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)
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
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
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
Chemistry, Medicinal
Juyoung Jung, Hongchul Yoon, Te-ik Sohn, Kyusic Jang, Yeongran Yoo, Ilji Jeong, Jae Eui Shin, Jin Hee Lee, Jihyae Ann, Jeewoo Lee
Summary: Through a structure-activity relationship study, the N-3-bromophenyl derivative 19 was identified as the most potent inhibitor of IDO1, with an IC50 value of 0.44 μM. Molecular modeling revealed that interactions with heme iron, halogen bonding with Cys129, and hydrophobic interactions were crucial for the high potency of compound 19.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Editorial Material
Public, Environmental & Occupational Health
Johannes Burtscher, Barbara Strasser, Gregoire P. Millet, Martin Burtscher
Summary: Traveling to high-altitude destinations carries risks such as high-altitude sicknesses and impaired sleep and performance. The benefits of antioxidant supplementation are inconclusive, leading to a lack of clear clinical guidelines. This article highlights the potential of the antioxidant compound melatonin, which surprisingly has been poorly studied in high-altitude settings.
JOURNAL OF TRAVEL MEDICINE
(2022)
Editorial Material
Geriatrics & Gerontology
Johannes Burtscher, Andrea Ticinesi, Gregoire P. Millet, Martin Burtscher, Barbara Strasser
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Article
Medicine, General & Internal
Julia Tevini, Sebastian K. Eder, Ursula Huber-Schoenauer, David Niederseer, Georg Strebinger, Johanna M. Gostner, Elmar Aigner, Christian Datz, Thomas K. Felder
Summary: This study uses serum metabolomics to identify the metabolic differences between colorectal cancer patients, adenoma patients, and healthy controls. The perturbations in lipid metabolism and amino acid metabolism provide a foundation for further mechanistic studies and highlight the importance of lipid metabolites. Biomarkers related to these pathways could improve the sensitivity and specificity of diagnosis, as well as the monitoring of therapies.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Veterinary Sciences
Claire Mindus, Nienke van Staaveren, Dietmar Fuchs, Johanna M. Gostner, Joergen B. Kjaer, Wolfgang Kunze, M. Firoz Mian, Anna K. Shoveller, Paul Forsythe, Alexandra Harlander-Matauschek
Summary: This study assessed the potential effects of probiotics on behavioral problems in birds, finding that supplementation of L. rhamnosus can reduce stress-induced severe feather pecking and plumage damage while also impacting the immune system. These findings suggest that bacteria may have beneficial effects on avian immune response, health, and welfare.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Medicine, General & Internal
Arvid Eden, Anna Grahn, Daniel Bremell, Anahit Aghvanyan, Pradeepthi Bathala, Dietmar Fuchs, Johanna Gostner, Lars Hagberg, Nelly Kanberg, Sunsanee Kanjananimmanont, Magnus Lindh, Salvia Misaghian, Staffan Nilsson, Michael Scholl, George Sigal, Erika Stentoft, Marie Studahl, Aylin Yilmaz, Mingyue Wang, Martin Stengelin, Henrik Zetterberg, Magnus Gisslen
Summary: In this study, viral antigen was detected in cerebrospinal fluid (CSF) of COVID-19 patients with neurological symptoms, indicating a correlation between viral antigen and central nervous system (CNS) immune activation. COVID-19 patients showed signs of neuroaxonal injury, with neurosymptomatic patients exhibiting a more pronounced inflammatory profile unrelated to disease severity.
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)
Review
Endocrinology & Metabolism
Barbara Strasser, Andrea Ticinesi
Summary: The intestinal microbiome plays a role in the risk of age-related chronic diseases and syndromes in older individuals, including frailty and neurodegenerative diseases. Recent research suggests that the diversity and composition of gut microbiota are associated with physical and cognitive performance in older age. Targeting the microbiota may be a potential intervention for healthy aging.
CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
(2023)
Article
Environmental Sciences
Carina S. Bichler, Martin Niedermeier, Katharina Huefner, Matyas Galffy, Johanna M. Gostner, Philipp Nelles, Stefanie E. Schoettl, Barbara Sperner-Unterweger, Martin Kopp
Summary: Participation in climbing, Nordic walking, and social contact groups demonstrated beneficial results for patients with anxiety disorders and PTSD, with no additional clinically relevant benefits observed in the climbing group compared to the other two groups. Larger sample sizes and qualitative insights are needed to further evaluate the potential benefits of climbing for this population.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)
Article
Biochemistry & Molecular Biology
Cornelia A. Karg, Lucia Parrakova, Dietmar Fuchs, Harald Schennach, Bernhard Kraeutler, Simone Moser, Johanna M. Gostner
Summary: Phyllobilins, derived from the degradation of chlorophyll, are natural products with antioxidant and immunomodulatory properties. However, their mechanisms of action and in vivo effects require further investigation.
Editorial Material
Hospitality, Leisure, Sport & Tourism
Johannes Burtscher, Barbara Strasser, Giuseppe D'Antona, Gregoire P. Millet, Martin Burtscher
JOURNAL OF SPORT AND HEALTH SCIENCE
(2023)
Article
Microbiology
Laura P. Kincer, Sarah Beth Joseph, Maria M. Gilleece, Blake M. Hauser, Sabrina Sizemore, Shuntai Zhou, Clara Di Germanio, Henrik Zetterberg, Dietmar Fuchs, Steven G. Deeks, Serena Spudich, Magnus Gisslen, Richard W. Price, Ronald Swanstrom
Summary: HIV-1 can persist in a latent reservoir in individuals receiving antiretroviral therapy, and rebound virus can be detected in the cerebrospinal fluid during treatment interruption. In this study, we found that high viral loads and clonally amplified viral lineages in the cerebrospinal fluid were correlated with the influx of white blood cells. Additionally, we did not observe rebound macrophage-tropic virus in the cerebrospinal fluid, indicating that the CNS may not be a source of this virus. We propose a model in which R5 T cell-tropic virus is released from infected T cells in the CNS during treatment interruption.
NATURE MICROBIOLOGY
(2023)
Article
Immunology
Arvid Eden, Frida Rydberg, Aylin Yilmaz, Lars Hagberg, Johanna Gostner, Staffan Nilsson, Dietmar Fuchs, Magnus Gisslen
Summary: For people with HIV initiating ART during chronic infection, the occurrence of residual CNS immune activation is not correlated with pretreatment immune status, even when treatment is initiated at high CD4(+) T-cell counts, suggesting that the CNS reservoir is not differentially affected by the timing of ART initiation during chronic infection.
OPEN FORUM INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Katharina Obermoser, Natascha Brigo, Andrea Schroll, Pablo Monfort-Lanzas, Johanna M. Gostner, Sabine Engl, Simon Geisler, Miriam Knoll, Harald Schennach, Guenter Weiss, Dietmar Fuchs, Rosa Bellmann-Weiler, Katharina Kurz
Summary: This pilot study investigated the effects of a multi-strain probiotic preparation on fatigue, depression, and quality of life in patients with post-infectious fatigue. The results showed that both the probiotic and placebo groups experienced improvements, but the probiotic group had greater improvements. After 6 months, the probiotic group had significantly lower fatigue and depression scores, as well as improved quality of life.