Exploring microRNAs in diabetic chronic cutaneous ulcers: Regulatory mechanisms and therapeutic potential.

Diabetic chronic cutaneous ulcers (DCU) are one of the serious complications of diabetes mellitus, occurring mainly in diabetic patients with peripheral neuropathy. Recent studies have indicated that microRNAs (miRNAs/miRs) and their target genes are essential regulators of cell physiology and pathology including biological processes that are involved in the regulation of diabetes and diabetes-related microvascular complications. in vivo and in vitro models have revealed that the expression of some miRNAs can be regulated in the inflammatory response, cell proliferation, and wound remodelling of DCU. Nevertheless, the potential application of miRNAs to clinical use is still limited. Here, we provide a contemporary overview of the miRNAs as well as their associated target genes and pathways (including Wnt/ß-catenin, NF-κB, TGF-ß/Smad, and PI3K/AKT/mTOR) related to DCU healing. We also summarize the current development of drugs for DCU treatment and discuss the therapeutic challenges of DCU treatment and its future research directions.

Asiaticoside nitric oxide gel accelerates diabetic cutaneous ulcers healing by activating Wnt/ß-catenin signaling pathway.

Diabetic ulcers, gangrene, local infections and other traumatic symptoms of wound healing are all directly related. Promoting the early healing of diabetic cutaneous ulcers (DCU) and reducing the disability and treatment costs is an important research project integrating traditional Chinese and Western medicine. Nitric oxide (NO) is a key component of wound healing, and endogenous NO secretion is insufficient during the development of DCU. It has been reported that exogenous NO can promote wound healing, but exogenous NO has a short half-life and is difficult to adhere to the skin. Asiaticoside (AC) is extracted from the traditional Chinese medicine Centella asiatica, and has angiogenic, anticancer, antioxidant, anti-inflammatory, and wound-healing effects. Therefore, our study is based on the hypothesis that the combination of AC and NO to treat DCU is possible. In this study we considered gels of AC and NO, and evaluated the effects of the gel on DCU healing. Based on our study, it was found that the combined effect of asiaticoside and NO could accelerate the healing rate of DCU wounds. The asiaticoside NO gel can inhibit the growth of bacteria in the wound surface, alleviate the inflammatory reaction of wound, and increase the expression of VEGF, iNOS, eNOS and CD34. Our research shows that asiaticoside NO gel may promote DCU wound healing by regulating Wnt/ß-Catenin signaling pathway. It will provide new targets and strategies for the diagnosis and treatment of DCU.

Regulatory Mechanisms of the Wnt/ß-Catenin Pathway in Diabetic Cutaneous Ulcers.

Skin ulcers are a serious complication of diabetes. Diabetic patients suffer from vascular lesions and complications such as peripheral neuritis, peripheral vascular lesions, and collagen abnormalities, which result in skin wounds that are refractory and often develop into chronic ulcers. The healing of skin ulcers requires an inflammatory reaction, wound proliferation, remodeling regulation, and control of stem cells. Studies investigating diabetic cutaneous ulcers have focused on cellular and molecular levels. Diabetes can cause nerve and blood vessel damage, and persistent high blood sugar levels can cause systemic multisite nerve damage based on peripheral neuropathy. The long-term hyperglycemia state enables the polyol glucose metabolism pathway to be activated, increasing the accumulation of toxic substances in the vascular injured nerve tissue cells. Sustained hyperglycemia leads to dysfunction of epithelial cells, leading to a decrease in pro-angiogenic signaling and nitric oxide production. In addition, due to impaired leukocyte function in hyperglycemia, immune function is impaired and the immune response at relevant sites is insufficient, making diabetic foot more difficult to heal. The Wnt/ß-catenin pathway is a highly conserved signal transduction pathway involved in a variety of biological processes, such as cell proliferation, apoptosis, and differentiation. It is considered an important pathway involved in the healing of skin wounds. This article summarizes the mechanism of action of the Wnt/ß-catenin pathway involved in the inflammatory responses to diabetic ulcers, wound proliferation, wound remodeling, and stem cells. The interactions between the Wnt signal pathway and other metabolic pathways are also discussed.