Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

CDC25B and CDC25C overexpression in nonmelanoma skin cancer suppresses cell death

Non‐melanoma skin cancer frequently results from chronic exposure to ultraviolet (UV) irradiation. UV‐induced DNA damage activates cell cycle arrest checkpoints through degradation of the cyclin‐dependent kinase activators, the cell division cycle 25 (CDC25) phosphatases. We previously reported increased CDC25A in nonmelanoma skin cancer, but CDC25B and CDC25C had not been previously examined. Consequently, we hypothesized that increased expression of CDC25B and CDC25C increases tumor cell proliferation and skin tumor growth. We found that CDC25B and CDC25C were increased in mouse and human skin cancers. CDC25B was primarily cytoplasmic in skin and skin tumors and was significantly increased in the squamous cell carcinoma (SCC), while CDC25C was mostly nuclear in the skin, with an increased cytoplasmic signal in the premalignant and malignant tumors. Surprisingly, forced expression of CDC25B or CDC25C in cultured SCC cells did not affect proliferation, but instead suppressed apoptosis, while CDC25C silencing increased apoptosis without impacting proliferation. Targeting CDC25C to the nucleus via mutation of its nuclear export sequence, however, increased proliferation in SCC cells. Overexpression of CDC25C in the nuclear compartment did not hinder the ability of CDC25C to suppress apoptosis, neither did mutation of sites necessary for its interaction with 14‐3‐3 proteins. Analysis of apoptotic signaling pathways revealed that CDC25C increased activating phosphorylation of Akt on Ser⁴⁷³, increased inhibitory phosphorylation of proapoptotic BAD on Ser¹³⁶, and increased the survival protein Survivin. Silencing of CDC25C significantly reduced Survivin levels. Taken together, these data suggest that increased expression of CDC25B or CDC25C are mechanisms by which skin cancers evade apoptotic cell death.     

Mechanisms of repigmentation induced by photobiomodulation therapy in vitiligo

Photobiomodulation (PBM) therapy is based on the exposure of biological tissues to low‐level laser light (coherent light) or light‐emitting diodes (LEDs; noncoherent light), leading to the modulation of cellular functions, such as proliferation and migration, which result in tissue regeneration. PBM therapy has important clinical applications in regenerative medicine. Vitiligo is an acquired depigmentary disorder resulting from disappearance of functional melanocytes in the involved skin. Vitiligo repigmentation depends on available melanocytes derived from (a) melanocyte stem cells located in the bulge area of hair follicles and (b) the epidermis at the lesional borders, which contains a pool of functional melanocytes. Since follicular melanoblasts (MBs) are derived from the melanocyte stem cells residing at the bulge area of hair follicle, the process of vitiligo repigmentation presents a research model for studying the regenerative effect of PBM therapy. Previous reports have shown favourable response for treatment of vitiligo with a low‐energy helium‐neon (He‐Ne) laser. This review focuses on the molecular events that took place during the repigmentation process of vitiligo triggered by He‐Ne laser (632.8 nm, red light). Monochromatic radiation in the visible and infrared A (IRA) range sustains matrix metalloproteinase (MMP), improves mitochondrial function, and increases adenosine triphosphate (ATP) synthesis and O₂ consumption, which lead to cellular regenerative pathways. Cytochrome c oxidase in the mitochondria was reported to be the photoacceptor upon which He‐Ne laser exerts its effects. Mitochondrial retrograde signalling is responsible for the cellular events by red light. This review shows that He‐Ne laser initiated mitochondrial retrograde signalling via a Ca²⁺‐dependent cascade. The impact on cytochrome c oxidase within the mitochondria, an event that results in activation of CREB (cyclic‐AMP response element binding protein)‐related cascade, is responsible for the He‐Ne laser promoting functional development at different stages of MBs and boosting functional melanocytes. He‐Ne laser irradiation induced (a) melanocyte stem cell differentiation; (b) immature outer root sheath MB migration; (c) differentiated outer root sheath MB melanogenesis and migration; and (d) perilesional melanocyte migration and proliferation. These photobiomodulation effects result in perifollocular and marginal repigmentation in vitiligo.