An injectable chitosan-based hydrogel incorporating carbon dots with dual enzyme-mimic activities for synergistically treatment of bacteria infected wounds.

Bacterial infections pose a serious threat to human health, and the emergence of superbugs and the growing antibiotic resistance phenomenon have made the development of novel antimicrobial products. In this paper, an ultrasmall Cu, N co-doped carbon dots (CDs-Cu-N) with excellent peroxidase mimic activity and enhanced catalase mimic activity was successfully prepared and anchored to an injectable chitosan (CS)-based hybrid hydrogel. As expected, the CDs-Cu-N-H2O2-CS hybrid hydrogel maintains the excellent enzyme-mimicking properties of CDs-Cu-N and shows superior antibacterial property, which has been proven to effectively promote the healing of S. aureus-infected wounds with good biocompatibility. Benefitting from the dual-enzyme-mimic activity of CDs-Cu-N, the hybrid hydrogel not only can catalyze the generation of highly toxic ROS from low concentration of H2O2 to inhibit the bacterial infections, but also can significantly promote the wound tissue repair and regeneration by improving the anoxic microenvironment and promoting neovascularization. In addition, this hybrid hydrogel also possessed excellent injectability and moldability. It can adapt to various the irregular shapes of acute wounds, maintaining a moist and safe microenvironment while prolonging the action time of nanozyme on wounds, thus promoting wound healing. This injectable hybrid hydrogel shows great potential applications in the field of wound infection management.

Bao Yuan decoction alleviates fatigue by restraining inflammation and oxidative stress via the AMPK/CRY2/PER1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Baoyuan Decoction (BYD) was initially recorded in the classic of "Bo Ai Xin Jian" in the Ming dynasty. It is traditionally used for treating weakness and cowardice, and deficiency of vital energy. In researches related to anti-fatigue effects, the reciprocal regulation of AMPK and circadian clocks likely plays an important role in anti-fatigue mechanism, while it has not yet been revealed. Therefore, we elucidated the anti-fatigue mechanism of BYD through AMPK/CRY2/PER1 pathway. AIM OF THE STUDY: To investigate the effect and mechanism of BYD in reducing fatigue, using pharmacodynamics, network pharmacology and transcriptomics through the AMPK/CRY2/PER1 signaling pathway. MATERIALS AND METHODS: Firstly, the chemical constituents of BYD were qualitatively identified by UHPLC-Q-Exactive Orbitrap/MS, establishing a comprehensive strategy with an in-house library, Xcalibur software and Pubchem combined. Secondly, a Na2SO3-induced fatigue model and 2,2'-Azobis (2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stress model were developed to evaluate the anti-fatigue and anti-oxidant activities of BYD using AB zebrafish. The anti-inflammatory activity of BYD was evaluated using CuSO4-induced and tail cutting-induced Tg (lyz: dsRed) transgenic zebrafish inflammation models. Then, target screening was performed by Swiss ADME, GeneCards, OMIM and DrugBank databases, the network was constructed using Cytoscape 3.9.0. Transcriptome and network pharmacology technology were used to investigate the related signaling pathways and potential mechanisms after treatment with BYD, which were verified by real-time quantitative PCR (RT-qPCR). RESULTS: In total, 114 compounds from the water extract of BYD were identified as major compounds. Na2SO3-induced fatigue model and AAPH-induced oxidative stress model indicated that BYD has significant anti-fatigue and antioxidant effects. Meanwhile, BYD showed significant anti-inflammatory effects on CuSO4-induced and tail cutting-induced zebrafish inflammation models. The KEGG result of network pharmacology showed that the anti-fatigue function of BYD was mainly effected through AMPK signaling pathway. Besides, transcriptome analysis indicated that the circadian rhythm, AMPK and IL-17 signaling pathways were recommended as the main pathways related to the anti-fatigue effect of BYD. The RT-qPCR results showed that compared with a model control group, the treatment of BYD significantly elevated the expression mRNA of AMPK, CRY2 and PER1. CONCLUSION: Herein, we identified 114 chemical constituents of BYD, performed zebrafish activity validation, while demonstrated that BYD can relieve fatigue by AMPK/CRY2/PER1 signaling pathway through network pharmacology and transcriptome.