Journal of Clinical Biochemistry and Nutrition
Online ISSN : 1880-5086
Print ISSN : 0912-0009
ISSN-L : 0912-0009
63 巻, 1 号
選択された号の論文の14件中1~14を表示しています
Review
  • Yuji Naito, Kazuhiko Uchiyama, Tomohisa Takagi
    原稿種別: Review
    2018 年 63 巻 1 号 p. 1-4
    発行日: 2018年
    公開日: 2018/07/01
    [早期公開] 公開日: 2018/06/20
    ジャーナル フリー

    Redox-related gaseous molecular species in the gastrointestinal tract are derived from the chemical oxidation-reduction reactions, enzymatic reactions, swallowing, and bacterial production. Recent studies have demonstrated the crucial roles of the microbiota and gaseous molecules in the pathogenesis of gastrointestinal inflammatory and functional diseases. Especially in the hypoxic condition of the large intestine, various bacteria produce acetic acid, methane, and hydrogen sulfide using hydrogen molecules generated by the fermentation reaction as an energy source. In this review, we summarized the recent advances in the biology of redox-related gaseous molecules in the gastrointestinal tract.

Serial Reviews
  • Hidekazu Suzuki
    原稿種別: Serial Review
    2018 年 63 巻 1 号 p. 5
    発行日: 2018年
    公開日: 2018/07/01
    [早期公開] 公開日: 2018/04/11
    ジャーナル フリー
  • Juntaro Matsuzaki, Takahiro Ochiya
    原稿種別: Serial Review
    2018 年 63 巻 1 号 p. 6-11
    発行日: 2018年
    公開日: 2018/07/01
    [早期公開] 公開日: 2018/04/11
    ジャーナル フリー

    Recent evidence has suggested that extracellular microRNAs have crucial roles in intercellular communications and are promising as minimally invasive biomarkers for various diseases including cancers. Oxidative stress also plays an essential role in homeostasis and disease development. This systematic review aims to clarify the current evidence on the interaction between oxidative stress and extracellular microRNAs. We identified 32 studies that provided information regarding the association between oxidative stress and extracellular microRNAs: 9 focused on the central nervous system, 11 focused on cardiovascular diseases, and 4 focused on liver injury. Endothelial cell-specific miR-126-3p was the most studied extracellular miRNA associated with oxidative stress. In addition, we highlight some reports that describe the mechanisms of how oxidative stress affects extracellular microRNA profiles in liver injury. In liver injury, the levels of miR-122-5p, miR-192-5p, miR-223-3p, and miR-1224-5p were reported to be elevated in the sera. The release of miR-122-5p, miR-192-5p, and miR-1224-5p from hepatocytes may be attributed to oxidative stress. miR-223-3p could be released from neutrophils and suppress oxidative stress in the liver. Elucidation of the mechanisms of the interaction between extracellular microRNAs and oxidative stress would improve our pathophysiological understanding as well as future medical practice.

  • Yasuaki Kabe, Hiroshi Handa, Makoto Suematsu
    原稿種別: Serial Review
    2018 年 63 巻 1 号 p. 12-17
    発行日: 2018年
    公開日: 2018/07/01
    [早期公開] 公開日: 2018/04/11
    ジャーナル フリー

    Progesterone receptor membrane associated component 1 is a multifunctional heme-binding protein that plays a role in several biological processes such as tumor progression, metabolic regulation, and viability control of nerve cells. Notably, progesterone receptor membrane associated component 1 is highly expressed in various types of cancer cells, and facilitates cancer proliferation and chemoresistance. Recently, progesterone receptor membrane associated component 1 structure has been explored by X-ray crystallographic analysis. Interestingly, whereas apo- progesterone receptor membrane associated component 1 exists as a monomer, the heme-bound progesterone receptor membrane associated component 1 converts into a stable dimer by forming a unique heme-heme stacking structure, leading to activation of epidermal growth factor receptor signaling and chemoresistance in cancer cells. Furthermore, the gas mediator carbon monoxide inhibits progesterone receptor membrane associated component 1-mediated activation in cancer cells by dissociating the heme-stacking dimer of progesterone receptor membrane associated component 1. The dynamic structural regulation of progesterone receptor membrane associated component 1 will provide new insights for understanding the mechanisms underlying its various functions.

  • Akinori Yanaka
    原稿種別: Serial Review
    2018 年 63 巻 1 号 p. 18-25
    発行日: 2018年
    公開日: 2018/07/01
    [早期公開] 公開日: 2018/05/03
    ジャーナル フリー

    The gastrointestinal tract is exposed to a variety of noxious factors, such as Helicobacter pylori, nonsteroidal anti-inflammatory drugs, gastric acid, ischemia-reperfusion, and mental stresses. Theses stressors generate free radicals within gastrointestinal tissues, causing organ injury and functional disturbance. Although the gastrointestinal tract can withstand such oxidative stresses to some extent by enhancing its antioxidant system via nuclear factor erythroid 2-related factor 2-Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1-mediated pathways, acute or chronic exposure to oxidative stress can cause several gastrointestinal tract disorders, such as inflammation, ulcers, cancers, and various functional disturbances. Recent studies have demonstrated that some natural compounds and drugs can upregulate the nuclear factor erythroid 2-related factor 2-mediated antioxidant system, ameliorating or preventing these disorders. Although these compounds may be useful as chemopreventive agents, sufficient evidence for their clinical efficacy has not yet been provided. In addition, it is important to note that excessive nuclear factor erythroid 2-related factor 2 stimulation can be harmful to human health, especially from the standpoint of tumor biology.

  • Yuji Nadatani, Toshio Watanabe, Sunao Shimada, Koji Otani, Tetsuya Tan ...
    原稿種別: Serial Review
    2018 年 63 巻 1 号 p. 26-32
    発行日: 2018年
    公開日: 2018/07/01
    [早期公開] 公開日: 2018/05/25
    ジャーナル フリー

    Intestinal ischemia/reperfusion injury is a severe disease associated with a high mortality. The mechanisms that cause ischemia/reperfusion injury are complex and many factors are involved in the injury formation process; however, the only available treatment is surgical intervention. Recent studies demonstrated that the intestinal microbiome plays a key role in intestinal ischemia/reperfusion injury and there are many factors associated with intestinal bacteria during the formation of the intestinal ischemia/reperfusion injury. Among the Toll-like receptors (TLR), TLR2, TLR4, and their adaptor protein, myeloid differentiation primary-response 88 (MyD88), have been reported to be involved in intestinal ischemia/reperfusion injury. Oxidative stress and nitric oxide are also associated with intestinal bacteria during the formation of the intestinal ischemia/reperfusion injury. This review focuses on our current understanding of the impact of the microbiome, including the roles of the TLRs, oxidative stress, and nitric oxide, on intestinal ischemia/reperfusion injury.

Mini Review
  • Yuji Naito, Kazuhiko Uchiyama, Tomohisa Takagi
    原稿種別: Mini Review
    2018 年 63 巻 1 号 p. 33-35
    発行日: 2018年
    公開日: 2018/07/01
    [早期公開] 公開日: 2018/06/20
    ジャーナル フリー

    There have been many reports on the roles of intestinal flora and intestinal environment in health promotion and disease prevention. Beneficial bacteria such as Bifidobacterium and lactic acid-producing bacteria have been shown to improve the intestinal environment, and yield a good effect on metabolism, immunity and nerve response. In this review, in addition to these beneficial bacteria, we introduced Akkermansia muciniphila as a next-generation beneficial microbe. Several reports indicate that Akkermansia muciniphila affects glucose metabolism, lipid metabolism, and intestinal immunity, and that certain food ingredients such as polyphenols may increase the abundance of Akkermansia muciniphila in the gut.

Original Articles
  • Masahiko Terasaki, Hiromu Ito, Hiromi Kurokawa, Masato Tamura, Susumu ...
    原稿種別: Original Article
    2018 年 63 巻 1 号 p. 36-41
    発行日: 2018年
    公開日: 2018/07/01
    [早期公開] 公開日: 2018/04/03
    ジャーナル フリー

    Acetic acid can cause cellular injury. We previously reported that acetic acid induces cancer cell-selective death in rat gastric cells. However, the mechanism is unclear. Generally, cancer cells are more sensitive to reactive oxygen species than normal cells. Accordingly, in this study, we investigated the involvement of oxidative stress in cancer cell-selective death by acetic acid using normal gastric mucosal cells and cancerous gastric mucosal cells. The cancer cell-selective death was induced at the concentration of 2–5 µM acetic acid. Cancerous gastric mucosal cells had increased expression of monocarboxylic transporter 1 and high uptake of acetic acid, compared to normal gastric mucosal cells. The exposure of cancerous gastric mucosal cells to acetic acid enhanced production of reactive oxygen species and expression of monocarboxylic transporter 1, and induced apoptosis. In contrast, acetic acid showed minor effects in normal gastric mucosal cells. These results indicate that acetic acid induced cancer cell-selective death in gastric cells through a mechanism involving oxidative stress.

  • Yu Matsumoto, Yuko Tousen, Yoshiko Ishimi
    原稿種別: Original Article
    2018 年 63 巻 1 号 p. 42-49
    発行日: 2018年
    公開日: 2018/07/01
    [早期公開] 公開日: 2018/05/25
    ジャーナル フリー

    β-Carotene has been reported to be useful to maintain a positive balance of bone turnover. However, the effects of β-carotene on bone loss remain to be elucidated in mice with hind limb unloading. Therefore, we investigated whether β-carotene prevented bone loss induced by skeletal hind limb unloading in mice. Female 8-week-old ddY mice were divided into six groups (n = 6–8 each) and subjected to: (1) normal housing, (2) sham unloading fed a control diet, (3) hind limb unloading fed a control diet, (4) hind limb unloading fed a 0.025% β-carotene-containing diet, (5) hind limb unloading fed a 0.05% β-carotene-containing diet, and (6) hind limb unloading fed a 0.25% β-carotene-containing diet. After 3 weeks, bone mineral density of the tibia was markedly reduced by unloading, which was prevented by 0.025% β-carotene. Histological analysis revealed a hind limb unloading-induced decrease in the calcified bone of the femur, which was slightly prevented by 0.025% β-carotene. The 0.025% β-carotene-containing diet increased the gene expression of osteoprotegerin in the bone marrow cells in unloading mice. These results suggest that a β-carotene-containing diet may preserve bone health in subjects with disabilities as well as in astronauts.

  • Yurika Okamura, Akira Omori, Norihiko Asada, Akifumi Ono
    原稿種別: Original Article
    2018 年 63 巻 1 号 p. 50-57
    発行日: 2018年
    公開日: 2018/07/01
    [早期公開] 公開日: 2018/04/03
    ジャーナル フリー

    The purpose of this study was to investigate the influence of vitamins C and E on the toxic action of alcohol in rat liver regeneration. Male Sprague-Dawley rats subjected to 70% partial hepatectomy were divided into five groups (Groups 1 to 5). Rats in Groups 2 to 5 were only provided alcohol for drinking. Additionally, vitamin C, vitamin E, and vitamin C in combination with vitamin E were administered to Groups 3, 4, and 5, respectively. Alcohol inhibits liver regeneration, resulting in an increase in free radicals produced by alcohol metabolism and thus causing cellular damage and altering liver function. During liver regeneration, vitamins C and E significantly ameliorated liver injury from alcohol administration by reducing hepatic lipid peroxidation. Vitamins C and E protect against liver injury and dysfunction, attenuate lipid peroxidation, and thus may be more effective in combination than either vitamin alone against alcohol-mediated toxic effects during liver regeneration.

  • Michihito Toda, Shinjiro Mizuguchi, Yukiko Minamiyama, Hiroko Yamamoto ...
    原稿種別: Original Article
    2018 年 63 巻 1 号 p. 58-65
    発行日: 2018年
    公開日: 2018/07/01
    [早期公開] 公開日: 2018/04/11
    ジャーナル フリー
    電子付録

    Pirfenidone is a representative medication to treat interstitial pulmonary fibrosis. Researchers reported pirfenidone (>100 µg/ml) significantly suppressed fibroblast growth in vitro. However, clinically, the maximum concentration of pirfenidone in the blood is approximately 10 µg/ml. We hypothesized there might be an additional mechanism of pirfenidone to fibroblasts indirectly. Macrophages are known to control the activation of fibroblasts via the regulation of inflammatory M1 and suppressive M2 polarization. The aim of this study was to investigate the effects of pirfenidone on alveolar macrophage polarization. Rat alveolar macrophages (NR8383) were stimulated in vitro with lipopolysaccharide (LPS) + interferon (IFN)-γ, or interleukin (IL)-4 + IL-13. Expression of M1 and M2 markers and supernatant’s levels of TGF-β1 were assessed after pirfenidone treatment (0–100 µg/ml). Treatment with LPS + INF-γ or IL-4 + IL-13 significantly increased the expression of M1 and M2 markers, respectively. In macrophage polarization assays, pirfenidone significantly reduced the expression of M2 markers at concentrations greater than 10 µg/ml but had no effect on the expression of M1 markers. At these concentrations, pirfenidone significantly reduced TGF-β1 levels in NR8383 culture supernatants. In rat lung fibroblasts treated with NR8383 culture supernatants, pirfenidone significantly suppressed proliferation, and the collagen mRNA and protein levels. In conclusion, our results demonstrated that pirfenidone suppressed polarization to M2 macrophages at clinically relevant concentrations and suppressed the rat lung fibroblasts fibrogenic activity.

  • Sayuri Nonaka, Susumu Fujii, Megumi Hara, Shigeki Morita, Eisaburo Sue ...
    原稿種別: Original Article
    2018 年 63 巻 1 号 p. 66-69
    発行日: 2018年
    公開日: 2018/07/01
    [早期公開] 公開日: 2018/04/11
    ジャーナル フリー

    This study aimed i) to investigate about items with high relevance for aspiration pneumonia during hospitalization among cases evaluated using Diagnosis Procedure Combination data, and ii) to determine whether the concern factors for aspiration pneumonia during hospitalization were exacerbated with the trend of the time. The Diagnosis Procedure Combination data were gathered from 2010 through to 2015 with 63,390 cases at Saga University Hospital. The occurrence of concern factors of aspiration pneumonia during hospitalization were compared in the two time periods set (2010–2012 and 2013–2015). The concern factors included: male, age, dysphagia at admission and during hospitalization, use and days in the emergency care unit or high care unit, use of the intensive care unit, and use of an ambulance. Age, dysphagia, and use of the intensive care unit were time-dependently exacerbated. The incidence of aspiration pneumonia during hospitalization in hospitalized cases did not differ between years 2010–2012 and 2013–2015. Aspiration pneumonia during hospitalization complicated with surgery and number days in the emergency care unit or high care unit diminished in years 2013–2015. Despite an increased concern of aspiration pneumonia during hospitalization, the complication rate of aspiration pneumonia during hospitalization did not increase.

  • Shinichi Goto, Takayuki Morikawa, Akiko Kubo, Keiyo Takubo, Keiichi Fu ...
    原稿種別: Original Article
    2018 年 63 巻 1 号 p. 70-79
    発行日: 2018年
    公開日: 2018/07/01
    [早期公開] 公開日: 2018/04/11
    ジャーナル フリー
    電子付録

    Carbon monoxide-generating heme oxygenase-2 is expressed in neurons and plays a crucial role for regulating hypoxic vasodilation through mechanisms unlocking carbon monoxide-dependent inhibition of H2S-generating cystathionine β-synthase expressed in astrocytes. This study aims to examine whether heme oxygenase-2 plays a protective role in mice against stroke. Focal ischemia was induced by middle cerebral artery occlusion. Regional differences in metabolites among ipsilateral and contralateral hemispheres were analysed by quantitative imaging mass spectrometry equipped with an image-processing platform to optimize comparison of local metabolite contents among different animals. Under normoxia, blood flow velocity in precapillary arterioles were significantly elevated in heme oxygenase-2-null mice vs controls, while metabolic intermediates of central carbon metabolism and glutamate synthesis were elevated in the brain of heme oxygenase-2-null mice, suggesting greater metabolic demands to induce hyperemia in these mice. In response to focal ischemia, heme oxygenase-2-null mice exhibited greater regions of ischemic core that coincide with notable decreases in energy metabolism in the contralateral hemisphere as well as in penumbra. In conclusion, these findings suggest that heme oxygenase-2 is involved in mechanisms by which not only protects against compromised energy metabolism of the ipsilateral hemisphere but also ameliorates transhemispheric diaschisis of the contralateral hemisphere in ischemic brain.

  • Kanji Ohkuma, Hiroshi Iida, Yumi Inoh, Kenji Kanoshima, Hidenori Ohkub ...
    原稿種別: Original Article
    2018 年 63 巻 1 号 p. 80-83
    発行日: 2018年
    公開日: 2018/07/01
    [早期公開] 公開日: 2018/05/09
    ジャーナル フリー

    To promote symptom relief from acid-related diseases, a medicine with a rapid-onset effect is ideal. The aim of this study was to investigate the early inhibitory effect on gastric acid secretion after a single oral administration of vonoprazan, which represents a new class of proton pump inhibitors, and to compare this effect with those of lansoprazole and famotidine. Ten Helicobacter pylori (HP)-negative male subjects participated in this randomized, three-way crossover study. A single oral administration of vonoprazan (20 mg), lansoprazole (30 mg) or famotidine (20 mg) was performed, and the intragastric pH was continuously monitored for 6 h. Each drug was administered at least seven days apart. The average intragastric pH during the 6-h period after the administration of famotidine was higher than that after the administration of lansoprazole (median: 4.45 vs 2.65; p = 0.0284). A similar result was observed for vonoprazan and lansoprazole (median: 4.30 vs 2.65; p = 0.0322). In conclusions, oral administration of vonoprazan and famotidine in HP-negative healthy male subjects caused the intragastric pH to rise more quickly than did lansoprazole. (Trial Registration: UMIN000020989)

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