Late sporogonic stages of Plasmodium parasites are susceptible to the melanization response in Anopheles gambiae mosquitoes.

The malaria-causing parasites have to complete a complex infection cycle in the mosquito vector that also involves attack by the insect's innate immune system, especially at the early stages of midgut infection. However, Anopheles immunity to the late Plasmodium sporogonic stages, such as oocysts, has received little attention as they are considered to be concealed from immune factors due to their location under the midgut basal lamina and for harboring an elaborate cell wall comprising an external layer derived from the basal lamina that confers self-properties to an otherwise foreign structure. Here, we investigated whether Plasmodium berghei oocysts and sporozoites are susceptible to melanization-based immunity in Anopheles gambiae. Silencing of the negative regulator of melanization response, CLIPA14, increased melanization prevalence without significantly increasing the numbers of melanized oocysts, while co-silencing CLIPA14 with CLIPA2, a second negative regulator of melanization, resulted in a significant increase in melanized oocysts and melanization prevalence. Only late-stage oocysts were found to be melanized, suggesting that oocyst rupture was a prerequisite for melanization-based immune attack, presumably due to the loss of the immune-evasive features of their wall. We also found melanized sporozoites inside oocysts and in the hemocoel, suggesting that sporozoites at different maturation stages are susceptible to melanization. Silencing the melanization promoting factors TEP1 and CLIPA28 rescued oocyst melanization in CLIPA2/CLIPA14 co-silenced mosquitoes. Interestingly, silencing of CTL4, that protects early stage ookinetes from melanization, had no effect on oocysts and sporozoites, indicating differential regulation of immunity to early and late sporogonic stages. Similar to previous studies addressing ookinete stage melanization, the melanization of Plasmodium falciparum oocysts was significantly lower than that observed for P. berghei. In summary, our results provide conclusive evidence that late sporogonic malaria parasite stages are susceptible to melanization, and we reveal distinct regulatory mechanisms for ookinete and oocyst melanization.

Monte Carlo simulation of the effect of melanin concentration on light-tissue interactions for transmittance pulse oximetry measurement.

Significance: Questions about the accuracy of pulse oximeters in measuring arterial oxygen saturation ( SpO 2 ) in individuals with darker skin pigmentation have resurfaced since the COVID-19 pandemic. This requires investigation to improve patient safety, clinical decision making, and research. Aim: We aim to use computational modeling to identify the potential causes of inaccuracy in SpO 2 measurement in individuals with dark skin and suggest practical solutions to minimize bias. Approach: An in silico model of the human finger was developed to explore how changing melanin concentration and arterial oxygen saturation ( SaO 2 ) affect pulse oximeter calibration algorithms using the Monte Carlo (MC) technique. The model generates calibration curves for Fitzpatrick skin types I, IV, and VI and an SaO 2 range between 70% and 100% in transmittance mode. SpO 2 was derived by inputting the computed ratio of ratios for light and dark skin into a widely used calibration algorithm equation to calculate bias ( SpO 2 - SaO 2 ). These were validated against an experimental study to suggest the validity of the Monte Carlo model. Further work included applying different multiplication factors to adjust the moderate and dark skin calibration curves relative to light skin. Results: Moderate and dark skin calibration curve equations were different from light skin, suggesting that a single algorithm may not be suitable for all skin types due to the varying behavior of light in different epidermal melanin concentrations, especially at 660 nm. The ratio between the mean bias in White and Black subjects in the cohort study was 6.6 and 5.47 for light and dark skin, respectively, from the Monte Carlo model. A linear multiplication factor of 1.23 and exponential factor of 1.8 were applied to moderate and dark skin calibration curves, resulting in similar alignment. Conclusions: This study underpins the careful re-assessment of pulse oximeter designs to minimize bias in SpO 2 measurements across diverse populations.

Laser-induced optical breakdown is a prior strategy for acquired melanin-increased disorder in dermal layer.

This brief report discusses the challenges in treating dermal melanosis and the limitations of current laser treatments due to inadequate tissue penetration and potential side effects. It introduces laser-induced optical breakdown (LIOB) as a novel therapeutic approach using a picosecond laser with a diffractive lens array (DLA) to target dermal pigmentation effectively. LIOB induces multiphoton ionization, leading to melanin clearance through phagocytosis and apoptotic cell removal, while also promoting dermal remodeling and collagen synthesis. We present a case of successful treatment of dermal pigmentation in a 55-year-old woman using 755 nm-picosecond alexandrite laser therapy, demonstrating significant improvement without recurrence. The findings suggest that LIOB offers a promising solution for acquired dermal hypermelanosis by addressing both diffuse and localized pigmentation effectively, leading to skin rejuvenation with minimal downtime and high patient satisfaction.

A melanin-like polymer bearing phenylboronic units as a suitable bioplatform for living cell display technology.

Surface display of functional groups with specific reactivity around living cells is an emerging, low cost and highly eco-compatible technology that serves multiple applications, ranging from basic biochemical studies to biomedicine, therapeutics and environmental sciences. Conversely to classical methods exploiting hazardous organic synthesis of precursors or monovalent functionalization via genetics, here we perform functional decoration of individual living microalgae using suitable biocoatings based on polydopamine, a melanin-like synthetic polymer. Here we demonstrate the one-pot synthesis of a functional polydopamine bearing phenylboronic units which can decorate the living cell surfaces via a direct ester formation between boronic units and surface glycoproteins. Furthermore, biosorption of fluorescent sugars on functionalized cell membranes is triggered, demonstrating that these organic coatings act as biocompatible soft shells, still functional and reactive after cell engineering.

Reprogramming the myocardial infarction microenvironment with melanin-based composite nanomedicines in mice.

Myocardial infarction (MI) has a 5-year mortality rate of more than 50% due to the lack of effective treatments. Interactions between cardiomyocytes and the MI microenvironment (MIM) can determine the progression and fate of infarcted myocardial tissue. Here, a specially designed Melanin-based composite nanomedicines (MCN) is developed to effectively treat MI by reprogramming the MIM. MCN is a nanocomposite composed of polydopamine (P), Prussian blue (PB) and cerium oxide (CexOy) with a Mayuan-like structure, which reprogramming the MIM by the efficient conversion of detrimental substances (H+, reactive oxygen species, and hypoxia) into beneficial status (O2 and H2O). In coronary artery ligation and ischemia reperfusion models of male mice, intravenously injecting MCN specifically targets the damaged area, resulting in restoration of cardiac function. With its promising therapeutic effects, MCN constitutes a new agent for MI treatment and demonstrates potential for clinical application.

Ceramide Ehux-C22 Targets the miR-199a-3p/mTOR Signaling Pathway to Regulate Melanosomal Autophagy in Mouse B16 Cells.

Melanosomes are specialized membrane-bound organelles where melanin is synthesized and stored. The levels of melanin can be effectively reduced by inhibiting melanin synthesis or promoting melanosome degradation via autophagy. Ceramide, a key component in the metabolism of sphingolipids, is crucial for preserving the skin barrier, keeping it hydrated, and warding off the signs of aging. Our preliminary study indicated that a long-chain C22-ceramide compound (Ehux-C22) isolated from the marine microalga Emiliania huxleyi, reduced melanin levels via melanosomal autophagy in B16 cells. Recently, microRNAs (miRNAs) were shown to act as melanogenesis-regulating molecules in melanocytes. However, whether the ceramide Ehux-C22 can induce melanosome autophagy at the post-transcriptional level, and which potential autophagy-dependent mechanisms are involved, remains unknown. Here, miR-199a-3p was screened and identified as a novel upregulated miRNA in Ehux-C22-treated B16 cells. An in vitro high melanin expression model in cultured mouse melanoma cells (B16 cells) was established by using 0.2 µM alpha-melanocyte-stimulating hormone(α-MSH) and used for subsequent analyses. miR-199a-3p overexpression significantly enhanced melanin degradation, as indicated by a reduction in the melanin level and an increase in melanosome autophagy. Further investigation demonstrated that in B16 cells, Ehux-C22 activated miR-199a-3p and inhibited mammalian target of rapamycin(mTOR) level, thus activating the mTOR-ULK1 signaling pathway by promoting the expression of unc-51-like autophagy activating kinase 1 (ULK1), B-cell lymphoma-2 (Bcl-2), Beclin-1, autophagy-related gene 5 (ATG5), and microtubule-associated protein light chain 3 (LC3-II) and degrading p62. Therefore, the roles of Ehux-C22-regulated miR-199a-3p and the mTOR pathway in melanosomal autophagy were elucidated. This research may provide novel perspectives on the post-translational regulation of melanin metabolism, which involves the coordinated control of melanosomes.

The Invisible Fraction within Melanin Capable of Absorbing UV Light and with Fluorescent Properties: Is It Lacking Consideration?

Expanding on earlier observations, we show that many melanin materials, in vitro synthesized from a wide range of precursors, can be fractionated into a dark-colored precipitate and a near-colorless, dispersible fraction. The dispersible fractions exhibited absorbance in the UVA and UVB range of the electromagnetic spectrum, but none in the visible range. In addition, fluorescent properties were associated with all dispersible fractions obtained. FT-IR spectroscopic analyses were performed to compare both types of fractions. Overall, it appears that some of the properties associated with melanin (UV absorbance, fluorescence) may not necessarily reside in the dark-colored portion of melanin, but in a colorless fraction of the material. It remains to be seen whether any of these in vitro observations have any relevance in vivo. However, we raise the possibility that the presence of a colorless fraction within melanin materials and their associated properties may have received inadequate attention. Given the important association between melanin, UV protection, and skin cancer, it is worthwhile to consider this additional aspect of melanin chemistry.

Progression from in vivo validation to in vitro screening in hazard assessment for leukoderma-inducible chemicals.

Chemicals are representative environmental factors that affect human health. Recently, external exposure to a chemical of rhododenol (RD) caused chemical leukoderma, an acquired patchy hypopigmentation, in about 20,000 Asian people. The development of a hazard assessment system for accurate determination of leukoderma-inducible chemicals is required for the prevention of such tragedies. Case studies in humans have shown 6 chemicals, including RD, with a constitutive leukoderma-inducible potency and 3 chemicals with a photosensitive but not a constitutive leukoderma-inducible potency. In this study, the 6 positive and 3 negative control chemicals with or without constitutive leukoderma-inducible potencies were investigated by our previously developed in vivo hazard assessment system using tail skin of mice. Based on the results of validation, this study aimed to develop an in vitro hazard assessment system to correctly determine chemicals with a constitutive leukoderma-inducible potency. As expected, external exposure to the 6 positive control chemicals, but not external exposure to the 3 negative control chemicals, resulted in development of constitutive leukoderma in mouse tail skin with a decreased level of skin melanin and decreased number of melanocytes. Moreover, the 6 positive and 3 negative control chemicals were correctly distinguished by the presence or absence of endoplasmic reticulum (ER) stress induction, but not by tyrosinase-dependent cell death or production of reactive oxygen species (ROS), in immortalized normal melanocytes. The hazard assessment system using tail skin could be a solid in vivo tool to reliably determine the chemical potency of a chemical for constitutive leukoderma induction. The hazard assessment system focusing on ER stress induction in normal melanocytes might be a novel and convenient in vitro tool for accurately evaluating chemicals with leukoderma-inducible potencies. Thus, this study contributed to environmentology through the development of a screening system for preventing an environmental factor-related disease.

In vitro efficacy of Rosa damascena solid state fermentation liquid and water extract on skin care.

BACKGROUND: As a medicinal and food homologous plant, Rosa damascena is not only highly ornamental, but also rich in a variety of active ingredients such as polyphenols and flavonoids. It is widely used in cosmetics, food and pharmaceutical industries. OBJECTIVE: To study the in vitro efficacy of Rosa damascena solid state fermentation liquid (RDF) and water extract (RDE). METHODS: Firstly, the effect of RDF and RDE on the proliferation rate of B16F10 cells was detected by CCK-8 method, and the melanin content was measured by sodium hydroxide lysis method to evaluate the whitening effect of them. Finally, the antioxidant, anti-wrinkling and soothing effects of RDF and RDE were evaluated by biochemical methods in vitro. RESULTS: RDF and RDE within a certain concentration range (0.05%-0.5%) had no effect on the proliferation of B16F10 cells. Compared with Rosa damascena extract (RDE), RDF showed significant effects on bleaching, antioxidant, anti-wrinkling and soothing, among which 0.5% RDF showed the best effect. CONCLUSION: Both RDF and RDE at a certain concentration have effect on skin care in vitro, but the effect of RDF is more significant than that of RDE.

Nanoscale synchrotron x-ray analysis of intranuclear iron in melanised neurons of Parkinson's substantia nigra.

Neuromelanin-pigmented neurons of the substantia nigra are selectively lost during the progression of Parkinson's disease. These neurons accumulate iron in the disease state, and iron-mediated neuron damage is implicated in cell death. Animal models of Parkinson's have evidenced iron loading inside the nucleoli of nigral neurons, however the nature of intranuclear iron deposition in the melanised neurons of the human substantia nigra is not understood. Here, scanning transmission x-ray microscopy (STXM) is used to probe iron foci in relation to the surrounding ultrastructure in melanised neurons of human substantia nigra from a confirmed Parkinson's case. In addition to the expected neuromelanin-bound iron, iron deposits are also associated with the edge of the cell nucleolus. Speciation analysis confirms these deposits to be ferric (Fe3+) iron. The function of intranuclear iron in these cells remains unresolved, although both damaging and protective mechanisms are considered. This finding shows that STXM is a powerful label-free tool for the in situ, nanoscale chemical characterisation of both organic and inorganic intracellular components. Future applications are likely to shed new light on incompletely understood biochemical mechanisms, such as metal dysregulation and morphological changes to cell nucleoli, that are important in understanding the pathogenesis of Parkinson's.

Epidermal and dermal hydration in relation to skin color parameters.

BACKGROUND: Our goal was to investigate linkages between skin color parameters and skin hydration. Since most prior studies focused on stratum corneum hydration, we focused on epidermal and dermal hydration in relation to skin color parameters in both sexes. MATERIALS AND METHODS: Thirty adults (16 female) with an age ± SD of 24.3 ± 0.6 years participated. Three sites on both volar forearms were evaluated for melanin index (MI), erythema index (EI), Individual Typology Angle (ITA), tissue dielectric constant (TDC) values to depths of 0.5 mm (TDC0.5) and 2.5 mm (TDC2.5), and Fitzpatrick skin type (FST). RESULTS: MI and EI were highly correlated (r = 0.800, p < 0.001) with maximum differences in MI and ITA along the arm of 3% and 6.3% with no difference between arms. Male MI was greater than females (p < 0.01). Male TDC2.5 was 36.1 ± 5.4 and correlated with EI (r = 0.231, p = 0.035). Contrastingly, female TDC25 was 28.5 ± 3.6 with no correlation with EI but was correlated with MI (r = -0.301, p = 0.003). These differential patterns held true for TDC0.5. For both sexes, FST and ITA were highly correlated (r = -0.756, p < 0.001). CONCLUSIONS: The findings revealed several correlations between skin color parameters and hydration that differed between males in females in some cases. The observed correlations may indicate that melanin may differentially impact water-holding capacity between sexes and provides a future research target. Further, these initial findings also may hold significance for dermatological assessments and the customization of skincare treatments tailored to individual skin types and demographics.

In Silico Identification and Molecular Mechanism of Novel Tyrosinase Inhibitory Peptides Derived from Nacre of Pinctada martensii.

Pearl and nacre powders have been valuable traditional Chinese medicines with whitening properties for thousands of years. We utilized a high-temperature and high-pressure method along with compound enzyme digestion to prepare the enzymatic hydrolysates of nacre powder of Pinctada martensii (NP-PMH). The peptides were identified using LC-MS/MS and screened through molecular docking and molecular dynamics simulations. The interactions between peptides and tyrosinase were elucidated through enzyme kinetics, circular dichroism spectropolarimetry, and isothermal titration calorimetry. Additionally, their inhibitory effects on B16F10 cells were explored. The results showed that a tyrosinase-inhibitory peptide (Ala-His-Tyr-Tyr-Asp, AHYYD) was identified, which inhibited tyrosinase with an IC50 value of 2.012 ± 0.088 mM. The results of the in vitro interactions showed that AHYYD exhibited a mixed-type inhibition of tyrosinase and also led to a more compact enzyme structure. The binding reactions of AHYYD with tyrosinase were spontaneous, leading to the formation of a new set of binding sites on the tyrosinase. The B16F10 cell-whitening assay revealed that AHYYD could reduce the melanin content of the cells by directly inhibiting the activity of intracellular tyrosinase. Additionally, it indirectly affects melanin production by acting as an antioxidant. These results suggest that AHYYD could be widely used as a tyrosinase inhibitor in whitening foods and pharmaceuticals.

Antioxidant and Skin-Whitening Efficacy of a Novel Decapeptide (DP, KGYSSYICDK) Derived from Fish By-Products.

The skin is vulnerable to damage from ultraviolet rays and oxidative stress, which can lead to aging and pigmentation issues. This study investigates the antioxidant and whitening efficacy of a decapeptide (DP, KGYSSYICDK) derived from marine fish by-products and evaluates its potential as a new skin-whitening agent. DP demonstrated high antioxidant activity, showing comparable or superior performance to Vitamin C (Vit. C) in ferric reducing antioxidant power (FRAP) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. In hydrogen peroxide (H2O2)-treated HaCaT cells, DP increased cell viability and reduced reactive oxygen species (ROS) generation. Furthermore, DP inhibited tyrosinase activity and decreased melanin production in α-melanocyte stimulating hormone (α-MSH)-induced B16F10 melanoma cells in a dose-dependent manner. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that DP reduces the mRNA expression of MITF, tyrosinase, and MC1R, thus suppressing melanin production. DP exhibits strong binding interactions with multiple amino acid residues of tyrosinase, indicating potent inhibitory effects on the enzyme. These results suggest that DP possesses significant antioxidant and whitening properties, highlighting its potential as a skin-whitening agent. Future research should focus on optimizing DP's structure and exploring structure-activity relationships.

Transcriptomic and Metabolomic Analyses Reveal Molecular Regulatory Networks for Pigmentation Deposition in Sheep.

Domestic animals have multiple phenotypes of skin and coat color, which arise from different genes and their products, such as proteins and metabolites responsible with melanin deposition. However, the complex regulatory network of melanin synthesis remains to be fully unraveled. Here, the skin and tongue tissues of Liangshan black sheep (black group) and Liangshan semi-fine-wool sheep (pink group) were collected, stained with hematoxylin-eosin (HE) and Masson-Fontana, and the transcriptomic and metabolomic data were further analyzed. We found a large deposit of melanin granules in the epidermis of the black skin and tongue. Transcriptome and metabolome analysis identified 744 differentially expressed genes (DEGs) and 443 differentially expressed metabolites (DEMs) between the pink and black groups. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses revealed the DEGs and DEMs were mainly enriched in the pathways of secondary metabolic processes, melanin biosynthesis processes, melanin metabolism processes, melanosome membranes, pigment granule membranes, melanosome, tyrosine metabolism, and melanogenesis. Notably, we revealed the gene ENSARG00020006042 may be a family member of YWHAs and involved in regulating melanin deposition. Furthermore, several essential genes (TYR, TYRP1, DCT, PMEL, MLANA, SLC45A2) were significantly associated with metabolite prostaglandins and compounds involved in sheep pigmentation. These findings provide new evidence of the strong correlation between prostaglandins and related compounds and key genes that regulate sheep melanin synthesis, furthering our understanding of the regulatory mechanisms and molecular breeding of pigmentation in sheep.

Mechanism of desuccinylation of G6PD mediated by SIRT7 to promote vitiligo disease progression.

BACKGROUND: Sirtuin 7 (SIRT7) is pivotal in diverse diseases progression. Importantly, SIRT7 is associated with melanin production. However, whether SIRT7 regulates vitiligo is unclear. Therefore, we aimed to investigate the effects of SIRT7 on pigmentation and the modification of glucose 6-phosphate dehydrogenase (G6PD). METHODS: After knockdown SIRT7 and G6PD, pigmentation of melanocytes was evaluated using commercial kits, immunofluorescence, and Western blot analysis. The succinylation of G6PD mediated by SIRT7 was analyzed using co-immunoprecipitation, immunofluorescence, Western blot analysis, and cycloheximide-chase experiment. RESULTS: We found that SIRT7 was highly expressed in vitiligo skin lesions. Knockdown of SIRT7 increased tyrosinase activity, melanin content, and the levels of α-melanocyte-stimulating hormone, MITF, TYR, TRP1, and TRP2. Additionally, SIRT7 directly interacted with G6PD. Silenced SIRT7 promoted the succinylation of G6PD and enhanced its protein stability. G6PD knockdown reversed the effect of reduced SIRT7 expression on melanin production. CONCLSUION: Silencing of SIRT7 promotes pigmentation of melanocytes by succinylating G6PD, suggesting that SIRT7-mediated G6PD desuccinylation may promote vitiligo progression.

Effect of proton pump inhibitors on susceptibility and melanogenesis of Sporothrix species.

Introduction. Sporotrichosis is a subcutaneous infection caused by dimorphic Sporothrix species embedded in the clinical clade. Fungi have virulence factors, such as biofilm and melanin production, which contribute to their survival and are related to the increase in the number of cases of therapeutic failure, making it necessary to search for new options.Gap statement. Proton pump inhibitors (PPIs) have already been shown to inhibit the growth and melanogenesis of other fungi.Aim. Therefore, this study aimed to evaluate the effect of the PPIs omeprazole (OMP), rabeprazole (RBP), esomeprazole, pantoprazole and lansoprazole on the susceptibility and melanogenesis of Sporothrix species, and their interactions with itraconazole, terbinafine and amphotericin B.Methodology. The antifungal activity of PPIs was evaluated using the microdilution method, and the combination of PPIs with itraconazole, terbinafine and amphotericin B was assessed using the checkerboard method. The assessment of melanogenesis inhibition was assessed using grey scale.Results. The OMP and RBP showed significant MIC results ranging from 32 to 256 µg ml-1 and 32 to 128 µg ml-1, respectively. Biofilms were sensitive, with a significant reduction (P<0.05) in metabolic activity of 52% for OMP and 50% for RBP at a concentration of 512 µg ml-1 and of biomass by 53% for OMP and 51% for RBP at concentrations of 512 µg ml-1. As for the inhibition of melanogenesis, only OMP showed inhibition, with a 54% reduction.Conclusion. It concludes that the PPIs OMP and RBP have antifungal activity in vitro against planktonic cells and biofilms of Sporothrix species and that, in addition, OMP can inhibit the melanization process in Sporothrix species.

New Aspects Regarding the Fluorescence Spectra of Melanin and Neuromelanin in Pigmented Human Tissue Concerning Hypoxia.

Melanin is a crucial pigment in melanomagenesis. Its fluorescence in human tissue is exceedingly weak but can be detected through advanced laser spectroscopy techniques. The spectral profile of melanin fluorescence distinctively varies among melanocytes, nevomelanocytes, and melanoma cells, with melanoma cells exhibiting a notably "red" fluorescence spectrum. This characteristic enables the diagnosis of melanoma both in vivo and in histological samples. Neuromelanin, a brain pigment akin to melanin, shares similar fluorescence properties. Its fluorescence can also be quantified with high spectral resolution using the same laser spectroscopic methods. Documented fluorescence spectra of neuromelanin in histological samples from the substantia nigra substantiate these findings. Our research reveals that the spectral behavior of neuromelanin fluorescence mirrors that of melanin in melanomas. This indicates that the typical red fluorescence is likely influenced by the microenvironment around (neuro)melanin, rather than by direct pigment interactions. Our ongoing studies aim to further explore this distinctive "red" fluorescence. We have observed this red fluorescence spectrum in post-mortem measurements of melanin in benign nevus. The characteristic red spectrum is also evident here (unlike the benign nevus in vivo), suggesting that hypoxia may contribute to this phenomenon. Given the central role of hypoxia in both melanoma development and treatment, as well as in fundamental Parkinson's disease mechanisms, this study discusses strategies aimed at reinforcing the hypothesis that red fluorescence from (neuro)melanin serves as an indicator of hypoxia.

Cyclo(l-Pro-l-Tyr) Isolated from the Human Skin Commensal Corynebacterium tuberculostearicum Inhibits Tyrosinase.

Melanin is produced by melanocytes to protect human skin from harmful ultraviolet radiation. During skin cell renewal, melanin and dead skin cells are disposed of. However, prolonged exposure to ultraviolet rays or aging can disturb this cycle, leading to skin hyperpigmentation due to melanin accumulation. Tyrosinase is a crucial enzyme involved in melanin biosynthesis. Although various compounds, including tyrosine inhibitors, that counteract melanin accumulation have been reported, some, such as hydroquinone, are toxic and can cause vitiligo. Meanwhile, the skin is the largest organ and the outermost layer of the immune system, containing a diverse range of bacteria that produce low-toxicity compounds. In the current study, we aim to identify metabolites produced by skin microbiota that inhibit tyrosinase. Specifically, mushroom tyrosinase served as the study model. Following commensal skin bacteria screening, Corynebacterium tuberculostearicum was found to inhibit tyrosinase activity. The active compound was cyclo(l-Pro-l-Tyr); commercially available cyclo(l-Pro-l-Tyr) also exhibited inhibitory activity. Docking simulations suggested that cyclo(l-Pro-l-Tyr) binds to the substrate-binding site of mushroom tyrosinase, obstructing the substrate pocket and preventing its activity. Hence, cyclo(l-Pro-l-Tyr) might have potential applications as a cosmetic agent and food additive.

Mechanism of the wine pomace tannin in hyperpigmentation inhibition: Impact on signaling pathways, cell proliferation, and tyrosinase activity.

After winemaking, tannins with high polymerization remain in the pomace. Utilizing these tannin fractions is a concern for the wine industry. While tannins show potential in treating hyperpigmentation, their mechanisms in vivo and at the cellular level are unclear. Herein, pomace tannin fractions (PTFs) were isolated post-winemaking. Nuclear magnetic resonance spectroscopy and mass spectrometry analysis showed PTFs were composed of (epi)catechin gallate and (epi)catechin as terminal and extensional units, with polymerization degrees of 10, 16, and 35. In vivo studies demonstrated that PTFs removed ∼76 % of skin melanin, comparable to hydroquinone. The inhibition by PTFs is due to: (1) Inhibition of the Wnt and melanogenesis pathways, downregulating key melanin synthesis proteins (TYR, TYRP1, TYRP2); (2) Inducing cell cycle arrest at the G1/S checkpoint, disrupting DNA, decreasing mitochondrial membrane potential and integrity, and slowing melanocyte proliferation; (3) Superior tyrosinase inhibitory activity by binding to tyrosinase, chelating copper ions, and demonstrating antioxidant properties. These findings suggest that PTFs inhibit melanin synthesis by the combination of the above mentioned ways, supporting the medical use of winemaking tannins.

UVB-induced TRPS1 regulates MITF transcription activity to promote skin pigmentation.

Hyperpigmented dermatoses are characterized by increased skin pigmentation caused by genetic, environmental factors and inflammation, which lasts a long time and is difficult to treat. Ultraviolet (UV), especially ultraviolet B (UVB), is the primary external factor inducing skin pigmentation. However, the specific regulatory mechanisms are not fully understood. Through analysis of GEO datasets from four UV-exposed skin cell/tissue samples, we found that TRPS1 is the only gene differentially expressed in multiple datasets (GSE22083, GSE67098 and GSE70280) and highly positively correlated with the expression of key melanogenesis genes. Consistently, we observed that TRPS1 is highly expressed in sun-exposed skin tissues compared to non-exposed skin. Additionally, the expression of TRPS1 was also significantly upregulated after UVB irradiation in isolated skin tissues and melanocytes, while knockdown of TRPS1 expression inhibited the UVB-induced melanogenesis. Further research revealed that overexpression of TRPS1 increased melanin content and tyrosinase activity in MNT1 cells, as well as upregulated the expression levels of key melanogenesis genes (MITF, TYR, TYRP1, DCT). In contrast, inhibition of TRPS1 expression showed the opposite effect. Moreover, we found that TRPS1 can bind to the promoter region of MITF, inhibiting the expression of MITF can antagonize the melanogenesis induced by TRPS1. In conclusion, UVB-induced TRPS1 promotes melanogenesis by activating the transcriptional activity of MITF.