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Article ; Online: Organ Specificity and Heterogeneity of Cancer-Associated Fibroblasts in Colorectal Cancer.

Miyashita, Naoya / Saito, Akira

International journal of molecular sciences

2021 Volume 22, Issue 20

Abstract: Fibroblasts constitute a ubiquitous mesenchymal cell type and produce the extracellular matrix (ECM) of connective tissue, thereby providing the structural basis of various organs. Fibroblasts display differential transcriptional patterns unique to the ... ...

Abstract	Fibroblasts constitute a ubiquitous mesenchymal cell type and produce the extracellular matrix (ECM) of connective tissue, thereby providing the structural basis of various organs. Fibroblasts display differential transcriptional patterns unique to the organ of their origin and they can be activated by common stimuli such as transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF) signaling. Cancer-associated fibroblasts (CAFs) reside in the cancer tissue and contribute to cancer progression by influencing cancer cell growth, invasion, angiogenesis and tumor immunity. CAFs impact on the tumor microenvironment by remodeling the ECM and secreting soluble factors such as chemokines and growth factors. Differential expression patterns of molecular markers suggest heterogeneous features of CAFs in terms of their function, pathogenic role and cellular origin. Recent studies elucidated the bimodal action of CAFs on cancer progression and suggest a subgroup of CAFs with tumor-suppressive effects. This review attempts to describe cellular features of colorectal CAFs with an emphasis on their heterogeneity and functional diversity.
MeSH term(s)	Cancer-Associated Fibroblasts/cytology ; Cancer-Associated Fibroblasts/metabolism ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Extracellular Matrix/metabolism ; Humans ; Immune Checkpoint Inhibitors/metabolism ; Organ Specificity ; Platelet-Derived Growth Factor/metabolism ; Signal Transduction ; Transforming Growth Factor beta/metabolism
Chemical Substances	Immune Checkpoint Inhibitors ; Platelet-Derived Growth Factor ; Transforming Growth Factor beta
Language	English
Publishing date	2021-10-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222010973
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Article: Bacterial Pneumonia in Elderly Japanese Populations.

Miyashita, Naoya / Yamauchi, Yasuhiro

Japanese clinical medicine

2018 Volume 9, Page(s) 1179670717751433

Abstract: Bacterial pneumonia is one of the most important infectious diseases in terms of incidence, effect on quality of life, mortality, and impact on society. Pneumonia was the third leading cause of death in Japan in 2011. In 2016, 119 650 Japanese people ... ...

Abstract	Bacterial pneumonia is one of the most important infectious diseases in terms of incidence, effect on quality of life, mortality, and impact on society. Pneumonia was the third leading cause of death in Japan in 2011. In 2016, 119 650 Japanese people died of pneumonia, 96% of whom were aged 65 years and above. The symptoms of pneumonia in elderly people are often atypical. Aspiration pneumonia is seen more frequently than in young people because of swallowing dysfunction in the elderly. The mortality rate is also higher in the elderly than in young people. In Japan, the population is aging at an unprecedented rate, and pneumonia in the elderly will be increasingly important in medicine and medical economics in the future. To manage pneumonia in the elderly, it is important to accurately evaluate its severity, administer appropriate antibiotic treatment, and implement effective preventive measures.
Language	English
Publishing date	2018-01-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2596434-3
ISSN	1179-6707
ISSN	1179-6707
DOI	10.1177/1179670717751433
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Article ; Online: An integrative epigenomic approach identifies ELF3 as an oncogenic regulator in ASCL1-positive neuroendocrine carcinoma.

Horie, Masafumi / Tanaka, Hidenori / Suzuki, Masami / Sato, Yoshihiko / Takata, So / Takai, Erina / Miyashita, Naoya / Saito, Akira / Nakatani, Yoichiro / Yachida, Shinichi

Cancer science

2023 Volume 114, Issue 6, Page(s) 2596–2608

Abstract: Neuroendocrine carcinoma (NEC) is a highly aggressive subtype of the neuroendocrine tumor with an extremely poor prognosis. We have previously conducted a comprehensive genomic analysis of over 100 cases of NEC of the gastrointestinal system (GIS-NEC) ... ...

Abstract	Neuroendocrine carcinoma (NEC) is a highly aggressive subtype of the neuroendocrine tumor with an extremely poor prognosis. We have previously conducted a comprehensive genomic analysis of over 100 cases of NEC of the gastrointestinal system (GIS-NEC) and unraveled its unique and organ-specific genomic drivers. However, the epigenomic features of GIS-NEC remain unexplored. In this study, we have described the epigenomic landscape of GIS-NEC and small cell lung carcinoma (SCLC) by integrating motif enrichment analysis from the assay of transposase-accessible chromatin sequencing (ATAC-seq) and enhancer profiling from a novel cleavage under targets and tagmentation (CUT&Tag) assay for H3K27ac and identified ELF3 as one of the super-enhancer-related transcriptional factors in NEC. By combining CUT&Tag and knockdown RNA sequencing for ELF3, we uncovered the transcriptional network regulated by ELF3 and defined its distinctive gene signature, including AURKA, CDC25B, CLDN4, ITGB6, and YWAHB. Furthermore, a loss-of-function assay revealed that ELF3 depletion led to poor cell viability. Finally, using gene expression of clinical samples, we successfully divided GIS-NEC patients into two subgroups according to the ELF3 signature and demonstrated that tumor-promoting pathways were activated in the ELF3 signature-high group. Our findings highlight the transcriptional regulation of ELF3 as an oncogenic transcription factor and its tumor-promoting properties in NEC.
MeSH term(s)	Humans ; Epigenomics ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Small Cell Lung Carcinoma/pathology ; Carcinoma, Neuroendocrine/genetics ; Lung Neoplasms/pathology ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; DNA-Binding Proteins/genetics ; Proto-Oncogene Proteins c-ets/genetics
Chemical Substances	Transcription Factors ; ASCL1 protein, human ; Basic Helix-Loop-Helix Transcription Factors ; ELF3 protein, human ; DNA-Binding Proteins ; Proto-Oncogene Proteins c-ets
Language	English
Publishing date	2023-03-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2115647-5
ISSN	1349-7006 ; 1349-7006
ISSN (online)	1349-7006
ISSN	1349-7006
DOI	10.1111/cas.15764
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Article ; Online: A Japanese herbal medicine (kampo), hochuekkito (TJ-41), has anti-inflammatory effects on the chronic obstructive pulmonary disease mouse model.

Yuki, Masaaki / Ishimori, Taro / Kono, Shiho / Nagoshi, Saki / Saito, Minako / Isago, Hideaki / Tamiya, Hiroyuki / Fukuda, Kensuke / Miyashita, Naoya / Ishii, Takashi / Matsuzaki, Hirotaka / Hiraishi, Yoshihisa / Saito, Akira / Jo, Taisuke / Nagase, Takahide / Mitani, Akihisa

Scientific reports

2024 Volume 14, Issue 1, Page(s) 10361

Abstract: Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by chronic airway inflammation. A Japanese herbal medicine, hochuekkito (TJ-41), is prominently used for chronic inflammatory diseases in Japan. This study aimed ... ...

Abstract	Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by chronic airway inflammation. A Japanese herbal medicine, hochuekkito (TJ-41), is prominently used for chronic inflammatory diseases in Japan. This study aimed to analyze the anti-inflammatory effect of TJ-41 in vivo and its underlying mechanisms. We created a COPD mouse model using intratracheal administration of porcine pancreatic elastase and lipopolysaccharide (LPS) and analyzed them with and without TJ-41 administration. A TJ-41-containing diet reduced inflammatory cell infiltration of the lungs in the acute and chronic phases and body weight loss in the acute phase. In vitro experiments revealed that TJ-41 treatment suppressed the LPS-induced inflammatory cytokines in BEAS-2B cells. Furthermore, TJ-41 administration activated the AMP-activated protein kinase (AMPK) pathway and inhibited the mechanistic target of the rapamycin (mTOR) pathway, both in cellular and mouse experiments. We concluded that TJ-41 administration reduced airway inflammation in the COPD mouse model, which might be regulated by the activated AMPK pathway, and inhibited the mTOR pathway.
MeSH term(s)	Animals ; Pulmonary Disease, Chronic Obstructive/drug therapy ; Pulmonary Disease, Chronic Obstructive/metabolism ; Pulmonary Disease, Chronic Obstructive/pathology ; Drugs, Chinese Herbal/pharmacology ; Disease Models, Animal ; Anti-Inflammatory Agents/pharmacology ; Mice ; Medicine, Kampo ; AMP-Activated Protein Kinases/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Humans ; Lipopolysaccharides ; Male ; Cytokines/metabolism ; Signal Transduction/drug effects ; Cell Line ; Lung/pathology ; Lung/drug effects ; Lung/metabolism ; Pancreatic Elastase/metabolism ; East Asian People
Chemical Substances	Drugs, Chinese Herbal ; Anti-Inflammatory Agents ; bu-zhong-yi-qi-tang ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Lipopolysaccharides ; Cytokines ; Pancreatic Elastase (EC 3.4.21.36)
Language	English
Publishing date	2024-05-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-60646-x
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Article ; Online: Endoscopic reflux esophagitis and decline in pulmonary function in nonsmokers: A retrospective cohort study.

Enokido, Takayoshi / Hiraishi, Yoshihisa / Jo, Taisuke / Urushiyama, Hirokazu / Saito, Akira / Noguchi, Satoshi / Hosoki, Keisuke / Ishii, Takashi / Miyashita, Naoya / Fukuda, Kensuke / Matsuki, Rei / Minatsuki, Chihiro / Shimamoto, Takeshi / Kage, Hidenori / Yamamichi, Nobutake / Matsuzaki, Hirotaka

Respiratory investigation

2024 Volume 62, Issue 4, Page(s) 599–605

Abstract: Background: The association between reflux esophagitis and pulmonary function remains controversial. Thus, evaluating the relationship between endoscopic reflux esophagitis and changes in pulmonary function over time in a nonsmoking population is an ... ...

Abstract	Background: The association between reflux esophagitis and pulmonary function remains controversial. Thus, evaluating the relationship between endoscopic reflux esophagitis and changes in pulmonary function over time in a nonsmoking population is an important clinical issue. Methods: In this single-center retrospective cohort study, a medical examination database at Kameda Medical Center Makuhari was employed to identify nonsmokers who underwent upper gastrointestinal endoscopy and spirometry in 2010 and were followed up in 2015. Gastroenterologists carefully double-checked the diagnosis of reflux esophagitis. Multiple linear regression analyses were performed to compare the decline in the percentage of predicted vital capacity (%VC), forced vital capacity (%FVC), and forced expiratory volume in 1 s (%FEV Results: We identified 3098 eligible subjects, including 72 and 44 participants who had a Los Angeles classification grade A and B-C (severe) reflux esophagitis in 2010, respectively. The decline in %VC was significantly larger in the participants with severe reflux esophagitis than in the control subjects (standardized coefficient, -0.037; 95% confidence interval, -0.071 to -0.004). Moreover, reflux esophagitis was significantly associated with a rapid decline in %VC and %FVC but not in %FEV Conclusions: Severe reflux esophagitis among nonsmokers had clinical disadvantages in terms of a decline in %VC.
Language	English
Publishing date	2024-05-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2660821-2
ISSN	2212-5353 ; 2212-5345
ISSN (online)	2212-5353
ISSN	2212-5345
DOI	10.1016/j.resinv.2024.04.017
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Article ; Online: Anti-Inflammatory Effects of Japanese Herbal Medicine Hochuekkito in a Mouse Model of Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Fukuda, Kensuke / Matsuzaki, Hirotaka / Hiraishi, Yoshihisa / Miyashita, Naoya / Ishii, Takashi / Yuki, Masaaki / Isago, Hideaki / Tamiya, Hiroyuki / Mitani, Akihisa / Saito, Akira / Jo, Taisuke / Nagase, Takahide

Pharmacology

2024 Volume 109, Issue 2, Page(s) 121–126

Abstract: Introduction: The traditional Japanese herbal medicine hochuekkito (TJ-41) has been reported to ameliorate systemic inflammation and malnutrition in patients with chronic obstructive pulmonary disease (COPD). TJ-41 has also been known to have preventive ...

Abstract	Introduction: The traditional Japanese herbal medicine hochuekkito (TJ-41) has been reported to ameliorate systemic inflammation and malnutrition in patients with chronic obstructive pulmonary disease (COPD). TJ-41 has also been known to have preventive effects against influenza virus infection. However, its role in the acute exacerbation of COPD (AECOPD) remains to be elucidated. Our previous study established a murine model of viral infection-associated AECOPD that was induced by intratracheal administration of porcine pancreatic elastase (PPE) and polyinosinic-polycytidylic acid [poly(I:C)]. Here, we used this model and investigated the effects of TJ-41 in AECOPD. Methods: Specific pathogen-free C57BL/6J mice were used. A COPD model was induced by treating mice intratracheally with PPE on day 0. To generate the murine model of AECOPD, poly(I:C) was administered intratracheally following PPE treatment on days 22-24. Mice were sacrificed and analyzed on day 25. Mice were fed a diet containing 2% TJ-41 or a control diet. Results: Daily oral intake of TJ-41 significantly decreased the numbers of neutrophils and lymphocytes in the bronchoalveolar lavage fluid (BALF), which was accompanied by decreased transcripts of CXC chemokines involved in neutrophil migration, viz., Cxcl1 and Cxcl2, in whole lung homogenates and reduced Cxcl2 concentration in BALF. Conclusion: This study demonstrates the anti-inflammatory effects of TJ-41 in a mouse model of AECOPD, suggesting the effectiveness of TJ-41 for the management of COPD. Clinical investigations evaluating the therapeutic efficacy of TJ-41 in AECOPD would be meaningful.
MeSH term(s)	Humans ; Mice ; Animals ; Swine ; Disease Models, Animal ; Japan ; Mice, Inbred C57BL ; Pulmonary Disease, Chronic Obstructive/drug therapy ; Pulmonary Disease, Chronic Obstructive/complications ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use
Chemical Substances	bu-zhong-yi-qi-tang ; Drugs, Chinese Herbal ; Anti-Inflammatory Agents
Language	English
Publishing date	2024-02-12
Publishing country	Switzerland
Document type	News
ZDB-ID	206671-3
ISSN	1423-0313 ; 0031-7012
ISSN (online)	1423-0313
ISSN	0031-7012
DOI	10.1159/000536348
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Article ; Online: The Diagnosis and Treatment of Primary Pulmonary Artery Sarcoma: Two Case Reports.

Funauchi, Yohei / Takase, Toru / Miyoshi, Tatsuya / Miyashita, Naoya / Kimura, Masatomo / Nakazawa, Gaku

Internal medicine (Tokyo, Japan)

2021 Volume 61, Issue 5, Page(s) 667–671

Abstract: Pulmonary artery sarcoma (PAS) is considered a very rare tumor with a poor prognosis. We herein report two cases of PAS that were diagnosed by positron emission tomography (PET)/computed tomography (CT). In both cases, PET was an effective option for ... ...

Abstract	Pulmonary artery sarcoma (PAS) is considered a very rare tumor with a poor prognosis. We herein report two cases of PAS that were diagnosed by positron emission tomography (PET)/computed tomography (CT). In both cases, PET was an effective option for diagnosing tumors, and surgical resection was a valid treatment for these diseases. If a pulmonary artery tumor is suspected, PET/CT is useful for diagnosing PAS and very helpful for choosing the surgical treatment strategy.
MeSH term(s)	Humans ; Lung Neoplasms/pathology ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Pulmonary Artery/diagnostic imaging ; Pulmonary Artery/pathology ; Pulmonary Artery/surgery ; Sarcoma/diagnostic imaging ; Sarcoma/surgery ; Vascular Neoplasms/diagnostic imaging ; Vascular Neoplasms/surgery
Language	English
Publishing date	2021-08-31
Publishing country	Japan
Document type	Case Reports ; Journal Article
ZDB-ID	32371-8
ISSN	1349-7235 ; 0021-5120 ; 0918-2918
ISSN (online)	1349-7235
ISSN	0021-5120 ; 0918-2918
DOI	10.2169/internalmedicine.7666-21
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Article ; Online: Co-deposition of MoS

Kim, Myeongok / Giteau, Maxime / Ahsan, Nazmul / Miyashita, Naoya / Thirumalaisamy, Logu / Chen, Chen / Redwing, Joan M / Okada, Yoshitaka

Nanotechnology

2022

Abstract: Transition metal dichalcogenides (TMDCs) are versatile layered materials with potential applications ranging from optoelectronic devices to water splitting. Top-down fabrication methods such as exfoliation are not practical for a large-scale production ... ...

Abstract	Transition metal dichalcogenides (TMDCs) are versatile layered materials with potential applications ranging from optoelectronic devices to water splitting. Top-down fabrication methods such as exfoliation are not practical for a large-scale production of high-quality devices: a bottom-up approach such as sputtering, a low-temperature deposition method, is more suitable. However, due to its anisotropic nature, the growth mechanism of molybdenum disulfide (MoS
Language	English
Publishing date	2022-05-18
Publishing country	England
Document type	Journal Article
ZDB-ID	1362365-5
ISSN	1361-6528 ; 0957-4484
ISSN (online)	1361-6528
ISSN	0957-4484
DOI	10.1088/1361-6528/ac70e3
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Article: Hybrid Repair for Mega-Aortic Syndrome due to Giant Cell Aortitis in a Heart Failure Patient.

Inoue, Takehiro / Fujii, Kosuke / Kino, Shigeo / Yukami, Shintaro / Miyashita, Naoya / Kitayama, Hitoshi

Annals of vascular diseases

2020 Volume 13, Issue 1, Page(s) 76–80

Abstract: The present report describes a case of mega-aortic syndrome accompanied with severe aortic regurgitation in a 75-year-old man who underwent a two-stage hybrid repair. Intraoperative pathologic findings at the first repair, consisting of Bentall operation ...

Abstract	The present report describes a case of mega-aortic syndrome accompanied with severe aortic regurgitation in a 75-year-old man who underwent a two-stage hybrid repair. Intraoperative pathologic findings at the first repair, consisting of Bentall operation and total arch replacement with a Lupiae graft, aided the identification of the giant cell aortitis. Despite complicating hemorrhagic stroke, steroid therapy was initiated and endovascular repair was subsequently completed. Over more than 2 years of follow-up, the patient continued steroid therapy and is doing well without any reintervention.
Language	English
Publishing date	2020-03-27
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2394256-3
ISSN	1881-6428 ; 1881-641X
ISSN (online)	1881-6428
ISSN	1881-641X
DOI	10.3400/avd.cr.19-00096
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Article ; Online: Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma.

Enokido, Takayoshi / Horie, Masafumi / Yoshino, Seiko / Suzuki, Hiroshi I / Matsuki, Rei / Brunnström, Hans / Micke, Patrick / Nagase, Takahide / Saito, Akira / Miyashita, Naoya

Molecular cancer research : MCR

2023 Volume 22, Issue 1, Page(s) 29–40

Abstract: Achaete-scute family bHLH transcription factor 1 (ASCL1) is a master transcription factor involved in neuroendocrine differentiation. ASCL1 is expressed in approximately 10% of lung adenocarcinomas (LUAD) and exerts tumor-promoting effects. Here, we ... ...

Abstract	Achaete-scute family bHLH transcription factor 1 (ASCL1) is a master transcription factor involved in neuroendocrine differentiation. ASCL1 is expressed in approximately 10% of lung adenocarcinomas (LUAD) and exerts tumor-promoting effects. Here, we explored miRNA profiles in ASCL1-positive LUADs and identified several miRNAs closely associated with ASCL1 expression, including miR-375, miR-95-3p/miR-95-5p, miR-124-3p, and members of the miR-17∼92 family. Similar to small cell lung cancer, Yes1 associated transcriptional regulator (YAP1), a representative miR-375 target gene, was suppressed in ASCL1-positive LUADs. ASCL1 knockdown followed by miRNA profiling in a cell culture model further revealed that ASCL1 positively regulates miR-124-3p and members of the miR-17∼92 family. Integrative transcriptomic analyses identified ZFP36 ring finger protein like 1 (ZFP36L1) as a target gene of miR-124-3p, and IHC studies demonstrated that ASCL1-positive LUADs are associated with low ZFP36L1 protein levels. Cell culture studies showed that ectopic ZFP36L1 expression inhibits cell proliferation, survival, and cell-cycle progression. Moreover, ZFP36L1 negatively regulated several genes including E2F transcription factor 1 (E2F1) and snail family transcriptional repressor 1 (SNAI1). In conclusion, our study revealed that suppression of ZFP36L1 via ASCL1-regulated miR-124-3p could modulate gene expression, providing evidence that ASCL1-mediated regulation of miRNAs shapes molecular features of ASCL1-positive LUADs. Implications: Our study revealed unique miRNA profiles of ASCL1-positive LUADs and identified ASCL1-regulated miRNAs with functional relevance.
MeSH term(s)	Humans ; Cell Line, Tumor ; Adenocarcinoma of Lung/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Small Cell Lung Carcinoma/genetics ; Cell Proliferation/genetics ; Lung Neoplasms/pathology ; Gene Expression Regulation, Neoplastic ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Butyrate Response Factor 1/genetics ; Butyrate Response Factor 1/metabolism
Chemical Substances	MicroRNAs ; ASCL1 protein, human ; Basic Helix-Loop-Helix Transcription Factors ; ZFP36L1 protein, human ; Butyrate Response Factor 1
Language	English
Publishing date	2023-10-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2098788-2
ISSN	1557-3125 ; 1541-7786
ISSN (online)	1557-3125
ISSN	1541-7786
DOI	10.1158/1541-7786.MCR-23-0229
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