The excessive production of melanin can cause skin diseases and hyperpigmentation. In this study, resveratrol contained in Dongjin rice seed (DJ526) was increased through callus induction. The antioxidant capacity of resveratrol-enriched rice callus was evaluated using the ABTS radical scavenging method and was equivalent to that of vitamin C. DJ526 rice callus extract significantly increased antioxidant activities in a concentration-dependent manner. The anti-melanogenesis effects of DJ526 rice callus extract were also evaluated in melan-a cells. Resveratrol-enriched rice callus extract significantly (i) decreased the size and number of melanin-containing cells, (ii) suppressed the activity of cellular tyrosinase and melanin content, (iii) downregulated the expression of microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2, (iv) increased the expression of phosphorylated extracellular signal-regulated kinase 1/2 and protein kinase B, and (v) inhibited the activation of phosphorylated p38 in melan-a cells. From the above observations, DJ526 rice callus extract showed strong antioxidant and anti-melanogenesis activity at the concentration test. These findings indicate the potential of resveratrol-enriched rice callus as a novel agent for controlling hyperpigmentation.

OBJECTIVE: Methylsulfonylmethane (MSM), which contains organic sulphur, has been used for a long time as a medicinal ingredient because of its benefits to human health. MSM is reported to be protective against certain skin disorders, but it is unknown whether it affects melanin synthesis. Therefore, in our current research, we examined the possibility of MSM controlling the production of melanin in Mel-Ab melanocytes.
METHODS: In Mel-Ab cells, melanin contents and tyrosinase activities were assessed and quantified. The expression of microphthalmia-associated transcription factor (MITF) and tyrosinase was evaluated using western blot analysis, while MSM-induced signalling pathways were investigated.
RESULTS: The MSM treatment significantly resulted in a dose-dependent increase in melanin production. Furthermore, MSM elevated melanin-related proteins, including MITF and tyrosinase. However, the rate-limiting enzyme of melanin production, tyrosinase, was not directly influenced by it. Therefore, we investigated potential melanogenesis-related signalling pathways that may have been triggered by MSM. Our findings showed that MSM did not influence the signalling pathways associated with glycogen synthase kinase 3β, cAMP response-element binding protein, extracellular signal-regulated kinase, or p38 mitogen-activated protein kinase. However, MSM phosphorylated c-Jun N-terminal kinases/stress-activated protein kinase (JNK/SAPK), which is known to induce melanogenesis. SP600125, a specific JNK inhibitor, inhibited MSM-induced melanogenesis.
CONCLUSIONS: Taken together, our study indicates that MSM induces melanin synthesis and may serve as a therapeutic option for hypopigmentary skin disorders such as vitiligo.
ZIEL: Methylsulfonylmethan (MSM), das organischen Schwefel enthält, wird aufgrund seiner Vorteile für die menschliche Gesundheit seit langem als medizinischer Inhaltsstoff verwendet. Es wird berichtet, dass MSM vor bestimmten Hauterkrankungen schützt, es ist jedoch nicht bekannt, ob es die Melaninsynthese beeinflusst. Daher haben wir in unserer aktuellen Forschung die Möglichkeit untersucht, dass MSM die Melaninproduktion in Mel‐Ab‐Melanozyten kontrolliert.
METHODS: In Mel‐Ab‐Zellen wurden der Melaningehalt und die Tyrosinase‐Aktivitäten bewertet und quantifiziert. Die Expression von Mikrophthalmie‐assoziiertem Transkriptionsfaktor (MITF) und Tyrosinase wurde mittels Western‐Blot‐Analyse bewertet, während MSM‐induzierte Signalwege untersucht wurden.
UNASSIGNED: Die MSM‐Behandlung führte signifikant zu einer dosisabhängigen Steigerung der Melaninproduktion. Darüber hinaus erhöhte MSM Melanin‐verwandte Proteine, einschließlich MITF und Tyrosinase. Das geschwindigkeitsbestimmende Enzym der Melaninproduktion, die Tyrosinase, wurde davon jedoch nicht direkt beeinflusst. Daher untersuchten wir mögliche Signalwege im Zusammenhang mit der Melanogenese, die möglicherweise durch MSM ausgelöst wurden. Unsere Ergebnisse zeigten, dass MSM keinen Einfluss auf die Signalwege hatte, die mit der Glykogensynthase‐Kinase 3β, dem cAMP‐Response‐Element‐Bindungsprotein, der extrazellulären signalregulierten Kinase oder der p38‐Mitogen‐aktivierten Proteinkinase verbunden sind. Allerdings phosphorylierte MSM c‐Jun N‐terminale Kinasen/stressaktivierte Proteinkinase (JNK/SAPK), von der bekannt ist, dass sie die Melanogenese induziert. SP600125, ein spezifischer JNK‐Inhibitor, hemmte die MSM‐induzierte Melanogenese.
UNASSIGNED: Zusammenfassend lässt unsere Studie darauf schließen, dass MSM die Melaninsynthese induziert und als Therapieoption für hypopigmentäre Hauterkrankungen wie Vitiligo dienen kann.
OBJECTIVE: le méthylsulfonylméthane (MSM), qui contient du soufre organique, est utilisé depuis longtemps comme ingrédient médicamenteux en raison de ses bénéfices pour la santé humaine. Le MSM aurait un effet protecteur contre certains troubles cutanés, mais on ignore s’il affecte la synthèse de la mélanine. Par conséquent, dans notre étude actuelle, nous avons examiné la possibilité que le MSM contrôle la production de mélanine dans les mélanocytes Mel‐Ab. MÉTHODES: dans les cellules Mel‐Ab, la teneur en mélanine et les activités de la tyrosinase ont été évaluées et quantifiées. L’expression du facteur de transcription associé à la microphtalmie (microphthalmia‐associated transcription factor, MITF) et de la tyrosinase a été évaluée à l’aide d’une analyse Western blot, tandis que les voies de signalisation induites par le MSM ont été étudiées. RÉSULTATS: le traitement par MSM a entraîné de manière significative une augmentation dose‐dépendante de la production de mélanine. En outre, le MSM a élevé les taux de protéines liées à la mélanine, notamment le MITF et la tyrosinase. Cependant, l’enzyme limitant la vitesse de production de la mélanine, la tyrosinase, n’a pas été directement influencée par celui‐ci. Par conséquent, nous avons étudié les voies de signalisation potentielles liées à la mélanogenèse qui pourraient avoir été déclenchées par le MSM. Nos résultats ont montré que le MSM n’influe pas sur les voies de signalisation associées à la protéine glycogène synthase kinase 3β, à la protéine de liaison à l’élément de réponse AMPc, à la kinase régulée par signal extracellulaire ou à la protéine kinase activée par mitogène p38. Cependant, le MSM a phosphorylé les kinases N‐terminales c‐Jun/la protéine kinase activée par le stress (c‐Jun N‐terminal kinases/stress‐activated protein kinase, JNK/SAPK), réaction connue pour induire une mélanogenèse. Le SP600125, un inhibiteur spécifique de la JNK, a inhibé la mélanogenèse induite par le MSM.
CONCLUSIONS: dans l’ensemble, notre étude indique que le MSM induit la synthèse de la mélanine et peut servir d’option thérapeutique pour les troubles cutanés hypopigmentaires tels que le vitiligo.

Melanocytes, located in the epidermis\' basal layer, are responsible for melanin pigment production, crucial for skin coloration and protection against UV radiation-induced damage. Melanin synthesis is intricately regulated by various factors, including the Wnt signaling pathway, particularly mediated by the microphthalmia-associated transcription factor (MITF). While MITF is recognized as a key regulator of pigmentation, its regulation by the Wnt pathway remains poorly understood. This study investigates the role of Sfrp5pepD, a peptide antagonist of the Wnt signaling pathway, in modulating melanogenesis and its potential therapeutic implications for pigmentary disorders. To tackle this issue, we investigated smaller peptides frequently utilized in cosmetics or pharmaceuticals. Nevertheless, there is a significant scarcity of reports on peptides associated with melanin-related signal modulation or inhibiting melanin production. Results indicate that Sfrp5pepD effectively inhibits Wnt signaling by disrupting the interaction between Axin-1 and β-catenin, thus impeding downstream melanogenic processes. Additionally, Sfrp5pepD suppresses the interaction between MITF and β-catenin, inhibiting their nuclear translocation and downregulating melanogenic enzyme expression, ultimately reducing melanin production. These inhibitory effects are validated in cell culture models suggesting potential clinical applications for hyperpigmentation disorders. Overall, this study elucidates the intricate interplay between Wnt signaling and melanogenesis, highlighting Sfrp5pepD as a promising therapeutic agent for pigmentary disorders. Sfrp5pepD, with a molecular weight of less than 500 Da, is anticipated to penetrate the skin unlike SFRPs. This suggests a strong potential for their use as cosmetics or transdermal absorption agents. Additional investigation into its mechanisms and clinical significance is necessary to enhance its effectiveness in addressing melanin-related skin conditions.

The skin-brain axis has been suggested to play a role in several pathophysiological conditions, including opioid addiction, Parkinson\'s disease and many others. Recent evidence suggests that pathways regulating skin pigmentation may directly and indirectly regulate behaviour. Conversely, CNS-driven neural and hormonal responses have been demonstrated to regulate pigmentation, e.g., under stress. Additionally, due to the shared neuroectodermal origins of the melanocytes and neurons in the CNS, certain CNS diseases may be linked to pigmentation-related changes due to common regulators, e.g., MC1R variations. Furthermore, the HPA analogue of the skin connects skin pigmentation to the endocrine system, thereby allowing the skin to index possible hormonal abnormalities visibly. In this review, insight is provided into skin pigment production and neuromelanin synthesis in the brain and recent findings are summarised on how signalling pathways in the skin, with a particular focus on pigmentation, are interconnected with the central nervous system. Thus, this review may supply a better understanding of the mechanism of several skin-brain associations in health and disease.

Structural variations (SVs) are a major source of domestication and improvement traits. We present the first duck pan-genome constructed using five genome assemblies capturing ∼40.98 Mb new sequences. This pan-genome together with high-depth sequencing data (∼46.5×) identified 101,041 SVs, of which substantial proportions were derived from transposable element (TE) activity. Many TE-derived SVs anchoring in a gene body or regulatory region are linked to duck\'s domestication and improvement. By combining quantitative genetics with molecular experiments, we, for the first time, unraveled a 6945 bp Gypsy insertion as a functional mutation of the major gene IGF2BP1 associated with duck bodyweight. This Gypsy insertion, to our knowledge, explains the largest effect on bodyweight among avian species (27.61% of phenotypic variation). In addition, we also examined another 6634 bp Gypsy insertion in MITF intron, which triggers a novel transcript of MITF, thereby contributing to the development of white plumage. Our findings highlight the importance of using a pan-genome as a reference in genomics studies and illuminate the impact of transposons in trait formation and livestock breeding.

Skin hyperpigmentation is mainly caused by excessive synthesis of melanin; however, there is still no safe and effective therapy for its removal. Here, we found that the dermal freezer was able to improve UVB-induced hyperpigmentation of guinea pigs without causing obvious epidermal damage. We also mimic freezing stimulation at the cellular level by rapid freezing and observed that freezing treatments <2.5 min could not decrease cell viability or induce cell apoptosis in B16F10 and Melan-A cells. Critically, melanin content and tyrosinase activity in two cells were greatly reduced after freezing treatments. The dramatic decrease in tyrosinase activity was associated with the downregulation of MITF, TYR, TRP-1 and TRP-2 protein expression in response to freezing treatments for two cells. Furthermore, our results first demonstrated that freezing treatments significantly reduced the levels of p-GSK3β and β-catenin and the nuclear accumulation of β-catenin in B16F10 and Melan-A cells. Together, these data suggest that fast freezing treatments can inhibit melanogenesis-related gene expression in melanocytes by regulating the Wnt/β-catenin signalling pathway. The inhibition of melanin production eventually contributed to the improvement in skin hyperpigmentation induced by UVB. Therefore, fast freezing treatments may be a new alternative of skin whitening in the clinic in the future.

Calcium (Ca2+) plays a pivotal role in cellular signal transmission by triggering downstream signaling in response to an increase in the cytosolic Ca2+ concentration. Intracellular organelles serve as Ca2+ stores that induce differently shaped Ca2+ signals. We discuss a study by Yuan et al. that investigated the interplay between the lysosomal two-pore channel 2 (TPC2) and endoplasmic reticulum (ER)-localized inositol 1,4,5-trisphosphate receptors (IP3Rs).

There has been a growing interest in skin beauty and antimelanogenic products. Melanogenesis is the process of melanin synthesis whereby melanocytes are activated by UV light or hormone stimulation to produce melanin. Melanogenesis is mediated by several enzymes, such as tyrosinase (TYR), microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1), and TRP-2. In this study, we investigated the effect of Tuber himalayense extract on melanin synthesis in α-melanocyte-stimulating hormone (α-MSH)-treated B16F10 melanoma cells. We confirmed that T. himalayense extract was not toxic to α-MSH-treated B16F10 melanoma cells and exhibited a significant inhibitory effect on melanin synthesis at concentrations of 25, 50, and 100 μg/ml. Additionally, the T. himalayense extract inhibited melanin, TRP-1, TRP-2, tyrosinase, and MITF, which are enzymes involved in melanin synthesis, in a concentration-dependent manner. Furthermore, T. himalayense extract inhibited the mitogen-activated protein kinase (MAPK) pathways, such as extracellular signal-regulated kinase-1/2 (ERK), c-Jun N-terminal kinase (JNK), and p38. Therefore, we hypothesized that various components of T. himalayense extract affect multiple factors involved in melanogenesis in B16F10 cells. Our results indicate that T. himalayense extract could potentially be used as a new material for preparing whitening cosmetics.

Spergularia marina is a plant that grows in salty regions along the coastline and exerts radical-scavenging and anti-inflammatory effects. In this study, we investigated the skin-whitening effects of S. marina extract (SME) in B16F10 melanoma cells. SME was found to exert radical-scavenging effects. It suppressed α-melanocyte-stimulating hormone-induced melanogenesis and tyrosinase activity. We also assessed the melanin production signaling pathway to identify the inhibitory action mechanism of SME on melanogenesis. SME decreased the protein expression levels of tyrosinase-related protein (TRP)-1, TRP-2, and tyrosinase, which play important roles in melanogenesis. Furthermore, western blotting revealed that SME inhibited the nuclear translocation of melanocyte inducing transcription factor (MITF), which is a transcription factor for TRP-1, TRP-2, and tyrosinase, suggesting that SME exerts its skin-whitening effect by inhibiting MITF nuclear translocation. Therefore, SME may potentially be used in skin-whitening medicines and cosmetics.

Since genome instability can drive cancer initiation and progression, cells have evolved highly effective and ubiquitous DNA damage response (DDR) programs. However, some cells (for example, in skin) are normally exposed to high levels of DNA-damaging agents. Whether such high-risk cells possess lineage-specific mechanisms that tailor DNA repair to the tissue remains largely unknown. Using melanoma as a model, we show here that the microphthalmia-associated transcription factor MITF, a lineage addition oncogene that coordinates many aspects of melanocyte and melanoma biology, plays a nontranscriptional role in shaping the DDR. On exposure to DNA-damaging agents, MITF is phosphorylated at S325, and its interactome is dramatically remodeled; most transcription cofactors dissociate, and instead MITF interacts with the MRE11-RAD50-NBS1 (MRN) complex. Consequently, cells with high MITF levels accumulate stalled replication forks and display defects in homologous recombination-mediated repair associated with impaired MRN recruitment to DNA damage. In agreement with this, high MITF levels are associated with increased single-nucleotide and copy number variant burdens in melanoma. Significantly, the SUMOylation-defective MITF-E318K melanoma predisposition mutation recapitulates the effects of DNA-PKcs-phosphorylated MITF. Our data suggest that a nontranscriptional function of a lineage-restricted transcription factor contributes to a tissue-specialized modulation of the DDR that can impact cancer initiation.