研究者詳細 - 寺井　崇二

論文 - 寺井　崇二

分割表示 1,104 件中 1 - 20 件目／全件表示 >>

Guidance on the clinical application of extracellular vesicles. 国際誌

Shuji Terai, Motohiro Asonuma, Ayuko Hoshino, Masahiro Kino-Oka, Takahiro Ochiya, Kiyoshi Okada, Yoji Sato, Yuki Takahashi, Morikuni Tobita, Atsunori Tsuchiya

Regenerative therapy 29 43 - 50 2025年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Therapies using extracellular vesicles (EVs), exosomes, or cell culture supernatants containing EVs or exosomes (referred to as "EV therapies" in this Guidance) have garnered an increasing amount of interest. However, pharmaceutical products containing EVs as their main active ingredient are yet to receive regulatory approval. The "Basic points to consider regarding the preparation of extracellular vesicles and their clinical applications in Japan," was announced by the Japanese Society for Regenerative Medicine (JSRM) on March 10, 2021, with a specific focus on exosomes among EVs to promote high safety standards in this evolving field and facilitate the application of EV clinically. The Scientific Committee of the Pharmaceuticals and Medical Devices Agency and the Japanese Society for Extracellular Vesicles have issued reports and statements regarding treatment, resulting in a growing momentum toward treatment in Japan. This article summarized the basic items that should be recognized comprehensively for clinical practice in three categories: (1) risk profiling, (2) preparation (manufacturing) process and quality, and (3) verification of EVs checking items and effectiveness. This guideline will be revised in the future with technological innovations and new findings; nevertheless, it will serve as a guide for the development of treatments.

DOI： 10.1016/j.reth.2025.02.008

Safety of edoxaban for delayed bleeding in gastrointestinal endoscopic procedures with a high risk of bleeding. 国際誌

Ken-Ichi Mizuno, Junji Yokoyama, Osamu Shibata, Yuichi Kojima, Yuzo Kawata, Kazuya Takahashi, Kentaro Tominaga, Igarashi Satoshi, Hayashi Kazunao, Shuji Terai

DEN open 5 ( 1 ) e70018 2025年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: There are limited reports on the safety of gastrointestinal endoscopic procedures in individuals taking edoxaban, one of the direct oral anticoagulants. We clarified the incidence of delayed bleeding in patients who were on edoxaban in the perioperative period of gastrointestinal endoscopic procedures with a high risk of bleeding. METHODS: This was an investigator-initiated, single-center, open-label, prospective, single-arm study. Patients on warfarin or edoxaban undergoing endoscopy with a high risk of bleeding were enrolled from June 2018 to September 2021. Warfarin was replaced with edoxaban in patients on warfarin. Patients taking other direct oral anticoagulants, and antiplatelet drugs, were excluded. The primary endpoint was severe delayed bleeding (Common Terminology Criteria for Adverse Events [CTCAE] grades III-V) and the secondary endpoints included thromboembolism, all adverse events, any delayed bleeding (CTCAE grades I or II), and hospital stay durations. RESULTS: Twenty-one patients on edoxaban underwent high-risk endoscopy. Three cases (14%) experienced CTCAE grade III delayed bleeding, requiring endoscopic hemostasis. No CTCAE grade I-II delayed bleeding or thromboembolic events occurred. Cholangitis and aspiration pneumonia (conservatively treated) occurred during the hospital stay. The median length of hospital stay was 8 days (range 3-24 days). Patients with delayed bleeding had higher systolic blood pressure at admission and longer hospital stays. CONCLUSIONS: The delayed bleeding incidence in high-risk endoscopic procedures for patients on edoxaban was acceptable. Higher blood pressure may be associated with increased risk, but further research is needed.

DOI： 10.1002/deo2.70018

Coexistence of Relapsing Polychondritis, Crohn's Disease, and Pyoderma Gangrenosum Treated Successfully with Adalimumab: A Case Report and Literature Review.

Shun Yamazaki, Kentaro Tominaga, Kotaro Watanabe, Makoto Watanabe, Shuhei Kondo, Norihiro Sakai, Tomoaki Yoshida, Yuichi Kojima, Yusuke Watanabe, Yuzo Kawata, Naruhiro Kimura, Kazuya Takahashi, Hiroki Sato, Satoshi Ikarashi, Hiroteru Kamimura, Kazunao Hayashi, Shuji Terai

Internal medicine (Tokyo, Japan) 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Relapsing polychondritis (RP) is a rare, progressive, immune-mediated systemic inflammatory disease of unknown etiology characterized by recurrent inflammation of cartilaginous structures. Approximately 30% of RP cases are associated with autoimmune disease. However, co-occurrence of RP and Crohn's disease (CD) has rarely been reported. We herein report a case of coexisting RP, CD, and pyoderma gangrenosum that was successfully treated with adalimumab in combination with methotrexate. We believe that this case and literature review will facilitate the accurate and prompt diagnosis and treatment of RP combined with CD and various other complications.

DOI： 10.2169/internalmedicine.5024-24

Current management and future perspectives of covert hepatic encephalopathy in Japan: a nationwide survey.

Takao Miwa, Mio Tsuruoka, Hajime Ueda, Tamami Abe, Hiroki Inada, Yoshimi Yukawa-Muto, Masatsugu Ohara, Taeang Arai, Yasuyuki Tamai, Hiroshi Isoda, Tomoko Tadokoro, Tatsunori Hanai, Takanori Ito, Nobuharu Tamaki, Akira Sakamaki, Yoshihiko Aoki, Fujimasa Tada, Sachiyo Yoshio, Hirokazu Takahashi, Asahiro Morishita, Tsuyoshi Ishikawa, Jun Inoue, Goki Suda, Chikara Ogawa, Masanori Atsukawa, Atsushi Hiraoka, Hidekatsu Kuroda, Tadashi Namisaki, Takashi Honda, Takumi Kawaguchi, Yasuhito Tanaka, Shuji Terai, Tadashi Ikegami, Hitoshi Yoshiji, Motoh Iwasa, Masahito Shimizu

Journal of gastroenterology 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Covert hepatic encephalopathy (CHE) leads to devastating outcomes in patients with cirrhosis. This study aims to elucidate the current management and future perspectives of CHE in Japan. METHODS: A questionnaire-based cross-sectional study was conducted among physicians involved in managing cirrhosis in Japan. The primary aim was to elucidate the real-world management of CHE, including testing and treatment. Factors influencing the implementation of CHE testing were analyzed using a logistic regression model. Limitations and future perspectives for improving the management of CHE were also evaluated. RESULTS: Of 511 physicians surveyed, 93.9% recognized CHE as a significant problem, and 86.9% agreed that it should be tested. Overall, 62.8% of physicians tested for CHE, whereas 37.2% did not. Multivariable analysis identified institutional factors and certifying board as significant determinants of CHE test implementation. The Stroop (68.2%) and neuropsychiatric tests (57.5%) were the most commonly used methods of identifying CHE. Among those who tested for CHE, 87.7% treated CHE; the most common treatments were lactulose (81.5%), rifaximin (76.3%), and branched-chain amino acids (70.4%). Among non-testers, the primary barrier was the time requirement for testing. Proposals to encourage CHE testing included the development of simple tests and integration of multidisciplinary teams. CONCLUSIONS: Most physicians involved in cirrhosis care in Japan recognize CHE as a significant problem that warrants testing. However, testing for CHE remains limited by institutional factors and physician specialties. Time requirements for CHE testing are the primary barrier, and simple tests and multidisciplinary teams are recommended to enhance CHE management.

DOI： 10.1007/s00535-025-02232-0

Targeted animal models for preclinical assessment of cellular and gene therapies in pancreatic and liver diseases: regulatory and practical insights. 国際誌

Hongjun Wang, Rachele Ciccocioppo, Shuji Terai, Sara Shoeibi, Gianluca Carnevale, Giulia De Marchi, Atsunori Tsuchiya, Soichi Ishii, Takafumi Tonouchi, Kaito Furuyama, Yuan Yang, Masaki Mito, Hiroyuki Abe, Rosanna Di Tinco, Vincenzo Cardinale

Cytotherapy 27 ( 3 ) 259 - 278 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cellular and gene therapy (CGT) products have emerged as a popular approach in regenerative medicine, showing promise in treating various pancreatic and liver diseases in numerous clinical trials. Before these therapies can be tested in human clinical trials, it is essential to evaluate their safety and efficacy in relevant animal models. Such preclinical testing is often required to obtain regulatory approval for investigational new drugs. However, there is a lack of detailed guidance on selecting appropriate animal models for CGT therapies targeting specific pancreatic and liver conditions, such as pancreatitis and chronic liver diseases. In this review, the gastrointestinal committee for the International Society for Cell and Gene Therapy provides a summary of current recommendations for animal species and disease model selection, as outlined by the US Food and Drug Administration, with references to EU EMA and Japan PMDA. We discuss a range of small and large animal models, as well as humanized models, that are suitable for preclinical testing of CGT products aimed at treating pancreatic and liver diseases. For each model, we cover the associated pathophysiology, commonly used metrics for assessing disease status, the pros and limitations of the models, and the relevance of these models to human conditions. We also summarize the use and application of humanized mouse and other animal models in evaluating the safety and efficacy of CGT products. This review aims to provide comprehensive guidance for selecting appropriate animal species and models to help bridge the gap between the preclinical research and clinical trials using CGT therapies for specific pancreatic and liver diseases.

DOI： 10.1016/j.jcyt.2024.11.008

Human placental extract improves liver cirrhosis in mice with regulation of macrophages and senescent cells. 国際誌

Natsuki Ishikawa, Yusuke Watanabe, Yuichirou Maeda, Tomoaki Yoshida, Naruhiro Kimura, Hiroyuki Abe, Akira Sakamaki, Hiroteru Kamimura, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

Regenerative therapy 28 509 - 516 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Cirrhosis is a disease with poor prognosis that requires the development of a novel therapeutic approach alternative to liver transplantation. In this study, we focused on the placenta and aimed to clarify the effects of human placental extract (HPE) on cirrhosis. METHODS: A mouse model of carbon tetrachloride-induced cirrhosis was used to evaluate the effect of HPE administration subcutaneously and compared with the control group (n = 8 for each group). In vitro and in vivo, real time-PCR and immunostaining were performed for HPE mechanistic analysis. Spatial transcriptomics was also performed for detailed analysis of the effect of HPE on cirrhosis. RESULTS: HPE administration improved serum ALT levels compared to control mice. Furthermore, there was a decrease in the number of senescent cells in the liver and the mRNA levels of secrete senescence-associated secretory phenotype factors and Cdkn2a (p16). In vitro, HPE induced macrophage polarization to the anti-inflammatory M2 phenotype. Spatial transcriptomics was also performed to analyze the underlying anti-inflammatory mechanism. The results showed that HPE strongly polarized macrophages to the M2 phenotype, especially in macrophage-rich regions in the liver. Gene expression pathway analysis using spatial transcriptomics also revealed the possibility of improving senescent cell-derived inflammation via mitochondrial function. CONCLUSIONS: HPE improves serum ALT levels via anti-inflammatory mechanisms in macrophages and senescent cells. HPE serves as a novel agent for cirrhosis treatment.

DOI： 10.1016/j.reth.2025.01.017

Extremely Rare Isolated Small-Intestinal Polyp Diagnosed by Double-Balloon Endoscopy in an Asymptomatic Adult Patient. 国際誌

Kentaro Tominaga, Annenkov Alexey, Yuto Tanaka, Osamu Shibata, Yuichi Kojima, Yuzo Kawata, Nao Nakajima, Kazuya Takahashi, Hiroki Sato, Satoshi Ikarashi, Kazunao Hayashi, Ken-Ichi Mizuno, Shuji Terai

Clinical case reports 13 ( 3 ) e70255 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

We present the first reported case of an isolated small-bowel intestinal juvenile polyp in an adult. This case is particularly noteworthy as it was asymptomatic, detected via computed tomography, localized by capsule endoscopy, and successfully resected via double-balloon endoscopy before the development of acute symptoms.

DOI： 10.1002/ccr3.70255

Small Intestinal Bacterial Overgrowth Is a Predictor of Overt Hepatic Encephalopathy in Patients with Liver Cirrhosis. 国際誌

Akira Sakamaki, Kunihiko Yokoyama, Hanako Yamazaki, Takuya Wakabayashi, Yuichi Kojima, Kentaro Tominaga, Atsunori Tsuchiya, Kenya Kamimura, Junji Yokoyama, Shuji Terai

Journal of clinical medicine 14 ( 5 ) 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Objective: Liver cirrhosis (LC) progression induces intestinal microbiota abnormalities, such as small intestinal bacterial overgrowth (SIBO), and these changes lead to the inflow of gut pathogens and their degradation products into the vessels, causing cirrhotic complications such as hepatic encephalopathy (HE). Methods: To clarify the relationship between the development of overt HE and SIBO, we conducted a three-year observation after assessment of SIBO in patients with LC. Results: In the analysis of 107 patients, with a mean follow-up duration of 29.4 months, 31 were diagnosed with SIBO and 30 with covert HE. In the Cox multivariate regression analysis for prognosis, the Child-Pugh score, blood urea nitrogen level, and the Union for International Cancer Control (UICC) stage of hepatocellular carcinoma were derived using the following five factors: white blood cell count, blood urea nitrogen level, Child-Pugh score, UICC stage, and serum aspartate aminotransferase and alkaline phosphatase levels (p = 0.002, hazard ratio [HR] 3.733, 95% confidence interval [CI] 1.592-8.754, p = 0.001, HR 1.076, 95% CI 1.030-1.123, and p < 0.001, HR 2.767, 95% CI 1.780-4.302, respectively). Furthermore, in the Cox multivariate regression analysis for overt HE development, covert HE and methane-producing SIBO were derived using the following four factors: methane-producing SIBO, UICC stage, covert HE, and serum ammonia levels (p = 0.038, HR 5.008, 95% CI 1.096-22.892 and p = 0.006, HR 8.597, 95% CI 1.881-39.291, respectively). Conclusions: M-SIBO positivity was a significant predictor of overt HE.

DOI： 10.3390/jcm14051491

Pruritus in Chronic Cholestatic Liver Diseases, Especially in Primary Biliary Cholangitis: A Narrative Review. 国際誌

Tatsuo Kanda, Reina Sasaki-Tanaka, Naruhiro Kimura, Hiroyuki Abe, Tomoaki Yoshida, Kazunao Hayashi, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Atsunori Tsuchiya, Kenya Kamimura, Shuji Terai

International journal of molecular sciences 26 ( 5 ) 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Patients with chronic cholestatic liver diseases often experience itch and struggle with this symptom. We discuss the mechanism of itch in patients with chronic cholestatic liver diseases, such as primary biliary cholangitis (PBC) and others, and their therapies, including ileal bile acid transporter (IBAT) inhibitors. In patients with PBC, there are high serum/plasma concentrations of multiple factors, including bile salts, bilirubin, endogenous opioids, lysophosphatidic acid (LPA), autotaxin, and histamine. Bile salts, bilirubin, LPA, and autotaxin affect itch mediators in the skin and sensory nerves, while the endogenous opioid balance affects mediators in the spinal cord. Itch is sensitized by both the peripheral and central nervous systems. Both mechanisms are involved in itch in patients with chronic cholestatic liver disease. Although IBAT inhibitors have been approved for use in pediatric cholestatic conditions, such as progressive familial intrahepatic cholestasis and Alagille syndrome, IBAT inhibition seems to be a promising treatment for chronic refractory itch in patients with PBC. A traditional non-systematic review results in this narrative review. Multidisciplinary cooperation, involving hepatologists, dermatologists, and pharmacists, could provide better treatment for PBC patients suffering from refractory itch. In conclusion, we summarized the existing knowledge on itch caused by chronic cholestatic liver diseases, especially in PBC with a focus on the mechanisms and therapies. This narrative review provides the mechanisms and therapeutic options for itch in patients with chronic cholestatic liver diseases.

DOI： 10.3390/ijms26051883

Real-World Setting of Efficacy and Safety of 3 Years of Rifaximin Administration in Japanese Patients with Hepatic Encephalopathy: A Multicenter Retrospective Study. 国際誌

Hideto Kawaratani, Tadashi Namisaki, Yasuteru Kondo, Ryoji Tatsumi, Naoto Kawabe, Norikazu Tanabe, Akira Sakamaki, Kyoko Hoshikawa, Yoshihito Uchida, Kei Endo, Takumi Kawaguchi, Tsunekazu Oikawa, Yoji Ishizu, Shuhei Hige, Taro Takami, Shuji Terai, Yoshiyuki Ueno, Satoshi Mochida, Kazuhiko Koike, Hitoshi Yoshiji

Journal of clinical medicine 14 ( 4 ) 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background/Objectives: Rifaximin is a therapeutic agent for patients with hepatic encephalopathy (HE); however, there is little data on the effects of its long-term (>1 year) administration in Japanese patients with cirrhosis. The effects and safety of 3-year rifaximin treatment on HE was investigated in Japan. Methods: A total of 190 Japanese patients with cirrhosis who were continuously administered rifaximin for more than 1 year suffered overt or covert HE, which was diagnosed by a physician. Laboratory data were collected at baseline, 3, 6, 12, 18, 24, 30, and 36 months following rifaximin administration. We examined the cumulative overt HE incidences, overall survival rates, and hepatic functional reserves following rifaximin treatment. The occurrence of adverse events was also assessed. Results: The levels of ammonia improved significantly after 3 months of rifaximin administration, which continued for 3 years. Serum albumin and prothrombin activity also significantly improved 3 years after initiation of rifaximin treatment. Cumulative overt HE incidences were 12.1%, 19.7%, and 24.9% at 1, 2, and 3 years, respectively. The survival rates following rifaximin treatment were 100%, 88.9%, and 77.8% at 1, 2, and 3 years, respectively. In contrast, renal function and electrolytes did not change following rifaximin administration. Only three (1.6%) patients discontinued rifaximin therapy because of severe diarrhea after 1 year of rifaximin administration. No other serious adverse events were observed. Conclusions: Three years of continuous rifaximin (RFX) treatment was both effective and safe for patients with hepatic encephalopathy. Liver function improved and did not worsen during treatment.

DOI： 10.3390/jcm14041358

Combination therapies with immune checkpoint inhibitor-based combination therapies for hepatocellular carcinoma with major vascular invasion. 国際誌

Tatsuo Kanda, Reina Sasaki-Tanaka, Shuji Terai

Hepatology international 2025年2月

Correction: Watanabe et al. Pemafibrate Improves Alanine Aminotransferase Levels Independently of Its Lipid-Lowering Effect. <i>Livers</i> 2023, <i>3</i>, 562–568

Azuma Watanabe, Ryoko Horigome, Yumiko Nakatsuka, Shuji Terai

Livers 2025年2月

Hepatitis B virus infection and its treatment in Eastern Ethiopia 国際誌

Tatsuo Kanda, Reina Sasaki-Tanaka, Atsunori Tsuchiya, Shuji Terai

World Journal of Hepatology 17 ( 1 ) 99209 - 99209 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Baishideng Publishing Group Inc.

Hepatitis B virus (HBV) infection causes acute and chronic hepatitis, compensated and decompensated cirrhosis, and hepatocellular carcinoma worldwide. The actual status of HBV infection and its treatment in certain regions of Asian and African countries, including Ethiopia, has not been well-documented thus far. Antiviral therapy for HBV infection can prevent the progression of HBV-related liver diseases and decrease the HBV-related symptoms, such as abdominal symptoms, fatigue, systemic symptoms and others. In Eastern Ethiopia, HBV-infected patients with cirrhosis were found to be positive for the HBV e antigen and to have a higher viral load than those without cirrhosis. Notably, 54.4% of patients practiced khat chewing and 18.1% consumed excessive amounts of alcohol. Tenofovir disoproxil fumarate effectively suppressed HBV DNA in those infected with HBV. It is important to elucidate the actual status of HBV infection in Eastern Ethiopia to eliminate HBV infection worldwide by 2030. HBV vaccination and the educational programs for Health Science students that provide practical strategies could help to reduce HBV infection in Eastern Ethiopia.

DOI： 10.4254/wjh.v17.i1.99209

Aligning cellular and molecular components in age-dependent tertiary lymphoid tissues of kidney and liver. 国際誌

Naoya Toriu, Yuki Sato, Hiroteru Kamimura, Takahisa Yoshikawa, Masaou Tanaka, Shinya Yamamoto, Shingo Fukuma, Masakazu Hattori, Shuji Terai, Motoko Yanagita

PloS one 20 ( 2 ) e0311193 2025年

記述言語：英語掲載種別：研究論文（学術雑誌）

Tertiary lymphoid tissues (TLTs) are ectopic lymphoid structures induced by multiple stimuli, including infection and tissue injuries; however, their clinical relevance in disease progression has remained unclear. We demonstrated previously that TLTs develop in mouse and human kidneys with aging and can be a potential marker of kidney injury and prognosis, and therapeutic targets. In addition, we found that two types of unique lymphocytes that emerge with aging, senescence-associated T cells and age-associated B cells, are essential for TLT formation in the kidney. Although TLTs develop with aging in other organs as well, their cellular and molecular components, and clinical significance remain unclear. In the present study, we found that TLTs developed in the liver with aging, and that their cellular and molecular components were similar to those in the kidneys. Notably, senescence-associated T cells and age-associated B cells were also present in hepatic TLTs. Furthermore, analysis of publicly available data on human liver biopsy transcriptomes revealed that the expression of TLT-related genes was elevated in the liver biopsy samples from hepatitis C virus (HCV)-infected patients compared with those without HCV infection and was associated with liver injury and fibrosis. Therefore, we analyzed liver biopsy samples from 47 HCV patients and found that TLTs were present in 87.2% of cases and that the numbers and stages of TLTs were higher in aged patients and cellular and molecular components of TLTs in humans were similar to those in mice. Our findings suggesting that age-dependent TLT formation is a systemic phenomenon across the tissues and aging is also a predisposing factor for TLT formation across organs.

DOI： 10.1371/journal.pone.0311193

Enrichment of Porphyromonas gingivalis in colonic mucosa-associated microbiota and its enhanced adhesion to epithelium in colorectal carcinogenesis: Insights from in vivo and clinical studies. 国際誌

Shunya Motosugi, Naoki Takahashi, Shuhei Mineo, Keisuke Sato, Takahiro Tsuzuno, Yukari Aoki-Nonaka, Nao Nakajima, Kazuya Takahashi, Hiroki Sato, Haruna Miyazawa, Koji Taniguchi, Shuji Terai, Koichi Tabeta

PloS one 20 ( 3 ) e0320383 2025年

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: The oral-gut axis is believed to play a role in the pathogenesis of colorectal cancer (CRC). Previous studies have demonstrated the transmission of oral microbiota to the gut, disrupting gut microbial balance and creating a protumorigenic microenvironment conducive to CRC progression. Fusobacterium nucleatum is a putative periodontal pathogen recognized as a specific bacterium that promotes CRC development. However, the possible involvement of other periodontal pathogens in CRC is poorly understood. This study aimed to explore the effects of ingested periodontal pathogens on experimental CRC in mice and elucidate the underlying mechanisms. METHODS: In this study, experimental colitis-induced CRC mouse models were used. The mice were orally administered periodontal pathogens (Porphyromonas gingivalis and Prevotella intermedia) three times a week during the experimental period. The CRC severity between the P. gingivalis-treated and P. intermedia-treated groups was compared. Lumen-associated microbiota (LAM) and mucosa-associated microbiota (MAM) were analyzed in both mouse and human samples. In vitro studies were conducted using intestinal epithelial cells to explore the possible mechanisms by which the periodontal pathogens affect the CRC development. RESULTS: The P. gingivalis-treated group exhibited significantly increased CRC severity compared to the other groups among azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse models. The LAM and MAM exhibited distinct bacterial compositions, and P. gingivalis was enriched more in MAM than in LAM. In vitro adhesion assays revealed that P. gingivalis had higher adhesive capacity to intestinal epithelial cells than P. intermedia and indicated the possible involvement of gingipains in such a capacity. CONCLUSION: P. gingivalis is enriched in MAM, and its subsequent adhesion to intestinal epithelial cells is potentially involved in the progression of CRC.

DOI： 10.1371/journal.pone.0320383

Persistent body-weight change on achalasia and peroral endoscopic myotomy: a multicenter cohort study.

Kazuya Takahashi, Hiroki Sato, Yuto Shimamura, Hirofumi Abe, Hironari Shiwaku, Junya Shiota, Chiaki Sato, Takuya Satomi, Masaki Ominami, Yoshitaka Hata, Hisashi Fukuda, Ryo Ogawa, Jun Nakamura, Tetsuya Tatsuta, Yuichiro Ikebuchi, Shuji Terai, Haruhiro Inoue

Journal of gastroenterology 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The distribution of body weight in patients with achalasia and after peroral endoscopic myotomy (POEM) has not been investigated. The role of body weight assessment after treatment remains unclear. METHODS: Using the multicenter achalasia cohort, the frequency of underweight (body mass index [BMI] < 18.5 kg/m2) and overweight (BMI ≥ 25.0 kg/m2) and their associated clinical characteristics were analyzed. After POEM, risk factors for insufficient- (underweight persistently) and excessive- (responded to overweight) weight gainers were investigated. The correlation between BMI-increase rate and severity of esophageal symptoms post-POEM was evaluated. RESULTS: Among 3,410 patients, 23.0% and 15.7% were underweight and overweight, respectively. Factors associated with underweight were higher age, female sex, severe symptoms, high lower esophageal sphincter (LES) pressure, and non-dilated esophagus (all p < 0.01). Longitudinal analyses revealed that weight gain post-POEM was achieved after a long duration (≥ 12 months; p < 0.01). In 528 patients post-POEM, the frequency of underweight reduced to 8.3% (p < 0.01). Risk factors for insufficient-weight gain (36.1% of underweight patients) included low BMI (p < 0.01) and high LES pressure (p = 0.03) and conversely for excessive-weight gain. Machine learning models based on patient characteristics successfully predicted insufficient- and excessive-weight gainers with an area under the curve value of 0.74 and 0.75, respectively. Esophageal symptoms post-POEM did not correlate with BMI increase. CONCLUSION: Underweight is not solely a condition of advanced achalasia. After POEM, insufficient- or excessive-weight gainers are not rare and can be predicted preoperatively. Body weight change is an independent nutrition parameter rather than a part of the assessment of residual esophageal symptoms.

DOI： 10.1007/s00535-024-02205-9

Dasatinib and Quercetin as Senolytic Drugs Improve Fat Deposition and Exhibit Antifibrotic Effects in the Medaka Metabolic Dysfunction-Associated Steatotic Liver Disease Model. 国際誌

Shunta Yakubo, Hiroyuki Abe, Yawen Li, Marina Kudo, Atsushi Kimura, Takuya Wakabayashi, Yusuke Watanabe, Naruhiro Kimura, Toru Setsu, Takeshi Yokoo, Akira Sakamaki, Hiroteru Kamimura, Atsunori Tsuchiya, Kenya Kamimura, Shuji Terai

Diseases (Basel, Switzerland) 12 ( 12 ) 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Metabolic dysfunction-associated steatotic liver disease (MASLD) causes cellular senescence due to oxidative stress, endoplasmic reticulum stress, and ectopic fat deposition in the liver. Recently, dasatinib, an antitumor agent, and quercetin, a dietary supplement, were combined as a senolytic drug to eliminate senescent cells. Thus, this study aimed to examine the effects of dasatinib and quercetin administration on removing senescent cells and their therapeutic effects on MASLD in a medaka MASLD model. Dasatinib and quercetin were administered to a medaka MASLD model, which was fed a high-fat diet by dissolving them in aquarium water. The results revealed that senescent cells in the liver were increased in the HFD group but improved in the treatment group. Hematoxylin and eosin staining also showed that treatment improved fat deposition in hepatocytes. In addition, TGFβ1, a driver factor of fibrosis, was reduced in the treatment group. Dasatinib and quercetin eliminated senescent cells in MASLD, attenuated fat deposition, and suppressed fibrosis gene expression. The results indicate that dasatinib and quercetin as senolytic drugs are novel therapeutic agents that reduce MASLD.

DOI： 10.3390/diseases12120317

ROI Selection to Improve Prediction Performance of CNN for Cirrhosis Detection Using Ultrasound Images 査読

Kazuma Nakata, Yusuke Fujita, Yoshihiro Mitani, Yoshihiko Hamamoto, Makoto Segawa, Shuji Terai

2024 IEEE 13th Global Conference on Consumer Electronics (GCCE) 636 - 640 2024年11月

Factors involved in gastroesophageal varix-related events in patients with hepatitis C virus-related compensated and decompensated cirrhosis after direct-acting antiviral therapy. 国際誌

Yuki Tahata, Hayato Hikita, Satoshi Mochida, Nobuyuki Enomoto, Norifumi Kawada, Akio Ido, Daiki Miki, Masayuki Kurosaki, Hitoshi Yoshiji, Ryotaro Sakamori, Hidekatsu Kuroda, Hiroshi Yatsuhashi, Taro Yamashita, Yoichi Hiasa, Naoya Kato, Hisamitsu Miyaaki, Yoshiyuki Ueno, Yoshito Itoh, Kentaro Matsuura, Taro Takami, Yasuhiro Asahina, Goki Suda, Norio Akuta, Ryosuke Tateishi, Yasunari Nakamoto, Eiji Kakazu, Shuji Terai, Masahito Shimizu, Masanori Miyazaki, Yasutoshi Nozaki, Satoshi Sobue, Hiroki Yano, Tomokatsu Miyaki, Akihiro Moriuchi, Takeshi Hori, Kumiko Shirai, Kazuhiro Murai, Yoshinobu Saito, Takahiro Kodama, Tomohide Tatsumi, Tomomi Yamada, Tetsuo Takehara

Hepatology research : the official journal of the Japan Society of Hepatology 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: The incidence of and factors involved in gastroesophageal varix-related events in hepatitis C virus-related cirrhosis patients, including decompensated cirrhosis, after direct-acting antiviral therapy are unclear. METHODS: We conducted a multicenter study using prospective data from 478 hepatitis C virus-related cirrhosis patients treated with direct-acting antiviral therapy from February 2019 to December 2021 at 33 Japanese hospitals. Gastroesophageal varices were classified as F1 (small-caliber), F2 (moderately enlarged), or F3 (markedly enlarged) according to the Japanese criteria. Patients without varix or with F1 without red color signs were defined as low-risk varix, and patients with ≥F2 or red color signs or a history of rupture were defined as high-risk varix. Varix-related events were defined as prophylactic treatment or rupture of gastroesophageal varix. RESULTS: The median age was 70 years, 43% of patients had decompensated cirrhosis, and 16% had high-risk varices (13% in compensated and 33% in decompensated, p < 0.001). Sustained virologic response rates were 94.9% for compensated cirrhosis and 91.3% for decompensated cirrhosis (p = 0.120). Across 35.7 months, 25 patients received prophylactic treatment, and four experienced varix rupture. The 3-year incidence rate of varix-related events was 6.2% (3.5% in compensated and 9.9% in decompensated, p = 0.001). In the multivariate analysis, high-risk varix (p < 0.001), high baseline gamma-glutamyl transpeptidase levels (p < 0.001), and virologic failure (p = 0.004) were significantly involved in varix-related events. CONCLUSIONS: The cumulative incidence rate of varix-related events was significantly higher in decompensated cirrhosis than in compensated cirrhosis. Baseline varix status, baseline gamma-glutamyl transpeptidase levels, and virologic response were related to varix-related events after direct-acting antiviral therapy.

DOI： 10.1111/hepr.14131

Association between Clinical Characteristics and Sarcopenia or Sarcopenic Obesity in Crohn's Disease.

Takumi Naruse, Hiroki Sato, Kazuya Takahashi, Chihiro Sato, Yuichi Kojima, Yuzo Kawata, Kentaro Tominaga, Ken-Ichi Mizuno, Shuji Terai

Internal medicine (Tokyo, Japan) 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Objective Crohn's disease (CD) is a chronic inflammatory bowel disease that is associated with malnutrition. Sarcopenia is a malnutrition condition characterized by skeletal muscle loss that impairs the physical function. We investigated the clinical characteristics of patients with CD with sarcopenia and sarcopenic obesity (sarcopenic-o). Methods The body composition of patients with CD was evaluated using a bioelectrical impedance analysis. The clinical characteristics of patients with sarcopenia and sarcopenic-o were analyzed, and a predictive model for sarcopenia was developed. Patients: Patients with CD recruited from 2019 to 2021 were included. Results Among the 104 patients, 35 (33.7%) and 10 (9.6%) had sarcopenia and sarcopenic-o, respectively. In the sarcopenia group, the skeletal muscle index (SMI) and body mass index (BMI) were lower than those in the control group (SMI, 6.3 kg/m2 vs. 7.7 kg/m2, p<0.01; BMI, 18.8 kg/m2 vs. 22.6 kg/m2, p<0.01), whereas the Crohn's disease activity index (CDAI) was higher than in the control group (114.2 vs. 42.0, p<0.01). The predictive models of sarcopenia using the BMI and CDAI revealed high performance with areas under the receiver operating characteristic curve (AUC) of 0.87 and 0.72, respectively, and high specificity (0.94) and sensitivity (0.71), respectively. Sarcopenic-o patients could not be screened using the BMI (25 kg/m2), and the SMI and body fat percentage were negatively correlated in patients with sarcopenia (p<0.01). Conclusion Sarcopenia and sarcopenic-o are relatively common conditions among patients with CD. Sarcopenia can be predicted using the clinical parameters of BMI and CDAI. Sarcopenic-o can be a severe form of sarcopenia.

DOI： 10.2169/internalmedicine.4420-24

　前のページ - 次のページ　