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
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
Immunology
Samuel R. Schnittman, Amelia N. Deitchman, Gabriele Beck-Engeser, HaeLee Ahn, Vanessa A. York, Heather Hartig, Frederick M. Hecht, Jeffrey N. Martin, Steven G. Deeks, Francesca T. Aweeka, Peter W. Hunt
Summary: While early-ART initiators restore near-normal levels of many inflammatory markers, the kynurenine pathway of tryptophan catabolism remains abnormally high. Because this pathway confers adaptive immune defects and predicts tuberculosis and cancer progression, this it may contribute to persistent risks of these complications in this setting.
JOURNAL OF INFECTIOUS DISEASES
(2021)
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
Pediatrics
Jeffrey I. Campbell, Mary Tabatneck, Mingwei Sun, Wei He, Nicholas Musinguzi, Bethany Hedt-Gauthier, Gabriella S. Lamb, Kezia Domond, Don Goldmann, Vishakha Sabharwal, Thomas J. Sandora, Jessica E. Haberer
Summary: The study aimed to characterize losses from the pediatric TB infection care cascade and identify ways to improve TB infection care delivery. A retrospective cohort study found that while testing completion rate was high, evaluation and treatment completion rates were moderate. Transitioning towards IGRA testing and addressing social determinants of health are important interventions to improve completion rates.
JOURNAL OF PEDIATRICS
(2023)
Review
Public, Environmental & Occupational Health
Madeleine Goldstein, Moherndran Archary, Julian Adong, Jessica E. Haberer, Lisa M. Kuhns, Ann Kurth, Keshet Ronen, Marguerita Lightfoot, Irene Inwani, Grace John-Stewart, Robert Garofalo, Brian C. Zanoni
Summary: Adolescents and young adults in low to middle income countries have poorer outcomes in HIV prevention and care compared to other age groups. The use of mHealth interventions shows promise in addressing these disparities, but more large-scale randomized trials are needed.
Editorial Material
Medicine, General & Internal
Jessica E. Haberer, Yap Boum
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Immunology
Mary E. Tabatneck, Wei He, Gabriella S. Lamb, Mingwei Sun, Don Goldmann, Vishakha Sabharwal, Thomas J. Sandora, Jessica E. Haberer, Jeffrey I. Campbell
Summary: This retrospective cohort study analyzed 321 IGRA results, of which 308 were valid and 13 were invalid/indeterminate. The study found a significantly higher proportion of invalid/indeterminate results among immunocompromised patients compared to immunocompetent patients. Discordant results were more common in bacille Calmette-Guerin-vaccinated patients. IGRAs should be considered as a diagnostic method for tuberculosis infection in certain clinical scenarios for children under 2 years of age.
PEDIATRIC INFECTIOUS DISEASE JOURNAL
(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
Elizabeth Hastie, Carlee Moser, Xin Sun, Jeffrey Lennox, Priscilla Y. Hsue, Ronald J. Bosch, Steven Deeks, Milenka Meneses, Michael M. Lederman, Peter Hunt, Timothy J. Henrich, Vincent C. Marconi, Sara Gianella
Summary: The immune-modulators ruxolitinib and sirolimus did not have a significant effect on CMV DNA shedding in people with HIV on suppressive antiretroviral therapy. However, higher CMV DNA levels were associated with immune markers related to HIV persistence and mortality rates. CMV is a known contributor to the persistent inflammation and immune dysfunction observed in HIV.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Review
Microbiology
Raphael J. Landovitz, Hyman Scott, Steven G. Deeks
Summary: In this Review, the authors explore the current state of HIV prevention and treatment, highlighting unmet needs and emerging tools. They discuss the combination of different approaches to achieve better outcomes, and describe recent progress in pre-exposure prophylaxis, vaccines, treatment, and cure. They emphasize the need for continued efforts to develop effective preventative vaccines and scalable cures, as the limitations of antiretroviral drugs become more apparent.
NATURE REVIEWS MICROBIOLOGY
(2023)
Editorial Material
Medicine, General & Internal
Suzanne Koven, Jessica E. Haberer, Deborah Gomez Kwolek
Summary: Residents who want to get pregnant often have few options to adjust their schedules without interrupting their careers. This situation highlights the need for both structural and cultural changes.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Medicine, Research & Experimental
Lauren Jennings, Rebecca L. West, Nafisa Halim, Jeanette L. Kaiser, Marya Gwadz, William B. MacLeod, Allen L. Gifford, Jessica E. Haberer, Catherine Orrell, Lora L. Sabin
Summary: This study aims to use the multiphase optimization strategy (MOST) framework to determine the most effective combination of HIV adherence monitoring and support intervention components for implementation in resource-limited clinics in South Africa. The study will evaluate factors such as acceptability, feasibility, and cost-effectiveness, and validate the results through a randomized controlled trial. The findings of this study will be crucial for pragmatic adherence support to end the HIV epidemic.
Article
Infectious Diseases
Abubaker Ibrahim Elbur, Musie Ghebremichael, Deborah Konkle-Parker, Deborah L. Jones, Shelby Collins, Adaora A. Adimora, Michael F. Schneider, Mardge H. Cohen, Bani Tamraz, Michael Plankey, Tracey Wilson, Adebola Adedimeji, Jessica E. Haberer, Denise L. Jacobson
Summary: This study aimed to investigate the interrelationship between adherence to antiretroviral therapy (ART) and polypharmacy. The results showed no significant interrelationship between ART adherence and polypharmacy. Future research should consider using objective measures of adherence to examine the relationship between these two variables.
AIDS RESEARCH AND THERAPY
(2023)
Review
Immunology
Jessica E. Haberer, Andrew Mujugira, Kenneth H. Mayer
Summary: The effectiveness of HIV pre-exposure prophylaxis (PrEP) is hindered by barriers such as poor access, discrimination, stigma, and lack of understanding. Barriers to adherence and persistence include individual factors (such as depression) and community support. However, opportunities to improve PrEP adherence exist through innovative delivery systems, tailored interventions, and monitoring strategies. Person-centred approaches to service delivery are crucial for improving PrEP adherence and facilitating healthcare access.
Article
Immunology
Jose R. Castillo-Mancilla, Mary Morrow, Peter W. Hunt, Samuel R. Schnittman, Andrew N. Phillips, Jason Baker, Jessica E. Haberer, Maria Joao Janeiro, Filipa Aragao, Cal Cohen, Nicholas Musinguzi, Todd T. Brown, Matthias Cavassini, Tracy R. Glass, Sergio Serrano-Villar, Samantha Mawhinney, Mark Siedner
Summary: Incomplete antiretroviral therapy (ART) adherence has been linked to adverse outcomes in people with HIV. The impact of improving adherence on the risk of severe non-AIDS events (SNAEs) and death is unknown.
OPEN FORUM INFECTIOUS DISEASES
(2023)
Article
Public, Environmental & Occupational Health
Elzette Rousseau, Linxuan Wu, Renee Heffron, Jared M. Baeten, Connie L. Celum, Danielle Travill, Sinead Delany-Moretlwe, Linda-Gail Bekker, Elizabeth Bukusi, Victor Omollo, Ariane van der Straten, Gabrielle O'Malley, Jessica E. Haberer, Jennifer F. Morton, Rachel E. Johnson, Sarah T. Roberts
Summary: Gendered power inequalities affect the sexual and reproductive health outcomes of adolescent girls and young women. This study explores the influence of sexual relationship power on their sexual and reproductive health outcomes, including HIV pre-exposure prophylaxis (PrEP) persistence. The study found that while sexual relationship power is associated with sexual and reproductive health outcomes, it does not affect PrEP persistence.
FRONTIERS IN REPRODUCTIVE HEALTH
(2023)
Article
Multidisciplinary Sciences
Daniel B. Reeves, Christian Gaebler, Thiago Y. Oliveira, Michael J. Peluso, Joshua T. Schiffer, Lillian B. Cohn, Steven G. Deeks, Michel C. Nussenzweig
Summary: Most proviruses in people living with HIV are defective, but intact proviruses can lead to viral rebound. The two-probe intact proviral DNA assay (IPDA) found 40-fold more intact proviruses compared to the near full length (nfl) Q4PCR. Both assays showed that defective proviruses did not decay over 10 years. However, the average half-lives of intact proviruses were different: 108 months for IPDA and 65 months for Q4PCR. Misclassified defective proviruses and very long-lived intact proviruses could explain this difference.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Daniel B. Reeves, Charline Bacchus-Souffan, Mark Fitch, Mohamed Abdel-Mohsen, Rebecca Hoh, Haelee Ahn, Mars Stone, Frederick Hecht, Jeffrey Martin, Steven G. Deeks, Marc K. Hellerstein, Joseph M. McCune, Joshua T. Schiffer, Peter W. Hunt
Summary: The persistence of HIV in people on suppressive antiretroviral therapy is linked to physiological mechanisms of CD4+ T cells. This study investigates the longitudinal kinetics of HIV DNA and cell turnover rates in different CD4 cell subsets. The results indicate that HIV clears faster in more proliferative/differentiated CD4 cell subsets and therapies targeting proliferation and differentiation may reduce HIV DNA levels.
NATURE COMMUNICATIONS
(2023)