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  1. Article ; Online: Impact of particulate microplastics generated from polyethylene terephthalate on gut pathology and immune microenvironments

    Akihito Harusato / Wooseok Seo / Hirohito Abo / Yoshitaka Nakanishi / Hiroyoshi Nishikawa / Yoshito Itoh

    iScience, Vol 26, Iss 4, Pp 106474- (2023)

    2023  

    Abstract: Summary: Environmental microplastics have emerged as a critical issue in maintaining the planetary ecosystem. In this study, we generated particulate microplastics from polyethylene terephthalate (PM-PET) and investigated their impact in the gut by using ...

    Abstract Summary: Environmental microplastics have emerged as a critical issue in maintaining the planetary ecosystem. In this study, we generated particulate microplastics from polyethylene terephthalate (PM-PET) and investigated their impact in the gut by using mouse models and implementing histological examinations, as well as multi-omics analysis for colonic immune cells and microbiota. As a result, histological approaches showed that chronic and physiological low dose exposure of PM-PET did not affect intestinal pathology and mucin barriers, respectively. Moreover, immunohistochemical analysis demonstrated that the numbers of T cells, B cells, macrophages, and granulocytes were not affected by the exposure to PM-PET. However, RNA-seq analysis revealed that PM-PET had a substantial impact on the transcriptome in gut immune cells and their metabolisms, while 16s rRNA metagenomic analysis showed that the composition of microbiota was modestly affected. These results suggest an unexpected role played by the PM-PET in affecting gut immune homeostasis without detectable inflammation.
    Keywords Immunology ; Pollution ; Science ; Q
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Higher Viral Stability and Ethanol Resistance of Avian Influenza A(H5N1) Virus on Human Skin

    Risa Bandou / Ryohei Hirose / Takaaki Nakaya / Hajime Miyazaki / Naoto Watanabe / Takuma Yoshida / Tomo Daidoji / Yoshito Itoh / Hiroshi Ikegaya

    Emerging Infectious Diseases, Vol 28, Iss 3, Pp 639-

    2022  Volume 649

    Abstract: Evaluating the stability of highly pathogenic avian influenza viruses on human skin and measuring the effectiveness of disinfectants are crucial for preventing contact disease transmission. We constructed an evaluation model using autopsy skin samples ... ...

    Abstract Evaluating the stability of highly pathogenic avian influenza viruses on human skin and measuring the effectiveness of disinfectants are crucial for preventing contact disease transmission. We constructed an evaluation model using autopsy skin samples and evaluated factors that affect the stability and disinfectant effectiveness for various subtypes. The survival time of the avian influenza A(H5N1) virus on plastic surfaces was ≈26 hours and on skin surfaces ≈4.5 hours, >2.5-fold longer than other subtypes. The effectiveness of a relatively low ethanol concentration (32%–36% wt/wt) against the H5N1 subtype was substantially reduced compared with other subtypes. Moreover, recombinant viruses with the neuraminidase gene of H5N1 survived longer on plastic and skin surfaces than other recombinant viruses and were resistant to ethanol. Our results imply that the H5N1 subtype poses a higher contact transmission risk because of its higher stability and ethanol resistance, which might depend on the neuraminidase protein.
    Keywords H5N1 ; avian influenza virus ; human skin ; stability ; disinfectant effectiveness ; hand hygiene ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
    Subject code 616
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Centers for Disease Control and Prevention
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Potential Therapeutic Targets and Promising Agents for Combating NAFLD

    Atsushi Umemura / Seita Kataoka / Keiichiro Okuda / Yuya Seko / Kanji Yamaguchi / Michihisa Moriguchi / Takeshi Okanoue / Yoshito Itoh

    Biomedicines, Vol 10, Iss 901, p

    2022  Volume 901

    Abstract: Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is a growing cause of liver cirrhosis and liver cancer worldwide because of the global increases in obesity, dyslipidemia, hypertension, and type 2 diabetes mellitus. ...

    Abstract Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is a growing cause of liver cirrhosis and liver cancer worldwide because of the global increases in obesity, dyslipidemia, hypertension, and type 2 diabetes mellitus. Contrary to the advancements in therapies for viral hepatitis, effective treatments remain unestablished for patients with NAFLD. NAFLD, including NASH, is characterized by steatosis, inflammation, hepatic necrosis, and fibrosis. Despite our understanding of its pathophysiology, there are currently no effective treatments for NAFLD. In this review, we provide an update on the known pathophysiological mechanisms involved in the development of NAFLD and the role of hepatic stellate cells, and summarize the potential therapeutic agents, including natural products, for NAFLD.
    Keywords NAFLD ; NASH ; HCC ; honokiol ; HSC ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Red dichromatic imaging improves visibility of bleeding during gastric endoscopic submucosal dissection

    Kohei Oka / Naoto Iwai / Takashi Okuda / Toshifumi Tsuji / Hiroaki Sakai / Chie Hattori / Masashi Taniguchi / Tasuku Hara / Toshiyuki Komaki / Junichi Sakagami / Keizo Kagawa / Osamu Dohi / Yoshito Itoh

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    2023  Volume 8

    Abstract: Abstract Bleeding frequently occurs during gastric endoscopic submucosal dissection (ESD) and bleeding points are sometimes difficult to detect. Red dichromatic imaging (RDI) was recently developed to improve the visibility of bleeding. Our study aimed ... ...

    Abstract Abstract Bleeding frequently occurs during gastric endoscopic submucosal dissection (ESD) and bleeding points are sometimes difficult to detect. Red dichromatic imaging (RDI) was recently developed to improve the visibility of bleeding. Our study aimed at examining the efficacy of RDI in improving the visibility of bleeding during gastric ESD. We retrospectively evaluated the visibility score and color difference of bleeding spot during gastric ESD during September 2020–January 2021. The visibility score was evaluated as four numeric values by operators, and the color difference between the bleeding spot and surroundings was evaluated using RDI and white light imaging (WLI). A further analysis to evaluate bleeding characteristics was performed to evaluate the possible beneficial effects of RDI. Twenty patients with a total of 85 bleedings were analyzed. The mean visibility score in RDI was significantly higher than that in WLI (3.69 ± 0.60 vs 3.20 ± 0.84, p < 0.01). The color difference with RDI was also significantly higher than that with WLI (19.51 ± 15.18 vs 14.80 ± 7.41, p < 0.01). Furthermore, in the bleedings with a higher visibility score in RDI, the color difference in RDI was significantly higher than that in WLI (23.99 ± 19.29 vs 14.33 ± 7.08, p < 0.01). The multivariate analysis of visibility scores revealed that submergence of bleeding points was independently associated with the superiority of RDI (odds ratio 10.35, 95% confidence interval: 2.76–38.81, p < 0.01). Our study demonstrates that RDI can improve the visibility of bleeding during gastric ESD.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Gut Microbiota Associated with Clinical Relapse in Patients with Quiescent Ulcerative Colitis

    Hiroaki Kitae / Tomohisa Takagi / Yuji Naito / Ryo Inoue / Yuka Azuma / Takashi Torii / Katsura Mizushima / Toshifumi Doi / Ken Inoue / Osamu Dohi / Naohisa Yoshida / Kazuhiro Kamada / Kazuhiko Uchiyama / Takeshi Ishikawa / Hideyuki Konishi / Yoshito Itoh

    Microorganisms, Vol 10, Iss 1044, p

    2022  Volume 1044

    Abstract: The microbiota associated with relapse in patients with quiescent ulcerative colitis (qUC) remains unclear. Our objective was to analyze the fecal microbiota of Japanese patients with qUC and identify the relapse-associated microbiota. In this study, 59 ... ...

    Abstract The microbiota associated with relapse in patients with quiescent ulcerative colitis (qUC) remains unclear. Our objective was to analyze the fecal microbiota of Japanese patients with qUC and identify the relapse-associated microbiota. In this study, 59 patients with qUC and 59 healthy controls (HCs) were enrolled (UMIN 000019486), and their fecal microbiota was compared using 16S rRNA gene amplicon sequencing. We followed their clinical course up to 3.5 years and analyzed the relapse-associated microbiota. Potential functional changes in the fecal microbiota were evaluated using PICRUSt software and the Kyoto Encyclopedia of Genes and Genomes database. There were significant differences in fecal microbiota diversity between HC and qUC subjects, with 13 taxa characterizing each subject. Despite no significant difference in variation of microbiota in a single sample (α diversity) between patients in sustained remission and relapsed patients, the variation in microbial communities between samples (β diversity) was significantly different. Prevotella was more abundant in the sustained remission patients, whereas Faecalibacterium and Bifidobacterium were more abundant in the relapsed patients. We clustered the entire cohort into four clusters, and Kaplan–Meier analysis revealed the subsequent clinical course of each cluster was different. We identified 48 metabolic pathways associated with each cluster using linear discriminant analysis effect size. We confirmed the difference in microbiota between patients with qUC and HCs and identified three genera associated with relapse. We found that the clusters based on these genera had different subsequent clinical courses and activated different metabolic pathways.
    Keywords quiescent ulcerative colitis ; fecal microbiota ; ulcerative colitis relapse ; LEfSe ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Loss of KAP3 decreases intercellular adhesion and impairs intracellular transport of laminin in signet ring cell carcinoma of the stomach

    Tomohiro Soda / Yasuyuki Gen / Kei Terasaki / Naoto Iwai / Tomoko Kitaichi / Osamu Dohi / Hiroyoshi Taketani / Yuya Seko / Atsushi Umemura / Taichiro Nishikawa / Kanji Yamaguchi / Michihisa Moriguchi / Hideyuki Konishi / Yuji Naito / Yoshito Itoh / Kohichiroh Yasui

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 12

    Abstract: Abstract Signet-ring cell carcinoma (SRCC) is a unique subtype of gastric cancer that is impaired for cell–cell adhesion. The pathogenesis of SRCC remains unclear. Here, we show that expression of kinesin-associated protein 3 (KAP3), a cargo adaptor ... ...

    Abstract Abstract Signet-ring cell carcinoma (SRCC) is a unique subtype of gastric cancer that is impaired for cell–cell adhesion. The pathogenesis of SRCC remains unclear. Here, we show that expression of kinesin-associated protein 3 (KAP3), a cargo adaptor subunit of the kinesin superfamily protein 3 (KIF3), a motor protein, is specifically decreased in SRCC of the stomach. CRISPR/Cas9-mediated gene knockout experiments indicated that loss of KAP3 impairs the formation of circumferential actomyosin cables by inactivating RhoA, leading to the weakening of cell–cell adhesion. Furthermore, in KAP3 knockout cells, post-Golgi transport of laminin, a key component of the basement membrane, was inhibited, resulting in impaired basement membrane formation. Together, these findings uncover a potential role for KAP3 in the pathogenesis of SRCC of the stomach.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Typing of the Gut Microbiota Community in Japanese Subjects

    Tomohisa Takagi / Ryo Inoue / Akira Oshima / Hiroshi Sakazume / Kenta Ogawa / Tomo Tominaga / Yoichi Mihara / Takeshi Sugaya / Katsura Mizushima / Kazuhiko Uchiyama / Yoshito Itoh / Yuji Naito

    Microorganisms, Vol 10, Iss 664, p

    2022  Volume 664

    Abstract: Gut microbiota are involved in both host health and disease and can be stratified based on bacteriological composition. However, gut microbiota clustering data are limited for Asians. In this study, fecal microbiota of 1803 Japanese subjects, including ... ...

    Abstract Gut microbiota are involved in both host health and disease and can be stratified based on bacteriological composition. However, gut microbiota clustering data are limited for Asians. In this study, fecal microbiota of 1803 Japanese subjects, including 283 healthy individuals, were analyzed by 16S rRNA sequencing and clustered using two models. The association of various diseases with each community type was also assessed. Five and fifteen communities were identified using partitioning around medoids (PAM) and the Dirichlet multinominal mixtures model, respectively. Bacteria exhibiting characteristically high abundance among the PAM-identified types were of the family Ruminococcaceae (Type A) and genera Bacteroides , Blautia , and Faecalibacterium (Type B); Bacteroides , Fusobacterium , and Proteus (Type C); and Bifidobacterium (Type D), and Prevotella (Type E). The most noteworthy community found in the Japanese subjects was the Bifidobacterium -rich community. The odds ratio based on type E, which had the largest population of healthy subjects, revealed that other types (especially types A, C, and D) were highly associated with various diseases, including inflammatory bowel disease, functional gastrointestinal disorder, and lifestyle-related diseases. Gut microbiota community typing reproducibly identified organisms that may represent enterotypes peculiar to Japanese individuals and that are partly different from those of indivuals from Western countries.
    Keywords gut microbiota community ; partitioning around medoids (PAM) model ; Dirichlet multinominal mixtures (DMM) model ; Bifidobacterium ; enterotype ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Epidemiology

    Yoshio Sumida / Toshihide Shima / Yasuhide Mitsumoto / Takafumi Katayama / Atsushi Umemura / Kanji Yamaguchi / Yoshito Itoh / Masashi Yoneda / Takeshi Okanoue

    International Journal of Molecular Sciences, Vol 21, Iss 4337, p

    Pathogenesis, and Diagnostic Strategy of Diabetic Liver Disease in Japan

    2020  Volume 4337

    Abstract: Type 2 diabetes (T2D) is closely associated with nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to cirrhosis, hepatocellular carcinoma (HCC), and hepatic decompensation. Patients with T2D ... ...

    Abstract Type 2 diabetes (T2D) is closely associated with nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to cirrhosis, hepatocellular carcinoma (HCC), and hepatic decompensation. Patients with T2D have twice the risk of HCC incidence compared with those without T2D. Because the hepatic fibrosis grade is the main determinant of mortality in patients with NAFLD, identifying patients with advanced fibrosis using non-invasive tests (NITs) or imaging modalities is crucial. Globally, the fibrosis-4 index (FIB-4 index), NAFLD fibrosis score, and enhanced liver fibrosis test have been established to evaluate hepatic fibrosis. Two-step algorithms using FIB-4 index as first triaging tool are globally accepted. It remains unknown which kinds of NITs or elastography are best as the second step tool. In Japan, type IV collagen 7s or the CA-fibrosis index (comprising type IV collagen 7s and aspartate aminotransferase (AST)) is believed to precisely predict advanced fibrosis in NAFLD. Patients with NAFLD who have high non-invasive test results should be screened for HCC or esophageal varices. Risk factors of rapid fibrosis progression in NAFLD includes age, severe obesity, presence of T2D, menopause in women, and a patatin-like phospholipase domain containing the 3 GG genotype. Patients with NAFLD who have these risk factors should be intensively treated with lifestyle modification or pharmacotherapies for preventing liver-related mortality.
    Keywords hepatic fibrosis ; type IV collagen 7s ; hepatocellular carcinoma ; patatin-like phospholipase domain containing 3 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Correction

    Hayato Miyake / Junichi Sakagami / Hiroaki Yasuda / Yoshio Sogame / Ryusuke Kato / Kanetoshi Suwa / Katsuyuki Dainaka / Tomoki Takata / Isao Yokota / Yoshito Itoh

    PLoS ONE, Vol 15, Iss 7, p e

    Association of fatty pancreas with pancreatic endocrine and exocrine function.

    2020  Volume 0236915

    Abstract: This corrects the article DOI:10.1371/journal.pone.0209448.]. ...

    Abstract [This corrects the article DOI:10.1371/journal.pone.0209448.].
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-β1/SMAD Signaling and Autophagy in Hepatic Stellate Cells

    Seita Kataoka / Atsushi Umemura / Keiichiro Okuda / Hiroyoshi Taketani / Yuya Seko / Taichiro Nishikawa / Kanji Yamaguchi / Michihisa Moriguchi / Yoshihiro Kanbara / Jack L. Arbiser / Toshihide Shima / Takeshi Okanoue / Yoshito Itoh

    International Journal of Molecular Sciences, Vol 22, Iss 13354, p

    2021  Volume 13354

    Abstract: Chronic liver injury may result in hepatic fibrosis, which can progress to cirrhosis and eventually liver failure. There are no drugs that are specifically approved for treating hepatic fibrosis. The natural product honokiol (HNK), a bioactive compound ... ...

    Abstract Chronic liver injury may result in hepatic fibrosis, which can progress to cirrhosis and eventually liver failure. There are no drugs that are specifically approved for treating hepatic fibrosis. The natural product honokiol (HNK), a bioactive compound extracted from Magnolia grandiflora , represents a potential tool in the management of hepatic fibrosis. Though HNK has been reported to exhibit suppressive effects in a rat fibrosis model, the mechanisms accounting for this suppression remain unclear. In the present study, the anti-fibrotic effects of HNK on the liver were evaluated in vivo and in vitro. In vivo studies utilized a murine liver fibrosis model, in which fibrosis is induced by treatment with carbon tetrachloride (CCl 4 ). For in vitro studies, LX-2 human hepatic stellate cells (HSCs) were treated with HNK, and expression of markers of fibrosis, cell viability, the transforming growth factor-β (TGF-β1)/SMAD signaling pathway, and autophagy were analyzed. HNK was well tolerated and significantly attenuated CCl 4 -induced liver fibrosis in vivo. Moreover, HNK decreased HSC activation and collagen expression by downregulating the TGF-β1/SMAD signaling pathway and autophagy. These results suggest that HNK is a new potential candidate for the treatment of hepatic fibrosis through suppressing both TGF-β1/SMAD signaling and autophagy in HSCs.
    Keywords hepatic fibrosis ; stellate cell ; honokiol ; autophagy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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