BPB Reports
Online ISSN : 2434-432X
Volume 6, Issue 6
Displaying 1-11 of 11 articles from this issue
Regular Article
  • Shunsuke Hirashima, Shinichiro Kaetsu, Yukino Kiyooka, Kimie Nakagawa
    2023 Volume 6 Issue 6 Pages 176-182
    Published: 2023
    Released on J-STAGE: November 16, 2023
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    Background: Vitamin K derivatives have an important role in bone formation and blood clotting. Vitamin K2 [menaquinone-4 (MK-4)] is used for the treatment and prevention of osteoporosis. Recently, vitamin K was found to be effective for the prevention of osteoarthritis and may play a role in cartilage formation; however, the function of UBIAD1 (MK-4 biosynthesis enzyme) and MK-4 in cartilage is unclear. In this study, we examined the function of UBIAD1 and MK-4 in chondrogenesis and differentiation using chondrogenically differentiated cells. Methods: Mouse chondrocyte progenitor ATDC5 cells were used for siRNA knockdown of UBIAD1 to determine its effects on cell proliferation and chondrogenic differentiation. Proliferation and differentiation were assessed using the WST-8 assay and Alcian blue staining, respectively. The effects of MK-4 treatment and transfection of a human UBIAD1 expression plasmid on UBIAD1 knockdown cells were also examined. RESULTS: UBIAD1 knockdown significantly decreased the proliferation and chondrogenic differentiation of ATDC5 cells. MK-4 treatment suppressed ATDC5 cell proliferation and chondrogenic differentiation. It also affected UBIAD1 knockdown ATDC5 cells during chondrogenic differentiation. However, overexpression of human UBIAD1 promoted ATDC5 cell proliferation and chondrogenic differentiation and exhibited a similar effect on UBIAD1 knockdown ATDC5 cells. These results suggest that MK-4 has an inhibitory effect on the proliferation and differentiation of UBIAD1, which exhibits a promoting effect. These results suggest that UBIAD1 and MK-4 have a role in regulating chondrocyte proliferation and differentiation and are important regulators of chondrogenic differentiation.

Corrigendum
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  • Shimako Tanaka, Sayuri Kawamoto, Yasuharu Kashiwagura, Akio Hakamata, ...
    2023 Volume 6 Issue 6 Pages 184-188
    Published: 2023
    Released on J-STAGE: November 30, 2023
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    Gummy drugs are dried jelly formulations prepared by adding a gelling agent to saccharides, which are then cooled and solidified. Epinastine hydrochloride (Epi) is commonly used to treat allergic diseases as a prescription and over-the-counter drug. However, the extremely bitter taste of Epi would affect its acceptability among patients. In this study, we aimed to improve the palatability of a gummy drug containing Epi (Epi-G) via organoleptic masking. Epi-G (10 mg of Epi/3.5 g of gummy drug) with two different organoleptic masking formulations, namely aspartame, cocoa powder, and chocolate flavoring (C-Epi-G) or aspartame, L-menthol, and lemon flavoring (L-Epi-G). The gustatory sensation test included six healthy adult volunteers (23.3 ± 1.8 years). We used a visual analogue scale (VAS) to evaluate bitterness, sweetness, and the overall palatability of each Epi-G formulation during chewing and after spitting out the drugs. In the gustatory sensation test, the VAS scores for bitterness and sweetness were decreased and increased for C-Epi-G and L-Epi-G, respectively, compared with the values for Epi-G without organoleptic masking. The VAS scores for overall palatability during chewing for C-Epi-G and L-Epi-G were significantly increased by 2.3- and 2.0-fold, respectively, versus the value for Epi-G. The score after spitting out C-Epi-G remained higher than that of Epi-G. These data illustrated that Epi-G with organoleptic masking had good palatability, which could improve patient adherence to treatment. The gummy drugs could represent an alternative dosing formulation for pediatric and geriatric patients by allowing them to take the drugs more easily than other oral formulations.

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  • Masato Noda, Chigusa Kikuchi, Ryota Tarui, Takashi Nakamura, Takayo Mu ...
    2023 Volume 6 Issue 6 Pages 189-192
    Published: 2023
    Released on J-STAGE: November 30, 2023
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    Xanthine oxidase (XO) produces reactive oxygen species (ROS) and has been associated with vascular endothelial dysfunction. While the effects of xanthine oxidoreductase (XOR) inhibitors on inhibiting the generation of uric acid from xanthine have been reported, much less is known about their effects on XO-induced ROS. The mechanisms of action of each XOR inhibitor vary, but it is not known whether XOR inhibitors’ effects on oxidative stress also vary. The purpose of this study is to compare the effects of different XOR inhibitors on XO-induced ROS. We used an in vitro chemiluminescence assay with clinically relevant doses of XOR inhibitors (allopurinol, oxypurinol, febuxostat, and topiroxostat) to investigate their effects on circulating XO-derived ROS. All XOR inhibitors significantly inhibited ROS production, with febuxostat and topiroxostat showing strong effects. These results confirm differences in the effects at clinical did among XOR inhibitors on XO, with topiroxostat demonstrating a strong suppression of ROS production. This study should help guide clinical practice in using XOR inhibitors to improve patient care and management.

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  • Ryoichi Murase, Genki Kato, Kentaro Oh-hashi
    2023 Volume 6 Issue 6 Pages 193-199
    Published: 2023
    Released on J-STAGE: December 05, 2023
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    Supplementary material

    EDEM2 plays an important role as the first enzyme that acts during mannose trimming of N-glycosylated proteins in the ERAD machinery. Although EDEM2 expression has been reported to be transcriptionally regulated by the IRE1-sXBP1 pathway, very little is known about how endogenous EDEM2 protein expression is regulated. In this work, three different ER stress inducers were used to treat HEK293 cells. Thapsigargan slightly increased both EDEM2 mRNA and protein levels in the cells. Treatment with MG132 did not increase the level of mature EDEM2 protein, and a truncated form of the protein appeared. In SEL1L-deficient cells, there was a slight increase in EDEM2 protein as well as in TXNDC11, a protein that has been reported to form disulfide bonds with EDEM2. On the other hand, EDEM2 protein level decreased in TXNDC11-deficient cells. DTT treatment decreased EDEM2 and TXNDC11 protein levels in a time-dependent manner. The decrease in EDEM2 protein after DTT treatment was attenuated by treatment of the cells with MG132 and by SEL1L deficiency. These findings demonstrate that endogenous EDEM2 protein is regulated posttranscriptionally and that it is in part an SEL1L-mediated ERAD substrate.

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  • Hideaki Shimizu, Wataru Aoki, Takaaki Fujieda, Tatsumi Adachi
    2023 Volume 6 Issue 6 Pages 200-203
    Published: 2023
    Released on J-STAGE: December 15, 2023
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    We recently found that the morphology of dibutyryl cyclic AMP (dbcAMP)-stimulated cultured cerebral hemisphere astrocytes changed from stellate to polygonal within 3 h after methylmercury (MeHg) exposure at 2 and 3 µM. To elucidate the mechanism of this change (spreading) in astrocytes induced by MeHg, the effects of inhibitors of Rho and its downstream effector, Rho kinase, and the expression levels of total and active RhoA were investigated under serum-free conditions in the presence of dbcAMP. Pretreatment with C3 transferase (a Rho inhibitor) completely inhibited the spreading of astrocytes induced by MeHg at both doses for 3 h. However, pretreatment with Y-27632 (a Rho kinase inhibitor) inhibited the spreading induced by MeHg at 2 µM, but not by that at 3 µM. Expression levels of total RhoA were similar under all conditions examined, including in the presence of MeHg. In contrast, the expression level of active RhoA in astrocytes exposed to MeHg at 2 or 3 µM for 30 min was markedly higher than that in astrocytes exposed to solvent alone, although no difference was observed in the level between astrocytes exposed to MeHg at either dose. In addition, the active RhoA levels in MeHg-exposed astrocytes at both doses were similar to the level in astrocytes maintained in 15% serum-containing medium. These results suggest that RhoA activation is involved in the change in shape of astrocytes induced by MeHg at 2-3 µM, and that Rho kinase is, at least partly, related to the shape change in its downstream signal transduction.

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  • Tsuyoshi Murahashi, Hanako Ueno, Akiko Koyama, Shoko Sasaki, Yui Hosok ...
    2023 Volume 6 Issue 6 Pages 204-208
    Published: 2023
    Released on J-STAGE: December 15, 2023
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    We measured the atmospheric concentrations of fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) on every Tuesday from 2016 to 2019 to reveal the characteristics of PM2.5 pollution in a suburban residential area of Saitama Prefecture, a commuter town of Tokyo, and obtained the following results. First, mean PM2.5 concentration over four years was 15.3 µg/m3, which was slightly higher than the long-term environmental standard of 15 µg/m3. Second, extremely high PM2.5 concentrations may have been caused by the arrival of the Yellow Sand; a high PAH concentration was also observed during this event. Third, in the area surrounding the fields, PM2.5 as well as PAH concentrations were increased from autumn to winter owing to open burning of biomass. Finally, the PM2.5 concentration in the suburban areas surrounding the fields was 70% of that in central Tokyo, and the PAH concentration in late winter was the same as that in central Tokyo. These findings suggest that PM2.5 and PAH concentrations in the suburban area surrounding the fields were high despite the area’s low population density because of PM2.5 accumulation in the metropolitan area and PM2.5 emission from biomass burning. To improve the living environment of suburban residential areas surrounding fields, it is necessary to restrict biomass burning.

Regular Article
  • Hiroshi Hasegawa, Mitsuki Daito, Mari Kondo, Kei Nakayama
    2023 Volume 6 Issue 6 Pages 209-216
    Published: 2023
    Released on J-STAGE: December 15, 2023
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    Ethanol, a widely used toxic chemical in human cultures, exerts its toxicity throughout the human body, with the nervous system being particularly vulnerable, leading to various neurological disorders. Despite the prevalence of peripheral neuropathies associated with alcohol abuse, the causal mechanism of ethanol-induced peripheral neuropathies remains largely unknown. This study investigated the impact of repeated ethanol intake on the histological features of trigeminal ganglia in mice. Histological analysis revealed that blood vessels in the trigeminal ganglia exhibited distinct morphological and molecular characteristics based on their location, specifically in regions where neuronal cell bodies or axonal fibers predominate. Administration of a binge level of ethanol for four consecutive days induced significant blood vessel remodeling in both regions. Unexpectedly, the morphology of trigeminal neurons and their axons remained unaffected by ethanol. Given the observed suppression of IBA1/AIF1-positive microglia-like cells by ethanol, we explored whether manipulative suppression of microglia-like cell activity with minocycline could recapitulate ethanol-induced effects. Remarkably, administration of minocycline, instead of ethanol, resulted in similar blood vessel remodeling, suggesting that the repeated intake of a binge level of ethanol causes blood vessel remodeling through the suppression of microglia-like cells in the trigeminal ganglia. These findings provide valuable insights into the complex interplay between ethanol exposure, microglia-like cell activity, and vascular changes in the trigeminal ganglia.

Regular Article
  • Naoya Nakagawa, Tomoyuki Enokiya, Shiro Tochitani, Maki Nakahigashi, K ...
    2023 Volume 6 Issue 6 Pages 217-225
    Published: 2023
    Released on J-STAGE: December 20, 2023
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    Background and aim: Zinc is one of the most important essential trace elements found in more than 300 enzymes in humans, and the risk of zinc deficiency has been shown to increase with age. Symptoms associated with zinc deficiency such as muscle weakness, impaired immune function, and delayed wound healing, have much in common with health problems faced by the elderly. However, the relationship between zinc deficiency and the health problems of the elderly has not yet been fully analyzed. Here, we analyzed the effects of zinc in terms of muscle strength, skin barrier function, and gut microbiota in the elderly. Methods: Thirty elderly residents of a special nursing home in Japan were divided into two groups: a zinc intake group (14 participants) and a zinc non-intake group (16 participants). Participants in the zinc intake group received zinc (10 mg/day) for 8 weeks. Changes in muscle mass indices such as calf circumference (CC) and dry skin indices such as stratum corneum water content (SWC) were observed before and after the study. Fecal analysis was also performed at week 8 to analyze the intestinal microflora and short-chain fatty acid (SCFA) content. Results: The values of CC and SWC increased with zinc administration. The analysis of intestinal microflora showed that zinc administration increased the occupancy of Rikenellaceae. This change was observed to be associated with increased CC values. Conclusion: This study suggested that zinc may be involved in maintaining muscle mass in the elderly via the gut microbiota.

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  • Rina Abe, Yuka Yagi, Hidenori Tani
    2023 Volume 6 Issue 6 Pages 226-228
    Published: 2023
    Released on J-STAGE: December 26, 2023
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    Long non-coding RNAs (lncRNAs) are transcripts exceeding 200 nucleotides in length that do not code for proteins. However, they play pivotal roles in various biological processes. The mechanisms by which bacterial infections induce lncRNA expression remain elusive. Our past study, we identified a unique class of lncRNAs with short half-lives, less than 4 h in human HeLa cells. These short-lived lncRNAs include to many regulatory functions, such as HOTAIR, NEAT1, or GAS5. Due to their potential influence on human biology, these short-lived lncRNAs might serve as important markers to gauge the stress from bacterial infections. In this study, we identified three lncRNAs, named MIR22HG, GABPB1-AS1, and IDI2-AS1. Their expression significantly decreased after exposure to lipopolysaccharide, simulating bacterial infection in human A549 cells. Our findings suggest that short-lived lncRNAs react to bacterial infections, with their expression levels dropping notably. We propose that these lncRNAs could act as potential indicators of cellular responses to bacteria.

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  • Masakazu Ishii, Hirotaka Katoh, Tamotsu Kijima, Ikumi Ito
    2023 Volume 6 Issue 6 Pages 229-235
    Published: 2023
    Released on J-STAGE: December 26, 2023
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    To clarify the current status and challenges of pharmacist involvement in headache treatment, we conducted a questionnaire survey of people who were aware of having headaches. A questionnaire survey was conducted on the Internet of 600 subjects between the ages of 20 and 40 who had suffered from headaches in the past three months. Subjects were divided into a migraine (n = 250, 55.2% women) and other headache (n = 350, 46.3% women) groups. The degree of interference with daily life was higher in the migraine group than in the other headache group. Regarding headache consultations with pharmacists, many people in the migraine group had not consulted a pharmacist even when the severity was high; however, 43.5% of those who had consulted a pharmacist had been recommended to see a doctor. Regarding the status of medical visits, approximately half of the migraine group did not visit a doctor even when the degree of disability was high, and only 44.4% of the migraine group were treated with prescription drugs. Regarding the level of awareness of headaches caused by overuse of analgesics, the majority of respondents in both groups answered “I don't know” or “I hardly know.” Since many people with headache are treated with over-the-counter (OTC) drugs, pharmacists are required to follow up with those who are treating their headaches with OTC drugs, and to recommend treatment with prescription drugs if their headaches are interfering with their daily lives.

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