Article
Pharmacology & Pharmacy
Sevda Shayesteh, Gilles J. Guillemin, Amir Rashidian, Hedyeh Faghir-Ghanesefat, Ali R. Mani, Seyed Mohammad Tavangar, Ahmad R. Dehpour
Summary: The kynurenine pathway is upregulated in liver disease and is associated with disease severity. In an experimental model of cirrhosis, inhibition of IDO with 1-MT improved cardiac dysfunction and reduced systemic inflammation. Chronic administration of 1-MT also attenuated hepatic inflammation, fibrosis, and ductular proliferation in rats with biliary cirrhosis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Ana Dolsak, Stanislav Gobec, Matej Sova
Summary: This review discusses the key step of tryptophan metabolism and the importance of relevant enzymes in pathological conditions. In recent years, many inhibitors targeting these enzymes have been developed, and these inhibitors have entered clinical trials.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Ilona Sadok, Kamila Rachwal, Ilona Jonik, Magdalena Staniszewska
Summary: A new HPLC-DAD method for determining IDO1 activity in human cancer cells has been developed and successfully validated, demonstrating its applicability in different cancer cell types. This approach provides a useful model for studying the role of the kynurenine pathway in cancer biology.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Nirmalya Pradhan, Nasim Akhtar, Barnali Nath, Jorge Pena-Garcia, Anjali Gupta, Horacio Perez-Sanchez, Sachin Kumar, Debasis Manna
Summary: Quinine derivatives effectively inhibit the activity of IDO1 by competing with heme, providing a potential avenue for immunotherapy-based drug discovery strategies.
CHEMICAL COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Jaswir Basran, Elizabeth S. Booth, Laura P. Campbell, Sarah J. Thackray, Mehul H. Jesani, Jonathan Clayden, Peter C. E. Moody, Christopher G. Mowat, Hanna Kwon, Emma L. Raven
Summary: 【】The kynurenine pathway is the major route of tryptophan metabolism, catalyzed by heme-dependent dioxygenase enzymes. The crystal structure of a bacterial TDO in complex with L-kynurenine is presented in this paper, revealing a mechanism for the hydrolysis of NFK in the active site. Hydrogen bonding interactions and heme 7-propionate anchor the L-kynurenine molecule into the pocket.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2021)
Review
Immunology
Florent Peyraud, Jean-Philippe Guegan, Dominique Bodet, Sophie Cousin, Alban Bessede, Antoine Italiano
Summary: Metabolism of tryptophan plays a crucial role in tumor malignancy and immune suppression, making it a potential target for cancer immunotherapy. While IDO1 inhibitors have shown promising preclinical data, their effectiveness in clinical trials has been questioned, highlighting the complexity of combinatorial approaches. This review explores the immunomodulatory role of tryptophan catabolism metabolites, discusses the shortcomings of IDO1 inhibitors in clinical trials, and examines alternative approaches in the field of immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Seyed-Alireza Esmaeili, Jafar Hajavi
Summary: This review discusses the mechanism of immune response regulation through manipulating tryptophan metabolism. Studies suggest that the IDO-kynurenine pathway may play different roles in regulating Th2 cells and Th1 cells immune responses.
MOLECULAR BIOLOGY REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Emina Sudar-Milovanovic, Zoran Gluvic, Milan Obradovic, Bozidarka Zaric, Esma R. Isenovic
Summary: This article reviews the link between mammalian tryptophan metabolism and its role in atherosclerosis and diabetes, and outlines intervention strategies.
CURRENT MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Frederike T. Fellendorf, Nina Bonkat, Nina Dalkner, Elena M. D. Schoenthaler, Mirko Manchia, Dietmar Fuchs, Eva Z. Reininghaus
Summary: This review highlights the inconsistent findings on KYN/TRP ratio in severe mental disorders. Although there are indications of inflammation associated with elevated IDO activity, no conclusive statements can be made. Considering factors such as inflammatory processes, metabolic activities, and psychological/neuropsychiatric symptoms are crucial for a deeper understanding of the underlying mechanisms.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2022)
Article
Rheumatology
Dan Wu, Mengya Chen, Shile Chen, Shimin Zhang, Yongheng Chen, Qian Zhao, Ke Xue, Feng Xue, Xiaosong Chen, Min Zhou, Hao Li, Jie Zheng, Yunchen Le, Hua Cao
Summary: Enhanced Trp-Kyn metabolism at disease onset in dermatomyositis (DM) is associated with more severe disease status and poor prognosis.
CLINICAL RHEUMATOLOGY
(2022)
Article
Immunology
Yvonne Grobben, Jos de Man, Antoon M. van Doornmalen, Michelle Muller, Nicole Willemsen-Seegers, Diep Vu-Pham, Winfried R. Mulder, Martine B. W. Prinsen, Joeri de Wit, Jan Gerard Sterrenburg, Freek van Cauter, Judith E. den Ouden, Anne M. van Altena, Leon F. Massuger, Joost C. M. Uitdehaag, Rogier C. Buijsman, Guido J. R. Zaman
Summary: NTRC 3883-0 is a novel small molecule IDO1 inhibitor that showed immunomodulatory activity by releasing the inhibitory effect of IDO1 on CD8-positive T cell proliferation. It effectively counteracted the IDO1-induced modulation of L-tryptophan and L-kynurenine levels in a syngeneic mouse model using IDO1-overexpressing B16F10 melanoma cells. The expression and activity of IDO1 in primary cell cultures from ovarian cancer patients' malignant ascites could be inhibited by NTRC 3883-0, suggesting its potential for patient stratification.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Chemistry, Medicinal
Rahul Singh, Deepak B. Salunke
Summary: IDO1 enzyme catalyzes the initial step of kynurenine pathway and is implicated in immune modulation, antioxidation, and cancer progression. Overexpression of IDO1 plays a pivotal role in immune evasion and cancer development. Research and development of IDO1 inhibitors holds significant potential in immunotherapy and disease treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
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)
Article
Biochemistry & Molecular Biology
Hui Phing Ang, Suzana Makpol, Muhammad Luqman Nasaruddin, Nurul Saadah Ahmad, Jen Kit Tan, Wan Asyraf Wan Zaidi, Hashim Embong
Summary: This study examined the role of IDO and TRP-KP in lipopolysaccharide-induced delirium in a chronic cerebral hypoperfusion model. The results showed that LPS treatment led to behavior deficits and increased IDO expression, suggesting a potential therapeutic target for delirium.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Ott Kiens, Egon Taalberg, Viktoria Ivanova, Ketlin Veevali, Triin Laurits, Ragne Tamm, Aigar Ottas, Kalle Kilk, Ursel Soomets, Alan Altraja
Summary: The study found significant alterations in serum profiles of amino acid and biogenic amines in patients with OSA compared to controls, suggesting vast pathophysiologic shifts reflected in the systemic metabolism. Significant elevations in alanine, proline, and kynurenine concentrations in OSA patients were detected, as well as changes in overnight dynamics of other amino acids.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Chidimma Agatha Akpa, Karsten Kleo, Elisabeth Oker, Nancy Tomaszewski, Clemens Messerschmidt, Cristina Lopez, Rabea Wagener, Kathrin Oehl-Huber, Katja Dettmer, Anne Schoeler, Dido Lenze, Peter J. Oefner, Dieter Beule, Reiner Siebert, David Capper, Lora Dimitrova, Michael Hummel
Article
Oncology
Shady Adnan Awad, Olli Dufva, Aleksandr Ianevski, Bishwa Ghimire, Jan Koski, Pilvi Maliniemi, Daniel Thomson, Andreas Schreiber, Caroline A. Heckman, Perttu Koskenvesa, Matti Korhonen, Kimmo Porkka, Susan Branford, Tero Aittokallio, Matti Kankainen, Satu Mustjoki
Summary: Blast-phase chronic myeloid leukemia (BP-CML) with additional chromosomal aberrations, particularly RUNX1 mutations, show enriched mutations in PHF6 and BCORL1, IKZF1 deletions, and AID/RAG-mediated rearrangements. Deregulation of interferon and TNF signaling, upregulation of stem cell and B-lymphoid factors, and sensitivity to CD19-CAR T cells were observed in primary RUNX1(mut) CML cells. High drug responsiveness to mTOR, BCL2, and VEGFR inhibitors and glucocorticoids were identified in leukemia cells from RUNX1(mut) patients.
Article
Immunology
Katie L. O'Brien, Nadine Assmann, Eimear O'Connor, Cathal Keane, Jessica Walls, Chloe Choi, Peter J. Oefner, Clair M. Gardiner, Katja Dettmer, David K. Finlay
Summary: Cellular metabolism plays a crucial role in regulating NK cell responses, with SREBP and cMyc controlling metabolic and functional responses. Polyamine synthesis is essential for NK cell glycolytic and oxidative metabolism, while spermidine supports protein translation. Inhibition of hypusination impacts NK cell metabolism and effector functions.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Critical Care Medicine
Selena Z. Kuo, Katja Dettmer, Medini K. Annavajhala, David H. Chong, Anne-Catrin Uhlemann, Julian A. Abrams, Peter J. Oefner, Daniel E. Freedberg
Summary: The study investigated the relationship between urinary 3-IS levels and patient outcomes in the ICU, finding that low 3-IS levels were associated with fewer ICU-free days and increased one-year mortality. Further research should explore urinary 3-IS as an ICU biomarker.
JOURNAL OF CRITICAL CARE
(2021)
Article
Multidisciplinary Sciences
Jennifer K. Dowling, Remsha Afzal, Linden J. Gearing, Mariana P. Cervantes-Silva, Stephanie Annett, Gavin M. Davis, Chiara De Santi, Nadine Assmann, Katja Dettmer, Daniel J. Gough, Glenn R. Bantug, Fidinny Hamid, Frances K. Nally, Conor P. Duffy, Aoife L. Gorman, Alex M. Liddicoat, Ed C. Lavelle, Christoph Hess, Peter J. Oefner, David K. Finlay, Gavin P. Davey, Tracy Robson, Annie M. Curtis, Paul J. Hertzog, Bryan R. G. Williams, Claire E. McCoy
Summary: The study reveals that Arg2 is a protein in inflammatory macrophages regulated by miR-155 and IL-10, crucial for IL-10-induced modulation of mitochondrial dynamics and oxidative respiration. Arg2 mediates this process by increasing the activity of complex II and is essential for IL-10-mediated downregulation of inflammatory mediators.
NATURE COMMUNICATIONS
(2021)
Article
Allergy
Anders O. Petersen, Martta Jokinen, Damian R. Plichta, Gerhard Liebisch, Wolfram Gronwald, Katja Dettmer, Peter J. Oefner, Hera Vlamakis, Daniel C. Chung, Annamari Ranki, Ramnik J. Xavier
Summary: The gut microbiome in APS-1 patients is correlated with APS-1 symptoms, and probiotic intervention can alleviate some gastrointestinal symptoms. Furthermore, autoantibodies against cytokines appear to shape the gut microbiome by positively correlating with a taxonomically consistent group of bacteria.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Oncology
Raffaela S. Berger, Christian J. Wachsmuth, Magdalena C. Waldhier, Kathrin Renner-Sattler, Simone Thomas, Anuhar Chaturvedi, Hans-Helmut Niller, Elisabeth Bumes, Peter Hau, Martin Proescholdt, Wolfram Gronwald, Michael Heuser, Marina Kreutz, Peter J. Oefner, Katja Dettmer
Summary: Somatic mutations in isocitrate dehydrogenase lead to excessive production of D-2-hydroxyglutarate in certain malignancies. A related metabolite, 2-hydroxyglutarate-gamma-lactone, was discovered and it may impact the anti-tumor immune response. The formation of the lactone is likely linked to transport processes across the cell membrane and favored at low environmental pH.
Article
Biochemistry & Molecular Biology
Stephanie Arndt, Fadi Fadil, Katja Dettmer, Petra Unger, Marko Boskovic, Claudia Samol, Anja-Katrin Bosserhoff, Julia L. Zimmermann, Michael Gruber, Wolfram Gronwald, Sigrid Karrer
Summary: Cold Atmospheric Plasma (CAP) has anti-tumor effects transmitted through direct treatment or plasma-treated solutions (PTS) containing various amino acids and vitamins. Different plasma modes and treatment durations affect the production of reactive species in PTS, influencing the composition of active components and anti-tumor mechanisms. The findings are crucial for plasma device development and tumor treatment effectiveness.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Dermatology
Part Peterson, Kai Kisand, Nicolas Kluger, Annamari Ranki
Summary: The autoimmune disease APECED reveals the existence and function of the autoimmune regulator gene, leading to a new period in immunology and understanding of central and peripheral tolerance. It also has great relevance to the study of various skin diseases.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Letter
Dermatology
T. Makila, L. Jeskanen, M. Butina, L. Harjama, A. Ranki, T. Malkonen, N. Kluger
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Eva Scholler, James Marks, Virginie Marchand, Astrid Bruckmann, Christopher A. Powell, Markus Reichold, Christian Daniel Mutti, Katja Dettmer, Regina Feederle, Stefan Huttelmaier, Mark Helm, Peter Oefner, Michal Minczuk, Yuri Motorin, Markus Hafner, Gunter Meister
Summary: The mitochondrial protein METTL8 plays a crucial role in facilitating m(3)C methylation on mt-tRNAs, impacting respiratory chain activity and pancreatic cancer development. This modification leads to optimal composition and function of the mitochondria respiratory chain, with implications for patient survival and cellular metabolism.
Article
Pharmacology & Pharmacy
Philipp Tauber, Frederick Sinha, Raffaela S. Berger, Wolfram Gronwald, Katja Dettmer, Michaela Kuhn, Maximilian Trum, Lars S. Maier, Stefan Wagner, Frank Schweda
Summary: Large-scale clinical outcome studies have shown the efficacy of SGLT2 inhibitors in type II diabetes patients, with significant renoprotection observed in non-diabetic individuals with chronic kidney disease. However, the mechanisms behind the renal protective effects of SGLT2 inhibitors remain largely unknown and speculative.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Analytical
Anna-Maria Raita-Hakola, Leevi Annala, Vivian Lindholm, Roberts Trops, Antti Nasila, Heikki Saari, Annamari Ranki, Ilkka Polonen
Summary: This study introduces a novel spectral imaging concept and validates its feasibility through a clinical pre-test. The developed imager is capable of imaging complex skin surfaces and classifying different skin lesions. Promising results were obtained, but further research is needed.
Letter
Allergy
Maria Pesonen, Markku J. T. Kallio, Annamari Ranki, Martti A. Siimes, Kirsi M. Jarvinen
CLINICAL AND EXPERIMENTAL ALLERGY
(2022)
Article
Immunology
Ushanandini Mohanraj, Tuomas Konttinen, Alexander Salava, Liisa Vakeva, Annamari Ranki, Maria Soderlund-Venermo
Summary: Cutavirus (CuV) is significantly associated with cutaneous T-cell lymphoma (CTCL) and its precursor, parapsoriasis. Our study shows a higher prevalence of CuV-DNA in swabs from parapsoriasis patients (6/13; 46.2%) compared to healthy adults (1/51; 1.96%). Among 12 patients, 8 (66.7%) had CuV DNA detection in skin biopsies, and 4 of them developed CTCL.
CLINICAL INFECTIOUS DISEASES
(2023)