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Book: Protein modifications in pathogenic dysregulation of signaling

Inoue, Jun-ichiro / Takekawa, Mutsuhiro

2015

Author's details	Jun-ichiro Inoue ; Mutsuhiro Takekawa ed
Keywords	Post-translational modification
Subject code	572.645
Language	English
Size	IX, 348 S. : Ill., graph. Darst., 24 cm
Publisher	Springer
Publishing place	Tokyo u.a.
Publishing country	Japan
Document type	Book
Note	Includes bibliographical references
HBZ-ID	HT018761817
ISBN	978-4-431-55560-5 ; 978-4-431-55561-2 ; 4-431-55560-9 ; 4-431-55561-7
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Efficacy of an eHealth self-management program in reducing irritable bowel syndrome symptom severity

Jun Tayama / Toyohiro Hamaguchi / Kohei Koizumi / Ryodai Yamamura / Ryo Okubo / Jun-ichiro Kawahara / Kenji Inoue / Atsushi Takeoka / Shin Fukudo

Scientific Reports, Vol 14, Iss 1, Pp 1-

a randomized controlled trial

2024 Volume 11

Abstract: Abstract This study aimed to verify whether an eHealth-based self-management program can reduce irritable bowel syndrome (IBS) symptom severity. An open-label simple randomized controlled trial was conducted that compared an intervention group (n = 21) ... ...

Abstract	Abstract This study aimed to verify whether an eHealth-based self-management program can reduce irritable bowel syndrome (IBS) symptom severity. An open-label simple randomized controlled trial was conducted that compared an intervention group (n = 21) participating in an eHealth self-management program, which involved studying IBS-related information from an established self-help guide followed by in-built quizzes, with a treatment-as-usual group (n = 19) that, except for pharmacotherapy, had no treatment restrictions. Participants were female Japanese university students. The eHealth group received unlimited access to the self-management program for 8 weeks on computers and mobile devices. The primary outcome, participants’ severity of IBS symptoms assessed using the IBS-severity index (IBS-SI), and the secondary outcomes of participants’ quality of life, gut bacteria, and electroencephalography alpha and beta power percentages were measured at baseline and 8 weeks. A significant difference was found in the net change in IBS-SI scores between the eHealth and treatment-as-usual groups, and the former had significantly lower IBS-SI scores following the 8-week intervention than at baseline. Moreover, there was a significant difference in the net change in phylum Cyanobacteria between the eHealth and treatment-as-usual groups. Thus, the eHealth-based self-management program successfully reduced the severity of IBS symptoms.
Keywords	Medicine ; R ; Science ; Q
Subject code	150
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Efficacy of an eHealth self-management program in reducing irritable bowel syndrome symptom severity: a randomized controlled trial.

Tayama, Jun / Hamaguchi, Toyohiro / Koizumi, Kohei / Yamamura, Ryodai / Okubo, Ryo / Kawahara, Jun-Ichiro / Inoue, Kenji / Takeoka, Atsushi / Fukudo, Shin

Scientific reports

2024 Volume 14, Issue 1, Page(s) 4

Abstract: This study aimed to verify whether an eHealth-based self-management program can reduce irritable bowel syndrome (IBS) symptom severity. An open-label simple randomized controlled trial was conducted that compared an intervention group (n = 21) ... ...

Abstract	This study aimed to verify whether an eHealth-based self-management program can reduce irritable bowel syndrome (IBS) symptom severity. An open-label simple randomized controlled trial was conducted that compared an intervention group (n = 21) participating in an eHealth self-management program, which involved studying IBS-related information from an established self-help guide followed by in-built quizzes, with a treatment-as-usual group (n = 19) that, except for pharmacotherapy, had no treatment restrictions. Participants were female Japanese university students. The eHealth group received unlimited access to the self-management program for 8 weeks on computers and mobile devices. The primary outcome, participants' severity of IBS symptoms assessed using the IBS-severity index (IBS-SI), and the secondary outcomes of participants' quality of life, gut bacteria, and electroencephalography alpha and beta power percentages were measured at baseline and 8 weeks. A significant difference was found in the net change in IBS-SI scores between the eHealth and treatment-as-usual groups, and the former had significantly lower IBS-SI scores following the 8-week intervention than at baseline. Moreover, there was a significant difference in the net change in phylum Cyanobacteria between the eHealth and treatment-as-usual groups. Thus, the eHealth-based self-management program successfully reduced the severity of IBS symptoms.
MeSH term(s)	Female ; Humans ; Irritable Bowel Syndrome/therapy ; Quality of Life ; Self-Management ; Telemedicine ; Treatment Outcome
Language	English
Publishing date	2024-01-03
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-50293-z
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Article ; Online: Postoperative disappearance of leptomeningeal enhancement around the brainstem in glioblastoma.

Inoue, Hirotaka / Kuroda, Jun-Ichiro / Uetani, Hiroyuki / Matsuyama, Tomohiko / Kaku, Yasuyuki / Shinojima, Naoki / Hirai, Toshinori / Mukasa, Akitake

Neuroradiology

2024 Volume 66, Issue 3, Page(s) 325–332

Abstract: Purpose: Leptomeningeal enhancement (LME) suggests leptomeningeal dissemination (LMD) of tumor cells, which is a complication of end-stage glioblastoma, and is associated with a poor prognosis. However, magnetic resonance imaging (MRI) occasionally ... ...

Abstract	Purpose: Leptomeningeal enhancement (LME) suggests leptomeningeal dissemination (LMD) of tumor cells, which is a complication of end-stage glioblastoma, and is associated with a poor prognosis. However, magnetic resonance imaging (MRI) occasionally indicates the disappearance of peri-brainstem LME after surgical resection of glioblastoma. Since preoperative LMD may affect treatment indications, we aimed to analyze the clinical significance of preoperative LME of the brainstem in glioblastoma. Methods: We retrospectively collected clinical and radiological data from consecutive patients with glioblastoma and preoperative LME of the brainstem, who were treated at our hospital between 2017 and 2020. Results: Among 112 patients with glioblastoma, nine (8%) showed preoperative LME of the brainstem. In comparison with tumors without LME, tumor size was significantly associated with the preoperative LME of the brainstem (p = 0.016). In addition, there was a trend toward significance for a relationship between deep tumor location and preoperative LME of the brainstem (p = 0.058). Notably, among six patients who underwent surgical resection for glioblastoma with LME of the brainstem, four showed significant radiological disappearance of the LME on postoperative MRI. This suggests that the LME did not result from LMD in these cases. Moreover, these four patients lived longer than would be expected from the presence of LMD. However, this LME disappearance was not observed after biopsy or chemoradiotherapy. Conclusions: These findings suggest that preoperative LME does not necessarily indicate the presence of untreatable LMD; moreover, LME may disappear after surgical tumor resection. Thus, transient preoperative LME could be attributed to other mechanisms, including impaired venous flow due to intratumoral arteriovenous shunts, which can be resolved by reducing the tumor burden.
MeSH term(s)	Humans ; Glioblastoma/diagnostic imaging ; Glioblastoma/surgery ; Glioblastoma/pathology ; Retrospective Studies ; Magnetic Resonance Imaging/methods ; Chemoradiotherapy ; Brain Stem/diagnostic imaging ; Brain Stem/surgery ; Brain Stem/pathology ; Brain Neoplasms/pathology
Language	English
Publishing date	2024-01-10
Publishing country	Germany
Document type	Journal Article
ZDB-ID	123305-1
ISSN	1432-1920 ; 0028-3940
ISSN (online)	1432-1920
ISSN	0028-3940
DOI	10.1007/s00234-023-03275-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Erratum to "Small Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Fusion by Targeting Cavities on Heptad Repeat Trimers" [Biomol Ther 28(4), 311-319 (2020)].

Kandeel, Mahmoud / Yamamoto, Mizuki / Al-Taher, Abdulla / Watanabe, Aya / Oh-Hashi, Kentaro / Park, Byoung Kwon / Kwon, Hyung-Joo / Inoue, Jun-Ichiro / Al-Nazawi, Mohammed

Biomolecules & therapeutics

2024 Volume 32, Issue 2, Page(s) 262–265

Language	English
Publishing date	2024-02-25
Publishing country	Korea (South)
Document type	Published Erratum
ZDB-ID	2734146-X
ISSN	2005-4483 ; 1976-9148
ISSN (online)	2005-4483
ISSN	1976-9148
DOI	10.4062/biomolther.2024.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Aberrant accumulation of NIK promotes tumor growth by dysregulating translation and post-translational modifications in breast cancer.

Hayashi, Yusuke / Nakayama, Jun / Yamamoto, Mizuki / Maekawa, Masashi / Watanabe, Shinya / Higashiyama, Shigeki / Inoue, Jun-Ichiro / Yamamoto, Yusuke / Semba, Kentaro

Cancer cell international

2023 Volume 23, Issue 1, Page(s) 57

Abstract: Background: In vivo investigations with cancer cells have powerful tools to discover cancer progression mechanisms and preclinical candidate drugs. Among these in vivo experimental models, the establishment of highly malignancy cell lines with xenograft ...

Abstract	Background: In vivo investigations with cancer cells have powerful tools to discover cancer progression mechanisms and preclinical candidate drugs. Among these in vivo experimental models, the establishment of highly malignancy cell lines with xenograft has been frequently used. However, few previous researches targeted malignancy-related genes whose protein levels translationally changed. Therefore, this study aimed to identify malignancy-related genes which contributed to cancer progression and changed at the protein level in the in vivo selected cancer cell lines. Methods: We established the high malignancy breast cancer cell line (LM05) by orthotopic xenograft as an in vivo selection method. To explore the altered genes by translational or post-translational regulation, we analyzed the protein production by western blotting in the highly malignant breast cancer cell line. Functional analyses of the altered genes were performed by in vitro and in vivo experiments. To reveal the molecular mechanisms of the regulation with protein level, we evaluated post-translational modification by immunoprecipitation. In addition, we evaluated translational production by click reaction-based purification of nascent protein. Results: As a result, NF-κB inducing kinase (NIK) increased at the protein level and promoted the nuclear localization of NF-κB2 (p52) and RelB in the highly malignant breast cancer cell line. The functional analyses indicated the NIK upregulation contributed to tumor malignancy via cancer-associated fibroblasts (CAFs) attraction and partially anti-apoptotic activities. Additionally, the immunoprecipitation experiment revealed that the ubiquitination of NIK decreased in LM05 cells. The decline in NIK ubiquitination was attributed to the translational downregulation of cIAP1. Conclusions: Our study identified a dysregulated mechanism of NIK production by the suppression of NIK post-modification and cIAP1 translation. The aberrant NIK accumulation promoted tumor growth in the highly malignant breast cancer cell line.
Language	English
Publishing date	2023-04-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2091573-1
ISSN	1475-2867
ISSN	1475-2867
DOI	10.1186/s12935-023-02904-y
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Article ; Online: TNF receptor-associated factor 6 (TRAF6) plays crucial roles in multiple biological systems through polyubiquitination-mediated NF-κB activation.

Yamamoto, Mizuki / Gohda, Jin / Akiyama, Taishin / Inoue, Jun-Ichiro

Proceedings of the Japan Academy. Series B, Physical and biological sciences

2021 Volume 97, Issue 4, Page(s) 145–160

Abstract: NF-κB was first identified in 1986 as a B cell-specific transcription factor inducing immunoglobulin κ light chain expression. Subsequent studies revealed that NF-κB plays important roles in development, organogenesis, immunity, inflammation, and ... ...

Abstract	NF-κB was first identified in 1986 as a B cell-specific transcription factor inducing immunoglobulin κ light chain expression. Subsequent studies revealed that NF-κB plays important roles in development, organogenesis, immunity, inflammation, and neurological functions by spatiotemporally regulating cell proliferation, differentiation, and apoptosis in several cell types. Furthermore, studies on the signal pathways that activate NF-κB led to the discovery of TRAF family proteins with E3 ubiquitin ligase activity, which function downstream of the receptor. This discovery led to the proposal of an entirely new signaling mechanism concept, wherein K63-ubiquitin chains act as a scaffold for the signaling complex to activate downstream kinases. This concept has revolutionized ubiquitin studies by revealing the importance of the nonproteolytic functions of ubiquitin not only in NF-κB signaling but also in a variety of other biological systems. TRAF6 is the most diverged among the TRAF family proteins, and our studies uncovered its notable physiological and pathological functions.
MeSH term(s)	Animals ; Humans ; NF-kappa B/metabolism ; Signal Transduction ; TNF Receptor-Associated Factor 6/metabolism ; Ubiquitination
Chemical Substances	NF-kappa B ; TNF Receptor-Associated Factor 6
Language	English
Publishing date	2021-03-26
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	161781-3
ISSN	1349-2896 ; 0386-2208
ISSN (online)	1349-2896
ISSN	0386-2208
DOI	10.2183/pjab.97.009
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: [Dystrophia myotonica Type 1 associated with glioblastoma: a case report].

Katayama, Takashi / Kuroda, Jun-Ichiro / Ohta, Kazutaka / Inoue, Yasuteru / Ueda, Mitsuharu / Mukasa, Akitake

Rinsho shinkeigaku = Clinical neurology

2022 Volume 62, Issue 11, Page(s) 844–849

Abstract: This case involved a 65-year-old woman, who had been suffered from weakness in both legs for 10 years. She had not been diagnosed of dystrophia myotonica type 1 (DM1) despite her son's diagnosis of DM and her distinct facial features and gait anomaly. ... ...

Abstract	This case involved a 65-year-old woman, who had been suffered from weakness in both legs for 10 years. She had not been diagnosed of dystrophia myotonica type 1 (DM1) despite her son's diagnosis of DM and her distinct facial features and gait anomaly. During her son's recent clinical visit, she was finally suspected of having DM. She was sent to our institution, where a distinct muscle atrophy and grip myotonia were observed and a genetical examination was performed. The sequencing data confirmed her diagnosis of DM1 due to the distinct 230-900 CTG repeats found in the dystrophia myotonica protein kinase gene 3' untranslated region. A brain MRI revealed an abnormal lesion with irregular ring-enhancement at the right temporal lobe. Because of the steady growth of the lesion during one month observation, a surgical intervention was performed in our institution. The histopathological examination gave a diagnosis of glioblastoma multiforme (GBM). The clinical management of the patient required special cares during the perioperative periods due to the distinct pathological manifestation of DM. The risk of developing cancer in DM patients has been estimated about twice as much as general population. Since GBM developed in the DM patient is rarely reported, we present this rare case with a few insights: the difficulties of the clinical management of DM patients under the perioperative stress; the pathological contribution of DM to the malignant transformation of the glial cells.
MeSH term(s)	Humans ; Female ; Aged ; Glioblastoma/complications ; Glioblastoma/diagnostic imaging ; Glioblastoma/therapy ; Myotonic Dystrophy/complications ; Myotonic Dystrophy/diagnosis ; Myotonic Dystrophy/genetics ; Magnetic Resonance Imaging
Language	Japanese
Publishing date	2022-10-26
Publishing country	Japan
Document type	Case Reports ; English Abstract ; Journal Article
ZDB-ID	604200-4
ISSN	1882-0654 ; 0009-918X
ISSN (online)	1882-0654
ISSN	0009-918X
DOI	10.5692/clinicalneurol.cn-001758
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Article ; Online: Reactive oxygen species are associated with the inhibitory effect of N-(4-hydroxyphenyl)-retinamide on the entry of the severe acute respiratory syndrome-coronavirus 2.

Hayashi, Yasuhiro / Huang, Xuhao / Tanikawa, Takashi / Tanigawa, Kazunari / Yamamoto, Mizuki / Gohda, Jin / Inoue, Jun-Ichiro / Fukase, Koichi / Kabayama, Kazuya

Journal of biochemistry

2023 Volume 173, Issue 5, Page(s) 337–342

Abstract: N-(4-hydroxyphenyl)-retinamide (4-HPR) inhibits the dihydroceramide Δ4-desaturase 1 (DEGS1) enzymatic activity. We previously reported that 4-HPR suppresses the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spike protein-mediated membrane ... ...

Abstract	N-(4-hydroxyphenyl)-retinamide (4-HPR) inhibits the dihydroceramide Δ4-desaturase 1 (DEGS1) enzymatic activity. We previously reported that 4-HPR suppresses the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spike protein-mediated membrane fusion through a decrease in membrane fluidity in a DEGS1-independent manner. However, the precise mechanism underlying the inhibition of viral entry by 4-HPR remains unclear. In this study, we examined the role of reactive oxygen species (ROS) in the inhibition of membrane fusion by 4-HPR because 4-HPR is a well-known ROS-inducing agent. Intracellular ROS generation was found to be increased in the target cells in a cell-cell fusion assay after 4-HPR treatment, which was attenuated by the addition of the antioxidant, α-tocopherol (TCP). The reduction in membrane fusion susceptibility by 4-HPR treatment in the cell-cell fusion assay was alleviated by TCP addition. Furthermore, fluorescence recovery after photobleaching analysis showed that the lateral diffusion of glycosylphosphatidylinositol-anchored protein and SARS CoV-2 receptor was reduced by 4-HPR treatment and restored by TCP addition. These results indicate that the decrease in SARS-CoV-2 spike protein-mediated membrane fusion and membrane fluidity by 4-HPR was due to ROS generation. Taken together, these results demonstrate that ROS production is associated with the 4-HPR inhibitory effect on SARS-CoV-2 entry.
MeSH term(s)	Humans ; Fenretinide/pharmacology ; Reactive Oxygen Species/metabolism ; Antineoplastic Agents/pharmacology ; SARS-CoV-2/metabolism ; Apoptosis ; COVID-19 ; Oxidoreductases
Chemical Substances	Fenretinide (187EJ7QEXL) ; Reactive Oxygen Species ; spike protein, SARS-CoV-2 ; Antineoplastic Agents ; retinamide (BQC43T81DZ) ; Oxidoreductases (EC 1.-)
Language	English
Publishing date	2023-03-01
Publishing country	England
Document type	Journal Article
ZDB-ID	218073-x
ISSN	1756-2651 ; 0021-924X
ISSN (online)	1756-2651
ISSN	0021-924X
DOI	10.1093/jb/mvad020
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Article ; Online: Melanotic pilocytic astrocytoma.

Yamada, Rin / Inoue, Hirotaka / Kuroda, Jun-Ichiro / Furuta, Takuya / Moritsubo, Mayuko / Shinojima, Naoki / Mukasa, Akitake / Mikami, Yoshiki

Neuropathology : official journal of the Japanese Society of Neuropathology

2022 Volume 43, Issue 2, Page(s) 197–199

MeSH term(s)	Humans ; Astrocytoma/pathology ; Brain Neoplasms/pathology
Language	English
Publishing date	2022-09-25
Publishing country	Australia
Document type	Letter
ZDB-ID	1483794-8
ISSN	1440-1789 ; 0919-6544
ISSN (online)	1440-1789
ISSN	0919-6544
DOI	10.1111/neup.12871
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