A non-healing diabetic foot ulcer (DFU) is a debilitating clinical problem amounting to socioeconomic and psychosocial burden. DFUs increase morbidity due to prolonged treatment and mortality in the case of non-treatable ulcers resulting in gangrene and septicemia. The overall amputation rate of the lower extremity with DFU ranges from 3.34% to 42.83%. Wound debridement, antibiotics, applying growth factors, negative pressure wound therapy, hyperbaric oxygen therapy, topical oxygen, and skin grafts are common therapies for DFU. However, recurrence and nonhealing ulcers are still major issues. Chronicity of inflammation, hypoxic environment, poor angiogenesis, and decreased formation of the extracellular matrix are common impediments leading to nonhealing patterns of DFUs. Angiogenesis is crucial for wound healing since proper vessel formation facilitates nutrients, oxygen, and immune cells to the ulcer tissue to help in clearing out debris and facilitate healing. However, poor angiogenesis due to decreased expression of angiogenic mediators and matrix formation results in nonhealing and ultimately amputation. Multiple proangiogenic mediators and VEGF therapy exist to enhance angiogenesis, but the results are not satisfactory. Thus, there is a need to investigate novel pro-angiogenic mediators that can either alone or in combination enhance the angiogenesis and healing of DFUs. In this article, we critically reviewed the existing pro-angiogenic mediators followed by potentially novel factors that might play a regulatory role in promoting angiogenesis and wound healing in DFUs.

Since cholesterol is not routinely measured in astronauts before and after their return from space, there is no data on the role of blood cholesterol level in muscle atrophy and microgravity. Since the first moon landing, aerospace medicine became outdated and has not pushed boundaries like its rocket engineering counterpart. Since the 2019 astronaut twin study, there has yet to be another scientific breakthrough for aerospace medicine. Microgravity-induced muscle atrophy is the most known consequence of spaceflight. Yet, so far, there is no therapeutic solution to prevent it or any real efforts in understanding it on a cellular or molecular level. The most obvious reason to this unprecedented level of research is due to the small cohort of astronauts. With the establishment of private space industries and exponential recruitment of astronauts, there is more reason to push forward spaceflight-related health guidelines and ensure the safety of the brave humans who risk their lives for the progression of mankind. Spaceflight is considered the most challenging job and the failure to prevent injury or harm should be considered reckless negligence by the institutions that actively prevented sophistication of aerospace medicine. In this critical review, role of cholesterol is analyzed across the NASA-established parameters of microgravity-induced muscle atrophy with a focus on potential therapeutic targets for research.