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Article ; Online: [New-generation Drug Innovation by Focusing on Elements Chemistry: Development of Innovative Biofunctional Molecules Based on Multi-elemental Compounds].

Ohta, Kiminori / Fujii, Shinya

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan

2023 Volume 143, Issue 5, Page(s) 419–420

Language	Japanese
Publishing date	2023-04-28
Publishing country	Japan
Document type	Journal Article
ZDB-ID	200514-1
ISSN	1347-5231 ; 0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
ISSN (online)	1347-5231
ISSN	0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
DOI	10.1248/yakushi.22-00205-F
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Article ; Online: [Developing the Next Generation Small-molecule Pharmaceuticals Using a Wide Variety of Elements].

Fujii, Shinya / Ohta, Kiminori

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan

2022 Volume 142, Issue 2, Page(s) 129–130

MeSH term(s)	Animals ; Drug Development/methods ; Drug Development/trends ; Drug Evaluation, Preclinical/methods ; Drug Evaluation, Preclinical/trends ; Elements ; Humans ; Molecular Weight ; Pharmaceutical Preparations/chemical synthesis ; Pharmaceutical Preparations/chemistry
Chemical Substances	Elements ; Pharmaceutical Preparations
Language	Japanese
Publishing date	2022-02-02
Publishing country	Japan
Document type	Editorial
ZDB-ID	200514-1
ISSN	1347-5231 ; 0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
ISSN (online)	1347-5231
ISSN	0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
DOI	10.1248/yakushi.21-00173-F
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Article ; Online: ChIP-Atlas 2021 update: a data-mining suite for exploring epigenomic landscapes by fully integrating ChIP-seq, ATAC-seq and Bisulfite-seq data.

Zou, Zhaonan / Ohta, Tazro / Miura, Fumihito / Oki, Shinya

Nucleic acids research

2023 Volume 50, Issue W1, Page(s) W175–W182

Abstract: ChIP-Atlas (https://chip-atlas.org) is a web service providing both GUI- and API-based data-mining tools to reveal the architecture of the transcription regulatory landscape. ChIP-Atlas is powered by comprehensively integrating all data sets from high- ... ...

Abstract	ChIP-Atlas (https://chip-atlas.org) is a web service providing both GUI- and API-based data-mining tools to reveal the architecture of the transcription regulatory landscape. ChIP-Atlas is powered by comprehensively integrating all data sets from high-throughput ChIP-seq and DNase-seq, a method for profiling chromatin regions accessible to DNase. In this update, we further collected all the ATAC-seq and whole-genome bisulfite-seq data for six model organisms (human, mouse, rat, fruit fly, nematode, and budding yeast) with the latest genome assemblies. These together with ChIP-seq data can be visualized with the Peak Browser tool and a genome browser to explore the epigenomic landscape of a query genomic locus, such as its chromatin accessibility, DNA methylation status, and protein-genome interactions. This epigenomic landscape can also be characterized for multiple genes and genomic loci by querying with the Enrichment Analysis tool, which, for example, revealed that inflammatory bowel disease-associated SNPs are the most significantly hypo-methylated in neutrophils. Therefore, ChIP-Atlas provides a panoramic view of the whole epigenomic landscape. All datasets are free to download via either a simple button on the web page or an API.
MeSH term(s)	Animals ; Humans ; Chromatin Immunoprecipitation Sequencing ; Data Mining ; Epigenomics/methods ; High-Throughput Nucleotide Sequencing/methods ; Sequence Analysis, DNA/methods ; Models, Animal ; Atlases as Topic ; Databases as Topic
Language	English
Publishing date	2023-03-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkac199
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Article: Steroidal Saponins Isolated from the Rhizome of

Okubo, Shinya / Ohta, Tomoe / Shoyama, Yukihiro / Uto, Takuhiro

Life (Basel, Switzerland)

2021 Volume 11, Issue 8

Abstract: Our preliminary screening identified an extract from the rhizome ... ...

Abstract	Our preliminary screening identified an extract from the rhizome of
Language	English
Publishing date	2021-07-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life11080749
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Article: Upregulation of brain-derived neurotrophic factor by Shiikuwasha (Citrus depressa Hayata).

Nakajima, Kensuke / Okubo, Shinya / Ohta, Tomoe / Uto, Takuhiro / Oiso, Shigeru

Journal of pharmaceutical health care and sciences

2023 Volume 9, Issue 1, Page(s) 40

Abstract: Background: A reduction in the brain-derived neurotrophic factor (BDNF) level in the brain causes depression, whereas an increase in its level has therapeutic benefits against depression. BDNF is synthesized in various peripheral tissues and transported ...

Abstract	Background: A reduction in the brain-derived neurotrophic factor (BDNF) level in the brain causes depression, whereas an increase in its level has therapeutic benefits against depression. BDNF is synthesized in various peripheral tissues and transported to the brain via the peripheral circulation across the blood-brain barrier. Therefore, substances that upregulate peripheral BDNF level may be used to prevent and treat depression. Previously, we demonstrated that Citrus unshiu peel (Chinpi) and C. natsudaidai increased BDNF level in a human renal adenocarcinoma cell line ACHN, which has BDNF-producing ability. Here, we evaluated whether Shiikuwasha (C. depressa Hayata), a citrus species cultivated in East Asia, can upregulate BDNF level in ACHN cells. Methods: We evaluated the effects of test samples on BDNF production by measuring BDNF level in the medium of ACHN cells after a 24 h cultivation in the presence of test samples. The BDNF mRNA level was measured by quantitative reverse transcription-polymerase chain reaction, and the phosphorylation level of cyclic adenosine monophosphate response element-binding protein (CREB), a transcription factor regulating BDNF expression, was determined using Western blotting. Results: We found that methanol extracts of Shiikuwasha peel, pulp, and seed increased the BDNF level in the culture medium of ACHN cells. Shiikuwasha peel and pulp extracts also upregulated BDNF mRNA level and phosphorylation of CREB. Conclusions: These results suggest that Shiikuwasha includes the candidate antidepressant substances with peripheral BDNF-upregulation effect.
Language	English
Publishing date	2023-12-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2809913-8
ISSN	2055-0294
ISSN	2055-0294
DOI	10.1186/s40780-023-00309-7
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Article ; Online: Chemo-Senolytic Therapeutic Potential against Angiosarcoma.

Wang, Xuebing / Yik-Lok Chung, Claire / Yoshioka, Ai / Hashimoto, Shinya / Jimbo, Haruki / Tanizawa, Hideki / Ohta, Shinya / Fukumoto, Takeshi / Noma, Ken-Ichi

The Journal of investigative dermatology

2024

Abstract: Angiosarcoma is an aggressive soft-tissue sarcoma with a poor prognosis. Chemotherapy for this cancer typically employs paclitaxel, a taxane (genotoxic drug), although it has a limited effect owing to chemoresistance to prolonged treatment. In this study, ...

Abstract	Angiosarcoma is an aggressive soft-tissue sarcoma with a poor prognosis. Chemotherapy for this cancer typically employs paclitaxel, a taxane (genotoxic drug), although it has a limited effect owing to chemoresistance to prolonged treatment. In this study, we examine an alternative angiosarcoma treatment approach that combines chemotherapeutic and senolytic agents. We find that the chemotherapeutic drugs cisplatin and paclitaxel efficiently induce senescence in angiosarcoma cells. Subsequent treatment with the senolytic agent ABT-263 eliminates senescent cells by activating the apoptotic pathway. In addition, expression analysis indicates that senescence-associated secretory phenotype genes are activated in senescent angiosarcoma cells and that ABT-263 treatment downregulates IFN-I pathway genes in senescent cells. Moreover, we show that cisplatin treatment alone requires high doses to remove angiosarcoma cells. In contrast, lower doses of cisplatin are sufficient to induce senescence, followed by the elimination of senescent cells by the senolytic treatment. This study sheds light on a potential therapeutic strategy against angiosarcoma by combining a relatively low dose of cisplatin with the ABT-263 senolytic agent, which can help ease the deleterious side effects of chemotherapy.
Language	English
Publishing date	2024-04-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2024.03.026
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Article ; Online: Long-term geometric quality assurance of radiation focal point and cone-beam computed tomography for Gamma Knife radiosurgery system.

Ohira, Shingo / Imae, Toshikazu / Minamitani, Masanari / Katano, Atsuto / Aoki, Atsushi / Ohta, Takeshi / Umekawa, Motoyuki / Shinya, Yuki / Hasegawa, Hirotaka / Nishio, Teiji / Koizumi, Masahiko / Yamashita, Hideomi / Saito, Nobuhito / Nakagawa, Keiichi

Radiological physics and technology

2024

Abstract: To investigate the geometric accuracy of the radiation focal point (RFP) and cone-beam computed tomography (CBCT) over long-term periods for the ICON Leksell Gamma Knife radiosurgery system. This phantom study utilized the ICON quality assurance tool ... ...

Abstract	To investigate the geometric accuracy of the radiation focal point (RFP) and cone-beam computed tomography (CBCT) over long-term periods for the ICON Leksell Gamma Knife radiosurgery system. This phantom study utilized the ICON quality assurance tool plus, and the phantom was manually set on the patient position system before the implementation of treatment for patients. The deviation of the RFP position from the unit center point (UCP) and the positions of the four ball bearings (BBs) in the CBCT from the reference position were automatically analyzed. During 544 days, a total of 269 analyses were performed on different days. The mean ± standard deviation (SD) of the deviation between measured RFP and UCP was 0.01 ± 0.03, 0.01 ± 0.03, and -0.01 ± 0.01 mm in the X, Y, and Z directions, respectively. The deviations with offset values after the cobalt-60 source replacement (0.00 ± 0.03, -0.01 ± 0.01, and -0.01 ± 0.01 mm in the X, Y, and Z directions, respectively) were significantly (p = 0.001) smaller than those before the replacement (0.02 ± 0.03, 0.02 ± 0.01, and -0.02 ± 0.01 mm in the X, Y, and Z directions, respectively). The overall mean ± SD of four BBs was -0.03 ± 0.03, -0.01 ± 0.05, and 0.01 ± 0.03 mm in the X, Y, and Z directions, respectively. Geometric positional accuracy was ensured to be within 0.1 mm on most days over a long-term period of more than 500 days.
Language	English
Publishing date	2024-03-11
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2433581-2
ISSN	1865-0341 ; 1865-0333
ISSN (online)	1865-0341
ISSN	1865-0333
DOI	10.1007/s12194-024-00788-9
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Article ; Online: CCDC86 is a novel Ki-67-interacting protein important for cell division.

Stamatiou, Konstantinos / Chmielewska, Aldona / Ohta, Shinya / Earnshaw, William C / Vagnarelli, Paola

Journal of cell science

2023 Volume 136, Issue 2

Abstract: The chromosome periphery is a network of proteins and RNAs that coats the outer surface of mitotic chromosomes. Despite the identification of new components, the functions of this complex compartment are poorly characterised. In this study, we identified ...

Abstract	The chromosome periphery is a network of proteins and RNAs that coats the outer surface of mitotic chromosomes. Despite the identification of new components, the functions of this complex compartment are poorly characterised. In this study, we identified a novel chromosome periphery-associated protein, CCDC86 (also known as cyclon). Using a combination of RNA interference, microscopy and biochemistry, we studied the functions of CCDC86 in mitosis. CCDC86 depletion resulted in partial disorganisation of the chromosome periphery with alterations in the localisation of Ki-67 (also known as MKI67) and nucleolin (NCL), and the formation of abnormal cytoplasmic aggregates. Furthermore, CCDC86-depleted cells displayed errors in chromosome alignment, altered spindle length and increased apoptosis. These results suggest that, within the chromosome periphery, different subcomplexes that include CCDC86, nucleolin and B23 (nucleophosmin or NPM1) are required for mitotic spindle regulation and correct kinetochore-microtubule attachments, thus contributing to chromosome segregation in mitosis. Moreover, we identified CCDC86 as a MYCN-regulated gene, the expression levels of which represent a powerful marker for prognostic outcomes in neuroblastoma.
MeSH term(s)	Humans ; Ki-67 Antigen/genetics ; Spindle Apparatus/genetics ; Spindle Apparatus/metabolism ; Mitosis/genetics ; Chromosomes/metabolism ; Chromosome Segregation/genetics ; Kinetochores/metabolism ; Microtubules/metabolism ; HeLa Cells
Chemical Substances	Ki-67 Antigen
Language	English
Publishing date	2023-01-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.260391
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Article ; Online: Steroidal Saponins Isolated from the Rhizome of Dioscorea tokoro Inhibit Cell Growth and Autophagy in Hepatocellular Carcinoma Cells

Shinya Okubo / Tomoe Ohta / Yukihiro Shoyama / Takuhiro Uto

Life, Vol 11, Iss 749, p

2021 Volume 749

Abstract: Our preliminary screening identified an extract from the rhizome of Dioscorea tokoro , which strongly suppressed the proliferation of HepG2 hepatocellular carcinoma cells and inhibited autophagy. This study aimed to isolate active compounds from the ... ...

Abstract	Our preliminary screening identified an extract from the rhizome of Dioscorea tokoro , which strongly suppressed the proliferation of HepG2 hepatocellular carcinoma cells and inhibited autophagy. This study aimed to isolate active compounds from the rhizome of D. tokoro that exert antiproliferative effects and inhibit autophagy. The bioassay-guided fractionation of the active fraction led to the isolation of two spirostan-type steroidal saponins, dioscin ( 1 ) and yamogenin 3- O - α - l -rhamnopyranosyl (1→4)- O - α - l -rhamnopyranosyl(1→2)- β - d -glucopyranoside ( 2 ), and the frostane-type steroidal saponin protodioscin ( 3 ) from the n -BuOH fraction. Furthermore, acid hydrolysis of 1 and 2 produced the aglycones diosgenin ( 4 ) and yamogenin ( 5 ), respectively. Compounds 1 – 5 suppressed proliferation of HepG2 cells. The analysis of structure-activity relationships indicated that the 25( R )-conformation, structures with a sugar moiety, and the spirostan-type aglycone moiety contributed to antiproliferative activity. Analysis of autophagy-related proteins demonstrated that 1 – 3 clearly increased the levels of both LC3-II and p62, implying that 1 – 3 deregulate the autophagic pathway by blocking autophagic flux, which results in p62 and LC3-II accumulation. In contrast, 1 – 3 did not significantly affect caspase-3 activation and PARP cleavage, suggesting that the antiproliferative activity of 1 – 3 occurred independently of caspase-3-mediated apoptosis. In summary, our study showed that 1 – 3 , active compounds in the rhizome of D. tokoro , suppressed cell proliferation and autophagy, and might be potential agents for autophagy research and cancer chemoprevention.
Keywords	autophagy ; hepatocellular carcinoma ; HepG2 ; LC3-II ; Beclin 1 ; p62 ; Science ; Q
Subject code	500
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Arctigenin suppresses cell proliferation via autophagy inhibition in hepatocellular carcinoma cells.

Okubo, Shinya / Ohta, Tomoe / Shoyama, Yukihiro / Uto, Takuhiro

Journal of natural medicines

2020 Volume 74, Issue 3, Page(s) 525–532

Abstract: Autophagy is a catabolic process that degrades dysfunctional proteins and organelles and plays critical roles in cancer development. Our preliminary screening identified that extracts of the fruits of Arctium lappa and the fruits of Forsythia suspensa ... ...

Abstract	Autophagy is a catabolic process that degrades dysfunctional proteins and organelles and plays critical roles in cancer development. Our preliminary screening identified that extracts of the fruits of Arctium lappa and the fruits of Forsythia suspensa notably suppressed the proliferation of hepatocellular carcinoma HepG2 cells and downregulated the autophagy. In this study, we explored the effect of arctigenin (ARG), a bioactive lignan in both extracts, on cell proliferation and autophagy-related proteins in HepG2 cells. ARG inhibited the proliferation of HepG2 cells. Analysis of autophagy-related proteins demonstrated that ARG might block the autophagy that leads to sequestosome 1/p62 (p62) accumulation. The stage of inhibition in autophagy by ARG differed from those by the autophagy inhibitors 3-methyladenine (3-MA) or chloroquine (CQ). ARG could also inhibit starvation-induced autophagy. Further analysis of apoptosis-related proteins indicated that ARG did not affect caspase-3 activation and PARP cleavage, suggesting that the antiproliferative effect of ARG can occur independently of apoptosis. In summary, our study showed that ARG suppresses cell proliferation and inhibits autophagy, and might lead to the development of agents for autophagy research and cancer chemoprevention.
MeSH term(s)	Adenine/analogs & derivatives ; Adenine/pharmacology ; Apoptosis/drug effects ; Apoptosis Regulatory Proteins/metabolism ; Arctium/chemistry ; Autophagy/drug effects ; Carcinoma, Hepatocellular/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Chloroquine/pharmacology ; Forsythia/chemistry ; Furans/pharmacology ; Hep G2 Cells ; Humans ; Lignans/pharmacology ; Liver Neoplasms/pathology ; Sequestosome-1 Protein
Chemical Substances	Apoptosis Regulatory Proteins ; Furans ; Lignans ; SQSTM1 protein, human ; Sequestosome-1 Protein ; 3-methyladenine (5142-23-4) ; Chloroquine (886U3H6UFF) ; Adenine (JAC85A2161) ; arctigenin (U76MR9VS6M)
Language	English
Publishing date	2020-03-23
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2227540-X
ISSN	1861-0293 ; 1340-3443
ISSN (online)	1861-0293
ISSN	1340-3443
DOI	10.1007/s11418-020-01396-8
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