Article
Hematology
Melanie E. Fields, Amy E. Mirro, Michael M. Binkley, Kristin P. Guilliams, Josiah B. Lewis, Slim Fellah, Yasheng Chen, Monica L. Hulbert, Hongyu An, Andria L. Ford, Jin-Moo Lee
Summary: This study found that children with sickle cell anemia (SCA) experience elevated oxygen extraction fraction (OEF) in the whole brain compared to anemic controls (AC) and healthy controls (HC). After controlling for the impact of anemia, SCA patients still show higher OEF levels, indicating that there may be other pathophysiological factors contributing to cerebral metabolic stress in these children.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Chemistry, Medicinal
Zheng-Sheng Lai, Teng-Kuang Yeh, Yu-Chi Chou, Tsu Hsu, Cheng-Tai Lu, Fang-Chun Kung, Ming-Yen Hsieh, Chun-Hung Lin, Chiung-Tong Chen, Che-Kun James Shen, Weir-Torn Jiaang
Summary: A more potent inducer, compound 13a, was discovered in this study, which can efficiently induce gamma-globin gene expression at non-cytotoxic concentrations and ameliorate anemia and related symptoms in SCD mice through oral administration.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Neha Kargutkar, Madhavi Sawant-Mulay, Priya Hariharan, S. Chandrakala, Anita Nadkarni
Summary: Hydroxyurea (HU) is beneficial in sickle cell anaemia (SCA) patients by increasing foetal haemoglobin (HbF), but the response varies. The role of miRNA in HbF regulation has been minimally investigated. In this study, miRNA expression and HbF induction were evaluated in relation to HU therapy. After 3 months of HU therapy, HbF levels increased significantly. Several miRNAs were up-regulated or down-regulated after HU therapy, and certain miRNAs were strongly associated with HbF induction. The study suggests that miR-210, miR16-1, miR-29a, and miR-96 play a role in regulating the gamma-globin gene and HbF induction.
SCIENTIFIC REPORTS
(2023)
Review
Chemistry, Medicinal
Annamaria Aprile, Silvia Sighinolfi, Laura Raggi, Giuliana Ferrari
Summary: Research in the last decade has shown multiple alterations of the BM niche in beta-thalassemia and sickle cell disease, emphasizing the importance of understanding the interaction between HSC biology and the BM microenvironment in improving clinical outcomes of transplantation.
Article
Pediatrics
Asmaa M. Zahran, Khaled Saad, Khalid Elsayh, Shaimaa M. Khalaf, Khaled Hashim Mahmoud, Amira Elhoufey, Helal F. Hetta
Summary: Among children with SCD, HU treatment exhibited significant qualitative and quantitative effects on Tregs. HU treatment in SCD decreases the frequency of Tregs, as well as the levels of the most suppressive Tregs: HLA-DR+, CD39+, and CD69+. At the same time, HU increases the proportion of naive CD45RA+ Tregs. Our study showed the impact of HU therapy on Tregs in children with SCD.
PEDIATRIC RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Anoosha Habibi, Giovanna Cannas, Pablo Bartolucci, Ersi Voskaridou, Laure Joseph, Emmanuelle Bernit, Justine Gellen-Dautremer, Corine Charneau, Stephanie Ngo, Frederic Galacteros
Summary: Sickle cell disease is a group of inherited hemoglobin disorders characterized by altered deformability of red blood cells and various complications. Hydroxyurea is a major therapeutic agent for sickle cell patients, but its safety during pregnancy is not well-established. This study aims to describe pregnancy outcomes in the European Sickle Cell Disease COhoRT-HydroxyUrea study and share the results with the scientific community.
Review
Biochemistry & Molecular Biology
Rayan Bou-Fakhredin, Lucia De Franceschi, Irene Motta, Assaad A. Eid, Ali T. Taher, Maria Domenica Cappellini
Summary: Beta-thalassemia and sickle cell disease lead to variations in hemoglobin, which affect the oxidative environment. Oxidative stress plays a significant role in these diseases, causing cellular damage. This review summarizes the mechanisms and therapeutic strategies of oxidative stress in these diseases, and discusses the role of targeted therapy.
Article
Multidisciplinary Sciences
Kongtana Trakarnsanga, Nontaphat Thongsin, Chanatip Metheetrairut, Chartsiam Tipgomut, Saiphon Poldee, Methichit Wattanapanitch
Summary: Beta-thalassaemia is a common genetic blood disease with over 300 mutations in the HBB gene, and recent advances in gene editing technology have provided a new approach for its treatment. The efficient genetic correction of HbE mutation in unique SiBBE cells offers an important research model for disease therapy validation.
SCIENTIFIC REPORTS
(2022)
Article
Hematology
Shehu U. Abdullahi, Surayya Sunusi, Mohammed Sani Abba, Saifuddeen Sani, Hauwau Aminu Inuwa, Safiya Gambo, Awwal Gambo, Bilya Musa, Brittany V. Covert Greene, Adetola A. Kassim, Mark Rodeghier, Nafiu Hussaini, Mariana Ciobanu, Muktar H. Aliyu, Lori C. Jordan, Michael R. DeBaun
Summary: This study investigated the effectiveness of fixed oral moderate-dose hydroxyurea compared with fixed oral low-dose hydroxyurea for secondary stroke prevention in children with sickle cell anemia. The results showed that there was no evidence to support the superiority of moderate-dose hydroxyurea in reducing the risk of stroke or death compared to low-dose hydroxyurea.
Review
Medicine, General & Internal
Raffaella Colombatti, Inga Hegemann, Morten Medici, Camilla Birkegard
Summary: Sickle cell disease is a genetic disorder with a high prevalence in sub-Saharan Africa, the Mediterranean basin, the Middle East, and India. A systematic literature review identified 115 publications on SCD epidemiology, showing highest prevalence in Africa, the Middle East, and India, and lowest in Europe. The study revealed a lack of systematic knowledge and the need for uniform data collection on SCD prevalence and mortality.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Akancha Pandey, Jeremie H. Estepp, Rubesh Raja, Guolian Kang, Doraiswami Ramkrishna
Summary: This study developed pharmacokinetics and pharmacodynamics models to investigate the dosing and efficacy of hydroxyurea treatment in children with sickle cell disease (SCD). The models provided excellent fits for individuals with known or correctly inferred adherence, and can be used to determine optimal dosing regimens and study the impact of non-adherence on treatment outcomes.
Review
Biochemistry & Molecular Biology
Pagona Flevari, Ersi Voskaridou, Frederic Galacteros, Giovanna Cannas, Gylna Loko, Laure Joseph, Pablo Bartolucci, Justine Gellen-Dautremer, Emmanuelle Bernit, Corine Charneau, Anoosha Habibi
Summary: This article reports a case of myelodysplastic syndrome and highlights the lack of significant conclusions due to the scarcity of similar cases.
Article
Chemistry, Multidisciplinary
Abhishek Gour, Pankul Kotwal, Ashish Dogra, Dilpreet Kour, Sumit Dhiman, Amit Kumar, Sanjeev Kumar Digra, Ajay Kumar, Gurdarshan Singh, Utpal Nandi
Summary: Andrographolide shows significant antisickling activity and may be a potential adjuvant therapy for sickle cell anemia. However, caution should be taken when used concomitantly with hydroxyurea.
Article
Hematology
Andrew M. Heitzer, Jennifer Longoria, Victoria Okhomina, Winfred C. Wang, Darcy Raches, Brian Potter, Lisa M. Jacola, Jerlym Porter, Jane E. Schreiber, Allison A. King, Guolian Kang, Jane S. Hankins
Summary: Neurocognitive impairment is common in sickle cell disease, and this study found that older age was associated with a decrease in overall intelligence quotient for patients with HbSS/HbS beta(0)-thalassaemia. Early initiation of hydroxyurea treatment was associated with higher neurocognitive scores across most domains, suggesting its potential in limiting the detrimental effects of SCD on cognitive functions.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Surgery
Alicia D. Menchaca, Candace C. Style, Anthony D. Villella, Maria Burdjalov, Tariku J. Beyene, Peter C. Minneci, Oluyinka O. Olutoye
Summary: This study investigated the association between hydroxyurea therapy and the need for surgical splenectomy in patients with sickle cell disease (SCD). The results showed that patients receiving hydroxyurea had a higher rate of surgical splenectomy and underwent the procedure at a younger age. These findings provide useful information for clinicians and patients.
JOURNAL OF SURGICAL RESEARCH
(2023)
Article
Oncology
Iris S. C. Verploegh, Andrea Conidi, Rutger W. W. Brouwer, Hayri E. Balcioglu, Panagiotis Karras, Samira Makhzami, Anne Korporaal, Jean-Christophe Marine, Martine Lamfers, Wilfred F. J. van IJcken, Sieger Leenstra, Danny Huylebroeck
Summary: This study characterized the cell viability of patient-derived GBM cultures in response to BMP4 and identified predictive markers for sensitivity to BMP4 using single-cell transcriptome profiling. The changes in composition of GBM cultures after BMP4 treatment correlated with treatment efficacy, with OLIG1/2 expression serving as a predictor and upregulation of RPL27A and RPS27 serving as useful early-response markers.
Article
Cell & Tissue Engineering
Anusha S. Shankar, Zhaoyu Du, Hector Tejeda Mora, Ruben Boers, Wanlu Cao, Thierry P. P. van den Bosch, Sander S. Korevaar, Joachim Boers, Wilfred F. J. van IJcken, Eric M. J. Bindels, Bert Eussen, Annelies de Klein, Qiuwei Pan, Lindsey Oudijk, Marian C. Clahsen-van Groningen, Ewout J. Hoorn, Carla C. Baan, Joost Gribnau, Martin J. Hoogduijn
Summary: Kidney organoids derived from induced pluripotent stem cells (iPSCs) have the potential for kidney tissue regeneration, but their long-term safety and stability raise concerns. This study found that kidney organoids can form tumors upon long-term implantation, possibly due to the presence of epigenetic modifications and arrested terminal differentiation.
Article
Biology
Job van Riet, Chinmoy Saha, Nikolaos Strepis, Rutger W. W. Brouwer, Elena S. Martens-Uzunova, Wesley S. van de Geer, Sigrid M. A. Swagemakers, Andrew Stubbs, Yassir Halimi, Sanne Voogd, Arif Mohammad Tanmoy, Malgorzata A. Komor, Youri Hoogstrate, Bart Janssen, Remond J. A. Fijneman, Yashar S. Niknafs, Arul M. Chinnaiyan, Wilfred F. J. van IJcken, Peter J. van der Spek, Guido Jenster, Rogier Louwen
Summary: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) have been discovered in the human genome, termed hCRISPRs, which are expressed as small non-coding RNAs (sncRNAs) and can distinguish normal from malignant tissues. These findings suggest the potential use of hCRISPRs as diagnostic biomarkers for cancer and the development of point-of-care tests based on their differential expression.
COMMUNICATIONS BIOLOGY
(2022)
Article
Immunology
Carmen W. E. Embregts, Annelieke S. Wentzel, Alexander T. den Dekker, Wilfred F. J. van IJcken, Ralph Stadhouders, Corine H. GeurtsvanKessel
Summary: Macrophages play a crucial role in the immune response to rabies virus (RABV). This study revealed that RABV induces activation and polarization of macrophages, leading to an antiviral response. The RABV-stimulated macrophages express multiple signature genes of M1, M2a, and M2c phenotypes, and activate pathways related to interferon and antiviral response.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Microbiology
Olaf Tyc, Purva Kulkarni, Adam Ossowicki, Vittorio Tracanna, Marnix H. Medema, Peter van Baarlen, W. F. J. van IJcken, Koen J. F. Verhoeven, Paolina Garbeva
Summary: Microbial community analysis has shown that bacteria with cell sizes of about 0.1 μm are an important component of aquatic environments, but it is unknown if they exist in terrestrial environments like soil. In this study, we isolated soil bacteria that passed through a 0.1 μm filter and identified one isolate as Hylemonella gracilis. Coculture assays demonstrated that H. gracilis grows better when interacting with other soil bacteria, and transcriptomics and metabolomics revealed that H. gracilis can induce gene expression, behavior, and biochemistry changes in other bacteria without direct contact. Our findings suggest the presence of small bacteria in soil that can pass through 0.1 μm filters and contribute to the symbiosis of soil bacterial communities.
Article
Biotechnology & Applied Microbiology
Ruben Boers, Joachim Boers, Beatrice Tan, Marieke E. van Leeuwen, Evelyne Wassenaar, Erlantz Gonzalez Sanchez, Esther Sleddens, Yasha Tenhagen, Eskeatnaf Mulugeta, Joop Laven, Menno Creyghton, Willy Baarends, Wilfred F. J. van IJcken, Joost Gribnau
Summary: In this study, a bacterial methylation mark was used to label transcribed genes and active enhancers, allowing for tracking of cell state changes. This technique revealed rapid and coordinated activation of enhancers and nearby genes during enterocyte differentiation in the intestine. Furthermore, it provided insights into the chromatin landscape of intestinal stem cells and their differentiation process.
NATURE BIOTECHNOLOGY
(2023)
Article
Genetics & Heredity
Judith C. C. Birkhoff, Anne L. L. Korporaal, Rutger W. W. Brouwer, Karol Nowosad, Claudia Milazzo, Lidia Mouratidou, Mirjam C. G. N. van den Hout, Wilfred F. J. van IJcken, Danny Huylebroeck, Andrea Conidi
Summary: Functional studies have shown that Zeb2 plays a crucial role in controlling cell fate decisions and differentiation. By editing mouse embryonic stem cells, researchers were able to identify DNA-binding sites for Zeb2 and found that autoregulation of Zeb2 is necessary for proper differentiation. Furthermore, the study also provided insights into developmental disorders and monogenic syndromes.
Article
Immunology
Mandy van Gulijk, Anneloes van Krimpen, Sjoerd Schetters, Mike Eterman, Marit van Elsas, Joanne Mankor, Larissa Klaase, Marjolein de Bruijn, Menno van Nimwegen, Tim van Tienhoven, Wilfred van Ijcken, Louis Boon, Johan van der Schoot, Martijn Verdoes, Ferenc Scheeren, Sjoerd H. van der Burg, Bart N. Lambrecht, Ralph Stadhouders, Floris Dammeijer, Joachim Aerts, Thorbald van Hall
Summary: Despite the success of immune checkpoint blockade (ICB) in some cancer types, most patients do not respond well and develop resistance to ICB. This study identified enhanced suppressive capacity of regulatory T cells (T-reg cells) in therapy-resistant tumors. T-reg cell depletion reversed resistance and increased effector T cells. Similar findings were observed in human patients, suggesting that targeting T-reg cells is important to enhance therapeutic efficacy.
SCIENCE IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Iris J. M. Levink, Maurice P. H. M. Jansen, Zakia Azmani, Wilfred van IJcken, Ronald van Marion, Maikel P. Peppelenbosch, Djuna L. Cahen, Gwenny M. Fuhler, Marco J. Bruno
Summary: Molecular profiling may aid in earlier detection and personalized treatment of pancreatic cancer. This study found higher cfDNA concentration in pancreatic juice (PJ) than in plasma, but similar mutation detection rates, suggesting the need for further research on the suitability of plasma and PJ for early PC detection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Elisabeth M. Jongbloed, Maurice P. H. M. Jansen, Vanja de Weerd, Jean A. Helmijr, Corine M. Beaufort, Marcel J. T. Reinders, Ronald van Marion, Wilfred F. J. van IJcken, Gabe S. Sonke, Inge R. Konings, Agnes Jager, John W. M. Martens, Saskia M. Wilting, Stavros Makrodimitris
Summary: Next generation sequencing of cfDNA is a promising method for treatment monitoring and therapy selection in MBC. However, distinguishing tumor-specific variants from sequencing artefacts and germline variation is challenging. To address this, a machine learning model was built to remove false positive variant calls and select tumor-derived variants.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Ellis L. Eikenboom, Saskia M. Wilting, Teoman Deger, Malgorzata I. Srebniak, Monique Van Veghel-Plandsoen, Ruben G. Boers, Joachim B. Boers, Wilfred F. J. van IJcken, Joost H. Gribnau, Peggy Atmodimedjo, Hendrikus J. Dubbink, John W. M. Martens, Manon C. W. Spaander, Anja Wagner
Summary: We assessed which ctDNA assay might be most suitable for a ctDNA-based CRC screening/surveillance blood test. The results showed that cfDNA methylation profiles could discriminate all microsatellite instable advanced neoplasia, making it a particularly promising tool for Lynch syndrome surveillance. Larger studies are needed to validate these findings.
Article
Immunology
Anne Onrust-van Schoonhoven, Marjolein J. W. de Bruijn, Bernard Stikker, Rutger W. W. Brouwer, Gert-Jan Braunstahl, Wilfred F. J. van IJcken, Thomas Graf, Danny Huylebroeck, Rudi W. Hendriks, Gregoire Stik, Ralph Stadhouders
Summary: This study reveals that human CD4(+) memory T helper 2 (T(H)2) cells undergo chromatin reprogramming at both one-dimensional and three-dimensional levels to efficiently recall an inflammatory transcriptional program. Distal enhancers organized in long-range three-dimensional chromatin hubs are responsible for epigenetically priming recall genes in memory T(H)2 cells. Key recall genes are precisely controlled within dedicated topologically associating domains through activation-associated promoter-enhancer interactions mediated by AP-1 transcription factors. Aberrant transcriptional control of recall responses is linked to chronic inflammation in resting memory T(H)2 cells from asthma patients. These findings highlight the importance of stable multiscale reprogramming of chromatin organization in T cell immunological memory and dysfunction.
SCIENCE IMMUNOLOGY
(2023)
Article
Genetics & Heredity
Stavroula Siamoglou, Ruben Boers, Maria Koromina, Joachim Boers, Anna Tsironi, Theodora Chatzilygeroudi, Vasileios Lazaris, Evgenia Verigou, Alexandra Kourakli, Wilfred F. J. van IJcken, Joost Gribnau, Argiris Symeonidis, George P. Patrinos
Summary: Myelodysplastic syndromes (MDS) are a group of hematological malignancies characterized by ineffective hematopoiesis, cytogenetic abnormalities, and a high risk of transformation to acute myeloid leukemia (AML). This study used methylated DNA sequencing (MeD-seq) to identify potential epigenomic targets associated with MDS subtypes. The results identified differentially methylated CpG islands, transcription start sites, and post-transcriptional start sites within the PCDHG and ZNF gene families. These findings provide important insights into the epigenomic component of MDS pathogenesis and the potential for targeted drug treatment.
Article
Biochemistry & Molecular Biology
Amy C. J. van der List, Nicolle H. R. Litjens, Rutger W. W. Brouwer, Mariska Klepper, Alexander T. den Dekker, Wilfred F. J. van Ijcken, Michiel G. H. Betjes
Summary: After kidney transplantation, recipient T cells develop low responsiveness to donor-specific antigens over time. Apoptosis was identified as a possible underlying mechanism. This study investigated the genetic and receptor profiles of individual alloreactive T cells from kidney transplant recipients using single-cell RNA sequencing. The findings suggest that post-transplantation, donor-reactive CD4+ T cell clones preferentially undergo apoptosis in stable kidney transplant recipients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Clinical Neurology
A. Fanciulli, F. Leys, F. Lehner, V. Sidoroff, V. Ruf, C. Raccagni, P. Mahlknecht, D. Kuipers, W. van IJcken, H. Stockner, T. Musacchio, J. Volkmann, C. Monoranu, I. Stankovic, G. Breedveld, F. Ferraro, C. Fevga, O. Windl, J. Herms, S. Kiechl, W. Poewe, K. Seppi, N. Stefanova, S. Scholz, V. Bonifati, G. Wenning
MOVEMENT DISORDERS
(2022)
