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Amniotic fluid stem cell extracellular vesicles as a novel fetal therapy for pulmonary hypoplasia: a review on mechanisms and translational potential.
Stem Cells Transl Med
January 2025
Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON, Canada M5G 0A4.
Disruption of developmental processes affecting the fetal lung leads to pulmonary hypoplasia. Pulmonary hypoplasia results from several conditions including congenital diaphragmatic hernia (CDH) and oligohydramnios. Both entities have high morbidity and mortality, and no effective therapy that fully restores normal lung development.
View Article and Find Full Text PDFPostnatal management of preterm infants with congenital diaphragmatic hernia.
Pediatr Surg Int
January 2025
Division of Neonatology, The Hospital for Sick Children, Toronto, ON, Canada.
Introduction: Congenital diaphragmatic hernia (CDH) in the preterm population is increasingly common in the current era of fetal endoluminal tracheal occlusion (FETO) therapy. There remains a lack of clinical guidance for clinicians and surgeons regarding optimal management strategies for such infants. We aimed to describe our experience in managing preterm CDH in a single quaternary neonatal intensive care unit (NICU).
View Article and Find Full Text PDFArtificial womb technology - A more physiologic solution to treating extreme prematurity.
Eur J Obstet Gynecol Reprod Biol X
March 2025
Department of Surgery, Duke University, Durham, NC, USA.
Treatment of extreme premature infants (EPI) is limited by developmental immaturity primarily of the lung. A paradigm shift towards a more physiologic treatment of EPI as fetal neonates or , by keeping them in a womb-like environment to allow continued organ maturation, is the rationale for artificial womb technology. In this review, we discuss the artificial placenta and womb technology, it's rationale, the history of its development, the most recent preclinical models described in the literature and finally pertinent ethical considerations.
View Article and Find Full Text PDFAlveolar type 2 (AT2) cells maintain lung health by acting as stem cells and producing pulmonary surfactant. AT2 dysfunction underlies many lung diseases, including interstitial lung disease (ILD), in which some inherited forms result from the mislocalization of surfactant protein C (SFTPC) variants. Lung disease modeling and dissection of the underlying mechanisms remain challenging due to complexities in deriving and maintaining human AT2 cells ex vivo.
View Article and Find Full Text PDFMutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans.
J Exp Med
February 2025
Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.
IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features.
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