Long-standing evidence implicates glioma stem cells (GSC) as the major driver for glioma propagation and recurrence. GSCs have a distinctive metabolic landscape characterized by elevated glycolysis. Lactate accumulation resulting from enhanced glycolytic activity can drive lysine lactylation to regulate protein functions, suggesting that elucidating the lactylation landscape in GSCs could provide insights into glioma biology. Herein, we have demonstrated that global lactylation was significantly elevated in GSCs compared with differentiated glioma cells. Polypyrimidine tract–binding protein 1 (PTBP1), a central regulator of RNA processing, was hyperlactylated in GSCs, and SIRT1 induced PTBP1 delactylation. PTBP1-K436 lactylation supported glioma progression and GSC maintenance. Mechanistically, K436 lactylation inhibited PTBP1 proteasomal degradation by attenuating the interaction with TRIM21. Moreover, PTBP1 lactylation enhanced RNA-binding capacity and facilitated PFKFB4 mRNA stabilization, which further increased glycolysis. Together, these findings uncovered a lactylation-mediated mechanism in GSCs driven by metabolic reprogramming that induces aberrant epigenetic modifications to further stimulate glycolysis, resulting in a vicious cycle to exacerbate tumorigenesis. Significance: Glycolysis-induced lactylation enhances the function of PTBP1 to promote glioma stem cell maintenance, indicating that PTBP1 lactylation could be a potential target for the development of innovative glioma therapies.

The overexpressed soluble fms-like tyrosine kinase 1 (sFLT-1) in placenta is considered to be a potential therapeutic target for preeclampsia (PE). How to achieve efficient intervention of sFLT1 expression in the placenta is an urgent problem to be solved. PEG-PLA nanoparticle generated by double-emulsion methods is a novel siRNA delivery system. Synthetic placental CSA binding peptide (P-CSA-BP) is effective for targeting lipid-polymer nanoparticle to the placenta. We conjugated P-CSA-BP to the surface of PEG-PLA nanoparticle to create a novel placenta specific sFLT1 siRNA delivery system for the therapy of PE. Nanoparticles were synthesized using double emulsion method and characterized by dynamic light scattering and transmission electron microscopy (TEM). RT-PCR was employed to evaluate mRNA level and protein level was analyzed by ELISA kit. The tissue distribution of nanoparticles was observed through ex vivo images. The concentrations of nanoparticles in organs were measured using high-performance liquid chromatography. T-NP_sisFLT1 had higher efficiency than NP_sisFLT1 in accumulating in HTR-8/SVneo cells and significantly decreased the expression of sFLT1. Intravenously administered T-NP_sisFLT1 specifically accumulated in placentas of mice. sFLT1 mRNA level in placenta and protein level in serum were declined by T-NP_sisFLT1. T-NP_sisFLT1 shown no obvious toxic effect on both mother and fetus. The utility of T-NPsisFLT1 nanoparticles as a sFLT1 siRNA placenta specific delivery system significantly silenced sFLT1 in mice and is safe for both mother and fetus. This nanoparticle is a novel potential therapeutic strategy for PE.

Ischemic stroke is one of the most severe neurological disorders with limited therapeutic strategies. The utilization of nanoparticle drug delivery systems is a burgeoning field and has been widely investigated. Among these, biomimetic drug delivery systems composed of biogenic membrane components and synthetic nanoparticles have been extensively highlighted in recent years. Biomimetic membrane camouflage presents an effective strategy to prolong circulation, reduce immunogenicity and enhance targeting. For one thing, biomimetic nanoparticles reserve the physical and chemical properties of intrinsic nanoparticle. For another, the biological functions of original source cells are completely inherited. Compared to conventional surface modification methods, this approach is more convenient and biocompatible. In this review, membrane-based nanoparticles derived from different donor cells were exemplified. The prospect of future biomimetic nanoparticles in ischemic stroke therapy was discussed.Graphic

Recurrent miscarriage (RM) is a complicated disease in reproductive medicine that impacts many families. Currently, the etiology of RM is thought to include chromosome abnormalities, reproductive tract malformations, autoimmune dysfunction, infection, and environmental factors. However, the underlying mechanisms of RM remain unknown. At present, research on long non-coding RNAs (lncRNAs) is rapidly emerging and becoming a hot research topic in epigenetic studies. Recent studies revealed that lncRNAs are strongly linked to RM and play a crucial role in epigenetic, cell cycle, cell differentiation regulation, and other life activities. This article mainly reviews the difference in lncRNA expression in patients with RM and regulation of susceptibility, endometrial receptivity, and the maternal-fetal interface. Meanwhile, the correlation between lncRNAs and RM is expounded, which provides new insights for the early diagnosis and treatment of RM.