Delivery of therapeutics to the brain is challenging because of efflux pumps located in the vascular endothelium. A detailed analysis of Wnt signaling in a human brain endothelial cell line indicates that expression and function of P-glycoprotein, a major efflux transporter, is controlled by non-canonical Wnt signaling. Inhibition of this pathway leads to downregulation of P-glycoprotein and increased transcellular drug transport and reveals a potential strategy for improving drug delivery for treatment of neurologic diseases.
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http://dx.doi.org/10.1038/jcbfm.2014.98 | DOI Listing |
Discov Oncol
January 2025
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, 563006, Guizhou, People's Republic of China.
Nonylphenol (NP) is a common environmental contaminant and endocrine disruptor. Our previous research demonstrated that NP could promote the proliferation and epithelial-mesenchymal transition (EMT) of colorectal cancer (CRC) cells; however, the specific mechanism remains unclear. miRNA sequencing revealed that NP upregulated the expression levels of microRNA(miR)-151a-3p in CRC.
View Article and Find Full Text PDFBiochem Biophys Rep
March 2025
Department of Nephrology, Pu'er People's Hospital, Pu'er, Yunnan, China.
Background: Chronic kidney disease (CKD) has become a worldwide health problem and the incidence rate and mortality of CKD have been rising. Renal fibrosis (RF) is the final common pathological feature of almost all kinds of CKD and Epithelial-mesenchymal transition (EMT) is the predominant stage of RF. β-catenin is a key component of the Wnt signaling pathway, which has been fully proven to promote EMT.
View Article and Find Full Text PDFUnlabelled: Hematopoietic stem and progenitor cells (HSPCs) arise only during embryonic development, and their identity specification, emergence from the floor of the dorsal aorta, and proliferation are all tightly regulated by molecular mechanisms such as signaling cues. Among these, Wnt signaling plays an important role in HSPC specification, differentiation, and self-renewal, requiring precise modulation for proper development and homeostasis. Wnt signaling is initiated when a Wnt ligand binds to cell surface receptors such as those encoded by the gene family, activating intracellular signaling pathways that regulate gene expression.
View Article and Find Full Text PDFDorsal-ventral patterning of neural progenitors in the posterior neural tube, which gives rise to the spinal cord, has served as a model system to understand how extracellular signals organize developing tissues. While previous work has shown that signaling gradients diversify progenitor fates at the dorsal and ventral ends of the tissue, the basis of fate specification in intermediate regions has remained unclear. Here we use zebrafish to investigate the neural plate, which precedes neural tube formation, and show that its pre-patterning by a distinct signaling environment enables intermediate fate specification.
View Article and Find Full Text PDFWhile clinical trials are ongoing using human pluripotent stem cell-derived midbrain dopamine (mDA) neuron precursor grafts in Parkinson's disease (PD), current protocols to derive mDA neurons remain suboptimal. In particular, the yield of TH+ mDA neurons after grafting and the expression of some mDA neuron and subtype-specific markers can be further improved. For example, characterization of mDA grafts by single cell transcriptomics has yielded only a small proportion of mDA neurons and a considerable fraction of contaminating cell populations.
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