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Article ; Online: Delivery of the reduced form of vitamin K

Toki, Erina / Goto, Shotaro / Setoguchi, Shuichi / Terada, Kazuki / Watase, Daisuke / Yamakawa, Hirofumi / Yamada, Ayano / Koga, Mitsuhisa / Kubota, Kaori / Iwasaki, Katsunori / Karube, Yoshiharu / Matsunaga, Kazuhisa / Takata, Jiro

Scientific reports

2022 Volume 12, Issue 1, Page(s) 19878

Abstract: ... Several reports have shown that menaquinone-4 (MK-4, vitamin K ...

Abstract	Mitochondria generate energy through the action of the electron transport chain (ETC) and ATP synthase. Mitochondrial malfunction can lead to various disorders, including neurodegenerative diseases. Several reports have shown that menaquinone-4 (MK-4, vitamin K
MeSH term(s)	Mice ; Animals ; Rotenone/toxicity ; Prodrugs/pharmacology ; Reactive Oxygen Species/metabolism ; Cell Death ; 3T3 Cells
Chemical Substances	Rotenone (03L9OT429T) ; Prodrugs ; Reactive Oxygen Species
Language	English
Publishing date	2022-11-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-24456-3
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Article ; Online: Development of Monascus purpureus monacolin K-hyperproducing mutant strains by synchrotron light irradiation and their comparative genome analysis.

Ketkaeo, Sittichoke / Nagano, Yukio / Baba, Shuichiro / Kimura, Kei / Futagami, Taiki / Sanpamongkolchai, Werasit / Kobayashi, Genta / Goto, Masatoshi

Journal of bioscience and bioengineering

2022 Volume 133, Issue 4, Page(s) 362–368

Abstract: ... purpureus characteristically produces monacolin K (MK), a secondary metabolite that competitively ...

Abstract	Monascus purpureus have been used for making koji and other fermented foods and supplements. M. purpureus characteristically produces monacolin K (MK), a secondary metabolite that competitively inhibits cholesterol synthesis. Synchrotron light irradiation was applied to induce mutation in the strain KUPM5 to improve the MK-producing ability of M. purpureus strain KUPM5. Screening by a bioassay utilizing sensitivities to yeast Saccharomyces cerevisiae from 936 colonies allows isolating three mutant strains: SC01, SC02, and SC03. These mutant strains and the parental strain KUPM5 were subjected to make koji using rice, and their metabolites were compared. All strains SC01, SC02, and SC03 in koji showed higher production of MK than the strain KUPM5. Particularly, the SC02 strain produced MK threefold higher than KUPM5 and maintained the production capabilities of other metabolites, including red, yellow, and orange pigments, mycelial contents, and α-amylase activity comparable to those of the strain KUPM5. Comparative genome analysis among strain KUPM5 and the mutants revealed that synchrotron light irradiation introduced mutations in approximately 90% of the total genes, including SNV, MNV, and indel mutations. The frequencies of SNV substitution in the whole genome occupied 68.96% of all mutations, of which 92.38% were transversions and 7.62% were transitions. This study, therefore, proved the synchrotron light irradiation was highly efficient for the strain improvement of a filamentous fungus, M. purpureus, and provided insights into the properties of mutation in the fungus by this mutagen.
MeSH term(s)	Fermentation ; Fermented Foods ; Lovastatin/metabolism ; Monascus/metabolism ; Pigments, Biological ; Synchrotrons
Chemical Substances	Pigments, Biological ; Lovastatin (9LHU78OQFD)
Language	English
Publishing date	2022-01-30
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1465387-4
ISSN	1347-4421 ; 1389-1723
ISSN (online)	1347-4421
ISSN	1389-1723
DOI	10.1016/j.jbiosc.2021.11.011
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Article ; Online: Na+/K+ ATPase α1 and β3 subunits are localized to the basolateral membrane of trophectoderm cells in human blastocysts.

Hirakawa, T / Goto, M / Takahashi, K / Iwasawa, T / Fujishima, A / Makino, K / Shirasawa, H / Sato, W / Sato, T / Kumazawa, Y / Terada, Y

Human reproduction (Oxford, England)

2022 Volume 37, Issue 7, Page(s) 1423–1430

Abstract: Study question: Is there a relation between specific Na+/K+ ATPase isoform expression and ... localization in human blastocysts and the developmental behavior of the embryo?: Summary answer: Na+/K+ ... known already: In mouse embryos, Na+/K+ ATPase α1 and β1 are expressed in the basolateral membrane ...

Abstract	Study question: Is there a relation between specific Na+/K+ ATPase isoform expression and localization in human blastocysts and the developmental behavior of the embryo? Summary answer: Na+/K+ ATPase α1, β1 and β3 are the main isoforms expressed in human blastocysts and no association was found between the expression level of their respective mRNAs and the rate of blastocyst expansion. What is known already: In mouse embryos, Na+/K+ ATPase α1 and β1 are expressed in the basolateral membrane of trophectoderm (TE) cells and are believed to be involved in blastocoel formation (cavitation). Study design, size, duration: A total of 20 surplus embryos from 11 patients who underwent IVF and embryo transfer at a university hospital between 2009 and 2018 were analyzed. Participants/materials, setting, methods: After freezing and thawing Day 5 human blastocysts, their developmental behavior was observed for 24 h using time-lapse imaging, and the expression of Na+/K+ ATPase isoforms was examined using quantitative RT-PCR (RT-qPCR). The expressed isoforms were then localized in blastocysts using fluorescent immunostaining. Main results and the role of chance: RT-qPCR results demonstrated the expression of Na+/K+ ATPase α1, β1 and β3 isoforms in human blastocysts. Isoforms α1 and β3 were localized to the basolateral membrane of TE cells, and β1 was localized between TE cells. A high level of β3 mRNA expression correlated with easier hatching (P = 0.0261). Large scale data: N/A. Limitations, reasons for caution: The expression of mRNA and the localization of proteins of interest were verified, but we have not been able to perform functional analysis. Wider implications of the findings: Of the various Na+/K+ ATPase isoforms, expression levels of the α1, β1 and β3 mRNAs were clearly higher than other isoforms in human blastocysts. Since α1 and β3 were localized to the basolateral membrane via fluorescent immunostaining, we believe that these subunits contribute to the dilation of the blastocoel. The β1 isoform is localized between TE cells and may be involved in tight junction formation, as previously reported in mouse embryos. Study funding/competing interest(s): This work was supported by the JSPS KAKENHI (https://www.jsps.go.jp/english/index.html), grant number 17K11215. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no conflicts of interest.
MeSH term(s)	Animals ; Blastocyst/metabolism ; Cell Membrane/metabolism ; Embryo, Mammalian/metabolism ; Humans ; Mice ; RNA, Messenger/metabolism ; Sodium-Potassium-Exchanging ATPase/genetics ; Sodium-Potassium-Exchanging ATPase/metabolism
Chemical Substances	RNA, Messenger ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13)
Language	English
Publishing date	2022-05-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632776-x
ISSN	1460-2350 ; 0268-1161 ; 1477-741X
ISSN (online)	1460-2350
ISSN	0268-1161 ; 1477-741X
DOI	10.1093/humrep/deac124
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Article ; Online: Ester derivatives of phyllohydroquinone effectively deliver the active form of vitamin K

Goto, Shotaro / Setoguchi, Shuichi / Nagata-Akaho, Nami / Terada, Kazuki / Watase, Daisuke / Yamakawa, Hirofumi / Toki, Erina / Koga, Mitsuhisa / Matsunaga, Kazuhisa / Karube, Yoshiharu / Takata, Jiro

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

2020 Volume 155, Page(s) 105519

Abstract: Topical application of phylloquinone (PK) is beneficial to the skin; however, its topical use is limited in Europe owing to its photosensitive properties such as photodegradation and phototoxicity. We evaluated the suitability of ester derivatives of ... ...

Abstract	Topical application of phylloquinone (PK) is beneficial to the skin; however, its topical use is limited in Europe owing to its photosensitive properties such as photodegradation and phototoxicity. We evaluated the suitability of ester derivatives of phyllohydroquinone (PKH), the active form of PK, for topical application to overcome the abovementioned problems of PK. We used the PKH derivatives PKH-1,4-bis-N,N-dimethylglycinate hydrochloride (PKH-DMG) and PKH-1,4-bis-hemisuccinate (PKH-SUC) for our studies. Photostability was determined by measuring the residual concentration after irradiation with artificial sunlight and multi-wavelength light. Phototoxicity after ultraviolet A (UVA) irradiation was assessed by measuring drug-induced singlet oxygen and intracellular reactive oxygen species (ROS) generation, and cell viability of a human epidermal keratinocyte cell line (HaCaT). Delivery of PKH into HaCaT cells was assessed by measuring PK epoxide (PKO) levels. The PKH derivatives showed higher photostability than PK. After UVA irradiation, PK induced high singlet oxygen levels and intracellular ROS generation, and reduced cell viability, whereas the PKH derivatives showed no effects. The PKH derivatives increased intracellular PKO levels. AUC
MeSH term(s)	Esters ; Europe ; Humans ; Keratinocytes ; Reactive Oxygen Species ; Ultraviolet Rays ; Vitamin K 1
Chemical Substances	Esters ; Reactive Oxygen Species ; Vitamin K 1 (84-80-0)
Language	English
Publishing date	2020-08-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1154366-8
ISSN	1879-0720 ; 0928-0987
ISSN (online)	1879-0720
ISSN	0928-0987
DOI	10.1016/j.ejps.2020.105519
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Article ; Online: Prodrugs for Skin Delivery of Menahydroquinone-4, an Active Form of Vitamin K

Goto, Shotaro / Setoguchi, Shuichi / Yamakawa, Hirofumi / Watase, Daisuke / Terada, Kazuki / Matsunaga, Kazuhisa / Karube, Yoshiharu / Takata, Jiro

International journal of molecular sciences

2019 Volume 20, Issue 10

Abstract: ... K ...

Abstract	The effective delivery of menahydroquinone-4 (MKH), an active form of menaquinone-4 (MK-4, vitamin K
MeSH term(s)	Cell Line ; Humans ; Hydroquinones/chemistry ; Hydroquinones/toxicity ; Keratinocytes/drug effects ; Keratinocytes/metabolism ; Prodrugs/chemistry ; Prodrugs/toxicity ; Reactive Oxygen Species/metabolism ; Vitamin K 2/analogs & derivatives ; Vitamin K 2/chemistry ; Vitamin K 2/toxicity
Chemical Substances	Hydroquinones ; Prodrugs ; Reactive Oxygen Species ; Vitamin K 2 (11032-49-8) ; menahydroquinone-4 (39776-45-9)
Language	English
Publishing date	2019-05-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20102548
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Article: Growth Inhibitory Effects of Ester Derivatives of Menahydroquinone-4, the Reduced Form of Vitamin K

Yamakawa, Hirofumi / Setoguchi, Shuichi / Goto, Shotaro / Watase, Daisuke / Terada, Kazuki / Nagata-Akaho, Nami / Toki, Erina / Koga, Mitsuhisa / Matsunaga, Kazuhisa / Karube, Yoshiharu / Takata, Jiro

Pharmaceutics

2021 Volume 13, Issue 5

Abstract: ... resistant APL is needed. Menaquinone-4 (MK-4, vitamin K ...

Abstract	The first-choice drug for acute promyelocytic leukemia (APL), all-trans retinoic acid (ATRA), frequently causes drug-resistance and some adverse effects. Thus, an effective and safe agent for ATRA-resistant APL is needed. Menaquinone-4 (MK-4, vitamin K
Language	English
Publishing date	2021-05-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics13050758
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Article ; Online: On-treatment Comparative Effectiveness of Vitamin K Antagonists and Direct Oral Anticoagulants in GARFIELD-VTE, and Focus on Cancer and Renal Disease.

TH open : companion journal to thrombosis and haemostasis

2022 Volume 6, Issue 4, Page(s) e354–e364

Abstract: ... ...

Abstract	Background
Language	English
Publishing date	2022-11-03
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2901738-5
ISSN	2512-9465 ; 2567-3459
ISSN (online)	2512-9465
ISSN	2567-3459
DOI	10.1055/s-0042-1757744
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Article ; Online: Cathepsin K activity controls cardiotoxin-induced skeletal muscle repair in mice.

Ogasawara, Shinyu / Cheng, Xian Wu / Inoue, Aiko / Hu, Lina / Piao, Limei / Yu, Chenglin / Goto, Hiroki / Xu, Wenhu / Zhao, Guangxian / Lei, Yanna / Yang, Guang / Kimura, Kaoru / Umegaki, Hiroyuki / Shi, Guo-Ping / Kuzuya, Masafumi

Journal of cachexia, sarcopenia and muscle

2017 Volume 9, Issue 1, Page(s) 160–175

Abstract: Background: Cathepsin K (CatK) is a widely expressed cysteine protease that has gained attention ...

Abstract	Background: Cathepsin K (CatK) is a widely expressed cysteine protease that has gained attention because of its enzymatic and non-enzymatic functions in signalling. Here, we examined whether CatK-deficiency (CatK Methods: Cardiotoxin (CTX, 20 μM/200 μL) was injected into the left gastrocnemius muscle of male wild-type (CatK Results: On post-injection Day 14, CatK deletion ameliorated muscle interstitial fibrosis and remodelling and performance. At an early time point (Day 3), CatK Conclusions: These results demonstrate that CatK plays an essential role in skeletal muscle loss and fibrosis in response to CTX injury, possibly via a reduction of inflammation and cell apoptosis, suggesting a novel therapeutic strategy for the control of skeletal muscle diseases by regulating CatK activity.
MeSH term(s)	Animals ; Apoptosis ; Cardiotoxins/metabolism ; Cathepsin K/metabolism ; Male ; Mice ; Muscle, Skeletal/metabolism
Chemical Substances	Cardiotoxins ; Cathepsin K (EC 3.4.22.38)
Language	English
Publishing date	2017-10-23
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2586864-0
ISSN	2190-6009 ; 2190-5991
ISSN (online)	2190-6009
ISSN	2190-5991
DOI	10.1002/jcsm.12248
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Article ; Online: Distinct chemotactic behavior in the original Escherichia coli K-12 depending on forward-and-backward swimming, not on run-tumble movements.

Kinosita, Yoshiaki / Ishida, Tsubasa / Yoshida, Myu / Ito, Rie / Morimoto, Yusuke V / Goto, Kazuki / Berry, Richard M / Nishizaka, Takayuki / Sowa, Yoshiyuki

Scientific reports

2020 Volume 10, Issue 1, Page(s) 15887

Abstract: ... in E. coli ATCC10798, which is one of the original K-12 clones. High-speed tracking of single ATCC10798 ... which is a derivative of K-12 and a wild-type for chemotaxis. The single point mutation of N87K in FliC ...

Abstract	Most motile bacteria are propelled by rigid, helical, flagellar filaments and display distinct swimming patterns to explore their favorable environments. Escherichia coli cells have a reversible rotary motor at the base of each filament. They exhibit a run-tumble swimming pattern, driven by switching of the rotational direction, which causes polymorphic flagellar transformation. Here we report a novel swimming mode in E. coli ATCC10798, which is one of the original K-12 clones. High-speed tracking of single ATCC10798 cells showed forward and backward swimming with an average turning angle of 150°. The flagellar helicity remained right-handed with a 1.3 μm pitch and 0.14 μm helix radius, which is consistent with the feature of a curly type, regardless of motor switching; the flagella of ATCC10798 did not show polymorphic transformation. The torque and rotational switching of the motor was almost identical to the E. coli W3110 strain, which is a derivative of K-12 and a wild-type for chemotaxis. The single point mutation of N87K in FliC, one of the filament subunits, is critical to the change in flagellar morphology and swimming pattern, and lack of flagellar polymorphism. E. coli cells expressing FliC(N87K) sensed ascending a chemotactic gradient in liquid but did not spread on a semi-solid surface. Based on these results, we concluded that a flagellar polymorphism is essential for spreading in structured environments.
MeSH term(s)	Chemotaxis/physiology ; Escherichia coli K12/physiology ; Flagella/physiology ; Models, Biological ; Mutation
Language	English
Publishing date	2020-09-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-72429-1
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Article: On-treatment Comparative Effectiveness of Vitamin K Antagonists and Direct Oral Anticoagulants in GARFIELD-VTE, and Focus on Cancer and Renal Disease

TH Open

2022 Volume 06, Issue 04, Page(s) e354–e364

Abstract: Background: Direct oral anticoagulants (DOACs) provide a safe, effective alternative to vitamin K ...

Abstract	Background: Direct oral anticoagulants (DOACs) provide a safe, effective alternative to vitamin K antagonists (VKAs) for venous thromboembolism (VTE) treatment, as shown via intention-to-treat comparative effectiveness analysis. However, on-treatment analysis is imperative in observational studies because anticoagulation choice and duration are at investigators' discretion. Objectives: The aim of the study is to compare the effectiveness of DOACs and VKAs on 12-month outcomes in VTE patients using on-treatment analysis. Methods: The Global Anticoagulant Registry in the FIELD - VTE (GARFIELD-VTE) is a world-wide, prospective, non-interventional study observing treatment of VTE in routine clinical practice. Results: In total, 8,034 patients received VKAs ( n = 3,043, 37.9%) or DOACs ( n = 4,991, 62.1%). After adjustment for baseline characteristics and follow-up bleeding events, and accounting for possible time-varying confounding, all-cause mortality was significantly lower with DOACs than VKAs (hazard ratio: 0.58 [95% confidence interval 0.42–0.79]). Furthermore, patients receiving VKAs were more likely to die of VTE complications (4.9 vs. 2.2%) or bleeding (4.9 vs. 0.0%). There was no significant difference in rates of recurrent VTE (hazard ratio: 0.74 [0.55–1.01]), major bleeding (hazard ratio: 0.76 [0.47–1.24]), or overall bleeding (hazard ratio: 0.87 [0.72–1.05]) with DOACs or VKAs. Unadjusted analyses suggested that VKA patients with active cancer or renal insufficiency were more likely to die than patients treated with DOAC (52.51 [37.33–73.86] vs. 26.52 [19.37–36.29] and 9.97 [7.51–13.23] vs. 4.70 [3.25–6.81] per 100 person-years, respectively). Conclusion: DOACs and VKAs had similar rates of recurrent VTE and major bleeding. However, DOACs were associated with reduced all-cause mortality and a lower likelihood of death from VTE or bleeding compared with VKAs.
Keywords	venous thromboembolism ; vitamin K antagonists ; direct oral anticoagulants ; on-treatment comparative effectiveness ; anticoagulation
Language	English
Publishing date	2022-10-01
Publisher	Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	2901738-5
ISSN	2512-9465 ; 2567-3459
ISSN (online)	2512-9465
ISSN	2567-3459
DOI	10.1055/s-0042-1757744
Database	Thieme publisher's database

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