著者

Tomoyuki Furuya Ryuichi Nishihama Kimitsune Ishizaki Takayuki Kohchi Hiroo Fukuda Yuki Kondo

出版者

Japanese Society for Plant Biotechnology

雑誌

Plant Biotechnology (ISSN:13424580)

巻号頁・発行日

pp.21.1219a, (Released:2022-02-18)

参考文献数

43

被引用文献数

6

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Plants precisely coordinate the balance between cell proliferation and differentiation to ensure the continuous development. In Arabidopsis thaliana, members of glycogen synthase kinase 3 (GSK3) family, which are highly conserved serine/threonine protein kinases among eukaryotes, play important roles in regulating cell proliferation and differentiation during various developmental processes. However, functional roles of GSK3s in the plant lineages except angiosperms remain to be elucidated. Here, we utilized a model liverwort, Marchantia polymorpha, for studies of GSK3, because it has a single GSK3-like kinase, MpGSK. When M. polymorpha was treated with a chemical compound, bikinin, which is known as a specific inhibitor for GSK3-like kinases, growth and morphologies were altered with an expansion of the meristematic region. Similarly, Mpgsk loss-of-function mutants accumulated undifferentiated cell mass with no differentiated tissues. By contrast, overexpression of MpGSK reduced the size of the meristem region. These results suggest that MpGSK plays important roles as a regulator for the balance between cell differentiation and proliferation in M. polymorpha.

著者

Tomoaki Ukaji Tetsuya Ishikawa Hidehiko Nakamura Yukiko Mizutani Kouta Yamada Masatoshi Shimura Yuki Kondo Yohei Tamura Yuri Koshikawa Itaru Hisauchi Shiro Nakahara Yuji Itabashi Sayuki Kobayashi Isao Taguchi

出版者

The Japanese Circulation Society

雑誌

Circulation Reports (ISSN:24340790)

巻号頁・発行日

pp.CR-22-0120, (Released:2023-03-15)

参考文献数

26

被引用文献数

1

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Background: The prognostic impact of CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-HS scores on clinical outcomes after drug-eluting stent (DES) placement has not been fully elucidated.Methods and Results: The present study was a retrospective, non-randomized, single-center, and lesion-based study. Target lesion failure (TLF), comprising cardiac death, non-fatal myocardial infarction, and target vessel revascularization, occurred in 7.1% of 872 consecutive de novo coronary lesions in 586 patients. These patients were electively and exclusively treated by DESs from January 2016 to January 2022 until July 2022 with a mean (±SD) observational interval of 411±438 days. Multivariate Cox proportional hazard analysis revealed that CHA2DS2-VASc-HS scores ≥7 (hazard ratio [HR] 1.800; 95% CI 1.06–3.05; P=0.029) was a significant predictor of cumulative TLF among 24 variables evaluated. CHADS2 scores ≥2 (HR 3.213; 95% CI 1.32–7.80; P=0.010) and CHA2DS2-VASc scores ≥5 (HR 1.980; 95% CI 1.10–3.55; P=0.022) were also significant in the multivariate analysis. Pairwise comparisons of receiver operating characteristic curves for CHADS2 score ≥2, CHA2DS2-VASc score ≥5, and CHA2DS2-VASc-HS score ≥7 showed they were equivalent in terms of predicting the incidence of TLF, with areas under the curve of 0.568, 0.575, and 0.573, respectively.Conclusions: All 3 cardiocerebrovascular thromboembolism risk scores were strong predictors of the incidence of cumulative mid-term TLF after elective DES placement, with cut-off values of 2, 5, and 7, respectively, and equivalent prognostic impacts.

著者

Reiko Fukuda Tetsuya Ishikawa Yuki Kondo Masatoshi Shimura Yukiko Mizutani Shiro Nakahara Isao Taguchi

出版者

The Japanese Circulation Society

雑誌

Circulation Reports (ISSN:24340790)

巻号頁・発行日

vol.3, no.1, pp.66-67, 2021-01-08 (Released:2021-01-08)

参考文献数

2

著者

Yoichi Ishitsuka Yuki Kondo Daisuke Kadowaki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.43, no.2, pp.195-206, 2020-02-01 (Released:2020-02-01)

参考文献数

154

被引用文献数

26

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Acetaminophen (paracetamol, N-acetyl-p-aminophenol; APAP) is the most popular analgesic/antipyretic agent in the world. APAP has been regarded as a safer drug compared with non-steroidal anti-inflammatory drugs (NSAIDs) particularly in terms of lower risks of renal dysfunction, gastrointestinal injury, and asthma/bronchospasm induction, even in high-risk patients such as the elderly, children, and pregnant women. On the other hand, the recent increasing use of APAP has raised concerns about its toxicity. In this article, we review recent pharmacological and toxicological findings about APAP from basic, clinical, and epidemiological studies, including spontaneous drug adverse events reporting system, especially focusing on drug-induced asthma and pre-and post-natal closure of ductus arteriosus. Hepatotoxicity is the greatest fault of APAP and the most frequent cause of drug-induced acute liver failure in Western countries. However, its precise mechanism remains unclear and no effective cure beyond N-acetylcysteine has been developed. Recent animal and cellular studies have demonstrated that some cellular events, such as c-jun N-terminal kinase (JNK) pathway activation, endoplasmic reticulum (ER) stress, and mitochondrial oxidative stress may play important roles in the development of hepatitis. Herein, the molecular mechanisms of APAP hepatotoxicity are summarized. We also discuss the not-so-familiar “dark side” of APAP as an otherwise safe analgesic/antipyretic drug.

著者

Yuki Kondo Sachimi Yoshihashi Kayo Mimori Ruri Ogihara Yoshinori Kanehama Yoshiyuki Maki Shin Enosawa Kouichi Kurose Takahiro Iwao Katsunori Nakamura Tamihide Matsunaga

出版者

日本薬物動態学会 会長/日本薬物動態学会 DMPK編集委員長

雑誌

Drug Metabolism and Pharmacokinetics (ISSN:13474367)

巻号頁・発行日

pp.DMPK-14-RG-022, (Released:2014-04-29)

参考文献数

22

被引用文献数

9

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This study aimed to establish culture conditions which are able to give the differentiation of induced pluripotent (iPS) cells to the hepatocytes. To this end, we examined the usefulness of culture medium containing the components involved in the intermediary metabolism in the liver. More specifically, we examined the effect of the 'modified L-15 medium' containing galactose, phenylalanine and ornitine, but deprived of glucose, tyrosine, arginine and pyruvic acid. The medium was altered according to changes in the expression of enzymes that participate in liver-specific pathways. After 25 days of differentiation, the differentiated cells expressed hepatocyte markers and drug-metabolizing enzymes. These expression levels were increased using modified L-15 medium. The survival of human fetal liver cells and the death of human fibroblasts were observed during culture in modified L-15 medium. Most of the cells that differentiated from human iPS cells using modified L-15 medium were stained by anti-human albumin antibody. These results suggest that iPS cells can be converted to high purity-differentiated hepatocytes by cultivating them in modified L-15 medium.

著者

Tomoyuki Furuya Yuki Kondo

出版者

The Genetics Society of Japan

雑誌

Genes & Genetic Systems (ISSN:13417568)

巻号頁・発行日

pp.23-00029, (Released:2023-06-16)

参考文献数

21

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Members of a plant-specific BES/BZR transcription factor (TF) family including BRI1-EMS-SUPPRESSOR 1 (BES1) and BRASSINAZOLE-RESISTANT 1 (BZR1) regulate various developmental processes and environmental responses. Recently, we reported that BES1/BZR1 Homolog 3 (BEH3) exhibited a competitive effect toward other BES/BZR TFs. In this study, we analyzed transcriptome profiles in BEH3-overexpressing plants and compared them with those of BES1 and BZR1 double gain-of-function mutants. We identified 46 differentially expressed genes (DEGs), which were downregulated in the gain-of-function mutants of BES1 and BZR1 but upregulated upon BEH3 overexpression. In these DEGs, putative BES1 and BZR1 direct-targeted genes were highly enriched. In addition, these DEGs contained not only known brassinosteroid biosynthetic enzymes, but also some NAC TFs, which negatively regulate brassinosteroid-inactivating enzymes. Moreover, the iron sensor and the iron-deficient response-related bHLH TFs were also included. Taken together, our findings indicate that a competitive relationship between BEH3 and other BES/BZR TFs exists in various BES/BZR binding target genes.

著者

Tomoyuki Furuya Ryuichi Nishihama Kimitsune Ishizaki Takayuki Kohchi Hiroo Fukuda Yuki Kondo

出版者

Japanese Society for Plant Biotechnology

雑誌

Plant Biotechnology (ISSN:13424580)

巻号頁・発行日

vol.39, no.1, pp.65-72, 2022-03-25 (Released:2022-03-25)

参考文献数

43

被引用文献数

6

---

Plants precisely coordinate the balance between cell proliferation and differentiation to ensure the continuous development. In Arabidopsis thaliana, members of glycogen synthase kinase 3 (GSK3) family, which are highly conserved serine/threonine protein kinases among eukaryotes, play important roles in regulating cell proliferation and differentiation during various developmental processes. However, functional roles of GSK3s in the plant lineages except angiosperms remain to be elucidated. Here, we utilized a model liverwort, Marchantia polymorpha, for studies of GSK3, because it has a single GSK3-like kinase, MpGSK. When M. polymorpha was treated with a chemical compound, bikinin, which is known as a specific inhibitor for GSK3-like kinases, growth and morphologies were altered with an expansion of the meristematic region. Similarly, Mpgsk loss-of-function mutants accumulated undifferentiated cell mass with no differentiated tissues. By contrast, overexpression of MpGSK reduced the size of the meristem region. These results suggest that MpGSK plays important roles as a regulator for the balance between cell differentiation and proliferation in M. polymorpha.

著者

Yuki Kondo

出版者

Japanese Society for Plant Biotechnology

雑誌

Plant Biotechnology (ISSN:13424580)

巻号頁・発行日

vol.39, no.1, pp.59-64, 2022-03-25 (Released:2022-03-25)

参考文献数

28

被引用文献数

1 6

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For permanent secondary growth in plants, cell proliferation and differentiation should be strictly controlled in the vascular meristem consisting of (pro)cambial cells. A peptide hormone tracheary element differentiation inhibitory factor (TDIF) functions to inhibit xylem differentiation, while a plant hormone brassinosteroid (BR) promotes xylem differentiation in (pro)cambial cells. However, it remains unclear how TDIF and BR cooperate to regulate xylem differentiation for the proper maintenance of the vascular meristem. In this study, I developed an easy evaluation method for xylem differentiation frequency in a vascular induction system Vascular cell Induction culture System Using Arabidopsis Leaves (VISUAL) by utilizing a xylem-specific luciferase reporter line. In this quantitative system, TDIF suppressed and BR promoted xylem differentiation in a dose-dependent manner, respectively. Moreover, simultaneous treatment of TDIF and BR with (pro)cambial cells revealed that they can cancel their each other’s effect on xylem differentiation, suggesting a competitive relationship between TDIF and BR. Thus, mutual inhibition of “ON” and “OFF” signal enables the fine-tuned regulation of xylem differentiation in the vascular meristem.

著者

Sakura Nakatani Keisuke Maeda Junji Akagi Misato Ichigi Marina Murakami Yoshihiko Harada Sara Utsumi Masaki Fukunaga Yuki Narita Yuki Kondo Yoichi Ishitsuka Tetsumi Irie Daisuke Kadowaki Sumio Hirata

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.8, pp.1350-1357, 2019-08-01 (Released:2019-08-01)

参考文献数

30

被引用文献数

1 7

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Creatinine (Cr) levels are strongly affected by muscle mass, and the estimated glomerular filtration rate (eGFR), a measure based on serum creatinine (SCr), is often overestimated in patients with sarcopenia. To evaluate the coefficient of determination (R2) between eGFR and the actual measured value, we performed a linear regression analysis of a modified GFR (mGFR: measured Cr clearance × 0.715) and various renal function estimates adjusted for muscle mass in 19 patients with sarcopenia. The eGFR values based on SCr (eGFRcr) were higher than those based on mGFR, although a high R2 (0.704; p < 0.001) was found between these values. There was no deviation between eGFR based on serum cystatin C (eGFRcys) and mGFR, although the R2 value 0.691 was equivalent to that of eGFRcr. In the equation used to calculate eGFRcr not adjusted for body surface area (mL/min), muscle mass parameters obtained from bioelectrical impedance analysis were used instead of actual body weight to recalculate the eGFRcr. The R2 between this eGFRcr and mGFR did not improve, although there was less deviation. However, assuming that all patients were female by using female coefficients for all patients, the R2 between eGFRcr-fcc (eGFRcr with female coefficient correction) and mGFR improved and was the highest (0.808) on substitution of appendicular skeletal muscle mass. The correlation between eGFRcr-fcc and mGFR improved over eGFRcys when muscle mass was substituted for body weight in the equation used to estimate eGFR in patients with sarcopenia and sex differences were removed.