Inflammatory dysfunction and angiogenesis inhibition are two main factors leading to the delayed healing of diabetic wounds. Hydrogels with anti-inflammatory and angiogenesis-promoting effects have been considered as promising wound care materials. Herein, a salvianolic acid B (SAB)-loaded hyaluronic acid (HA) self-healing hydrogel (HA/SAB) with anti-inflammatory and pro-angiogenesis capacities for diabetic wound healing is reported. The HA hydrogel was prepared via the covalent cross-linking of aldehyde groups in oxidized HA (OHA) and hydrazide groups in adipic dihydrazide (ADH)-modified HA (HA-ADH) with the formation of reversible acylhydrazone bonds. The obtained HA hydrogel exhibited multiple favorable properties such as porous structures, excellent self-healing properties, a sustainable release capacity of SAB, as well as excellent cytocompatibility. In addition, the effects of the SAB-loaded HA self-healing hydrogel were investigated via a full-thickness skin defect model using diabetic rats. The HA/SAB hydrogel showed enhanced skin regeneration effects with accelerated wound closure, shorter remaining dermal space length, thicker granulation tissue formation, and more collagen deposition. Furthermore, reduced inflammatory response and enhanced vascularization were found with HA/SAB2.5 hydrogel-treated wounds, indicating that the hydrogel promotes diabetic wound healing through the promotion of anti-inflammation and angiogenesis. Our results suggest that the fabricated SAB-loaded HA self-healing hydrogel is promising as a wound dressing for the treatment of diabetic wounds.
Rhizoma Atractylodes macrocephala polysaccharides (RAMP) have been reported to have a variety of important biological activities. In this study, an ultrasonic-assisted enzymatic extraction (UAEE) was employed to obtain the highest extraction yield and strongest antioxidant activity of RAMP and optimized by a multi-response optimization process. A three-level four-factor Box-Behnken design (BBD) was performed as response surface methodology (RSM) with desirability function (DF) to attain the optimal extraction parameters. The DPPH scavenging percentage was used to represent the antioxidant ability of RAMP. The maximum D value (0.328), along with the maximum yield (59.92%) and DPPH scavenging percentage (13.28%) were achieved at 90.54 min, 57.99 °C, 1.95% cellulase and 225.29 W. These values were further validated and found to be in good agreement with the predicted values. Compared to the other extraction methods, both the yield and scavenging percentage of RAMP obtained by UAEE was favorable and the method appeared to be time-saving and of high efficiency. These results demostrated that UAEE is an appropriate and effective extraction technique. Moreover, RSM with DF approach has been proved to be adequate for the design and optimization of the extraction parameters for RAMP. This work has a wide range of implications for the design and operation of polysaccharide extraction processes.
Since the 20th century, mortality rate due to cardiovascular diseases has increased, posing a substantial economic burden on society. Atherosclerosis is a common cardiovascular disease that requires urgent and careful attention. This study was conducted to predict and validate the potential molecular targets and pathways of Astragalus membranaceus and Angelica sinensis (A&A) in the treatment of atherosclerosis using network pharmacology. The active ingredients of A&A were obtained using the TCMSP database, while the target genes of atherosclerosis were acquired using 2 databases, namely GeneCards and DrugBank. The disease-target-component model map and the core network were obtained using Cytoscape 3.8.2 and MCODE plug-in, respectively. The core network was then imported into the STRING database to obtain the protein-protein interaction (PPI) network diagram. Moreover, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed using the HIPLOT online website. Finally, the small molecules related to key signaling pathways were molecularly docked and visualized. Under the screening conditions of oral bioavailability ≥ 30% and drug-likeness ≥ 0.18, 22 active ingredients were identified from A&A, and 174 relevant targets were obtained. Additionally, 54 active ingredients were found in the extracted core network. Interleukin (IL)-17 signaling pathway, tumor necrosis factor (TNF) signaling pathway, and Toll-like receptor (TLR) signaling pathway were selected as the main subjects through KEGG enrichment analysis. Core targets (RELA, IKBKB, CHUK, and MMP3) and active ingredients (kaempferol, quercetin, and isorhamnetin) were selected and validated using molecular docking. This study identified multiple molecular targets and pathways for A&A in the treatment of atherosclerosis. A&A has the potential to treat atherosclerosis through an antiinflammatory approach.
Impaired healing of diabetic wounds harms patients’ quality of life and even leads to disability and death, which is an urgent issue to be solved clinically. Despite the great progress that has been achieved, it remains a worldwide challenge to develop effective therapeutic treatments for diabetic wounds. Recently, exosomes have attracted special attention because they can be involved in immune response, antigen presentation, cell migration, cell differentiation, tumor invasion and other processes. Meanwhile, exosomes have been proven to hold great potential in the treatment of diabetic wounds. Mechanistic studies of exosomes based on signaling pathways could not only help to uncover the mechanisms by which exosomes promote diabetic wound healing but could also provide a theoretical basis for the clinical application of exosomes. Herein, our mini-review aims to summarize the progress of research on the use of various exosomes derived from different cell types to promote diabetic wound healing, with a focus on the classical signaling pathways, including PI3K/Akt, Wnt, NF-κB, MAPK, Notch, Nrf2, HIF-1α/VEGF and TGF-β/Smad. The results show that exosomes could regulate these signaling pathways to down-regulate inflammation, reduce oxidative stress, increase angiogenesis, promote fibroblast proliferation, induce re-epithelization and inhibit scar formation, making exosomes attractive candidates for the treatment of diabetic wounds.
The species Hylotelephium erythrostictum is well known as an ornamental plant in China. Here, we report the complete chloroplast genome (cp) of H. erythrostictum using the next-generation sequencing. It shows a total length of 151,707 bp with typical quadripartite structure. The genome is composed of the large single copy region (LSC) of 83,070 bp, the small single copy region (SSC) of 17,018 bp, and two separated inverted regions (IRs) of 25,793 bp, respectively. It contains 134 genes, including 80 protein-coding genes (PCGs), 8 rRNA genes, and 37 tRNA genes. The overall GC content of the cp genome is 37.7%. Maximum likelihood (ML) tree based on ten complete chloroplast genomes of Crassulaceae and one outgroup species suggested a monophyly formed by H. erythrostictum together with Hylotelephium ewersii, which demonstrate a comparably closer phylogenetic relationship. The complete chloroplast genome of this H. erythrostictum provides valuable information and further phylogenetic reconstruction of the Crassulaceae family.
Sedum tricarpum Makino., is a perennial succulent herb, which was first discovered and established as a new species ten years ago. Here, we report the complete chloroplast genome of S. tricarpum. It shows a typical quadripartite structure with a total length of 149,349 bp, including the large single-copy region (LSC) of 81,644 bp, the small single-copy region (SSC) of 16,643 bp, and two separated inverted regions (IRs) of 25,531 bp, respectively. For the whole genome, there are a total of 131 genes, including 85 protein-coding genes (PCGs), 8 rRNA genes, and 37 tRNA genes. The overall GC content of the cp genome is 37.8%. A well-supported phylogenetic tree revealed monophyly formed by S. tricarpum and S. sarmentosum, suggesting a relatively closer phylogenetic relationship with the clade consisting of S. lineare and Graptopetalum amethystinum. The complete chloroplast genome of S. tricarpum provides valuable information for further phylogenetic reconstruction of the Crassulaceae family.