Review
Nutrition & Dietetics
Halima Sultana, Michio Komai, Hitoshi Shirakawa
Summary: Vitamin K plays a critical role in liver diseases, particularly in conditions related to cholestasis. By modulating PXR, vitamin K may have a positive impact on cholestasis and liver fibrosis.
Article
Chemistry, Multidisciplinary
Jia-Xu Zhou, Cui-Na Li, Ya-Meng Liu, Su-Qin Lin, Ying Wang, Cen Xie, Fa-Jun Nan
Summary: In this study, novel 9,11-seco-cholesterol derivatives were designed and synthesized as FXR antagonists, with compound 9a exhibiting the best FXR antagonistic activity and reducing the expression of FXR target genes.
Article
Biochemistry & Molecular Biology
Ran Meng, Xueli Zhang, Haina Wang, Danlu Zhang, Xin Zhao
Summary: The study showed that the induction effects of Praziquantel (PZQ) on CYP3A4 vary between racemate and enantiomers, mediated through PXR, and are influenced by PXR gene polymorphism.
CURRENT DRUG METABOLISM
(2021)
Review
Gastroenterology & Hepatology
Nicolas Richard, Guillaume Savoye, Mathilde Leboutte, Asma Amamou, Subrata Ghosh, Rachel Marion-Letellier
Summary: Crohn's disease is an immune-mediated inflammatory bowel disease with alternating flares and remission periods. The ileum is frequently affected in this disease, and the ileal type of Crohn's disease has specific epidemiological characteristics such as a younger age at onset, smoking, and genetic susceptibility. Environmental factors, such as diet, along with the histological and anatomical features of the ileum, play a role in the susceptibility to inflammation. Different immune responses and cellular healing processes are observed between ileal and non-ileal Crohn's disease, suggesting the need for a dedicated therapeutic approach for managing ileal CD.
WORLD JOURNAL OF GASTROENTEROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lijuan Feng, Nan Zhou, Zichun Li, Dongni Fu, Ying Guo, Xuefeng Gao, Xiaowei Liu
Summary: This study elucidates the relationship between gut microbiota, bile acid metabolism, and psychological comorbidity in Crohn's disease. The findings suggest that changes in the gut microbiota composition and alterations in bile acid metabolism may contribute to the development of psychological disorders in CD patients.
Article
Medicine, General & Internal
Wen Huang, Jin Zhou, Juanjuan Guo, Wen Hu, Guanghui Chen, Bin Li, Yajie Wen, Yimin Jiang, Kaili Fu, Huichang Bi, Yuanzhen Zhang, Hui Wang
Summary: Prenatal dexamethasone exposure can have lasting adverse effects on bile acid metabolism in offspring by affecting placental BA transporters and inducing imbalanced fetal-placental-maternal BA circulation, leading to increased levels of primary BAs in fetal serum.
Article
Pharmacology & Pharmacy
Ines L. Paraiso, Thai Q. Tran, Armando Alcazar Magana, Payel Kundu, Jaewoo Choi, Claudia S. Maier, Gerd Bobe, Jacob Raber, Chrissa Kioussi, Jan F. Stevens
Summary: This study demonstrated that XN supplementation in a high-fat diet can alleviate hepatic steatosis and reduce BA concentrations in FXR-deficient mice, with a stronger effect in males. XN also induced the expression of CAR, PXR, and GR genes in the livers of FXR-deficient mice, suggesting activation of BA detoxification pathways as the predominant mechanism. These findings indicate a sex-dependent relationship between FXR, lipids, and BAs, and suggest that XN improves HFD-induced liver dysfunction through both FXR-dependent and independent signaling pathways.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Endocrinology & Metabolism
Ye Lv, Yi-Yang Luo, Hui-Wen Ren, Cheng-Jie Li, Zhi-Xin Xiang, Zhi-Lin Luan
Summary: This article summarizes the functions of pregnane X receptor (PXR) in the metabolism of various substances and discusses the application of its ligands in specific diseases.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Pharmacology & Pharmacy
Alzbeta Stefela, Miroslav Kaspar, Martin Drastik, Thales Kronenberger, Stanislav Micuda, Martin Dracinsky, Blanka Klepetarova, Eva Kudova, Petr Pavek
Summary: The study identified 7-ethylidene-lithocholic acid (7-ELCA) as a novel combined FXR antagonist/GPBAR1 agonist, which can regulate glucose, lipid, and energy homeostasis as well as stimulate the production of GLP-1 to improve postprandial glucose utilization. The dual modulation of GPBAR1 and FXR by 7-ELCA may offer a promising approach for the treatment of type II diabetes.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Integrative & Complementary Medicine
Jia-Cheng Shen, Qin Qi, Dong Han, Yuan Lu, Rong Huang, Yi Zhu, Lin-Shan Zhang, Xiu-Di Qin, Fang Zhang, Huan-Gan Wu, Hui-Rong Liu
Summary: This study explored the mechanism of moxibustion in regulating intestinal inflammation and barrier repair in Crohn's disease (CD) through bile acid (BA) enterohepatic circulation and intestinal farnesoid X receptor (FXR). The results showed that moxibustion improved CD symptoms, inhibited inflammation, and repaired mucosal damage in CD rats. Moxibustion also regulated the abnormal expression of BA, downregulated interferon-c expression, upregulated FXR mRNA expression, and inhibited TLR4 and MyD88 mRNA expression. Additionally, moxibustion upregulated FXR and mucin2 expression, inhibited TLR4 expression, and regulated the TLR4/MyD88 pathway. Overall, moxibustion improved CD by regulating BA circulation, activating FXR, inhibiting inflammation, and repairing the intestinal mucosal barrier.
JOURNAL OF INTEGRATIVE MEDICINE-JIM
(2023)
Article
Biochemistry & Molecular Biology
Yinglin Guo, Qing Peng, Liyuan Hao, Jingmin Ji, Zhiqin Zhang, Yu Xue, Yiwei Liu, Yuting Gao, Caige Li, Xinli Shi
Summary: The bile acid receptor FXR is positively correlated with better prognosis in liver cancer patients. Dihydroartemisinin (DHA) can improve FXR levels and reduce YAP1 expression, thereby suppressing bile acid metabolism. Therefore, FXR may serve as a potential therapeutic target in HCC.
Article
Pharmacology & Pharmacy
Dajana Lichtenstein, Alexandra Lasch, Jimmy Alarcan, Almut Mentz, Joern Kalinowski, Felix F. Schmidt, Oliver Poetz, Philip Marx-Stoelting, Albert Braeuning
Summary: In real life, organisms are exposed to complex mixtures of chemicals at low concentration levels, whereas research on toxicological effects is mostly focused on single compounds at comparably high doses. Mixture effects deviating from the assumption of additivity, especially synergistic effects, are of concern. This study demonstrates the enhanced triglyceride accumulation in human liver cells caused by a mixture of fatty chemicals at low concentrations, revealing potentially synergistic effects. Mathematical modeling and transcript pattern analysis further support the existence of more than additive behavior in mixture effects.
Article
Pharmacology & Pharmacy
Sijing Dong, Min Zhu, Ke Wang, Xiaoye Zhao, Longlong Hu, Wanghui Jing, Haitao Lu, Sicen Wang
Summary: Recent studies have shown that DHM can alleviate IBD by modulating gut microbiota and microbial BA metabolism, leading to improvements in intestinal barrier integrity. This research provides insights into the development of novel DHM-derived drugs for the management of inflammatory bowel disease.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Lili Ding, Eryun Zhang, Qiaoling Yang, Lihua Jin, Kyle M. Sousa, Bingning Dong, Yangmeng Wang, Jui Tu, Xiaoxiao Ma, Jingyan Tian, Hongli Zhang, Zhipeng Fang, Ana Guan, Yixin Zhang, Zhengtao Wang, David D. Moore, Li Yang, Wendong Huang
Summary: The study suggests that vertical sleeve gastrectomy (VSG) achieves its metabolic benefits by reducing intestinal bile acids and fat absorption levels.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Sydney Stern, Dongdong Liang, Linhao Li, Ritika Kurian, Caitlin Lynch, Srilatha Sakamuru, Scott Heyward, Junran Zhang, Kafayat Ajoke Kareem, Young Wook Chun, Ruili Huang, Menghang Xia, Charles C. Hong, Fengtian Xue, Hongbing Wang
Summary: CN06 is a dual activator of CAR and Nrf2, enhancing the bioactivation of CPA and decreasing the cytotoxicity of DOX in vitro. In a multicellular coculture model, CN06 increased the toxicity of CPA/DOX towards TNBC cells, while protecting cardiomyocytes from DOX-induced cardiotoxicity by selectively activating Nrf2-antioxidant signaling.
Article
Biochemistry & Molecular Biology
Shoichi Komine, Teruo Miyazaki, Keisuke Ishikura, Takashi Matsui, Takashi Miyoshi, Song-Gyu Ra, Akira Honda, Hideaki Soya, Shumpei Miyakawa, Hajime Ohmori
Summary: Taurine supplementation enhances endurance capacity by delaying the decrease in blood glucose concentration during exercise through increases of lipolysis in adipose tissues and fatty acid oxidation in skeletal muscles.
Article
Oncology
Taisuke Matsubara, Eiji Nakajima, Haruka Namikawa, Shotaro Ono, Ikki Takada, Tatsuo Ohira, Yukio Morishita, Teruo Miyazaki, Kinya Furukawa, Norihiko Ikeda
Summary: This study revealed the true frequency of EGFR mutations in NSCLC that are usually undetectable by PCR methods. The findings suggest that a selective mutation detection method may decrease the opportunity for patients to receive EGFR-TKI therapy.
MOLECULAR AND CLINICAL ONCOLOGY
(2022)
Article
Neurosciences
Yuhei Yajima, Alato Okuno, Isamu Nakamura, Teruo Miyazaki, Akira Honda, Atsushi Toyoda
Summary: The kynurenine pathway plays a crucial role in inflammation-induced disorders. This study found that feed ingredients significantly affect the levels of critical metabolites in the kynurenine pathway in central and peripheral tissues. The urine metabolome analysis also revealed the impact of feed ingredients on the excretion of various metabolites.
INTERNATIONAL JOURNAL OF TRYPTOPHAN RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Yuki Kasai, Takaomi Kessoku, Kosuke Tanaka, Atsushi Yamamoto, Kota Takahashi, Takashi Kobayashi, Michihiro Iwaki, Anna Ozaki, Asako Nogami, Yasushi Honda, Yuji Ogawa, Shingo Kato, Kento Imajo, Takuma Higurashi, Kunihiro Hosono, Masato Yoneda, Haruki Usuda, Koichiro Wada, Miwa Kawanaka, Takumi Kawaguchi, Takuji Torimura, Masayoshi Kage, Hideyuki Hyogo, Hirokazu Takahashi, Yuichiro Eguchi, Shinichi Aishima, Noritoshi Kobayashi, Yoshio Sumida, Akira Honda, Shunsuke Oyamada, Satoru Shinoda, Satoru Saito, Atsushi Nakajima
Summary: The study found that the concentrations of fecal and serum BAs were significantly higher in patients with NAFLD as fibrosis worsened, indicating the involvement of abnormal BA metabolism in the progression of fibrosis in NAFLD. Abnormalities in BA metabolism may be a potential therapeutic target in NAFLD with fibrosis.
CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY
(2022)
Article
Multidisciplinary Sciences
Hajime Ueda, Akira Honda, Teruo Miyazaki, Yukio Morishita, Takeshi Hirayama, Junichi Iwamoto, Nobuhiro Nakamoto, Tadashi Ikegami
Summary: Oral administration of UDCA prevented abnormal delivery and liver injury in DKO mice. However, liver injury emerged in 20-week-old female DKO mice with prolonged UDCA treatment, but not in males. UDCA treatment markedly reduced the BA hydrophobicity index in the male liver but not in females, which appears to be why UDCA treatment causes liver injury in 20-week-old female mice.
Article
Gastroenterology & Hepatology
Shigeki Bamba, Osamu Inatomi, Atsushi Nishida, Masashi Ohno, Takayuki Imai, Kenichiro Takahashi, Yuji Naito, Junichi Iwamoto, Akira Honda, Naohiro Inohara, Akira Andoh
Summary: This study revealed mucosa-associated dysbiosis and alterations in bile acid composition in the ileum of Crohn's disease patients, potentially playing a role in the pathophysiology of ileal lesions in Crohn's disease patients.
INTESTINAL RESEARCH
(2022)
Review
Medicine, General & Internal
Tadakuni Monma, Junichi Iwamoto, Hajime Ueda, Makoto Tamamushi, Fumio Kakizaki, Naoki Konishi, Shoichiro Yara, Teruo Miyazaki, Takeshi Hirayama, Tadashi Ikegami, Akira Honda
Summary: Dysbiosis in the intestinal microflora can lead to the development of various diseases by affecting the production of microbial metabolites and disrupting the barrier function of the intestinal wall. Decreased levels of Clostridium subcluster XIVa are associated with intestinal dysbiosis in inflammatory bowel disease and Clostridium difficile infection. The ratio of deoxycholic acid/cholic acid can be used to predict the proportion of intestinal XIVa. A lower proportion of XIVa in IBD patients may be a precondition for IBD onset. The bile acid profile can serve as a surrogate marker of the intestinal dysbiosis caused by decreased XIVa.
WORLD JOURNAL OF CLINICAL CASES
(2022)
Article
Immunology
Maho Yamashita, Akira Honda, Shin Shimoyama, Masahiro Umemura, Kazuyoshi Ohta, Takeshi Chida, Hidenao Noritake, Nobuhito Kurono, Mayuko Ichimura-Shimizu, Koichi Tsuneyama, Teruo Miyazaki, Atsushi Tanaka, Patrick S. C. Leung, M. Eric Gershwin, Takafumi Suda, Kazuhito Kawata
Summary: Primary biliary cholangitis (PBC) is an autoimmune disease characterized by loss of tolerance to self-antigens, with bile acids (BA) playing a major role in biliary inflammation and immune response dysregulation in PBC. This study aimed to investigate the impact of human-like hydrophobic BA composition on the development of autoimmune cholangitis and hepatic fibrosis. Using a unique mouse model with human-like BA composition, the researchers observed exacerbated portal inflammation, bile duct damage, and progression of hepatic fibrosis in mice treated with a mimic of the major mitochondrial autoantigen of PBC. These findings suggest that both the loss of tolerance and the effect of hydrophobic BA are crucial for the progression of PBC.
JOURNAL OF AUTOIMMUNITY
(2023)
Review
Medicine, General & Internal
Yasunori Miyamoto, Akira Honda, Seiji Yokose, Mariko Nagata, Jiro Miyamoto
Summary: Decompensated liver cirrhosis often leads to refractory ascites, which is a poor prognostic factor for patients with liver cirrhosis. Current treatment for ascites in cirrhosis patients involves the use of aldosterone blockers, loop diuretics, and sometimes vasopressin receptor antagonists. Recent reports suggest that sodium-glucose cotransporter 2 (SGLT2) inhibitors may provide a new treatment option with different mechanisms for refractory ascites. The mechanisms of ascites reduction with SGLT2 inhibitors include natriuresis, osmotic diuresis, improvements in glucose metabolism and nutritional status, hepatoprotection, amelioration of the sympathetic nervous system, and inhibition of the renin-angiotensin-aldosterone system. This literature review discusses previous cases in which SGLT2 inhibitors effectively treated ascites caused by liver cirrhosis and provides insights into the potential use of SGLT2 therapy for ascites in the future.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Yoichi Takimoto, Po-sung Chu, Nobuhiro Nakamoto, Yuya Hagihara, Yohei Mikami, Kentar Miyamoto, Rei Morikawa, Toshiaki Teratani, Nobuhito Taniki, Sota Fujimori, Takahiro Suzuki, Yuzo Koda, Rino Ishihara, Masataka Ichikawa, Akira Honda, Takanori Kanai
Summary: The resolution process of liver fibrosis after liver injury withdrawal is still not fully understood. In this study, the pro-fibrogenic role of Toll-like receptor 4 (TLR4) signaling in tissue fibroblasts was explored. Interestingly, pharmacological inhibition of TLR4 signaling in vivo in two murine models resulted in a significant delay in fibrosis resolution. Single-cell transcriptome analysis revealed a cluster of Tlr4-expressing myeloid cells that played a restorative role in the resolution process. Further investigation suggested a microbiome-dependent nature of the delayed resolution after gut sterilization. These findings provide insights into the pro-fibrolytic role of myeloid TLR4 signaling and potential targets for anti-fibrotic therapy.
Article
Multidisciplinary Sciences
Wataru Aoi, Ryo Inoue, Katsura Mizushima, Akira Honda, Marie Bjornholm, Tomohisa Takagi, Yuji Naito
Summary: Habitual exercise alters the intestinal microbiota composition, which improves skeletal muscle metabolism and glucose tolerance in HFD-fed mice through the transplantation of exercise-acclimated fecal microbiota. This is mediated by promoting AMPK and insulin growth factor-1 levels in skeletal muscle and enhancing bile acid deconjugation and AMPK signaling in plasma. These findings provide insights into the prevention and treatment of metabolic diseases.
Letter
Dermatology
Mirei Kanzaki, Akira Honda, Yasumasa Sawai, Kiyoka Suda, Ayumi Suda, Yasuhiro Kawachi
JOURNAL OF DERMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Teruo Miyazaki, Tadashi Ikegami, Hajime Ueda, Akira Honda
Summary: This study confirmed, for the first time in mice, that FXR activation can simultaneously upregulate both taurine synthesis and bile acid amidation pathways by comparing mice with different bile acid compositions in the liver.
