Exercise, Diet and Sleeping as Regenerative Medicine Adjuvants: Obesity and Ageing as Illustrations

Regenerative medicine uses the biological and medical knowledge on how the cells and tissue regenerate and evolve in order to develop novel therapies. Health conditions such as ageing, obesity and cancer lead to an impaired regeneration ability. Exercise, diet choices and sleeping pattern have significant impacts on regeneration biology via diverse pathways including reducing the inflammatory and oxidative components. Thus, exercise, diet and sleeping management can be optimized towards therapeutic applications in regenerative medicine. It could allow to prevent degeneration, optimize the biological regeneration and also provide adjuvants for regenerative medicine.

Aged Microglia in Neurodegenerative Diseases: Microglia Lifespan and Culture Methods

Microglia have been recognized as macrophages of the central nervous system (CNS) that are regarded as a culprit of neuroinflammation in neurodegenerative diseases. Thus, microglia have been considered as a cell that should be suppressed for maintaining a homeostatic CNS environment. However, microglia ontogeny, fate, heterogeneity, and their function in health and disease have been defined better with advances in single-cell and imaging technologies, and how to maintain homeostatic microglial function has become an emerging issue for targeting neurodegenerative diseases. Microglia are long-lived cells of yolk sac origin and have limited repopulating capacity. So, microglial perturbation in their lifespan is associated with not only neurodevelopmental disorders but also neurodegenerative diseases with aging. Considering that microglia are long-lived cells and may lose their functional capacity as they age, we can expect that aged microglia contribute to various neurodegenerative diseases. Thus, understanding microglial development and aging may represent an opportunity for clarifying CNS disease mechanisms and developing novel therapies.

2021 Biomaterials Science Emerging Investigators Issue: Antioxidant Response Activating nanoParticles (ARAPas) localize to atherosclerotic plaque and locally activate the Nrf2 pathway

Atherosclerotic disease is the leading cause of death world-wide with few novel therapies available despite the ongoing health burden. Redox dysfunction is a well-established driver of atherosclerotic progression; however, the...

Crosstalk with keratinocytes causes GNAQ oncogene specificity in melanoma

Different melanoma subtypes exhibit specific and non-overlapping sets of oncogene and tumor suppressor mutations, despite a common cell of origin in melanocytes. For example, activation of the Gαq/11 signaling pathway is a characteristic initiating event in primary melanomas that arise in the dermis, uveal tract or central nervous system. It is rare in melanomas arising in the epidermis. The mechanism for this specificity is unknown. Here, we present evidence that in the mouse, crosstalk with the epidermal microenvironment actively impairs the survival of melanocytes expressing the GNAQQ209L oncogene. We found that GNAQQ209L, in combination with signaling from the interfollicular epidermis (IFE), stimulates dendrite extension, leads to actin cytoskeleton disorganization, inhibits proliferation and promotes apoptosis in melanocytes. The effect was reversible and paracrine. In contrast, the epidermal environment increased the survival of wildtype and BrafV600E expressing melanocytes. Hence, our studies reveal the flip side of Gaq/11 signaling, which was hitherto unsuspected. In the future, the identification of the epidermal signals that restrain the GNAQQ209L oncogene could suggest novel therapies for GNAQ and GNA11 mutant melanomas.