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Type 2 diabetes (T2D) is a metabolic disorder that causes numerous complications including impaired wound healing and poses a significant challenge for the management of diabetic patients. Epigallocatechin‐3‐gallate (EGCG) is a natural polyphenol that exhibits anti‐inflammatory and anti‐oxidative benefits in skin wounds, however, the direct effect of EGCG on epidermal keratinocytes, the primary cells required for re‐epithelialization in wound healing remains unknown. Our study aims to examine the underlying mechanisms of EGCG's ability to promote re‐epithelialization and wound healing in T2D‐induced wounds. Murine models of wound healing in T2D were established via feeding high‐fat high‐fructose diet (HFFD) and the creation of full‐thickness wounds. Mice were administered daily with EGCG or vehicle to examine the wound healing response and underlying molecular mechanisms of EGCG's protective effects. Systemic administration of EGCG in T2D mice robustly accelerated the wound healing response following injury. EGCG induced nuclear translocation of nuclear factor erythroid 2‐related factor 2 (NRF2) and promoted cytokeratin 16 (K16) expression to activate epidermal keratinocytes and robustly promoted re‐epithelialization of wounds in diabetic mice. Further, EGCG demonstrated high binding affinity with Kelch‐like ECH‐associated protein 1 (KEAP1), thereby inhibiting KEAP1‐mediated degradation of NRF2. Our findings provide important evidence that EGCG accelerates the wound healing response in diabetic mice by activating epidermal keratinocytes, thereby promoting re‐epithelialization of wounds via K16/NRF2/KEAP1 signaling axis. These mechanistic insights into the protective effects of EGCG further suggest its therapeutic potential as a promising drug for treating chronic wounds in T2D. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is one of the leading causes of death worldwide, and due to the widespread and irreversible damage caused, new therapeutic treatments are urgently needed in order to limit the degree of ischaemic damage following MI. Aberrant activation of Wnt/β‐catenin signalling pathway often occurs during cardiovascular diseases including MI, which results in excess production of reactive oxygen species (ROS) and further promotes myocardial dysfunction. Huoxin pill (HXP) is a Traditional Chinese Medicine formula that has been widely used in the treatment of coronary heart disease and angina; however, its mechanisms remain unclear. Here, we performed mouse models of MI and examined the effects and mechanisms of HXP in protecting against MI‐induced ischaemic damage. Our study showed that administration with HXP robustly protected against MI‐induced cardiac injuries, decreased infarct size and improved cardiac function. Moreover, HXP attenuated ischaemia‐induced DNA damage occurrence in vivo and H2O2‐induced DNA damage occurrence in vitro, via potent inhibition of adverse Wnt/β‑catenin signalling activation. Our study thus elucidated the role and mechanism of HXP in protecting against MI and oxidative stress‐induced injuries and suggests new therapeutic strategies in ischaemic heart disease via inhibition of Wnt/β‐catenin signalling pathway. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) is a well‐known angiogenic factor, however its ability in promoting therapeutic angiogenesis following myocardial infarction (MI) is limited. Here, we aimed to investigate whether dual treatment with insulin‐like growth factor binding protein‐4 (IGFBP‐4), an agent that protects against early oxidative damage, can be effective in enhancing the therapeutic effect of VEGF following MI. Combined treatment with IGFBP‐4 enhanced VEGF‐induced angiogenesis and prevented cell damage via enhancing the expression of a key angiogenic factor angiopoietin‐1. Dual treatment with the two agents synergistically decreased cardiac fibrosis markers collagen‐I and collagen‐III following MI. Importantly, while the protective action of IGFBP‐4 occurs at an early stage of ischemic injury, the action of VEGF occurs at a later stage, at the onset angiogenesis. Our findings demonstrate that VEGF treatment alone is often not enough to protect against oxidative stress and promote post‐ischemic angiogenesis, whereas the combined treatment with IGFBP4 and VEGF can utilize the dual roles of these agents to effectively protect against ischemic and oxidative injury, and promote angiogenesis. These findings provide important insights into the roles of these agents in the clinical setting, and suggest new strategies in the treatment of ischemic heart disease. [ABSTRACT FROM AUTHOR]