Xinyan Tao,Yuan Liu,Zhenhua Ding,Shuang Xie,Wenxiong Cao,Xiaohong Li
Obesity has become a worldwide public health problem and continues to be one of the leading causes of chronic diseases. Obesity treatment is challenged by large drug doses, high administration frequencies and severe side effects. Herein, we propose an antiobesity strategy through the local administration of HaRChr fiber rods loaded with chrysin and grafted with hyaluronic acid and AtsFRk fiber fragments loaded with raspberry ketone and grafted with adipocyte target sequences (ATSs). The hyaluronic acid grafts double the uptake levels of HaRChr by M1 macrophages to promote phenotype transformation from M1 to M2 through upregulating CD206 and downregulating CD86 expressions. ATS-mediated targeting and sustained release of raspberry ketone from AtsFRk increase the secretion of glycerol and adiponectin, and Oil red O staining shows much fewer lipid droplets in adipocytes. The combination treatment with AtsFRk and the conditioned media from HaRChr-treated macrophages elevates adiponectin levels, suggesting that M2 macrophages may secrete anti-inflammatory factors to stimulate adipocytes to produce adiponectin. Diet-induced obese mice showed significant weight losses of inguinal (49.7%) and epididymal (32.5%) adipose tissues after HaRChr/AtsFRk treatment, but no effect was observed on food intake. HaRChr/AtsFRk treatment reduces adipocyte volumes, lowers serum levels of triglycerides and total cholesterol and restores adiponectin levels to those of normal mice. In the meantime, HaRChr/AtsFRk treatment significantly elevates the gene expression of adiponectin and interleukin-10 and downregulates tissue necrosis factor-α expression in the inguinal adipose tissues. Thus, local injection of cell-targeting fiber rods and fragments demonstrates a feasible and effective antiobesity strategy through improving lipid metabolism and normalizing the inflammatory microenvironment.
Non-healing diabetic foot ulcers are the knotty public health issue due to the uncontrolled bacterial infection, prolonged inflammation, and inferior vessel remodeling. In this work, polypyrrole (Ppy) was added into the hybrid hydrogel containing polyvinyl alcohol (PVA), polyethylene glycol (PEG), and hyaluronan (HA) to acquire superior mechanism and photothermal ability. The Ppy composited hybrid hydrogel could effectively kill bacteria through accumulating heat on the hydrogel surface. RNA-Seq analysis shows that the heat accumulation could enhance phagosome of macrophage and M1 activation, which further accelerate bacteria clearance. Benefitting from the bacteria clearance, macrophage could transform its phenotype to M2 in Ppy composited hybrid hydrogel group with near infrared light (NIR) stimulation. The related genes expression in keratinization, keratinocyte differentiation, and establishment of the skin barrier in the skin were up-regulated and collagen and vascular endothelial growth factor (VEGF) expression level are also enhanced. In summary, Ppy composited hybrid hydrogel could effectively solve the issues of infection and poor wound healing in diabetic foot ulcers, making it an ideal candidate dressing for the treatment of chronic wounds.
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