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Article: Nagasaki university medical association.

Matsuyama, Toshifumi

Japan Medical Association journal : JMAJ

2014 Volume 55, Issue 4, Page(s) 339–341

Language	English
Publishing date	2014-08-07
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2052217-4
ISSN	1346-8650
ISSN	1346-8650
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Article ; Online: IDO1, FAT10, IFI6, and GILT Are Involved in the Antiretroviral Activity of γ-Interferon and IDO1 Restricts Retrovirus Infection by Autophagy Enhancement.

Kubo, Yoshinao / Yasui, Kiyoshi / Izumida, Mai / Hayashi, Hideki / Matsuyama, Toshifumi

Cells

2022 Volume 11, Issue 14

Abstract: Gamma-interferon (γ-IFN) significantly inhibits infection by replication-defective viral vectors derived from the human immunodeficiency virus type 1 (HIV-1) or murine leukemia virus (MLV) but the underlying mechanism remains unclear. Previously we ... ...

Abstract	Gamma-interferon (γ-IFN) significantly inhibits infection by replication-defective viral vectors derived from the human immunodeficiency virus type 1 (HIV-1) or murine leukemia virus (MLV) but the underlying mechanism remains unclear. Previously we reported that knockdown of γ-IFN-inducible lysosomal thiolreductase (GILT) abrogates the antiviral activity of γ-IFN in TE671 cells but not in HeLa cells, suggesting that other γ-IFN-inducible host factors are involved in its antiviral activity in HeLa cells. We identified cellular factors, the expression of which are induced by γ-IFN in HeLa cells, using a microarray, and analyzed the effects of 11 γ-IFN-induced factors on retroviral vector infection. Our results showed that the exogenous expression of FAT10, IFI6, or IDO1 significantly inhibits both HIV-1- and MLV-based vector infections. The antiviral activity of γ-IFN was decreased in HeLa cells, in which the function of IDO1, IFI6, FAT10, and GILT were simultaneously inhibited. IDO1 is an enzyme that metabolizes an essential amino acid, tryptophan. However, IDO1 did not restrict retroviral vector infection in Atg3-silencing HeLa cells, in which autophagy did not occur. This study found that IDO1, IFI6, FAT10, and GILT are involved in the antiviral activity of γ-IFN, and IDO1 inhibits retroviral infection by inducing autophagy.
MeSH term(s)	Anti-Retroviral Agents/pharmacology ; Antiviral Agents/pharmacology ; Autophagy ; HIV Infections/drug therapy ; HIV-1/metabolism ; HeLa Cells ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Interferon-gamma/metabolism ; Interferon-gamma/pharmacology ; Leukemia Virus, Murine ; Mitochondrial Proteins ; Oxidoreductases Acting on Sulfur Group Donors ; Retroviridae Infections ; Ubiquitins/pharmacology
Chemical Substances	Anti-Retroviral Agents ; Antiviral Agents ; IDO1 protein, human ; IFI6 protein, human ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Mitochondrial Proteins ; UBD protein, human ; Ubiquitins ; Interferon-gamma (82115-62-6) ; IFI30 protein, human (EC 1.8.-) ; Oxidoreductases Acting on Sulfur Group Donors (EC 1.8.-)
Language	English
Publishing date	2022-07-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11142240
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Article ; Online: Efficient viral delivery of Cas9 into human safe harbor.

Hayashi, Hideki / Kubo, Yoshinao / Izumida, Mai / Matsuyama, Toshifumi

Scientific reports

2020 Volume 10, Issue 1, Page(s) 21474

Abstract: Gene editing using CRISPR/Cas9 is a promising method to cure many human genetic diseases. We have developed an efficient system to deliver Cas9 into the adeno-associated virus integration site 1 (AAVS1) locus, known as a safe harbor, using lentivirus and ...

Abstract	Gene editing using CRISPR/Cas9 is a promising method to cure many human genetic diseases. We have developed an efficient system to deliver Cas9 into the adeno-associated virus integration site 1 (AAVS1) locus, known as a safe harbor, using lentivirus and AAV viral vectors, as a step toward future in vivo transduction. First, we introduced Cas9v1 (derived from Streptococcus pyogenes) at random into the genome using a lentiviral vector. Cas9v1 activity was used when the N-terminal 1.9 kb, and C-terminal 2.3 kb fragments of another Cas9v2 (human codon-optimized) were employed sequentially with specific single-guide RNAs (sgRNAs) and homology donors carried by AAV vectors into the AAVS1 locus. Then, Cas9v1 was removed from the genome by another AAV vector containing sgRNA targeting the long terminal repeat of the lentivirus vector. The reconstituted Cas9v2 in the AAVS1 locus was functional and gene editing was efficient.
MeSH term(s)	CRISPR-Associated Protein 9/genetics ; CRISPR-Cas Systems ; Dependovirus/genetics ; Gene Editing ; Gene Transfer Techniques ; Genetic Loci ; Genetic Vectors/genetics ; HEK293 Cells ; Humans ; Lentivirus/genetics ; RNA, Guide, CRISPR-Cas Systems/genetics ; Streptococcus pyogenes/genetics ; Transduction, Genetic/methods
Chemical Substances	RNA, Guide, CRISPR-Cas Systems ; CRISPR-Associated Protein 9 (EC 3.1.-)
Language	English
Publishing date	2020-12-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-78450-8
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Article ; Online: Comorbidity-associated glutamine deficiency is a predisposition to severe COVID-19.

Matsuyama, Toshifumi / Yoshinaga, Steven K / Shibue, Kimitaka / Mak, Tak W

Cell death and differentiation

2021 Volume 28, Issue 12, Page(s) 3199–3213

Abstract: SARS-CoV-2 vaccinations have greatly reduced COVID-19 cases, but we must continue to develop our understanding of the nature of the disease and its effects on human immunity. Previously, we suggested that a dysregulated STAT3 pathway following SARS-Co-2 ... ...

Abstract	SARS-CoV-2 vaccinations have greatly reduced COVID-19 cases, but we must continue to develop our understanding of the nature of the disease and its effects on human immunity. Previously, we suggested that a dysregulated STAT3 pathway following SARS-Co-2 infection ultimately leads to PAI-1 activation and cascades of pathologies. The major COVID-19-associated metabolic risks (old age, hypertension, cardiovascular diseases, diabetes, and obesity) share high PAI-1 levels and could predispose certain groups to severe COVID-19 complications. In this review article, we describe the common metabolic profile that is shared between all of these high-risk groups and COVID-19. This profile not only involves high levels of PAI-1 and STAT3 as previously described, but also includes low levels of glutamine and NAD
MeSH term(s)	Animals ; COVID-19/blood ; COVID-19/epidemiology ; COVID-19/physiopathology ; Comorbidity ; Glutamine/blood ; Glutamine/deficiency ; Humans ; Hyaluronic Acid/blood ; Metabolome ; Plasminogen Activator Inhibitor 1/blood ; Risk Factors ; Severity of Illness Index
Chemical Substances	Plasminogen Activator Inhibitor 1 ; SERPINE1 protein, human ; Glutamine (0RH81L854J) ; Hyaluronic Acid (9004-61-9)
Language	English
Publishing date	2021-10-18
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1225672-9
ISSN	1476-5403 ; 1350-9047
ISSN (online)	1476-5403
ISSN	1350-9047
DOI	10.1038/s41418-021-00892-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Rab3a, a small GTP-binding protein, is required for the stabilization of the murine leukaemia virus Gag protein.

Izumida, Mai / Kakoki, Katsura / Hayashi, Hideki / Matsuyama, Toshifumi / Kubo, Yoshinao

Small GTPases

2021 Volume 13, Issue 1, Page(s) 162–182

Abstract: We recently identified a CD63-interacting protein to understand the role of CD63 in virion production of the human immunodeficiency virus type 1, and we have found that Rab3a forms a complex with CD63. In this study, we analysed the effect of Rab3a on ... ...

Abstract	We recently identified a CD63-interacting protein to understand the role of CD63 in virion production of the human immunodeficiency virus type 1, and we have found that Rab3a forms a complex with CD63. In this study, we analysed the effect of Rab3a on virion production of the murine leukaemia virus (MLV), which is another member of the retrovirus family. We found that Rab3a silencing induced lysosomal degradation of the MLV Gag protein, and recovery of the Rab3a expression restored the level of the Gag protein through a complex formation of MLV Gag and Rab3a, indicating that Rab3a is required for MLV Gag protein expression. In contrast, CD63 silencing decreased the infectivity of released virions but had no effect on virion production, indicating that CD63 facilitates the infectivity of released MLV particles. Although Rab3a induced CD63 degradation in uninfected cells, the complex of MLV Gag and Rab3a suppressed the Rab3a-mediated CD63 degradation in MLV-infected cells. Finally, we found that the MLV Gag protein interacts with Rab3a to stabilize its own protein and CD63 that facilitates the infectivity of released MLV particles. Considering the involvement of Rab3a in lysosome trafficking to the plasma membrane, it may also induce cell surface transport of the MLV Gag protein.
MeSH term(s)	Mice ; Animals ; Humans ; Gene Products, gag/metabolism ; Leukemia Virus, Murine/metabolism ; Virion/metabolism ; Cell Membrane/metabolism ; GTP-Binding Proteins/metabolism
Chemical Substances	Gene Products, gag ; GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2021-06-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2682247-7
ISSN	2154-1256 ; 2154-1248
ISSN (online)	2154-1256
ISSN	2154-1248
DOI	10.1080/21541248.2021.1939631
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Article ; Online: Efficient viral delivery of Cas9 into human safe harbor

Hideki Hayashi / Yoshinao Kubo / Mai Izumida / Toshifumi Matsuyama

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 14

Abstract: Abstract Gene editing using CRISPR/Cas9 is a promising method to cure many human genetic diseases. We have developed an efficient system to deliver Cas9 into the adeno-associated virus integration site 1 (AAVS1) locus, known as a safe harbor, using ... ...

Abstract	Abstract Gene editing using CRISPR/Cas9 is a promising method to cure many human genetic diseases. We have developed an efficient system to deliver Cas9 into the adeno-associated virus integration site 1 (AAVS1) locus, known as a safe harbor, using lentivirus and AAV viral vectors, as a step toward future in vivo transduction. First, we introduced Cas9v1 (derived from Streptococcus pyogenes) at random into the genome using a lentiviral vector. Cas9v1 activity was used when the N-terminal 1.9 kb, and C-terminal 2.3 kb fragments of another Cas9v2 (human codon-optimized) were employed sequentially with specific single-guide RNAs (sgRNAs) and homology donors carried by AAV vectors into the AAVS1 locus. Then, Cas9v1 was removed from the genome by another AAV vector containing sgRNA targeting the long terminal repeat of the lentivirus vector. The reconstituted Cas9v2 in the AAVS1 locus was functional and gene editing was efficient.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article: Production of Vesicular Stomatitis Virus Glycoprotein-Pseudotyped Lentiviral Vector Is Enhanced by Ezrin Silencing.

Izumida, Mai / Togawa, Kei / Hayashi, Hideki / Matsuyama, Toshifumi / Kubo, Yoshinao

Frontiers in bioengineering and biotechnology

2020 Volume 8, Page(s) 368

Abstract: Human immunodeficiency virus type 1 (HIV-1)-based viral vector is widely used as a biomaterial to transfer a gene of interest into target cells in many biological study fields including gene therapy. Vesicular stomatitis virus glycoprotein (VSV-G)- ... ...

Abstract	Human immunodeficiency virus type 1 (HIV-1)-based viral vector is widely used as a biomaterial to transfer a gene of interest into target cells in many biological study fields including gene therapy. Vesicular stomatitis virus glycoprotein (VSV-G)-containing HIV-1 vector much more efficiently transduces various mammalian cells than other viral envelope proteins-containing vectors. Understanding the mechanism would contribute to development of a novel method of efficient HIV-1 vector production. HIV-1 vector is generally constructed by transient transfection of human 293T or African green monkey COS7 cells. It was found in this study that HIV-1 Gag protein is constitutively digested in lysosomes of African green monkey cells. Surprisingly, VSV-G elevated HIV-1 Gag protein levels, suggesting that VSV-G protects Gag protein from the lysosomal degradation. Unphosphorylated ezrin, but not phosphorylated ezrin, was detected in COS7 cells, and ezrin silencing elevated Gag protein levels in the presence of VSV-G. Expression of unphosphorylated ezrin reduced Gag protein amounts. These results indicate that unphosphorylated ezrin proteins inhibit the VSV-G-mediated stabilization of HIV-1 Gag protein. Trafficking of HIV-1 Gag-associated intracellular vesicles may be controlled by ezrin. Finally, this study found that ezrin silencing yields higher amount of VSV-G-pseudotyped HIV-1 vector.
Language	English
Publishing date	2020-04-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2020.00368
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Article: [Complete Response to Immune Checkpoint Inhibitors in Unresectable Gastric Cancer-A Report of Five Cases].

Saito, Toshifumi / Ishiguro, Toru / Ito, Tetsuya / Ishii, Takahiro / Ishikawa, Hiroyasu / Chiyonobu, Norimichi / Sugino, Aoi / Chika, Noriyasu / Hatano, Satoshi / Mori, Yoshiko / Suzuki, Okihide / Matsuyama, Takatoshi / Kumagai, Yoichi / Ishida, Hideyuki

Gan to kagaku ryoho. Cancer & chemotherapy

2023 Volume 50, Issue 10, Page(s) 1123–1125

Abstract: Immune checkpoint inhibitors(ICIs)are widely used for the treatment of unresectable gastric cancer. We treated approximately 70 patients with ICIs. ICI treatment with pembrolizumab was administered for MSI-high cases and nivolumab for MSS cases in the ... ...

Abstract	Immune checkpoint inhibitors(ICIs)are widely used for the treatment of unresectable gastric cancer. We treated approximately 70 patients with ICIs. ICI treatment with pembrolizumab was administered for MSI-high cases and nivolumab for MSS cases in the second- or third-line chemotherapy. We observed 5 cases of complete response. Among these, 2 patients presented with liver metastases, 2 with peritoneal disseminations, and 1 with pulmonary metastasis. In 1 patient, the primary tumor invaded the diaphragm and descending aorta; whereas, in another patient the primary tumor invaded the pancreas and liver. All patients had progressive disease after first-line chemotherapy.
MeSH term(s)	Humans ; Immune Checkpoint Inhibitors ; Stomach Neoplasms/drug therapy ; Nivolumab/therapeutic use ; Diaphragm ; Liver
Chemical Substances	Immune Checkpoint Inhibitors ; Nivolumab (31YO63LBSN)
Language	Japanese
Publishing date	2023-11-30
Publishing country	Japan
Document type	Case Reports ; English Abstract ; Journal Article
ZDB-ID	604842-0
ISSN	0385-0684
ISSN	0385-0684
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Article ; Online: Japanese version of Patient-Rated Elbow Evaluation is a useful outcome measure that potentially reflects hand function in patients with rheumatoid arthritis who underwent total elbow arthroplasty.

Harada, Ryozo / Nishida, Keiichiro / Matsuyama, Yoshiyuki / Hashizume, Kenzo / Wada, Takuro / Nasu, Yoshihisa / Nakahara, Ryuichi / Horita, Masahiro / Senda, Masuo / Ozaki, Toshifumi

Modern rheumatology

2022 Volume 32, Issue 6, Page(s) 1041–1046

Abstract: Objectives: We examined the relationship between the Japanese version of Patient-Rated Elbow Evaluation (PREE-J) and other established subjective and objective outcome measures in Japanese patients with rheumatoid arthritis (RA) who underwent total ... ...

Abstract	Objectives: We examined the relationship between the Japanese version of Patient-Rated Elbow Evaluation (PREE-J) and other established subjective and objective outcome measures in Japanese patients with rheumatoid arthritis (RA) who underwent total elbow arthroplasty (TEA). Materials and methods: This study involved 46 elbows of 40 RA patients. We collected clinical data 1 year after surgery, including the PREE-J, the Mayo Elbow Performance Score (MEPS), Disability of the Arm, Shoulder, and Hand (DASH), and Hand20. The correlation and responsiveness to PREE-J were evaluated compared with other outcome measures preoperatively and postoperatively. Results: Almost all outcome measures were improved significantly after surgery. Preoperative PREE-J was significantly correlated with preoperative DASH, Hand20, and MEPS. Interestingly, postoperative PREE-J did not correlate with postoperative MEPS. Multiple regression analyses revealed that preoperative grip strength [B = -0.09; 95% confidence interval (95% CI) -0.17 to -0.01, p = 0.03] and preoperative Hand20 (B = 0.31, 95% CI 0.03-0.58, p = 0.03) were significant factors that might influence the postoperative PREE-J. Conclusions: The PREE-J was shown to correlate well with other preoperative outcome measures among the RA patients included in the current study. The postoperative PREE-J after TEA was influenced by the preoperative grip strength and function of the hand.
MeSH term(s)	Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/surgery ; Arthroplasty ; Arthroplasty, Replacement, Elbow ; Elbow/surgery ; Elbow Joint/surgery ; Humans ; Japan ; Outcome Assessment, Health Care ; Range of Motion, Articular ; Surveys and Questionnaires ; Treatment Outcome
Language	English
Publishing date	2022-08-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2078157-X
ISSN	1439-7609 ; 1439-7595
ISSN (online)	1439-7609
ISSN	1439-7595
DOI	10.1093/mr/roab100
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Article ; Online: An aberrant STAT pathway is central to COVID-19.

Matsuyama, Toshifumi / Kubli, Shawn P / Yoshinaga, Steven K / Pfeffer, Klaus / Mak, Tak W

Cell death and differentiation

2020 Volume 27, Issue 12, Page(s) 3209–3225

Abstract: COVID-19 is caused by SARS-CoV-2 infection and characterized by diverse clinical symptoms. Type I interferon (IFN-I) production is impaired and severe cases lead to ARDS and widespread coagulopathy. We propose that COVID-19 pathophysiology is initiated ... ...

Abstract	COVID-19 is caused by SARS-CoV-2 infection and characterized by diverse clinical symptoms. Type I interferon (IFN-I) production is impaired and severe cases lead to ARDS and widespread coagulopathy. We propose that COVID-19 pathophysiology is initiated by SARS-CoV-2 gene products, the NSP1 and ORF6 proteins, leading to a catastrophic cascade of failures. These viral components induce signal transducer and activator of transcription 1 (STAT1) dysfunction and compensatory hyperactivation of STAT3. In SARS-CoV-2-infected cells, a positive feedback loop established between STAT3 and plasminogen activator inhibitor-1 (PAI-1) may lead to an escalating cycle of activation in common with the interdependent signaling networks affected in COVID-19. Specifically, PAI-1 upregulation leads to coagulopathy characterized by intravascular thrombi. Overproduced PAI-1 binds to TLR4 on macrophages, inducing the secretion of proinflammatory cytokines and chemokines. The recruitment and subsequent activation of innate immune cells within an infected lung drives the destruction of lung architecture, which leads to the infection of regional endothelial cells and produces a hypoxic environment that further stimulates PAI-1 production. Acute lung injury also activates EGFR and leads to the phosphorylation of STAT3. COVID-19 patients' autopsies frequently exhibit diffuse alveolar damage (DAD) and increased hyaluronan (HA) production which also leads to higher levels of PAI-1. COVID-19 risk factors are consistent with this scenario, as PAI-1 levels are increased in hypertension, obesity, diabetes, cardiovascular diseases, and old age. We discuss the possibility of using various approved drugs, or drugs currently in clinical development, to treat COVID-19. This perspective suggests to enhance STAT1 activity and/or inhibit STAT3 functions for COVID-19 treatment. This might derail the escalating STAT3/PAI-1 cycle central to COVID-19.
MeSH term(s)	COVID-19/metabolism ; COVID-19/pathology ; COVID-19/virology ; Chemokines/metabolism ; Cytokines/metabolism ; ErbB Receptors/metabolism ; Humans ; Interferon Type I/metabolism ; SARS-CoV-2/isolation & purification ; SARS-CoV-2/metabolism ; STAT Transcription Factors/chemistry ; STAT Transcription Factors/metabolism ; Signal Transduction/physiology ; Viral Nonstructural Proteins/chemistry ; Viral Nonstructural Proteins/metabolism
Chemical Substances	Chemokines ; Cytokines ; Interferon Type I ; STAT Transcription Factors ; Viral Nonstructural Proteins ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
Keywords	covid19
Language	English
Publishing date	2020-10-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1225672-9
ISSN	1476-5403 ; 1350-9047
ISSN (online)	1476-5403
ISSN	1350-9047
DOI	10.1038/s41418-020-00633-7
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