Mechanism of damage of HIF-1 signaling in chronic diabetic foot ulcers and its related therapeutic perspectives

Zhu, Dong; Wei, Wuhan; Zhang, Jingyu; Zhao, Bingkun; Li, Qiang; Jin, Peisheng

doi:10.1016/j.heliyon.2024.e24656

Cited by 6 publications

(2 citation statements)

References 66 publications

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“…89 However, in DFU, HIF-1 signaling is inhibited due to hyperglycemia, leading to downregulation of HIF-1/VEGF expression, and hence ischemia and hypoxia. 90 Overall, the combination of impaired vascular regeneration, increased hypoxic conditions, and attenuated cellular responses to hypoxia contribute to delayed wound healing in DFU. The ischemic and hypoxic environment is insufficient to supply the large amount of energy required for wound healing, resulting in a crisis of energy supply.…”

Section: High Level Proteasementioning

confidence: 99%

“…Under normoxic conditions, HIF-1 is activated and stimulates the expression of downstream genes that promote erythropoiesis and the production of growth factors (e.g., VEGF, PDGF, and basic fibroblast growth factor [bFGF]), which are essential for the regulation of hypoxia . However, in DFU, HIF-1 signaling is inhibited due to hyperglycemia, leading to downregulation of HIF-1/VEGF expression, and hence ischemia and hypoxia . Overall, the combination of impaired vascular regeneration, increased hypoxic conditions, and attenuated cellular responses to hypoxia contribute to delayed wound healing in DFU.…”

Section: Dfu Wound Microenvironmentmentioning

confidence: 99%

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Nanozymes for the Therapeutic Treatment of Diabetic Foot Ulcers

Xiao,

Zhao,

DuBois

et al. 2024

ACS Biomater. Sci. Eng.

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Diabetic foot ulcers (DFU) are chronic, refractory wounds caused by diabetic neuropathy, vascular disease, and bacterial infection, and have become one of the most serious and persistent complications of diabetes mellitus because of their high incidence and difficulty in healing. Its malignancy results from a complex microenvironment that includes a series of unfriendly physiological states secondary to hyperglycemia, such as recurrent infections, excessive oxidative stress, persistent inflammation, and ischemia and hypoxia. However, current common clinical treatments, such as antibiotic therapy, insulin therapy, surgical debridement, and conventional wound dressings all have drawbacks, and suboptimal outcomes exacerbate the financial and physical burdens of diabetic patients. Therefore, development of new, effective and affordable treatments for DFU represents a top priority to improve the quality of life of diabetic patients. In recent years, nanozymes-based diabetic wound therapy systems have been attracting extensive interest by integrating the unique advantages of nanomaterials and natural enzymes. Compared with natural enzymes, nanozymes possess more stable catalytic activity, lower production cost and greater maneuverability. Remarkably, many nanozymes possess multienzyme activities that can cascade multiple enzymecatalyzed reactions simultaneously throughout the recovery process of DFU. Additionally, their favorable photothermal-acoustic properties can be exploited for further enhancement of the therapeutic effects. In this review we first describe the characteristic pathological microenvironment of DFU, then discuss the therapeutic mechanisms and applications of nanozymes in DFU healing, and finally, highlight the challenges and perspectives of nanozyme development for DFU treatment.

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Section: High Level Proteasementioning

confidence: 99%

Section: Dfu Wound Microenvironmentmentioning

confidence: 99%