Review
Cell Biology
Michaela E. Trautman, Nicole E. Richardson, Dudley W. Lamming
Summary: The proportion of people suffering from age-related diseases is increasing worldwide. Recent research has shown that low protein diets, particularly those low in branched-chain amino acids (BCAAs), can reduce mortality and promote metabolic health and extended lifespan in both humans and rodents. This article discusses the emerging evidence that BCAAs play a crucial role in healthy metabolism and longevity, and explores the physiological and molecular mechanisms behind the benefits of restricting dietary BCAAs. The findings suggest that the quality of protein, specifically the composition of dietary protein, may be a previously overlooked factor in metabolic dysfunction and reducing dietary BCAAs could be a promising new approach to delaying and preventing age-related diseases.
Article
Pharmacology & Pharmacy
Tiangang Wu, Mengling Wang, Fengling Ning, Shilin Zhou, Xuetao Hu, Hong Xin, Svetlana Reilly, Xuemei Zhang
Summary: Fibrosis, characterized by excessive production of extracellular matrix, is a common pathological feature of organ diseases. Metabolic alterations, especially in the regulation of branched-chain amino acids (BCAAs), have been found to play significant roles in fibrogenesis. Dysregulation of BCAAs metabolism has been implicated in various diseases. This review summarizes the metabolic regulation of fibrosis, changes in BCAAs metabolism associated with fibrosis, and the effects and mechanisms of BCAAs intervention in hepatic, renal, and cardiac fibrosis, with a focus on liver fibrosis and associated hepatocellular carcinoma.
PHARMACOLOGICAL RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Chong Song, Xian Long, Jianbin He, Yongpan Huang
Summary: Non-alcoholic fatty liver disease (NAFLD) is a common chronic metabolic liver disorder characterized by fat accumulation in the liver. Inflammation is a significant mechanism that can lead to cell death and tissue injury in NAFLD. Inhibition of inflammation improves NAFLD by reducing fat content, inducing hepato-protective autophagy, overexpressing peroxisome proliferator-activated receptor- gamma (PPAR-gamma), and increasing insulin sensitivity. Understanding the molecular mechanisms and signaling pathways in NAFLD is crucial for its prevention and treatment.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Genetics & Heredity
Can Chen, Hassan Naveed, Keping Chen
Summary: This article introduces the important role of branched-chain amino acid aminotransferases in cellular metabolism, summarizes the related research in animals, plants, microorganisms, and humans, and analyzes the molecular mechanism. It has been found that disorders in branched-chain amino acid metabolism are closely related to various diseases, especially tumor development.
FRONTIERS IN GENETICS
(2023)
Article
Gastroenterology & Hepatology
Stephen A. Harrison, Seth J. Baum, Nadege T. Gunn, Ziad H. Younes, Anita Kohli, Rashmee Patil, Margaret J. Koziel, Harinder Chera, Jeff Zhao, Manu V. Chakravarthy
Summary: AXA1125 and AXA1957 are novel orally administered endogenous metabolic modulator compositions designed to support multiple metabolic and fibroinflammatory pathways associated with NAFLD. The study found that AXA1125 demonstrated greater biologic activity compared to AXA1957 or placebo over 16 weeks, showing promising therapeutic effects for NAFLD.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Huilan Zeng, Alina V. Dumitrescu, David Wadkins, Benjamin W. Elwood, Oliver W. Gramlich, Markus H. Kuehn
Summary: Neuroinflammation is a significant factor in the pathophysiology of neurodegenerative diseases, including glaucoma. Pioglitazone, an agonist of PPAR gamma, shows potential in protecting retinal ganglion cells and reversing vision loss in glaucomatous retina.
Article
Nutrition & Dietetics
Katarzyna Paczkowska, Dominik Rachon, Andrzej Berg, Jacek Rybka, Katarzyna Kapczynska, Marek Bolanowski, Jacek Daroszewski
Summary: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that predisposes women to metabolic disturbances. Recent research suggests that alterations in amino acid profiles may be indicative of metabolic disorders. This study found elevated levels of aromatic amino acids in PCOS women, and significant differences in amino acid concentrations between metabolically healthy and unhealthy obesity subgroups of PCOS women.
Article
Nutrition & Dietetics
Huan Xu, Xuanyang Wang, Xiaoqing Xu, Lin Liu, Yuntao Zhang, Xuemin Yan, Yingfeng Zhang, Keke Dang, Ying Li
Summary: This study using Mendelian randomization analysis found that increased circulating levels of BCAAs were associated with an increased risk of squamous cell lung cancer, but no causal link was found between BCAAs and other types of cancer.
CLINICAL NUTRITION
(2023)
Article
Nutrition & Dietetics
Yuyan Liu, Chengwen Zhang, Yuan Zhang, Xuheng Jiang, Yuanhong Liang, Huan Wang, Yongfang Li, Guifan Sun
Summary: This study aimed to investigate the relationship between dietary intake of branched-chain amino acids (BCAAs) and hypertension risk in the Chinese population. The findings showed that dietary BCAAs intake was positively associated with both systolic and diastolic blood pressure values, as well as an increased risk of hypertension.
Review
Immunology
Berkay Yahsi, Gurcan Gunaydin
Summary: Immunometabolism, especially in terms of augmenting anti-tumor immune responses, has been extensively researched. Regulatory T cells (Tregs) are known for their immunosuppressive roles in anti-tumor immune responses. Targeting Tregs specifically in the tumor microenvironment (TME) is crucial for successful and specific treatment. Recent studies have shown an association between Tregs and isoleucine, which may play a major role in affecting Tregs. Targeting the immunometabolic pathways of Tregs could be a rational approach for treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Paola Cuomo, Rosanna Capparelli, Antonio Iannelli, Domenico Iannelli
Summary: Branched-chain amino acids (BCAAs) play an important role in human health. High levels of BCAAs are associated with various metabolic diseases, while low levels are beneficial for metabolic health. However, the exact mechanisms underlying the dysregulation caused by high levels of BCAAs are still under debate.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Daniel Ferguson, Sophie J. Eichler, Nicole K. H. Yiew, Jerry R. Colca, Kevin Cho, Gary J. Patti, Trevor M. Shew, Andrew J. Lutkewitte, Sandip Mukherjee, Kyle S. McCommis, Natalie M. Niemi, Brian N. Finck
Summary: The study evaluated the effects of MPC inhibitors (MPCi) on branched chain amino acid (BCAA) metabolism and found that MPCi can lower plasma BCAA concentrations and activate AMPK and mTOR signaling pathways. However, the effects on glucose homeostasis may be separate from BCAA concentrations.
MOLECULAR METABOLISM
(2023)
Article
Nutrition & Dietetics
Alexander Christian Reisinger, Florian Posch, Gerald Hackl, Gunther Marsche, Harald Sourij, Benjamin Bourgeois, Kathrin Eller, Tobias Madl, Philipp Eller
Summary: Metabolomics using H-1 NMR spectroscopy shows promise for personalized medicine in sepsis, with distinct differences in metabolites between sepsis patients and controls, as well as between septic shock survivors and non-survivors. Branched-chain amino acids (BCAA), including valine, leucine, and isoleucine, were significantly lower in sepsis non-survivors and serve as potential early biomarkers for predicting outcomes in ICU and 28-day mortality.
Review
Oncology
Xiazhen Nong, Caiyun Zhang, Junmin Wang, Peilun Ding, Guang Ji, Tao Wu
Summary: This article reviews the role and mechanism of BCAT in different diseases, as well as the recent biomedical research progress, providing new research ideas for the treatment, prognosis, and prevention of certain diseases.
FRONTIERS IN ONCOLOGY
(2022)
Article
Nutrition & Dietetics
Qiu-Ming Shen, Jing Wang, Zhuo-Ying Li, Jia-Yi Tuo, Yu-Ting Tan, Hong-Lan Li, Yong-Bing Xiang
Summary: This study found no significant correlations between dietary intakes and plasma concentrations of branched-chain amino acids (BCAA) in Chinese male and female adults.
JOURNAL OF NUTRITION
(2023)
Article
Gastroenterology & Hepatology
Takeshi Matsui, Susumu Hamada-Tsutsumi, Yutaka Naito, Masanori Nojima, Etsuko Iio, Akihiro Tamori, Shoji Kubo, Tatsuya Ide, Yasuteru Kondo, Yuichiro Eguchi, Atsumasa Komori, Yuji Morine, Mitsuo Shimada, Tohru Utsunomiya, Ken Shirabe, Koichi Kimura, Yoichi Hiasa, Natthaya Chuaypen, Pisit Tangkijvanich, Aya Naiki-Ito, Satoru Takahashi, Takahiro Ochiya, Yasuhito Tanaka
Summary: The miRNA clusters miR-183/96/182 and miR-217/216a/216b are significantly upregulated in nonviral hepatocellular carcinoma (NBNC-HCC). High levels of miR-182-5p and miR-217-5p, but low levels of miR-96-5p, in tumor tissues are associated with poor recurrence-free survival of NBNC-HCC patients. Further upregulation of miR-96-5p in tumors may have an inhibitory effect on recurrence, suggesting its potential as a tumor suppressor in NBNC-HCC patients at high risk of recurrence. Transfection of miR-96-5p mimic induced apoptosis of HepG2 cells and suppressed proliferation and invasion, indicating its potential antitumor effects.
HEPATOLOGY RESEARCH
(2022)
Article
Endocrinology & Metabolism
Makoto Saegusa, Yumi Matsuda, Tsuneo Konta, Takafumi Saitoh, Kaori Sakurada, Midori Furuse, Chisaki Uno, Takamasa Kayama, Yoshiyuki Ueno
Summary: This study found that serum cholinesterase (ChE) levels are independent predictors of all-cause mortality in a community-based population, while serum albumin (Alb) levels do not have this effect.
ANNALS OF NUTRITION AND METABOLISM
(2022)
Review
Gastroenterology & Hepatology
Tomohiro Katsumi, Yoshiyuki Ueno
Summary: Autoimmune hepatitis (AIH) is a chronic liver disease that mainly affects hepatocytes. Recent epidemiological studies in Asia have revealed regional characteristics of AIH, with type 1 being predominant in East Asia and type 2 being as frequent as in Europe and the USA in South Asia. The prevalence of AIH is increasing worldwide, and early diagnosis and treatment can improve the situation in Asia.
LIVER INTERNATIONAL
(2022)
Article
Gastroenterology & Hepatology
Hiromasa Ohira, Atsushi Takahashi, Mikio Zeniya, Masanori Abe, Teruko Arinaga-Hino, Satoru Joshita, Akinobu Takaki, Nobuhiro Nakamoto, Jong-Hon Kang, Yoshiyuki Suzuki, Tsuyosi Sogo, Ayano Inui, Kazuhiko Koike, Kenichi Harada, Yasunari Nakamoto, Yasuteru Kondo, Takuya Genda, Koichi Tsuneyama, Tsuyoshi Matsui, Atsushi Tanaka
HEPATOLOGY RESEARCH
(2022)
Article
Multidisciplinary Sciences
Yasuteru Kondo, Junichi Akahira, Tatsuki Morosawa, Yukihiro Toi, Akashi Endo, Hiroaki Satio, Mareyuki Endo, Shunichi Sugawara, Yasuhito Tanaka
Summary: Various iCIs have been found to induce immune-related liver damage. In this retrospective study, NSCLC patients treated with PD-1 antibodies were analyzed to identify useful biomarkers for diagnosing iCIs-related hepatitis. The presence of anti-nuclear antibodies and characteristic liver histology were found to be potential biomarkers for iCIs-related hepatitis in NSCLC patients.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, General & Internal
Hideto Kawaratani, Yasuteru Kondo, Ryoji Tatsumi, Naoto Kawabe, Norikazu Tanabe, Akira Sakamaki, Kazuo Okumoto, Yoshihito Uchida, Kei Endo, Takumi Kawaguchi, Tsunekazu Oikawa, Yoji Ishizu, Shuhei Hige, Taro Takami, Shuji Terai, Yoshiyuki Ueno, Satoshi Mochida, Yasuhiro Takikawa, Takuji Torimura, Tomokazu Matsuura, Masatoshi Ishigami, Kazuhiko Koike, Hitoshi Yoshiji
Summary: This study found that long-term treatment with rifaximin is effective and safe for patients with hepatic encephalopathy. Ammonia levels significantly improved after 3 months of treatment and remained improved until 12 months. There were no serious adverse events reported, and the incidence of overt hepatic encephalopathy was low.
JOURNAL OF CLINICAL MEDICINE
(2022)
Letter
Gastroenterology & Hepatology
Y. Sasaki, Y. Abe, S. Nishise, Y. Ueno
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Multidisciplinary Sciences
Yasuteru Kondo, Tatsuki Morosawa, Soichiro Minami, Yasuhito Tanaka
Summary: This study analyzed the efficacy and safety of drug-eluting beads-transcatheter arterial chemoembolization with low-dose FP therapy in difficult-to-treat hepatocellular carcinoma (HCC) patients. The results showed that Ultra-FP therapy had a high objective response rate and overall survival in difficult-to-treat HCC patients.
SCIENTIFIC REPORTS
(2022)
Review
Medicine, General & Internal
Yu Sasaki, Yasuhiko Abe, Naoko Mizumoto, Eiki Nomura, Yoshiyuki Ueno
Summary: Eosinophilic gastroenteritis (EoGE) is a rare digestive disorder characterized by eosinophilic infiltration in the stomach and intestines. The endoscopic findings of EoGE in the small intestine are not well understood, but this literature review identified common findings such as redness, villous atrophy, erosion, ulceration, edema, and stenosis. These findings contribute to the development of EoGE practice.
Review
Medicine, General & Internal
Yasuhiko Abe, Yu Sasaki, Makoto Yagi, Naoko Mizumoto, Yusuke Onozato, Matsuki Umehara, Yoshiyuki Ueno
Summary: Eosinophilic esophagitis is a chronic immune-mediated inflammatory disease characterized by esophageal dysfunction and intense eosinophil infiltration. The recognition of characteristic endoscopic features and subsequent biopsy are crucial for early diagnosis and treatment, but the diagnostic consistency among endoscopists is still inadequate. Image-enhanced endoscopy holds promise for improving diagnostic efficiency.
Article
Pharmacology & Pharmacy
Junji Furuse, Namiki Izumi, Kenta Motomura, Yoshitaka Inaba, Yoshio Katamura, Yasuteru Kondo, Kazuhisa Yabushita, Katsuaki Motoyoshi, Masatoshi Kudo
Summary: This study aimed to evaluate the real-world safety and effectiveness of Lenvatinib for unresectable hepatocellular carcinoma (uHCC) in clinical practice in Japan. Data of 703 uHCC patients were analyzed, and it was found that the treatment response rate and median overall survival of Lenvatinib were similar to or better than the results of the global Phase III REFLECT trial.
DRUGS-REAL WORLD OUTCOMES
(2023)
Article
Biochemistry & Molecular Biology
Shinpei Sugahara, Hiroaki Haga, Chisaki Ikeda, Naohiko Makino, Akiko Matsuda, Yasuharu Kakizaki, Kyoko Hoshikawa, Tomohiro Katsumi, Tetsuya Ishizawa, Toshikazu Kobayashi, Keita Maki, Fumiya Suzuki, Ryoko Murakami, Hidenori Sato, Yoshiyuki Ueno
Summary: Despite extensive study on liver regeneration, the impact of bile-derived extracellular vesicles (bile EVs) on hepatocytes remains unclear. Using a rat model of partial hepatectomy (PH), this study found that bile EVs released 12 hours after PH significantly promoted hepatocyte proliferation. Transcriptome analysis revealed an upregulation of genes promoting cell cycle progression in hepatocytes treated with PH24-EVs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Takayuki Tokunaga, Masakuni Tateyama, Yasuteru Kondo, Satoshi Miuma, Shiho Miyase, Kentaro Tanaka, Satoshi Narahara, Hiroki Inada, Sotaro Kurano, Yoko Yoshimaru, Katsuya Nagaoka, Takehisa Watanabe, Hiroko Setoyama, Kotaro Fukubayashi, Motohiko Tanaka, Yasuhito Tanaka
Summary: This study aimed to evaluate the impact of therapeutic modifications of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (uHCC). Patients with therapeutic modifications other than discontinuation of both drugs had favorable overall survival and time to progression, while those with discontinuation of both drugs had unfavorable outcomes. Modified liver function and immune-related adverse events increased the risk of discontinuation without other therapeutic modifications. Avoiding discontinuation without other therapeutic modifications may be the optimal management for uHCC.
Article
Oncology
Masatoshi Kudo, Kazuomi Ueshima, Issei Saeki, Toru Ishikawa, Yoshitaka Inaba, Naoki Morimoto, Hiroshi Aikata, Nobukazu Tanabe, Yoshiyuki Wada, Yasuteru Kondo, Masahiro Tsuda, Kazuhiko Nakao, Takanori Ito, Tetsuya Hosaka, Yusuke Kawamura, Teiji Kuzuya, Shunsuke Nojiri, Chikara Ogawa, Hironori Koga, Keisuke Hino, Masafumi Ikeda, Michihisa Moriguchi, Takashi Hisai, Kenichi Yoshimura, Junji Furuse, Yasuaki Arai
Summary: The TACTICS-L trial investigated the efficacy and safety of TACE plus lenvatinib in patients with unresectable intermediate-stage HCC. The results showed that LEN-TACE has significant anti-tumor activity and an acceptable safety profile.