Journal of Clinical Biochemistry and Nutrition
Online ISSN : 1880-5086
Print ISSN : 0912-0009
ISSN-L : 0912-0009
Current issue
Showing 1-17 articles out of 17 articles from the selected issue
Editorial
Letter
  • Hideki Mori, Jan Tack, Hidekazu Suzuki
    Type: Letter
    2020 Volume 67 Issue 2 Pages 114-115
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: August 22, 2020
    JOURNALS FREE ACCESS

    To ensure the safety of medical personnel is important during the new coronavirus infectious disease (COVID-19) pandemic. Although high-resolution manometry (HRM) is an essential device for diagnosis of functional gastrointestinal disorders, it contains risks of droplet infection, contact infection and aerosol-borne infection. Screening tests such as PCR, serology test to detect COVID-19 antibodies, and CT scan should be considered as well as body temperature check and anamnestic risk assessment. Moreover, the provision of protective equipment such as a mask with face shield (or goggles + mask), gloves, cap or hairnet, and a long-sleeved gown would be necessary to reduce the risk of COVID-19.

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Original Articles
  • Chenchen Wei, Ya Liu, Yu Li, Yi Zhang, Ming Zhong, Xiao Meng
    Type: Original Article
    2020 Volume 67 Issue 2 Pages 116-121
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: August 06, 2020
    JOURNALS FREE ACCESS
    Supplementary material

    COVID-19 has been a global health threat. We aimed to investigate the nutrition status of COVID-19 patients and evaluate the prognostic value of the controlling nutritional status (CONUT) score in these patients. 348 severe patients with COVID-19 were collected. Based on the CONUT score, 161 (46.3%) patients had mild malnutrition while 139 (39.9%) patients had moderate-severe malnutrition. Compared to the patients in normal and mild groups, the patients in moderate-severe group were older, more male, had higher counts of white blood cell and neutrophil as well as higher serum levels of C-reactive protein. Nearly half of patients (44.6%) in moderate-severe group developed acute cardiac injury, while 6.3% and 15.5% patients in normal and mild group, respectively. Patients with moderate-severe malnutrition exhibited a higher mortality than those patients with normal and mild malnutrition. Multivariate regression analysis showed the CONUT score was the independent predictor of death in patients with COVID-19 (odds ratio: 1.410; 95%CI: 1.089–1.825; p = 0.009). Malnutrition is significantly associated with poor outcome of COVID-19, while the prognosis of patients with normal nutrition status is relative favorable. The CONUT score independently predicts the prognosis of COVID-19 patients, which can help physicians to clarify patients with poor prognosis.

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  • Yuji Naito, Tomohisa Takagi, Tetsuro Yamamoto, Shaw Watanabe
    Type: Original Article
    2020 Volume 67 Issue 2 Pages 122-125
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: August 21, 2020
    JOURNALS FREE ACCESS

    The purpose of this study was to propose a hypothesis that there is a potential association between the incidence of selective IgA deficiency in various countries and COVID-19 cases. The number of deaths due to COVID-19 increased in clear proportion to the number of infected patients, and the difference in the number of deaths by country was due to the difference in the number of infected patients. The frequency of selective IgA deficiency has a strong positive correlation with the prevalence of COVID-19 per population. The low infection rate contributed to the low death rate from COVID-19 in Japan, suggesting that the extremely low frequency of selective IgA deficiency may be a contributing factor.

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  • Liu Lin, Kaiyuan Hu, Shuijiang Cai, Xilong Deng, Xinning Shao, Ying Li ...
    Type: Original Article
    2020 Volume 67 Issue 2 Pages 126-130
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: August 06, 2020
    JOURNALS FREE ACCESS

    Severe patients of the coronavirus disease 2019 (COVID-19) may progress rapidly to critical stage. This study aimed to identify factors useful for predicting the progress. 33 severe COVID-19 patients at the intensive care unit were included in this study. During treatment, 13 patients deteriorated and required further treatment for supporting organ function. The remaining 20 patients alleviated and were transferred to the general wards. The multivariate COX regression analyses showed that hypoproteinemia was an independent risk factor associated with deterioration of severe patients (HR, 0.763; 95% CI, 0.596 to 0.978; p = 0.033). The restricted cubic spline indicated that when HR = 1, the corresponding value of albumin is 29.6 g/L. We used the cutoff of 29.6 g/L to divide these patients. Kaplan–Meier curves showed that the survival rate of the high-albumin group was higher than that of the low-albumin group. Therefore, hypoalbuminemia may be an independent risk factor to evaluate poor prognosis of severely patients with COVID-19, especially when albumin levels were below 29.6 g/L.

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  • Tomoko Komatsu, Kyo Kobayashi, Yoshinari Morimoto, Eva Helmerhorst, Fr ...
    Type: Original Article
    2020 Volume 67 Issue 2 Pages 131-136
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: June 09, 2020
    JOURNALS FREE ACCESS

    Proline-rich proteins are associated with the formation of an acquired protein layer overlying the tooth enamel surface. Previous studies have described the antioxidant activity of salivary histatin against the hydroxyl radical from Fenton’s reaction, acting as the critical reactive oxygen species. However, the role of proline-rich proteins in mitigating the oxidative stress caused by reactive oxygen species in the oral cavity remains unclear. In this study, we investigated the antioxidant effects of proline-rich proteins 2 on direct reactive oxygen species using electron spin resonance spectroscopy. For the first time, we demonstrated that proline-rich proteins 2 exhibits antioxidant activity directly against the hydroxyl radical produced by hydrogen peroxide with ultraviolet. Considering that identical results were obtained when assaying 30 residues of proline-rich proteins 2, the direct antioxidant effects against the hydroxyl radical by proline-rich proteins 2 may be related to these specific 30 residues.

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  • Bowen Wu, Wusi Zeng, Wei Ouyang, Qiang Xu, Jian Chen, Biao Wang, Xipin ...
    Type: Original Article
    2020 Volume 67 Issue 2 Pages 137-145
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: March 06, 2020
    JOURNALS FREE ACCESS

    Osteosarcoma is a primary bone aggressive cancer, affecting adolescents worldwide. Quercetin (a natural polyphenolic compound) is a polyphenolic flavonoid compound found in a variety of plants. It has been demonstrated to exert cytostatic activity against a variety of human cancer, including the human osteosarcoma. However, its efficacy in the treatment of osteosarcoma and the underlying antitumor mechanism has not been fully elucidated yet. In this study, we exposed MG-63 cells to different concentrations of quercetin (50, 100 and 200 µM) for 24 h. Here, we show that quercetin increased autophagic flux in the MG-63 cells, as evidenced by the upregulation of LC3B-II/LC3B-I and downregulation of P62/SQSTM1. Moreover, the autophagy inhibitor Bafilomycin A1 or genetic blocking autophagy with ATG5 knockdown decreased quercetin-induced cell death, indicating quercetin triggered autophagic cell death in MG-63 cells. Specifically, quercetin increased NUPR1 expression and activated of NUPR1 reporter activity, which contributed to the expression of autophagy-related genes and subsequent initiated autophagic cell death in osteosarcoma cells. Importantly, the increased expression NUPR1 were tightly related to the disturbance of reactive oxygen species (ROS) homeostasis, which could be prevented by inhibiting intracellular ROS with NAC. Finally, NAC also abolished quercetin-induced autophagic cell death in vivo. Taken together, these data demonstrate that quercetin induces osteosarcoma cell death via inducing excessive autophagy, which is mediated through the ROS-NUPR1 pathway. Quercetin application may be a promising and practical strategy for osteosarcoma treatment in clinical practice.

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  • Li-Ying Xu, Min Mu, Man-Li Wang, Jin-Cheng Liu, Yuan-Jie Zhou, Jing Wu ...
    Type: Original Article
    2020 Volume 67 Issue 2 Pages 146-152
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: April 17, 2020
    JOURNALS FREE ACCESS

    Our study was to understand the autophagy induce by different ratios and concentrations of LA/DHA on Raw264.7 cell, and then to investigate the effect of Raw264.7 autophagy on the clearance of Staphylococcus aureus. Raw264.7 cells was treated by LA/DHA in different concentrations (50/100 µmol/L) and ratios (4:1, 6:1, 8:1, 1:4, 1:6 and 1:8) for 6/12/24 h, cell viability assay was assessed by Cell Counting Kit-8, LC3B, p62, P-mTOR, P-Akt, P-PI3K and BECN 1 were detected by the Western blot. LA/DHA could induce autophagy of Raw264.7 cells through the PI3K-Akt-mTOR signaling pathway, the strong effect on autophagy by the concentration is 100 µmol/L, the ratio is 6:1 of LA/DHA, and the treatment time is 24 h. Compared with the images in the control group obtained by merging red and green fluorescence channels, the treatment of LA, DHA in a ratio of 6:1 at a concentration of 100 µmol/L for 24 h significantly lead to a substantial number of autophagosomes (yellow) as well as autolysosomes (red), enhancing autophagy flux. Autophagy induce by LA/DHA can devour and damage intracellular and extracellular Staphylococcus aureus. These results indicate that LA/DHA cloud induce autophagy and enhance the phagocytosis and killing ability of macrophages to intracellular parasitic bacteria.

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  • Yuhei Ohta, Mitsuyasu Kawaguchi, Naoya Ieda, Hidehiko Nakagawa
    Type: Original Article
    2020 Volume 67 Issue 2 Pages 153-158
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: May 15, 2020
    JOURNALS FREE ACCESS
    Supplementary material

    Lysine methylation is one of the most important modification, which is regulated by histone lysine methyltransferases and histone lysine demethylases. Lysine-specific demethylase 1 (LSD1) specifically demethylates mono- and dimethyl-lysine on histone H3 (H3K4Me/Me2, H3K9Me/Me2) to control chromatin structure, resulting in transcriptional repression or activation of target genes. Furthermore, LSD1 is overexpressed in various cancers. Therefore, LSD1 inhibitors would be not only potential therapeutic agents for cancers but also chemical tools to research biological significance of LSD1 in physiological and pathological events. However, known assay methods to date have some inherent drawbacks. The development of simple method in detecting LSD1 activity has been indispensable to identify useful inhibitors. In this study, we designed and synthesized artificial substrates based on inhibitors of LSD1 to examine LSD1 activity by an absorption increment.

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  • Sakiko Amekura, Misuzu Nakajima, Mami Watanabe, Makoto Saitoh, Sayaka ...
    Type: Original Article
    2020 Volume 67 Issue 2 Pages 159-166
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: April 09, 2020
    JOURNALS FREE ACCESS

    3-Methyl-1-phenyl-2-pyrazolin-5-one (edaravone) is a synthetic one-electron antioxidant used as a drug for treatment against acute phase cerebral infarction in Japan. This drug also reacts with two-electron oxidants like peroxynitrite to give predominantly 4-nitrosoedaravone but no one-electron oxidation products. It is believed that this plays a significant role in amelioration of amyotrophic lateral sclerosis. The drug was approved for treatment of amyotrophic lateral sclerosis in Japan and USA in 2015 and 2017, respectively. In this study, we examined the reaction of edaravone with another two-electron oxidant, hypochlorite anion (ClO). Edaravone reacted with ClO in 50% methanolic phosphate buffer (pH 7.4) solution containing typical two-electron reductants, such as glutathione, cysteine, methionine, and uric acid, as internal references. The concentration of edaravone decreased at a similar rate as each co-existing reference, indicating that it showed comparable reactivity toward ClO as those references. Furthermore, 4-Cl-edaravone and (E)-2-chloro-3-[(E)-phenyldiazenyl]-2-butenoic acid (CPB) were identified as primary and end products, respectively, and no one-electron oxidation products were detected. These results suggest that edaravone treatment can bring greater benefit against ClO-related injury such as inflammation, and 4-Cl-edaravone and CPB can be good biomarkers for ClO-induced oxidative stress.

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  • Yurie Mori, Shinji Oikawa, Shota Kurimoto, Yuki Kitamura, Saeko Tada-O ...
    Type: Original Article
    2020 Volume 67 Issue 2 Pages 167-173
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: April 09, 2020
    JOURNALS FREE ACCESS

    It is well-known that the cornu Ammonis 1 (CA1) sector of hippocampus is vulnerable for the ischemic insult, whereas the dentate gyrus (DG) is resistant. Here, to elucidate its underlying mechanism, alternations of protein oxidation and expression of DG in the monkey hippocampus after ischemia-reperfusion by the proteomic analysis were studied by comparing CA1 data. Oxidative damage to proteins such as protein carbonylation interrupt the protein function. Carbonyl modification of molecular chaperone, heat shock 70 kDa protein 1 (Hsp70.1) was increased remarkably in CA1, but slightly in DG. In addition, expression levels of nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase sirtuin-2 (SIRT2) was significantly increased in DG after ischemia, but decreased in CA1. Accordingly, it is likely that SIRT2 upregulation and negligible changes of carbonylation of Hsp70.1 exert its neuroprotective effect in DG. On the contrary, carbonylation level of dihydropyrimidinase related protein 2 (DRP-2) and l-lactate dehydrogenase B chain (LDHB) were slightly increased in CA1 as shown previously, but remarkably increased in DG after ischemia. It is considered that DRP-2 and LDHB are specific targets of oxidative stress by ischemia insult and high carbonylation levels of DRP-2 may play an important role in modulating ischemic neuronal death.

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  • Ken-ichiro Matsumoto, Megumi Ueno, Ikuo Nakanishi, Hiroko P. Indo, Hid ...
    Type: Original Article
    2020 Volume 67 Issue 2 Pages 174-178
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: June 03, 2020
    JOURNALS FREE ACCESS

    To clarify a possible index for long-term and low-dose irradiation, the effects of repeated low-dose X-ray irradiation on the amount of melanin-derived radicals in mouse hair and tail skin were investigated. Eight-week-old female C3H/HeSlc mice were irradiated by X-rays at a dose of 100 mGy/day 5 days/week for 12 weeks. Similarly, a 4-week irradiation experiment was carried out at 500 mGy/day for C3H/HeSlc mice, or at 10, 100, and 500 mGy/day for 8-week-old female C57BL/6NCrSlc mice. The hair sample (~10 mg) was weighed accurately and stuffed into a plastic tube. The 2-cm tip of the tail was sampled and lyophilized. Melanin-derived radicals in hair and tail samples were measured by X-band electron paramagnetic resonance spectrometry. After X-ray irradiation at 100 mGy/day for 12 weeks, no difference was found in the amount of melanin-derived radicals in the hair of the irradiated and non-irradiated groups. X-ray irradiation at 500 mGy/day for 4 weeks increased the amount of melanin-derived radicals in hair compared with the non-irradiated group, but the baseline amount of melanin-derived radicals in hair was varied. The amount of melanin-derived radicals in the tail skin dose-dependently increased. Melanin-derived radicals in skin may be an endogenous marker for long-term and low-dose irradiation.

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  • Yuki Niida, Masashi Masuda, Yuichiro Adachi, Aika Yoshizawa, Hirokazu ...
    Type: Original Article
    2020 Volume 67 Issue 2 Pages 179-187
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: June 09, 2020
    JOURNALS FREE ACCESS

    Skeletal muscle atrophy is associated with mortality and poor prognosis in patients with chronic kidney disease (CKD). However, underlying mechanism by which CKD causes muscle atrophy has not been completely understood. The quality of lipids (lipoquality), which is defined as the functional features of diverse lipid species, has recently been recognized as the pathology of various diseases. In this study, we investigated the roles of the stearoyl-CoA desaturase (SCD), which catalyzes the conversion of saturated fatty acids into monounsaturated fatty acids, in skeletal muscle on muscle atrophy in CKD model animals. In comparison to control rats, CKD rats decreased the SCD activity and its gene expression in atrophic gastrocnemius muscle. Next, oleic acid blocked the reduction of the thickness of C2C12 myotubes and the increase of the endoplasmic reticulum stress induced by SCD inhibitor. Furthermore, endoplasmic reticulum stress inhibitor ameliorated CKD-induced muscle atrophy (the weakness of grip strength and the decrease of muscle fiber size of gastrocnemius muscle) in mice and the reduction of the thickness of C2C12 myotubes by SCD inhibitor. These results suggest that the repression of SCD activity causes muscle atrophy through excessive endoplasmic reticulum stress in CKD.

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  • Sunmin Park, Ting Zhang, Xuangao Wu, Jing Yi Qiu
    Type: Original Article
    2020 Volume 67 Issue 2 Pages 188-198
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: March 20, 2020
    JOURNALS FREE ACCESS

    The benefits of ketone production regimens remain controversial. Here, we hypothesized that the ketone-producing regimens modulated cognitive impairment, glucose metabolism, and inflammation while altering the gut microbiome. The hypothesis and the mechanism were explored in amyloid-β infused rats. Rats that received an amyloid-β(25–35) infusion into the hippocampus had either ketogenic diet (AD-KD), intermittent fasting (AD-IMF), 30 energy percent fat diet (AD-CON), or high carbohydrate (starch) diet (AD-CHO) for 8 weeks. AD-IMF and AD-CHO, but not AD-KD, lowered the hippocampal amyloid-β deposition compared to the AD-CON despite serum ketone concentrations being elevated in both AD-KD and AD-IMF. AD-IMF and AD-CHO, but not AD-KD, improved memory function in passive avoidance, Y maze, and water maze tests compared to the AD-CON. Hippocampal insulin signaling (pAkt→pGSK-3β) was potentiated and pTau was attenuated in AD-IMF and AD-CHO much more than AD-CON. AD-IMF and AD-CON had similar glucose tolerance results during OGTT, but AD-KD and AD-IMF exhibited glucose intolerance. AD-KD exacerbated gut dysbiosis by increasing Proteobacteria, and AD-CHO improved it by elevating Bacteriodetes. In conclusion, ketone production itself might not improve memory function, insulin resistance, neuroinflammation or the gut microbiome when induced by ketone-producing remedies. Intermittent fasting and a high carbohydrate diet containing high starch may be beneficial for people with dementia.

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  • Hiroko Morita, Yasuo Shimizu, Yusuke Nakamura, Hiroaki Okutomi, Taiji ...
    Type: Original Article
    2020 Volume 67 Issue 2 Pages 199-205
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: May 15, 2020
    JOURNALS FREE ACCESS
    Supplementary material

    Some patients with interstitial pneumonia (IP) have auto-antibodies, but do not fit the criteria for specific connective tissue diseases. Examination of auto-antibodies is recommended for diagnosis idiopathic pulmonary fibrosis. A prospective cohort study was performed in 285 patients with IP. Eleven auto-antibodies were assessed and patients were followed for 2 years. All 285 patients underwent the myositis panel test (MPT) for 11 auto-antibodies. Among them, 23.5% (67/285) of the patients had a positive MPT and 14.7% (42/285) had connective tissue diseases. Among the 49 MPT positive patients without connective tissue diseases, 29 patients (59.2%) were positive for Ro52, including 17 patients with Ro52 mono-positivity. Among interstitial pneumonia patients without connective tissue diseases, the Ro52 mono-positive patients showed worse at 2-years survival than those who were Ro52 negative (p = 0.022, HR = 5.88, 95% CI 1.29–26.75). Most of the Ro52 positive patients also showed a low titer of anti-nucleolar antibody. About 20% of IP patients had auto-antibodies detectable by the MPT, and Ro52 positive patients accounted for more than half of the MPT positive patients without connective tissue diseases. Detection of Ro52 auto-antibodies may be useful for assessing the risk of progression in idiopathic interstitial pneumonia patients without connective tissue diseases and a low anti-nucleolar antibody titer.

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  • Chung Hyun Tae, Hye-Kyung Jung, Seong-Eun Kim, Sung-Ae Jung, Sun Ha Je ...
    Type: Original Article
    2020 Volume 67 Issue 2 Pages 206-213
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: July 16, 2020
    JOURNALS FREE ACCESS

    A strong causal relationship between obesity and erosive esophagitis has been proposed. Obesity may affect the pathogenesis of erosive esophagitis through adipokines as well as acid reflux. We evaluated the involvement of adiponectin in obesity-associated erosive esophagitis. In total, 1,902 patients who underwent endoscopy during medical check-ups were selected for study. Variables including the body mass index (BMI) and adiponectin level were compared between subjects with erosive esophagitis and normal controls. The subjects were classified by quartiles (Qs) of adiponectin level. Q4 was the reference group. The median adiponectin level differed by gender (men, 5.3 µg/ml vs women, 9.3 µg/ml; p<0.001). As the severity of erosive esophagitis increased in men, the BMI increased (p<0.001) while the adiponectin level decreased (p = 0.026). The multivariate odds ratio for erosive esophagitis was 1.79 for Q1, 1.73 for Q2, 2.34 for obesity, and 27.40 for hiatal hernia in men. When classified by obesity, the multivariate odds ratio for erosive esophagitis was 1.94 for Q1, 2.10 for Q2, and 18.47 for hiatal hernia only in obese men. In women, there were no trends in BMI, adiponectin levels, or severity of erosive esophagitis. We demonstrated that low adiponectin levels are involved in obesity-associated erosive esophagitis in men but not women.

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  • Tomoyoshi Tamura, Masaru Suzuki, Kei Hayashida, Yosuke Kobayashi, Joe ...
    Type: Original Article
    2020 Volume 67 Issue 2 Pages 214-221
    Published: 2020
    Released: September 01, 2020
    [Advance publication] Released: April 03, 2020
    JOURNALS FREE ACCESS
    Supplementary material

    Oxidative stress plays a key role in the pathophysiology of post-cardiac arrest syndrome. Molecular hydrogen reduces oxidative stress and exerts anti-inflammatory effects in an animal model of cardiac arrest. However, its effect on human post-cardiac arrest syndrome is unclear. We consecutively enrolled five comatose post-cardiac arrest patients (three males; mean age, 65 ± 15 years; four cardiogenic, one septic cardiac arrest) and evaluated temporal changes in oxidative stress markers and cytokines with inhaled hydrogen. All patients were treated with target temperature management. Hydrogen gas inhalation (2% hydrogen with titrated oxygen) was initiated upon admission for 18 h. Blood hydrogen concentrations, plasma and urine oxidative stress markers (derivatives of reactive oxygen metabolites, biological antioxidant potential, 8-hydroxy-2'-deoxyguanosine, Nɛ-hexanoyl-lysine, lipid hydroperoxide), and cytokines (interleukin-6 and tumor necrosis factor-α) were measured before and 3, 9, 18, and 24 h after hydrogen gas inhalation. Arterial hydrogen concentration was measurable and it was equilibrated with inhaled hydrogen. Oxidative stress was reduced and cytokine levels were unchanged in cardiogenic patients, whereas oxidative stress was unchanged and cytokine levels were diminished in the septic patient. The effect of inhaled hydrogen on oxidative stress and cytokines in comatose post-cardiac arrest patients remains indefinite because of methodological weaknesses.

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