Article
Biochemistry & Molecular Biology
Mihai Oltean, Jasmine Bagge, George Dindelegan, Diarmuid Kenny, Antonio Molinaro, Mats Hellstrom, Ola Nilsson, Carina Sihlbom, Anna Casselbrant, Marcela Davila, Michael Olausson
Summary: This study conducted a proteome-wide analysis in a mouse model of intestinal transplantation and identified proteome changes associated with rejection, potentially serving as biomarkers for intestinal rejection.
Article
Biology
Carolin Steinack, Ariana Gaspert, Fiorenza Gautschi, Rene Hage, Bart Vrugt, Alex Soltermann, Mace Matthew Schuurmans, Daniel Franzen
Summary: This study found that transbronchial cryobiopsy (CB) provided an improved diagnostic yield for acute cellular rejection (ACR) compared to transbronchial forceps biopsy (FB), leading to reclassification and changes in treatment strategies in 28.6% of cases.
Article
Biochemistry & Molecular Biology
Zhiqiang Zhang, Qi Li, Yongxiong Huang, Zhou Xu, Xinjin Chen, Baijian Jiang, Yu Huang, Jichang Jian
Summary: This study identified and characterized the VIP precursor gene and its receptor gene in Nile tilapia, and investigated their roles in immune modulation and protection against bacterial infection. The results showed that both genes were highly expressed in the intestine and induced by Streptococcus agalatiae. In vitro and in vivo experiments demonstrated immune functions of VIP, including inflammation suppression and promotion of apoptosis and pyroptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Amalia Guzman-Gomez, Hosam F. Ahmed, Alia Dani, Farhan Zafar, David G. Lehenbauer, Andrew S. Potter, David L. S. Morales, Assem G. Ziady, Don Hayes Jr
Summary: The study aims to determine whether transplant center volume affects ACR-related outcomes in children after lung transplantation. The study found that children treated for ACR at high-volume centers have higher survival rates compared to low-volume centers, but similar survival rates to medium-volume centers. ACR incidence is lowest at high-volume centers, and post-ACR treatment survival outcomes are also superior.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2023)
Review
Biochemistry & Molecular Biology
Martin Rumbo, Mihai Oltean
Summary: Intestinal transplantation (ITx) is a life-saving option for patients with irreversible intestinal failure. However, ITx is highly immunogenic due to the unique immunobiology of the intestines and the lack of reliable non-invasive biomarkers for rejection surveillance. Various assays have been tested, but none have shown sufficient sensitivity and specificity for diagnosing acute rejection. This review integrates the mechanistic aspects of graft rejection with the current knowledge of ITx immunobiology and summarizes the search for a noninvasive biomarker of rejection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Endocrinology & Metabolism
Xintong Hou, Dan Yang, Guimei Yang, Mengnan Li, Jian Zhang, Jiaxin Zhang, Yi Zhang, Yunfeng Liu
Summary: This review summarizes the physiological significance of vasoactive intestinal peptide (VIP) in glucose homeostasis and the potential therapeutic value of VPAC2-selective agonists in type 2 diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Immunology
Xiaofan Song, Shanyao Pi, Yueming Gao, Fengxia Zhou, Shuqi Yan, Yue Chen, Lei Qiao, Xina Dou, Dongyan Shao, Chunlan Xu
Summary: The study demonstrated that VIP pretreatment inhibited the activation of mast cells and the release of certain enzymes. The protective effect of L. casei ATCC 393 on ETEC K88-induced intestinal mucosal immune barrier dysfunction was abolished by aVIP.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Surgery
Carolyn P. Smullin, Robert S. Venick, Elizabeth A. Marcus, Bita Naini, Douglas G. Farmer
Summary: REG3 alpha plays a crucial role in monitoring acute allograft rejection after intestinal transplantation, with the ability to predict rejection one week in advance. Analysis of two adult cases confirmed that increases in REG3 alpha corresponded with acute allograft rejection and preceded histopathological changes.
CLINICAL TRANSPLANTATION
(2021)
Article
Biochemistry & Molecular Biology
Raul Villanueva-Romero, Alicia Cabrera-Martin, Emigdio alvarez-Corrales, Mar Carrion, Selene Perez-Garcia, Amalia Lamana, David Castro-Vazquez, Carmen Martinez, Rosa P. Gomariz, Irene Gutierrez-Canas, Yasmina Juarranz
Summary: This study investigates the behavior of human CD4(+)CD45RA(+) T cells after in vitro activation and the role of the VIP system in this process. The findings show that without polarizing conditions, these T cells mainly differentiate into pathogenic Th17 subset and an unpaired Treg subset. The study also confirms the important immunomodulatory role of VIP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Respiratory System
Tomoyuki Nakagiri, Sabine Wrenger, Kokilavani Sivaraman, Fabio Ius, Tobias Goecke, Patrick Zardo, Veronika Grau, Tobias Welte, Axel Haverich, Ann-Kathrin Knofel, Sabina Janciauskiene
Summary: Therapy with AAT suppresses acute rejection after LuTx in a mouse model, with beneficial effects involving anti-protease and immunomodulatory activities of AAT.
RESPIRATORY RESEARCH
(2021)
Article
Biology
Evgeny Privalov, Matthias Zenkel, Ursula Schloetzer-Schrehardt, Stefanie Kuerten, Antonio Bergua, Bettina Hohberger
Summary: The purpose of this study was to investigate the level of choroidal VIP (VIPchor) in the presence of an increased atmospheric pressure in a chicken model. The results showed that VIPchor level was significantly increased at 40 mmHg compared to the ambient pressure. This finding suggests that the accumulation of VIP within the neurons would decrease vasodilation and choroidal thickness.
Article
Immunology
Yusheng Li, Hengzhen Li, Lijie Wang, Wenqing Xie, Dongliang Yuan, Zeqin Wen, Tiancheng Zhang, Jieyu Lai, Zixuan Xiong, Yunhan Shan, Wei Jiang
Summary: Targeting inflammatory pathways is important in treating osteoarthritis (OA), however, the role and mechanism of VIP in OA is unclear. This study found that the p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop modulates various phenotypes in OA chondrocytes, including cell apoptosis, ROS accumulation, extracellular matrix deposition, and inflammatory response.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Gastroenterology & Hepatology
Jonas Varkey
Summary: Intestinal transplantation is a life-saving treatment option for patients with irreversible intestinal failure, with short-term survival improvement, but limited long-term survival. Acute cellular rejection is a common cause of graft loss, making graft monitoring and early rejection detection essential. The use of histology continues to be supported for diagnosing acute rejection, while the role of biomarkers remains debatable.
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
(2021)
Review
Critical Care Medicine
Benjamin Renaud-Picard, Angela Koutsokera, Michael Cabanero, Tereza Martinu
Summary: This review summarizes the most recent evidence on acute cellular rejection after lung transplantation, including mechanisms, risk factors, diagnosis, treatment, and prognosis. It specifically focuses on novel biomarkers under investigation and highlights areas for future research.
SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Xiaoxi Xie, Chong Geng, Xiao Li, Juan Liao, Yanni Li, Yaoyu Guo, Chunhui Wang
Summary: The intestinal barrier is a dynamic multilayer system that prevents the passage of harmful substances into the body and maintains the normal development of the gut barrier and the immune system. Gut barrier damage is associated with various intestinal and extraintestinal diseases. Gastrointestinal peptides, such as somatostatin and vasoactive intestinal peptide, play a crucial role in regulating the intestinal barrier by enhancing epithelial barrier activity and restoring gut barrier function.
Review
Pharmacology & Pharmacy
Birte Ohm, Isabelle Moneke, Wolfgang Jungraithmayr
Summary: CD26/DPP4 plays a significant role in fibroproliferative disorders, and inhibiting CD26/DPP4 can reduce fibrotic changes. CD26/DPP4 inhibitors have the potential to be an effective treatment for fibrosis and have been proven to be safe in clinical use.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Immunology
Anastasios D. Giannou, Jan Kempski, Ahmad Mustafa Shiri, Joran Luecke, Tao Zhang, Lilan Zhao, Dimitra E. Zazara, Filippo Cortesi, Kristoffer Riecken, Maria Carolina Amezcua Vesely, Jun Siong Low, Hao Xu, Eleanna Kaffe, Laura Garcia-Perez, Theodora Agalioti, Yoshito Yamada, Wolfgang Jungraithmayr, Ehud Zigmond, Karl-Frederick Karstens, Babett Steglich, Jonas Wagner, Leonie Konczalla, Antonella Carambia, Kornelius Schulze, Johann von Felden, Peter May, Daria Briukhovetska, Tanja Bedke, Leonie Brockmann, Sarah Starzonek, Tobias Lange, Claudia Koch, Sabine Riethdorf, Penelope Pelczar, Marius Boettcher, Morsal Sabihi, Francis J. Huber, Matthias Reeh, Julia Kristin Grass, Ramez Wahib, Hannes Seese, Bjorn-Ole Stueben, Mohammad Fard-Aghaie, Anna Dupree, Pasquale Scognamiglio, Gabriel Plitzko, Jan Meiners, Shiwa Soukou, Agnes Wittek, Caroline Manthey, Ioannis C. Maroulis, Petra C. Arck, Daniel Perez, Bin Gao, Sotirios G. Zarogiannis, Till Strowig, Renata Pasqualini, Wadih Arap, Javier Suarez Gosalvez, Sebastian Kobold, Immo Prinz, Andreas H. Guse, Michael Tachezy, Tarik Ghadban, Asmus Heumann, Jun Li, Nathaniel Melling, Oliver Mann, Jakob R. Izbicki, Klaus Pantel, Udo Schumacher, Ansgar W. Lohse, Richard A. Flavell, Nicola Gagliani, Samuel Huber
Summary: During metastasis, cancer cells go through a series of steps including invasion, intravasation, circulation, extravasation, and colonization of target organs. This study investigated the role of interleukin (IL)-22 in metastasis and found that IL-22 promotes metastasis through its action on endothelial cells and induction of endothelial aminopeptidase N. IL-22-producing iNKT cells were identified as a source of IL-22 and were shown to be tissue resident. Thus, IL-22 may be a potential therapeutic target for preventing metastasis.
Review
Biochemistry & Molecular Biology
Aiva Plotniece, Arkadij Sobolev, Claudiu T. Supuran, Fabrizio Carta, Fredrik Bjoerkling, Henrik Franzyk, Jari Yli-Kauhaluoma, Koen Augustyns, Paul Cos, Linda De Vooght, Matthias Govaerts, Juliana Aizawa, Paeivi Tammela, Raivis Zalubovskis
Summary: Natural products and analogues are valuable sources for the discovery of antibacterial drugs. The identification of bacterial metalloenzymes and the synthesis of selective inhibitors are interesting for the development of antibacterial agents due to increasing drug resistance. Peptide nucleic acids represent a novel strategy for targeting pathogens through antisense inhibition and development of antisense peptide nucleic acids. The review also discusses alternative therapeutic options and optimized in vitro and in vivo models for studying biofilm-related infections along with an overview of drug delivery nanosystems.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Cardiac & Cardiovascular Systems
Isabelle Moneke, Ecem Deniz Ogutur, Johannes Kalbhenn, Ina Hettich, Bernward Passlick, Wolfgang Jungraithmayr, Omer Senbaklavaci
Summary: This study retrospectively analyzed the medical records of 221 lung transplant recipients and found a high incidence of thromboembolism (TE) after lung transplantation (LTX). Independent predictors for TE included a BMI > 25 and age > 55, as well as cardiovascular risk factors closely associated with the metabolic syndrome. These findings highlight the need for intensified research to assess the risks and benefits of regular screening or prolonged TE prophylaxis in these patients.
JOURNAL OF THROMBOSIS AND THROMBOLYSIS
(2023)
Article
Chemistry, Multidisciplinary
Alba Ramos-Llorca, Lisse Decraecker, Valerie M. Y. Cacheux, Irena Zeiburlina, Michelle De Bruyn, Louise Battut, Carlos Moreno-Cinos, Davide Ceradini, Eric Espinosa, Gilles Dietrich, Maya Berg, Ingrid De Meester, Pieter van der Veken, Guy Boeckxstaens, Anne-Marie Lambeir, Alexandre Denadai-Souza, Koen Augustyns
Summary: Activity-based probes (ABP) are valuable tools for target identification and drug discovery. In this study, novel activity-based probes targeting serine proteases were synthesized and characterized. A library of probes with diverse chemical structures was developed, and their inhibitory potency and kinetic profile on a panel of serine proteases were determined. Surprisingly, reversible inhibitory mechanisms were observed for some of the high-affinity probes, challenging the conventional view of irreversible probes. This unexpected finding expands the potential applications of activity-based probes in proteomic studies and drug discovery.
FRONTIERS IN CHEMISTRY
(2023)
Review
Oncology
Birte Ohm, Wolfgang Jungraithmayr
Summary: Treatment options for advanced thymic malignancies are limited. Immune checkpoint inhibitors are effective against thymic epithelial tumors, but carry a high risk of adverse events. This article aims to provide new insights on predictive markers for treatment efficacy and risk of adverse events, allowing for safe and precise clinical indications for immunotherapy in thymic malignancies.
Article
Pharmacology & Pharmacy
Anusha Balla, Bao Tran, Annika Valtari, Philipp Steven, Camilla Scarpellini, Koen Augustyns, Arto Urtti, Kati-Sisko Vellonen, Marika Ruponen
Summary: In this study, the positive effect of a novel ferroptosis inhibitor, UAMC-3203, on corneal epithelial wound healing was investigated using in vitro and ex vivo models. The drug solution at a concentration of 100 μM showed no toxicity when applied topically in rats for 5 days. Furthermore, the distribution of UAMC-3203 in the cornea revealed significantly higher concentration in the epithelium compared to the stroma.
Article
Peripheral Vascular Disease
Pauline Puylaert, Lynn Roth, Melissa Van Praet, Isabel Pintelon, Catalina Dumitrascu, Alexander van Nuijs, Greta Klejborowska, Pieter-Jan Guns, Tom Vanden Berghe, Koen Augustyns, Guido R. Y. De Meyer, Wim Martinet
Summary: IP angiogenesis is a key feature in the development of atherosclerotic plaques. Erythrophagocytosis-induced ferroptosis during IP angiogenesis leads to larger atherosclerotic plaques, which can be prevented by the ferroptosis inhibitor UAMC-3203.
Article
Biochemistry & Molecular Biology
Yang Zheng, Susanne Schroeder, Georgi K. Kanev, Sanaa S. Botros, Samia William, Abdel-Nasser A. Sabra, Louis Maes, Guy Caljon, Carmen Gil, Ana Martinez, Irene G. Salado, Koen Augustyns, Ewald Edink, Maarten Sijm, Erik de Heuvel, Iwan J. P. de Esch, Tiffany van der Meer, Marco Siderius, Geert Jan Sterk, David Brown, Rob Leurs
Summary: This study investigated the potential of Schistosoma mansoni phosphodiesterase SmPDE4A as a new drug target for schistosomiasis. The researchers cloned, isolated, and characterized the full-length and catalytic domains of SmPDE4A. They found that SmPDE4A resembles human PDE4 more than parasite PDEs. Screening of PDE inhibitors identified tetrahydrophthalazinones and benzamides as potential hits, but further evaluation showed that the inhibitors were not effective against S. mansoni, suggesting that SmPDE4A is not a suitable target for anti-schistosomiasis therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Yoshito Yamada, Tuan Thanh Nguyen, Daniela Impellizzieri, Katsutaka Mineura, Rintaro Shibuya, Alvaro Gomariz, Martina Haberecker, Jakob Nilsson, Cesar Nombela-Arrieta, Wolfgang Jungraithmayr, Onur Boyman
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Camilla Scarpellini, Sophie Valembois, Kenneth Goossens, Mike Vadi, Caroline Lanthier, Greta Klejborowska, Pieter Van der Veken, Hans De Winter, Mathieu J. M. Bertrand, Koen Augustyns
Summary: RIPK1 is a key driver of inflammation and its activity indirectly promotes inflammation by triggering cell death. Researchers have optimized the structure of GSK'157 to develop a novel class of more selective RIPK1 inhibitors.
FRONTIERS IN CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Emily Van San, Angela C. C. Debruyne, Geraldine Veeckmans, Yulia Y. Y. Tyurina, Vladimir A. A. Tyurin, Hao Zheng, Sze Men Choi, Koen Augustyns, Geert van Loo, Bernhard Michalke, Vivek Venkataramani, Shinya Toyokuni, Huelya Bayir, Peter Vandenabeele, Behrouz Hassannia, Tom Vanden Berghe
Summary: Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by CNS demyelination and neurological deficits. The study reveals that ferroptosis, a form of cell death, contributes to the progression of MS. Inhibiting ferroptosis can delay disease relapse and improve disease progression in a preclinical model of MS.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Chemistry, Medicinal
Siham Benramdane, Joni De Loose, Nicolo Filippi, Margarida Espadinha, Olivier Beyens, Yentl Van Rymenant, Laura Dirkx, Murat Bozdag, Pim-Bart Feijens, Koen Augustyns, Guy Caljon, Hans De Winter, Ingrid De Meester, Pieter van der Veken
Summary: Selective inhibitors of DPP9, compounds 42 and 47, were discovered with high selectivity indices. These inhibitors are important for studying the role of DPP9 in inflammatory cell death and for potential therapeutics for acute myeloid leukemias.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Karuna Adhikari, Jonatan Dewulf, Christel Vangestel, Pieter van der Veken, Sigrid Stroobants, Filipe Elvas, Koen Augustyns
Summary: This study developed a series of fast-reacting fluorinated d-TCO derivatives and successfully achieved tumor-specific visualization through a pretargeted blocking approach. However, further optimization of the radiotracer is needed to enhance the tumor-to-background ratios for pretargeted imaging.
Meeting Abstract
Cardiac & Cardiovascular Systems
I. Moneke, J. Burkle, E. Pfaffendorf, P. Bronsert, G. Zissel, S. Faendrich, B. Passlick, S. Diederichs, W. Jungraithmayr
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2023)