Salvianolic acid B enhances tissue repair and regeneration by regulating immune cell migration and Caveolin-1-mediated blastema formation in zebrafish.

INTRODUCTION: Non-healing wounds resulting from trauma, surgery, and chronic diseases annually affect millions of individuals globally, with limited therapeutic strategies available due to the incomplete understanding of the molecular processes governing tissue repair and regeneration. Salvianolic acid B (Sal B) has shown promising bioactivities in promoting angiogenesis and inhibiting inflammation. However, its regulatory mechanisms in tissue regeneration remain unclear. PURPOSE: This study aims to investigate the effects of Sal B on wound healing and regeneration processes, along with its underlying molecular mechanisms, by employing zebrafish as a model organism. METHODS: In this study, we employed a multifaceted approach to evaluate the impact of Sal B on zebrafish tail fin regeneration. We utilized whole-fish immunofluorescence, TUNEL staining, mitochondrial membrane potential (MMP), and Acridine Orange (AO) probes to analyze the tissue repair and regenerative under Sal B treatment. Additionally, we utilized transgenic zebrafish strains to investigate the migration of inflammatory cells during different phases of fin regeneration. To validate the importance of Caveolin-1 (Cav1) in tissue regeneration, we delved into its functional role using molecular docking and Morpholino-based gene knockdown techniques. Additionally, we quantified Cav1 expression levels through the application of in situ hybridization. RESULTS: Our findings demonstrated that Sal B expedites zebrafish tail fin regeneration through a multifaceted mechanism involving the promotion of cell proliferation, suppression of apoptosis, and enhancement of MMP. Furthermore, Sal B was found to exert regulatory control over the dynamic aggregation and subsequent regression of immune cells during tissue regenerative processes. Importantly, we observed that the knockdown of Cav1 significantly compromised tissue regeneration, leading to an excessive infiltration of immune cells and increased levels of apoptosis. Moreover, the knockdown of Cav1 also affects blastema formation, a critical process influenced by Cav1 in tissue regeneration. CONCLUSION: The results of this study showed that Sal B facilitated tissue repair and regeneration through regulating of immune cell migration and Cav1-mediated fibroblast activation, promoting blastema formation and development. This study highlighted the potential pharmacological effects of Sal B in promoting tissue regeneration. These findings contributed to the advancement of regenerative medicine research and the development of novel therapeutic approaches for trauma.

Pozzolanic activity experimental dataset of calcined coal gangue.

The coal gangue in this dataset was subjected to a series of processes, including drying, crushing, and milling. Subsequently, the coal gangue powder was subjected to high-temperature calcination in a muffle furnace, with a heating rate of 4 â„ƒ/min. The pozzolanic activity of coal gangue powder was investigated at various calcination temperatures (600 â„ƒ, 700 â„ƒ, 800 â„ƒ, 900 â„ƒ) and different holding times (1h, 2h). Cement mortar specimens containing calcined coal gangue powder were prepared, and their compressive and flexural strengths were tested to evaluate the reactivity of the calcined coal gangue. In addition, the Rapid, Relevant and Reliable (R3) activity test was conducted to test the reactivity. The thermogravimetric analyzer was employed to determine the TG-DTG curves of coal gangue powder. X-ray diffractometer, Fourier infrared spectrometer and scanning electron microscope were utilized to investigate the microstructure of activated coal gangue powder at different temperature ranges. These data can be used for determining the optimal calcination scheme of coal gangue to maximize its potential as a partial cement clinker replacement in cement production, thereby contributing to cost reduction and carbon emission mitigation.

Mechanism insight on licorice flavonoids release from Carbopol hydrogels: Role of "release steric hindrance" and drug solubility in the release medium.

The present study was to systematically evaluate different licorice flavonoids (LFs) compounds release behaviors from the single payload hydrogel and LFs extracts hydrogels based on the drug solubility in the release medium (DSRM), intermolecular strength of the hydrogel and the "release steric hindrance" (RSH). Two kinds of LFs (LFs 1: LFs 2 = 5:1, W/W) hydrogels were prepared with Carbopol 940 (CBP) as the thickener, and ten LFs single payload hydrogels were prepared according to the actual content in the LFs 1 extracts. The drug release mechanisms were confirmed by in vitro release experiments and molecular dynamic simulation analysis, and evaluated using novel indicators of ERLFs 1/Sin (the enhancement ratio (ER) of drug release percent of LFs 1-CBP hydrogel to the single payload hydrogel), ERLFs 2/ LFs 1 (ER of drug release percent of LFs 2-CBP hydrogel to LFs 1-CBP hydrogel) and ERrelease medium (ER of drug release percent in different release medium). We found that LFs 1-CBP possessed a significantly higher intermolecular strength and RSH than LFs 2-CBP, resulting in a higher viscosity, which had a positive correlation with the payload content and a negative correlation with the drug release percent. Therefore, the ERLFs 2/ LFs 1 values of ten LFs compounds were all higher than 1. For liquiritigenin and retrochalcone with higher DSRM, they displayed similar ERLFs 1/ Sin, ERLFs 2/ LFs 1 and ERrelease medium values (≈1). For formononetin, licoflavone A and licochalcone A with low DSRM, they exhibited ERLFs 1/Sin values >1. The low DSRM was the decisive factor to restrict their release from the single payload hydrogel. The presence of glycyrrhizin acid (GA) in the LFs could facilitate their release from the LFs extracts hydrogel. For isoliquiritin, isoliquiritigenin and glabridin with a lower content in the LFs extracts, they exhibited ERLFs 1/Sin values <1. The RSH predominantly restricted its release. The study provided guidelines for the reasonable design of LFs extracts hydrogel in pharmaceutical topical formulations.