Journal of Clinical Biochemistry and Nutrition
Online ISSN : 1880-5086
Print ISSN : 0912-0009
ISSN-L : 0912-0009
Advance online publication
Showing 1-34 articles out of 34 articles from Advance online publication
  • Yugo Kato, Hayami Uchiumi, Ryo Usami, Hirokatsu Takatsu, Yoshinori Aok ...
    Type: Original Article
    Article ID: 21-10
    Published: 2021
    [Advance publication] Released: June 11, 2021
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    Obesity induces severe disorders such as type 2 diabetes and cardiovascular events, and the number of people with obesity is increasing all over the world. Furthermore, it is possible that obesity increases the risk of cognitive dysfunction via the acceleration of oxidative damage. Tocotrienols, which are part of the vitamin E family, have antioxidant and anti-obesity effects. However, the effects of tocotrienols on high-fat diet-treated mice have not been completely elucidated. In this study, we assessed changes in body weight, spatial reference memory acquisition, liver lipid droplet size, blood brain barrier-related protein expressions and antioxidative defense systems in high-fat diet-treated mice in the presence or absence of tocotrienols. The results showed that tocotrienols significantly inhibited body weight gain and lipid droplet synthesis. Although the amount was very small, it was confirmed that tocotrienols surely reached the brain in the perfused brain. Treatment with tocotrienols was tended to improve cognitive function in the control mice. However, tocotrienols did not modulate blood brain barrier-related protein expressions or antioxidative defense systems. These results indicate that treatment with tocotrienols could be effective for the prevention of obesity and cognitive dysfunction. Further extended research is needed to elucidate the relationship between anti-obesity and antioxidant effects of tocotrienols, especially in the brain.

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  • Shihona Ogino, Noriyoshi Ogino, Kotomi Tomizuka, Masamitsu Eitoku, Yos ...
    Type: Original Article
    Article ID: 21-24
    Published: 2021
    [Advance publication] Released: May 08, 2021
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    Supplementary material

    The health-promoting effects of exercise are explained by the biological adaptation to oxidative stress via maintenance of mitochondrial function especially in muscles. Although the induction of antioxidant enzymes in muscle is a useful indicator of exercise, it is not widely used due to the invasiveness of muscle biopsies. To explore more suitable biomarkers for exercise, we examined mRNA levels of antioxidant enzymes in peripheral blood mono­nuclear cells of 14 volunteers in an exercise intervention study. These results were validated in a cross-sectional study of 392 healthy individuals, and we investigated the association between exercise habits, smoking, alcohol consumption, mitochondrial DNA, malondialdehyde, and various clinical features. The 2-week exercise increased superoxide dismutase 1 at the end of exercise and superoxide dismutase 2 from week 4 onwards. In the cross-sectional study, superoxide dismutase 2 correlated positively with exercise habits and number of mitochondrial DNA, and negatively with malondialdehyde levels. Multivariate binominal regression analysis showed that superoxide dismutase 2 was positively associated with exercise habits in nonsmoking individuals. These results suggest that mRNA levels of superoxide dismutase 2 in blood might be a potentially useful biomarker for exercise in healthy individuals. This study was registered with University Hospital Medical Information Network (No: 000038034).

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  • Masahide Hamaguchi, Tetsuya Nojiri, Takuro Okamura, Yoshitaka Hashimot ...
    Type: Original Article
    Article ID: 21-31
    Published: 2021
    [Advance publication] Released: June 04, 2021
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    Supplementary material

    The spread of coronavirus disease 2019 (COVID-19) has led to drastic changes in people’s lifestyles, including teleworking and restrictions on socializing. In the context of observing social distancing for preventing infection, the need to maintain fitness and health has attracted particular attention. We aimed to determine the relationship between the increase in the number of active users of online diet management applications and COVID-19 infection rates in Japan. A total of 1.5 million rows of log data was analyzed. The active number of users of online diet management applications increased with increase in the number of COVID-19 infections. The active user number in Kanagawa Prefecture, where the first cases of COVID-19 were reported in Japan, was particularly high. Moreover, there was a significant increase in the user number in prefectures under a state of emergency when compared to that in prefectures not under a state of emergency. The social anxiety caused by COVID-19 is expected to increase the demand for online health management applications further. The use of such programs can aid in achieving social distancing while enabling users to maintain healthy lifestyles.

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  • Shiho Ohnishi, Keiichi Hiramoto, Ning Ma, Shosuke Kawanishi
    Type: Original Article
    Article ID: 20-189
    Published: 2021
    [Advance publication] Released: May 28, 2021
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    Inflammation is a primary risk factor for cancer. Epidemiological studies previously demonstrated that aspirin decreased the incidence of cancer and specifically reduced the risk of colorectal cancer. However, the number of animal studies that have confirmed the efficacy of aspirin remains limited. Therefore, the purpose of the present study was to investigate the mechanisms by which aspirin prevents colorectal cancer in mice. ICR mice were treated with azoxymethane and the ulcerative colitis inducer, dextran sodium sulfate, to induce colorectal tumors. Aspirin was orally administered three times per week for 12 weeks. Aspirin significantly reduced the number and size of colorectal tumors. Aspirin also significantly decreased tumor necrosis factor alpha and reactive oxygen species (ROS) levels in the plasma. Immunohistochemical analyses and western blots showed that cyclooxygenase 2 (COX2), inducible nitric oxide synthase (iNOS), and the active form of Yes-associated protein 1 (YAP1), and cytosolic high mobility group box 1 (HMGB1) were strongly expressed at colorectal tumor sites and clearly suppressed by aspirin. An indicator of inflammation-related DNA damage, 8-nitroguanine, also accumulated in the colorectal tissues and was suppressed by aspirin. The present results suggest that the ingestion of aspirin suppressed carcinogenesis caused by inflammation through decreases in COX2 and ROS levels, resulting in reductions in DNA damage and oncogenic YAP1.

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  • Yasuki Higashimura, Misaki Hirabayashi, Hitomi Nishikawa, Ryo Inoue, E ...
    Type: Original Article
    Article ID: 20-203
    Published: 2021
    [Advance publication] Released: May 28, 2021
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    Consumption of yacon (Smallanthus sonchifolius) is associated with beneficial effects such as prevention of metabolic diseases. Yacon root is known to contain various bioactive components including indigestible carbohydrates, but the alteration of intestinal environment after treatment with yacon has not been fully investigated. This study investigated yacon-containing diet effects on the intestinal environment in mice, including microbial composition, short-chain fatty acid levels, and mucus content. After mice were administered yacon-containing diet for 4 weeks, 16S rRNA gene sequencing analyses revealed their fecal microbiota profiles. Organic acid concentrations in cecal contents were measured using an HPLC system. Compared to the control group, yacon-containing diet-received mice had significantly higher the concentrations of succinic acid, lactic acid, acetic acid, and propionic acid. The fecal mucin content was also higher in yacon-containing diet-received mice. Results of 16S rRNA gene sequencing analyses showed that the relative abundances of 27 taxa differed significantly in yacon-containing diet-received mice. Furthermore, results show effects of yacon administration on intestinal inflammation using 2,4,6-trinitrobenzene sulfonic acid induced colitis model in mice. Increased colonic damage and myeloperoxidase activity after 2,4,6-trinitrobenzene sulfonic acid treatment were suppressed in yacon-containing diet-received mice. Results suggest that oral intake of yacon root modulates the intestinal environment, thereby inhibiting intestinal inflammation.

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  • Yuto Saijo, Hiroshi Okada, Masahide Hamaguchi, Takuro Okamura, Yoshita ...
    Type: Original Article
    Article ID: 21-15
    Published: 2021
    [Advance publication] Released: May 28, 2021
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    It has been reported that oral health is associated with some co-morbid conditions, including cardiovascular disease, in people with type 2 diabetes mellitus. The present study investigated the association between the frequency of toothbrushing and lifestyle in people with type 2 diabetes mellitus. This cross-sectional study included 624 outpatients at the Kyoto Prefectural University of Medicine in Kyoto, Japan from January 2014 to January 2016. Lifestyle was evaluated using a self-administered questionnaire. The average age and hemoglobin A1c level were 67.6 ± 10.9 years and 7.2 ± 1.1%, respectively. The number of patients who brushed their teeth twice or more a day was 189 (50.3%) in men and 198 (79.8%) in women. Among men, the proportion of patients living alone was lower in those who brushed their teeth twice or more a day than those who brushed their teeth never/rarely or once a day. The logistic regression analysis, after adjusting for confounding factors, revealed that living alone (odds ratio 2.88; 95% confidence interval 1.53–5.66) was associated with the increased odds of the low frequency of toothbrushing (never/rarely or once a day) in men, but not in women. In conclusion, the results of our study suggest that living alone was associated with the low frequency of toothbrushing in people with type 2 diabetes mellitus, particularly in men.

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  • Ji-Sook Kong, Hye Won Woo, Yu-Mi Kim, Mi Kyung Kim
    Type: Original Article
    Article ID: 21-20
    Published: 2021
    [Advance publication] Released: May 28, 2021
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    Supplementary material

    This study examined the associations between specific non-alcoholic beverages and high-sensitivity C-reactive protein (hs-CRP) and their interactions with obesity. The study participants were 4,999 adults aged 19–64 years from the 2015–2016 Korean National Health and Nutrition Examination Survey. The odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multivariable logistic regression analyses. In women, there was an inverse linear trend between coffee and hs-CRP status (ptrend = 0.0137), and a positive linear trend for soda was also found (≥1/week vs never or almost never, OR = 1.79, 95% CI 1.23–2.61, ptrend = 0.0127). In the stratification analyses, the associa­tions were only observed in obese women. The associations were inverse for coffee and tea but linearly positive for soda in obese women (ptrend<0.05). In men, an inverted J-shaped association between commercial fruit juice/drink and hs-CRP status was found; but after stratification by obesity, the association was linear only in obese men (ptrend<0.05, OR = 2.44, 95% CI 1.44–4.16 in ≥1/week vs never or almost never). Coffee and tea in women may be beneficially associated with hs-CRP status, but soda in women and commercial fruit juice/drink in men may be adversely, particularly for obese adults.

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  • Jeong Min Seong, Chang Eun Park, Mi Young Gi, Ju Ae Cha, Ae Eun Moon, ...
    Type: Original Article
    Article ID: 21-26
    Published: 2021
    [Advance publication] Released: May 28, 2021
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    Supplementary material

    This study was conducted to assess the relationship between vitamin D deficiency and anemia, by gender, in Korean adults. The data of 16,060 adults were analyzed (men, 6,840; premenopausal women, 4,916; postmenopausal women, 4,340) from the fifth Korean National Health and Nutrition Examination Survey (KNHANES V) (2010–2012). There were several key findings. First, after adjusting for related variables, the odds ratio (OR) of anemia [hemoglobin (Hb) <13 g/dl in men or Hb <12 g/dl in women] using the vitamin D normal group {25-hydroxyvitamin [25(OH)D] ≥15.0 ng/ml} as reference, was significant for the vitamin D deficient group [25(OH)D <15.0 ng/ml] in the overall population [OR, 1.310; 95% confidence interval (CI), 1.168–1.470]. Second, the OR of anemia, using the vitamin D normal group as reference, was significant for the vitamin D deficient group in premenopausal women (OR, 1.293; 95% CI, 1.105–1.513). However, vitamin D deficiency in the vitamin D normal group in men (OR, 1.093; 95% CI, 0.806–1.484) and postmenopausal women (OR, 1.130; 95% CI, 0.906–1.409) was not significant. In conclusion, Vitamin D deficiency is positively associated with anemia in premenopausal women, but not in men and postmenopausal women.

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  • Jun Nishihira, Mie Nishimura, Masanori Kurimoto, Hiroyo Kagami-Katsuya ...
    Type: Original Article
    Article ID: 21-17
    Published: 2021
    [Advance publication] Released: May 21, 2021
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    Supplementary material

    Quercetin, a type of flavonoid, is believed to reduce age-related cognitive decline. To elucidate its potential function, we carried out a randomized, double-blind, placebo-controlled, parallel-group comparative clinical trial involving 24-week continuous intake of quercetin-rich onion compared to quercetin-free onion as a placebo. Seventy healthy Japanese individuals (aged 60 to 79 years old) were enrolled in this study. We examined the effect of quercetin-rich onion (the active test food) on cognitive function using the Mini-Mental State Examination, Cognitive Assessment for Dementia iPad version, and Neuropsychiatric Inventory Nursing Home version. The Mini-Mental State Examination scores were significantly improved in the active test food group (daily quercetin intake, 50 mg as aglycone equivalent) compared to the placebo food group after 24 weeks. On the Cognitive Assessment for Dementia iPad version for emotional function evaluation, we found that the scores of the active test food group were significantly improved, suggesting that quercetin prevents cognitive decline by improving depressive symptoms and elevating motivation. On the Neuropsychiatric Inventory Nursing Home version, we found significant effects on reducing the burden on study partners. Taking all the data together, we concluded that 24-week continuous intake of quercetin-rich onion reduces age-related cognitive decline, possibly by improving emotional conditions. Clinical trial register and their clinical registration number: This study was registered with UMIN (approval number UMIN000036276, 5 April 2019).

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  • Yutong Zou, Bo Guo, Songlin Yu, Danchen Wang, Ling Qiu, Yu Jiang
    Type: Review
    Article ID: 20-165
    Published: 2021
    [Advance publication] Released: May 07, 2021
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    Supplementary material

    Objective of the present study was to evaluate the effect of vitamin D supplementation on glycose homeostasis, islet function, and diabetes progress. Literatures were searched via electronic databases, websites, and previous reviews from the earliest available time to the end of May 2020. Randomized controlled trials initially designed for diabetes and prediabetes with 25-dihydroxyvitamin D [25(OH)D]<30 ng/ml were included. All data were analyzed and presented based on the Cochrane guidelines and PRISMA guidelines. In total, 27 articles (n = 1,932) were enrolled in this study. Vitamin D supplementation significantly improved fasting blood glucose, postprandial blood glucose, and quantitative insulin sensitivity check index in diabetes and prediabetes with baseline 25(OH)D<30 ng/ml. Higher percentages regressing from prediabetes to normal glucose status [1.60 (1.19, 2.17), p = 0.002, n = 564] and lower percentage progressing from prediabetes to diabetes [0.68 (0.36, 1.27), p = 0.23, n = 569] were found in the supplementation group. The positive effects of vitamin D supplementation on body mass index, waist, HDL-C, LDL-C, and CRP were also demonstrated. In conclusion, modest improvements in vitamin D supplementation on short-term glycose homeostasis, insulin sensitivity, and disease development in diabetes and prediabetes with 25(OH)D<30 ng/ml were demonstrated, but more research needs to be conducted in the future to support the clinical application. (Register ID: CRD42020186004)

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  • Yukitoshi Mine, Takayuki Takahashi, Tadashi Okamoto
    Type: Original Article
    Article ID: 20-185
    Published: 2021
    [Advance publication] Released: May 07, 2021
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    Cellular senescence is an intricate and multifactorial phenomenon, which is characterized by an irreversible cellular growth arrest, it is caused in response to irretrievably DNA damage, telomere shorting, activation of oncogene, and oxidative stress. Human diploid fibroblasts are a well-established experimental model for premature senescence-related studies, and exposure of fibroblasts to H2O2 is widely used as a SIPS model. Recently, it has been reported many studies of CoQ10 as to anti-aging effects, however the effect of CoQ10 on H2O2-induced SIPS model of human skin fibroblasts has not been understood. So that, we investigated that human skin fibroblasts were used to investigate the prevention effect of CoQ10 against H2O2-induced SIPS model. We created SIPS model fibroblasts with treatment of 100 μM H2O2 for 2 h. In this study, CoQ10 also increased cell viability and mRNA levels of type I, IV collagen and protein level of type I collagen. Moreover, it is shown that CoQ10 suppressed oxidative stress, degradation of collagen by increasing MMP expression, and decreasing senescence-associated phenotypes (e.g. SA-βgal positive staining and SASP) for preventing skin aging via H2O2-induced SIPS model. These results suggested that CoQ10 has possibility to be contributory for extension of healthy life expectancy in Japan.

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  • Yoshitaka Hashimoto, Hisami Yasuzawa, Tsutomu Ishida, Yuichi Miyazaki, ...
    Type: Original Article
    Article ID: 21-5
    Published: 2021
    [Advance publication] Released: May 07, 2021
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    Supplementary material

    To investigate the patients’ consciousness regarding the use of metformin and medical cost in Japanese patients with type 2 diabetes taking metformin. This cross-sectional study investigated patients’ general characteristics and consciousness regarding medical cost, kidney function, liver function, and metformin usage, using a self-administered, internet-based questionnaire. Among 1,000 patients, 81.0% felt unsatisfied with treatment for type 2 diabetes, with the main reason for dissatisfaction being high medical cost, with 540 patients reporting this. In addition, 16.8% of patients experienced treatment disruption and among them, 48.2% (81/168) answered that the reason was high medical cost. Over half of the patients did not understand their kidney and liver functions, respectively. Only 8.9% and 7.1% of patients knew both the words and meanings behind sick days and lactic acidosis, respectively. In conclusion, many patients with type 2 diabetes taking metformin were not satisfied with their treatments, with the main reason being high medical cost. Moreover, they did not have sufficient knowledge of sick days and/or lactic acidosis.

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  • Jong Min Park, Won Hee Lee, Hochan Seo, Ji Young Oh, Dong Yoon Lee, Se ...
    Type: Original Article
    Article ID: 20-123
    Published: 2021
    [Advance publication] Released: April 10, 2021
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    Supplementary material

    Korean fermented kimchi is probiotic food preventing Helicobacter pylori (H. pylori)-associated atrophic gastritis in both animal and human trial. In order to reveal the effect of fermented kimchi against H. pylori infection, we performed clinical trial to docu­ment the changes of fecal microbiota in 32 volunteers (H. pylori (−) chronic superficial gastritis (CSG), H. pylori (+) CSG, and H. pylori (+) chronic atrophic gastritis (CAG) with 10 weeks kimchi. Each amplicon is sequenced on MiSeq of Illumina and the sequence reads were clustered into operational taxonomic units using VSEARCH and the Chao, Simpson, and Shannon Indices. Though significant difference in α- or β-diversity was not seen in three groups, kimchi intake led to significant diversity of fecal microbiome. As results, Klebsiella, Enterococcus, Ruminococcaceae, Streptococcus, Roseburia, and Clostirdiumsensu were significantly increased in H. pylori (+) CAG, while Akkermansia, Citrobacter, and Lactobacillus were significantly decreased in H. pylori (+) CAG. With 10 weeks of kimchi administration, Bifidobacterium, Lactobacillus, and Ruminococcus were significantly increased in H. pylori (+) CAG, whereas Bacteroides, Subdoligranulum, and Eubacterium coprostanolines were significantly decreased in H. pylori (−) CAG. 10 weeks of kimchi intake significantly improved pepsinogen I/II ratio (p<0.01) with significant decreases in interleukin-1β. Conclusively, fermented kimchi significantly changed fecal microbiota to mitigate H. pylori-associated atrophic gastritis.

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  • Shuang Liu, Huaqi Zhang, Bei Yan, Hui Zhao, Yanhui Wang, Tianlin Gao, ...
    Type: Original Article
    Article ID: 21-19
    Published: 2021
    [Advance publication] Released: April 09, 2021
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    We aimed to determine the impact of high-fructose intake during pregnancy on the fetal-placental unit in rats, which may be the initial mechanism of the programming effect of fructose. Pregnant Sprague–Dawley rats were randomly assigned to three groups and respectively provided tap water (n = 10), 10% (w/v) fructose solution (n = 10), and 10% (w/v) glucose solution (n = 10) from embryonic day 0 to 20. Compared with the control and glucose groups, significantly lower fetal length, fetal weight, placental weight, and fetus/placenta ratio were found in the fructose group on embryonic day 20 (all p<0.05). In parallel with markedly increased uric acid concentrations in the dams, significantly decreased antioxidant enzymes activities and mRNA expression levels were observed in placentas in the fructose group (all p<0.05). In the fructose group, placental mRNA and protein expression of nuclear factor erythroid 2-related factor 2 was markedly downregulated and kelch-like ECH-associated protein 1 was significantly upregulated (all p<0.05). In conclusion, high-fructose consumption during pregnancy drives augmented oxidative stress in rats. Placental insufficiency under oxidative stress contributes to asymmetrical fetal growth restriction.

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  • Yukimi Yano, Chihiro Maeda, Ichiro Kaneko, Yukiko Kobayashi, Wataru Ao ...
    Type: Original Article
    Article ID: 20-146
    Published: 2021
    [Advance publication] Released: April 07, 2021
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    We recently reported that dietary cystine maintained plasma mercaptalbumin levels in rats fed low-protein diets. The present study aimed to compare the influence of low-protein diets supplemented with cystine and methionine, which is another sulfur amino acid, on plasma mercaptalbumin levels in rats. Male Sprague–Dawley rats were fed a 20% soy protein isolate diet (control group), 5% soy protein isolate diet (low-protein group) or 5% soy protein isolate diet supplemented with either methionine (low-protein + Met group) or cystine (low-protein + Cyss group) for 1 week. The percentage of mercaptalbumin within total plasma albumin of the low-protein + Met group was significantly lower than that of the control and low-protein + Cyss groups. No significant differences in the mRNA levels of tumor necrosis factor-α, interleukin-6, interleukin-1β, and cyclooxygenase 2 in blood cells were observed between the low-protein + Met and low-protein + Cyss groups. Treatment with buthionine-(S,R)-sulfoximine, an inhibitor of glutathione synthesis, did not influence the percentage of mercaptalbumin within total plasma albumin in rats fed the low-protein diet supplemented with cystine. These results suggest that supplementation with cystine may be more effective than that with methionine to maintain plasma mercaptalbumin levels in rats with protein malnutrition. Cystine might regulate plasma mercaptalbumin levels via the glutathione-independent pathway.

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  • Hiromi Kurokawa, Atsushi Taninaka, Hidemi Shigekawa, Hirofumi Matsui
    Type: Original Article
    Article ID: 20-197
    Published: 2021
    [Advance publication] Released: April 07, 2021
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    Monascus pigment is derived from red-mold rice fermented by monascus purpureus and utilized as a natural coloring agent and natural food additive in East Asia. Monascus pigment works as a radical scavenger. Some antioxidant combine cancer chemo­therapy to protect normal tissue because chemotherapy induce side effect for normal tissue. This combination therapy can attenuate the cytotoxicity of anti­cancer drugs by antioxidants effects. However, the effect of this combination therapy for cancer cells dose not investigate enough. In this study, we investigated the combination effect of anti­oxidants and anti­cancer drugs. We selected an anti­oxidant as monascus pigment and following four anti­cancer drugs: doxorubicin, tamoxifen, paclitaxicel, and cyclophosphamide. Combination treatment with monascus pigment and cyclophosphamide enhanced the cytotoxicity of cyclophosphamide. Moreover, this combination treatment accelerated apoptosis. The spot on TLC assay board of the monascus pigment and cyclophosphamide mixture is different from the spot of monascus pigment alone and cyclophosphamide alone. The interaction between monascus pigment and cyclo­phosphamide can produce some cytotoxicity compounds or accelerate intracellular cyclophosphamide accumulation. Hence, we concluded that the interaction of both cyclophosphamide and monascus pigment involved enhancement of cyclophosphamide cytotoxicity.

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  • Kumiko Kirita, Yasuhiro Kodaka, Yoshiaki Shibata, Nobue Ueki, Shuhei A ...
    Type: Original Article
    Article ID: 20-140
    Published: 2021
    [Advance publication] Released: April 03, 2021
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    Since there were no available data about colonic diverticular bleeding in extremely elderly patients (>80 years old) treated with direct oral anticoagulants (DOACs), we tried to determine clinical characteristics in those with colonic diverticular bleeding taking DOACs and to compare clinical outcomes of those in DOAC-treated to those in warfarin-treated . We enrolled DOAC-treated (n = 20) and warfarin-treated (n = 23) extremely elderly patients with diverticular bleeding diagnosed by colonoscopy. We performed a retrospective review of patients’ medical charts and endoscopic findings. We classified colonic diverticular bleeding based on endoscopic features due to modified previous study following three groups, type A (active bleeding), type B (non-active bleeding) and type C (bleeding suspected). Clinical outcomes such as number of recurrent bleeding, thrombotic events and mortality were estimated. There were no differences in endoscopical features and clinical characteristics between patients treated with DOAC and warfarin therapy. However, the number of recurrent bleeding, frequency of required blood transfusions and units of blood transfusion in warfarin-treated patients were significantly higher (p<0.05) compared to those in DOAC-treated groups. In addition, mortality and thrombotic events did not differ between DOAC- and warfarin-treated patients. Clinical outcomes suggest that DOACs can be recommended for extremely elderly patients with colonic diverticular disease.

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  • Naoko Suga, Akira Murakami, Hideyuki Arimitsu, Kazuya Shiogama, Sarasa ...
    Type: Original Article
    Article ID: 20-161
    Published: 2021
    [Advance publication] Released: April 03, 2021
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    Supplementary material

    Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, are chronic inflammatory disorders associated with oxidative stress. The intestines produce 5-hydroxytryptamine that may negatively affect disease state under inflammatory conditions when overproduced. 5-Hydroxytryptamine is a sub­strate for myeloperoxidase and is converted into reactive tryptamine-4,5-dione. Here, an experimental colitis model was established through oral administration of 5% dextran sulfate sodium to ICR mice for 7 days. Furthermore, the formation of tryptamine-4,5-dione in the colorectal mucosa/submucosa and colorectal tissue was analyzed by chemical and immunochemical methodologies. First, free tryptamine-4,5-dione in the homogenate was chemically trapped by o-phenylenediamine and analyzed as the stable phenazine derivative. Tryptamine-4,5-dione locali­zation as adducted proteins in the colorectal tissue was immunohistochemically confirmed, and as demonstrated by both methods, this resulted in the significant increase of tryptamine-4,5-dione in dextran sulfate sodium-challenged mice compared with control mice. Immunohistochemical staining confirmed tryptamine-4,5-dione-positive staining at the myeloperoxidase accumulation site in dextran sulfate sodium-challenged mice colorectal tissue. The tryptamine-4,5-dione locus in the mice was partly matched with that of a specific marker for myeloperoxidase, halogenated tyrosine. Overall, the results possibly indicate that tryptamine-4,5-dione is generated by neutrophil myeloperoxidase in inflammatory tissue and may contribute to the development of inflammatory bowel disease.

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  • Akari Kondo-Kawai, Tohru Sakai, Junji Terao, Rie Mukai
    Type: Original Article
    Article ID: 20-190
    Published: 2021
    [Advance publication] Released: April 03, 2021
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    Caveolin-1 is a major protein of the caveolae structure in vascular endothelial cell membrane. Phosphorylation of caveolin-1 is one of the initial events leading to exacerbation of vascular permeability caused by oxidative stress. Although quercetin is known to be an anti-atherosclerosis factor that acts as a dietary antioxidant, little is known about its role in the regulation of caveolin-1 phosphorylation. In this study, we investigated the inhibitory effect of quercetin on hydrogen peroxide-induced caveolin-1 phosphorylation in human umbilical vein endothelial cells. Quercetin inhibited caveolin-1 phosphorylation in cells pretreated with quercetin for 24 h and then exposed to hydrogen peroxide. However, quercetin 3-O-β-glucuronide, a conjugated metabolite of quercetin, did not exert this inhibitory effect. Exposure to hydrogen peroxide increased vascular permeability and reduced mRNA expression of the intercellular adhesion protein, vascular endothelial cadherin (VE-cadherin). By contrast, pretreatment with quercetin suppressed the increase in vascular permeability and decreased VE-cadherin expression. These results indicate that deconjugated quercetin can play a role in the prevention of altered vascular permeability under oxidative stress by suppressing caveolin-1 phosphorylation. Thus, dietary quercetin may be beneficial for the maintenance of endothelial cell function.

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  • Naoko Suga, Akira Murakami, Hideyuki Arimitsu, Toshiyuki Nakamura, Yos ...
    Type: Original Article
    Article ID: 20-192
    Published: 2021
    [Advance publication] Released: April 03, 2021
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    Supplementary material

    Increased 5-hydroxytryptamine may be associated with the development and progression of inflammatory bowel disease. In this study, we examined the suppressive effect of flavonoids on the increased intra- and extracellular 5-hydroxytryptamine levels in rat mast RBL-2H3 cells, known to produce 5-hydroxytryptamine by the phorbol 12-myristate 13-acetate stimulation. Among the flavonoids examined, luteolin and quercetin significantly reduced the cellular 5-hydroxytryptamine concentration. Gene and protein expression analyses revealed that luteolin significantly suppressed cellular tryptophan hydroxylase 1 expression induced by phorbol 12-myristate 13-acetate stimulation. Mitogen-activated protein kinase/extracellular signal-regulated kinase signaling was also suppressed by luteolin, suggesting that this pathway is one of targets of 5-hydroxytryptamine modulation by luteolin. An in vivo experimental colitis model was prepared by administering 2.5% dextran sodium sulfate in drinking water to C57BL/6 mice for seven days. The ingestion of 0.1% dietary luteolin suppressed the increasing 5-hydroxytryptamine in the colorectal mucosa. In conclusion, luteolin possesses a suppressive effect on extensive 5-hydroxytryptamine formation in both experimental RBL-2H3 cells and colitis models.

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  • Satoshi Osaga, Koji Nakada, Katsuhiko Iwakiri, Ken Haruma, Takashi Joh ...
    Type: Original Article
    Article ID: 20-202
    Published: 2021
    [Advance publication] Released: April 03, 2021
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Reflux esophagitis is known to be more prevalent in males, and previous studies have suggested sex differences in its risk factors. However, little is known about sex differences in the time-course of risk factors before reflux esophagitis onset. Thus, we conducted a retrospective longitudinal study using health checkup records. From the records of 230,056 individuals obtained from nine institutes in Japan, we selected 1,558 male reflux esophagitis cases, 3,116 male controls, 508 female reflux esophagitis cases, and 1,016 female controls were selected. We compared time-courses of risk factors between the case and control groups and identified abdominal circumference (AC), diastolic blood pressure, alanine transaminase (ALT), and current smoking in males and body mass index (BMI) in females as sex-specific risk factors. We also found that AC and ALT in males and BMI in females were significantly different between the reflux esophagitis case and control groups during the five years before reflux esophagitis onset. Our results suggest that visceral fat-type obesity and fatty liver in males and higher BMI in females are more frequently observed in reflux esophagitis cases several years before reflux esophagitis onset, and that proactive intervention to lifestyle can help prevent reflux esophagitis in both males and females.

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  • Jong-Min Park, Young-Min Han, Ji-Young Oh, Dong-Yoon Lee, Seung-Hye Ch ...
    Type: Original Article
    Article ID: 20-116
    Published: 2021
    [Advance publication] Released: March 27, 2021
    JOURNALS FREE ACCESS ADVANCE PUBLICATION
    Supplementary material

    Dietary intervention to prevent Helicobacter pylori (H. pylori)-gastric cancer might be ideal because of no risk of bacterial resistance, safety, and rejuvenating action of atrophic gastritis. We have published data about the potential of fermented kimchi as nutritional approach for H. pylori. Hence recent advances in RNAseq analysis lead us to investigate the transcriptome analysis to explain these beneficiary actions of kimchi. gastric cells were infected with either H. pylori or H. pylori plus kimchi. 943 genes were identified as significantly increased or decreased genes according to H. pylori infection and 68 genes as significantly changed between H. pylori infection and H. pylori plus kimchi (p<0.05). Gene classification and Medline database showed DLL4, FGF18, PTPRN, SLC7A11, CHAC1, FGF21, ASAN, CTH, and CREBRF were identified as significantly increased after H. pylori, but significantly decreased with kimchi and NEO1, CLDN8, KLRG1, and IGFBP1 were identified as significantly decreased after H. pylori, but increased with kimchi. After KEGG and STRING-GO analysis, oxidative stress, ER stress, cell adhesion, and apoptosis genes were up-regulated with H. pylori infection but down-regulated with kimchi, whereas tissue regeneration, cellular anti­oxidative response, and anti-inflammation genes were reversely regulated with kimchi (p<0.01). Conclusively, transcriptomes of H. pylori plus kimchi showed significant biological actions.

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  • Jong Min Park, Young Min Han, Sun Jin Hwang, Seong Jin Kim, Ki Baik Ha ...
    Type: Original Article
    Article ID: 20-151
    Published: 2021
    [Advance publication] Released: March 27, 2021
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Supported with significant rejuvenating and regenerating actions of mesenchymal stem cells (MSCs) in various gastrointestinal diseases including Helicobacter pylori (H. pylori)-associated gastric diseases, we have compared these actions among placenta derived-MSCs (PD-MSCs), umbilical cord derived-MSCs (UC-MSCs), and adipose tissue derived-MSCs (AD-MSCs) and explored contributing genes implicated in rejuvenation of H. pylori-chronic atrophic gastritis (CAG) and tumorigenesis. In this study adopting H. pylori-initiated, high salt diet-promoted gastric carcinogenesis model, we have administered three kinds of MSCs around 15–18 weeks in H. pylori infected C57BL/6 mice and sacrificed at 24 and 48 weeks, respectively, in order to either assess the rejuvenating capability or anti-tumorigenesis. At 24 weeks, MSCs all led to significantly mitigated atrophic gastritis, for which significant inductions of autophagy, preservation of tumor suppressive 15-PGDH, attenuated apoptosis, and efficient efferocytosis was imposed with MSCs administration during atrophic gastritis. At 48 weeks, MSCs administered during H. pylori-associated atrophic gastritis afforded significant blocking the progression of CAG, as evidenced with statistically significant reduction in H. pylori-associated gastric tumor (p<0.05) accompanied with significant decreases in IL-1β, COX-2, STAT3, and NF-κB. Combined together with the changes of stanniocalcin-1 (STC-1), thrombospondin-1 (TSP-1), and IL-10 known as biomarkers reflecting stem cell activities at 48 weeks after H. pylori, PD-MSCs among MSCs afforded the best rejuvenating action against H. pylori-associated CAG via additional actions of efferocytosis, autophagy, and anti-apoptosis at 24 weeks. In conclusion, MSCs, especially PD-MSCs, exerted rejuvenating actions against H. pylori-associated CAG via anti-mutagenesis of IL-10, CD-36, ATG5 and cancer suppressive influences of STC-1, TSP-1, and 15-PGDH.

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  • Jong Min Park, Young Min Han, Ji Young Oh, Dong Yoon Lee, Seung Hye Ch ...
    Type: Original Article
    Article ID: 20-180
    Published: 2021
    [Advance publication] Released: March 27, 2021
    JOURNALS FREE ACCESS ADVANCE PUBLICATION
    Supplementary material

    Dietary intervention to prevent Helicobacter pylori (H. pylori)-gastric cancer might be ideal by long-term intervention, rejuvenating action, and no risk of bacterial resistance. Stimulated with finding that kimchi prevented H. pylori-gastric cancer, we compared the efficacy of cancer preventive kimchi (cpkimchi) and standard recipe kimchi (skimchi) and the efficacy between fermented kimchi and non-fermented kimchi in H. pylori-initiated gastric cancer model and explored novel mechanisms hinted from RNAseq transcriptome analysis. Animal models assessing gastric pathology on 24 and 36 weeks after H. pylori initiated, salt diet-promoted gastric mutagenesis model showed fermented cpkimchi afforded the best outcome of either rejuvenating atrophic gastritis or inhibiting tumorigenesis compared to skimchi and kimuchi. Highest inhibition of atrophic gastritis was achieved with cpkimchi, while significantly lower in non-fermented kimuchi. Transcriptomic analysis showed ameliorated-endoplasmic reticulum (ER) stress, -oxidative stress, and -apoptosis as major rejuvenating action of cpkimchi. Homogenates from animal model showed that elevated expressions of p-PERK, IRE, ATF6, p-elf, and XBP1 in control group, while significantly decreased with dietary intake of only cpkimchi. Significantly increased expressions of HO-1 and γ-GCS were only noted with cpkimchi. Conclusively, long-term dietary intervention of fermented cpkimchi can be potential way preventing H. pylori-associated carcinogenesis via rejuvenation of atrophic gastritis.

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  • Akiko Nakamoto, Yuwa Hirabayashi, Chieri Anzaki, Mariko Nakamoto, Emi ...
    Type: Original Article
    Article ID: 20-178
    Published: 2021
    [Advance publication] Released: March 25, 2021
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Multiple sclerosis is an organ-specific autoimmune disease that targets the myelin antigen in the central nervous system. Nobiletin is a dietary polymethoxylated flavonoid found in citrus fruits. In this study, we investigated how nobiletin affects the disease state and immune responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis mice. Nobiletin was administered orally from 14 days before immunization until the end of the experiment, and clinical scores were determined. The production levels of interleukin-17A and interferon-γ were measured in a culture supernatant of splenocytes stimulated with myelin oligodendrocyte glycoprotein. In addition, flow cytometric analysis was performed to examine the effect of nobiletin on T cell differentiation in vitro. Admin­istration of nobiletin significantly decreased the clinical score and interleukin-17A production in splenocytes. Furthermore, in vitro analysis showed that nobiletin significantly suppressed Th17 cell differentiation and interleukin-17A production in a dose-dependent manner. The results suggest that nobiletin attenuates experimental autoimmune encephalomyelitis severity through modulation of Th17 cell differentiation.

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  • Kazuhisa Okamoto, Masaaki Kodama, Kazuhiro Mizukami, Tadayoshi Okimoto ...
    Type: Original Article
    Article ID: 20-179
    Published: 2021
    [Advance publication] Released: March 25, 2021
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    In this study, the level of cell damage were analyzed immuno­histochemically to clarify the association between nodular gastritis and undifferentiated gastric cancer. Thirty patients of nodular gastritis were enrolled as the nodular gastritis group. Thirty patients of non-nodular gastritis were enrolled as the control group. They were evaluated according to the updated Sydney system and used for immunohistochemical staining (p53, Ki-67, E-cadherin, and 8-OHdG). The scores based on the updated Sydney system were significantly higher in the nodular group than in the non-nodular group for histologically assessed inflammation and activity in the gastric corpus (1.91 ± 0.77 vs 1.58 ± 0.60, p = 0.049, 0.83 ± 0.81 vs 0.44 ± 0.64, p = 0.032). On immunostaining, the detection of E-cadherin was lower in the nodular group for both the antrum (1.0 ± 0.62 vs 1.47 ± 0.85, p = 0.047) and the corpus (1.16 ± 0.81 vs 1.48 ± 0.71, p = 0.043) and the p53 labeling index of the gastric corpus was higher in the nodular group than in the non-nodular group (3.06 ± 1.94 vs 2.03 ± 1.99, p = 0.015). Nodular gastritis showed significant severe inflammation and immunohistochemical cell damage compared with non-nodular gastritis. These findings may play an important role in the oncogenesis of undifferentiated gastric cancer in nodular gastritis.

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  • Junichi Fujii
    Type: Review
    Article ID: 20-181
    Published: 2021
    [Advance publication] Released: March 25, 2021
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Ascorbate (vitamin C) is an essential micronutrient in primates, and exhibits multiple physiological functions. In addition to antioxidative action, ascorbate provides reducing power to α-ketoglutarate-dependent non-heme iron dioxygenases, such as prolyl hydroxylases. Demethylation of histones and DNA with the aid of ascorbate results in the reactivation of epigenetically silenced genes. Ascorbate and its oxidized form, dehydroascorbate, have attracted interest in terms of their roles in cancer therapy. The last step in the biosynthesis of ascorbate is catalyzed by l-gulono-γ-lactone oxidase whose gene Gulo is commonly mutated in all animals that do not synthesize ascorbate. One common explanation for this deficiency is based on the increased availability of ascorbate from foods. In fact, pathways for ascorbate synthesis and the detoxification of xenobiotics by glucuronate conjugation share the metabolic processes up to UDP-glucuronate, which prompts another hypothesis, namely, that ascorbate-incompetent animals might have developed stronger detoxification systems in return for their lack of ability to produce ascorbate, which would allow them to cope with their situation. Here, we overview recent advances in ascorbate research and propose that an enhanced glucuronate conjugation reaction may have applied positive selection pressure on ascorbate-incompetent animals, thus allowing them to dominate the animal kingdom.

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  • Yuri Fujihara, Yasumasa Kodo, Shin-ichi Miyoshi, Ritsuko Watanabe, Hir ...
    Type: Original Article
    Article ID: 20-201
    Published: 2021
    [Advance publication] Released: March 25, 2021
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Non-alcoholic steatohepatitis is the chronic liver disease leading to cirrhosis and cancer and its prevalence is increasing. Some agents are under clinical trials for non-alcoholic steatohepatitis treatment. We previously reported Spirulina (Arthrospira) platensis effectively prevented non-alcoholic steatohepatitis progression in our model rats. The contribution of phycocyanin, an ingredient of Spirulina (Arthrospira) platensis, was limited. We, therefore, have looked for more active components of Spirulina (Arthrospira) platensis. In this study, we pursued the effect of biopterin glucoside, another bioactive ingredient of Spirulina (Arthrospira) platensis. We found Spirulina (Arthrospira) platensis and biopterin glucoside oral administrations effectively alleviated oxidative stress, inflammation and insulin signal failure, and prevented fibroblast growth factor 21 gene overexpression in non-alcoholic steatohepatitis rat livers. We concluded biopterin glucoside is a major component of Spirulina (Arthrospira) platensis action.

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  • Akiko Kuwabara, Kazuhiro Uenishi, Kiyoshi Tanaka
    Type: Review
    Article ID: 20-64
    Published: 2021
    [Advance publication] Released: March 25, 2021
    JOURNALS FREE ACCESS ADVANCE PUBLICATION
    Supplementary material

    The most fundamental function of vitamin K is to activate the blood coagulation factors in the liver. Despite the recent recognition of its extra-hepatic actions, the current Dietary Reference Intakes for vitamin K is based on the amount necessary for maintaining the normal blood coagulation in many countries. To define the Dietary Reference Intake for vitamin K, appropriate biomarkers well-reflecting the vitamin K status are essential. Unfortunately, however, no markers are currently available with properties enabling us to properly define the vitamin K status; i.g., no interference by other factors and the presence of widely approved cut-off values. Thus, Adequate Intake is determined, which is an index based on the representative dietary intake data from healthy individuals. Recently, epidemiological studies have been reported regarding the relationship between vitamin K and noncommunicable diseases including osteoporotic fracture. Furthermore, studies focusing on the relationship between vitamin K intake and metabolic syndrome, physical function, depression, cognition, and all-cause mortality have become available, although limited in number. This review summarizes the recent findings in favor of the novel functions of vitamin K. More epidemiological studies are needed to define the appropriate vitamin K intake value based on the prevention of various disorders.

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  • Keiichi Hiramoto, Yurika Yamate, Kenji Goto, Shiho Ohnishi, Akihiro Mo ...
    Type: Original Article
    Article ID: 20-125
    Published: 2021
    [Advance publication] Released: March 09, 2021
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Metastasis, which accounts for the majority of all cancer-related deaths, occurs through several steps, namely, local invasion, intravasation, transport, extravasation, and colonization. Glycyrrhizin has been reported to inhibit pulmonary metastasis in mice inoculated with B16 melanoma. This study aimed to identify the mechanism through which glycyrrhizin ameliorates the extravasation of melanoma cells into mouse lungs. Following B16 melanoma cell injection, mice were orally administered glycyrrhizin once every two days over 2 weeks; lung samples were then obtained and analyzed. Blood samples were collected on the final day, and cytokine plasma levels were determined. We found that glycyrrhizin ameliorated the extravasation of melanoma cells into the lungs and suppressed the plasma levels of interleukin-6, tumor necrosis factor-α, and transforming growth factor-β. Furthermore, glycyrrhizin ameliorated the lung tissue expression of high mobility group box-1 protein (HMGB1), receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)-4, RAS, extracellular signal-related kinase, NF-κB, myeloid differentiation primary response 88, IκB kinase complex, epithelial-mesenchymal transition markers, and vascular endothelial growth factor-A. Our study demonstrates that glycyrrhizin ameliorates melanoma metastasis by regulating the HMGB1/RAGE and HMGB1/TLR-4 signal transduction pathways.

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  • Yuya Kawasaki, Yun-Shan Li, Sintaroo Watanabe, Yuko Ootsuyama, Kazuaki ...
    Type: Original Article
    Article ID: 20-183
    Published: 2021
    [Advance publication] Released: March 09, 2021
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Concerns have recently grown about the health effects of secondhand smoke exposure and heated tobacco products. The analysis of tobacco smoke biomarkers is critical to assess the health effects of tobacco smoke exposure. For this purpose, the simultaneous determinations of exposure markers and health effect markers would provide a better evaluation of smoke exposure. In this study, nicotine metabolites (nicotine, cotinine, trans-3'-hydroxycotinine) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in urine were analyzed as exposure markers. The DNA damage markers, 7-methylguanine and 8-hydroxy-2'-deoxyguanosine, were simultaneously measured as health effect markers. The results revealed significant levels of urinary nicotine metabolites and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in the subjects exposed to secondhand smoke and heated tobacco products. In addition, the urinary levels of 7-methylguanine and 8-hydroxy-2'-deoxyguanosine tended to be high for secondhand smoke and heated tobacco products exposures, as compared to those of non-smokers. These biomarkers will be useful for evaluating tobacco smoke exposure.

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  • Yuki Kizawa, Takahiro Sekikawa, Masakatsu Kageyama, Haruna Tomobe, Riy ...
    Type: Original Article
    Article ID: 20-149
    Published: 2021
    [Advance publication] Released: February 05, 2021
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    We examined the effects of a test food containing anthocyanin, astaxanthin, and lutein on the eye function in healthy Japanese adults with eye fatigue after operating visual display terminals. Forty-four subjects were randomly but equally assigned to the active or placebo group. Two active or placebo capsules were taken once daily for 6 weeks. Accommodative function, tear film break-up time, visual acuity, the value of Schirmer’s test, macular pigment optical density level, muscle hardness, and a questionnaire were evaluated before and after a 6-week intervention. Each group included 20 subjects in the efficacy analysis. The active group showed a significant improvement in the percentage of pupillary response of an average of both eyes and dominant eye pre- and post-visual display terminal operation at 6 weeks compared with the placebo group. Moreover, the active group showed a significant improvement in the scores of “A sensation of trouble in focusing the eyes” and “Difficulty in seeing objects in one’s hand and nearby, or fine print” compared with the placebo group between before and after ingestion. Therefore, 6-weeks consumption of the test food inhibited a decrease in the accommodative function caused by visual display terminal operation (UMIN000036989).

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  • Rina Horinouchi, Yorihiro Yamamoto, Akio Fujisawa
    Type: Original Article
    Article ID: 20-101
    Published: 2021
    [Advance publication] Released: January 16, 2021
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Singlet oxygen prefers to react with an electron-rich double bonds. We observed that the oxidation rate for uric acid with singlet oxygen increased with increasing pH and the oxidation rate dramatically was elevated at around pH 5.4 and 9.8, which are the acidity constants of uric acid, pKa1 and pKa2, respectively. Furthermore, we observed that the absorbance near 200 nm and the molar extinction coefficient (ɛ) increased with increasing pH, similar to the change in oxidation rate. Computer calculations by Chong [Chong, J Theor Comput Sci 2013; 1(1)] revealed that uric acid elongates its C=N conjugated diene structure with increasing pH. This is correlated with an increase in the UV absorbance of C=C double bonds near 200 nm, and may indicate higher electron density in the double bonds. Therefore, we concluded that the increased oxidation rate is due to elongation of the C=N conjugated polyene system at higher pH. On the other hand, the major products were 4-hydroxyallantoin and parabanic acid (hydrolyzed to oxaluric acid at pH 10.7), suggesting that the reaction pathways were the same regardless of pH. Finally, possible reaction schemes are presented.

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  • Aki Hirayama, Satomi Akazaki, Yumiko Nagano, Atsushi Ueda, Masaichi Ch ...
    Type: Original Article
    Article ID: 20-141
    Published: 2021
    [Advance publication] Released: January 16, 2021
    JOURNALS FREE ACCESS ADVANCE PUBLICATION
    Supplementary material

    Leukocyte activation and the resulting oxidative stress induced by bioincompatible materials during hemodialysis impact the prognosis of patients. Despite multiple advances in hemodialysis dialyzers, the prognosis of hemodialysis patients with complications deeply related to oxidative stress, such as diabetes mellitus, remains poor. Thus, we re-evaluated the effects of hemodialysis on multiple reactive oxygen species using electron spin resonance-based methods for further improvement of biocompatibility in hemodialysis. We enrolled 31 patients in a stable condition undergoing hemodialysis using high-flux polysulfone dialyzers. The effects of hemodialysis on reactive oxygen species were evaluated by two methods: MULTIS, which evaluates serum scavenging activities against multiple hydrophilic reactive oxygen species, and i-STrap, which detects lipophilic carbon-center radicals. Similar to previous studies, we found that serum hydroxyl radical scavenging activity significantly improved after hemodialysis. Unlike previous studies, we discovered that scavenging activity against alkoxyl radical was significantly reduced after hemodialysis. Moreover, patients with diabetes mellitus showed a decrease in serum scavenging activity against alkyl peroxyl radicals and an increase in lipophilic carbon-center radicals after hemodialysis. These results suggest that despite extensive improvements in dialyzer membranes, the forms of reactive oxygen species that can be eliminated during dialysis are limited, and multiple reactive oxygen species still remain at increased levels during hemodialysis.

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