Article
Chemistry, Medicinal
Jiangxin Liu, Jian Ren, Kun Yang, Shuang Chen, Xinni Yang, Qin-Shi Zhao
Summary: This study reports the potential of synthetic analogues from Danshen as IDO1 and TDO inhibitors in cancer immunotherapy. The most potent compound, 30, was found to inhibit cancer cell growth by promoting apoptosis. These results contribute to the clinical application of tanshinone analogues.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Ying Tan, Miaomiao Liu, Ming Li, Yujuan Chen, Meng Ren
Summary: L-tryptophan metabolism is involved in the regulation of various physiological processes. Inhibiting the enzyme IDO1, which catalyzes the conversion of tryptophan, has therapeutic benefits for several diseases. Natural compounds, such as quinones, polyphenols, alkaloids, and others, have been found to have inhibitory activity against IDO1 and can be further optimized for potential use as IDO1 inhibitors.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Oncology
Yu Yao, Heng Liang, Xin Fang, Shengnan Zhang, Zikang Xing, Lei Shi, Chunxiang Kuang, Barbara Seliger, Qing Yang
Summary: IDO1, a heme-containing enzyme, plays a crucial role in the kynurenine pathway of tryptophan metabolism, with implications in immunity and neuronal function. Despite potential applications in cancer and neurodegenerative diseases, cautionary notes from clinical trials indicate a need for better understanding of IDO1 inhibition mechanisms.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Review
Oncology
Xinting Huang, Feng Zhang, Xiaobo Wang, Ke Liu
Summary: In this article, we review the immunosuppression mechanisms mediated by the IDO1 pathway in tumor growth and discuss the challenges and current clinical research progress in using IDO1 as a new tumor immunotherapy target.
Article
Immunology
Claudio Giacinto Atene, Stefania Fiorcari, Nicolo Mesini, Silvia Alboni, Silvia Martinelli, Monica Maccaferri, Giovanna Leonardi, Leonardo Potenza, Mario Luppi, Rossana Maffei, Roberto Marasca
Summary: The IDO1/Kyn/AHR signaling pathway plays an important role in chronic lymphocytic leukemia and represents a potential therapeutic target. Modulating this pathway can affect cell apoptosis and survival.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Medicinal
Teng-Kuang Yeh, Jen-Shin Song, Po-Wei Chang, Jin-Chen Yu, Chia-Hwa Chang, Fang-Yu Liao, Ya-Wen Tien, Ramajayam Kuppusamy, An-Siou Li, Chi-Han Chen, Chieh-Wen Chen, Li-Mei Lin, Hsin-Huei Chang, Chih-Hsiang Huang, Jau-Ying Yao, Mine-Hsine Wu, Yi-Hui Peng, Ching-Cheng Hsueh, Wen-Chi Hsiao, Pei-Husan Chen, Chin-Yu Lin, Su-Huei Hsieh, Chuan Shih, Ming-Shiu Hung, Su-Ying Wu, Ching-Chuan Kuo, Shau-Hua Ueng
Summary: This study describes the development of two series of ID01 inhibitors and the improvement in cellular activity and pharmacokinetic properties of these compounds. Compound 27a showed significant in vivo target inhibition and this strategy can be applied to discover ID01 inhibitors for other diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Cristina C. Clement, Angelo D'Alessandro, Sangeetha Thangaswamy, Samantha Chalmers, Raquel Furtado, Sheila Spada, Giada Mondanelli, Federica Ianni, Sarah Gehrke, Marco Gargaro, Giorgia Manni, Luisa Carlota Lopez Cara, Peter Runge, Wanxia Li Tsai, Sinem Karaman, Jorge Arasa, Ruben Fernandez-Rodriguez, Amanda Beck, Antonio Macchiarulo, Massimo Gadina, Cornelia Halin, Francesca Fallarino, Mihaela Skobe, Marc Veldhoen, Simone Moretti, Silvia Formenti, Sandra Demaria, Rajesh K. Soni, Roberta Galarini, Roccaldo Sardella, Gregoire Lauvau, Chaim Putterman, Kari Alitalo, Ursula Grohmann, Laura Santambrogio
Summary: 3-hydroxy-L-kynurenamine (3-HKA) is a metabolite deriving from a lateral pathway of tryptophan catabolism. The authors identify 3-HKA as a biogenic amine with anti-inflammatory properties, showing its protective effects against psoriasis and nephrotoxic nephritis in mice.
NATURE COMMUNICATIONS
(2021)
Article
Engineering, Biomedical
Jiankun Guan, Yuxin Wu, Xin Liu, Huimin Wang, Ningbing Ye, Zheng Li, Chen Xiao, Zhijie Zhang, Zifu Li, Xiangliang Yang
Summary: The study introduces a novel prodrug and its nanoformulation that effectively suppress CSCs by regulating their niche in TNBC tumors, indicating promising potential for treating intractable TNBC.
Article
Chemistry, Medicinal
Marta Cecchi, Sara Paccosi, Angela Silvano, Ali Hussein Eid, Astrid Parenti
Summary: The study found that dexamethasone can up-regulate TDO and its downstream effector AHR, as well as promote cell proliferation and migration in melanoma cells, indicating that TDO may be a promising target for the treatment of melanoma progression.
Article
Chemistry, Applied
Roshan Y. Nimje, Prakasam Kuppusamy, Suresh Krishnamoorthy, Yoganand Shanmugam, Duraisamy Ramasamy, Haridhas Manoharan, Pirama Nayagam Arunachalam, Aaron Balog, Emily C. Cherney, Liping Zhang, Robert M. Borzilleri, Zhenqiu Hong, James Kempson, Richard R. Rampulla, Arvind Mathur, Anuradha Gupta
Summary: The current work presents a stereoselective and scalable route to a specific compound, achieved through an efficient synthesis of key intermediates and the use of a stereoselective methodology. This advancement provides a competent and cost-effective approach to accessing the target compound in an enantioselective, safe, and scalable manner.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Microbiology
Thiara Manuele Alves de Souza, Caroline Fernandes-Santos, Jessica Araujo da Paixao de Oliveira, Larissa Cristina Teixeira Tome, Victor Edgar Fiestas-Solorzano, Priscila Conrado Guerra Nunes, Gabriel Macedo Costa Guimaraes, Juan Camilo Sanchez-Arcila, Iury Amancio Paiva, Luis Jose de Souza, Paulo Vieira Damasco, Valber da Silva Frutuoso, Manoela Heringer, Luzia Maria De Oliveira-Pinto, Roberta Olmo Pinheiro, Flavia Barreto dos Santos, Elzinandes Leal de Azeredo
Summary: This study evaluated the activity of IDO-1 and the patterns of cytokines/chemokines in CHIKV patients. It was found that IDO-1 activity increased during the early acute phase of infection and decreased in the chronic phase. In the acute phase, concentrations of TNF-alpha, IL-6, IFN-gamma, CCL2/MCP-1, and CXCL10/IP-10 were increased. In the chronic phase, concentrations of CCL4/MIP-1 beta were increased, especially in patients with arthritis.
Review
Oncology
Hamed Hosseinalizadeh, Mehrdad Mahmoodpour, Ali Akbar Samadani, Mehryar Habibi Roudkenar
Summary: This article reviews the role of IDO1 in immune escape in brain tumors, the immunomodulatory effects of its primary catabolites, preclinical research targeting this enzymatic pathway, and various issues that need to be overcome to increase the prospective immunotherapeutic relevance in the treatment of GBM malignancy.
Article
Chemistry, Medicinal
Xin He, Guangchao He, Zhaoxing Chu, Huanhuan Wu, Junjie Wang, Yiran Ge, Hui Shen, Shan Zhang, Jinxi Shan, Kewen Peng, Zhifeng Wei, Yi Zou, Yungen Xu, Qihua Zhu
Summary: The study identified compound4t as the first inhibitor targeting both IDO1/2 with excellent in vitro inhibitory activity. This compound demonstrated significantly stronger in vivo antitumor potency compared to existing drugs in mouse models, highlighting the advantages of IDO1/2 dual inhibitors for tumor immunotherapy. Further mechanistic studies confirmed that 4t exerts its antitumor effect by inhibiting IDO1/2.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biotechnology & Applied Microbiology
Parisa Badiee, Michelle F. Maritz, Pouya Dehghankelishadi, Nicole Dmochowska, Benjamin Thierry
Summary: This study introduces a nanoformulation of the IDO inhibitor navoximod within polymeric nanoparticles, prepared using a high-throughput microfluidic mixing device. The nanoformulation efficiently inhibits IDO and enhances the anti-cancer cytotoxicity of T-cells through synergy with PD-1 antibodies.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Rui Qin, Chen Zhao, Chen-Ji Wang, Wei Xu, Jian-Yuan Zhao, Yan Lin, Yi-Yuan Yuan, Peng-Cheng Lin, Yao Li, Shimin Zhao, Yan Huang
Summary: This study demonstrated that IDO inhibitors activate CD8(+) T cells by increasing tryptophan levels and consequently downregulating PD-1 expression. Tryptophan and IDO inhibitors both potentiate CD8(+) T cells to induce apoptosis of cancer cells through different mechanisms, suggesting a potential synergistic effect in anticancer treatments.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Rina Nagata, Nanami Akai, Shu Kondo, Kuniaki Saito, Shizue Ohsawa, Tatsushi Igaki
Summary: Mutations in the tumor-suppressor Hippo pathway activate the transcriptional coactivator Yorkie, leading to autonomous cell proliferation and non-autonomous cell death. This study reveals that Yki-induced supercompetition is crucial for tumorigenesis and is driven by non-autonomous induction of autophagy.
Article
Genetics & Heredity
Kohei Hamanaka, Keita Miyoshi, Jia-Hui Sun, Keisuke Hamada, Takao Komatsubara, Ken Saida, Naomi Tsuchida, Yuri Uchiyama, Atsushi Fujita, Takeshi Mizuguchi, Benedicte Gerard, Allan Bayat, Berardo Rinaldi, Mitsuhiro Kato, Jun Tohyama, Kazuhiro Ogata, Yun Stone Shi, Kuniaki Saito, Satoko Miyatake, Naomichi Matsumoto
Summary: A gain-of-function variant in the GRIA3 gene was found to cause a distinct neurodevelopmental disorder phenotype compared to loss-of-function variants. Drugs that suppress glutamatergic neurotransmission may improve the symptoms of this phenotype. This study is significant for the clinical management of GRIA3-related NDDs.
Article
Genetics & Heredity
Kenji Ichiyanagi, Kuniaki Saito
Summary: The fifth Japanese meeting on host-transposon interactions focused on the diverse roles of transposable elements in genome function and evolution, as well as host defense systems against TE mobility through chromatin and RNA modifications and protein-protein interactions.
Article
Chemistry, Multidisciplinary
Mizuki Yoshida, Atsushi Teramoto, Kohei Kudo, Shoji Matsumoto, Kuniaki Saito, Hiroshi Fujita
Summary: This study utilized CycleGAN to generate pseudo patient images and improve the accuracy of cerebral infarction region extraction. The results showed that the method with CycleGAN significantly improved the Dice index of U-Net and reduced the number of false positives.
APPLIED SCIENCES-BASEL
(2022)
Article
Oncology
Kyoka Yamazaki, Masato Hoshi, Hiroyuki Tezuka, Nanaka Morita, Masaya Hirayama, Fumiaki Sato, Sayaka Yoshida, Kuniaki Saito
Summary: D-Allose, a rare sugar, can inhibit tumor cell growth by blocking glucose uptake. However, some cells develop resistance to D-Allose. In this study, the researchers established a D-Allose-resistant tumor cell line and a mouse xenograft model. They found that combined treatment with D-Allose and an autophagy inhibitor effectively suppressed tumor growth and selectively induced autophagy at the tumor site.
Article
Chemistry, Multidisciplinary
Yoshitaka Isobe, Atsushi Teramoto, Fujio Morita, Kuniaki Saito, Hiroshi Fujita
Summary: In computed tomography colonography (CTC), an electronic cleansing method using CycleGAN was developed to assist diagnosis and accurately visualize the colon.
APPLIED SCIENCES-BASEL
(2022)
Article
Medicine, General & Internal
Atsushi Teramoto, Tomoyuki Shibata, Hyuga Yamada, Yoshiki Hirooka, Kuniaki Saito, Hiroshi Fujita
Summary: In this study, a cascaded deep learning model was proposed for the classification of endoscopic images and identification of the invasive region, achieving good detection results.
Article
Cardiac & Cardiovascular Systems
Eirin Sakaguchi, Akira Yamada, Hiroyuki Naruse, Hidekazu Hattori, Hideto Nishimura, Hideki Kawai, Takashi Muramatsu, Junnichi Ishii, Tadayoshi Hata, Kuniaki Saito, Hideo Izawa
Summary: Changes in GLS values are associated with the long-term prognosis of patients with a preserved LVEF and acute decompensated heart failure (HFpEF).
Article
Oncology
Tatsuya Ando, Masato Hoshi, Hiroyuki Tezuka, Hiroyasu Ito, Kentaro Nakamoto, Yasuko Yamamoto, Kuniaki Saito
Summary: The partial loss of liver due to liver transplantation or acute liver failure induces rapid liver regeneration. Recently, we reported that the selective inhibition of indoleamine 2,3-dioxygenase (Ido) 1 promotes early liver regeneration. However, the role of Ido2 in liver regeneration remains unclear.
MOLECULAR MEDICINE REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Chikara Takeuchi, Moe Yokoshi, Shu Kondo, Aoi Shibuya, Kuniaki Saito, Takashi Fukaya, Haruhiko Siomi, Yuka W. Iwasaki
Summary: In Drosophila, specific splice variants of the insulator protein Mod(mdg4)-N repress HeT-A expression by blocking subtelomeric enhancers and associating with the subtelomeric sequences. Furthermore, Mod(mdg4)-N recruits RNA polymerase II to the subtelomeres, reinforcing its enhancer-blocking function.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Medicine, General & Internal
Atsushi Teramoto, Tetsuya Tsukamoto, Ayano Michiba, Yuka Kiriyama, Eiko Sakurai, Kazuyoshi Imaizumi, Kuniaki Saito, Hiroshi Fujita
Summary: This study proposes an automatic classification method for idiopathic interstitial pneumonia (IIP) using deep learning, and compensates for the lack of data on rare diseases by generating pathological images using a generative adversarial network (GAN). The results show that this method is effective for the diagnosis of idiopathic pulmonary fibrosis (IPF), with high accuracy.
Review
Cell Biology
Yuki Murakami, Yukio Imamura, Yoshiyuki Kasahara, Chihiro Yoshida, Yuta Momono, Ke Fang, Daisuke Sakai, Yukuo Konishi, Toshimasa Nishiyama
Summary: Several studies have shown that genetic and environmental factors play significant roles in the development and progression of neurodevelopmental disorders. Maternal immune activation during pregnancy is considered a major environmental factor in this process. The activation of the kynurenine pathway following neuro-inflammation generates neuroactive metabolites that can affect brain functions and behaviors. Investigating the role of kynurenine pathway metabolites during neurodevelopment can provide valuable insights into the pathophysiology of neurodevelopmental disorders. Evaluating clinical data and animal models, this review examines the impact of perinatal kynurenine pathway elevation on long-term biochemical, neuropathological, and behavioral deficits, with the aim of informing new therapeutic strategies and interventions for these disorders.
Article
Engineering, Biomedical
Terumasa Kondo, Atsushi Teramoto, Eiichi Watanabe, Yoshihiro Sobue, Hideo Izawa, Kuniaki Saito, Hiroshi Fujita
Summary: In this study, a two-dimensional convolutional neural network (CNN) was used to predict the short-term prognosis of CCU patients by converting their ECG data into image data. The prediction accuracy was 77.3%. The results suggest that this method could be used to predict the short-term prognosis of CCU patients using ECG waveforms, which has clinical significance in determining treatment strategies and treatment intensity.
IEEE JOURNAL OF TRANSLATIONAL ENGINEERING IN HEALTH AND MEDICINE
(2023)
Meeting Abstract
Oncology
Kuniaki Saito, Yuta Sasaki, Saki Shimizu, Jun Nagai, Yuki Yamagishi, Nobuyoshi Sasaki, Keiichi Kobayashi, Yoshiaki Shiokawa, Hirofumi Nakatomi, Motoo Nagane
Article
Neurosciences
Ryosuke Jozuka, Hiroki Kimura, Takashi Uematsu, Hidetsugu Fujigaki, Yasuko Yamamoto, Masato Kobayashi, Kazuya Kawabata, Haruki Koike, Toshiya Inada, Kuniaki Saito, Masahisa Katsuno, Norio Ozaki
Summary: This case highlights the importance of recognizing that even apparently mild COVID-19-related respiratory symptoms can lead to severe and persistent neuropsychiatric symptoms. It also underscores the need to elucidate the mechanisms, treatment, and long-term course of COVID-19-related neuropsychiatric symptoms in the future.
NEUROPSYCHOPHARMACOLOGY REPORTS
(2022)
