We investigated the effect of an 11β-HSD1 inhibitor (H8) on hepatic steatosis and its mechanism of action. Although H8, a curcumin derivative, has been shown to alleviate insulin resistance, its effect on non-alcoholic fatty liver disease (NAFLD) remains unknown. Rats were fed a high-fat diet (HFD) for 8 weeks, intraperitoneally injected with streptozotocin (STZ) to induce NAFLD, and, then, treated with H8 (3 or 6 mg/kg/day) or curcumin (6 mg/kg/day) for 4 weeks, to evaluate the effects of H8 on NAFLD. H8 significantly alleviated HFD+STZ-induced lipid accumulation, fibrosis, and inflammation as well as improved liver function. Moreover, 11β-HSD1 overexpression was established by transfecting animals and HepG2 cells with lentivirus, carrying the 11β-HSD1 gene, to confirm that H8 improved NAFLD, by reducing 11β-HSD1. An AMP-activated protein kinase (AMPK) inhibitor (Compound C, 10 μM for 2 h) was used to confirm that H8 increased AMPK, by inhibiting 11β-HSD1, thereby restoring lipid metabolic homeostasis. A silencing-related enzyme 1 (SIRT1) inhibitor (EX572, 10 μM for 4 h) and a SIRT1 activator (SRT1720, 1 μM for 4 h) were used to confirm that H8 exerted anti-inflammatory effects, by elevating SIRT1 expression. Our findings demonstrate that H8 alleviates hepatic steatosis, by inhibiting 11β-HSD1, which activates the AMPK/SIRT1 signaling pathway.

No abstract

Diabetic wounds are one of the most challenging public health issues of the 21st century due to their inadequate vascular supply, bacterial infections, high levels of oxidative stress, and abnormalities in antioxidant defenses, whereas there is no effective treatment for diabetic wounds. Due to the distinct properties of nanoparticles, such as their small particle size, elevated cellular uptake, low cytotoxicity, antibacterial activity, good biocompatibility, and biodegradability. The application of nanoparticles has been widely used in the treatment of diabetic wound healing due to their superior anti-inflammatory, antibacterial, and antioxidant activities. These nanoparticles can also be loaded with various agents, such as organic molecules (eg, exosomes, small molecule compounds, etc.), inorganic molecules (metals, nonmetals, etc.), or complexed with various biomaterials, such as smart hydrogels (HG), chitosan (CS), and hyaluronic acid (HA), to augment their therapeutic potential in diabetic wounds. This paper reviews the therapeutic potential and future perspective of nanoparticles in the treatment of diabetic wounds. Together, nanoparticles represent a promising strategy in the treatment of diabetic wound healing. The future direction may be to develop novel nanoparticles with multiple effects that not only act in wound healing at all stages of diabetes but also provide a stable physiological environment throughout the wound-healing process.

No abstract

No abstract