Tokushima University / Educator and Researcher Directory --- Shimizu, Mayuko

Personal Web Page

https://researchmap.jp/mayuko_nutri_pathol (researchmap)

Field of Study

○	Pathology
○	Allergology
○	Nutrition

Subject of Study

○	NASH線維化の病態解明と治療法の確立 (NASHモデル, 肝線維化モデル, 高脂肪コレステロール食, macrophage)
○	- (epicutaneous sensitization, food allergy, 甲殻類アレルギー, Tropmyosin, model animal of food allergy by epicutaneous sensitization, deep sea water, 職業性食物アレルギー)
○

Book / Paper

Book:

1.	Mayuko Shimizu, Nakanishi Atsuko, Kitagishi Yasuko and Matsuda Satoru : Function of the RUN Domain on RUFY Family Proteins, Springer, Jun. 2018. (Keyword) RUFY
2.	Akari Minami, Toshiyuki Murai, Atsuko Nakanishi, Yasuko Kitagishi, Mayuko Shimizu and Satoru Matsuda : Cell cycle regulation via the p53, PTEN, and BRCA1 tumor suppressors, InTech, 2016.

Academic Paper (Judged Full Paper):

1.	Masahiro Umemura, Akira Honda, Maho Yamashita, Takeshi Chida, Hidenao Noritake, Kenta Yamamoto, Takashi Honda, Mayuko Shimizu, Koichi Tsuneyama, Teruo Miyazaki, Nobuhito Kurono, C Patrick S Leung, Eric M Gershwin, Takafumi Suda and Kazuhito Kawata : High-fat diet modulates bile acid composition and gut microbiota, affecting severe cholangitis and cirrhotic change in murine primary biliary cholangitis., Journal of Autoimmunity, Vol.148, 2024. (Summary) Increasing evidence suggests that, in addition to a loss of tolerance, bile acid (BA) modulates the natural history of primary biliary cholangitis (PBC). We focused on the impacts of dietary changes on the immunopathology of PBC, along with alterations in BA composition and gut microbiota. In this study, we have taken advantage of our unique PBC model, a Cyp2c70/Cyp2a12 double knockout (DKO), which includes a human-like BA composition, and develops progressive cholangitis following immunization with the PDC-E2 mimic, 2-octynoic acid (2OA). We compared the effects of a ten-week high-fat diet (HFD) (60% kcal from fat) and a normal diet (ND) on 2OA-treated DKO mice. Importantly, we report that 2OA-treated DKO mice fed HFD had significantly exacerbated cholangitis, leading to cirrhosis, with increased hepatic expression of Th1 cytokines/chemokines and hepatic fibrotic markers. Serum lithocholic acid (LCA) levels and the ratio of chenodeoxycholic acid (CDCA)-derived BAs to cholic acid-derived BAs were significantly increased by HFD. This was also associated with downregulated expression of key regulators of BA synthesis, including Cyp8b1, Cyp3a11, and Sult2a1. In addition, there were increases in the relative abundances of Acetatifactor and Lactococcus and decreases in Desulfovibrio and Lachnospiraceae_NK4A136_group, which corresponded to the abundances of CDCA and LCA. In conclusion, HFD and HFD-induced alterations in the gut microbiota modulate BA composition and nuclear receptor activation, leading to cirrhotic change in this murine PBC model. These findings have significant implications for understanding the progression of human PBC. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.jaut.2024.103287 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 39033687 ● Search Scopus @ Elsevier (PMID): 39033687 ● Search Scopus @ Elsevier (DOI): 10.1016/j.jaut.2024.103287 (DOI: 10.1016/j.jaut.2024.103287, PubMed: 39033687)
2.	Saya Matsuzaki, Eiji Hase, Hiroki Takanari, Yuri Hayashi, Yusaku Hayashi, Haruto Oshikata, Takeo Minamikawa, Satoko Kimura, Mayuko Shimizu, Takeshi Yasui, Masafumi Harada and Koichi Tsuneyama : Quantification of collagen fiber properties in alcoholic liver fibrosis using polarization-resolved second harmonic generation microscopy., Scientific Reports, Vol.13, No.1, 22100, 2023. (Summary) Liver fibrosis is assessed mainly by conventional staining or second harmonic generation (SHG) microscopy, which can only provide collagen content in fibrotic area. We propose to use polarization-resolved SHG (PR-SHG) microscopy to quantify liver fibrosis in terms of collagen fiber orientation and crystallization. Liver samples obtained from autopsy cases with fibrosis stage of F0-F4 were evaluated with an SHG microscope, and 12 consecutive PR-SHG images were acquired while changing the polarization azimuth angle of the irradiated laser from 0° to 165° in 15° increments using polarizer. The fiber orientation angle (φ) and degree (ρ) of collagen were estimated from the images. The SHG-positive area increased as the fibrosis stage progressed, which was well consistent with Sirius Red staining. The value of φ was random regardless of fibrosis stage. The mean value of ρ (ρ-mean), which represents collagen fiber crystallinity, varied more as fibrosis progressed to stage F3, and converged to a significantly higher value in F4 than in other stages. Spatial dispersion of ρ (ρ-entropy) also showed increased variation in the stage F3 and decreased variation in the stage F4. It was shown that PR-SHG could provide new information on the properties of collagen fibers in human liver fibrosis. (Keyword) Humans / Second Harmonic Generation Microscopy / Collagen / Liver Cirrhosis / Refraction, Ocular / Coloring Agents (Link to Publication Site) ● Publication site (DOI): 10.1038/s41598-023-48887-8 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38092851 ● Search Scopus @ Elsevier (PMID): 38092851 ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-023-48887-8 (DOI: 10.1038/s41598-023-48887-8, PubMed: 38092851)
3.	Mayuko Shimizu, Masami Kojima, Shingo Suzuki, Misaki Miyata, Yui Osaki, Konomi Matsui, Toshiyuki Mizui and Koichi Tsuneyama : Brain-derived neurotrophic factor knock-out mice develop non-alcoholic steatohepatitis., The Journal of Pathology, Vol.261, No.4, 465-476, 2023. (Summary) mice developed hepatocellular damage and showed infiltration of inflammatory cells, including neutrophils in the liver, despite having body weights and blood parameters that were comparable to those of controls. This is the first report demonstrating that reduced BDNF expression plays a role in the pathogenic mechanism of NASH, which is a hepatic manifestation of metabolic syndrome. © 2023 The Pathological Society of Great Britain and Ireland. (Keyword) Humans / Mice / Animals / Non-alcoholic Fatty Liver Disease / Brain-Derived Neurotrophic Factor / Mice, Knockout / Liver / Inflammation / Obesity / Mice, Inbred C57BL / Disease Models, Animal / Diet, High-Fat (Tokushima University Institutional Repository) ● Metadata: 119260 (Link to Publication Site) ● Publication site (DOI): 10.1002/path.6204 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37781961 ● Search Scopus @ Elsevier (PMID): 37781961 ● Search Scopus @ Elsevier (DOI): 10.1002/path.6204 (Tokushima University Institutional Repository: 119260, DOI: 10.1002/path.6204, PubMed: 37781961)
4.	Nana Makiuchi, Shun Takano, Yuki Tada, Kaichi Kasai, Naoya Igarashi, Koudai Kani, Miyuna Kato, Kana Goto, Yudai Matsuura, Mayuko Shimizu, Yukihiro Furusawa, Koichi Tsuneyama and Yoshinori Nagai : Dynamics of Liver Macrophage Subsets in a Novel Mouse Model of Non-Alcoholic Steatohepatitis Using C57BL/6 Mice., Biomedicines, Vol.11, No.10, 2659, 2023. (Summary) cells were not distinct populations in the iHFC-fed TSNO mice. Thus, differences in cholic acid content and mouse strain affect the macrophage subsets that accumulate in the liver. (Link to Publication Site) ● Publication site (DOI): 10.3390/biomedicines11102659 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37893033 ● Summary page in Scopus @ Elsevier: 2-s2.0-85175452293 (DOI: 10.3390/biomedicines11102659, PubMed: 37893033, Elsevier: Scopus)
5.	Wenhua Shao, Mayuko Shimizu, Hirohisa Ogawa, Shengjian Jin, Mitsuko Sutoh, Satoko Nakamura, Miki Onodera, Hirosuke Tawara, Shunji Toyohara, Ryoji Hokao, Yasusei Kudo, Takeshi Oya and Koichi Tsuneyama : Establishment of repeated liver biopsy technique in experimental mice., Heliyon, Vol.9, No.6, e16978, 2023. (Summary) Biopsy is a commonly used method for determining pathological diagnoses by directly using human tissues and cells. Biopsies are widely used to determine disease progression and treatment efficacy. Although organs and tissues are usually obtained by sacrifice during animal experiments, it is theoretically possible to use the same biopsy techniques in humans. In the present study, we examined the feasibility of performing four repeated liver biopsies in a spontaneous metabolic syndrome mouse model. Even though a small number of mice died accidently, most mice were able to undergo four liver biopsies without significant adverse events. We also performed three liver biopsies in mouse liver tumor carcinogen models at 4, 8, and 12 weeks of age. In addition to the sample collected at 16 weeks of age during sacrifice, we successfully collected four liver samples from the same mice at different stages of disease progression. The application of this liver biopsy technique might make it possible for direct evaluation of pathological conditions in the same individual over time, thereby reducing the number of experimental animals. (Tokushima University Institutional Repository) ● Metadata: 118954 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.heliyon.2023.e16978 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37484353 ● Summary page in Scopus @ Elsevier: 2-s2.0-85161065015 (Tokushima University Institutional Repository: 118954, DOI: 10.1016/j.heliyon.2023.e16978, PubMed: 37484353, Elsevier: Scopus)
6.	Takumi Kakimoto, Masato Hosokawa, Mayuko Shimizu, Hirohisa Ogawa, Yuko Miyakami, Satoshi Sumida and Koichi Tsuneyama : Accumulation of α-synuclein in hepatocytes in nonalcoholic steatohepatitis and its usefulness in pathological diagnosis., Pathology, Research and Practice, Vol.247, 154525, 2023. (Summary) Nonalcoholic steatohepatitis (NASH) is characterized by fat deposition, inflammation, and hepatocellular damage. The diagnosis of NASH is confirmed pathologically, and hepatocyte ballooning is an important finding for definite diagnosis. Recently, α-synuclein deposition in multiple organs was reported in Parkinson's disease. Since it was reported that α-synuclein is taken up by hepatocytes via connexin 32, the expression of α-synuclein in the liver in NASH is of interest. The accumulation of α-synuclein in the liver in NASH was investigated. Immunostaining for p62, ubiquitin, and α-synuclein was performed, and the usefulness of immunostaining in pathological diagnosis was examined. Liver biopsy tissue specimens from 20 patients were evaluated. Several antibodies against α-synuclein, as well as antibodies against connexin 32, p62, and ubiquitin were used for immunohistochemical analyses. Staining results were evaluated by several pathologists with varying experience, and the diagnostic accuracy of ballooning was compared. Polyclonal α-synuclein antibody, not the monoclonal antibody, reacted with eosinophilic aggregates in ballooning cells. Expression of connexin 32 in degenerating cells was also demonstrated. Antibodies against p62 and ubiquitin also reacted with some of the ballooning cells. In the pathologists' evaluations, the highest interobserver agreement was obtained with hematoxylin and eosin (H&E)-stained slides, followed by slides immunostained for p62 and α-synuclein, and there were cases with different results between H&E staining and immunostaining CONCLUSION: These results indicate the incorporation of degenerated α-synuclein into ballooning cells, suggesting the involvement of α-synuclein in the pathogenesis of NASH. The combination of immunostaining including polyclonal α-synuclein may contribute to improving the diagnosis of NASH. (Keyword) α-synuclein / NASH / Ballooning (Tokushima University Institutional Repository) ● Metadata: 118741 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.prp.2023.154525 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37209576 ● Search Scopus @ Elsevier (PMID): 37209576 ● Search Scopus @ Elsevier (DOI): 10.1016/j.prp.2023.154525 (Tokushima University Institutional Repository: 118741, DOI: 10.1016/j.prp.2023.154525, PubMed: 37209576)
7.	Koudai Kani, Kaichi Kasai, Yuki Tada, Riko Ishibashi, Shun Takano, Naoya Igarashi, Mayuko Shimizu, Koichi Tsuneyama, Yukihiro Furusawa and Yoshinori Nagai : The innate immune receptor RP105 promotes metabolic syndrome by altering gut microbiota composition and intestinal barrier function., Biochemical and Biophysical Research Communications, Vol.664, 77-85, 2023. (Summary) mice. A 16S rRNA sequence analysis indicated that RP105 modified gut microbiota composition and was involved in the maintenance of its diversity. Thus, RP105 promotes metabolic syndrome by altering gut microbiota composition and intestinal barrier function. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2023.04.068 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37146560 ● Summary page in Scopus @ Elsevier: 2-s2.0-85153938087 (DOI: 10.1016/j.bbrc.2023.04.068, PubMed: 37146560, Elsevier: Scopus)
8.	Yuko Miyakami, Takeo Minamikawa, Hirohisa Ogawa, Mayuko Shimizu and Koichi Tsuneyama : Definitive Confirmation of Erythropoietic Protoporphyria via Re-biopsy Three Years After Initial Liver Biopsy at Age 15., Curēus, Vol.15, No.4, e38017, 2023. (Summary) Erythropoietic protoporphyria (EPP) is a rare inherited disorder of porphyrin metabolism that can cause liver damage and cholestatic hepatocellular failure. We report a case of EPP in a teenaged male who underwent liver biopsy for investigation of liver dysfunction of unknown cause. The diagnosis was not made until a re-biopsy approximately three years later, when the patient presented with recurrent skin lesions and elevated blood and urinary protoporphyrin levels. The liver biopsies contained brownish deposits that exhibited birefringence under polarized light and porphyrin fluorescence under fluorescence spectroscopy. EPP should be considered in young patients with unexplained liver dysfunction, skin symptoms, and seasonal changes in symptoms. Fluorescence spectroscopy of liver biopsy tissue can be a useful tool in the diagnosis of EPP. (Link to Publication Site) ● Publication site (DOI): 10.7759/cureus.38017 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37228562 ● Search Scopus @ Elsevier (PMID): 37228562 ● Search Scopus @ Elsevier (DOI): 10.7759/cureus.38017 (DOI: 10.7759/cureus.38017, PubMed: 37228562)
9.	Maho Yamashita, Akira Honda, Shin Shimoyama, Masahiro Umemura, Kazuyoshi Ohta, Takeshi Chida, Hidenao Noritake, Nobuhito Kurono, Mayuko Shimizu, Koichi Tsuneyama, Teruo Miyazaki, Atsushi Tanaka, C Patrick S Leung, Eric M Gershwin, Takafumi Suda and Kazuhito Kawata : Breach of tolerance versus burden of bile acids: Resolving the conundrum in the immunopathogenesis and natural history of primary biliary cholangitis., Journal of Autoimmunity, Vol.136, No.103027, 2023. (Summary) Primary biliary cholangitis (PBC) is a classic autoimmune disease due to the loss of tolerance to self-antigens. Bile acids (BA) reportedly play a major role in biliary inflammation and/or in the modulation of dysregulated immune responses in PBC. Several murine models have indicated that molecular mimicry plays a role in autoimmune cholangitis; however, they have all been limited by the relative failure to develop hepatic fibrosis. We hypothesized that species-specific differences in the BA composition between mice and humans were the primary reason for this limited pathology. Here, we aimed to study the impact of human-like hydrophobic BA composition on the development of autoimmune cholangitis and hepatic fibrosis. We took advantage of a unique construct, Cyp2c70/Cyp2a12 double knockout (DKO) mice, which have human-like BA composition, and immunized them with a well-defined mimic of the major mitochondrial autoantigen of PBC, namely 2-octynoic acid (2OA). 2OA-treated DKO mice were significantly exacerbated portal inflammation and bile duct damage with increased Th1 cytokines/chemokines at 8 weeks post-initial immunization. Most importantly, there was clear progression of hepatic fibrosis and increased expression of hepatic fibrosis-related genes. Interestingly, these mice demonstrated increased serum BA concentrations and decreased biliary BA concentrations; hepatic BA levels did not increase because of the upregulation of transporters responsible for the basolateral efflux of BA. Furthermore, cholangitis and hepatic fibrosis were more advanced at 24 weeks post-initial immunization. These results indicate that both the loss of tolerance and the effect of hydrophobic BA are essential for the progression of PBC. (Keyword) Humans / Animals / Mice / Liver Cirrhosis, Biliary / Bile Acids and Salts / Cholangitis / Autoimmune Diseases / Liver Cirrhosis / inflammation / Autoantigens / Disease Models, Animal (Link to Publication Site) ● Publication site (DOI): 10.1016/j.jaut.2023.103027 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36996700 ● Summary page in Scopus @ Elsevier: 2-s2.0-85151413932 (DOI: 10.1016/j.jaut.2023.103027, PubMed: 36996700, Elsevier: Scopus)
10.	Minoru Matsumoto, Takuya Ohmura, Yuto Hanibuchi, Mayuko Shimizu, Yasuyo Saijo, Hirohisa Ogawa, Ryuichiro Miyazawa, Junko Morimoto, Koichi Tsuneyama, Mitsuru Matsumoto and Takeshi Oya : AIRE illuminates the feature of medullary thymic epithelial cells in thymic carcinoma., Cancer Medicine, 2023. (Summary) Despite the clear distinction between cortical (cTECs) and medullary thymic epithelial cells (mTECs) in physiology, the cell of origin of thymic carcinomas (TCs) and other thymic epithelial tumors remained enigmatic. We addressed this issue by focusing on AIRE, an mTEC-specific transcriptional regulator that is required for immunological self-tolerance. We found that a large proportion of TCs expressed AIRE with typical nuclear dot morphology by immunohistochemistry. AIRE expression in TCs was supported by the RNA-seq data in the TCGA-THYM database. Furthermore, our bioinformatics approach to the recent single-cell RNA-seq data on human thymi has revealed that TCs hold molecular characteristics of multiple mTEC subpopulations. In contrast, TCs lacked the gene signatures for cTECs. We propose that TCs are tumors derived from mTECs. (Link to Publication Site) ● Publication site (DOI): 10.1002/cam4.5777 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36912123 ● Search Scopus @ Elsevier (PMID): 36912123 ● Search Scopus @ Elsevier (DOI): 10.1002/cam4.5777 (DOI: 10.1002/cam4.5777, PubMed: 36912123)
11.	Kaichi Kasai, Naoya Igarashi, Yuki Tada, Koudai Kani, Shun Takano, Tsutomu Yanagibashi, Fumitake Usui-Kawanishi, Shiho Fujisaka, Shiro Watanabe, Mayuko Shimizu, Kiyoshi Takatsu, Kazuyuki Tobe, Koichi Tsuneyama, Yukihiro Furusawa and Yoshinori Nagai : Impact of Vancomycin Treatment and Gut Microbiota on Bile Acid Metabolism and the Development of Non-Alcoholic Steatohepatitis in Mice., International Journal of Molecular Sciences, Vol.24, No.4, 2023. (Summary) -recruited macrophages into the liver, forming hepatic crown-like structures, was enhanced by vancomycin treatment. The co-localization of this macrophage subset with collagen was greatly augmented in the liver of vancomycin-treated iHFC-fed mice. These changes were rarely seen with the administration of metronidazole, which targets anaerobic organisms, in iHFC-fed mice. Finally, the vancomycin treatment dramatically modulated the level and composition of bile acid in iHFC-fed mice. Thus, our data demonstrate that changes in inflammation and fibrosis in the liver by the iHFC diet can be modified by antibiotic-induced changes in gut microbiota and shed light on their roles in the pathogenesis of advanced liver fibrosis. (Keyword) Animals / Mice / Anti-Bacterial Agents / Bile Acids and Salts / Diet, High-Fat / Disease Models, Animal / Gastrointestinal Microbiome / Liver / Liver Cirrhosis / Mice, Inbred C57BL / Non-alcoholic Fatty Liver Disease / Vancomycin (Tokushima University Institutional Repository) ● Metadata: 118835 (Link to Publication Site) ● Publication site (DOI): 10.3390/ijms24044050 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36835461 ● Summary page in Scopus @ Elsevier: 2-s2.0-85149053873 (Tokushima University Institutional Repository: 118835, DOI: 10.3390/ijms24044050, PubMed: 36835461, Elsevier: Scopus)
12.	Shin-ichiro Yamada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saitou, Mayuko Shimizu, Koichi Tsuneyama, Mitsue Nishiyama, Shiori Ishizawa and Mitsuo Shimada : Effect of daikenchuto (TU-100) on carcinogenesis in non-alcoholic steatohepatitis., The Journal of Medical Investigation : JMI, Vol.70, No.1.2, 66-73, 2023. (Summary) TU-100 regulates the intestinal microbiome and may suppress subsequent hepatocarcinogenesis in the NASH model. J. Med. Invest. 70 : 66-73, February, 2023. (Keyword) Mice / Animals / Non-alcoholic Fatty Liver Disease / Carcinoma, Hepatocellular / Liver Neoplasms / Liver / Carcinogenesis (Tokushima University Institutional Repository) ● Metadata: 118309 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.70.66 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37164745 ● Search Scopus @ Elsevier (PMID): 37164745 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.70.66 (Tokushima University Institutional Repository: 118309, DOI: 10.2152/jmi.70.66, PubMed: 37164745)
13.	Shin-ichiro Yamada, Yuji Morine, Tetsuya Ikemoto, Yu Saitou, Katsuki Miyazaki, Mayuko Shimizu, Koichi Tsuneyama and Mitsuo Shimada : Inhibitory effect of non-alcoholic steatohepatitis on colon cancer liver metastasis., EJSO - European Journal of Surgical Oncology, Vol.49, No.2, 410-415, 2023. (Summary) The WD-fed NASH mouse model showed an inhibitory effect on CLM. Suppressed interleukin-6/signal transducer and activator of transcription 3 signaling and serum amyloid A/matrix metalloproteinase 9 expression may affect this phenomenon. (Keyword) Male / Mice / Animals / Non-alcoholic Fatty Liver Disease / Mice, Inbred C57BL / Liver / Liver Neoplasms / Disease Models, Animal / Colonic Neoplasms / RNA, Messenger (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ejso.2022.11.002 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36371329 ● Search Scopus @ Elsevier (PMID): 36371329 ● Search Scopus @ Elsevier (DOI): 10.1016/j.ejso.2022.11.002 (DOI: 10.1016/j.ejso.2022.11.002, PubMed: 36371329)
14.	Katsuhisa Omagari, Ayumi Maruta, Natsuki Yayama, Yuki Yoshida, Kyoko Okamoto, Bungo Shirouchi, Shouhei Takeuchi, Kazuhito Suruga, Kazunori Koba, Mayuko Shimizu and Koichi Tsuneyama : The Effects of Overnight Fasting Duration on Glucose and Lipid Metabolism in a Sprague-Dawley Rat Model of Nonalcoholic Steatohepatitis with Advanced Fibrosis., Journal of Nutritional Science and Vitaminology, Vol.69, No.5, 357-369, 2023. (Summary) Nonalcoholic steatohepatitis (NASH) can progress to hepatic fibrosis, and is associated with cardiovascular and liver-related mortality. To understand the pathogenesis of NASH, reliable animal models of the disease are useful. In animal studies, the animals are usually fasted overnight before biospecimens are taken, but little is known about the effects of fasting. Here, we investigated the impact of overnight fasting for approximately 9 to 17 h on glucose and lipid metabolism in a Sprague-Dawley (SD) rat model of diet-induced moderate and advanced NASH in comparison to normal SD rats. Our results revealed that in the moderate NASH model rats, the fasting duration did not affect glucose and lipid metabolism, the histopathological findings, or the hepatic mRNA expression levels of genes related to lipid metabolism, cholesterol metabolism, inflammation, fibrosis, and oxidative stress. In contrast, in the normal rats, significant fasting time-dependent reductions were observed in the epididymal fat pad weight and the hepatic mRNA expression levels of adipose differentiation-related protein and heme oxygenase-1. Moreover, in the advanced NASH model rats, a significant fasting time-dependent reduction and increase were observed in the serum insulin level and mRNA expression level of alpha-smooth muscle actin, respectively. Our present results suggest that the influence of the overnight fasting duration differs among the healthy condition, moderate NASH, and advanced NASH statuses. Further studies are needed in humans to determine the appropriate overnight fasting duration for the accurate evaluation of glucose and lipid metabolism in NASH patients. (Keyword) Humans / Rats / Animals / Non-alcoholic Fatty Liver Disease / Rats, Sprague-Dawley / glucose / Lipid Metabolism / Diet, High-Fat / Liver / Liver Cirrhosis / Fasting / RNA, Messenger / Disease Models, Animal (Link to Publication Site) ● Publication site (DOI): 10.3177/jnsv.69.357 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37940576 ● Summary page in Scopus @ Elsevier: 2-s2.0-85176421950 (DOI: 10.3177/jnsv.69.357, PubMed: 37940576, Elsevier: Scopus)
15.	Satoshi Sumida, Mayuko Shimizu, Yuko Miyakami, Takumi Kakimoto, Tomoko Kobayashi, Yasuyo Saijo, Minoru Matsumoto, Hirohisa Ogawa, Takeshi Oya, Yoshimi Bando, Hisanori Uehara, Shu Taira, Mitsuo Shimada and Koichi Tsuneyama : Histological and immunohistochemical analysis of epithelial cells in epidermoid cysts in intrapancreatic accessory spleen., The Journal of Medical Investigation : JMI, Vol.70, No.1.2, 251-259, 2023. (Summary) Novel histological features of epithelial cells of ECIPAS were indicated. Although more cases need to be evaluated, we propose that the cause of ECIPAS may be different from that of pancreatic ductal origin. J. Med. Invest. 70 : 251-259, February, 2023. (Keyword) Humans / Epidermal Cyst / Spleen / Pancreatic Diseases / Epithelial Cells / Immunohistochemistry (Tokushima University Institutional Repository) ● Metadata: 118205 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.70.251 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37164730 ● Search Scopus @ Elsevier (PMID): 37164730 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.70.251 (Tokushima University Institutional Repository: 118205, DOI: 10.2152/jmi.70.251, PubMed: 37164730)
16.	Wenhua Shao, Orgil Jargalsaikhan, Mayuko Shimizu, Qinyi Cai, Hirohisa Ogawa, Yuko Miyakami, Kengo Atsumi, Mitsuru Tomita, Mitsuko Sutoh, Shunji Toyohara, Ryoji Hokao, Yasusei Kudo, Takeshi Oya and Koichi Tsuneyama : Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice., International Journal of Molecular Sciences, Vol.23, No.19, 2022. (Summary) Male Tsumura-Suzuki Obese Diabetes (TSOD) mice, a spontaneous metabolic syndrome model, develop non-alcoholic steatohepatitis and liver tumors by feeding on a standard mouse diet. Nearly 70% of liver tumors express glutamine synthetase (GS), a marker of hepatocellular carcinoma. In contrast, approximately 30% are GS-negative without prominent nuclear or structural atypia. In this study, we examined the characteristics of the GS-negative tumors of TSOD mice. Twenty male TSOD mice were sacrificed at 40 weeks and a total of 21 tumors were analyzed by HE staining and immunostaining of GS, liver fatty acid-binding protein (L-FABP), serum amyloid A (SAA), and beta-catenin. With immunostaining for GS, six (29%) tumors were negative. Based on the histological and immunohistological characteristics, six GS-negative tumors were classified into several subtypes of human hepatocellular adenoma (HCA). One large tumor showed generally similar findings to inflammatory HCA, but contained small atypical foci with GS staining and partial nuclear beta-catenin expression suggesting malignant transformation. GS-negative tumors of TSOD mice contained features similar to various subtypes of HCA. Different HCA subtypes occurring in the same liver have been reported in humans; however, the diversity of patient backgrounds limits the ability to conduct a detailed, multifaceted analysis. TSOD mice may share similar mechanisms of HCA development as in humans. It is timely to review the pathogenesis of HCA from both genetic and environmental perspectives, and it is expected that TSOD mice will make further contributions in this regard. (Keyword) Adenoma, Liver Cell / Animals / Carcinoma, Hepatocellular / diabetes mellitus / Fatty Acid-Binding Proteins / Glutamate-Ammonia Ligase / Humans / immunohistochemistry / Liver Neoplasms / male / Metabolic Syndrome / Mice / Mice, Obese / Non-alcoholic Fatty Liver Disease / Serum Amyloid A Protein / beta Catenin (Tokushima University Institutional Repository) ● Metadata: 118862 (Link to Publication Site) ● Publication site (DOI): 10.3390/ijms231911923 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36233225 ● Summary page in Scopus @ Elsevier: 2-s2.0-85139812612 (Tokushima University Institutional Repository: 118862, DOI: 10.3390/ijms231911923, PubMed: 36233225, Elsevier: Scopus)
17.	Ryosuke Nagatomo, Haruki Kaneko, Shihori Kamatsuki, Mayuko Shimizu, Naozumi Ishimaru, Koichi Tsuneyama and Koichi Inoue : Short-chain fatty acid profiling in biological samples from a mouse model of Sjögrens syndrome based on derivatized LC-MS/MS assay., Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, Vol.1210, 123432, 2022. (Summary) An analytical platform is required to characterize the short-chain fatty acids (SCFAs) in a mouse model of pathological immune conditions. Therefore, liquid chromatography tandem mass spectrometry combined with 2-picolylamine derivatization and a comprehensive study of SCFAs distribution based on serum, saliva, feces, liver, and brain from a mouse model of Sjögren's syndrome (SS) is performed. The design of experiments is used to achieve efficient 2-picolylamine derivatization, and optimize the reaction conditions. Twelve SCFAs are derivatized, and separated on a reversed-phase C column. All SCFAs show high linearity (r > 0.995) and intra/inter-day accuracy values from 71.6% to 115.6% (precision < 13.7%). This method was used to determine SCFAs concentrations in the serum, saliva, feces, liver, and brain of an SS model mice, and isobutyric acid, valeric acid, isovaleric acid, and 2-methylbutyric acid in liver from SS were significantly different compared with control group. Moreover, the preliminary evaluation of propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid in saliva is conducted based on the respective SS stages and are correlated with these histological scores. This analytical platform for the widely SCFAs profiling in several tissues can be a clue for studying unclear immune pathophysiology. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.jchromb.2022.123432 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36063699 ● Summary page in Scopus @ Elsevier: 2-s2.0-85137093675 (DOI: 10.1016/j.jchromb.2022.123432, PubMed: 36063699, Elsevier: Scopus)
18.	Mayuko Shimizu, Shiro Watanabe, Yuka Kashirajima, Ami Nagatomo, Hitomi Wada, Koichi Tsuneyama and Katsuhisa Omagari : Dietary Cholic Acid Exacerbates Liver Fibrosis in NASH Model of Sprague-Dawley Rats Fed a High-Fat and High-Cholesterol Diet., International Journal of Molecular Sciences, Vol.23, No.16, 2022. (Summary) Adding CA to the HFC diet altered bile acid metabolism and inflammatory response and triggered the development of fibrosis in the rat liver. (Keyword) Animals / Cholesterol / Cholesterol, Dietary / Cholic Acid / Diet / Diet, High-Fat / Disease Models, Animal / Hypercholesterolemia / Hyperlipidemias / Inflammation / Liver / Liver Cirrhosis / Male / Non-alcoholic Fatty Liver Disease / Rats / Rats, Sprague-Dawley (Link to Publication Site) ● Publication site (DOI): 10.3390/ijms23169268 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36012527 ● Search Scopus @ Elsevier (PMID): 36012527 ● Search Scopus @ Elsevier (DOI): 10.3390/ijms23169268 (DOI: 10.3390/ijms23169268, PubMed: 36012527)
19.	Kenta Yagi, Yasutaka Sato, Satoshi Sakaguchi, Mitsuhiro Goda, Hirofumi Hamano, Fuka Aizawa, Mayuko Shimizu, Arisa Inoue-Hamano, Toshihide Nishimori, Masato Tagi, Marina Kanno, Rie Matsuoka-Ando, Toshihiko Yoshioka, Yoshiko Matstubara, Yuki Izawa-Ishizawa, Rieko Shimizu, Akinori Maruo, Yurika Kuniki, Yoshika Sakamoto, Sayuri Itobayashi, Yoshito Zamami, Hiroaki Yanagawa and Keisuke Ishizawa : A web-based survey of educational opportunities of medical professionals based on changes in conference design during the COVID-19 pandemic., Education and Information Technologies, Vol.27, 10371-10386, 2022. (Summary) The online version contains supplementary material available at 10.1007/s10639-022-11032-5. (Link to Publication Site) ● Publication site (DOI): 10.1007/s10639-022-11032-5 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35464114 ● Search Scopus @ Elsevier (PMID): 35464114 ● Search Scopus @ Elsevier (DOI): 10.1007/s10639-022-11032-5 (DOI: 10.1007/s10639-022-11032-5, PubMed: 35464114)
20.	Mayuko Shimizu, Soichiroh Ishimaru, Wai Yee Yan Christine, Takeo Minamikawa, Takaaki Tsunematsu, Aiko Endoh, Takumi Kojima, Minoru Matsumoto, Tomoko Kobayashi, Satoshi Sumida, Takumi Kakimoto, MIYAGAMI Yuko, Hirohisa Ogawa, Takeshi Oya and Koichi Tsuneyama : Establishment of an epicutaneously sensitized murine model of shellfish allergy and evaluation of skin condition by Raman microscopy., Applied Sciences, Vol.12, No.3566, 2022. (Tokushima University Institutional Repository) ● Metadata: 117211 (Link to Publication Site) ● Publication site (DOI): 10.3390/app12073566 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.3390/app12073566 (Tokushima University Institutional Repository: 117211, DOI: 10.3390/app12073566)
21.	Hirohisa Ogawa, Masahiko Azuma, Aya Umeno, Mayuko Shimizu, Kazutoshi Murotomi, Yasukazu Yoshida, Yasuhiko Nishioka and Koichi Tsuneyama : Singlet oxygen -derived nerve growth factor exacerbates airway hyperresponsiveness in a mouse model of asthma with mixed inflammation., Allergology International, Vol.71, No.3, 395-404, 2022. (Summary) Our findings suggest that neutrophil MPO-derived singlet oxygen induces increased NGF production, leading to AHR and 10- and 12-(Z,E)-HODEs production. These findings may help to develop new therapies targeting this mechanism and to establish a new biomarker for non-type 2 and refractory asthma. (Keyword) Animals / Asthma / Bronchial Hyperreactivity / Disease Models, Animal / Inflammation / Lung / Mice / Mice, Inbred BALB C / Nerve Growth Factor / Respiratory Hypersensitivity / Singlet Oxygen (Tokushima University Institutional Repository) ● Metadata: 117273 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.alit.2022.02.005 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35346582 ● Search Scopus @ Elsevier (PMID): 35346582 ● Search Scopus @ Elsevier (DOI): 10.1016/j.alit.2022.02.005 (Tokushima University Institutional Repository: 117273, DOI: 10.1016/j.alit.2022.02.005, PubMed: 35346582)
22.	Takeo Minamikawa, Eiji Hase, Mayuko Shimizu, Yuki Morimoto, Akihiro Suzuki, Takeshi Yasui, Satoko Nakamura, Akemi Tsutsui, Koichi Takaguchi and Koichi Tsuneyama : Assessment of Ultra-Early-Stage Liver Fibrosis in Human Non-Alcoholic Fatty Liver Disease by Second-Harmonic Generation Microscopy., International Journal of Molecular Sciences, Vol.23, No.6, 3357, 2022. (Summary) Non-alcoholic fatty liver disease (NAFLD) is associated with the chronic progression of fibrosis. In general, the progression of liver fibrosis is determined by a histopathological assessment with a collagen-stained section; however, the ultra-early stage of liver fibrosis is challenging to identify because of the low sensitivity in the collagen-selective staining method. In the present study, we demonstrate the feasibility of second-harmonic generation (SHG) microscopy in the histopathological diagnosis of the liver of NAFLD patients for the quantitative assessment of the ultra-early stage of fibrosis. We investigated four representative NAFLD patients with early stages of fibrosis. SHG microscopy visualised well-matured fibrotic structures and early fibrosis diffusely involving liver tissues, whereas early fibrosis is challenging to be identified by conventional histopathological methods. Furthermore, the SHG emission directionality analysis revealed the maturation of each collagen fibre of each patient. As a result, SHG microscopy is feasible for assessing liver fibrosis on NAFLD patients, including the ultra-early stage of liver fibrosis that is difficult to diagnose by the conventional histopathological method. The assessment method of the ultra-early fibrosis by using SHG microscopy may serve as a crucial means for pathological, clinical, and prognostic diagnosis of NAFLD patients. (Keyword) Biopsy / Collagen / Fibrosis / Humans / Liver / Liver Cirrhosis / Non-alcoholic Fatty Liver Disease / Second Harmonic Generation Microscopy (Tokushima University Institutional Repository) ● Metadata: 117221 (Link to Publication Site) ● Publication site (DOI): 10.3390/ijms23063357 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35328778 ● Summary page in Scopus @ Elsevier: 2-s2.0-85126575411 (Tokushima University Institutional Repository: 117221, DOI: 10.3390/ijms23063357, PubMed: 35328778, Elsevier: Scopus)
23.	Katsuhisa Omagari, Miku Uchida, Yumeno Tagawa, Mizuki Yogo, Kae Inagaki, Ryoko Hongo, Shouhei Takeuchi, Kazuhito Suruga, Kazunori Koba, Mayuko Shimizu and Koichi Tsuneyama : Influence of Fasting Time on Serum and Hepatic Lipid Profiles in a Sprague-Dawley Rat Model of Nonalcoholic Steatohepatitis., Journal of Nutritional Science and Vitaminology, Vol.68, No.5, 409-419, 2022. (Summary) Nonalcoholic steatohepatitis (NASH) is associated with several cardiovascular risk factors, including atherogenic dyslipidemia. Recently, fasting prior to lipid profile evaluation has been thought to be unnecessary for most individuals. We investigated the impact of fasting for up to 9 h on the serum and hepatic lipid profiles in Sprague-Dawley (SD) rats of dietary-induced NASH model in comparison to SD rats fed a normal diet. In both groups, fasting affected the serum and hepatic triglyceride (TG), serum free fatty acid (FFA) and leptin levels, histopathologically assessed hepatocyte ballooning, and hepatic mRNA expression levels of several genes related to lipid metabolism. In contrast, the serum adiponectin and aminotransferase levels, serum and hepatic total cholesterol contents, and liver histopathological findings of hepatic steatosis, lobular inflammation and fibrosis were not influenced by fasting. A significant fasting time-dependent reduction was seen in the serum TG level only in the normal SD rats group. Regarding the hepatic TG level, a significant fasting time-dependent increase was seen only in the NASH model rat group. A significant fasting time-dependent reduction was also seen in the serum FFA level only in the NASH model rat group. Our present results indicate that excessive fasting can be avoided before blood or hepatic tissue sampling for the evaluation of several parameters in non-NASH and/or NASH model rats. Further investigations are needed in humans to determine whether excessive fasting before blood or hepatic tissue sampling can be avoided in both healthy individuals and NASH patients. (Keyword) Animals / Rats / Disease Models, Animal / Fasting / Liver / Non-alcoholic Fatty Liver Disease / Rats, Sprague-Dawley / Triglycerides / Lipid Metabolism (Link to Publication Site) ● Publication site (DOI): 10.3177/jnsv.68.409 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36310075 ● Summary page in Scopus @ Elsevier: 2-s2.0-85140853234 (DOI: 10.3177/jnsv.68.409, PubMed: 36310075, Elsevier: Scopus)
24.	Mayuko Shimizu, Yosuke Tsuchiyama, Yuki Morimoto, Minoru Matsumoto, Tomoko Kobayashi, Satoshi Sumida, Takumi Kakimoto, Takeshi Oya, Hirohisa Ogawa, Michiko Yamashita, Satoru Matsuda, Katsuhisa Omagari, Shu Taira and Koichi Tsuneyama : A novel mouse model of non-alcoholic steatohepatitis suggests that liver fibrosis initiates around lipid-laden macrophages, The American Journal of Pathology, Vol.192, No.1, 31-42, 2022. (Summary) Various cells, such as macrophages and hepatic stellate cells, interact in the generation of fibrosis in nonalcoholic steatohepatitis (NASH), but the mechanism remains unclear. We employed a high-fat/cholesterol/cholate (HFCC) diet to generate a model of NASH-related fibrosis and investigate the pathogenesis of fibrosis. Two mouse strains differing in susceptibility to obesity, the susceptible strain C57BL/6J and the relatively resistant strain A/J, developed hepatic histologic features of NASH, including fat deposition, intralobular inflammation, hepatocyte ballooning, and fibrosis, after 9 weeks of HFCC diet feeding. The severity of hepatic inflammation and fibrosis was greater in A/J mice than in C57BL/6J mice. A/J mice fed the HFCC diet exhibited characteristic CD204-positive lipid-laden macrophage aggregation in hepatic parenchyma. Polarized light visualized the Maltese cross (namely, cholesterol crystals within the aggregated macrophages). Moreover, fibrosis developed in a ring shape from the periphery of the aggregated macrophages (ie, the starting point of fibrosis could be visualized histologically). Furthermore, matrix-assisted laser desorption/ionization mass spectrometry imaging analysis detected a molecule at m/z 772.462, which corresponds to the protonated ion of phosphatidylcholine [P-18:1 (11Z)/18:0] and phosphatidylethanolamine [18:0/20:2 (11Z, 14Z)], in aggregated macrophages adjacent to the fibrotic lesions. In conclusion, the present HFCC diet-fed A/J model provides an ideal tool to study fibrogenesis and enables novel insights into the pathophysiology of NASH-related fibrosis. (Keyword) Liver fibrosis / macrophage / animal model / cholesterol / cholate (Tokushima University Institutional Repository) ● Metadata: 116411 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ajpath.2021.10.002 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34710382 ● CiNii @ National Institute of Informatics (CRID): 1360857593792147200 ● Search Scopus @ Elsevier (PMID): 34710382 ● Search Scopus @ Elsevier (DOI): 10.1016/j.ajpath.2021.10.002 (Tokushima University Institutional Repository: 116411, DOI: 10.1016/j.ajpath.2021.10.002, PubMed: 34710382, CiNii: 1360857593792147200)
25.	Mayuko Shimizu, Takeshi Kageyama, Takeshi Oya, Hirohisa Ogawa, Minoru Matsumoto, Satoshi Sumida, Takumi Kakimoto, Yuko Miyakami, Ryosuke Nagatomo, Koichi Inoue, Chunmei Cheng and Koichi Tsuneyama : Verification of the Impact of Blood Glucose Level on Liver Carcinogenesis and the Efficacy of a Dietary Intervention in a Spontaneous Metabolic Syndrome Model, International Journal of Molecular Sciences, Vol.22, No.23, 12844, 2021. (Summary) Metabolic syndrome (MS) is a risk factor for type 2 diabetes mellitus, vascular inflammation, atherosclerosis, and renal, liver, and heart diseases. Non-alcoholic steatohepatitis (NASH) is a progressive representative liver disease and may lead to the irreversible calamities of cirrhosis and hepatocellular carcinoma. Metabolic disorders such as hyperglycemia have been broadly reported to be related to hepatocarcinogenesis in NASH; however, direct evidence of a link between hyperglycemia and carcinogenesis is still lacking. Tsumura Suzuki Obese Diabetic (TSOD) mice spontaneously develop metabolic syndrome, including obesity, insulin resistance, and NASH-like liver phenotype, and eventually develop hepatocellular carcinomas. TSOD mice provide a spontaneous human MS-like model, even with significant individual variations. In this study, we monitored mice in terms of their changes in blood glucose levels, body weights, and pancreatic and liver lesions over time. As a result, liver carcinogenesis was delayed in non-hyperglycemic TSOD mice compared to hyperglycemic mice. Moreover, at the termination point of 40 weeks, liver tumors appeared in 18 of 24 (75%) hyperglycemic TSOD mice; in contrast, they only appeared in 5 of 24 (20.8%) non-hyperglycemic mice. Next, we investigated three kinds of oligosaccharide that could lower blood glucose levels in hyperglycemic TSOD mice. We monitored the levels of blood and urinary glucose and assessed pancreatic lesions among the experimental groups. As expected, significantly lower levels of blood and urinary glucose and smaller deletions of Langerhans cells were found in TSOD mice fed with milk-derived oligosaccharides (galactooligosaccharides and lactosucrose). At the age of 24 weeks, mild steatohepatitis was found in the liver but there was no evidence of liver carcinogenesis. Steatosis in the liver was alleviated in the milk-derived oligosaccharide-administered group. Taken together, suppressing the increase in blood glucose level from a young age prevented susceptible individuals from diabetes and the onset of NAFLD/NASH, as well as carcinogenesis. Milk-derived oligosaccharides showed a lowering effect on blood glucose levels, which may be expected to prevent liver carcinogenesis. (Tokushima University Institutional Repository) ● Metadata: 116736 (Link to Publication Site) ● Publication site (DOI): 10.3390/ijms222312844 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34884650 ● Search Scopus @ Elsevier (PMID): 34884650 ● Search Scopus @ Elsevier (DOI): 10.3390/ijms222312844 (Tokushima University Institutional Repository: 116736, DOI: 10.3390/ijms222312844, PubMed: 34884650)
26.	Tomoko Kobayashi, Mayuko Shimizu, Takeshi Oya, Hirohisa Ogawa, Minoru Matsumoto, Yuki Morimoto, Satoshi Sumida, Takumi Kakimoto, Michiko Yamashita, Mitsuko Sutoh, Shunji Toyohara, Ryoji Hokao, Chunmei Cheng and Koichi Tsuneyama : Neonatal streptozotocin treatment rapidly causes different subtype of hepatocellular carcinoma without persistent hyperglycemia in 4CS mice fed on a normal diet., Pathology, Research and Practice, Vol.225, No.153559, 2021. (Summary) Although diabetes mellitus (DM) is a well-known risk factor for hepatocellular carcinoma (HCC), the underlying mechanisms have not yet to be defined. We previously reported that DIAR mice fed with standard murine diet developed type 1 diabetes and HCC at age of 16 weeks old with a neonatal streptozotocin treatment (n-STZ). Because DIAR mice did not manifest obesity nor develop steatohepatitis, hyperglycemia with streptozotocin trigger or streptozotocin alone might turn on the hepato-carcinogenesis. An insulin-recruitment to DIAR-nSTZ mice showed an increased frequency of HCC during the first 12 weeks of age, although the diabetic indications notably improved. To elucidate the role of hyperglycemia in hepato-carcinogenesis, we performed a head-to-head comparative study by using 4CS mice and DIAR mice with n-STZ treatment. Newborn 4CS mice and DIAR mice were divided into STZ treated group and control group. The blood glucose levels of DIAR-nSTZ mice increased at age of eight weeks, while that of 4CS-nSTZ mice were maintained in the normal range. At eight weeks old, three out of five DIAR-nSTZ mice (60%) and one out of ten 4CS-nSTZ mice (10%) developed multiple liver tumors. At age of 12 weeks old, all eight of DIAR-nSTZ mice (100%) and two of 10 4CS-nSTZ mice (20%) developed multiple liver tumors. At 16 weeks old, all animals of DIAR-nSTZ and 4CS-nSTZ mice occurred liver tumors. DIAR-nSTZ showed hyperglycemia and HCC, and 4CS-nSTZ developed HCC without hyperglycemia. These results were interpreted that the onset of HCC maybe not related to the presence or absence of hyperglycemia but nSTZ treatment. On the other hand, since the carcinogenesis of 4CS-nSTZ is delayed compared to DIAR-nSTZ, hyperglycemia may play a role in the progression of carcinogenesis. Histologically, the liver tumor appeared irregularly trabecular arrangements of hepatocytes with various degrees of nuclear atypia. By immunohistochemical analyses, all liver tumors showed positive staining of glutamine synthetase (GS), an established human HCC marker. The expression pattern of GS was divided into a strong diffuse pattern and weak patchy pattern, respectively. The liver tumor showing the weak GS-patchy pattern expressed biliary/stem markers, EpCAM, and SALL4, partially. Because 4CS-nSTZ mice did not show any metabolic complications such as gaining body weight or high blood glucose level, it is a unique animal model with a simple condition to investigate hepatic carcinogenesis by excluding other factors. (Tokushima University Institutional Repository) ● Metadata: 118286 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.prp.2021.153559 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34325313 ● Search Scopus @ Elsevier (PMID): 34325313 ● Search Scopus @ Elsevier (DOI): 10.1016/j.prp.2021.153559 (Tokushima University Institutional Repository: 118286, DOI: 10.1016/j.prp.2021.153559, PubMed: 34325313)
27.	Yuki Morimoto, Takeshi Oya, Mayuko Shimizu, Minoru Matsumoto, Hirohisa Ogawa, Tomoko Kobayashi, Satoshi Sumida, Takumi Kakimoto, Michiko Yamashita, Chunmei Cheng and Koichi Tsuneyama : Applying Probe Electrospray Ionization Mass Spectrometry to Cytological Diagnosis: A Preliminary Study by Using Cultured Lung Cancer Cells., Acta Cytologica, Vol.65, No.5, 430-439, 2021. (Summary) PESI-MS presented a promising potential as a novel diagnostic modality for swiftly acquiring specific cytological information. (Tokushima University Institutional Repository) ● Metadata: 116345 (Link to Publication Site) ● Publication site (DOI): 10.1159/000516639 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34098551 ● Search Scopus @ Elsevier (PMID): 34098551 ● Search Scopus @ Elsevier (DOI): 10.1159/000516639 (Tokushima University Institutional Repository: 116345, DOI: 10.1159/000516639, PubMed: 34098551)
28.	Mayuko Shimizu, Katsuhisa Omagari, Michiko Yamashita and Koichi Tsuneyama : Development of a novel mouse model of diet-induced nonalcoholic steatohepatitis-related progressive bridging fibrosis., Bioscience, Biotechnology, and Biochemistry, Vol.85, No.4, 941-947, 2021. (Summary) Nonalcoholic steatohepatitis (NASH) progresses to liver fibrosis and cirrhosis. Existing mouse models of NASH rarely develop diet-induced severe fibrosis. We aimed to establish a dietary model of NASH with rapid progression to fibrosis. Six-week-old male Tsumura-Suzuki obese diabetes (TSOD) mice (a model of spontaneous metabolic syndrome) and corresponding control Tsumura-Suzuki nonobese (TSNO) mice were fed a novel diet high in fat, cholesterol, and cholate (iHFC). Histologic steatohepatitis, including steatosis, inflammation, and fibrosis, were observed in both TSNO and TSOD iHFC diet-fed mice at 20 weeks of age. As compared with TSOD mice, TSNO mice developed much more severe fibrosis and reached stage 3 of bridging fibrosis within 14 weeks under the iHFC diet feeding. Perivenular/perisinusoidal pattern of fibrosis in TSNO mice resembled human NASH. Our model of NASH with advanced fibrosis by simple diet offers many advantages useful in studying the mechanism of liver fibrosis and preclinical drug testing. (Link to Publication Site) ● Publication site (DOI): 10.1093/bbb/zbaa107 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33620426 ● Search Scopus @ Elsevier (PMID): 33620426 ● Search Scopus @ Elsevier (DOI): 10.1093/bbb/zbaa107 (DOI: 10.1093/bbb/zbaa107, PubMed: 33620426)
29.	Takeo Minamikawa, Mayuko Shimizu, Hiroki Takanari, Yuki Morimoto, Ryosuke Shiomi, Tanioka Hiroki, Eiji Hase, Takeshi Yasui and Koichi Tsuneyama : Molecular imaging analysis of microvesicular and macrovesicular lipid droplets in non-alcoholic fatty liver disease by Raman microscopy., Scientific Reports, Vol.10, No.1, 18548, 2020. (Summary) Predominant evidence of non-alcoholic fatty liver disease (NAFLD) is the accumulation of excess lipids in the liver. A small group with NAFLD may have a more serious condition named non-alcoholic steatohepatitis (NASH). However, there is a lack of investigation of the accumulated lipids with spatial and molecular information. Raman microscopy has the potential to characterise molecular species and structures of lipids based on molecular vibration and can achieve high spatial resolution at the organelle level. In this study, we aim to demonstrate the feasibility of Raman microscopy for the investigation of NAFLD based on the molecular features of accumulated lipids. By applying the Raman microscopy to the liver of the NASH model mice, we succeeded in visualising the distribution of lipid droplets (LDs) in hepatocytes. The detailed analysis of Raman spectra revealed the difference of molecular structural features of the LDs, such as the degree of saturation of lipids in the LDs. We also found that the inhomogeneous distribution of cholesterol in the LDs depending on the histology of lipid accumulation. We visualised and characterised the lipids of NASH model mice by Raman microscopy at organelle level. Our findings demonstrated that the Raman imaging analysis was feasible to characterise the NAFLD in terms of the molecular species and structures of lipids. (Tokushima University Institutional Repository) ● Metadata: 115619 (Link to Publication Site) ● Publication site (DOI): 10.1038/s41598-020-75604-6 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33122711 ● Search Scopus @ Elsevier (PMID): 33122711 ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-020-75604-6 (Tokushima University Institutional Repository: 115619, DOI: 10.1038/s41598-020-75604-6, PubMed: 33122711)
30.	Omagari Katsuhisa, Suzuta Masako, Taniguchi Asami, Kuramoto Risa, Koyama Yuko, Suruga Kazuhito, Mayuko Shimizu and Koichi Tsuneyama : A non-obese, diet-induced animal model of nonalcoholic steatohepatitis in Wistar/ST rats compared to Sprague-Dawley rats, Clinical Nutrition Experimental, Vol.30, 1-14, 2020. (Keyword) Non-alcoholic fatty liver disease / obesity / Wistar rat / Sprague-Dawley rat / High-fat diet / cholesterol (Tokushima University Institutional Repository) ● Metadata: 116726 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.yclnex.2020.03.001 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-85082200359 (Tokushima University Institutional Repository: 116726, DOI: 10.1016/j.yclnex.2020.03.001, Elsevier: Scopus)
31.	Atsuko Takai, Kentaro Kikuchi, Mayuko Shimizu, Koichi Tsuneyama, Yuki Moritoki, Kotaro Matsumoto, Hiromichi Tsunashima, Takeshi Onda, Noriyuki Kuniyoshi, Tomoyuki Nariyama, Sho Ohyatsu, Juri Kubota, Kozue Nagumo, Shinpei Sato, Masumi Hara and Hiroshi Miyakawa : Fructo-oligosaccharides ameliorate steatohepatitis, visceral adiposity, and associated chronic inflammation via increased production of short-chain fatty acids in a mouse model of non-alcoholic steatohepatitis., BMC Gastroenterology, Vol.20, No.1, 46, 2020. (Summary) FOS ameliorates steatohepatitis, visceral adiposity, and chronic inflammation by increasing SCFA production. (Tokushima University Institutional Repository) ● Metadata: 114532 (Link to Publication Site) ● Publication site (DOI): 10.1186/s12876-020-01194-2 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32103741 ● Summary page in Scopus @ Elsevier: 2-s2.0-85080096657 (Tokushima University Institutional Repository: 114532, DOI: 10.1186/s12876-020-01194-2, PubMed: 32103741, Elsevier: Scopus)
32.	Kanehiko Suwa, Takashi Yamaguchi, Katsunori Yoshida, Miki Murata, Mayuko Shimizu, Koichi Tsuneyama, Toshihito Seki and Kazuichi Okazaki : Smad Phospho-Isoforms for Hepatocellular Carcinoma Risk Assessment in Patients with Nonalcoholic Steatohepatitis., Cancers, Vol.12, No.2, 286, 2020. (Summary) Nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) sometimes occurs in mildly fibrotic livers, while HCC incidence in NASH-related cirrhosis is lower than and less predictable than in hepatitis C virus (HCV)-related cirrhosis. Transforming growth factor (TGF)-β signaling in hepatocytic nuclei is implicated in fibrosis and carcinogenesis. TGF-βtype I receptor (TβRI) and c-Jun N-terminal kinase (JNK) differentially phosphorylate the mediator Smad3, resulting in 2 distinct phospho-isoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). In mature hepatocytes, oncogenic signaling via the JNK/pSmad3L pathway antagonizes signaling via the tumor-suppressive TβRI/pSmad3C pathway. We immunohistochemically examined domain-specific Smad3 phosphorylation in liver biopsy specimens from 30 NASH patients representing different fibrotic stages and 20 chronically infected hepatitis C patients as controls, correlating Smad3 phosphorylation with clinical course. HCC occurred during follow-up in 11 of 12 NASH patients with abundant pSmad3L and limited pSmad3C but in only 2 of 18 with limited pSmad3L. In contrast, HCC developed in 12 of 15 NASH patients with limited pSmad3C but only 1 of 15 with abundant pSmad3C. Two of fourteen NASH patients with mild fibrosis developed HCC, their hepatocytic nuclei showed abundant pSmad3L and limited pSmad3C. Five of sixteen patients with severe fibrosis did not develop HCC, their hepatocytic nuclei showed limited pSmad3L and abundant pSmad3C. Smad phospho-isoforms may represent important biomarkers predicting HCC in NASH and potential therapeutic targets for preventing NASH-related HCC. (Tokushima University Institutional Repository) ● Metadata: 115043 (Link to Publication Site) ● Publication site (DOI): 10.3390/cancers12020286 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31991602 ● Summary page in Scopus @ Elsevier: 2-s2.0-85078751865 (Tokushima University Institutional Repository: 115043, DOI: 10.3390/cancers12020286, PubMed: 31991602, Elsevier: Scopus)
33.	Ayumi Fukuda, Marin Sasao, Eri Asakawa, Sumire Narita, Mei Hisano, Kazuhito Suruga, Mayuko Shimizu, Koichi Tsuneyama, Kazunari Tanaka and Katsuhisa Omagari : Dietary fat, cholesterol, and cholic acid affect the histopathologic severity of nonalcoholic steatohepatitis in Sprague-Dawley rats, Pathology, Research and Practice, Vol.215, No.11, 152599, 2019. (Summary) Understanding of the pathogenesis of nonalcoholic steatohepatitis (NASH)-associated fibrosis has been hampered by the lack of a comprehensive and physiological small animal model of NASH with fibrosis. Feeding a high-fat and high-cholesterol (HFC) diet supplemented with cholic acid to rats is known to replicate human NASH pathology, and it induces fibrosis earlier than with an HFC diet alone. In the present study, physiological and histopathological observations from 65 Sprague-Dawley (SD) rats fed an HFC diet with or without cholic acid for 9 or 18 weeks in our laboratory between January 2013 and February 2018 were retrospectively reviewed. The liver weight/body weight ratio at the end of the rearing period was higher in rats fed an HFC diet than in rats fed a normal diet in a cholesterol dose-, cholic acid dose-, or rearing period dependent manner. Dietary fat, cholesterol and/or cholic acid and rearing period affected the histopathologic severity of NASH. Overall, 56 (86.2%) of 65 SD rats fed an HFC diet for 9 or 18 weeks developed histopathologically proven NASH. It is noted that the SD rats fed an HFC diet supplemented with 2% (w/w) cholic acid for 18 weeks frequently developed advanced fibrosis, including cirrhosis. Thus, this diet-induced NASH rat model is likely to be a highly reproducible. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.prp.2019.152599 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31564568 ● Summary page in Scopus @ Elsevier: 2-s2.0-85072600425 (DOI: 10.1016/j.prp.2019.152599, PubMed: 31564568, Elsevier: Scopus)
34.	Katsuhisa Omagari, Eri Asakawa, Marin Sasao, Sumire Narita, Mei Hisano, Ayumi Fukuda, Kazuhiro Suruga, Mayuko Shimizu and Koichi Tsuneyama : Age-related alterations of nonalcoholic steatohepatitis in Sprague-Dawley rats fed a high-fat and high-cholesterol diet., Journal of Nutritional Science and Vitaminology, Vol.65, No.4, 349-356, 2019. (Summary) Nonalcoholic steatohepatitis (NASH), a subtype of nonalcoholic fatty liver disease (NAFLD), has a potentially progressive course that can lead to liver cirrhosis. Age is strongly associated with the development and progression of NAFLD/NASH, but the natural history of pediatric NAFLD is still not fully understood. Here, we evaluated the age-related alterations of NASH in 5-, 9- and 13-wk-old male Sprague-Dawley rats that were fed a high-fat and high-cholesterol diet (30% fat, 1.25% cholesterol and 0.5% sodium cholate, w/w) for 9 wk (6 rats/group). Our results showed that the cumulative energy intake, body weight gain and food efficacy during the 9-wk rearing period were highest in the youngest group and lowest in the oldest group. Serologically, almost all parameters including the serum triglyceride and total cholesterol were similar regardless of age. Histopathological findings, such as hepatic steatosis, lobular inflammation and hepatocyte ballooning, were also similar regardless of age, but hepatic fibrosis was more evident in the oldest group. Also, the mRNA expression levels of some fibrogenic, inflammatory, oxidative stress and cholesterol or lipid metabolism-related genes in the liver were highest in the oldest group and lowest in the youngest group, although the difference was not statistically significant. These results indicated that aging is likely associated with the development of NASH. Because the cumulative energy intake and daily food intake/body weight were not similar among groups in the present study, further studies designed with an equivalent daily food intake/body weight among groups are needed in order to interpret the exact nutritional effect. (Link to Publication Site) ● Publication site (DOI): 10.3177/jnsv.65.349 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31474685 ● Summary page in Scopus @ Elsevier: 2-s2.0-85071749525 (DOI: 10.3177/jnsv.65.349, PubMed: 31474685, Elsevier: Scopus)
35.	Ayaka Iida, Sachi Kuranuki, Ryoko Yamamoto, Masaya Uchida, Masanori Ohta, Mayuko Shimizu, Koichi Tsuneyama, Takayuki Masaki, Masataka Seike and Tsuyoshi Nakamura : Analysis of amino acid profiles of blood over time and biomarkers associated with non-alcoholic steatohepatitis in STAM mice., Experimental Animals, Vol.68, No.4, 417-428, 2019. (Summary) The changes in free amino acid (AA) levels in blood during the progression from non-alcoholic steatohepatitis (NASH) to hepatocellular carcinoma (HCC) are unclear. We investigated serum AA levels, along with biochemical and histological events, in a mouse model of NASH. We induced NASH in male C57BL/6J mice with a streptozotocin injection and high-fat diet after 4 weeks of age (STAM group). We chronologically (6, 8, 10, 12, and 16 weeks, n=4-12 mice/group) evaluated the progression from steatohepatitis to HCC by biochemical and histological analyses. The serum AA levels were determined using an AA analyzer. Serum aspartate aminotransferase and alanine aminotransferase levels were higher in the STAM group than in the normal group (non-NASH-induced mice). Histological analysis revealed that STAM mice had fatty liver, NASH, and fibrosis at 6, 8, and 10 weeks, respectively. Moreover, the mice exhibited fibrosis and HCC at 16 weeks. The serum branched-chain AA levels were higher in the STAM group than in the normal group, especially at 8 and 10 weeks. The Fischer ratio decreased at 16 weeks in the STAM group, with increasing aromatic AA levels. These results suggested that this model sequentially depicts the development of fatty liver, NASH, cirrhosis, HCC, and AA metabolism disorders within a short experimental period. Additionally, serum amyloid A was suggested to be a useful inflammation biomarker associated with NASH. We believe that the STAM model will be useful for studying AA metabolism and/or pharmacological effects in NASH. (Tokushima University Institutional Repository) ● Metadata: 115102 (Link to Publication Site) ● Publication site (DOI): 10.1538/expanim.18-0152 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31155606 ● Search Scopus @ Elsevier (PMID): 31155606 ● Search Scopus @ Elsevier (DOI): 10.1538/expanim.18-0152 (Tokushima University Institutional Repository: 115102, DOI: 10.1538/expanim.18-0152, PubMed: 31155606)
36.	Katsuhisa Omagari, Ayumi Fukuda, Machiko Suga, Ayumi Ogata, Shinta Nishioka, Kazuhito Suruga, Mayuko Shimizu and Koichi Tsuneyama : Peptides Obtained by Enzymatic Decomposition of Mackerel Prevent Nonalcoholic Steatohepatitis in Sprague-Dawley Rats fed a High-fat and High-cholesterol Diet, OBM Hepatology and Gastroenterology, Vol.2, No.3, 2018. (Link to Publication Site) ● Publication site (DOI): 10.21926/obm.hg.1803008 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.21926/obm.hg.1803008 (DOI: 10.21926/obm.hg.1803008)
37.	Ryosuke Nagatomo, Yasuki Okada, Mayuko Shimizu, Koichi Tsuneyama and Koichi Inoue : Application of 2-Picolylamine Derivatized Ultra-high Performance Liquid Chromatography Tandem Mass Spectrometry for Determination of Short-chain Fatty Acids in Feces Samples., Analytical Sciences, Vol.34, No.9, 1031-1036, 2018. (Link to Publication Site) ● Publication site (DOI): 10.2116/analsci.18SCP10 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30078818 ● Search Scopus @ Elsevier (PMID): 30078818 ● Search Scopus @ Elsevier (DOI): 10.2116/analsci.18SCP10 (DOI: 10.2116/analsci.18SCP10, PubMed: 30078818)
38.	Katsuhisa Omagari, Kazuhito Suruga, Akira Kyogoku, Satomi Nakamura, Ai Sakamoto, Shinta Nishioka, Mayuko Shimizu, Yuji Miyata, Koichi Tajima, Koichi Tsuneyama and Kazunari Tanaka : A fermented mixed tea made with camellia (Camellia japonica) and third-crop green tea leaves prevents nonalcoholic steatohepatitis in Sprague-Dawley rats fed a high-fat and high-cholesterol diet., Hepatobiliary Surgery and Nutrition, Vol.7, No.3, 175-184, 2017. (Summary) Established treatments for non-alcoholic steatohepatitis (NASH) are few, thus it is imperative to develop novel dietary strategies that can prevent NASH. A fermented mixed tea (FMT) made with Camellia japonica (Japanese camellia) and third- crop green tea leaves by tea-rolling processing was reported to reduce body weight and adipose tissue weight in Sprague-Dawley (SD) rats. Because visceral fat is one of the most important factors for the development of hepatic steatosis, this FMT supplementation can be a candidate dietary strategy for the prevention of NASH. Nine-week-old male SD rats were fed a high-fat and high-cholesterol (HFC) diets with or without FMT (camellia and third-crop green tea leaves at ratios of 1:5, 1:2 and 1:1) for 9 weeks (n=6-7/group). Histopathology, serology and expressions of fibrogenetic, proinflammatory, oxidative stress and lipid metabolism-related genes in the liver were evaluated. Histologically, HFC diet with FMT at a ratio of 1:5 dramatically reduced NASH progression (14%) compared to the HFC diet without FMT (100%). FMT at a ratio of 1:5 reduced hepatic steatosis due to the activation of microsomal triglyceride transfer protein, and FMT at a ratio of 1:2 reduced mRNA levels of some proinflammatory, lipid metabolism-related, fibrogenic and oxidative stress marker genes. Our data suggest that FMT at a ratio of 1:5 or 1:2 likely possesses a preventive effect on NASH progression. (Link to Publication Site) ● Publication site (DOI): 10.21037/hbsn.2017.08.03 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30046568 ● Search Scopus @ Elsevier (PMID): 30046568 ● Search Scopus @ Elsevier (DOI): 10.21037/hbsn.2017.08.03 (DOI: 10.21037/hbsn.2017.08.03, PubMed: 30046568)
39.	Kotaro Matsumoto, Mayuko Shimizu, Koichi Tsuneyama, Yuki Moritoki, Hiromichi Tsunashima, Katsuhisa Omagari, Masumi Hara, Ichiro Yasuda, Hiroshi Miyakawa and Kentaro Kikuchi : Fructo-oligosaccharides and intestinal barrier function in a methionine-choline-deficient mouse model of nonalcoholic steatohepatitis., PLoS ONE, Vol.12, No.6, e0175406, 2017. (Summary) Impairments in intestinal barrier function, epithelial mucins, and tight junction proteins have been reported to be associated with nonalcoholic steatohepatitis. Prebiotic fructo-oligosaccharides restore balance in the gastrointestinal microbiome. This study was conducted to determine the effects of dietary fructo-oligosaccharides on intestinal barrier function and steatohepatitis in methionine-choline-deficient mice. Three groups of 12-week-old male C57BL/6J mice were studied for 3 weeks; specifically, mice were fed a methionine-choline-deficient diet, a methionine-choline-deficient diet plus 5% fructo-oligosaccharides in water, or a normal control diet. Fecal bacteria, short-chain fatty acids, and immunoglobulin A (IgA) levels were investigated. Histological and immunohistochemical examinations were performed using mice livers for CD14 and Toll-like receptor-4 (TLR4) expression and intestinal tissue samples for IgA and zonula occludens-1 expression in epithelial tight junctions. The methionine-choline-deficient mice administered 5% fructo-oligosaccharides maintained a normal gastrointestinal microbiome, whereas methionine-choline-deficient mice without prebiotic supplementation displayed increases in Clostridium cluster XI and subcluster XIVa populations and a reduction in Lactobacillales spp. counts. Methionine-choline-deficient mice given 5% fructo-oligosaccharides exhibited significantly decreased hepatic steatosis (p = 0.003), decreased liver inflammation (p = 0.005), a decreased proportion of CD14-positive Kupffer cells (p = 0.01), decreased expression of TLR4 (p = 0.04), and increases in fecal short-chain fatty acid and IgA concentrations (p < 0.04) compared with the findings in methionine-choline-deficient mice that were not administered this prebiotic. This study illustrated that in the methionine-choline-deficient mouse model, dietary fructo-oligosaccharides can restore normal gastrointestinal microflora and normal intestinal epithelial barrier function, and decrease steatohepatitis. The findings support the role of prebiotics, such as fructo-oligosaccharides, in maintaining a normal gastrointestinal microbiome; they also support the need for further studies on preventing or treating nonalcoholic steatohepatitis using dietary fructo-oligosaccharides. (Tokushima University Institutional Repository) ● Metadata: 112342 (Link to Publication Site) ● Publication site (DOI): 10.1371/journal.pone.0175406 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28632732 ● Search Scopus @ Elsevier (PMID): 28632732 ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0175406 (Tokushima University Institutional Repository: 112342, DOI: 10.1371/journal.pone.0175406, PubMed: 28632732)
40.	Mayuko Shimizu, Miki Masuzumi, Miku Kawase, Mika Sakaki, Shizuka Tamaru, Yasuo Nagata, Kazunari Tanaka, Kazuhito Suruga, Koichi Tsuneyama, Satoru Matsuda and Katsuhisa Omagari : A diet-induced Sprague-Dawley rat model of nonalcoholic steatohepatitis-related cirrhosis., The Journal of Nutritional Biochemistry, Vol.40, 62-69, 2017. (Summary) Certain modified diets containing saturated fatty acids, cholesterol or fructose lead to the development of nonalcoholic steatohepatitis (NASH)-related fibrosis in rodents; however, progression to cirrhosis is rare. Experimental liver cirrhosis models have relied on genetic manipulation or administration of hepatotoxins. This study aimed to establish a reliable dietary model of NASH-related cirrhosis in a relatively short period. Male Sprague-Dawley rats (9 weeks of age) were randomly assigned to normal, high-fat (HF), or two types (1.25% or 2.5% cholesterol) of high-fat and high-cholesterol (HFC) diets for 18 weeks. All HFC diets contained 2% cholic acid by weight. Histopathological analysis revealed that the HFC diets induced obvious hepatic steatosis, inflammation with hepatocyte ballooning and advanced fibrosis (stage 3-4) in all 12 rats at 27 weeks of age. In contrast, all five rats given the HF diet developed mild steatosis and inflammation without fibrosis. The amount of cholesterol in the liver and hepatocellular mitochondrial and microsomal fractions was significantly higher in rats fed the HFC diets than the normal or HF diets. The HFC diets significantly suppressed mRNA levels of microsomal triglyceride transfer protein, adenosine triphosphate binding cassette transporter G5, bile acid CoA: amino acid N-acyltransferase and bile salt export pump, as well as the enzymatic activity of carnitine palmitoyltransferase in the liver. In conclusion, the HFC diets induced liver cirrhosis in conjunction with hepatic features of NASH in Sprague-Dawley rats within 18 weeks, and altered gene expression and enzyme activity to accumulate lipid and bile acid in the liver. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.jnutbio.2016.10.007 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27863346 ● Search Scopus @ Elsevier (PMID): 27863346 ● Search Scopus @ Elsevier (DOI): 10.1016/j.jnutbio.2016.10.007 (DOI: 10.1016/j.jnutbio.2016.10.007, PubMed: 27863346)
41.	Katsuhisa Omagari, Mika Sakaki, Yuki Tsujimoto, Yukiko Shiogama, Akiko Iwanaga, Makiko Ishimoto, Asami Yamaguchi, Miki Masuzumi, Miku Kawase, Mayuko Shimizu, Takatoshi Yoshitake and Yoshiyuki Miyahara : Coffee consumption is inversely associated with depressive status in Japanese patients with type 2 diabetes., Journal of Clinical Biochemistry and Nutrition, Vol.55, No.2, 135-142, 2014. (Summary) Depression has been reported to be more prevalent among diabetic patients than non-diabetic individuals. Although depression and diabetes are causally and bi-directionally related, the influence of food intake frequency on depressive symptoms in diabetic patients has not been fully evaluated. This cross-sectional study analyzed data obtained from 89 patients with type 2 diabetes who completed self-administered questionnaires regarding food intake frequency, diabetic variables, physical activity and depressive states. The prevalence of a "definite" depressive state was 16.9%. The duration of diabetes, hemoglobin A1c levels, diabetic microvascular complications and physical activity levels were similar between depressed and non-depressed patients. Daily intakes of total lipids, n-6 polyunsaturated fatty acids and lipid energy ratios were significantly lower, and the carbohydrate energy ratio was significantly higher in depressed than in non-depressed patients. Coffee consumption was inversely associated with depressive symptoms, but no significant association was found between tea or green tea consumption and depressive symptoms. The logistic regression analysis showed that coffee consumption was an independent predictor of non-depressed status in diabetic patients. This might be due to biologically active compounds containing in coffee other than caffeine. (Link to Publication Site) ● Publication site (DOI): 10.3164/jcbn.14-30 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25320461 ● Search Scopus @ Elsevier (PMID): 25320461 ● Search Scopus @ Elsevier (DOI): 10.3164/jcbn.14-30 (DOI: 10.3164/jcbn.14-30, PubMed: 25320461)
42.	Mayuko Shimizu, Miku Kawase, Miki Masuzumi, Mika Sakaki, Yasuo Nagata, Kazunari Tanaka, Kazuhito Suruga, Shizuka Tamaru, Shigeko Kato, Koichi Tsuneyama and Katsuhisa Omagari : High-fat and high-cholesterol diet rapidly induces non-alcoholic steatohepatitis with advanced fibrosis in Sprague-Dawley rats., Hepatology Research, Vol.45, No.4, 458-469, 2014. (Summary) The development of fibrosis is considered an important phase in the progress of non-alcoholic steatohepatitis (NASH) towards the end stage of liver disease, including cirrhosis. However, few small animal models can display NASH-associated fibrosis. We aimed to establish a dietary model of NASH with rapid progression to fibrosis using genetically normal rats. Nine-week-old male Sprague-Dawley rats were fed with normal, high-fat (HF), or two types of high-fat and high-cholesterol (HFC) diets for 9 weeks (n = 5 each). All HFC diets contained 1.25% or 2.5% cholesterol. The rats fed with the HF diet developed mild steatosis and inflammation without fibrosis at 18 weeks of age, whereas all rats given the HFC diet developed obvious steatosis and inflammation with hepatocyte ballooning and fibrosis. Two of five (40%) rats given the HFC diet containing 2.5% cholesterol progressed to liver cirrhosis. Hepatic total cholesterol levels were significantly higher in rats given the HFC, than the normal or HF diets. The HFC diet significantly and dose-dependently decreased microsomal triglyceride transfer protein expression. Cholesterol tended to suppress carnitine palmitoyltransferase activity and adenosine triphosphate-binding cassette transporter G5 expression. Adding cholesterol to the HF diet modified hepatic lipid metabolism at the molecular level. The HFC diet induced hepatic features of NASH and eventually progressed cirrhosis in Sprague-Dawley rats within 9 weeks. (Link to Publication Site) ● Publication site (DOI): 10.1111/hepr.12358 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24827559 ● Search Scopus @ Elsevier (PMID): 24827559 ● Search Scopus @ Elsevier (DOI): 10.1111/hepr.12358 (DOI: 10.1111/hepr.12358, PubMed: 24827559)
43.	Katsuhisa Omagari, Chisato Yoshikawa, Shin-ichi Inoue, Yuna Tanaka, Toshie Murayama, Mayuko Shimizu, Ayako Miyata, Sawako Mori, Mai Kamogawa, Eri Hirao, Shigeko Kato, Kazuhito Suruga and Koichi Tsuneyama : Abdominal subcutaneous adipose tissue accumulation is positively correlated with hepatic steatosis in Sprague-Dawley rats, Acta Medica Nagasakiensia, Vol.59, No.2, 47-56, 2014. (Summary) The precise roles of visceral (VAT) or subcutaneous adipose tissue (SAT) on hepatic fat accumulation have not been fullyelucidated. In this report, we examined the correlation between VAT or SAT volume and severity of hepatic fat accumulation. Inthe present study, Sprague-Dawley (SD) rats were fed a standard diet containing 10% fat or a high-fat diet containing 45% or 60%fat for 16 weeks. Abdominal VAT and SAT volume, as well as fat percentage of the liver were measured by computed tomography(CT). Hepatic triglyceride (TG) content and histopathological findings of hepatic steatosis were also examined. Abdominal SATweight/body weight ratio was positively and strongly correlated with abdominal VAT weight/body weight ratio. Fat percentage ofthe liver by CT evaluation, hepatic TG content, and hepatic steatosis score by histopathological evaluation showed positive correlationswith one another. Fat percentage of the liver by CT evaluation and hepatic TG content was positively correlated withboth the abdominal VAT weight/body weight ratio and SAT weight/body weight ratio, respectively. Furthermore, hepatic TG contentwas negatively correlated with the abdominal VAT weight/SAT weight ratio. Our data suggest that abdominal SAT accumulationis positively correlated with hepatic steatosis in SD rats, rather than abdominal VAT accumulation. Further investigations areneeded in order to clarify the precise mechanisms of SAT and VAT effects on the development of hepatic fat accumulation. (Keyword) hepatic steatosis / subcutaneous adipose tissue / visceral adipose tissue / computed tomography / Sprague-Dawley (SD) rats (Link to Publication Site) ● Publication site (DOI): 10.11343/amn.59.47 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390001204675540224 ● Summary page in Scopus @ Elsevier: 2-s2.0-84920993154 (DOI: 10.11343/amn.59.47, CiNii: 1390001204675540224, Elsevier: Scopus)
44.	Mayuko Shimizu, Shigeko Kato, Koichi Tsuneyama, Sachiko Matsutake, Mai Kamogawa, Eri Hirao, Ayako Miyata, Sawako Mori, Noriaki Yamaguchi, Kazuhito Suruga and Katsuhisa Omagari : Phycocyanin prevents hypertension and low serum adiponectin level in a rat model of metabolic syndrome., Nutrition Research, Vol.33, No.5, 397-405, 2013. (Summary) Endothelial dysfunction is associated with hypertension, atherosclerosis, and metabolic syndrome. Phycocyanin is a pigment found in the blue-green algae, Spirulina, which possesses antihypertensive effect. In this study, we hypothesized that phycocyanin derived from Spirulina exerts antihypertensive actions by improving endothelial dysfunction in metabolic syndrome. Spontaneously hypertensive/NIH-corpulent (SHR/NDmcr-cp) rats were divided into 4 groups then fed a normal diet with or without phycocyanin (2500-, 5000-, or 10,000-mg/kg diet) for 25 weeks. At 34 weeks of age, although systolic blood pressure was not significantly different among groups, phycocyanin-fed groups exhibited a dose-dependent decrease in blood pressure. Serum levels of adiponectin and messenger RNA levels of adiponectin and CCAAT/enhancer-binding protein in the adipose tissue of rats fed diets containing phycocyanin tended to be higher than those of rats fed a normal diet, but the differences were not statistically significant. Immunohistochemistry analysis showed a significant and positive correlation between aortic endothelial nitric oxide synthase (eNOS) expression levels, a downstream target of the adiponectin receptor, and serum adiponectin levels, although there were no significant differences in eNOS expression among groups. There was also no significant correlation between eNOS expression levels and systolic blood pressure. These results suggest that long-term administration of phycocyanin may ameliorate systemic blood pressure by enhancing eNOS expression in aorta that is stimulated by adiponectin. Phycocyanin may be beneficial for preventing endothelial dysfunction-related diseases in metabolic syndrome. (Keyword) Adiponectin / Animals / Antihypertensive Agents / Aorta / Blood Pressure / Body Weight / CCAAT-Enhancer-Binding Protein-alpha / Cyanobacteria / Disease Models, Animal / Endothelium, Vascular / Energy Intake / Hypertension / Liver / Male / Metabolic Syndrome X / Nitric Oxide Synthase Type III / Organ Size / Phycocyanin / Rats / Rats, Inbred SHR / Receptors, Adiponectin (Link to Publication Site) ● Publication site (DOI): 10.1016/j.nutres.2013.03.006 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23684441 ● Search Scopus @ Elsevier (PMID): 23684441 ● Search Scopus @ Elsevier (DOI): 10.1016/j.nutres.2013.03.006 (DOI: 10.1016/j.nutres.2013.03.006, PubMed: 23684441)
45.	松竹幸子, 大曲勝久, 加藤滋子, Mayuko Shimizu, 石井由夏, 加地真奈美, 岩見春香, 市川辰樹 and 中尾一彦 : C型慢性肝炎に対する抗ウィルス療法の治療効果に及ぼす栄養状態の影響, Journal of Japanese Society of Clinical Nutrition, Vol.35, 39-48, 2013. (Keyword) chronic hepatitis C / anti-viral therapy / sustained virologic response / nutritional status (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520290883137026432 (CiNii: 1520290883137026432)
46.	Katsuhisa Omagari, Toshie Murayama, Yuna Tanaka, Chisato Yoshikawa, Shin-ichi Inoue, Mayuko Shimizu, Maiko Hatanaka, Mari Saimei, Keiko Muto, Takuro Tobina, Motofumi Masaki and Shigeko Kato : Mental, physical, dietary, and nutritional effects on irritable bowel syndrome in young Japanese women., Internal Medicine, Vol.52, No.12, 1295-1301, 2013. (Summary) The prevalence of IBS observed in this study was similar to that reported in previous studies conducted in Japan and other countries. Mental, physical, dietary and nutritional factors have an impact on IBS. (Keyword) Adolescent / adult / Animals / Anxiety / Asian Continental Ancestry Group / Cross-Sectional Studies / Depression / Diet / female / Humans / Irritable Bowel Syndrome / Japan / lifestyle / Logistic Models / Milk / Motor Activity / Prevalence / Surveys and Questionnaires / Young Adult (Link to Publication Site) ● Publication site (DOI): 10.2169/internalmedicine.52.0248 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23774537 ● Search Scopus @ Elsevier (PMID): 23774537 ● Search Scopus @ Elsevier (DOI): 10.2169/internalmedicine.52.0248 (DOI: 10.2169/internalmedicine.52.0248, PubMed: 23774537)
47.	Katsuhisa Omagari, Rika Takamura, Sachiko Matsutake, Mayuko Shimizu, Shigeko Kato, Shun-Ichi Morikawa, Seiko Nagaoka and Masayuki Osabe : Serum alanine aminotransferase concentration as a predictive factor for the development or regression of fatty liver., Journal of Clinical Biochemistry and Nutrition, Vol.49, No.3, 200-206, 2011. (Summary) Serum alanine aminotransferase (ALT) concentration is the most commonly used marker for hepatocellular injury. We investigated the suitable cutoff value of serum ALT for the diagnosis or prediction of fatty liver. In 1578 Japanese adults (1208 men, 370 women; 35-69 years of age) who visited our center both in 2000 and between April 2007 and March 2008 (2007-2008), serum ALT concentration was an independent predictor of fatty liver in men in 2000 and in both sexes in 2007-2008. A significant increase in the frequency of fatty liver was detected in participants with elevated serum ALT concentrations, and serum levels of ALT in 2000 were associated with fatty liver in 2007-2008 when the cutoff value was set at 30IU/L in men and 19IU/L in women. The frequency of fatty liver in 2007-2008 was significantly lower in participants without fatty liver in 2000 whose serum ALT decreased between 2000 and 2007-2008. Our results suggest that serum ALT might be not only an indicator of fatty liver but also a predictor of the regression of fatty liver, and cutoff values of serum ALT of 30IU/L in men and 19IU/L in women are suitable for the screening of fatty liver. (Link to Publication Site) ● Publication site (DOI): 10.3164/jcbn.11-27 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22128220 ● Search Scopus @ Elsevier (PMID): 22128220 ● Search Scopus @ Elsevier (DOI): 10.3164/jcbn.11-27 (DOI: 10.3164/jcbn.11-27, PubMed: 22128220)

Academic Paper (Unrefereed Paper):

1.	福田歩美, 駿河和仁, 古場一哲, Mayuko Shimizu, Koichi Tsuneyama and 大曲勝久 : 非アルコール性脂肪肝炎モデルラットにおける NAFLD activity scoreとFLIPアルゴリズムによる組織学的評価の比較検討, 長崎県立大学看護栄養学部紀要, Vol.20, 121-128, 2022. (Summary) type:Article (Keyword) 非アルコール性脂肪肝炎 / ラットモデル / 肝組織像 / NAS スコア / FLIP アルゴリズム (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1050010610491153920 (CiNii: 1050010610491153920)
2.	中野紀子, 南明里, Mayuko Shimizu and 松田覚 : A Report on the Collaboration Project Between Nara Prefecture and Nara Women's University Called "Nara Nutrition College", 教育システム研究, Vol.12, 91-98, 2017. (Summary) type:Article (Keyword) 食育 / 実践活動 / 高齢者 / 幼児 / 奈良県 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1050282813368708480 (CiNii: 1050282813368708480)
3.	Katsuhisa Omagari, Haruna Torii, Shiho Goto, Ai Sakamoto, Miki Hattori, Toshie Murayama-Kinjo, Mayuko Shimizu, Kenichi Tanabe and Sachiko Matsumoto : Dietary intake, mental status, physical activity, and lifestyle affecting bowel movement frequency and stool texture in young Japanese women, Acta Medica Nagasakiensia, Vol.60, 85-95, 2016. (Link to Publication Site) ● Publication site (DOI): 10.11343/amn.60.85 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-84969983676 (DOI: 10.11343/amn.60.85, Elsevier: Scopus)
4.	大曲勝久, 服部美紀, 後藤紫方, 坂元藍, 鳥居春菜, Mayuko Shimizu and 田辺賢一 : 非アルコール性脂肪肝炎発症モデルラットの肝組織所見に及ぼす食餌性コレステロールの影響, 長崎県立大学看護栄養学部紀要, Vol.14, 23-30, 2016. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1050564287381690496 (CiNii: 1050564287381690496)
5.	Katsuhisa Omagari, Haruka Iwami, Manami Kaji, Yuka Ishii, Sachiko Matsutake, Mayuko Shimizu, Shigeko Kato, Shigeyuki Takeshita, Tatsuki Ichikawa and Kazuhiko Nakao : The relationship between energy expenditure and type or stage of cancer, Acta Medica Nagasakiensia, Vol.57, No.2, 33-40, 2012. (Link to Publication Site) ● Publication site (DOI): 10.11343/amn.57.33 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-84873892865 (DOI: 10.11343/amn.57.33, Elsevier: Scopus)
6.	Katsuhisa Omagari, Manami Kaji, Yuka Ishii, Haruka Iwami, Mayuko Shimizu, Sachiko Matsutake, Shigeko Kato, Shigeyuki Takeshita, Tatsuki Ichikawa and Kazuhiko Nakao : Protein-energy malnutrition in patients with liver cirrhosis, Acta Medica Nagasakiensia, Vol.57, 5-12, 2012. (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-84865834982 (Elsevier: Scopus)
7.	Katsuhisa Omagari, Shigeko Kato, Koichi Tsuneyama, Hideki Hatta, Mayuko Shimizu, Chisato Urata, Yasuko Sumiyama, Ayako Nishizaki, Sakiko Hashimoto, Mai Harada, Shizuka Tamaru and Kazunari Tanaka : The Effect of Olive Leaf Extract on Hepatic Fat Accumulation in Sprague- Dawley Rats Fed a High-fat Diet, Acta Medica Nagasakiensia, Vol.55, No.1, 29-39, 2010. (Keyword) Non-alcoholic fatty liver disease, / Olive leaf extract / Oleuropein / High-fat diet / Sprague-Dawley (SD) rats (Link to Publication Site) ● Publication site (DOI): 10.11343/amn.55.29 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-79960148276 (DOI: 10.11343/amn.55.29, Elsevier: Scopus)

Academic Letter:

1.	Mayuko Shimizu, Maiko Hatanaka, Koichi Tsuneyama, Shigeko Kato and Katsuhisa Omagari : An SHR/NDmcr-cp rat model of non-alcoholic steatohepatitis with advanced fibrosis induced by a high-fat, high-cholesterol diet., J Obes Wt Loss Ther, Vol.5, 1, 2015. (Keyword) SHR/NDmcr-cp rat / cholesterol

Review, Commentary:

1.	Mayuko Shimizu, Khuleshwari Kurrey, Misaki Miyata, Takuya Dezawa, Koichi Tsuneyama and Masami Kojima : Emerging Insights into the Role of BDNF on Health and Disease in Periphery., Biomolecules, Vol.14, No.4, Apr. 2024. (Summary) Brain-derived neurotrophic factor (BDNF) is a growth factor that promotes the survival and growth of developing neurons. It also enhances circuit formation to synaptic transmission for mature neurons in the brain. However, reduced BDNF expression and single nucleotide polymorphisms (SNP) are reported to be associated with functional deficit and disease development in the brain, suggesting that BDNF is a crucial molecule for brain health. Interestingly, BDNF is also expressed in the hypothalamus in appetite and energy metabolism. Previous reports demonstrated that BDNF knockout mice exhibited overeating and obesity phenotypes remarkably. Therefore, we could raise a hypothesis that the loss of function of BDNF may be associated with metabolic syndrome and peripheral diseases. In this review, we describe our recent finding that BDNF knockout mice develop metabolic dysfunction-associated steatohepatitis and recent reports demonstrating the role of one of the BDNF receptors, TrkB-T1, in some peripheral organ functions and diseases, and would provide an insight into the role of BDNF beyond the brain. (Keyword) Brain-Derived Neurotrophic Factor / Animals / Humans / Receptor, trkB / knockout mice / knockout mice / energy metabolism / obesity / Polymorphism, Single Nucleotide (Link to Publication Site) ● Publication site (DOI): 10.3390/biom14040444 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38672461 ● Search Scopus @ Elsevier (PMID): 38672461 ● Search Scopus @ Elsevier (DOI): 10.3390/biom14040444 (DOI: 10.3390/biom14040444, PubMed: 38672461)
2.	菊池健太郎, 松本光太郎, 高井敦子, Mayuko Shimizu, 守時由起, Koichi Tsuneyama, 原眞純 and 宮川浩 : Gastrointestinal microbiome and non-alcoholic steatohepatitis, Diabetology, Endocrinology & Metabolology, Vol.53, No.3, 356-360, Sep. 2021. (Keyword) fructo-oligosaccharides / intestinal barrier function / nonalcoholic steatohepatitis / NASH / monosodium glutamate / microbiome (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1521980706163941632 (CiNii: 1521980706163941632)
3.	Mayuko Shimizu : 非アルコール性脂肪肝炎および脳機能障害における脂質の挙動, アグリバイオ, Vol.5, No.6, 521-525, Jun. 2021. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520010381278661888 (CiNii: 1520010381278661888)
4.	Koichi Tsuneyama, Mayuko Shimizu, Takeshi Oya, Minoru Matsumoto, Tomoko Kobayashi, Hirohisa Ogawa, Kazuchika Nishitsuji and Michiko Yamashita : 肝臓病理所見のとり方とその解釈, 法医病理, Vol.25, No.1, 1-12, Jul. 2019.
5.	Akari Minami, Mako Ogino, Noriko Nakano, Mayuko Shimizu, Atsuko Nakanishi, Toshiyuki Murai, Yasuko Kitagishi and Satoru Matsuda : Roles of oncogenes and tumor-suppressor genes in osteoclastogenesis (Review)., International Journal of Molecular Medicine, Vol.39, No.2, 261-267, Jan. 2017. (Summary) Osteoporosis is a bone disease that poses a tremendous burden to health care. The receptor activator of nuclear factor-κB (RANK) and its ligand (RANKL) have been a major focus of this research field. RANKL signaling not only activates a variety of downstream signaling pathways required for osteoclast development, but crosstalk with other signaling pathways also adjusts bone homeostasis both in normal physiology and in bone disease. Consequently, novel drugs specifically targeting RANK-RANKL and their signaling pathways in osteoclasts are expected to revolutionize the treatment of various bone diseases such as osteoporosis. Osteoclasts are the exclusive cells involved in bone resorption. Abnormal activation of osteoclasts can lead to reduced bone density, resulting in osteopenia, osteoporosis and other bone disorders. To date, the mechanism of how osteoclast precursors differentiate into mature osteoclasts remains elusive. Cell proliferation and cell death may be key processes in the progression as well as other cell types. Oncogene products and tumor-suppressor molecules play a pivotal role in regulating the processes, which are important in regulating the configuration of bone disorders. Based on the understanding of these processes, promising alternatives to the use of medications against osteoporosis include specific diets with plant-derived supplements to modulate the expression and/or activity of these molecules. In this review, we summarize the progress of research with a focus on the modulatory roles of oncogene products and tumor-suppressor molecules and suggest the scope of further research concerning the prevention of osteoporosis in this field. (Keyword) Animals / Bone Resorption / Gene Expression Regulation / Genes, Tumor Suppressor / Humans / Oncogenes / Osteoclasts / Osteoporosis / Signal Transduction (Link to Publication Site) ● Publication site (DOI): 10.3892/ijmm.2017.2847 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28075460 ● Search Scopus @ Elsevier (PMID): 28075460 ● Search Scopus @ Elsevier (DOI): 10.3892/ijmm.2017.2847 (DOI: 10.3892/ijmm.2017.2847, PubMed: 28075460)
6.	Noriko Nakano, Satoru Matsuda, Mayuko Shimizu, Akari Minami, Mako Ogino, Toshiyuki Murai and Yasuko Kitagishi : PI3K/AKT signaling mediated by G protein-coupled receptors is involved in neurodegenerative Parkinson's disease (Review)., International Journal of Molecular Medicine, Vol.39, No.2, 253-260, Dec. 2016. (Summary) Parkinson's disease (PD) is a common progressive and multifactorial neurodegenerative disease, characterized by the loss of midbrain dopaminergic neurons. Numerous pathological processes including, inflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalance, and apoptosis as well as genetic factors may lead to neuronal degeneration. Motor deficits in PD are due mostly to the progressive loss of nigrostriatal dopaminergic neurons. Neuroprotection of functional neurons is of significance in the treatment of PD. G protein‑coupled receptors (GPCRs) have been implicated in the neuroprotection against PD through the survival of dopaminergic neurons. In addition, phosphatidyl‑inositol‑3‑kinase (PI3K)/AKT signaling has also been demonstrated to be neuroprotective. Knowledge of the mechanisms involved in this cellular protection could be critical for developing treatments to prevent this neurodegenerative disorder. In this review, we highlight the protective roles of the PI3K/AKT signaling pathway in the function of representative serotonin GPCRs. Particular attention is given to the molecular mechanisms of this pathway proposed to explain the favorable effects of food ingredients against neurodegenerative disease. (Keyword) Animals / Dopaminergic Neurons / Humans / Monomeric GTP-Binding Proteins / Nerve Degeneration / Neurodegenerative Diseases / Neuroprotective Agents / Parkinson Disease / Phosphatidylinositol 3-Kinases / Proto-Oncogene Proteins c-akt / Receptors, G-Protein-Coupled / Serotonin / Signal Transduction (Link to Publication Site) ● Publication site (DOI): 10.3892/ijmm.2016.2833 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28000847 ● Search Scopus @ Elsevier (PMID): 28000847 ● Search Scopus @ Elsevier (DOI): 10.3892/ijmm.2016.2833 (DOI: 10.3892/ijmm.2016.2833, PubMed: 28000847)
7.	Yasuko Kitagishi, Noriko Nakano, Mako Ogino, Mayuko Shimizu, Akari Minami and Satoru Matsuda : PINK1 signaling in mitochondrial homeostasis and in aging (Review)., International Journal of Molecular Medicine, Vol.39, No.1, 3-8, Dec. 2016. (Summary) Mitochondrial dysfunction is involved in the pathology of Parkinson's disease, an age-associated neurodegenerative disorder. Phosphatase and tensin homolog (PTEN)-induced putative kinase protein 1 (PINK1) is responsible for the most common form of recessive Parkinson's disease. PINK1 is a mitochondrial kinase that is involved in mitrochondrial quality control and promotes cell survival. PINK1 has been shown to protect against neuronal cell death induced by oxidative stress. Accordingly, PINK1 deficiency is associated with mitochondrial dysfunction as well as increased oxidative cellular stress and subsequent neuronal cell death. In addition, several mitochondrial chaperone proteins have been shown to be substrates of the PINK1 kinase. In this review, we discuss recent studies concerning the signaling cascades and molecular mechanisms involved in the process of mitophagy, which is implicated in neurodegeneration and in related aging associated with oxidative stress. Particular attention will be given to the molecular mechanisms proposed to explain the effects of natural compounds and/or food ingredients against oxidative stress. Knowledge of the molecular mechanisms involved in this cellular protection could be critical for developing treatments to prevent and control excessive progression of neurodegenerative disorders. (Keyword) aging / Diet / homeostasis / Humans / mitochondria / Protein Kinases / signal transduction (Link to Publication Site) ● Publication site (DOI): 10.3892/ijmm.2016.2827 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27959386 ● Search Scopus @ Elsevier (PMID): 27959386 ● Search Scopus @ Elsevier (DOI): 10.3892/ijmm.2016.2827 (DOI: 10.3892/ijmm.2016.2827, PubMed: 27959386)
8.	Satoru Matsuda, Mayuko Shimizu, Mako Ogino, Noriko Nakano, Akari Minami, Toshiyuki Murai and Yasuko Kitagishi : Effective PI3K modulators for improved therapy against malignant tumors and for neuroprotection of brain damage after tumor therapy (Review)., International Journal of Oncology, Vol.49, No.5, 1785-1790, Sep. 2016. (Summary) Due to the key role in various cellular processes including cell proliferation and cell survival on many cell types, dysregulation of the PI3K/AKT pathway represents a crucial step of the pathogenesis in many diseases. Furthermore, the tumor suppressor PTEN negatively regulates the PI3K/AKT pathway through its lipid phosphatase activity, which is recognized as one of the most frequently deleted and/or mutated genes in human cancer. Given the pervasive involvement of this pathway, the development of the molecules that modulate this PI3K/AKT signaling has been initiated in studies which focus on the extensive effective drug discovery. Consequently, the PI3K/AKT pathway appears to be an attractive pharmacological target both for cancer therapy and for neurological protection necessary after the therapy. A better understanding of the molecular relations could reveal new targets for treatment development. We review recent studies on the features of PI3K/AKT and PTEN, and their pleiotropic functions relevant to the signaling pathways involved in cancer progress and in neuronal damage by the therapy. (Keyword) Animals / Brain Diseases / Combined Modality Therapy / Humans / Molecular Targeted Therapy / Neoplasms / Neuroprotection / Phosphoinositide-3 Kinase Inhibitors / Protein Kinase Inhibitors / signal transduction (Link to Publication Site) ● Publication site (DOI): 10.3892/ijo.2016.3710 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27826621 ● Search Scopus @ Elsevier (PMID): 27826621 ● Search Scopus @ Elsevier (DOI): 10.3892/ijo.2016.3710 (DOI: 10.3892/ijo.2016.3710, PubMed: 27826621)
9.	Mako Ogino, Mayuko Shimizu, Noriko Nakano, Akari Minami, Yasuko Kitagishi and Satoru Matsuda : Roles of PTEN with DNA Repair in Parkinson's Disease., International Journal of Molecular Sciences, Vol.17, No.6, Jun. 2016. (Summary) Oxidative stress is considered to play key roles in aging and pathogenesis of many neurodegenerative diseases such as Parkinson's disease, which could bring DNA damage by cells. The DNA damage may lead to the cell apoptosis, which could contribute to the degeneration of neuronal tissues. Recent evidence suggests that PTEN (phosphatase and tensin homolog on chromosome 10) may be involved in the pathophysiology of the neurodegenerative disorders. Since PTEN expression appears to be one dominant determinant of the neuronal cell death, PTEN should be a potential molecular target of novel therapeutic strategies against Parkinson's disease. In addition, defects in DNA damage response and DNA repair are often associated with modulation of hormone signaling pathways. Especially, many observations imply a role for estrogen in a regulation of the DNA repair action. In the present review, we have attempted to summarize the function of DNA repair molecules at a viewpoint of the PTEN signaling pathway and the hormone related functional modulation of cells, providing a broad interpretation on the molecular mechanisms for treatment of Parkinson's disease. Particular attention will be paid to the mechanisms proposed to explain the health effects of food ingredients against Parkinson's disease related to reduce oxidative stress for an efficient therapeutic intervention. (Keyword) Animals / BRCA1 Protein / Cell Survival / DNA Damage / DNA Repair / Diet / Estrogens / Humans / Nerve Degeneration / Neurodegenerative Diseases / oxidative stress / PTEN Phosphohydrolase / Parkinson's disease / Phosphatidylinositol 3-Kinases / Proto-Oncogene Proteins c-akt / Reactive Oxygen Species / Receptors, Estrogen / signal transduction (Tokushima University Institutional Repository) ● Metadata: 115630 (Link to Publication Site) ● Publication site (DOI): 10.3390/ijms17060954 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27314344 ● Search Scopus @ Elsevier (PMID): 27314344 ● Search Scopus @ Elsevier (DOI): 10.3390/ijms17060954 (Tokushima University Institutional Repository: 115630, DOI: 10.3390/ijms17060954, PubMed: 27314344)
10.	Mayuko Shimizu, Akari Minami, Noriko Nakano, Yasuko Kitagishi, Toshiyuki Murai and Satoru Matsuda : Cigarette smoke may be an exacerbation factor in nonalcoholic fatty liver disease via the modulation for PI3K/AKT pathway, AIMS Molecular Science, Vol.2, 427-439, 2015.

Proceeding of International Conference:

1.	Koichi Tsuneyama, Takumi Kakimoto and Mayuko Shimizu : Connexin 32 expression and alpha-synuclein accumulation in ballooning cells of non-alcoholic steatohepatitis (NASH) and other inflammatory liver diseases, AASLD 2024, Nov. 2023.
2.	Mayuko Shimizu, M Kojima, M Miyata, S Suzuki and Koichi Tsuneyama : Brain-derived neurotrophic factor knock-out mice develop nonalcoholic steatohepatitis, EASL, Jun. 2023.
3.	Kazuki Yasumaru, Mayuko Shimizu, Eiji Hase, Takeshi Yasui, Koichi Tsuneyama and Takeo Minamikawa : Raman and SHG spectroscopic analyses of lipid droplets accumulated in the liver of a mouse model of nonalcoholic fatty liver disease, pLED International symposium 2023: Exploring Invisible Light Technology, P-11, Tokushima, Mar. 2023.
4.	Miyakami Yuko, Mayuko Shimizu, Yoshimura Kentaro, Tsutsui Akemi and Koichi Tsuneyama : ESTABLISHMENT of EARLY FIBROSIS MARKER in NASH USING SERUM PHOSPHOLIPIDS, APASL2023, Feb. 2023.
5.	Koichi Tsuneyama, Wenhua Shao and Mayuko Shimizu : Various type of hepatocellular adenomas occurred spontaneously in the liver of metabolic syndrome-associated steatohepatitis model, TSOD mice, AASLD The Liver meeting 2022, Nov. 2022.
6.	Mayuko Shimizu : Characterization of skin conditions leading to sensitization, a pre-phase of food allergy: a mouse model study, The 8the Asian Congress of Dietetics, Aug. 2022. (Keyword) epicutaneous sensitization / food allergy
7.	Takumi Kakimoto, Mayuko Shimizu, Koichi Tsuneyama, Minoru Matsumoto, Takeshi Oya, Hosokawa Masato and Koichi Tsuneyama : Accumulation of α-synuclein in hepatocytes in NASH liver and usefulness in pathological diagnosis, Digestive Disease Week 2022, May 2022.
8.	Kikuchi Kentaro, Matsumoto Kotaro, Takai Atsuko, Mayuko Shimizu, Moritoki Yuki, Koichi Tsuneyama and Hara Masumi : Fructo-oligosaccharides ameliorate steatohepatitis via increased production of short-chain fatty acids in mice, JSH International Liver Conference 2021, Oct. 2021.
9.	Mayuko Shimizu, 富永俊弼 and Koichi Tsuneyama : A novel image analysis technology that can verify quantification and progress pattern of NASH fibrosis, The Liver Meeting 2020, Boston, Nov. 2020.
10.	Mayuko Shimizu and Koichi Tsuneyama : Phellodendron bark and its component berberine prevent nonalcoholic steatohepatitis-related fibrosis in mice, 29th Asian Pacific Association for the Study of the Liver (APASL) 2020, Bali, Mar. 2020.
11.	Eiji Hase, Hiroki Takanari, Mayuko Shimizu, Hayashi Yuri, Takeo Minamikawa, Takeshi Yasui and Koichi Tsuneyama : Characterization of fibrosis in non-alcoholic steatohepatitis by use of second-harmonic-generation microscopy, Asian Pacific Association for the Study of the Liver 2020 (APASL 2020), Bali, Indonesia, Mar. 2020.
12.	Takeo Minamikawa, Mayuko Shimizu, Hiroki Takanari, Shiomi Ryosuke, Kusaka Hiroki, Tanioka Hiroki, Eiji Hase, Takeshi Yasui and Koichi Tsuneyama : Molecular imaging analysis of accumulated fats in non-alcoholic steatohepatitis by Raman microscopy, Asian Pacific Association for the Study of the Liver 2020 (APASL 2020), Bali, Indonesia, Mar. 2020.
13.	Mayuko Shimizu and Koichi Tsuneyama : Fibrosis begins around lipid-phagocytic macrophages in high fat/cholesterol/cholate diet-induced nonalcoholic steatohepatitis model, The Liver Meeting 2019, Boston, Nov. 2019.
14.	Mayuko Shimizu, Hirohisa Ogawa, Minoru Matsumoto and Koichi Tsuneyama : Establishment of a novel dietary-induced mouse model showing steatohepatitis with severe fibrosis, UEG Week 2019, Barcelona, Oct. 2019.
15.	Mayuko Shimizu, Takeshi Oya and Koichi Tsuneyama : Fibrogenesis of nonalcoholic steatohepatitis begins around cholesterol-laden macrophage in the experimental mouse model, UEG Week 2019, Barcelona, Oct. 2019.
16.	Ayumi Sugitani, Mayuko Shimizu, Shu Taira, Takaaki Tsunematsu and Koichi Tsuneyama : Analysis of fibrogenic roles of liver infiltrating macrophages in a novel Non-alcoholic steatohepatitis (NASH) rat model with liver cirrhosis, Hepatology, Vol.66, No.S1, 1099A-1100A, Oct. 2017.
17.	Mayuko Shimizu, Kawase Miku, Masuzumi Miki, Sakaki Mika, Nagata Yasuo, Tanaka Kazunari, Suruga Kazuhito, Koichi Tsuneyama and Omagari Katsuhisa : High-fat and high-cholesterol diet rapidly induces nonalcoholic steatohepatitis with advanced fibrosis in Sprague-Dawley rats, 23th Asian Pacific Association for the Study of the Liver, Mar. 2014.

Proceeding of Domestic Conference:

1.	Junji Chida, Eiji Hara, Mayuko Shimizu, Koichi Tsuneyama and Suehiro Sakaguchi : Anti-prion antibody treatment attenuates liver inflammation and fibrosis in experimental non-alcoholic steatohepatitis mouse modelAnti-prion antibody treatment attenuates liver inflammation and fibrosis in experimental non-alcoholic steatohepatitis mouse model,
2.	ISHIKAWA Ryuji, OHNISHI Hikari, Mayuko Shimizu, Akiko Sakurai and Keiko Kataoka : 幼若期のアンピシリン暴露が食餌誘導性NASHモデルマウスに及ぼす影響, 第97回日本細菌学会総会, Aug. 2024.
3.	Masaki Kanazawa, Eiji Hase, Mayuko Shimizu, Koichi Tsuneyama, Takeshi Yasui, Katsuya SATO and Takeo Minamikawa : 代謝機能障害に伴う脂肪性肝疾患(MASLD)診断に向けたマルチモーダル分光イメージング法の開発, 2024年度応用物理・物理系学会中国四国支部合同学術講演会, Aa-11, Jul. 2024.
4.	Hirohisa Ogawa, Mayuko Shimizu and Koichi Tsuneyama : γ-アミノ酪酸 (GABA)は喘息における粘液細胞過形成に関与するのか?, 第112 回日本病理学会総会, Apr. 2024.
5.	立花尚太郎, Hirohisa Ogawa, Koichi Tsuneyama and Mayuko Shimizu : 慢性気管支喘息においてリゾフォスファチジン酸(LPA)はLPA1受容体を介して杯細胞過形成を促進する, 第113回日本病理学会総会, Mar. 2024.
6.	前川勇輔, Hirohisa Ogawa, Koichi Tsuneyama and Mayuko Shimizu : 喘息の気道周囲の線維化におけるM1,M2マクロファージの役割, 第113回日本病理学会総会, Mar. 2024.
7.	黒田翔, Mayuko Shimizu, Hirohisa Ogawa and Koichi Tsuneyama : 代謝障害関連脂肪肝炎におけるマクロファージに対するBerberineの作用, 第112回日本病理学会総会, Mar. 2024.
8.	Kazuki Yasumaru, Tsuyoshi Takashina, Eiji Hase, Mayuko Shimizu, Takeshi Yasui, Koichi Tsuneyama and Takeo Minamikawa : 代謝性脂肪性肝疾患モデルマウスの肝臓に蓄積した脂肪滴内分子構造の解明, Optics & Photonics Japan 2023,, 28pG15, Nov. 2023.
9.	Hirohisa Ogawa, Mayuko Shimizu, 平修, Hiroki Bandoh, Seidai Satou, Koichi Tsuneyama and Yasuhiko Nishioka : メタボローム解析による複数抗原感作喘息モデルにおける難治性因子の探索, 第72回日本アレルギー学会学術大会, Oct. 2023.
10.	Tomohiro Tamaki, Takeo Minamikawa, Eiji Hase, Mayuko Shimizu, Yuki Morimoto, Akihiro Suzuki, Takeshi Yasui, 中村聡子, Akemi Tsutsui, 高口浩一 and Koichi Tsuneyama : ヒト非アルコール性脂肪性肝疾患における超早期肝線維化のSHG偏光顕微鏡解析, 第84回応用物理学会秋季学術講演会, 20p-A305-13, Sep. 2023.
11.	Mayuko Shimizu, Yuko Miyakami, 筒井朱美 and Koichi Tsuneyama : 複数の血清リン脂質を用いたNASH線維化バイオマーカーの検討, 第59回肝臓学会総会, Jun. 2023.
12.	高野峻, Mayuko Shimizu, Koichi Tsuneyama and 長井良憲 : 抗生剤投与による腸内細菌叢変化がNASH の発症・病態に与える影響の解析, 第59 回日本肝臓学会, Jun. 2023.
13.	五十嵐直哉, Mayuko Shimizu, Koichi Tsuneyama and 長井良憲 : 肝臓構成細胞に着目した非アルコール性脂肪性肝炎進展の差異に関する研究, 第59 回日本肝臓学会, Jun. 2023.
14.	Mayuko Shimizu, 西村百夏, 中原穂乃佳, Hirohisa Ogawa and Koichi Tsuneyama : Inhibitory effects of berberine on liver fibrosis in NASH model mice, 第77回日本栄養・食糧学会大会, May 2023.
15.	Hirohisa Ogawa, Mayuko Shimizu and Koichi Tsuneyama : γ-アミノ酪酸(GABA)は喘息における粘液細胞過形成に関与するのか?, 第112回日本病理学会総会, Apr. 2023.
16.	Mayuko Shimizu, Takeo Minamikawa, Eiji Hase, 筒井朱美, Hirohisa Ogawa and Koichi Tsuneyama : A New Approach to Evaluate NASH Pathophysiology Using Liver Tissue, 第112回日本病理学会総会, Apr. 2023. (Keyword) NASH / liver biopsy / SHG / Raman
17.	Mayuko Shimizu : 経皮感作による食物アレルギー, 日本バイオマテリアル学会, Dec. 2022.
18.	TOMOHIRO Tamaki, Takeo Minamikawa, Eiji Hase, Mayuko Shimizu, 森本友樹, 鈴木昭浩, Takeshi Yasui, 中村聡子, 筒井朱美, 高口浩一 and Koichi Tsuneyama : SHG 顕微鏡によるヒト非アルコール性脂肪性肝疾患の超早期肝線維化の評価, 第7回フォトニクスワークショップ, 1-P-12, Nov. 2022.
19.	KAZUKI Yasumaru, Takeo Minamikawa, Eiji Hase, Mayuko Shimizu, Takeshi Yasui and Koichi Tsuneyama : 非アルコール性脂肪性肝疾患の肝臓中に蓄積した脂肪滴の分光学的観察, 第7回フォトニクスワークショップ, 1-P-8, Nov. 2022.
20.	Hidenori Koresawa, Takeo Minamikawa, Yutaro Onishi, Hayata Tadamasa, Mayuko Shimizu, 森本友樹, Eiji Hase, Takeshi Yasui and Koichi Tsuneyama : ラマン顕微鏡による非アルコール性脂肪性肝疾患における脂肪滴の解析, Optics and Photonics Japan 2022, 16pD6, Nov. 2022.
21.	KAZUKI Yasumaru, Takeo Minamikawa, Eiji Hase, Mayuko Shimizu, Takeshi Yasui and Koichi Tsuneyama : 非アルコール性脂肪性肝疾患モデルマウスの肝臓に蓄積した脂肪滴のラマン・SHGイメージング, Optics and Photonics Japan 2022, 16pD5, Nov. 2022.
22.	TOMOHIRO Tamaki, Takeo Minamikawa, Eiji Hase, Mayuko Shimizu, 森本友樹, 鈴木昭浩, Takeshi Yasui, 中村聡子, 筒井朱美, 高口浩一 and Koichi Tsuneyama : SHG顕微鏡によるヒト非アルコール性脂肪性肝疾患の超早期肝線維化の評価, Optics and Photonics Japan 2022, 16pD4, Nov. 2022.
23.	Hirohisa Ogawa, Mayuko Shimizu, Seidai Satou, Koichi Tsuneyama and Yasuhiko Nishioka : リゾホスファチジン酸(LPA)はLPA1受容体を介して粘液細胞過形成を促進する, 第71回日本アレルギー学会学術大会, Oct. 2022.
24.	Yutaro Onishi, Takeo Minamikawa, Hidenori Koresawa, Hayata Tadamasa, Mayuko Shimizu, 森本友樹, Eiji Hase, Takeshi Yasui and Koichi Tsuneyama : ラマン顕微鏡を用いた非アルコール性脂肪性肝疾患における脂肪滴サイズと脂質分子物性の関係解析, 第83回応用物理学会秋季学術講演会, 20p-C301-8, Sep. 2022.
25.	葛西海智, 多田有希, 五十嵐直哉, 渡辺志朗, Mayuko Shimizu, Koichi Tsuneyama, 古澤之裕 and ⾧井良憲 : 新規NASH モデルマウス``3-F マウス''の炎症・線維性変化に与える抗生剤投与の影響, 第43回日本炎症・再生医学会, Jul. 2022.
26.	多田有希, 葛西海智, Mayuko Shimizu, Koichi Tsuneyama and ⾧井良憲 : 新規NASH モデルマウス``3-F マウス''における肝臓自然免疫系細胞サブセットの解析, 第43回日本炎症・再生医学会, Jul. 2022.
27.	Mayuko Shimizu and Koichi Tsuneyama : リソソーム酸性リパーゼ欠損症および高脂肪・コレステロール・コール酸食誘導NASHモデルマウスの病理所見の近似性, 第58回肝臓学会総会, Jun. 2022.
28.	葛西海智, 古澤之裕, 多田有希, 五十嵐直哉, 渡辺志朗, 藤坂志帆, 戸邉一之, Mayuko Shimizu, Koichi Tsuneyama and 長井良憲 : 非アルコール性脂肪性肝炎の新規モデルマウス``3-Fマウス''における腸内細菌叢及び胆汁酸組成の解析, 第65回日本糖尿病学会年次学術集会, May 2022.
29.	Honoka Nakahara, Asuka Watanabe, Mayuko Shimizu, Hirohisa Ogawa and Koichi Tsuneyama : Inhibitory effects of berberine on liver fibrosis in NASH model mice, 第111回日本病理学会総会, Apr. 2022.
30.	Soichiroh Ishimaru, Mayuko Shimizu, Hirohisa Ogawa and Koichi Tsuneyama : An Application of Raman Microscopy to Analyzing Dermal Changes in Cutaneously Sensitized Food Allergy Mice, 第111回日本病理学会総会, Apr. 2022.
31.	Minoru Matsumoto, Yasuyo Saijo, Mayuko Shimizu, Hirohisa Ogawa, Koichi Tsuneyama, Mitsuru Matsumoto and Takeshi Oya : 胸腺癌におけるAIRE発現と胸腺髄質上皮細胞との類似性, Proceedings of the Japanese Society of Pathology, Vol.111, No.1, 243, Apr. 2022.
32.	Mayuko Shimizu : 新規 brain-liver axis モデルの報告:うつ病マウスにおける脂肪肝炎, COI学術交流会, Feb. 2022.
33.	長友涼介, Mayuko Shimizu, Koichi Tsuneyama and 井之上浩一 : 2-ピコリルアミン誘導体化LC-MS/MS法を用いた病態モデルマウス体液及び組織中短鎖脂肪酸の分析法開発, 第32回クロマトグラフィー科学会議, Nov. 2021.
34.	柿本拓海, Mayuko Shimizu, Hirohisa Ogawa, Minoru Matsumoto, Takeshi Oya and Koichi Tsuneyama : Validation of α -synuclein immunohistochemical staining in the diagnosis of non-alcoholic steatohepatitis, The 67th Autumn Annual Meeting of Japanese Society of Pathology, Nov. 2021.
35.	Takeo Minamikawa, Mayuko Shimizu, Hiroki Tanioka, Eiji Hase, Yuki Morimoto, Hiroki Takanari, Takeshi Yasui and Koichi Tsuneyama : ラマン散乱分光法を用いた非アルコール性脂肪性肝疾患の脂質分子構造イメージング解析, レーザ顕微鏡研究会第46回講演会, Nov. 2021.
36.	Mayuko Shimizu, 遠藤亜衣子, 石丸漱一郎 and Koichi Tsuneyama : 経皮感作によるエビアレルギーモデルマウスの確立と予防法の検討, 第54回日本栄養・食糧学会中国・四国支部大会第7回日本栄養改善学会四国支部学術総会合同大会, Oct. 2021.
37.	Takumi Kakimoto, Mayuko Shimizu, Hirohisa Ogawa and Koichi Tsuneyama : 非アルコール性脂肪性肝炎の診断におけるα-synuclein免疫組織化学染色の有用性, Proceedings of the Japanese Society of Pathology, Vol.110, No.2, 102, Oct. 2021. (Keyword) 免疫組織化学 Alpha-Synuclein *肝疾患-非アルコール性脂肪性(病理学) ヒト
38.	Hirohisa Ogawa, 立花尚太郎, Mayuko Shimizu and Koichi Tsuneyama : Lysophosphatidic acid is involved in the formation of airway remodeling in chronic bronchial asthma, Proceedings of the Japanese Society of Pathology, Vol.110, No.2, 98, Oct. 2021. (Keyword) Lysophospholipids / 喘息(実験的) / 気道リモデリング / lysophosphatidic acid / マウス / 動物
39.	Hiroki Tanioka, Takeo Minamikawa, Mayuko Shimizu, Yuki Morimoto, Hiroki Takanari, Yutaro Onishi, Eiji Hase, Takeshi Yasui and Koichi Tsuneyama : 表面増強ラマン散乱分光法を用いた非アルコール性脂肪肝疾患モデルの高感度ラマンイメージング, 第82回応用物理学会秋季学術講演会予稿集, 13a-N202-9, Sep. 2021.
40.	Kensei Nishida, Mayuko Shimizu, Masahiko Azuma, Koichi Tsuneyama and Masashi Akaike : オンラインPBLチュートリアルの実施から見えてきた課題, 第53回日本医学教育学会大会, Jul. 2021.
41.	長友涼介, Mayuko Shimizu, Koichi Tsuneyama, Naozumi Ishimaru and 井之上浩一 : 誘導体化LC-MS/MSによる網羅的短鎖脂肪酸解析: モデルマウス病態への応用, 第 6 回日本医用マススペクトル学会西部会, Jul. 2021.
42.	Takeo Minamikawa, Mayuko Shimizu and Koichi Tsuneyama : Molecular structural imaging analysis for non-alcoholic fatty liver disease by Raman spectroscopy, The 57th Annual Meeting of the Japan Society of Hepatology, Jun. 2021.
43.	Katsuki Miyazaki, Yu Saitou, Mayuko Shimizu, Yuji Morine, Tetsuya Ikemoto, Shin-ichiro Yamada, Koichi Tsuneyama and Mitsuo Shimada : 小胞体ストレス応答に着目した非アルコール性脂肪肝炎の肝切除後肝再生/肝不全に関する研究, 第47回日本急性肝不全研究会, Jun. 2021.
44.	Katsuki Miyazaki, Yu Saitou, Mayuko Shimizu, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Shin-ichiro Yamada, Kazunori Tokuda, Koichi Tsuneyama and Mitsuo Shimada : Endoplasmic reticulum stress response deficiency is a major cause of poor liver regeneration after hepatectomy in nonalcoholic steatohepatitis, 第33回日本肝胆膵外科学会学術集会, Jun. 2021.
45.	Mayuko Shimizu, 富永俊弼 and 筒井朱美 : NASH線維化の連続的数値による定量的評価のための新規画像解析法の開発, 第57回日本肝臓学会総会, Jun. 2021.
46.	Mayuko Shimizu, 平修, Hirohisa Ogawa and Koichi Tsuneyama : Phospholipids Imaging of the Liver and Brain in a Mouse Model of Nonalcoholic Steatohepatitis, 第69回質量分析総合討論会2021, May 2021. (Keyword) pathogen lipids / Mass spectrometry imaging
47.	Mayuko Shimizu, 遠藤亜衣子, 石丸漱一郎, 小島拓海, Hirohisa Ogawa and Koichi Tsuneyama : Epicutaneous sensitization conditions for food allergens in animal models, 第110回日本病理学会総会, Apr. 2021.
48.	住田智志, Mayuko Shimizu, 西條康代, Minoru Matsumoto, Hirohisa Ogawa, Takeshi Oya, Yoshimi Bando, Hisanori Uehara and Koichi Tsuneyama : Pathological features and pathogenesis of epidermoid cyst in intrapancreatic accessory spleen, 第110回日本病理学会総会, Apr. 2021.
49.	Katsuki Miyazaki, Yu Saitou, Mayuko Shimizu, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Shin-ichiro Yamada, Kazunori Tokuda, Shohei Okikawa, Shoko Yamashita, Koichi Tsuneyama and Mitsuo Shimada : 非アルコール性脂肪性肝疾患(NAFLD)における肝切除後肝再生機能不全に関する研究- 小胞体ストレス応答不全の観点より -, 第 121 回日本外科学会定期学術集会, Apr. 2021.
50.	Hiroki Tanioka, Takeo Minamikawa, Mayuko Shimizu, Yuki Morimoto, Hiroki Takanari, Ryosuke Shiomi, Eiji Hase, Takeshi Yasui and Koichi Tsuneyama : 非アルコール性脂肪性肝炎診断に対するラマン顕微鏡法の適用可能性の検証計, 第68回応用物理学会春季学術講演会予稿集, 19a-Z04-9, Mar. 2021.
51.	Hirohisa Ogawa, Kayu Kinouchi, Mayuko Shimizu and Koichi Tsuneyama : 喘息モデルにおける脳由来神経栄養因子(BDNF)の産生とその役割, Proceedings of the Japanese Society of Pathology, Vol.110, No.1, 291, Mar. 2021. (Keyword) Substance P / 気管支肺胞洗浄液 / 喘息 / Th2細胞 / 脳由来神経栄養因子 / マウス / animal
52.	Mayuko Shimizu, 富永俊弼 and 筒井朱美 : NASH線維化の連続的数値による定量的評価のための新規画像解析法の開発, Acta Hepatologica Japonica, Vol.62, No.suppl.1, A132, Mar. 2021. (Keyword) NASH / fibrosis / 画像解析 / 定量
53.	Kensei Nishida, Mayuko Shimizu, Koichi Tsuneyama and Masashi Akaike : オンラインPBLチュートリアルの実施報告ならびにその効果と課題, 大学教育カンファレンスin徳島, Jan. 2021.
54.	長友涼介, 福田敦子, Mayuko Shimizu, Koichi Tsuneyama and 井之上浩一 : 実験計画法を用いた高感度2-ピコリルアミン誘導体化UHPLC-ESI-MS/MS法の開発: 血中短鎖脂肪酸測定への応用, 第31回クロマトグラフィー科学会議, Nov. 2020.
55.	Mayuko Shimizu, 大曲勝久 and Koichi Tsuneyama : 実験的モデル動物作成に用いられる高脂肪・コレステロール食に含まれるコール酸のNASH病態形成への影響, 第56回日本肝臓学会総会, Aug. 2020.
56.	Mayuko Shimizu : Make a food-based healthy body to counter the unprecedented crisis, 第3回COI学術交流会, Jul. 2020.
57.	Mayuko Shimizu, 平修, Minoru Matsumoto, Takeshi Oya, Hirohisa Ogawa and Koichi Tsuneyama : イメージング質量分析によるNASH線維化肝で増加する脂質の同定, 第109回日本病理学会総会, Jul. 2020.
58.	Mayuko Shimizu, Riku Yamaguchi, CHIYAMOTO Mana, OSAKI Yui and Koichi Tsuneyama : Antibacterial agent for external use promotes epicutaneous sensitization of food allergen in experimental mice, 第74回日本栄養食糧学会大会, May 2020.
59.	Mayuko Shimizu, 平修, Minoru Matsumoto, Takeshi Oya, Hirohisa Ogawa and Koichi Tsuneyama : NASH線維化肝におけるpathogen lipidsの同定, 第260回徳島医学会学術集会, Feb. 2020.
60.	Koichi Tsuneyama, Mayuko Shimizu, Takeshi Oya, Minoru Matsumoto and Hirohisa Ogawa : 自然発症メタボリックシンドローム-NASH-HCCモデルマウスにおけるプレバイオティクスによる腸内細菌叢への介入効果の検討, 第30回日本消化器癌発生学会総会, Nov. 2019.
61.	Mayuko Shimizu, 大曲勝久 and Koichi Tsuneyama : 食餌摂取による高度な線維化を伴うNASHモデルマウスの開発, 第55回日本肝臓学会総会, May 2019. (Keyword) Liver fibrosis / mouse model / TSOD mice / TSNO mice
62.	Koichi Tsuneyama and Mayuko Shimizu : 免疫チェックポイント阻害薬による肝障害を来した4例の病理学的特徴, 第55回日本肝臓学会総会, May 2019. (Keyword) 免疫チェックポイント阻害薬 / 肝障害
63.	飯田綾香, 甲斐瑠衣子, 倉貫早智, Mayuko Shimizu, Koichi Tsuneyama and 中村強 : Nonalcoholic fatty liver Disease in Western Diet-Loaded C57BL/6J mice, 第73回日本栄養食糧学会大会, May 2019. (Keyword) nonalcoholic steatohepatitis / 疾患モデル動物
64.	福田歩美, 佐々尾真鈴, 浅川惠理, 成田純令, 久野萌偉, 駿河和仁, Mayuko Shimizu, Koichi Tsuneyama, 田中一成 and 大曲勝久 : Incidence of non-alcoholic steatohepatitis in SD rats fed a high-fat and high-cholesterol diet., 第73回日本栄養食糧学会大会, May 2019. (Keyword) nonalcoholic steatohepatitis / mouse model / high fat and high cholesterol diet
65.	Mayuko Shimizu, 大曲勝久 and Koichi Tsuneyama : Establishment of dietary model of nonalcoholic steatohepatitis-related fibrosis, 第73回日本栄養食糧学会大会, May 2019. (Keyword) Liver fibrosis / nonalcoholic steatohepatitis / mouse model / high fat and high cholesterol diet
66.	Mayuko Shimizu, Takeshi Oya, Hirohisa Ogawa, 大曲勝久 and Koichi Tsuneyama : Cholesterol-loaded macrophage is associated with development of hepatic fibrosis in mice, 第108回日本病理学会総会, May 2019. (Keyword) liver fibrosis / macrophage / cholesterol / nonalcoholic steatohepatitis
67.	長友涼介, 福田敦子, Mayuko Shimizu, 赤津裕康, Koichi Tsuneyama and 井之上浩一 : 2-ピコリルアミン誘導体化UHPLC-ESI-MS/MS法を用いた短鎖脂肪酸のマウス臓器分布解析, 日本薬学会第139年会, Mar. 2019.
68.	Koichi Tsuneyama, Mayuko Shimizu, Takeshi Oya, Minoru Matsumoto and Hirohisa Ogawa : 異なる系統で作成したストレプトゾトシン誘導肝細胞癌モデルマウスの病態比較, 第29回日本消化器癌発生学会総会, Nov. 2018.
69.	天野久実, 中川友希江, Mayuko Shimizu, 辻愛, 北岸靖子 and 松田覚 : オウバク成分は非アルコール性脂肪肝疾患(NAFLD)改善に関与するか?, 第91回日本生化学会大会, Sep. 2018. (Keyword) lifestyle-related disease / オウバク / NAFLD / SOD
70.	中川友希江, 天野久実, Mayuko Shimizu, 辻愛, 北岸靖子 and 松田覚 : 脂肪性肝障害に対する少量アセトアルデヒド摂取の影響, 第91回日本生化学会大会, Sep. 2018. (Keyword) 肝疾患 / NAFLD / AKTキナーゼ / SOD
71.	Mayuko Shimizu, Kazuchika Nishitsuji, 清水金忠, Hirohisa Ogawa, Takaaki Tsunematsu, 梅本ひとみ, 森本友樹, 赤津裕康, 井之上浩一 and Koichi Tsuneyama : TSODマウスにおけるNAFLDの発症およびコーヒーの投与による腸内細菌叢および短鎖脂肪酸プロファイルの変化, 第5回肝臓と糖尿病・代謝研究会, Jul. 2018. (Keyword) TSOD mice / short chain fatty acid / microbiota / coffee
72.	Mayuko Shimizu, 大曲勝久 and Koichi Tsuneyama : The morphological changes of the liver of TSOD and TSNO mice fed the high-fat plus cholesterol diet, 第107回日本病理学会総会, Jun. 2018. (Keyword) TSOD mice / TSNO mice / NASH / HFC diet
73.	井邉有未, Mayuko Shimizu and 松田覚 : 小学校低学年とその保護者を対象とした食育活動, 第64回日本栄養改善学会学術総会, Sep. 2017.
74.	Mayuko Shimizu, 井邉有未 and 松田覚 : 親子で学ぶ食育教室の意義 ―奈良県地域栄養カレッジにおける実践例から―, 第64回日本栄養改善学会学術総会, Sep. 2017.
75.	Mayuko Shimizu and 松田覚 : 地域住民向け食育活動『奈良県地域栄養カレッジ』実施報告, 奈良県栄養士会研究発表会, Aug. 2017.
76.	中村禎子, 田辺賢一, Mayuko Shimizu, 森田茂樹, 大曲勝久 and 奥恒行 : 過剰鉄による肝障害モデルラットにおけるフラクトオリゴ糖摂取の症状軽減作用, 日本栄養食糧学会, May 2017.
77.	Mayuko Shimizu, Koichi Tsuneyama, 守時由起, 松本光太郎, 綱島弘道, 大曲勝久 and 菊池健太郎 : 異なる非アルコール性脂肪肝炎モデル間におけるフラクトオリゴ糖による肝脂肪化抑制機序の違い, Acta Hepatologica Japonica, Vol.58, No.Suppl.1, A395, Apr. 2017.
78.	菊池健太郎, Koichi Tsuneyama, Mayuko Shimizu, 守時由起, 松本光太郎, 綱島弘道, 大曲勝久, 安田一朗, 原眞純 and 宮川浩 : monosodium glutamate投与によるNASHモデルマウスに対するフラクトオリゴ糖の効果, Acta Hepatologica Japonica, Vol.58, No.Suppl.1, A388, Apr. 2017.
79.	Koichi Tsuneyama, Mayuko Shimizu and 大曲勝久 : 食餌誘導NASH 肝線維化モデルラットにおける肝浸潤マクロファージの性状, Acta Hepatologica Japonica, Vol.58, No.Suppl.1, A396, Apr. 2017.
80.	Ayumi Sugitani, Ryusei Takahashi, Kohki Kai, Mayuko Shimizu, 平修, 川口誠, Hirohisa Ogawa, Takaaki Tsunematsu, Koichi Tsuneyama, 野本一博 and Koichi Tsuneyama : A case of lipid-rich carcinoma of the breast with numerous hyaline globules, Proceedings of the Japanese Society of Pathology, Vol.106, No.1, 492-493, Mar. 2017.
81.	杉谷鮎美, 高橋立成, 甲斐幸樹, Mayuko Shimizu, 平修, 川口誠, Hirohisa Ogawa, Takaaki Tsunematsu, Koichi Tsuneyama, 野本一博 and 常山幸一 : A case of lipid-rich carcinoma of the breast with numerous hyaline globules(和訳中), Proceedings of the Japanese Society of Pathology, Vol.106, No.1, 492-493, Mar. 2017.
82.	南明里, 中野紀子, Mayuko Shimizu and 松田覚 : Effect of food ingredients on osteoclast differentiation, 第70回日本栄養食糧学会大会, May 2016. (Keyword) osteoclast / 骨粗鬆症
83.	西明眞理, 幸田菜摘, 矢野詩織, Mayuko Shimizu, 川本忠文 and 片山吉穂 : The effect of diallyl sulfide(DAS) on body conposition and energy metabolism in rats., 第67回日本栄養食糧学会大会, May 2013. (Keyword) osteoclast / 骨粗鬆症
84.	Mayuko Shimizu, 畑中麻衣子, Koichi Tsuneyama, 加藤滋子 and 大曲勝久 : An animal model of NASH with advanced fibrosis induced by high-fat and high-cholesterol diet, 第67回日本栄養食糧学会大会, May 2013. (Keyword) NASH / SHR/NDmcr-cp rat / high fat and high cholesterol diet / fibrosis

Et cetera, Workshop:

1.	藤本悠 and Mayuko Shimizu : 地理学と病理学∼地球を観る目で病理を覗く∼, 第11回 TR推進合同フォーラム・ライフサイエンス技術交流会, Jan. 2024.
2.	OKUBO Naoya, Eiji Hase, YASUMARU Kazuki, Yu Tokizane, Mayuko Shimizu, Koichi Tsuneyama, Takeo Minamikawa and Takeshi Yasui : ブリルアン散乱顕微鏡を用いた代謝機能障害に伴う脂肪性肝疾患における蓄積脂質の分子物性解析, 次世代光フォーラム2024 in 徳島, P-6, Jan. 2024.
3.	TOMOHIRO Tamaki, Takeo Minamikawa, Eiji Hase, Mayuko Shimizu, Yuki Morimoto, Akihiro Suzuki, Takeshi Yasui, 中村聡子, Akemi Tsutsui, 高口浩一 and Koichi Tsuneyama : ヒト非アルコール性脂肪性肝疾患における超早期肝線維化のSHG 偏光顕微鏡解析, 次世代光フォーラム2023 in 徳島, P-12, Feb. 2023.
4.	Mayuko Shimizu : 肝線維化始発点を可視化する新規NASHモデルマウスの作出, 第3回高齢化と生体恒常性研究会, May 2022.
5.	Kohta Hata, Ryoga Yuasa, Sarina Takeuchi, Michiko Yamashita, Takeshi Oya, Koichi Tsuneyama and Mayuko Shimizu : 骨髄膠様変性時，臨床検査値と造血幹細胞ニッチはどう変化しているか, THE TOKUSHIMA JOURNAL OF MEDICAL TECHNOLOGY, 28, Dec. 2021.
6.	Hiroki Tanioka, Takeo Minamikawa, Mayuko Shimizu, 森本友樹, Hiroki Takanari, Ryosuke Shiomi, Eiji Hase, Takeshi Yasui and Koichi Tsuneyama : 非アルコール性脂肪肝炎の蓄積した脂肪に着目したラマン分光イメージング, LED総合フォーラム2021 in 徳島, P-14, Feb. 2021.
7.	Yurie Kobayashi, Sarina Takeuchi, Michiko Yamashita, Koichi Tsuneyama and Mayuko Shimizu : Statistical study of laboratory values correlated with gelatinous degeneration of bone marrow, THE TOKUSHIMA JOURNAL OF MEDICAL TECHNOLOGY, 19, Dec. 2020.
8.	Mayuko Shimizu : コレステロール添加高脂肪飼料を用いたNASH病態モデル動物の開発, 奈良女子大学家政学会, Vol.62, 57-61, 2015.

Patent:

1.	Mayuko Shimizu, Koichi Tsuneyama and 大曲勝久 : 肝の線維化を伴い得るNAFLDモデル動物，その作製方法，及びそれを作製するための飼料, (Oct. 2017), .

Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)

難治性喘息における抗原由来難治化因子の機能解明 -新しい治療戦略にむけて (Project/Area Number: 24K13440 )
Elucidation of the pathogenesis and new therapeutic strategies for brain- and gut-related steatohepatitis based on brain-derived neurotrophic factor (Project/Area Number: 22K07024 )
The role of macrophages in the progression of fibrosis of NASH and its regulation by nutritional factors (Project/Area Number: 20K19676 )
Search for functional ingredients and foods altering cholesterol-bile acid metabolism for prevention of NASH development (Project/Area Number: 17K17883 )
Search by Researcher Number (20759021)

Associate Professor : Shimizu, Mayuko

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Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)