{'fraction_non_alphanumeric': 0.030453697949036667, 'fraction_numerical': 0.01305158483530143, 'mean_word_length': 5.363636363636363, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Glucose-Dependent Foxo1 Switch in Healing Wounds: A Shred of Hope for Diabetic Ulcers?

Diabetes mellitus (DM) has been labeled the epidemic of the 21st century, claiming its toll on both quality and duration of life and posing a major economic burden to society (1). By the year 2050, it is predicted that 10% of the population will be diagnosed with DM. Approximately 15% of diabetic patients will develop a nonhealing wound or diabetic foot ulcer. These wounds are the number one cause of lower-limb amputations (2). Several defects have been proposed to explain impaired wound healing in diabetic patients including compromised angiogenesis, inadequate expression of growth factors, excessive cytokine release at the site of injury, reduced epithelial cell migration, and proliferation and defective insulin action in the skin (3–5). However, the specific molecular events leading to impaired wound repair in DM are still unknown. Against this backdrop, it is perhaps not surprising that effective therapeutic strategies to treat these wounds remain limited.

The Foxo1 transcription factor is a member of the evolutionarily conserved, mammalian forkhead box O class (Foxo) family that also includes Foxo3, Foxo4, and Foxo6. These transcription factors play a major role in diverse processes including cellular differentiation, proliferation, apoptosis, stress resistance, and glucose metabolism. Foxos are negatively regulated by the insulin-like growth factor 1 (IGF1)/insulin pathway, and they are activated by oxidative stress through Jun N-terminal kinase signaling. Foxo regulation is orchestrated …