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Background: The main causes of abnormal white matter development (periventricular leukomalacia) in premature infants are perinatal inflammation and the consequent oxidant/antioxidant imbalance in oligodendrocyte precursor cells (OPCs); however, the underlying mechanisms remain largely unclear. In this work, a rat model of prenatal inflammation was used to examine the mechanism by which artemisinin (ART) protects against white matter dysplasia.
Methods: We established a primary OPC model and rat model of perinatal inflammation. ART was identified from the FDA-approved medicinal chemical library to be beneficial for treating OPC inflammation in model systems. Based on bioinformatics analysis of protein interactions and molecular docking analysis, we further identified the possible targets of ART and evaluated its specific effects and the underlying molecular mechanisms in vivo and in vitro.
Results: Following inflammatory stimulation, ART strongly promoted the maturation of OPCs and the development of white matter in the brain. A Cellular thermal shift assay (CETSA) demonstrated that interleukin-1 receptor-associated kinase-4 (IRAK-4) and interleukin-1 receptor-associated kinase-1 (IRAK-1) may be targets of ART, which was consistent with the findings from molecular modelling with Autodock software. Experiments conducted both in vivo and in vitro demonstrated the activation of the IRAK-4/IRAK-1/nuclear factor kappa-B (NF-κB) pathway and the production of inflammatory factors (IL-1β, IL-6, and TNF-α) in OPCs were greatly suppressed in the group treated with ART compared to the lipopolysaccharide (LPS)-treated group. Moreover, ART dramatically decreased reactive oxygen species (ROS) levels in OPCs while increasing nuclear factor e2-related factor 2 (Nrf2) levels.
Conclusion: Our findings suggest that ART can significantly reduce OPC perinatal inflammation and consequent oxidative stress. The targeted inhibition of IRAK-4 and IRAK-1 by ART may be a potential therapeutic strategy for alleviating abnormalities in white matter development in premature newborns.
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http://dx.doi.org/10.1016/j.intimp.2024.113117 | DOI Listing |
Lancet Reg Health Eur
February 2025
Department of General Paediatrics, Paediatric Internal Medicine, Rheumatology and Infectious Diseases, National Reference Centre for Rare Paediatric Inflammatory Rheumatisms and Systemic Autoimmune Diseases (RAISE), Robert-Debré University Hospital, Assistance Publique-Hôpitaux de Paris, F-75019, Paris, France.
Background: Scurvy, historically rare in-high income countries, has re-emerged as an indicator of socioeconomic and dietary disparities. Limited data exist on scurvy trends among European children, particularly following socioeconomic changes since the COVID-19 pandemic. This study analysed scurvy incidence trends among French children over a nine-year period, examining potential post-pandemic increases.
View Article and Find Full Text PDFJ Transl Med
December 2024
Department of Anesthesiology, West China Second University Hospital, Sichuan University, No. 20, Section 3, South of Renmin Road, Chengdu, 610041, Sichuan, China.
Background: Preterm birth, a leading cause of perinatal mortality and morbidity, is often associated with inflammation and aberrant myometrial contractions. This study investigates the role of Piezo1, a mechanosensitive ion channel, in myometrium contraction and inflammation-associated preterm birth.
Methods: We employed Western blotting, Immunofluorescence, and Quantitative real-time PCR techniques to examine Piezo1 expression in uterine tissues.
Mol Neurobiol
December 2024
Department of Pediatrics, the Second School of Medicine, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
White matter injury (WMI) is a common complication of preterm birth, potentially resulting in long-term behavioral and motor abnormalities. The objective of this study is to investigate the neuroprotective effects of glycyrrhizin (GLY) on WMI, and try to elucidate the potential mechanisms. In vivo chronic hypoxia-induced WMI mouse model and in vitro oxygen-glucose deprivation (OGD) induced WMI cell model were established, and the effects of GLY on WMI were explored through multiple assays, such as western blotting, immunofluorescence, immunohistochemistry, behavioral experiments, real-time quantitative polymerase chain reaction (RT-qPCR), transmission electron microscope (TEM), molecular docking, and bioinformatics analysis.
View Article and Find Full Text PDFIntensive Care Med Exp
December 2024
Department of Anesthesiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan.
Background: Sepsis is commonly associated with acute respiratory distress syndrome (ARDS). Although the exaggerated inflammation may damage intact lung tissues, a percentage of patients with ARDS are reportedly immunocompromised, with worse outcomes. Herein, using a murine sepsis model, time-course immune reprogramming after sepsis was evaluated to explore whether the host is immunocompromised.
View Article and Find Full Text PDFEur J Obstet Gynecol Reprod Biol
December 2024
Maternal-Fetal Medicine Unit, Department of Obstetrics, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Chorioamnionitis is a significant contributor to non-hypoxic fetal compromise, increasing the risk of neonatal encephalopathy and cerebral palsy. This paper highlights the limitations of traditional diagnostic methods for chorioamnionitis, which rely on histopathology, microbiology, and clinical signs, and emphasizes the importance of recognizing the fetal inflammatory response using intrapartum cardiotocography (CTG). By understanding the physiological pathways of inflammation, clinicians can identify characteristic CTG patterns.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!