Photobiomodulation Using 830 nm Lighting-Emitting Diode Inhibits Melanogenesis via FOXO3a in Human Melanocyte.

Photobiomodulation (PBM) using 830 nm light-emitting diode (LED) benefits tissue regeneration, wound healing and neural stimulation. However, there is not much exploration of its effect on melanocytes and ex vivo skin model. This study aims to investigate the mechanism behind the anti-melanogenic activity of 830 nm LED and provides evidence for its activity in human ex vivo skin model. Our results showed that 830 nm LED at fluences ranging from 5 to 20 J/cm2 inhibited melanosome maturation and reduced melanin content, tyrosinase activity and melanogenesis-related proteins. 830 nm LED inhibited the phosphorylation of AKT and its downstream FOXO3a, leading to nuclear translocation of FOXO3a. Furthermore, FOXO3a knockdown and AKT activator like SC79 could reverse the melanogenesis inhibition phenotype induced by 830 nm LED. In human ex vivo skin model, Fontana-Masson staining revealed a decrease in epidermal basal pigmentation after 830 nm LED irradiation. Taken together, 830 nm LED demonstrated the anti-melanogenic activity via FOXO3a.

Unveiling the mystery of Riehl's melanosis: An update from pathogenesis, diagnosis to treatment.

Riehl's melanosis is a hyperpigmentation disorder that has a significant psychological and social impact on individuals. In the past 10 years, new categories have been developed, raising questions about how to classify Riehl's melanosis. The mechanism of this disease remains unclear, although the type IV hypersensitivity response caused by allergic sensitization, as well as genetic, ultraviolet radiation, and autoimmune factors, is to blame. Clinical manifestation, dermoscopy, reflectance confocal microscopy, patch/photopatch testing, histopathology, and a novel multimodality skin imaging system have been used for the diagnosis. A variety of therapies including topical skin-lightening agents, oral tranexamic acid, glycyrrhizin compound, chemical peels, and lasers and light therapies (intense pulsed light, 1064-nm Q-Switched Nd: YAG laser, 755-nm PicoWay laser, nonablative 1927-nm fractional thulium fiber laser, new pulsed-type microneedling radiofrequency), with improved effectiveness. The latest findings on possible biomarkers and their relationship to other autoimmune diseases were also summarized.

Altered expression of ferroptosis markers and iron metabolism reveals a potential role of ferroptosis in vitiligo.

Oxidative stress is one of the triggering factors for vitiligo, which leads to melanocyte (MC) destruction in vitiligo lesions. Ferroptosis, which is characterized by iron-dependent increase in oxidative stress and lipid peroxidation, has been widely explored in numerous diseases, whereas whether ferroptosis plays a role in MC loss of vitiligo remains to be elucidated. Quantitative real-time PCR and western blot analysis were used to determine the expression of ferroptosis markers in vitiligo patients. Immunonephelometry and electrochemiluminescence were performed to analyze iron status. Reactive oxygen species (ROS), Fe2+ , and lipid ROS were assessed by flow cytometry. The expression of ferroptosis markers was significantly altered in the epidermis of vitiligo patients. Iron deficiency was revealed in the blood of patients. Erastin reduced cell viability and led to oxidative stress, iron overload as well as lipid peroxide accumulation in human epidermal MCs in vitro. Altered expression of ferroptosis markers and inhibition of melanin synthesis in MCs were induced by erastin, which was attenuated by N-acetyl-L-cysteine (NAC) pretreatment or post-treatment in vitro. In conclusion, ferroptosis might take place during the process of vitiligo. Erastin could induce ferroptosis in human epidermal MCs and NAC could protect MCs from ferroptosis in vitro.

New insights into segmental vitiligo: A clinical and immunological comparison with nonsegmental vitiligo.

The overlaps between segmental vitiligo (SV) and nonsegmental vitiligo (NSV) suggest the underlying features of SV, which may be helpful for treating SV. In this study, 379 vitiligo patients were recruited and divided into SV (33.2%), mild-to-moderate NSV (M-NSV, affected body affected area [BSA] ≤10%, 34.0%), and severe NSV (S-NSV, affected BSA >10%, 32.7%) groups. Demographics and clinical data were collected through in-person interviews. The disease activity, progression, and prognosis were assessed through 6 months' follow-up. Serum cytokines profile and tissue-infiltrating immune cells were measured by ELISA assay and immunofluorescence, respectively. The SV exhibited lower rates of autoimmune comorbidities and recurrence than the S-NSV, but performed similar to the M-NSV. Moreover, the disease activity, progression, serum cytokines profile, and tissue-infiltrating Th/c1 cells in the active SV and M-NSV were comparable, but differed significantly from those of the active S-NSV. The clinical and immunological similarities between SV and M-NSV presented a deeper autoimmune understanding of SV. Additionally, a classification of active vitiligo according to disease extent may be more clinically meaningful than subtypes for guiding immunomodulatory treatment.

CCN1/Cyr61 Stimulates Melanogenesis through Integrin α6ß1, p38 MAPK, and ERK1/2 Signaling Pathways in Human Epidermal Melanocytes.

Fibroblast-derived melanogenic paracrine mediators are known to play a role in melanogenesis. To investigate the effect of CCN1 (also called CYR61 or cysteine-rich 61) on melanogenesis, normal human epidermal melanocytes were treated with recombinant CCN1 protein. Our findings show that CCN1 activates melanogenesis through promoting melanosome maturation and up-regulation of MITF, TRP-1, and tyrosinase via the integrin α6ß1, p38 MAPK, and ERK signaling pathways. Furthermore, we found that UVB irradiation stimulates the secretion of CCN1 from normal human dermal fibroblasts, and CCN1 knockdown in fibroblasts attenuates melanogenesis in melanocyte-fibroblast co-culture system. Moreover, using immunohistochemistry and immunofluorescence staining, we discovered that CCN1 is overexpressed in the dermis of both solar lentigines and Riehl's melanosis lesions. These findings suggest that CCN1 is a fibroblast-derived melanogenic paracrine mediator that is secreted under UVB irradiation, and it may play an important role in the development of hyperpigmentation diseases such as Riehl's melanosis.