Urolithin A as a Potential Drug for the Treatment of Spinal Cord Injuries: A Mechanistic Study Using Network Pharmacology Approaches.

Objective: This research was focused to examine the potential targets, action network, and mechanism of urolithin A (UA) in spinal cord injury (SCI) management exploiting the network pharmacology (NP). Methods: We used the SwissTargetPrediction, PharmMapper, and TargetNet databases to obtain UA action targets. We searched the OMIM, GeneCards, CTD, and DrugBank databases to screen selected target genes for SCI treatment. The intersection of target genes between the UA and SCI databases was obtained by constructing Venn diagrams, which led to the identification of common druggable targets for the disease. The relationship network of the targets was built with Cytoscape 3.7.2, and the protein interaction network was analyzed with the STRING platform. The protein-protein interaction (PPI) network can be built on the STRING database. Gene Ontology (GO) function and KEGG pathway analyses of target intersections were completed with the DAVID 6.8 database. We constructed preliminary network targets for actions underlying UA-SCI interactions. Using the AutoDock software, we examined the molecular docking interactions between UA and its target proteins and further verified the mechanism of the action of UA. Results: We obtained 318 UA drug targets and 1492 SCI disease targets. We identified a total of 118 common UA-SCI targets. Based on the PPI analysis, we identified MAPK1, SRC, AKT1, HRAS, MAPK8, HSP90AA1, MAPK14, JAK2, ESR1, and NF-κB1 as possible therapeutic targets. Enrichment analysis revealed that the PI3K-AKT, VEGF, and TNF signaling pathways could be critical for the NP analysis. Molecular docking indicated that UA had a strong affinity for docked proteins (binding energy range: -6.3 to -9.3 kcal mol-1). Conclusions: We employed an NP approach to validate and predict the underlying mechanisms associated with UA therapy for SCI. An additional purpose of this study was to provide a theoretical basis for further experimental studies on UA's potential in SCI treatment.

Near-infrared-II photothermal ultra-small carbon dots promoting anticancer efficiency by enhancing tumor penetration.

Because of the particular environment of the tumor microenvironment, improving the deep penetration of drugs in tumor sites is a critical problem to improve the therapeutic effect of the tumor. The ultra-small nanoparticles can achieve deep tumor tissue penetration without modification, which shows tremendous significance in tumor therapy. In this work, the ultra-small permeable carbon dots (PCD) have been developed with near-infrared-II (NIR-II) window photothermal irradiation and good biocompatibility. These PCD showed multi-color fluorescence under visible light and photoacoustic signals under an excitation of 808 nm, guiding fluorescence and photoacoustic imaging for location and distribution in vitro and vivo. The PCD could penetrate the deep tissue in tumor spheroids and tissues. Meanwhile, the irradiated depth of the NIR-II window can provide sufficient photothermal energy with the deep penetration of PCD in tumor tissue to cause tumor ablation. Therefore, this PCD can be used as a safe, fluorescent, and photoacoustic imaging agent for guided NIR-II photothermal tumor therapy, which provides a new direction for the use of ultra-small carbon dots in anticancer therapy in the future.

Porous Organic Polymer-Coated Band-Aids for Phototherapy of Bacteria-Induced Wound Infection.

Band-Aids have been widely used for wound care. For most adhesive bandages, however, they have a limited capacity to speed up the wound healing process, which in turn may cause serious wound infections. In this study, antibacterial Band-Aids, combining porphyrin-based porous organic polymers (POPs) with commercial antibiotic-free Band-Aids, are designed. Under white light irradiation, POPs can produce effective photothermal heat, as well as highly reactive oxygen species (ROS), thereby triggering the potent hyperthermia and simultaneous ROS increase on wounds. Additionally, white light is similar to sunlight, which makes POP-based Band-Aids (PBAs) ideal wound dressings for wound disinfection.