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Article ; Online: Chronic Ethanol Intake Impairs Niacin Nutritional Status in Mice.

Mizutani, Amane / Goto, Chihiro / Fujigaki, Hidetsugu / Yamamoto, Yasuko / Saito, Kuniaki / Hatayama, Sho / Fukuwatari, Tsutomu

Journal of nutritional science and vitaminology

2024 Volume 70, Issue 1, Page(s) 1–8

Abstract: Niacin is involved in many biological reactions relating energy metabolism, redox reactions, DNA repair and longevity. Since niacin deficiency has been reported in alcoholic patients, and niacin coenzyme NAD is used as substrate to dehydrogenate ethanol ... ...

Abstract	Niacin is involved in many biological reactions relating energy metabolism, redox reactions, DNA repair and longevity. Since niacin deficiency has been reported in alcoholic patients, and niacin coenzyme NAD is used as substrate to dehydrogenate ethanol in the liver, ethanol consumption can be a factor to impair niacin nutritional status. We have recently established the niacin insufficient model mice using kynurenine 3-monooxygenase knock out (KMO
MeSH term(s)	Humans ; Mice ; Animals ; Niacin/metabolism ; Nutritional Status ; NAD/metabolism ; Alcoholism ; Niacinamide ; Body Weight
Chemical Substances	Niacin (2679MF687A) ; NAD (0U46U6E8UK) ; Niacinamide (25X51I8RD4)
Language	English
Publishing date	2024-02-22
Publishing country	Japan
Document type	Journal Article
ZDB-ID	191366-9
ISSN	1881-7742 ; 0301-4800
ISSN (online)	1881-7742
ISSN	0301-4800
DOI	10.3177/jnsv.70.1
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Article ; Online: Antibody testing for COVID-19 in patients with acute coronary syndrome in Aichi Prefecture.

Yoshinaga, Masataka / Muramatsu, Takashi / Fujigaki, Hidetsugu / Saito, Kuniaki / Izawa, Hideo

Fujita medical journal

2021 Volume 8, Issue 2, Page(s) 65–66

Language	English
Publishing date	2021-08-20
Publishing country	Japan
Document type	Journal Article
ZDB-ID	3011241-2
ISSN	2189-7255 ; 2189-7247
ISSN (online)	2189-7255
ISSN	2189-7247
DOI	10.20407/fmj.2020-032
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Article ; Online: Establishment of Model Mice to Evaluate Low Niacin Nutritional Status.

Mizutani, Amane / Sato, Miu / Fujigaki, Hidetsugu / Yamamoto, Yasuko / Saito, Kuniaki / Hatayama, Sho / Fukuwatari, Tsutomu

Journal of nutritional science and vitaminology

2023 Volume 69, Issue 5, Page(s) 305–313

Abstract: Niacin is involved in many biological reactions relating energy metabolism, redox reactions, DNA repair and longevity, and low NAD levels with aging and feeding high fat diets develop and progress age-related diseases. Although recent findings suggest ... ...

Abstract	Niacin is involved in many biological reactions relating energy metabolism, redox reactions, DNA repair and longevity, and low NAD levels with aging and feeding high fat diets develop and progress age-related diseases. Although recent findings suggest the requirement of niacin insufficient animal model to further study, appropriate animal models have not been established yet because niacin is biosynthesized from tryptophan via tryptophan-nicotinamide pathway. To establish model mice to evaluate niacin nutritional status, we used kynurenine 3-monooxygenase knock out (KMO
MeSH term(s)	Mice ; Animals ; Niacin/metabolism ; Nutritional Status ; Tryptophan/metabolism ; NAD/metabolism ; Niacinamide
Chemical Substances	Niacin (2679MF687A) ; Tryptophan (8DUH1N11BX) ; NAD (0U46U6E8UK) ; Niacinamide (25X51I8RD4)
Language	English
Publishing date	2023-11-08
Publishing country	Japan
Document type	Journal Article
ZDB-ID	191366-9
ISSN	1881-7742 ; 0301-4800
ISSN (online)	1881-7742
ISSN	0301-4800
DOI	10.3177/jnsv.69.305
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Article ; Online: Optimal timing of SARS-CoV-2 vaccination prior to cardiovascular surgery under cardiopulmonary bypass.

Hayashi, Ryosuke / Takami, Yoshiyuki / Fujigaki, Hidetsugu / Amano, Kentaro / Akita, Kiyotoshi / Yamana, Koji / Maekawa, Atsuo / Saito, Kuniaki / Takagi, Yasushi

The International journal of artificial organs

2024 Volume 47, Issue 3, Page(s) 147–154

Abstract: Background: mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became common. We investigated the optimal timing for inoculation against SARS-COV-2 in the candidates for cardiac surgery under cardiopulmonary bypass (CPB).! ...

Abstract	Background: mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became common. We investigated the optimal timing for inoculation against SARS-COV-2 in the candidates for cardiac surgery under cardiopulmonary bypass (CPB). Methods: In 100 patients with preoperative vaccination, who underwent CPB surgery between July 2021 and February 2022, the IgG against the receptor binding domain (RBD-IgG), with a threshold of >100 binding antibody unit (BAU)/mL for adequate immunity, was measured. Results: The vaccines, including 87 BNT162b2 (Pfizer/BioNTech) and 13 mRNA-1273 (Moderna), were inoculated at 98.8 ± 59.4 days before surgery. The median RBD-IgG titers before surgery, 1 day after surgery, and 1 month after surgery were 166.8, 100.0, and 84.0 BAU/mL, respectively. The standby interval (SBI) from the vaccination to the surgery showed a significantly negative correlations with the RBD-IgG titer before the surgery ( Conclusions: Although 40% of the RBD-IgG titers reduce 1 day after CPB surgery, the patients who received the SARS-COV-2 vaccination within an 81-day window prior to the surgery maintained a desirable RBD-IgG level, even up to 1 month after surgery. It may be important to schedule the surgery no later than 81 days after the vaccination.
MeSH term(s)	Humans ; Cardiopulmonary Bypass ; COVID-19 Vaccines ; SARS-CoV-2 ; BNT162 Vaccine ; COVID-19 ; Vaccination ; Immunoglobulin G
Chemical Substances	COVID-19 Vaccines ; BNT162 Vaccine ; Immunoglobulin G
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	80456-3
ISSN	1724-6040 ; 0391-3988
ISSN (online)	1724-6040
ISSN	0391-3988
DOI	10.1177/03913988241234475
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Article ; Online: Antibody testing for COVID-19 in patients with acute coronary syndrome in Aichi Prefecture

Masataka Yoshinaga / Takashi Muramatsu / Hidetsugu Fujigaki / Kuniaki Saito / Hideo Izawa

Fujita Medical Journal, Vol 8, Iss 2, Pp 65-

2022 Volume 66

Keywords	covid-19 ; japan ; acute coronary syndrome ; antibody ; screening ; Medicine (General) ; R5-920
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Fujita Medical Society
Document type	Article ; Online
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Article ; Online: Identification of 2',4',6'-Trihydroxyacetophenone as Promising Cysteine Conjugate Beta-Lyase Inhibitor for Preventing Cisplatin-Induced Nephrotoxicity.

Sukeda, Nao / Fujigaki, Hidetsugu / Ando, Tatsuya / Ando, Honomi / Yamamoto, Yasuko / Saito, Kuniaki

Molecular cancer therapeutics

2023 , Page(s) OF1–OF9

Abstract: Cisplatin is a chemotherapeutic agent used to treat many types of malignant tumors. However, irrespective of its potent anticancer properties and efficacy, nephrotoxicity is the dose-limiting factor of cisplatin treatment. Cisplatin infiltrates renal ... ...

Abstract	Cisplatin is a chemotherapeutic agent used to treat many types of malignant tumors. However, irrespective of its potent anticancer properties and efficacy, nephrotoxicity is the dose-limiting factor of cisplatin treatment. Cisplatin infiltrates renal tubular cells in the kidneys and is metabolized by cysteine conjugate-beta lyase 1 (CCBL1) to form highly reactive thiol-cisplatin; this may mediate cisplatin's nephrotoxicity. Therefore, CCBL1 inhibition may prevent cisplatin-induced nephrotoxicity. Using a high-throughput screening assay, we identified 2',4',6'-trihydroxyacetophenone (THA) as an inhibitor of CCBL1. THA inhibited human CCBL1 β-elimination activity in a concentration-dependent manner. We further investigated the preventive effect of THA on cisplatin-induced nephrotoxicity. THA attenuated the effect of cisplatin on the viability of confluent renal tubular cells (LLC-PK1 cells) but had no effect on cisplatin-induced reduction of proliferation in the tumor cell lines (LLC and MDA-MB-231). THA pretreatment significantly attenuated cisplatin-induced increases in blood urea nitrogen, creatinine, cell damage score, and apoptosis of renal tubular cells in mice in a dose-dependent manner. Furthermore, THA pretreatment attenuated cisplatin-induced nephrotoxicity without compromising its antitumor activities in mice bearing subcutaneous syngeneic LLC tumors. THA could help prevent cisplatin-induced nephrotoxicity and may provide a new strategy for cisplatin-inclusive cancer treatments.
Language	English
Publishing date	2023-06-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-22-0564
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Article ; Online: Identification of 2',4',6'-trihydroxyacetophenone as promising cysteine conjugate beta-lyase inhibitor for preventing cisplatin-induced nephrotoxicity.

Sukeda, Nao / Fujigaki, Hidetsugu / Ando, Tatsuya / Ando, Honomi / Yamamoto, Yasuko / Saito, Kuniaki

Molecular cancer therapeutics

2023

Abstract	Cisplatin is a chemotherapeutic agent used to treat many types of malignant tumors. However, irrespective of its potent anticancer properties and efficacy, nephrotoxicity is the dose-limiting factor of cisplatin treatment. Cisplatin infiltrates renal tubular cells in the kidneys and is metabolized by cysteine conjugate-beta lyase 1 (CCBL1) to form highly reactive thiol-cisplatin; this may mediate cisplatin's nephrotoxicity. Therefore, CCBL1 inhibition may prevent cisplatin-induced nephrotoxicity. Using a high-throughput screening assay, we identified 2',4',6'-trihydroxyacetophenone (THA) as an inhibitor of CCBL1. THA inhibited human CCBL1 beta-elimination activity in a concentration-dependent manner. We further investigated the preventive effect of THA on cisplatin-induced nephrotoxicity. THA attenuated the effect of cisplatin on the viability of confluent renal tubular cells (LLC-PK1 cells) but had no effect on cisplatin-induced reduction of proliferation in the tumor cell lines (LLC and MDA-MB-231). THA pre-treatment significantly attenuated cisplatin-induced increases in blood urea nitrogen, creatinine, cell damage score, and apoptosis of renal tubular cells in mice in a dose-dependent manner. Furthermore, THA pre-treatment attenuated cisplatin-induced nephrotoxicity without compromising its anti-tumor activities in mice bearing subcutaneous syngeneic LLC tumors. THA could help prevent cisplatin-induced nephrotoxicity and may provide a new strategy for cisplatin-inclusive cancer treatments.
Language	English
Publishing date	2023-05-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-22-0564
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Article ; Online: Indoleamine 2,3-dioxygenase 2 deficiency associates with autism-like behavior via dopaminergic neuronal dysfunction.

Ishikawa, Masaki / Yamamoto, Yasuko / Wulaer, Bolati / Kunisawa, Kazuo / Fujigaki, Hidetsugu / Ando, Tatsuya / Kimura, Hiroki / Kushima, Itaru / Arioka, Yuko / Torii, Youta / Mouri, Akihiro / Ozaki, Norio / Nabeshima, Toshitaka / Saito, Kuniaki

The FEBS journal

2024 Volume 291, Issue 5, Page(s) 945–964

Abstract: Indoleamine 2,3-dioxygenase 2 (IDO2) is an enzyme of the tryptophan-kynurenine pathway that is constitutively expressed in the brain. To provide insight into the physiological role of IDO2 in the brain, behavioral and neurochemical analyses in IDO2 ... ...

Abstract	Indoleamine 2,3-dioxygenase 2 (IDO2) is an enzyme of the tryptophan-kynurenine pathway that is constitutively expressed in the brain. To provide insight into the physiological role of IDO2 in the brain, behavioral and neurochemical analyses in IDO2 knockout (KO) mice were performed. IDO2 KO mice showed stereotyped behavior, restricted interest and social deficits, traits that are associated with behavioral endophenotypes of autism spectrum disorder (ASD). IDO2 was colocalized immunohistochemically with tyrosine-hydroxylase-positive cells in dopaminergic neurons. In the striatum and amygdala of IDO2 KO mice, decreased dopamine turnover was associated with increased α-synuclein level. Correspondingly, levels of downstream dopamine D1 receptor signaling molecules such as brain-derived neurotrophic factor and c-Fos positive proteins were decreased. Furthermore, decreased abundance of ramified-type microglia resulted in increased dendritic spine density in the striatum of IDO2 KO mice. Both chemogenetic activation of dopaminergic neurons and treatment with methylphenidate, a dopamine reuptake inhibitor, ameliorated the ASD-like behavior of IDO2 KO mice. Sequencing analysis of exon regions in IDO2 from 309 ASD samples identified a rare canonical splice site variant in one ASD case. These results suggest that the IDO2 gene is, at least in part, a factor closely related to the development of psychiatric disorders.
MeSH term(s)	Animals ; Humans ; Mice ; Autism Spectrum Disorder/genetics ; Autistic Disorder ; Dopamine ; Dopaminergic Neurons ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics
Chemical Substances	Dopamine (VTD58H1Z2X) ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; IDO2 protein, mouse
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.17019
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Article ; Online: Effects of cardiopulmonary bypass on immunoglobulin G antibody titres after SARS-CoV2 vaccination.

Hayashi, Ryosuke / Takami, Yoshiyuki / Fujigaki, Hidetsugu / Amano, Kentaro / Sakurai, Yusuke / Akita, Kiyotoshi / Yamana, Koji / Maekawa, Atsuo / Saito, Kuniaki / Takagi, Yasushi

Interactive cardiovascular and thoracic surgery

2022 Volume 35, Issue 3

Abstract: Objectives: Patients with cardiovascular disease are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Although SARS-CoV2 vaccination may be effective, its impact on surgical patients is not well studied. We ... ...

Abstract	Objectives: Patients with cardiovascular disease are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Although SARS-CoV2 vaccination may be effective, its impact on surgical patients is not well studied. We investigated the effects of cardiovascular surgery, especially under cardiopulmonary bypass (CPB), on the antibody titres after SARS-CoV2 vaccination. Methods: A prospective observational study was designed for patients undergoing surgery between July and November 2021. The immunoglobulin G against the receptor-binding domain was measured and antibody preserved rate (APR) was calculated from perioperative titres comparison. Results: Enrolled 63 study patients were divided into 39 undergoing surgery with CPB (Group CPB) and 24 without CPB (Group None). Preoperative vaccines were BNT162b2 (Pfizer/BioNTech) (n = 58, 92%) and mRNA-1273 (Moderna) (n = 5, 8%). While immunoglobulin G against the receptor-binding domain titres did not significantly decrease after surgery in Group None, they decreased significantly in Group CPB from 21.80 [11.15, 37.85] to 11.95 [6.80, 18.18] U/ml (P < 0.001) a day after surgery, 11.40 [7.85, 22.65] U/ml (P < 0.001) 14 days after surgery and 7.60 [4.80, 17.60] U/ml (P < 0.001) a month after surgery. The APRs a day after the surgery were significantly lower in Group CPB (0.46 [0.41, 0.60]) than in Group None (0.80 [0.68, 0.87]) (P < 0.001). Conclusions: The SARS-CoV2 antibody titres significantly decreased with lower APRs immediately after surgery under CPB. Based on our informative results, careful considerations of vaccination schedule might be required for surgery under CPB.
MeSH term(s)	BNT162 Vaccine ; COVID-19 ; Cardiopulmonary Bypass ; Humans ; Immunoglobulin G ; RNA, Viral ; SARS-CoV-2 ; Vaccination
Chemical Substances	Immunoglobulin G ; RNA, Viral ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2022-05-06
Publishing country	England
Document type	Journal Article ; Observational Study
ZDB-ID	2095298-3
ISSN	1569-9285 ; 1569-9293
ISSN (online)	1569-9285
ISSN	1569-9293
DOI	10.1093/icvts/ivac123
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Article ; Online: Deficiency of kynurenine 3-monooxygenase exacerbates impairment of prepulse inhibition induced by phencyclidine.

Kubota, Hisayoshi / Kunisawa, Kazuo / Niijima, Moe / Hirakawa, Mami / Mori, Yuko / Hasegawa, Masaya / Fujigaki, Suwako / Fujigaki, Hidetsugu / Yamamoto, Yasuko / Saito, Kuniaki / Nabeshima, Toshitaka / Mouri, Akihiro

Biochemical and biophysical research communications

2022 Volume 629, Page(s) 142–151

Abstract: Phencyclidine (PCP) causes mental symptoms that closely resemble schizophrenia through the inhibition of the glutamatergic system. The kynurenine (KYN) pathway (KP) generates metabolites that modulate glutamatergic systems such as kynurenic acid (KA), ... ...

Abstract	Phencyclidine (PCP) causes mental symptoms that closely resemble schizophrenia through the inhibition of the glutamatergic system. The kynurenine (KYN) pathway (KP) generates metabolites that modulate glutamatergic systems such as kynurenic acid (KA), quinolinic acid (QA), and xanthurenic acid (XA). Kynurenine 3-monooxygenase (KMO) metabolizes KYN to 3-hydroxykynurenine (3-HK), an upstream metabolite of QA and XA. Clinical studies have reported lower KMO mRNA and higher KA levels in the postmortem brains of patients with schizophrenia and exacerbation of symptoms in schizophrenia by PCP. However, the association between KMO deficiency and PCP remains elusive. Here, we demonstrated that a non-effective dose of PCP induced impairment of prepulse inhibition (PPI) in KMO KO mice. KA levels were increased in the prefrontal cortex (PFC) and hippocampus (HIP) of KMO KO mice, but 3-HK levels were decreased. In wild-type C57BL/6 N mice, the PPI impairment induced by PCP is exacerbated by KA, while attenuated by 3-HK, QA and XA. Taken together, KMO KO mice were vulnerable to the PPI impairment induced by PCP through an increase in KA and a decrease in 3-HK, suggesting that an increase in the ratio of KA to 3-HK (QA and XA) may play an important role in the pathophysiology of schizophrenia.
MeSH term(s)	Animals ; Kynurenic Acid/metabolism ; Kynurenine/metabolism ; Kynurenine 3-Monooxygenase/genetics ; Kynurenine 3-Monooxygenase/metabolism ; Mice ; Mice, Inbred C57BL ; Phencyclidine ; Prepulse Inhibition ; Quinolinic Acid/metabolism ; RNA, Messenger
Chemical Substances	RNA, Messenger ; Kynurenine (343-65-7) ; Kynurenine 3-Monooxygenase (EC 1.14.13.9) ; Quinolinic Acid (F6F0HK1URN) ; Kynurenic Acid (H030S2S85J) ; Phencyclidine (J1DOI7UV76)
Language	English
Publishing date	2022-09-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2022.09.003
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