A novel thermogel system of self-assembling peptides was created by enzyme-instructed self-assembly (EISA), which was useful for 3D cell culture.

The endothelial-mesenchymal transition (EndMT) is known to be involved in the transformation of vascular endothelial cells to mesenchymal cells. EndMT has been confirmedthat occur in various pathologic conditions. Transforming growth factor β1 (TGF-β1) is a potent stimulator of the vascular endothelial to mesenchymal transition (EMT). Aspirin-triggered resolvin D1 (ATRvD1) has been known to be involved in the resolution of inflammation,but whether it has effects on TGF-β1-induced EndMT is not yet clear. Therefore, we investigated the effects of AT-RvD1 on the EndMT of human umbilical vein vascular endothelial cells line (HUVECs). Treatment with TGF-β1 reduced the expression of Nrf2 and enhanced the level of F-actin, which is associated with paracellular permeability. The expression of endothelial marker VE-cadherin in HUVEC cells was reduced, and the expression of mesenchymal marker vimentin was enhanced. AT-RvD1 restored the expression of Nrf2 and vimentin and enhanced the expression of VE-cadherin. AT-RvD1 did also affect the migration of HUVEC cells. Inhibitory κB kinase 16 (IKK 16), which is known to inhibit the NF-kB pathway, had an ability to increase the expression of Nrf2 and was associated with the inhibition effect of AT-RvD1 on TGF-β1-induced EndMT, but it had no effect on TGF-β1-induced EndMT alone. Smad7, which is a key regulator of TGF-β/Smads signaling by negative feedback loops, was significantlyincreased with the treatment of AT-RvD1. These results suggest the possibility that AT-RvD1 suppresses the TGF-β1-induced EndMT through increasing the expression of Smad7 and is closely related to oxidative stress.

Chronic wound healing is a significant challenge in diabetes. Puerarin is an active compound extracted from the traditional Chinese medicine Pueraria lobata. Puerarin has been used in the treatment of diabetes and derives benefits from its antioxidant, anti-inflammatory, antibacterial, and pro-angiogenesis properties, but its efficacy is hampered by poor water solubility and bioavailability. In this study, we designed a polyvinyl alcohol (PVA)–borax–puerarin (BP) hydrogel system that self-assembled via boronic ester bonds. The BP hydrogel exhibited exceptional physical characteristics, including adaptability, injectability, plasticity, self-healing capabilities, and robust compressive strength, as well as good biocompatibility. In the chronic wound diabetic rats model, the BP hydrogel significantly accelerated wound healing, as evidenced by hematoxylin and eosin (HE) staining, as well as Masson and picrosirius red (PSR) staining. RNA–sequencing and multiple immunohistochemistry (mIHC) analyses revealed that the BP hydrogel exerts a therapeutic effect by modulating macrophage polarization, promoting angiogenesis, and regulating collagen remodeling. Our findings suggest that the BP hydrogel represents a promising wound dressing and holds great potential for clinical applications in acute and chronic wound management.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a malignancy characterized by the aberrant accumulation of immature B-cell precursors in bone marrow and other lymphoid organs. Although several intrinsic regulatory signals participating in BCP-ALL have been clarified, detailed intrinsic and extrinsic mechanisms that regulate BCP-ALL progression have not been fully understood. In the current study, we report that miR-582 is downregulated in BCP-ALL cells compared with normal B cells. Forced overexpression of miR-582 attenuated BCP-ALL cell proliferation and survival. We found that miR-582 overexpression disturbed the mitochondrial metabolism of BCP-ALL cells, leading to less ATP but more ROS production. Mechanistically, we identified PPTC7 as a direct target of miR-582. MiR-582 overexpression inhibited the activity of CoQ10, which is downstream of PPTC7 and played an important positive regulatory role in mitochondrial electron transportation. Finally, we found that overexpression of miR-582 upregulated the expression of immune checkpoint molecule CD276 and reduced NK cell-mediated cytotoxicity against BCP-ALL cells. CD276 blockade significantly increased NK cell-mediated cytotoxicity against miR-582-overexpressing BCP-ALL cells. Together, our research demonstrates that miR-582 acts as a negative regulator of BCP-ALL cells by reducing proliferation and survival, but protects BCP-ALL cells from NK cell-mediated cytotoxicity, suggesting that miR-582 may be a new therapeutic biomarker for BCP-ALL with CD276 blocker.

Tyroservatide (YSV), a bioactive tripeptide, holds potential as an anti-tumor agent. However, its specific effects on oral squamous cell carcinoma (OSCC) have not been elucidated. This study aims to investigate the inhibitory effects of YSV on OSCC and explore the underlying molecular mechanisms. A series of in vitro experiments were conducted to assess the impact of YSV on OSCC cell viability, colony formation, cell cycle, and apoptosis. RNA sequencing (RNA-seq), molecular docking, and western blotting were employed to investigate the molecular mechanisms. Additionally, a subcutaneous tumor model was established to validate the in vitro findings. Furthermore, PI3K inhibitors LY294002 and PI3K-IN-1, were used to confirm the role of the PTEN/PI3K/AKT pathway in YSV-mediated OSCC inhibition. Cell cycle and apoptosis were analyzed to assess the combined effect of YSV and LY294002. YSV significantly inhibited OSCC proliferation by inducing cell cycle arrest and apoptosis. RNA-seq and molecular docking revealed that YSV regulated the PTEN/PI3K/AKT signaling pathway. Western blotting confirmed the modulation of this pathway both in vitro and in vivo. The use of PI3K inhibitors, LY294002 and PI3K-IN-1, further validated the involvement of the PTEN/PI3K/AKT pathway in YSV-induced anti-tumor effects. Notably, the combination of YSV and LY294002 synergistically enhanced cell cycle arrest and apoptosis, demonstrating effective anti-tumor activity. In vivo experiments also supported these findings. YSV inhibited the progression of OSCC by promoting cell cycle arrest and apoptosis through the regulation of the PTEN/PI3K/AKT signaling pathway. The combination of YSV and PI3K inhibitors, such as LY294002, exhibited enhanced anti-tumor activity, suggesting potential therapeutic strategies for OSCC treatment.