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Article ; Online: New Mechanistic Insight Into Biased Signaling of Proteinase-Activated Receptor 1.

Hirano, Katsuya

Arteriosclerosis, thrombosis, and vascular biology

2024 Volume 44, Issue 3, Page(s) 617–619

MeSH term(s)	Thrombin/metabolism ; Receptor, PAR-1/metabolism ; Thrombomodulin ; Signal Transduction ; Phosphorylation
Chemical Substances	Thrombin (EC 3.4.21.5) ; Receptor, PAR-1 ; Thrombomodulin
Language	English
Publishing date	2024-01-25
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.123.320616
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Article ; Online: Effects of mifepristone on adipocyte differentiation in mouse 3T3-L1 cells.

Hashimoto, Takeshi / Hirano, Katsuya

Cellular & molecular biology letters

2024 Volume 29, Issue 1, Page(s) 45

Abstract: Background: Both glucocorticoid receptor and peroxisome proliferator-activated receptor-γ (PPARγ) play a critical role in adipocyte differentiation. Mifepristone is not only an antagonist of the glucocorticoid receptor but also an agonist of PPARγ. ... ...

Abstract	Background: Both glucocorticoid receptor and peroxisome proliferator-activated receptor-γ (PPARγ) play a critical role in adipocyte differentiation. Mifepristone is not only an antagonist of the glucocorticoid receptor but also an agonist of PPARγ. Therefore, the present study investigated the effect of mifepristone on adipocyte differentiation. Methods: Mouse 3T3-L1 cells were used as a model for adipocyte differentiation. The lipid droplet formation was evaluated with Bodipy493/503 staining and the expression of adipocyte markers [adiponectin and adipocyte fatty acid binding protein-4 (Fabp4)] was evaluated with quantitative PCR and immunoblot analyses for indication of adipocyte differentiation. siRNA and neutralizing antibodies were used to elucidate the molecular mechanism of mifepristone-induced adipocyte differentiation. Luciferase reporter assay was used to examine the effect of mifepristone on the promoter activity of PPAR-response element (PPRE). The DNA microarray analysis was used to characterize the transcriptome of the mifepristone-induced adipocytes. In vivo adipogenic effect of mifepristone was examined in mice. Results: Mifepristone not only enhanced adipocyte differentiation induced by the conventional protocol consisting of insulin, dexamethasone and 3-isobutyl-1-methylxanthine but also induced adipocyte differentiation alone, as evidenced by lipid droplets formation and induction of the expression of adiponectin and Fabp4. These effects were inhibited by an adiponectin-neutralizing antibody and a PPARγ antagonist. Mifepristone activated the promoter activity of PPRE in a manner sensitive to PPARγ antagonist. A principal component analysis (PCA) of DNA microarray data revealed that the mifepristone-induced adipocytes represent some characteristics of the in situ adipocytes in normal adipose tissues to a greater extent than those induced by the conventional protocol. Mifepristone administration induced an increase in the weight of epididymal, perirenal and gluteofemoral adipose tissues. Conclusions: Mifepristone alone is capable of inducing adipocyte differentiation in 3T3-L1 cells and adipogenesis in vivo. PPARγ plays a critical role in the mifepristone-induced adipocyte differentiation. Mifepristone-induced adipocytes are closer to the in situ adipocytes than those induced by the conventional protocol. The present study proposes a single treatment with mifepristone as a novel protocol to induce more physiologically relevant adipocytes in 3T3-L1 cells than the conventional protocol.
MeSH term(s)	Mice ; Animals ; Adiponectin/metabolism ; Adiponectin/pharmacology ; Mifepristone/pharmacology ; Mifepristone/metabolism ; PPAR gamma/metabolism ; 3T3-L1 Cells ; Receptors, Glucocorticoid/metabolism ; Cell Differentiation ; Adipogenesis/genetics ; Adipocytes/metabolism
Chemical Substances	Adiponectin ; Mifepristone (320T6RNW1F) ; PPAR gamma ; Receptors, Glucocorticoid
Language	English
Publishing date	2024-03-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2108724-6
ISSN	1689-1392 ; 1689-1392
ISSN (online)	1689-1392
ISSN	1689-1392
DOI	10.1186/s11658-024-00559-9
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Article ; Online: Critical role of Rho proteins in myosin light chain di-phosphorylation during early phase of endothelial barrier disruption.

Hirano, Mayumi / Hirano, Katsuya

The journal of physiological sciences : JPS

2022 Volume 72, Issue 1, Page(s) 32

Abstract: We previously reported the Rho-associated coiled-coil containing protein kinase (ROCK)-mediated di-phosphorylation of myosin light chain (MLC) and actin bundle formation at the cell periphery as early events of the endothelial barrier disruption. We ... ...

Abstract	We previously reported the Rho-associated coiled-coil containing protein kinase (ROCK)-mediated di-phosphorylation of myosin light chain (MLC) and actin bundle formation at the cell periphery as early events of the endothelial barrier disruption. We herein examined the role of RhoA during early events of barrier disruption. Treatment of cultured porcine aortic endothelial cells with simvastatin prevented the decrease in trans-endothelial electrical resistance, MLC di-phosphorylation and peripheral actin bundle formation seen 3 min after thrombin stimulation. Co-treatment with geranylgeranyl pyrophosphate rescued the thrombin-induced events. Thrombin increased a GTP-bound form of RhoA and phosphorylation of myosin phosphatase target subunit 1 (MYPT1) at the ROCK site. The intracellular introduction of the inhibitory protein of RhoA inhibited the thrombin-induced di-phosphorylation of MLC. However, knockdown of either one of RhoA, RhoB or RhoC failed to inhibit thrombin-induced MLC di-phosphorylation. The findings suggest that Rho proteins play a critical role during early events of thrombin-induced barrier disruption.
MeSH term(s)	Animals ; Swine ; Myosin Light Chains ; Actins ; Thrombin/pharmacology ; Endothelial Cells
Chemical Substances	Myosin Light Chains ; Actins ; Thrombin (EC 3.4.21.5)
Language	English
Publishing date	2022-12-07
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2234472-X
ISSN	1880-6562 ; 1880-6546
ISSN (online)	1880-6562
ISSN	1880-6546
DOI	10.1186/s12576-022-00857-x
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Article ; Online: Short-term and Long-term Outcomes After Laparoscopic Surgery for Pathological Stage T4a and T4b Colon Cancer.

Ishiyama, Yasuhiro / Hirano, Yasumitsu / Tanaka, Hiroto / Fujii, Takatsugu / Okazaki, Naoto / Hiranuma, Chikashi / Deguchi, Katsuya

Journal of gastrointestinal cancer

2024

Language	English
Publishing date	2024-01-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2452514-5
ISSN	1941-6636 ; 1559-0739 ; 1941-6628 ; 1537-3649
ISSN (online)	1941-6636 ; 1559-0739
ISSN	1941-6628 ; 1537-3649
DOI	10.1007/s12029-024-01017-7
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Zs.A 2184: Show issues

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Article ; Online: Assessing Interferon Regulatory Factor 4 Complex Formation: Differential Behavior of Homocomplexes Versus Heterocomplexes Induced by Mutations.

Li, Yupeng / Hirano, Setoka / Sato, Katsuya / Osawa, Masatake / Nagaoka, Hitoshi

Biochemistry

2024 Volume 63, Issue 6, Page(s) 767–776

Abstract: Interferon regulatory factor 4 (IRF4) is a crucial transcription factor that plays a vital role in lymphocyte development, including in the fate-determining steps in terminal differentiation. It is also implicated in the development of lymphoid tumors ... ...

Abstract	Interferon regulatory factor 4 (IRF4) is a crucial transcription factor that plays a vital role in lymphocyte development, including in the fate-determining steps in terminal differentiation. It is also implicated in the development of lymphoid tumors such as multiple myeloma and adult T-cell leukemia. IRF4 can form a homodimer and multiple heterocomplexes with other transcription factors such as purine-rich box1 and activator protein 1. Each protein complex binds to specific DNA sequences to regulate a distinct set of genes. However, the precise relationship among these complex formations remains unclear. Herein, we investigated the abilities of IRF4 proteins with functional mutations in the IRF-association domain and autoinhibitory region to form complexes using luciferase reporter assays. The assays allowed us to selectively assess the activity of each complex. Our results revealed that certain IRF-association domain mutants, previously known to have impaired heterocomplex formation, maintained or even enhanced homodimer activity. This discrepancy suggests that the mutated amino acid residues selectively influence homodimer activity. Conversely, a phosphomimetic serine mutation in the autoinhibitory region displayed strong activating effects in all complexes. Furthermore, we observed that partner proteins involved in heterocomplex formation could disrupt the activity of the homodimer, suggesting a potential competition between homocomplexes and heterocomplexes. Our findings provide new insights into the mechanistic function of IRF4.
MeSH term(s)	Base Sequence ; Gene Expression Regulation ; Interferon Regulatory Factor-3/genetics ; Interferon Regulatory Factor-3/metabolism ; Interferon Regulatory Factors/genetics ; Interferon Regulatory Factors/metabolism ; Mutation ; Transcription Factor AP-1/metabolism ; Humans ; HEK293 Cells
Chemical Substances	Interferon Regulatory Factor-3 ; Interferon Regulatory Factors ; Transcription Factor AP-1
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/acs.biochem.3c00512
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Zs.A 217: Show issues

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Article ; Online: Reducing anastomotic leakage in TaTME by mucosal coverage of staple lines: a pilot study with preliminary results.

Deguchi, Katsuya / Hirano, Yasumitsu / Okazaki, Naoto

BMC surgery

2023 Volume 23, Issue 1, Page(s) 155

Abstract: Purpose: We have performed a single stapled anastomosis with double purse-string sutures as a Trans anal Total Mesorectal Excision (TaTME) reconstruction for low rectal cancer. We report an attempt to control local infection and reduce anastomotic ... ...

Abstract	Purpose: We have performed a single stapled anastomosis with double purse-string sutures as a Trans anal Total Mesorectal Excision (TaTME) reconstruction for low rectal cancer. We report an attempt to control local infection and reduce anastomotic leakage (AL) at this anastomotic site. Patients and methods: Fifty-one patients who underwent TaTME for low rectal cancer from April 2021 to October 2022 were included. TaTME was performed by two teams, and reconstruction was performed by anastomosis with a single stapling technique (SST). After the anastomosis was thoroughly cleaned, Z sutures were placed parallel to the staple line to suture the mucosa on the oral and anal side of the staple line and to cover the staple line circumferentially. Data on operative time, Distal Margin (DM), recurrence and postoperative complications including AL were prospectively collected. Results: The mean age of patients was 67 years. There were 36 males and 15 females. The overall mean operative time was 283.1 min, and the mean Distal Margin was 2.2 cm. Postoperative complications were observed in 5.9% of the patients, but no AL was observed, nor any serious complications with Clavien-Dindo ≥ 3 grade. Of the 49 cases excluding Stage 4, postoperative recurrence was observed in 2 cases (4.9%). Conclusion: In patients with lower rectal cancer who underwent TaTME, additional mucosal coverage of the anastomotic staple line by transanal manipulation after reconstruction may be associated with a reduction in the incidence of postoperative AL. Further studies including late anastomotic complications are needed.
MeSH term(s)	Male ; Female ; Humans ; Aged ; Anastomotic Leak/etiology ; Rectum/surgery ; Pilot Projects ; Rectal Neoplasms/surgery ; Rectal Neoplasms/complications ; Postoperative Complications/epidemiology ; Laparoscopy/methods ; Treatment Outcome
Language	English
Publishing date	2023-06-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2050442-1
ISSN	1471-2482 ; 1471-2482
ISSN (online)	1471-2482
ISSN	1471-2482
DOI	10.1186/s12893-023-02071-x
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Article: [Role of microvasculature in regulation of coronary blood flow].

Hirano, Katsuya

Nihon rinsho. Japanese journal of clinical medicine

2016 Volume 74 Suppl 4 Pt 1, Page(s) 57–61

MeSH term(s)	Coronary Circulation/physiology ; Humans ; Microvessels/physiology ; Muscle, Smooth, Vascular/physiology
Language	Japanese
Publishing date	2016-06-20
Publishing country	Japan
Document type	Journal Article
ZDB-ID	390903-7
ISSN	0047-1852
ISSN	0047-1852
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Zs.A 429: Show issues

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Article ; Online: Continuous immunotherapy beyond progression in clinical practice for small cell lung cancer.

Yamamoto, Ken / Ninomaru, Taira / Okada, Hideaki / Hirano, Katsuya / Shimada, Temiko / Hata, Akito

Thoracic cancer

2024

Abstract: In non-small-cell lung cancer, continuous immune-checkpoint inhibitors (ICIs) beyond progression are often used in clinical practice. On the other hand, there is almost no data on whether the concept of continuous ICIs beyond progression can be adopted ... ...

Abstract	In non-small-cell lung cancer, continuous immune-checkpoint inhibitors (ICIs) beyond progression are often used in clinical practice. On the other hand, there is almost no data on whether the concept of continuous ICIs beyond progression can be adopted in small-cell lung cancer (SCLC). We describe the effectiveness of continuous ICIs beyond progression in SCLC. Medical courses of SCLC patients treated with chemo-immunotherapy were retrospectively reviewed at our hospital. The study included 36 patients with a median age of 73 years (range 46-83 years) who introduced chemo-immunotherapy between September 2019 and December 2022. Atezolizumab and durvalumab in combination with platinum plus etoposide were administered in 24 and 12 patients, respectively. The overall response rate was 67% and the disease control rate was 86%. The median progression-free survival and time to treatment failure (TTF) were 5.1 and 10.3 months, respectively. The median cycle of ICIs was 5 (range 1-42). The median overall survival was 13.6 months. ICIs were administered beyond progression in 14 (39%) patients: five were treated again with chemo-immunotherapy and local ablative radiotherapy, four with local ablative radiotherapy and continuous ICIs, three with chemo-immunotherapy, and two with continuous ICIs alone. TTF exceeded 12 months in 12 (86%) of the 14 cases, six of which were still on ICIs. Adverse events ≥grade 3 were observed in 21 (58%) patients. A notable TTF suggested a benefit of continuous ICIs beyond progression. The concept could be suitably adopted and provide a favorable prognosis in selected cases of SCLC that were previously regarded as an aggressive malignancy.
Language	English
Publishing date	2024-04-16
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	2625856-0
ISSN	1759-7714 ; 1759-7706
ISSN (online)	1759-7714
ISSN	1759-7706
DOI	10.1111/1759-7714.15308
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Article ; Online: Continuous oxygen saturation and risk of retinopathy of prematurity in a Japanese cohort.

Kubota, Hiroshi / Fukushima, Yoko / Kawasaki, Ryo / Endo, Takao / Hatsukawa, Yoshikazu / Ineyama, Hiromi / Hirata, Katsuya / Hirano, Shinya / Wada, Kazuko / Nishida, Kohji

The British journal of ophthalmology

2024

Abstract: Background/aims: We assessed the associations between retinopathy of prematurity (ROP) and continuous measurements of oxygen saturation (SpO: Methods: This retrospective study included infants who were born before 30 weeks of gestation between August ...

Abstract	Background/aims: We assessed the associations between retinopathy of prematurity (ROP) and continuous measurements of oxygen saturation (SpO Methods: This retrospective study included infants who were born before 30 weeks of gestation between August 2009 and January 2019 and who were screened for ROP at a single hospital in Japan. We extracted data on birth weight (BW), birth length, gestational age (GA) and minute-by-minute SpO Results: Among 350 infants, 83 (23.7%) required ROP treatment. The SpO Conclusion: Data obtained by continuous SpO
Language	English
Publishing date	2024-03-06
Publishing country	England
Document type	Journal Article
ZDB-ID	80078-8
ISSN	1468-2079 ; 0007-1161
ISSN (online)	1468-2079
ISSN	0007-1161
DOI	10.1136/bjo-2023-324225
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Article ; Online: Kidney Disease After Allogeneic Hematopoietic Stem Cell Transplantation Is Associated With Decreased Physical Function.

Hirano, Yuma / Hanajima, Wataru / Yamauchi, Katsuya

Transplantation proceedings

2022 Volume 54, Issue 8, Page(s) 2352–2356

Abstract: Objective/background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved outcomes and prognosis, but it has many complications and is associated with impaired physical function. To solve this problem, it is necessary to further ... ...

Abstract	Objective/background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved outcomes and prognosis, but it has many complications and is associated with impaired physical function. To solve this problem, it is necessary to further analyze the factors that cause the decline in physical function. In the present study, we hypothesized that kidney disease following allo-HSCT would be associated with impaired physical function, in addition to conventional factors, and tested this hypothesis retrospectively. Methods: Thirty-one patients who underwent allo-HSCT at the Department of Hematology in our hospital from January 2016 to October 2021 were included in the analysis. Correlation analysis and stepwise multiple regression analysis with change in 30-second sit to stand test (Δ30-s STS) as the dependent variable were performed to identify predictors of physical function decline from pretransplant to discharge. Results: The mean age of participants was 43.9 years (SD = 11.8), the mean time from transplant to discharge was 103.1 days (SD = 35.0), and approximately 30% of patients had kidney disease following allo-HSCT. All patients were ambulatory and independent at discharge, but 30-s STS was significantly reduced (P < .001). Among various factors, age (β = -0.464, P < .05), total corticosteroid dose (β = -0.380, P < .05), and kidney disease after allo-HSCT (β = -0.307, P < .05) were the independent predictors of Δ30-s STS (R Conclusion: Kidney disease after allo-HSCT is one of the factors that may contribute to poor physical function, and patients who experience this condition may require additional follow-up to improve physical function.
MeSH term(s)	Humans ; Adult ; Transplantation, Homologous/adverse effects ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects ; Prognosis ; Kidney Diseases
Language	English
Publishing date	2022-10-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	82046-5
ISSN	1873-2623 ; 0041-1345
ISSN (online)	1873-2623
ISSN	0041-1345
DOI	10.1016/j.transproceed.2022.08.040
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