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Formation of the mitochondrial permeability transition pore (MPTP) facilitates the release of cytotoxic factors, including cytochrome c and ROS, into the cytoplasm, exacerbating oxidative stress and perpetuating the activation cycle (66, 67)

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Other factors include increased serum matrix metalloproteinases (Li et al., 2013), decreased collagen type ratio, dysregulated expression of skin neuropeptides (Nowak et al., 2021), lack of thrombin activated fibrinolytic inhibitor (Bryk-Wizania and Undas, 2021), reduced platelet growth factor and modification of late phase three advanced glycation end products (Nass et al., 2010), decreased number of epidermal nerves (Alavi et al., 2014), and the increase of extracellular matrix components and the matrix metalloproteinase reconstitution are imbalanced (Alavi et al., 2014)

Polymorphisms in factor II and factor VII genes modulate oral anticoagulation with warfarin