Proceedings of the Japan Academy, Series B
Online ISSN : 1349-2896
Print ISSN : 0386-2208
ISSN-L : 0386-2208
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Displaying 1-4 of 4 articles from this issue
Reviews
  • Masaharu NODA, Takashi MATSUDA
    2022 Volume 98 Issue 7 Pages 283-324
    Published: July 29, 2022
    Released on J-STAGE: July 29, 2022
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    Extracellular fluids, including blood, lymphatic fluid, and cerebrospinal fluid, are collectively called body fluids. The Na+ concentration ([Na+]) in body fluids is maintained at 135–145 mM and is broadly conserved among terrestrial animals. Homeostatic osmoregulation by Na+ is vital for life because severe hyper- or hypotonicity elicits irreversible organ damage and lethal neurological trauma. To achieve “body fluid homeostasis” or “Na homeostasis”, the brain continuously monitors [Na+] in body fluids and controls water/salt intake and water/salt excretion by the kidneys. These physiological functions are primarily regulated based on information on [Na+] and relevant circulating hormones, such as angiotensin II, aldosterone, and vasopressin. In this review, we discuss sensing mechanisms for [Na+] and hormones in the brain that control water/salt intake behaviors, together with the responsible sensors (receptors) and relevant neural pathways. We also describe mechanisms in the brain by which [Na+] increases in body fluids activate the sympathetic neural activity leading to hypertension.

  • Kohzoh IMAI, Hiroaki TANIGUCHI
    2022 Volume 98 Issue 7 Pages 325-335
    Published: July 29, 2022
    Released on J-STAGE: July 29, 2022
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    PRDI-BF1 and RIZ (PR) domain zinc finger protein 14 (PRDM14), first reported in 2007 to be overexpressed in breast cancer, plays an important role in breast cancer proliferation. Subsequent studies reported that PRDM14 is expressed in embryonic stem cells, primordial germ cells, and various cancers. PRDM14 was reported to confer stemness properties to cancer cells. These properties induce cancer initiation, cancer progression, therapeutic resistance, distant metastasis, and recurrence in refractory tumors. Therefore, PRDM14 may be an ideal therapeutic target for various types of tumors. Silencing PRDM14 expression using PRDM14-specific siRNA delivered through an innovative intravenous drug delivery system reduced the size of inoculated tumors, incidence of distant metastases, and increased overall survival in nude mice without causing adverse effects. Therapeutic siRNA targeting PRDM14 is now being evaluated in a human phase I clinical trial for patients with refractory breast cancer, including triple-negative breast cancer.

  • Seiichiro OGAWA, Shinichi KUNO, Tatsushi TOYOKUNI
    2022 Volume 98 Issue 7 Pages 336-360
    Published: July 29, 2022
    Released on J-STAGE: July 29, 2022
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    For over 50 years, our group has been involved in synthetic studies on biologically active cyclitols including carbasugars. Among a variety of compounds synthesized, this review focuses on carbaglycosylamine glycosidase inhibitors, highlighting the following: (1) the naturally occurring N-linked carbaoligosaccharide α-amylase inhibitor acarbose and related compounds; (2) the novel synthetic β-glycosidase inhibitors, 1′-epi-acarviosin and its 6-hydroxy analogue as well as β-valienaminylceramide and its 4′-epimer; (3) the discovery of the β-glycosidase inhibitors with chaperone activity, N-octyl-β-valienamine (NOV) and its 4-epimer (NOEV); and (4) the recent development of the potential pharmacological chaperone N-alkyl-conduramine F-4 derivatives.

Original Article
  • Chao GU, Yuan GAO, Ruilan HAN, Min GUO, Hong LIU, Jie GAO, Yang LIU, B ...
    2022 Volume 98 Issue 7 Pages 361-377
    Published: July 29, 2022
    Released on J-STAGE: July 29, 2022
    JOURNAL OPEN ACCESS FULL-TEXT HTML
    Supplementary material

    Previous studies showed that lanthanum hydroxide (LH) has a therapeutic effect on chronic kidney disease (CKD) and vascular calcification, which suggests that it might have clinical value. However, the target and mechanism of action of LH are unclear. Metabolomics of clinical samples can be used to predict the mechanism of drug action. In this study, metabolomic profiles in patients with end-stage renal disease (ESRD) were used to screen related signaling pathways, and we verified the influence of LH on the ROS-PI3K-AKT-mTOR-HIF-1α signaling pathway by western blotting and quantitative real-time RT-qPCR in vivo and in vitro. We found that ROS and SLC16A10 genes were activated in patients with ESRD. The SLC16A10 gene is associated with six significant metabolites (L-cysteine, L-cystine, L-isoleucine, L-arginine, L-aspartic acid, and L-phenylalanine) and the PI3K-AKT signaling pathway. The results showed that LH inhibits the ESRD process and its cardiovascular complications by inhibiting the ROS-PI3K-AKT-mTOR-HIF-1α signaling pathway. Collectively, LH may be a candidate phosphorus binder for the treatment of vascular calcification in ESRD.

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