Leukemia inhibitory factor (LIF) is a growth factor with pleiotropic biological functions. It has been reported that LIF acts at different stages during mesoderm development. Also, it has been shown that LIF has a cytoprotective effect on neonatal murine cardiomyocytes (CMs) in culture, but little is known about the role of LIF during human cardiogenesis. Thus, we analyzed the effects of LIF on human pluripotent stem cells (PSC) undergoing cardiac differentiation. We first showed that LIF is expressed in the human heart during early development. We found that the addition of LIF within a precise time window during the in vitro differentiation process significantly increased CMs viability. This finding was associated to a decrease in the expression of pro-apoptotic protein Bax, which coincides with a reduction of the apoptotic rate. Therefore, the addition of LIF may represent a promising strategy for increasing CMs survival derived from PSCs.
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http://dx.doi.org/10.1007/s12265-017-9769-6 | DOI Listing |
Pharmaceuticals (Basel)
January 2025
Centro de Química Médica, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7780272, Chile.
Acute myeloid leukemia (AML) presents significant therapeutic challenges, particularly in cases driven by mutations in the FLT3 tyrosine kinase. This study aimed to develop a robust and user-friendly machine learning-based quantitative structure-activity relationship (QSAR) model to predict the inhibitory potency (pIC values) of FLT3 inhibitors, addressing the limitations of previous models in dataset size, diversity, and predictive accuracy. Using a dataset which was 14 times larger than those employed in prior studies (1350 compounds with 1269 molecular descriptors), we trained a random forest regressor, chosen due to its superior predictive performance and resistance to overfitting.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Department of Surgery, University of Rochester Medical Center, Rochester, NY 14642, USA.
: Pancreatic ductal adenocarcinoma (PDAC), expecting to be the second leading cause of cancer deaths by 2030, resists immune checkpoint therapies due to its immunosuppressive tumor microenvironment (TME). Leukemia inhibitory factor (LIF) is a key target in PDAC, promoting stemness, epithelial-mesenchymal transition (EMT), and therapy resistance. Phase 1 clinical trials showed anti-LIF therapy is safe but with limited efficacy, suggesting better outcomes when combined with chemotherapy, radiotherapy, or immunotherapy.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
January 2025
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
Background: The benefit of universal CAR-T cells over autologous CAR-T cell therapy is that they are a treatment that is ready to use. However, the prevention of graft-versus-host disease (GVHD) and host-versus-graft reaction (HVGR) remains challenging. Deleting class I of human leukocyte antigen (HLA-I) and class II of human leukocyte antigen (HLA-II) can prevent rejection by allogeneic T cells; however, natural killer (NK) cell rejection due to the loss of self-recognition remains unresolved.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Laboratory of Genome Dynamics in the Immune, INSERM UMR 116, Équipe Labellisée LIGUE 2023, Paris, France.
Oncostatin M (OSM) is a cytokine with the unique ability to interact with both the OSM receptor (OSMR) and the leukemia inhibitory factor receptor (LIFR). On the other hand, OSMR interacts with IL31RA to form the interleukin-31 receptor. This intricate network of cytokines and receptors makes it difficult to understand the specific function of OSM.
View Article and Find Full Text PDFCureus
December 2024
Laboratory of Histology-Embryology, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, GRC.
Introduction: Maternal infections such as chorioamnionitis could impact fetal lung development by altering cell proliferation and apoptosis. Chorioamnionitis favors the multiple pleiotropic cytokines production such as LIF (leukemia inhibitory factor) and an inflammation-related protein p53. The cytokine production can lead to lung tissue damage and lung disease development.
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