Wakabayashi, Yukari Totsuka, Yuichiro Hirayama, Kumiko Ogawa, Takeji Takamura-Enya, Takeshi Toyoda, Kohei Matsushita, Yuya Tajima, Takanori Yamada, Kenji Watanabe, and Noriyuki Miyoshi
- Subjects
chemistry.chemical_classification ,0303 health sciences ,DNA damage ,organic chemicals ,Metabolite ,Aromatic amine ,General Medicine ,010501 environmental sciences ,Toxicology ,01 natural sciences ,Molecular biology ,Adduct ,03 medical and health sciences ,chemistry.chemical_compound ,Enzyme ,chemistry ,DNA adduct ,bacteria ,Carcinogen ,DNA ,030304 developmental biology ,0105 earth and related environmental sciences - Abstract
o-Toluidine (o-Tol), a monocyclic aromatic amine, causes bladder cancer in humans and experimental animals and is therefore classified as a Group 1 carcinogen (IARC) in which the carcinogenicity of o-Tol is involved in metabolic activation, DNA damage, and DNA adduct formation. In the DNA adduct formation mechanism, o-Tol is metabolized by N-hydroxylation, N-acetoxylation, and then deacetoxylation to produce an electrophilic nitrenium ion, which is able to bind to a DNA base, such as dG-C8. Therefore, dG-C8-o-Tol is thought to be a plausible DNA adduct of o-Tol exposure. However, direct detection of dG-C8-o-Tol in biological samples has not been reported yet. Here, we show that a novel o-Tol metabolite, 2-methyl-N1-(2-methylphenyl)benzene-1,4-diamine (MMBD), a dimer by head-to-tail binding, was identified for the first time in o-Tol-exposed rat urine. MMBD was also detected in a reaction of o-Tol and S9 mix, indicating the formation was catalyzed by an enzymatic reaction. Moreover, MMBD showed a potent stronger mutagenicity in N-acetyltransferase overexpressed Salmonella typhimurium strains,and cytotoxicity in human bladder carcinoma T24 cells and human spleen lymphoblastoid TK6 cells compared with o-Tol. Furthermore, a DNA adduct (m/z 478.1) corresponding to dG-MMBD was detected in the reaction of calf thymus DNA with rat urine containing MMBD, and also in hepatic DNA of rats treated with o-Tol. These results therefore suggested that o-Tol-induced bladder carcinogenesis could be at least partly attributed to MMBD formation. The possible dimerization of monocyclic aromatic amines should be considered in the evaluation of the risk of bladder carcinogenesis after exposure.
- Published
- 2020
39. Elevated levels of proinflammatory volatile metabolites in feces of high fat diet fed KK-A y mice
- Author
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Yuko Yoshikawa, Yuto Yoshikawa, Michio Sato, Takuji Suzuki, Yuta Tsunematsu, Misaki Uchikawa, Noriyuki Miyoshi, Akika Nagata, Shunsuke Sanada, Kenji Watanabe, Tsutomu Hashidume, and Mai Kato
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Nonanal ,lcsh:Medicine ,Inflammation ,Proinflammatory cytokine ,Pathogenesis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Diabetes mellitus ,medicine ,lcsh:Science ,Feces ,Multidisciplinary ,Chemistry ,lcsh:R ,medicine.disease ,Obesity ,030104 developmental biology ,Endocrinology ,030211 gastroenterology & hepatology ,Composition (visual arts) ,lcsh:Q ,medicine.symptom - Abstract
When the microfloral composition deteriorates, it triggers low-level chronic inflammation associated with several lifestyle-related diseases including obesity and diabetic mellitus. Fecal volatile organic compounds (VOCs) have been found to differ in gastrointestinal diseases as well as intestinal infection. In this study, to evaluate a potential association between the pathogenesis of lifestyle-related diseases and VOCs in the intestinal tract, fecal VOCs from obese/diabetic KK-Ay mice (KK) or controls (C57BL/6J mice; BL) fed a normal or high fat diet (NFD or HFD) were investigated using headspace sampler-GC-EI-MS. Principal component analysis (PCA) of fecal VOC profiles clearly separated the experimental groups depending on the mouse lineage (KK vs BL) and the diet type (NFD vs HFD). 16 s rRNA sequencing revealed that the PCA distribution of VOCs was in parallel with the microfloral composition. We identified that some volatile metabolites including n-alkanals (nonanal and octanal), acetone and phenol were significantly increased in the HFD and/or KK groups. Additionally, these volatile metabolites induced proinflammatory activity in the RAW264 murine macrophage cell line indicating these bioactive metabolites might trigger low-level chronic inflammation. These results suggest that proinflammatory VOCs detected in HFD-fed and/or diabetic model mice might be novel noninvasive diagnosis biomarkers for diabetes.
- Published
- 2020
40. Induction of DNA Damage in Mouse Colorectum by Administration of Colibactin-producing
- Author
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Takumi, Narita, Yuta, Tsunematsu, Noriyuki, Miyoshi, Masami, Komiya, Takahiro, Hamoya, Gen, Fujii, Yuko, Yoshikawa, Michio, Sato, Masanobu, Kawanishi, Haruhiko, Sugimura, Yuji, Iwashita, Yukari, Totsuka, Masaru, Terasaki, Kenji, Watanabe, Keiji, Wakabayashi, and Michihiro, Mutoh
- Subjects
Mice ,Polyketides ,Escherichia coli ,Animals ,Humans ,Female ,Colorectal Neoplasms ,Peptides ,Escherichia coli Infections ,DNA Damage ,Rats ,Research Article - Abstract
Background/Aim: Among colorectal cancer-associated intestinal microbiota, colibactin-producing (clb(+)) bacteria are attracting attention. We aimed to clarify the interaction between clb(+) Escherichia coli and normal colorectal epithelial cells in vivo and in vitro. Materials and Methods: Five-week-old female Balb/c mice were divided in an untreated group, a group treated with clb(+) E. coli isolated from a Japanese patient with colorectal cancer (E. coli-50), and a group treated with non colibactin-producing E. coli (E. coli-50/ΔclbP). Mice were sacrificed at 18 weeks of treatment. Results: Treatment with clb(+) E. coli increased positivity for H2A histone family member X phosphorylated at Ser-139 (γH2AX) in epithelial cells of the luminal surface of the mouse rectum but this did not occur in the E. coli-50/ΔclbP and untreated groups. In an in vitro setting, the ratio of apoptotic cells was increased and cell counts were reduced by treatment with clb(+) E. coli more than in untreated cells and normal rat colorectal epithelial cells. Conclusion: E. coli-50 induced DNA damage in the mouse rectum, possibly by direct interaction between clb(+) E. coli and normal colorectal epithelial cells. Our findings imply that regulation of clb(+) E. coli infection may be a useful strategy for colorectal cancer control.
- Published
- 2021
41. Toward Engineered Biosynthesis of Drugs in Human Cells
- Author
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Shinya Matsuda, Yuta Tsunematsu, Takuma Matsushita, Yuji Ogata, Shihomi Hachiya, Shinji Kishimoto, Noriyuki Miyoshi, and Kenji Watanabe
- Subjects
Antifungal Agents ,Dose-Response Relationship, Drug ,Molecular Structure ,Cell Survival ,Aspergillus fumigatus ,Organic Chemistry ,Microbial Sensitivity Tests ,Biochemistry ,Structure-Activity Relationship ,Cytochrome P-450 Enzyme System ,Molecular Medicine ,Humans ,Molecular Biology ,Sesquiterpenes ,HeLa Cells - Abstract
Biosynthetic genes are not only responsible for the formation of bioactive substances but also suited for other applications including gene therapy. To test the feasibility of human cells producing antibiotics in situ when provided with a heterologous biosynthetic gene, we focused on cytochrome P450, the class of enzymes important in conferring bioactivity to natural product precursors. We selected Fma-P450 that plays a central role in the fumagillin antimicrobial biosynthesis in Aspergillus fumigatus to examine fungal metabolite production by HeLa cells that express fma-P450 heterologously. Here we show that HeLa cells harboring fma-P450 can biosynthesize 5-hydroxyl-β-trans-bergamoten and cytotoxic 5-epi-demethoxyfumagillol when supplemented with the nontoxic precursor β-trans-bergamotene. While the production level was insufficient to effect cell death, we demonstrate that programming human cells to autogenerate antibiotics by introducing a heterologous biosynthetic gene is feasible.
- Published
- 2021
42. Nitrogen Balance and Bioavailability of Amino Acids in Spirulina Diet-Fed Wistar Rats
- Author
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Takuya Yoshida, Noriyuki Miyoshi, Takuma Kobayashi, Tomoka Otagiri, Yasukiyo Yoshioka, Tatsuya Sasada, Keita Onoda, and Yudai Shioji
- Subjects
Nitrogen balance ,Nitrogen ,Biological Availability ,Systemic circulation ,Amino acid score ,Casein ,Spirulina ,Animals ,Food science ,Amino Acids ,Rats, Wistar ,Spirulina (genus) ,chemistry.chemical_classification ,biology ,General Chemistry ,biology.organism_classification ,Animal Feed ,Bioavailability ,Amino acid ,Diet ,Rats ,chemistry ,Animal Nutritional Physiological Phenomena ,Digestion ,General Agricultural and Biological Sciences - Abstract
Spirulina widely known to consumers as a health food is mainly a dried product. Since data for raw spirulina as a protein source are insufficient, the nutritional values of dry and raw spirulina diets in Wistar rats were determined. Digestibility coefficients were significantly lower in the dry (84.1 ± 0.5%) and raw (85.7 ± 0.4%) spirulina diets than that in the casein diet (96.6 ± 0.2%), although biological values of dry (86.3 ± 1.3%) and raw (77.9 ± 2.6%) spirulina diets were significantly higher than that of the casein diet (71.9 ± 2.5%). The protein digestibility-corrected amino acid score of raw spirulina (86.6 ± 0.5%) was significantly higher than that of dry spirulina (85.1 ± 0.5%). Additionally, amino acid profiling of portal/venous blood in spirulina diet-fed rats revealed that Ala, Gly, Val, and Leu/Ile were markedly decreased after systemic circulation. These results suggest that dry and raw spirulina diets may be effective not only as a protein source but also as a supplement to support protein/amino acid bioavailability.
- Published
- 2021
43. Chemoenzymatic synthesis of 3-ethyl-2,5-dimethylpyrazine by L-threonine 3-dehydrogenase and 2-amino-3-ketobutyrate CoA ligase/L-threonine aldolase
- Author
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Fumihito Hasebe, Tomoharu Motoyama, Shogo Nakano, Noriyuki Miyoshi, Shigenori Kumazawa, Sohei Ito, and Ryo Miyata
- Subjects
0301 basic medicine ,Stereochemistry ,Reaction intermediate ,Biochemistry ,Threonine aldolase activity ,03 medical and health sciences ,chemistry.chemical_compound ,symbols.namesake ,0302 clinical medicine ,Materials Chemistry ,Environmental Chemistry ,Threonine ,QD1-999 ,chemistry.chemical_classification ,DNA ligase ,biology ,Aldolase A ,Acetaldehyde ,General Chemistry ,Condensation reaction ,Chemistry ,Maillard reaction ,030104 developmental biology ,chemistry ,symbols ,biology.protein ,030217 neurology & neurosurgery - Abstract
Pyrazines are typically formed from amino acids and sugars in chemical reactions such as the Maillard reaction. In this study, we demonstrate that 3-ethyl-2,5-dimethylpyrazine can be produced from L-Thr by a simple bacterial operon. We conclude that EDMP is synthesized chemoenzymatically from L-Thr via the condensation reaction of two molecules of aminoacetone and one molecule of acetaldehyde. Aminoacetone is supplied by L-threonine 3-dehydrogenase using L-Thr as a substrate via 2-amino-3-ketobutyrate. Acetaldehyde is supplied by 2-amino-3-ketobutyrate CoA ligase bearing threonine aldolase activity from L-Thr when CoA was at low concentrations. Considering the rate of EDMP production, the reaction intermediate is stable for a certain time, and moderate reaction temperature is important for the synthesis of EDMP. When the precursor was supplied from L-Thr by these enzymes, the yield of EDMP was increased up to 20.2%. Furthermore, we demonstrate that this reaction is useful for synthesizing various alkylpyrazines. Threonine is a biosynthetic precursor to dimethylpyrazine derivatives, but the pathway by which this occurs is not fully established. Here l-throenine-3-dehydrogenase and 2-amino-3-ketobutyrate CoA ligase together are shown to convert l-threonine to dimethylpyrazine derivatives as a byproduct of glycine metabolism.
- Published
- 2021
44. Activity-Based Probe for Screening of High-Colibactin Producers from Clinical Samples
- Author
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Nobuo Matsuzaki, Fumihiko Tanioka, Yuji Iwashita, Michio Sato, Yuta Tsunematsu, Ryota Tamafune, Kenji Watanabe, Michihiro Mutoh, Yuichiro Hirayama, Hideki Ishikawa, Keiji Wakabayashi, Noriyuki Miyoshi, Haruhiko Sugimura, Ippei Ohnishi, and Yuko Yoshikawa
- Subjects
Molecular Structure ,010405 organic chemistry ,Chemistry ,Escherichia coli Proteins ,Organic Chemistry ,Computational biology ,010402 general chemistry ,medicine.disease_cause ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Polyketides ,Colibactin ,Escherichia coli ,medicine ,Humans ,Identification (biology) ,Physical and Theoretical Chemistry ,Diagnostic screening ,Colorectal Neoplasms ,Peptides ,Fluorescent Dyes - Abstract
While high-colibactin-producing Escherichia coli is thought to be associated with colorectal oncogenesis, this study is complicated part due to an inability to isolate colibactin adequately. Here, we created fluorescent probes activated by ClbP, the colibactin-maturing peptidase, to identify high-colibactin-producing strains. Our probe served as a valuable clinical diagnostic tool that allowed simple high-throughput diagnostic screening of clinical samples. Furthermore, the probe also allowed identification of high-colibactin producers that would help advance our understanding of colibactin biosynthesis.
- Published
- 2019
45. Distinct differences in the mechanisms of mucosal damage and γ-H2AX formation in the rat urinary bladder treated with o-toluidine and o-anisidine
- Author
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Tomomi Morikawa, Takanori Yamada, Takeshi Toyoda, Kumiko Ogawa, Kohei Matsushita, and Noriyuki Miyoshi
- Subjects
Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Toluidines ,DNA damage ,Health, Toxicology and Mutagenesis ,Urinary Bladder ,Inflammation ,010501 environmental sciences ,Toxicology ,01 natural sciences ,Histones ,03 medical and health sciences ,Toxicity Tests ,medicine ,Animals ,Carcinogen ,0105 earth and related environmental sciences ,Aniline Compounds ,Urinary bladder ,Chemistry ,Granulation tissue ,General Medicine ,Hyperplasia ,Phosphoproteins ,medicine.disease ,Rats, Inbred F344 ,Rats ,Mononuclear cell infiltration ,030104 developmental biology ,medicine.anatomical_structure ,Carcinogens ,Histopathology ,medicine.symptom ,Biomarkers ,DNA Damage - Abstract
Although aromatic amines are widely used as raw materials for dyes, some of them have been concerned about carcinogenicity in the urinary bladder. We examined early changes in histopathology and the formation of γ-H2AX, a biomarker of DNA damage, in the urinary bladder of rats to investigate the mechanisms of mucosal damage induced by monocyclic aromatic amines. 6-week-old male F344 rats were administered 0.4% or 0.8% o-toluidine, 0.3% or 1.0% o-anisidine, 0.4% 2,4-xylidine, 0.2% p-toluidine, or 0.6% aniline in the diet for 4 weeks. Animals were sequentially killed from day 2 to after 2 weeks of recovery, and histopathological and immunohistochemical analyses were performed. In the 0.8% o-toluidine group, there was sequential progression of bladder lesions, characterized by edematous changes and intramucosal hemorrhage at day 2 and formation of granulation tissue with mononuclear cell infiltration at week 1, followed by diffuse hyperplasia at weeks 2 and 4. In the 1.0% o-anisidine group, simple hyperplasia only with slight inflammation was detected from week 1. Whereas γ-H2AX-positive bladder epithelial cells in the 1.0% o-anisidine group were significantly increased in a time-dependent manner, transient increases in γ-H2AX-positive cells were detected at day 2 and week 1 in the 0.8% o-toluidine group. No apparent bladder lesions or increases in γ-H2AX formation were observed in any other groups. These results revealed different mechanisms of bladder mucosal damage associated with o-toluidine and o-anisidine. Moreover, immunohistochemical analysis for γ-H2AX suggested that both compounds may induce DNA damage in epithelial cells, mainly basal cells, of the bladder mucosa.
- Published
- 2019
46. In vitro genotoxicity analyses of colibactin-producing E. coli isolated from a Japanese colorectal cancer patient
- Author
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Takashi Yagi, Yoshimitsu Oda, Michio Sato, Yuuta Hisatomi, Yuta Tsunematsu, Yuko Yoshikawa, Haruhiko Sugimura, Yuichiro Hirayama, Chiaki Shimohara, Yuji Iwashita, Kenji Watanabe, Michihiro Mutoh, Keiji Wakabayashi, Hideki Ishikawa, Masanobu Kawanishi, and Noriyuki Miyoshi
- Subjects
Salmonella ,DNA damage ,Mutant ,010501 environmental sciences ,Biology ,Toxicology ,medicine.disease_cause ,030226 pharmacology & pharmacy ,01 natural sciences ,Molecular biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Gene cluster ,Micronucleus test ,medicine ,SOS response ,DNA ,Genotoxicity ,0105 earth and related environmental sciences - Abstract
Colibactin is a polyketide-peptide genotoxin produced by enteric bacteria such as E. coli, and is considered to contribute to the development of colorectal cancer. We previously isolated E. coli strains from Japanese colorectal cancer patients, and in the present study we investigated the genotoxic potency of the colibactin-producing (clb+) E. coli strains that carry the polyketide synthases "pks" gene cluster (pks+) and an isogenic clb- mutant in which the colibactin-producing ability is impaired. Measurement of phosphorylated histone H2AX indicated that DNA double strand breaks were induced in mammalian CHO AA8 cells infected with the clb+ E. coli strains. Induction of DNA damage response (SOS response) by crude extract of the clb+ strains was 1.7 times higher than that of the clb- E. coli in an umu assay with a Salmonella typhimurium TA1535/pSK1002 tester strain. Micronucleus test with CHO AA8 cells revealed that infection with the clb+ strains induced genotoxicity, i.e., the frequencies of micronucleated cells infected with clb+ strain were 4-6 times higher than with the clb- strain. Since the intestinal flora are affected by dietary habits that are strongly associated with ethnicity, these data may contribute to both risk evaluation and prevention of colorectal cancer in the Japanese population.
- Published
- 2019
47. Beneficial effects of the consumption of sun‐dried radishes ( Raphanus sativus cv. YR‐Hyuga‐Risou) on dyslipidemia in apolipoprotein E‐deficient mice
- Author
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Hideyuki Michimoto, Tatsuo Miyazaki, Noriyuki Miyoshi, Hiroyuki Sakakibara, Hiroki Matsuyama, and Wataru Tanaka
- Subjects
Apolipoprotein E ,Apolipoprotein B ,030309 nutrition & dietetics ,Biophysics ,Raphanus ,Decreased body weight ,Weight Gain ,Body weight ,Mice ,03 medical and health sciences ,Apolipoproteins E ,0404 agricultural biotechnology ,Animal science ,medicine ,Deficient mouse ,Animals ,Beneficial effects ,Dyslipidemias ,Pharmacology ,0303 health sciences ,biology ,business.industry ,04 agricultural and veterinary sciences ,Cell Biology ,medicine.disease ,biology.organism_classification ,040401 food science ,Diet ,biology.protein ,business ,Dyslipidemia ,Food Science - Abstract
In the present study, we evaluated the effects of daily consumption of raw (RR) or sun-dried (SDR) radishes (Raphanus sativus cv. YR-Hyuga-Risou) on apolipoprotein E-deficient (ApoE-/- ) mice. Daily consumption of RR for 16 weeks significantly decreased body weight gain in the both wild-type and ApoE-/- mice. The wild-type mice fed the SDR diet gained significantly less body weight than the ApoE-/- mice fed the same diet, although the ApoE-/- mice showed a trend toward decreased body weight gain. Consumption of both diets led to a marked decrease in visceral fat weight and serum triglyceride levels in ApoE-/- mice. Oral fat tolerance tests indicated that pretreatment with RR or SDR mitigated the increase in serum triglyceride levels seen after oil administration. In conclusion, we found that daily consumption of both RR- and SDR-containing diets can help us to prevent from dyslipidemia by inhibiting fat absorption.
- Published
- 2021
48. Isolation of New Colibactin Metabolites from Wild-Type
- Author
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Tao, Zhou, Yuichiro, Hirayama, Yuta, Tsunematsu, Nanami, Suzuki, Seiji, Tanaka, Nahoko, Uchiyama, Yukihiro, Goda, Yuko, Yoshikawa, Yuji, Iwashita, Michio, Sato, Noriyuki, Miyoshi, Michihiro, Mutoh, Hideki, Ishikawa, Haruhiko, Sugimura, Keiji, Wakabayashi, and Kenji, Watanabe
- Subjects
Polyketides ,Escherichia coli ,Temperature ,Humans ,Peptides - Abstract
Colibactin is a polyketide-nonribosomal peptide hybrid secondary metabolite that can form interstrand cross-links in double-stranded DNA. Colibactin-producing
- Published
- 2021
49. Fasting increases 18:2-containing phosphatidylcholines to complement the decrease in 22:6-containing phosphatidylcholines in mouse skeletal muscle
- Author
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Shinji Miura, Takumi Akahori, Hiyori Ichida, Nanami Senoo, Noriyuki Miyoshi, Hideo Shindou, Takao Shimizu, and Akihito Morita
- Subjects
0301 basic medicine ,Male ,Physiology ,Structural diversity ,Gene Expression ,Biochemistry ,Mass Spectrometry ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Endocrinology ,Medicine and Health Sciences ,Insulin ,Musculoskeletal System ,Chromatography, High Pressure Liquid ,Phospholipids ,chemistry.chemical_classification ,Mice, Knockout ,Principal Component Analysis ,Multidisciplinary ,Muscles ,Fatty Acids ,Fasting ,Muscle Analysis ,Lipids ,humanities ,medicine.anatomical_structure ,Bioassays and Physiological Analysis ,Physiological Parameters ,Fatty Acids, Unsaturated ,Phosphatidylcholines ,Medicine ,lipids (amino acids, peptides, and proteins) ,Anatomy ,Polyunsaturated fatty acid ,Research Article ,medicine.medical_specialty ,Science ,Cellular functions ,Phospholipid ,Research and Analysis Methods ,behavioral disciplines and activities ,Lysophosphatidic acid acyltransferase ,Diabetes Mellitus, Experimental ,03 medical and health sciences ,Internal medicine ,medicine ,Genetics ,Animals ,Muscle, Skeletal ,Diabetic Endocrinology ,Catabolism ,Body Weight ,Skeletal muscle ,Biology and Life Sciences ,Soleus Muscles ,Hormones ,Mice, Inbred C57BL ,030104 developmental biology ,chemistry ,Skeletal Muscles ,030217 neurology & neurosurgery ,Acyltransferases - Abstract
Fasting stimulates catabolic reactions in skeletal muscle to survive nutrient deprivation. Cellular phospholipids have large structural diversity due to various polar-heads and acyl-chains that affect many cellular functions. Skeletal muscle phospholipid profiles have been suggested to be associated with muscle adaptations to nutritional and environmental status. However, the effect of fasting on skeletal muscle phospholipid profiles remains unknown. Here, we analyzed phospholipids using liquid chromatography mass spectrometry. We determined that fasting resulted in a decrease in 22:6-containing phosphatidylcholines (PCs) (22:6-PCs) and an increase in 18:2-containing PCs (18:2-PCs). The fasting-induced increase in 18:2-PCs was sufficient to complement 22:6-PCs loss, resulting in the maintenance of the total amount of polyunsaturated fatty acid (PUFA)-containing PCs. Similar phospholipid alterations occurred in insulin-deficient mice, which indicate that these observed phospholipid perturbations were characteristic of catabolic skeletal muscle. In lysophosphatidic acid acyltransferase 3-knockout muscles that mostly lack 22:6-PCs, other PUFA-containing PCs, mainly 18:2-PCs, accumulated. This suggests a compensatory mechanism for skeletal muscles to maintain PUFA-containing PCs.
- Published
- 2021
50. Metastasis of Breast Cancer Promoted by Circadian Rhythm Disruption due to Light/Dark Shift and its Prevention by Dietary Quercetin in Mice
- Author
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Nobuhiko Miura, Akane Hirano, Kazutoshi Sayama, Masa-Aki Shibata, Minoru Numata, Kayoko Shimoi, Noriyuki Miyoshi, Yukika Yamamoto, Tomohiro Asai, Michiko Yasuda, and Naoto Oku
- Subjects
circadian rhythm ,Physiology ,030209 endocrinology & metabolism ,Malignancy ,Metastasis ,quercetin ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,breast cancer ,medicine ,Circadian rhythm ,lcsh:QH301-705.5 ,Food Science, Nutritional Chemistry ,light/dark shift ,lymph node metastasis ,Endocrine and Autonomic Systems ,business.industry ,Cancer ,medicine.disease ,lcsh:Biology (General) ,Cancer research ,Chronic inflammatory response ,Distant Lymph Node ,Lymph ,business ,030217 neurology & neurosurgery ,Research Article - Abstract
Epidemiological studies have indicated that a disturbed circadian rhythm resulting from night-shift work is a potential risk factor for breast cancer. However, the mechanism of increased risk of breast cancer by night-shift work remains unclear, and there have been few in vivo studies conducted to definitively associate the two factors. In this study, BJMC3879Luc2 mouse breast cancer cells were transplanted into BALB/c mice. Mice were maintained under lighting conditions that modeled the two-shift system and were investigated for the effect of light/dark cycle disruption on tumor growth and lymph node metastasis. Circadian dysfunction, which was confirmed by measuring circadian locomotor activities using a nano tag device in our light/dark shift model, did not affect tumor growth. However, a significant increase in the number of lymph nodes with distant metastasis was observed. Neutrophil-to-lymphocyte ratio, which is an adverse prognostic factor of breast cancer and also indicator of inflammation, also increased. It has been demonstrated that a chronic inflammatory response is associated with cancer malignancy and poor prognosis in various cancers. These results suggest that night-shift work may also affect distant metastasis and prognosis. In addition, we investigated whether dietary quercetin has anti-metastatic activity against light/dark shift-induced metastasis. A diet containing 0.3 % quercetin significantly inhibited distant lymph node metastasis, particularly metastasis to the iliac and kidney lymph nodes. Our results contribute to our understandings of the effects of the external light environment on breast cancer metastasis and provide a glimpse into potential protective effects of dietary quercetin on light/dark disturbance-induced metastasis.
- Published
- 2021
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