Bioactive self-healing umbilical cord blood exosomes hydrogel for promoting chronic diabetic wound healing.

The deleterious effects of diabetes mellitus on wound healing have become a major public health concern worldwide. Given the complex microenvironment of diabetic wounds and the high prevalence of diabetes, the design and development of novel wound dressing materials with versatile capabilities is urgent. Extracellular vesicles (EVs) derived from human umbilical cord blood have demonstrated the potential to counter inflammation and accelerate wound healing. Herein, we explored the efficacy of incorporating human umbilical cord blood-derived exosomes (UCB-Exos) into an ABA-type amphiphilic hydrogel, which possesses the attributes of exosome (Exo) encapsulation, temperature-triggered reversible sol-gel conversion, and Exo-regulated release, for enhancing the stability and retention of Exos. We sought to examine the feasibility of this strategy in augmenting the therapeutic efficacy of UCB-Exos for the healing of diabetes-related wounds. The injectable hydrogel was conveniently applied directly onto the wound surface and the enclosed Exo significantly facilitated the healing process, resulting in faster wound closure, enhanced collagen deposition, accelerated re-epithelialization, and enhanced neo-vascularization within two weeks compared with the hydrogel-only treatment group. In summary, some hydrogels hold great promise for promoting wound healing in diabetics and represent a novel therapeutic option for diabetes-related ulcers.

Luteolin activates M2 macrophages and suppresses M1 macrophages by upregulation of hsa_circ_0001326 in THP-1 derived macrophages.

Asthma is accompanied by inflammatory progression. Macrophages are a major type of cells to response inflammation caused by different type of factors by polarized into specific phenotypes. Luteolin and glycyrrhizic acid exert protect role in asthma; however, their role in THP-1 derived macrophages polarization whether through regulating the expression of hsa_circ_0001326 is still unknown. The effect of luteolin and glycyrrhizic acid on THP-1 derived macrophages polarization were evaluated using qRT-PCR, Western blotting, and ELISA assay. The function of hsa_circ_0001326 on macrophages polarization in luteolin treated THP-1 derived macrophages were assessed after silence of hsa_circ_0001326. And the expression of its' potential downstream gene, including hsa-miR-136-5p and ubiquitin-specific protease 4 (USP4), were detected using qRT-PCR and Western blot analysis. Furthermore, the potential mechanism of hsa_circ_0001326 were validated using rescue experiment. Results showed that luteolin promoted M2 polarization and inhibited M1 polarization in THP-1 induced macrophages, but glycyrrhizic acid had no these effects. Hsa_circ_0001326 expression was upregulated in luteolin treat THP-1 derived macrophages. Silence of hsa_circ_0001326 reversed the function of luteolin on macrophages polarization. In addition, hsa_circ_0001326 attenuated the inhibition effect of luteolin on hsa-miR-136-5p expression, and the promotion effect on USP4 expression. Furthermore, hsa-miR-136-5p inhibitor reversed the effect of hsa_circ_0001326 on macrophages polarization and the USP4 expression. Taken together, luteolin activates M2 macrophages and suppresses M1 macrophages by upregulation of hsa_circ_0001326. Further mechanism maybe by regulating hsa_circ_0001326 downstream gene expression, including hsa-miR-136-5p and USP4, in THP-1 derived macrophages. These findings provide a new insight for macrophage polarization under stimulation of luteolin.